ÖZET
Son dönem mitral yetmezliğinde (MY) mitral kapak replasmanı (MVR) postoperatif dönemde yüksek mortalite ve morbidite ile seyretmektedir. Bu gibi hastalarda kapak tamiri öncelikle düşünülmelidir. Tamir uygun değilse mitral kapak yaprakları kısmen veya tamamen korunarak MVR önerilmektedir. Ejeksiyon farksiyonu (EF) oldukça düşmüş ve sol ventrikül çapları ileri derecede artmış olan son dönem MY’li iki ayrı hastamızda, kardiyopulmoner baypas (KPB) eşliğinde, çalışan kalpte, kros-klemp konmaksızın, kapak yaprakları tamamen korunarak MVR yapıldı. Ayrıca hastalardan birine anestezi indüksiyonu ile beraber Levosimendan başlandı.  Heriki hastada da KPB’ den sorunsuz çıkıldı, hastalar postoperatif 5. ve 6. günlerde şifa ile taburcu edildi. 

 

GİRİŞ

Çalışan kalpte KPB kullanılarak mitral kapak cerrahisi özellikle düşük ventrikül fonksiyonu olan hastalarda kardiyak fonksiyonları korumada önemli bir avantaj sunmakta ve  son zamanlarda kullanımı artmaktadır. Kardiyak rezervleri sınırlı hastalarda arrest sağlanarak yapılan girişimlerde önemli morbidite ve mortalite artışı görülmektedir. Çalışan kalpte KPB eşliğinde düşük ventrikül fonksiyonlu hastalarda kardiyak fonksiyonlar daha iyi korunabilir. Çalışan kalpte KPB eşliğinde yapılan mitral kapak cerrahisinde kardiyopleji solusyonu verilmediği için miyokard reperfüzyon hasarından korunacağı gibi, koroner perfüzyon da devam etmektedir. Böylece normotermik koroner perfüzyon ile normal  kardiyak fizyoloji devam ettirilebilmektedir.(1) 

Yapılan kardiyak cerrahinin sol ventrikül fonksiyonlarını ve geometrisini koruması oldukça önem taşır. Bu bağlamda subvalvüler aparatusun  korunması da  oldukça önemlidir. Subvalvüler aparatusun  korunmasının, hem erken dönemde mortalite- morbiditeyi azalttığı, hemde geç dönem sağ kalımı ve foksiyonel kapasiteyi iyileştirdiği bildirilmektedir  (2,3). 

Levosimendan, hücre içi kalsiyum düzeyini ve oksijen tüketimini  artırmaksızın, kontraktiliteyi arttırabilen ve dekompanse kalp yetmezliği ile KPB’den ayrılmakta zorlanan postoperatif hastalarda kullanılan yeni nesil bir pozitif inotrop ilaçtır (4). Biz de bu hastalardan birinde KPB’den ayrılmayı kolaylaştırmak amacı ile proflaktik olarak Levosimendan kullandık.

 

OLGU SUNUSU 1

60 yaşında erkek hasta nefes darlığı, çarpıntı, çabuk yorulma ve göğüs ağrısı şikayetleriyle kliniğimize başvurdu. Yaklaşık on yıldır şikayetleri olan ve son zamanlarda şikayetleri artan hastaya dış merkezde yapılan ekokardiyografi de (EKO) 3-4 derece mitral yetmezliği saptanmıştı. Bilinen aile öyküsü olmayan hastanın ek hastalık olarak inguinal hernisi mevcuttu. Fizik muaynesinde  tansiyon:110/70mmHg, nabız:80/dk ve aritmik idi. Dinlemekle apekste 5/6 sistolik üfürüm mevcuttu. Akciğerlerde dinlemekle bilateral bazallerde raller mevcut idi. Hastanın NYHA fonksiyonel kapasitesi III idi.  Elektrokardiyogramda ritm atriyal fibrilasyon idi. Telekardiyografi de bilateral akciğer bazal zonlarda hafif yüklenme bulguları ve kardiyomegali vardı. EKO da 3-4 derece eksantrik ciddi mitral yetmezlik, ejeksiyon fraksiyonu %25, sol ventrikül diyastol sonu çapı: 7,0cm, sol ventrikül sistol sonu çapı: 6,5cm, sol atrium: 6,7cm, sol ventrikül ve sağ ventrikül de yaygın hipokinetik alanlar mevcuttu. Ayrıca 2 derece triküspit yetmezliği olan hastada pulmoner arter basıncı: 50 mmHg olarak ölçüldü. Yapılan koroner anjiografisinde koroner arterler normal olarak değerlendirildi. Hastanın rutin kan tetkiklerinde patoloji saptanmadı.

Bu bulgularla ameliyata alınan hastaya anestezi indüksiyonu ile beraber, 12 mikrogram/kg/dk bolus ve ardından 0,1mikrogram/kg/dk 24 saatlik infüzyon dozu ile Levosimendan  başlandı. Mediyan sternotomiyi takiben standart aorto-bikaval kanülasyon yapıldı. KPB’ ye girildi hasta soğutulmadı ve kros-klemp konmadı. Normotermik çalışan kalpte, hasta baş aşağı pozisyonda ve aortik vent maksimum vent ederken sol atrıyotomi yapılarak mitral kapağa ulaşıldı. Anterior leaflet kalınlaşmış ,fibrotik ve prolapsus mevcud idi, posterior leaflet fibrotikti ve tamire uygun değildi. Subvalvuler aparatusun tamamı korunarak (anterior ve posterior leafletler serbestlenerek pledgitli dikişlerle annulusa tespit edilerek orifis sağlandı, kordalar korunarak ventrikül geometrisi korundu) tek tek pledgitli süturlarla 27 no St jude medical mekanik kapak ile MVR yapıldı. Sol atriyotomi kapatıldı, hava çıkarıldı, 5mcg dopamin ve levosimendan infüzyonu eşliğinde kardiyopulmoner bypass’tan sorunsuz çıkıldı. Dekanülasyonu sorunsuz yapılan hastanın komplikasyonsuz olarak ameliyatı tamamlandı. Hastanın CPB süresi 80dk., operasyon süresi 160dk. idi.  Postoperatif takibinde sorun olmadı. Hasta postoperatif 3. satte uyandı, serebrovasküler olay olmadı ve 15. saatte extübe oldu. Hastanın yoğun bakım takiplerinde hemodinamisi stabil seyretti. Postoperatif 1.günde servise alındı. Postop bakılan rutin tetkiklerinde problem olmayan hasta postop 5.günde şifa ile taburcu edildi.

 

OLGU SUNUSU 2

63 yaşında bayan hasta ciddi nefes darlığı ve eforla gelen çarpıntı şikayetleriyle başvurdu. Hastanın NYHA ya göre fonksiyonel kapasitesi III idi. Muaynesinde  tansiyon:130/60mmHg, nabız:92/dk ve aritmik idi. Dinlemekle apekste 4/6 sistolik üfürüm mevcuttu.. Hastanın NYHA fonksiyonel kapasitesi III idi. Telekardiyografi de bilateral akciğer bazal zonlarda hafif yüklenme bulguları ve kardiyomegali vardı. Hipertansiyon’u olan hastanın Elektrokardiyogramda ritmi Atriyal Fibrilasyon idi.EKO bulgularına bakıldığında ;6.8CM ,LVESÇ:5.8CM, EF:%29, 3OMitral Yetmezlik , CPAB:34mmHG , sol atrium dilate, Posterior mitral valve sistolik hareketi kısıtlı,inferior daha belirgin olmak üzere global hipokinezi şeklindeydi. Yine standart prosedür sonrası çalışan kalpte sol atriyotomi yapıldı.Venöz kan geldiği görüldü.Subvalvuler aparey uzamış,incelmiş ve tamire uygun değildi.Anterior ve posterior leafletler korunarak 27 no ST.JUDE MEDİCAL metal kapak replasmanı ve secundum ASD primer tamiri yapıldı.CPB’den sorunsuz çıkıldı.CPB süresi:91 dk..Hasta postoperatif 14.saatte sorunsuz extübe ve postop 6.günde şifa ile taburcu edildi.

 

TARTIŞMA

Levosimendan, hücre içi kalsiyum düzeyini ve oksijen tüketimini  artırmaksızın, kontraktiliteyi arttırabilen ve dekompanse kalp yetmezliği ile CPB’den ayrılmakta zorlanan postoperatif hastalarda kullanılan yeni nesil bir pozitif inotrop ilaçtır. Levosimendanın miyokardiyal kontraktiliteyi artırmadaki asıl etki mekanizması sitoplazmik kalsiyuma kardiyak troponin-C’nin duyarlılığını artırmasına dayanır.(4). Bu inotropik etki sırasında hücre içi kalsiyum düzeyinin artmaması en önemli özelliktir; bu sayede adrenerjik inotropların neden olduğu hücre içi kalsiyum artışına bağlı kardiyak miyosit disfonksiyonu ve aritmi gibi önemli yan etkiler önlenmiş olur. Levosimendan ile diyastolik gevşeme bozulmadığı gibi kalbin hem önyükünü hemde ardyükünü azaltır.Bu süreç miyokardın oksijen tüketimini artırmadan meydana gelir. Ayrıca, koroner arterlerde dilatasyon yapıcı etkisi nedeniyle levosimendanın anti-iskemik etkisi söz konusudur. (4,5)

Çalışan kalpte CPB eşliğinde düşük ventrikül fonksiyonlu hastalarda kardiyak fonksiyonlar daha iyi korunabilir. Çalışan kalpte CPB eşliğinde yapılan mitral kapak cerrahisinde kardiyopleji solusyonu verilmediği için miyokard reperfüzyon hasarından korunmuş olduğu gibi,koroner perfüzyon da devam etmektedir.Normotermi sayesinde kardiyak fizyoloji devam etmektedir .(1,6) Posterior leafletin korunmasının postoperatif dönemde sol ventrikül fonksiyonlarına olan olumlu etkilerinin kabul görmesinden sonra mitral kapak apareyinin bütünüyle korunmasına yönelik uygulamalar sürdürülmektedir. Mitral kapak apareyinin işlevi sadece kapak fonksiyonları ile sınırlı kalmayıp, sol ventrikül fonksiyonlarında önemli bir yeri vardır.  Sınırlı sayıda yapılmış olan klinik çalışmalarda, teknik farklı da olsa sonuç olarak daima kapak apareyinin korunmasının sol ventrikül fonksiyonlarını koruduğu ya da iyileştirdiği bildirilmektedir (7-11).  Mitral kapak replasmanı sonrasında oluşan ani afterload artışının yanısıra, kordal yapıların çıkarılması sonucunda annuler-kordal-papiller-adale-sol ventrikül duvarı devamlılığının bozulmasının, postoperatif erken dönemde sol ventrikül disfonksiyonuna katkısının olduğu, birçok yazar tarafından bildirilmiştir. Yine bu yazarlar, mitral yetmezliğinde onarım tekniklerinin uygulanmasından sonra alınan daha iyi hemodinamik sonuçları ve düşük mortaliteyi bu tekniklerde annuler-papiller-ventriküler devamlılığın korunmasına bağlamaktadırlar (8-9). Kronik mitral yetmezlikli hastalarda, replasman sonrasında sol ventrikül disfonksiyonunun en önemli nedeninin, mitral yetmezlik sırasında sol atriuma olan düşük impedanslı akımın kapak replasmanı sonrası ortadan kalkması ile oluşan ani afterload artışı sonucu, sol ventrikül duvarında oluşan gerilimin olduğu kabul edilir. Sol ventrikülün, bu ani gelişen afterloada karşı koymak için kordal gerilimin devam etmesine ve papiller adelelerin tutundukları bölgede destekleyici etkilerine mutlak ihtiyaç vardır. Sol ventrikül, özellikle diastolik boyutlarını ve kasılma esnasında ideal geometrisini devam ettirerek, kavite basıncının artmasını engelleyerek, kontraktil fonksiyonlarını koruyabilir (9-11).   Bu olgularda anterior leaflet annulusa 2-3 mm mesafeden kesilerek kordal bağlantılara zarar vermeyecek şekilde pledgitli süturlarla annulusa tespit edilerek mitral orifis genişletildi.  Fazla kapakçık dokusu traşlandı. Posterior leaflet doğal haliyle bırakıldı.

 Burada özellikle anterior yaprağın da bütünüyle korunması  anterior yaprak dokusunun sistolik öne hareketi ile sol ventrikül çıkış yolu obstrüksiyonuna neden olabilir.Bu nedenle ideal bir orifis sağlanmalıdır. İkinci potansiyel problem, korunan papiller adele ve onun kordalarının, takılan protez kapakla olan olumsuz etkileşimi sonucunda gelişen, protez kapak disfonksiyonudur. Sonuç olarak saf mitral yetmezliği veya hemodinamik olarak mitral yetmezliği önemli olan romatizmal mitral kapak hastalarında mümkünse rekonstrüktif cerrahi, rekonstrüktif cerrahi için uygun olmayan hastalar için alternatif cerrahi olarak subvalvüler apareyi tamamen koruyarak mitral kapak cerrahisi yapılmasının uygun olduğunu düşünüyoruz.Çalışan kalpte kardiyopulmoner bypass kullanılarak mitral kapak cerrahisi teknik olarak kullanımı kolay ve komplikasyonları diğer konvansiyonel yöntemlere göre daha az olabilir (1). Bu hastada düşük EF li ve kardiyak cerrahinin yüksek riskli olduğu olgularda hem levosimendanın etkilerinden faydalanarak,hemde kardiyak fonksiyonları çalışan kalpte daha iyi koruduğumuzu düşünerek iyi bir sonuç aldık. Yine de daha ileri deneyimler bu konudaki bilgilerimize katkı sağlayacaktır.

 

KAYNAKLAR

 1. .On-pump beating heart mitral valve surgery without cross-clamping the aorta.Katircioglu SF, Cicekcioglu F, Tutun U, Parlar AI, Babaroglu S, Mungan U, Aksoyek A. J Card Surg. 2008 Jul-Aug;23(4):307-11.

 2.  Hani AH, Michael J, Cristopher DS: Left ventricular func- tion in experimental mitral regurgitation with intact chordae tendineae. Thorac Cardiovasc Surg, 1993;105:624-32.

 3.  Yutaka O, Shigehito M, Kenzi K: Analysis of Left vent- ricular motion after mitral valve replacement with technique of preservation of all chordac tendineae. J Thorac Cardiovasc Surg, 1992; 104:786-95

 4.  Haikala H, Linden IB. Mechanisms of action of calcium-sensitizing drugs. J Cardiovasc Pharmacol 1995;26 Suppl 1:S10-9

 5 .Hasenfuss G, Pieske B, castell M, Kretschmann B, Maier LS, Just H. Influence of the novel inotropic agent levosimendan on isometric tension and calcium cycling in failing human myocardium. Circulation 1998;98:2141-7.

J Card Surg. 2008 Mar-Apr;23(2):156-8. 

 6. Mitral valve replacement on a beating heart through right thoracotomy in a patient with patent coronary grafts.Ciçekcioğlu F, Tütün U, Parlar AI, Aksöyek A, Babaroğlu S, Katircioğlu SF.

Anadolu Kardiyol Derg. 2007 Jun;7(2):247-8.

 7. Yutaka O, Shigehito M, Kenzi K: Analysis of Left vent- ricular motion after mitral valve replacement with a technique of preservation of all chordac tendineae. J Thorac Cardiovasc Surg, 1992; 104:786-95.

 8. Hani AH, Michael J, Cristopher DS: Left ventricular func- tion in experimental mitral regurgitation with intact chordae tendineae. Thorac Cardiovasc Surg, 1993;105:624-32.

 9 . David EH, George EH, Marek AN: Physiologic role of the mitral apparatus in left ventricular regional mechanics, con- traction synergy, and global systolic performance. J Thorac Cardiovasc Surg, 1989;97:521-33.

10. Vincenzo D, Luca B, Antonio L: Inital experience of mitral valve replacement with total preservation of both valve leaflets. Texas Heart Institute Journal, 1994;21:215-9.

11. John DR, Blase AC, Bruce WU: Mitral valve replacement with and without chordal preservation in patients with choronic mitral regurgitasyon. Circulation 1992;86:1718-26

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.Percutaneous transcatheter closure of patent foramen ovale in patients with paradoxical embolism.

Cryptogenic stroke remains the final diagnosis in 40% of ischemic acute cerebrovascular events. Until now there are no clinical evidences that the percutaneous closure of patent foramen ovale (PFO) is able to prevent the recurrence of stroke or transient ischemic attack (TIA).¹-² Stroke is the leading cause of disability and the third leading cause of death in the developed Countries. Stroke by cardiac source is provoked by various reasons, but PFO, especially if associated with atrial septal aneurysms (ASA) is among the most frequent  and complex to investigate . Identifying the cause of neurologic  ischemic syndromes is essential to any strategy intended to prevent the catastrophic consequences of cerebral infarction. Since the initial reports of unexpectedly high prevalence of in younger patients with cryptogenic stroke appeared in 1998, there has been growing interest and experience in diagnosing and treating these patients both medically and/or with percutaneous closure in particular for the potential to eliminate paradoxical embolism via PFO that is a likely mechanism for stroke in these patients. ³-4 The aim of this study was to evaluate the incidence of recurrence of stroke and/or TIA in patients successfully treated percutaneously by using five different well established occlude devices through transcranial Doppler(TCD), transesophageal echocardiography(TEE) and clinical evaluation. Moreover we try to understand whether the selection of the device can influence the outcome in the middle and long term follow-up.
Material and methods.

From February 2004 to November 2009, 72 consecutive patients, (40 females and 32 males), average  age 46 years, range 14-66), admitted with diagnosis of recurrent ischemic neurologic events(58 stroke and 14 TIA) confirmed by cerebral imaging, underwent percutaneous closure of PFO by using five different occlude devices. Three PTS were scuba-divers and 31 (44%) of the 72 PTS had  a concomitant history of migraine, 16 of whom(51%, that is the 22%of total amount )with aura. In 18 pts (25%) the PFO was associated with ASA. According our protocol, the gold standard  method for diagnosing PFO in symptomatic patients was been TEE  (5) associated  with TCD evaluation. The TEE was performed during intravenous injection of agitated saline as a contrast agent, usually accompanied by provocative maneuvers as Valsalva. TCD was performed with intravenous agitated saline in all patients generally without sedation according to the Venice Consensus Conference in 1999 and showed the appearance of reflective bubbles in the intracranial circulation with or without “curtain” effect. Provocative measures are imployed, and the timing of the appearance of contrast after such maneuvers allowed to distinguish between intracardiac and extracardiac (e.g. pulmonary arteriovenous fistula) shunts. In all patients  a permanent from moderate to severe right-to-left shunt was found . PFO length generally range from 4mm to 25 mm(average 12-13 mm). patients with alternative or additional sources of thromboemboli( atrial fibrillation, deep  vein thrombosis) 6 were exclude from the percutaneuos treatment. The detection of inherited  thrombophilic disorders, in particular factor V Leiden and prothrombin gene mutation in six patients of our opulation study since is a risk factor of paradoxical embolism in subjects with PFO, in our thought, did not represented a contraindication for percutaneous  closure. The selection of the appropriate  occlude device was made taking in account the morphology of the defect (septum primum and septum  secundum characteristics) and the association with an aneurysms of a fossa ovalis (ASA) defined according  the definition of Mugge et al. (7)  as an interatrial septum of abnormal mobility with protrusion of the septum into the left or right atrium of leatst  10 mm beyond baseline , or with other atrial defects. Altogether , 74 occluder device s were implanted. In particular , we implanted 27 Premere  Occlusion System (St Jude Medical Inc., Maple Grove, MN, USA), 28 Amplatzer Occluder , 12 Atriasept, 5 Biosatar (NMT Medical Inc, Boston, MA, USA), 2 Solysafe System . In two patients implantation of a double devce was performed due to the persistence of a moderate  right to left shunt after the procedure. The Amplatzer PFO or cribiform device was selected in case of highly redundant and floppy septum primum, associated ASA, or when septum primum tissue  was plentifully defective or showed  multifenestrated aspect. The Premere device, due  to its low profile, was chosen in case of tunnel –like morphology especially with very long channels (>15mm), in absence of ASA, in presence of a PFO with minimal distance between the two septa and a medium or long  longitudinal diameter . The Atriatsept was selected in those patients presenting  a septum  secundum very thick or complex  connections between the two septa. The introduction of intracardiac  echocardiography (8)  (ICE) Acunav 8fr, Acuson Siemens) has made intraprocedural TEE necessary only in the first 12 treated patients of our series, so the procedure was performed using local anesthesia under mild conscious sedation in less than 20 minutes in almost all patients . Bilateral venous access was gained via the right and left femoral vein and the PFO was catheterized using a multipurpose  catheter under ICE guidance. The difference  occluder devices were implanted in accordance to the specific Company implantation recommendations. All patients received 100IU/Kg heparin i.v. at the time of the procedure and antibiotic prophylaxis. All treated patients were studied during the follow-up by clinical neurologic evaluation (Rankin modified scale)and TCD with microbubbles test in basal condition and after Valsalva manoeuvre at 6 months and by transthoracic echocardiography at 1.6 and 12 months. If at 6 months a moderate  shunt is detected (>10 microbubbles ), transesophageal echocardiography was performed. The follow-up was 100% complete in all treated patients.

Results.
Successful device deployment is achieved in 100% of patients without any intra or periprocedural major complication. Only in two patients atrial arrhythmia have occurred: in one case within the first hours after catheter-based therapy and and spontaneously cessed, while in the second successful DC shock cardioversion  was performed at the end of the procedure. In the follow-up period only one patient developed some episodes
In the follow-up period only  one patient developed some episodes of paroxysmal supraventricular tachycardia that convert back to sinus rhythm spontaneously. Significantly, the use of a double vein approach for ICE probe introduction and implantation procedure did not increase the overall incidence of periinterventional vascular complications (1 patient with a small arteriovenous fistula which didn't require surgical treatment but only pressure bandage). All pts were discharged within 3 days in good overall conditions.In all pts a double antiplatelet regimen was adopted for 3-6 months. All patients received a scheme for prophylaxis of bacterial endocarditis as usually recommended for all adult congenital heart diseases. The follow-up was complete in 100% of the cases (median 30, range 3-58 months). At five years of follow-up there was no recurrent episode of stroke and/or TIA documented by nuclear magnetic resonance (NMR) and neurological examination, and no cases of recurrence of acute cerebrovascular events was observed in older patients irrespective of the device used. Moreover, in 52 of them (89.6%), the Rankin scale reduced to 0 whereas only in 4 patients score 1 was reached. In 19 of the 31 patients with concomitant migraine (61%), the intensity and the frequency of the attacks decreased over time in particular in those forms of migraines preceded by aura, while the others form of headache don't  seems to improve particularly after the closure. At 6 months TCD, 3 patients resulted slightly positive for microembolic signals (10-12 HITS detected one of them after Valsalva manoeuvre), while in 2 patients a moderate right-to-left shunt (22 and 34 HITS without curtain effect and only after Valsalva manoeuvre) was detected despite the optimal sealing of the implanted device and the absence of any device-related thrombotic formation. All these patients received an Amplatzer PFO or cribriform device. However, no recurrent neurological event occurred documented at the MRI evaluation performed in these patients and the contrast- TEE performed confirmed the presence of residual shunt in all five patient except one. In our experience it's important to perform TCD starting from the 6 month from the procedure because the endothelisation process is almost complete. The TTC evaluation at 1,6 and 12 month showed an optimal sealing of all device, without any signs of erosion, malapposition, dislodgement or incomplete closure and thrombus formation around the device.

Discussion
Stroke represents the major cause of disability in most European populations, contributing in large part to the escalating costs of health care. In particular cryptogenic stroke is a devastating experience since affected young, full force, healthy persons and their familial entourage. 9,10 Form this point of view, it's important to offer a safe and less invasive therapeutic chance to these kind of patients that minimizes the treatment and allows the patient to timely undergo rehabilitation program. Our experience suggests that percutaneous treatment of PFO appears safe and beneficial for secondary prevention since it is able to prevent the clinical recurrence of acute cerebrovascular events reducing the incidence of these  latter nearly to 0% and making our results comparable or less frequent to others surveys.11,12 This is true also in elderly treated patients. Moreover, the remarkable improvement of the Rankin scale in patients admitted with stroke diagnosis (who are the majority), demonstrated that the catheter-based therapy is effective not only for secondary prevention but also in terms of improvement of considerable improvement in migraine attacks frequency and or intensity after PFO closure (61%), especially in those patients whose migraine is preceded by aura, is in line with the literature data 13, 14 and can offers in some cases a cure since migraine represents today an important health problem accounting for a high social cost due to the fact that heavily affect the quality of life, not to mention that, some observational studies reported that migraine may be for itself a risk for subclinical brain lesions and stroke.15 The principal determinant of a successful procedure is the choice of the appropriate device for the specific morphology of the defect. Our experience suggests that the effectiveness of each kind of occluder device is likely to depend form different anatomy of the defect. The foramen ovale has a various anatomic configuration, and therefore the transesophagel echocardiographic evaluation prior of treatment is essential for the catheter-based strategy. The morphology of foramen ovale show a remarkable variability from case to case, both from a pathological and echocardiographic point of view. Some aspects can have great relevance form a clinical and or technical point view in relation to a possible closure procedure and therefore must be carefully investigated by transesophageal evaluation. When the defect has a tunnel-like morphology especially with very long channels (>15 mm), in absence of ASA, or when minimal distance between the two septa and a medium or long longitudinal diameter are found, the most performing device in terms of lower mechanical impact over interatrial septum is, the Premere occluder device; this latter has demonstrated its validity also during the follow-up period since no residual shunt was detected at TCD evaluation in all 27 patients that received it and all the patients remained asymptomatic. Similar good performance showed the Atriasept and Biostar  device even thought a small number of patients received them. Notably the Atriasept device due to its high flexibility is especially suitable for very thick septum secundum until some pictures of "lipomatous septum" observed, in which the thickness is more than 1 cm. On the other hand, five patients revealed in the follow-up period a residual right-to-left shunt, remaining however asymptomatic, and all received an Amplatzer device. In all these patients the PFO was associated with ASA. This finding can be partially explained by the consideration that the complexity of the atrial defect, the larger PFO diameter, a multifenestrated anatomy and the associaton with ASA and remnants structures as Eustachian valve and Chiari's network founded in these patients prior to closure has required the use of a device3, as the Amplatzer, with an higher mechanical impact and a more ability to stabilize the atrial septum between the two discs of the device. The presence of ASA is often associated with large tunnel PFO and relevant right-to-left shunt and this seems to increase the risk of stroke in these patients. Infact the coexistence of PFO and ASA results in a two-to fourfold increase in the risk of recurrent thrombo-embolic events in patients with cryptogenic stroke as compared to patients with PFO alone. 16 Moreover the aneurysm morphology is more often associated with persistent remnants venous valves that, according with what was recently reported, seems for itself increase the risk for stroke.17 The Chiari's network is a remnant of the right valve of the sinus venosus and is constitutes from  a network of thin filaments poorly echoic originates from a region of the eustachian valves with attachment the upper wall of the right atrium or atrial septum, floating inside the right atrium. The eustachian valve is a membranous structure, with high eco-reflectivity that extends from the junction between the inferior vena cava and right atrium, with in the right atrium, toward the entrance of PFO. The Eustachian valve is considerate reduntant when his lenght exceed 10 mm. A recent study using contrast enhanced TEE found a frequent association between Chiari's network and PFO and between large right-to-left shunting and Chiari's network. This study also detected Chiari's network in 24% of patients with ASA. Moreover the Chiari's network is more common in cryptogenic stroke patients than in patients evaluated for other indications and it may facilitate paradoxic embolism.18 In two patients with residual shunt treated with cribrioform Amplatzer device, the analysis performed prior to closure by TEE, showed a septum primum widely defective containing multiple fenestrations: they are small interatrial communications in the context of septum primum, more frequently associated with ASA. They are located in contiguity with the entrance of PFO in the right atrium, or near to the entrance of inferior vena cava in the right atrium, in the inferoposterior portion of the septum primum. They must be carefully sought at TEE since can be a cause of significant residual right-to-left shunt after transcatheter closure of PFO. In follow-up, we observed that if TCD is negative, no further examination may be necessary; whereas in all cases in which TCD showed a residual shunt, it is advisable to perform a TEE investigation. In conclusion in patient with history of cryptogenic thrombo-embolic events potentially correlated to the presence of PFO a carefully anatomic and functional evaluation of the morphology of the defect with TEE is mandatory for any strategy intended to close the PFO and the associated defects. On the other hand transcatheter -based therapy in symptomatic patients is a safe and effective procedure and has demonstrated on the medium term follow-up the potential to reduce the risk of recurrent neurological events irrespective of the five devices used appeared basically superior over the others. The present study showed that beside the extensive use of consolidates devices a reasonable good outcome, that required further studies with a larger patient population, was observed in particular with the use of Premere occluder device.

References.
1. Sacco RL, Ellenbergh JH, Mohr JP, Tatemichi TK, Hier DB, Price TR et al. Infract of undetermined cause: the NINCDS Stroke Data Bank. Ann Neurol 1989;25:382-90.
2. Sherman DG. Prevention of Cardioembolic Stroke. In: Norris JW, Hachinski VC,editors. Prevention of Stroke. New York, NY: Springer Verlag; 1991.p.149-59.
3. Lechat P, Mas JL, Lacault G, Loron P, Theard M, Klimczac M et al. Prevalence of patient foramen ovale in patients with Stroke. N Engl J Med 1988;318:1148-52.
4. Webster MW, Chancellor AM, Smith HJ, Swift DL, Sharpe DN, Bass NM et al. Patent foramen ovale in young stroke patients. Lancet 1988;2:11-2.
5. Cabanes L, Mas JL, Cohen A, Amarenco P, Cabanes PA, Oubary P et al. Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age: a study using transesophagel echocardigraphy. Stroke 1993;24:1865-73.
6. Cramer SC, Rordor G, Maki JH, Kramer LA, Grotta JC, Buring WS et al. Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical Emboli formLarge Veins in cryptogenic stroke (PELVIS) study. Stroke 2004;35:46-50.
7. Mugge A, Daniel WG, Angermann C, Spes C, Khanderia BK, Kronzon I et al. Atrial septal aneurysm in adults patients. A multicenter study using transthoracic and transesophageal echocariography. Circulation 1995;91:2785-92.
8. Zanchetta M, Rigatelli G, Onorato E. Intracardiac echocardigraphy and transcranial Doppler ultrasound to guide closure of patent foramen ovale.J Invas Cardiol 2003;15:93-6.
9.Di Tullio M, Sacco RL, Gopal A, Mohr JP, Homma S. Patent foramen ovale as a risck factor for cryptogenic stroke. Ann Intern Med 1992;117:461-5.
10. Bogousslavsky J,Garanzi S,Jeanrenaud X, Aebischer N, Van Melle G. Stroke recurrence in patients with patent foramen ovale. The Lausanne Study. Lausanne Stroke with Paradoxical Embolism Study Group. Neurology 1996;46:1301-5.
11. Windeker S, Wahl A, Chatterjee T, Grachemani A, Eberli FR, Seiler C, Meier B. Percutaneous clouse of patent foramen ovale in patients with paradoxical embolism: long-term risk of recurrent thromboembolic events. Circulation 2000;101:893-8.
12. Martin F, Sanchez PL, Doherty E, Colon-Hernandez PJ, Delago G, Inglessis I et al. Percutaneous transcatheter closure of patent foramen ovale in patients with paradoxical embolism. Circulation 2002;106:1121-6.
13. Schwerzamann M, Wiher S, Nedelttchev K. Percutaneous closure of patent foraman ovale reduces the frequency of migraine attaks. Neurology 2004;2:1399-401.
14. Giardini A, Donti A, Formigari R, Salomone L, Prandstraller D, Bonvicini M et al. Transcatherter patent foramen ovale closure mitigates aura migraine headaches abolishing spontaneous rigth-to-left shunting. Am Heart J 2006;151:922. E 1-5.
15. Ferrarini G, Malferrari G, Zucco R, Gaddi O, Norina M, Pini LA. Hight prevalence of patent foramen ovale in migraine with aura. J Headache Pain 2005;6:71-6.
16. De castro S, Cartoni D, Fiorelli M,Rasura M, Anzini A, Zanette EM et al. Morphological and functional characteristic of patent foramen ovale and their embolic implications. Stroke 2000; 31:2407-13.
17. Rigatelli G, Dell'Avvocata F, Braggion G,Giordan M, Chinaglia M, Cardaioli P. Persistent venous valves correlate with increate shunt and multiple preceding embolic events in patients with patent foram ovale: an intracardiac echocardiographi study. Cathete Cardiovasc Interv 2008;72:973-6.
18. Schneider B, Hofmann T, Justen MH, Meinertz T. Chiari's network : normal anatomic variant or risk factor for arterial embolic events? J Am Coll Cardiol 1995;26:203-10.

 

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New Type of Pump for the Heart-Lung Bypass System
Khodeli N.1, Shengelia O.2, Chkhaidze Z.1, Partsakhashvili D.3, Sologashvili T.4
1. Tbilisi State University, Medical Faculty; 2. Department of Technological Researches of Philips Corporation; 3. Scientific-training Center of Experimental Surgery; 4. Open Heart Clinic

Majority of currently operating systems of artificial blood circulation for heart-lung bypass applies roller pumps as injecting units [4, 7]. Though currently these units and their control systems are very well developed, number of authors report on complications in the process of their functioning. Complications, related to the constructional characteristics of the roller pumps declare themselves in a form of homeostasis disorder of various degrees, buffer deviations, centralization of blood circulation, accumulation of sub-oxide products, impairment of entirety of membranes of the blood cells etc. [1, 3, 10, 13]. Non-physiological blood flow, caused by the roller pump in the aorta and large vessels is regarded as the major reason for such complications. Numerous attempts of some authors to replace the roller pumps with other pressurizing devices [2, 11] remained within the experimental laboratories. At the same time, there exists the reliable alternative to the roller pumps – the artificial heart ventricles, which form in the arterial bed the flood flow maximally close to the physiological, excluding traumas of the blood cells [6, 12]. Ventricular Assist Device are widely applied in clinics as the systems of assisted blood circulation, though they are not used in the HLB machines. Supposedly, this is caused by their high prices.

Goal of the research: development of new, simple and cheap perfusion device for HLB machines and study of their hydrodynamic characteristics in the experiments with animals.

Materials and methods: as a basis model of the pump we used the device developed in our laboratory [9]. In the pump module of the developed device the blood accumulation and its forcing function was unified in two hermetic transparent reservoirs with rigid walls, with the volume selected for given experimental animal. For simplification of assembling of the experimental pump devices (see Fig. 1) used for relatively large test animals we employed cardiotomic reservoirs of used traditional children’s disposable HLB systems, with volume of 1000 ml each. In the assembly scheme of each perfusion machine two such reservoirs were located before membrane oxigenator on the level of surgical table. Two inlet jets for blood (inner diameter up to 6 mm) of each of the reservoirs were connected with each other and supply venous trunk (inner diameter up to 10 mm). Outlet jets are connected with each other and the trunk leading to the oxigenator (inner diameter up to 6 mm). In each of the reservoirs the jets of the air outlets are connected with the pneumatic receivers of positive and negative pressures with special external valves controlled electronically, included into the pump unit, provided filling of one of the reservoirs, creating negative pressure in it, if the outlet trunk is closed and simultaneously, from the other reservoir there was provided pressurizing, supplying positive pressure with the closed inlet trunk. In the trunk connecting the outlet of oxigenator with the inlet of arterial filter there was placed the external pulsating unit also included into the pump unit. Electronically controlled pulsating unit, pressing the trunk to certain level, allowed changing of the frequency of contractions, steepness of growth and fall of pressure (dp/dt) and duration of systole and diastole. In the control system there is also included the unit for control of the level of liquid in the reservoirs and switch of valves, regulating sequence of functions of letdown and pressurizing. For use of the perfusion system on small laboratory animals only the volume of the pump reservoirs and diameters of connecting trunks were changed. Thus, the total volume of system filling was changed.
Monitoring of the pneumatic pressure in the chambers of the reservoirs and pressure of pulsation frequency, volume of blood flow in the connecting trunks and vessels of the biological model was pro­vided by means of the electromagnetic sensors of polygraph "Mingograf-81" - Elema Shonander (Sweden) and flow meter “Nihon Kohden” (Japan). In the experiments with the animals there was also measured the temperature in the rectum and oesophagus and cardiogram was made. Acid-base condition of the blood was measured by means of gas analyzer “Astrup” – Denmark.

Results and consideration. Stand tests were conducted with the purpose of determining of hydrodynamic capacities of the pump device and reliability of its control system. They allowed for identification of basic characteristics of the pump device and the machine as a whole. The system, assembled entirely on the vertical holder allows for maximal approach to the object of perfusion, thus significantly reducing the volume of filling [8]. In the closed regime of circulation, with 6-mm connecting trunks capacity of the machine was 8.5 l/min. Pressure on the outlet trunk was regulated within 0 – 300 mmHg and within the system it mainly was dependent on resistance of oxigenator and arterial filter. In the regime “Stop” levels of the liquids in the pump reservoirs was maintained unchanged and this did not require pressing of the trunks. Pump control system allowed for creation of both, laminar and pulsating flow of the liquid on the outflow trunk.
The perfusion system was tested in the acute experiments (14 experiments) on the mongrel dogs of both sexes, with up to 20 kg weights, on which, in the conditions of intravenous narcosis and sternotomy, by means of standard techniques, there was conducted cannulation of the vena cavas and aorta. The perfusion system was filled with the blood substitute (total volume of filling was 900 – 1000 ml of Ringer’s solution with 5000 units of heparin), in the recirculation process there were removed the bubbles of air and the system was stopped. Arterial trunk was connected from the filter to the aortal cannula and the inflow, venous trunk - to the triple connection of the venous cannulas. The parallel heart-lung bypass in the direction of blood flow was commenced in one of the pump reservoirs. After its filling to the conditional mark (corresponding to 700 ml), flow of venous blood was directed to another reservoir and to the first one, air was supplied from the receivers under the pressure (150-200 mmHg). Thus, the blood pressing through the arterial filter into aorta was commenced. Capacity of the system was no more than 1200 ml/min. Redistribution of blood in the reservoirs, as well as providing pressure and relieve in turns in the chambers was provided automatically from the control system. We conducted simultaneous normothermal perfusion with the operating heart and natural oxygenation for the period up to 1 hour. Further we provided full HLB, carrying out cardioplegia, clamping aorta and terminating artificial ventilation of lungs. Duration of full heart-lung bypass achieved 3 hours. Systolic pressure was maintained within 120-130 mmHg; diastolic – 70 – 80 mmHg (average pressure in the femoral artery for entire period of perfusion was no less than 75 mmHg). Volume velocity of blood flow in the arch of aorta was within 950 – 1100 ml/min and in the femoral artery – 60 – 80 ml/min.
Regarding requirements of the experimenters in this sphere [5] there was developed miniature version of the perfusion system, tested in the first experiments on 17 rats, to which it was connected by the scheme: left middle – descending aorta, with retrograde pressurizing of blood (without occlusion of ascending aorta, in the conditions of cold cardioplegia (fibrillation of the ventricles). As a result of full heart-lung bypass in 13 cases there was observed spontaneous restoration of heart operation after 30-minute perfusion. In no one of the conducted experiments hemolysis was not observed in the blood tests.   

Conclusion. First attempts of operation in the experiments on non-traditional systems of heart-lung bypass and pulsatile perfusion showed possibility of achievement if hemodynamic characteristics identical to physiological ones. In comparison with the traditional machines the system has minimal volume of filling and does not damage blood cells. Constructive pumping system and entire perfusion system are quite simple and the control system allows achievement of hemodynamic characteristics maximally close to physiological ones. In addition, the system could be applied on the experiments on both, large and small experimental animals.

REFERENCES

1. Зацепина Н.Е. Влияние некоторых параметров перфузии на функциональную характеристику тромбоцитов. //  Анестезиол. и реанимат.-1999.-№5.-С.32-4.
2. Ходели Н.Г., Гиоргадзе О.П., Григолия Г.Г. Искусственные желудочки сердца в сис­те­мах искусственного и вспомогательного кровообращения: хирургическое, анесте­зиоло­гическое и техническое обеспечение экспериментов // XII конф. хируругов Закавк. госуд. (Матер. междунар. науч. конф.).-Тбилиси.-1999.-Т.2.-С.241-2.
3. Ashraf  S., Bhattacharya K., Zacharias S. et all. Serum S100 release coronary after bypass grafting: roller versus centrifugal pump // Ann. Thorac. Surg.-1998.-Vol.66.-N5.-P.1958.
4. Asimakopoulos G., Smith P.L., Ratnatunga C.P., Taylor K.M. Lung injury and acute respi­ra­­­tory distress syndrome after cardiopulmonary bypass // Ann. Thorac. Surg.-1999.-Vol. 68.-N3.-P.1107-15. 
5. Ballaux P.K., Gourlay T., Ratnatunga C.P., Taylor K.M. A literature review of cardio­pulmonary bypass models for rats // Perfusion 1999.- Vol.14.- N6, p. 411-7. 
6. Chilaia S.M., Khodeli N.G.  Biventricular Bypass: alternative to Univentricular Bypass and Total Artificial Heart-Bridge // Artificial Organs.-1991.-Vol.15.-№5.-P.357-62.
7. Gundry S.R., Romano M.A., Howard Shattuck O.   Seven-year follow-up coronary artery bypasses performed with and without cardiopulmonary bypass.// J.Thorac. Cardiovasc. Surg. 1998.- Vol.115.- N6, p.1273.
8. Khodeli N., Chanturia R., Landau I., Mumladze M. The pulsatile flow device for the heart-lung bypass. Statepatent P 2467. Georgia.1999.
9. Khodeli N., Partsakhashvili D. The pulsatile flow device for the heart-lung bypass. Statepatent P 3975. Georgia. 2004.
10. McCusker K., Lee S. Post cardiopulmonary bypass bleeding: an intraductory review // J. Extra Corpor Technol.- 1999.-Vol.31.-N1.-P.23-36.
11. Mulay A.V., Zacharias S., Hansbro S.D. Should intraaortic ballon countrpulsation be continued during cardiopulmonary bypass? // J.Thorac. Cardiovasc. Surg.-1997.-Vol.114.-N6.-P.1128.
12. Rakhorst G., Hensens A.G., Verkerke G.J. In -vivo evaluation of the "HIA-VAD": a new German ventricular assist device // J.Thorac.Cardiovasc.Surg.1994.- Vol.42.-N3, p.136-40.
13. Sistino J.J., Acsell J.R. Systemic inflammatory response syndrome (SIRS) following emergency cardiopulmonary bypass: a case report and literature review. // J. Extra Corpor Technol 1999.- Vol.31.- N1, p.37-43.

SUMMARY
New Type of Pump for the Heart-Lung Bypass System
Khodeli N.1, Shengelia O.2, Chkhaidze Z.1, Partsakhashvili D.3, Sologashvili T.4
1. Tbilisi State University, Medical Faculty; 2. Department of Technological Researches of Philips Corporation; 3. Scientific-training Center of Experimental Surgery; 4. Open Heart Clinic

Objective: Complications arising from roller pump usage in modern heart-lung bypass (HLB) systems are widely known. alternative to roller pumps has existed as various devices. This work is dedicated to developing new, considerably simpler and less expensive pump device for HLB systems, which provides maximally physiological pulsating blood flow.  
Methods: We used pediatric cardiotomy reservoirs of HLB systems as blood chambers. Two such reservoirs were placed in front of the oxygenator, with their in-flow tubes connected to the venous blood tubes, and the outflow tubes – to the entry to the oxygenator.  In each reservoir, 2 air outlets tubes were connected to pneumo-receivers of positive and negative pressure. We filled up one of the reservoirs whith closed of exit blood tube by creating negative pressure in it. Simultaneously, with closed entry blood tube of the second reservoir, we ejected blood from it by created positive pressure. Used external pulsator.
Results: In stand testing under re-circulation regime, productivity of the device was 12,5 liters/minute. Pressure on exit blood pump was within 0 to 300mm.Hg. The pump operating system enabled laminar, as well as pulsating flow of liquid, with frequency of 0-200 pulses/minute. 
Research is based on experiments conducted on 14 mongrel dogs weighing 20 kg. Standard methodology was used to cannulate Venae cavae and aorta, and to connect perfusion system to body. Duration of complete HLB reached 2 hours.  Systolic pressure was maintained within 120-130mm.Hg.; diastolic  - 70-80 mmHg. Velocity of blood flow in the aorta arc fluctuated within 950-1100 ml/min; in the femoral artery – within 60-80 ml/min.
Conclusion: Preliminary tests of the new pump indicate that its hemodynamic characteristics are maximally approximated to physiological ones.
In comparison to modern machines, a perfusion system with new pump type has minimal volume of fill-up and does not damage formative elements of blood.

Keywords: Pulsatille Flow, Blood Pump, Perfusion

  

Figure 1. Principal Scheme and Phases of Pump Operation

1. First chamber of pump; 2. Second chamber of pump; 3. Air and fluid switching valves; 4. Pulsator;
5. Blood outflow tube from the pmp; 6. Blood inflow tube in the pump; 7. Tubes for creating air ressure and vacuum; 8. Electrical connections to the control system.

А – Phase one (Filling of chamber 1 and emptying of chamber 2). Filling and emptying of pump chambers is regulated by a control block so, that as the first chamber of the pump fills with liquid, the second is emptied. In the beginning position, the second chamber is filled with liquid up to the uppermost punctuated line. The occlusive device 3 cutts off the air pressure tube 8 and opens the vacuum tube 8 in chamber 1.  Simultaniously, the occlusive device 4 cuts off the vacuum tube 9 and opens the air pressure tube 9 in chamber 2. In this manner, liquid through tube 7 gets into chamber 1 and fills up gradually up to the punctuated line. The occlusive device 6 of the outlet tube of chamber 1 is closed, while the occlusive device of outlet tube of chamber 2 opens. In this way, liquid from chamber 2, under pressure injected through pulsator into the outlet tube for liquids.
In the second phase (B) the chamber 1 empties while the chamber 2 is filled. Switching of the occlusive devices is controlled by liquid level sensores in chambers.