A ministernotomia szerepe az aortabillentyű-sebészetben

Absztrakt Bevezetés: A modern aortabillentyű-sebészetben egyre hangsúlyosabbá válnak a kisebb behatolási kapukkal járó sebészeti eljárások. A műbillentyűk technikai fejlődése, különös tekintettel a varrás nélküli billentyűkre, nagymértékben hozzájárul ahhoz, hogy kis műtéti területen, kevés manipulációval, egyszerűen hajtsanak végre aortabillentyű-műtéteket. Célkitűzés: A szerzők célja az volt, hogy a jelen publikációval, a történelmi áttekintés mellett, a minimális behatolással végzett aortabillentyű-cserének módozatait ismertessék, különös tekintettel a varrat nélküli biológiai aortaprotézisek használatára, továbbá hogy a saját műtéti eredményeiket bemutassák. Módszer: A Szegedi Tudományegyetem Szívsebészeti Osztályán még limitált számú, 13 beteg adatainak feldolgozásával a szerzők rávilágítanak a rendszer technikai szükségleteire, a konvencionális teljes sternotomia közötti különbségekre. Eredmények és következtetések: A szerzők megállapítják, hogy a minimális behatolással végzett aortabillentyű-cserének jelentős speciális eszközigénye nincs, technikailag nehezebben kivitelezhető, azonban könnyen tanulható. Az intraoperatív és posztoperatív műtéti eredmények megegyeznek a teljes sternotomiában végzett aortabillentyű-csere eredményeivel, azonban a rövid metszés kevesebb fájdalommal és jelentős kozmetikai előnnyel jár. Orv. Hetil., 2016, 157(23), 901–904

Restricting excessive cardiac action potential and QT prolongation: a vital role for IKs in human ventricular muscle

Background - Although pharmacological block of the slow, delayed rectifier potassium current (I-Ks) by chromanol 293B, L-735,821, or HMR-1556 produces little effect on action potential duration (APD) in isolated rabbit and dog ventricular myocytes, the effect of IKs block on normal human ventricular muscle APD is not known. Therefore, studies were conducted to elucidate the role of IKs in normal human ventricular muscle and in preparations in which both repolarization reserve was attenuated and sympathetic activation was increased by exogenous dofetilide and adrenaline. Methods and Results - Preparations were obtained from undiseased organ donors. Action potentials were measured in ventricular trabeculae and papillary muscles using conventional microelectrode techniques; membrane currents were measured in ventricular myocytes using voltage-clamp techniques. Chromanol 293B (10 mu mol/L), L-735,821 (100 nmol/L), and HMR-1556 (100 nmol/L and 1 mu mol/L) produced a < 12-ms change in APD while pacing at cycle lengths ranging from 300 to 5000 ms, whereas the I-Kr blockers sotalol and E-4031 markedly lengthened APD. In voltage-clamp experiments, L- 735,821 and chromanol 293B each blocked IKs in the presence of E-4031 to block IKr. The E-4031-sensitive current (I-Kr) at the end of a 150-ms-long test pulse to 30 mV was 32.9 +/- 6.7 pA (n = 8); the L-735,821-sensitive current (I-Ks) magnitude was 17.8 +/- 2.94 pA (n = 10). During a longer 500-ms test pulse, IKr was not substantially changed (33.6 +/- 6.1 pA; n = 8), and I-Ks was significantly increased (49.6 +/- 7.24 pA; n = 10). On application of an "action potential-like" test pulse, I-Kr increased as voltage became more negative, whereas I-Ks remained small throughout all phases of the action potential - like test pulse. In experiments in which APD was first lengthened by 50 nmol/L dofetilide and sympathetic activation was increased by 1 mu mol/L adrenaline, 1 mu mol/L HMR-1556 significantly increased APD by 14.7 +/- 3.2% (P < 0.05; n = 3). Conclusions - Pharmacological IKs block in the absence of sympathetic stimulation plays little role in increasing normal human ventricular muscle APD. However, when human ventricular muscle repolarization reserve is attenuated, IKs plays an increasingly important role in limiting action potential prolongation

Electrical Restitution and Its Modifications by Antiarrhythmic Drugs in Undiseased Human Ventricular Muscle

Introduction: Re-entry is a basic mechanism of ventricular fibrillation, which can be elicited by extrasystolic activity, but the timing of an extrasystole can be critical. The action potential duration (APD) of an extrasystole depends on the proximity of the preceding beat, and the relation between its timing and its APD is called electrical restitution. The aim of the present work was to study and compare the effect of several antiarrhythmic drugs on restitution in preparations from undiseased human ventricular muscle, and other mammalian species. Methods: Action potentials were recorded in preparations obtained from rat, guinea pig, rabbit, and dog hearts; and from undiseased human donor hearts using the conventional microelectrode technique. Preparations were stimulated with different basic cycle lengths (BCLs) ranging from 300 to 5,000 ms. To study restitution, single test pulses were applied at every 20th beat while the preparation was driven at 1,000 ms BCL. Results: Marked differences were found between the animal and human preparations regarding restitution and steady-state frequency dependent curves. In human ventricular muscle, restitution kinetics were slower in preparations with large phase 1 repolarization with shorter APDs at 1000 ms BCL compared to preparations with small phase 1. Preparations having APD longer than 300 ms at 1000 ms BCL had slower restitution kinetics than those having APD shorter than 250 ms. The selective IKr inhibitors E-4031 and sotalol increased overall APD and slowed the restitution kinetics, while IKs inhibition did not influence APD and electrical restitution. Mexiletine and nisoldipine shortened APD, but only mexiletine slowed restitution kinetics. Discussion: Frequency dependent APD changes, including electrical restitution, were partly determined by the APD at the BCL. Small phase 1 associated with slower restitution suggests a role of Ito in restitution. APD prolonging drugs slowed restitution, while mexiletine, a known inhibitor of INa, shortened basic APD but also slowed restitution

Kv1.1 potassium channel subunit deficiency alters ventricular arrhythmia susceptibility, contractility, and repolarization

Epilepsy-associated Kv1.1 voltage-gated potassium channel subunits encoded by the Kcna1 gene have traditionally been considered absent in heart, but recent studies reveal they are expressed in cardiomyocytes where they could regulate intrinsic cardiac electrophysiology. Although Kv1.1 now has a demonstrated functional role in atria, its role in the ventricles has never been investigated. In this work, electrophysiological, histological, and gene expression approaches were used to explore the consequences of Kv1.1 deficiency in the ventricles of Kcna1 knockout (KO) mice at the organ, cellular, and molecular levels to determine whether the absence of Kv1.1 leads to ventricular dysfunction that increases the risk of premature or sudden death. When subjected to intracardiac pacing, KO mice showed normal baseline susceptibility to inducible ventricular arrhythmias (VA) but resistance to VA under conditions of sympathetic challenge with isoproterenol. Echocardiography revealed cardiac contractile dysfunction manifesting as decreased ejection fraction and fractional shortening. In whole-cell patch-clamp recordings, KO ventricular cardiomyocytes exhibited action potential prolongation indicative of impaired repolarization. Imaging, histological, and transcript analyses showed no evidence of structural or channel gene expression remodeling, suggesting that the observed deficits are likely electrogenic due to Kv1.1 deficiency. Immunoblots of patient heart samples detected the presence of Kv1.1 at relatively high levels, implying that Kv1.1 contributes to human cardiac electrophysiology. Taken together, this work describes an important functional role for Kv1.1 in ventricles where its absence causes repolarization and contractility deficits but reduced susceptibility to arrhythmia under conditions of sympathetic drive

A szívritmuszavarok és a myocardiális repolarizáció mechanizmusainak vizsgálata; antiaritmiás és proaritmiás gyógyszerhatások elemzése = Study of the mechanism of cardiac arrhythmias and repolarization, antiarrhythmic and proarrhythmic drug action

A kardiovaszkuláris betegségek és azon belül is az életet veszélyeztető kamrai és pitvari aritmiák a fő halálozási okok közé tartoznak a fejlett ipari országokban, de Magyarországon is. Ezzel összhangban, a jelen kutatási projekt is a különböző életet veszélyeztető aritmiák megelőzésének a lehetőségét, és a különböző gyógyszerek antiaritmiás és proaritmiás hatásainak a kutatását tűzte ki célul. Vizsgálataink során megállapítottuk, hogy kísérletes diabetes mellitusban mind kutyán, mind nyúlon az IKs áram és következményesen a repolarizációs rezerv csökkenése következik be amely emberben vélhetően hozzájárulhat e betegségben észlelt hirtelen szívhalál kockázat növekedéséhez. Molekuláris biológiai vizsgálatokban sikerült feltérképeznünk az emberi szívizom különféle ioncsatornáinak denzitását is. A proaritmiás gyógyszerhatások elemzésére újszerű módszert dolgoztunk ki, amelynek gyógyszerbiztonsági klinikai jelentősége és hasznosulása várható. A projekt teljesítése során további új ismereteket szereztünk a Na+/Ca2+ cseremechanizmus (NCX) repolarizációban betöltött szerepét illetően. In vivo kutya kísérletekben vizsgáltuk a peroxynitrit és gap junction csatornák szerepét az ischaemiás prekondicionálásban. Ezek az eredmények várhatóan hozzájárulnak egyrészt a szívizomzat élettani, kórélettani (aritmia mechanizmusok) ismereteinek a gyarapításában, másrészt új és biztonságos antiaritmiás terápiák kifejlesztéséhez. | Cardiovascular diseases, including life threatening ventricular and supraventricular arrhythmias, are the leading causes of mortality in industrialized countries and also in Hungary. In harmony with this, the major goal of the project was to investigate the mechanisms involved in cardiac repolarization and in antiarrhythmic and proarrhythmic drug actions. Representing important findings during the project, we established that in experimental diabetes mellitus the IKs potassium current is down-regulated resulting in the attenuation of repolarization reserve which may contribute to the increased proarrhythmic risk of diabetic patients. Using molecular biological methods we have analyzed the transmembrane ion channel densities of the human heart. To assess proarrhyhtmic drug side effects we developed a novel method which can be expected to contribute to better prediction of proarrhythmic risk in both preclinical and clinical safety pharmacology investigations. During the project, we have gained further insights regarding the role of NCX in the cardiac repolarization process. In in vivo studies we have investigated the possible role of peroxynitrite and gap junctions in ischaemic preconditioning. These results can be expected to help to better understand the physiology and pathophysiology of cardiac muscle, and arrhythmias, and should significantly contribute to the development of safer and more effective antiarrhythmic treatment modalities

Ionic mechanisms limiting cardiac repolarization-reserve in humans compared to dogs.

The species-specific determinants of repolarization are poorly understood. This study compared the contribution of various currents to cardiac repolarization in canine and human ventricle. Conventional microelectrode, whole-cell patch-clamp, molecular biological and mathematical modelling techniques were used. Selective IKr block (50–100 nmol l−1 dofetilide) lengthened AP duration at 90% of repolarization (APD90) >3-fold more in human than dog, suggesting smaller repolarization reserve in humans. Selective IK1 block (10 μmol l−1 BaCl2) and IKs block (1 μmol l−1 HMR-1556) increased APD90 more in canine than human right ventricular papillary muscle. Ion current measurements in isolated cardiomyocytes showed that IK1 and IKs densities were 3- and 4.5-fold larger in dogs than humans, respectively. IKr density and kinetics were similar in human versus dog. ICa and Ito were respectively ∼30% larger and ∼29% smaller in human, and Na+–Ca2+ exchange current was comparable. Cardiac mRNA levels for the main IK1 ion channel subunit Kir2.1 and the IKs accessory subunit minK were significantly lower, but mRNA expression of ERG and KvLQT1 (IKr and IKsα-subunits) were not significantly different, in human versus dog. Immunostaining suggested lower Kir2.1 and minK, and higher KvLQT1 protein expression in human versus canine cardiomyocytes. IK1 and IKs inhibition increased the APD-prolonging effect of IKr block more in dog (by 56% and 49%, respectively) than human (34 and 16%), indicating that both currents contribute to increased repolarization reserve in the dog. A mathematical model incorporating observed human–canine ion current differences confirmed the role of IK1 and IKs in repolarization reserve differences. Thus, humans show greater repolarization-delaying effects of IKr block than dogs, because of lower repolarization reserve contributions from IK1 and IKs, emphasizing species-specific determinants of repolarization and the limitations of animal models for human disease

Infective endocarditis complicated with coronary artery septic embolization: is it worth to be mentioned? Case presentation and review of the literature

Coronary artery septic embolization is a rare, but severe complication of infective endocarditis involving the leftside of the valves. The first case mentioned in the literature was a postmortem finding of a left anterior descending coronary artery occlusion by a vegetation fragment. Since this case, there have been several therapeutic strategies published with this clinical setting including medical treatment, percutaneous coronary angioplasty addressing coronary occlusion, surgical intervention for both the infected valve and coronary embolization, and hybrid procedures with transcatheter septic embolus aspiration followed by surgical valvular interventions. Out of the three interventions mentioned, the latter provided the best results and was in concordance with results observed in a case of mitral valve infected endocarditis complicated with acute occlusion of the left anterior descending coronary artery in patient whose comorbidities included hypertrophic obstructive cardiomyopathy. A transcatheter left anterior descending coronary artery embolus aspiration was performed , followed by a surgical mitral valve replacement and septal myectomy with an uneventful postoperative course. Although rare, this severe complication of infective endocarditis has a specific clinical course and therapeutic strategy, and in our opinion, it could be mentioned as a separate entity among embolic complications of infective endocarditis in future guidelines. Previously published cases suggest that the hybrid intervention might be the therapy of choice for this clinical setting; however, larger studies are necessary for confirmation

Kezdeti tapasztalatok a Sorin Perceval S aorta biológiai billentyű beültetésével [Early experiences with the Sorin Perceval S arteficial biological valve]

OBJECTIVES: We examined the Sorin Perceval S artificial biological valve implantation techniques, and present the initial experiences in our unit. METHODS: In the last 1.5 years, 27 patients had been implanted with Sorin Perceval S biological arteficial valve due to aortic valve disease. The device was mainly used in high-risk patients, in reoperative circumstances, in cases of calcified aortic root, and in elderly patients. RESULTS: The valve implantation time, aortic cross clamp time is shorter, but the risk of the operation cannot be eliminated entirely, because of the high risk patients' severe comorbidities. Furthermore, we performed echocardiography in the postoperative period, which demonstrated that the valve function is excellent, the valve fitted tightly in the anulus, and there was no paravalvular leakage. CONCLUSIONS: The Sorin Perceval S biological arteficial aortic valve is safe to use in high risk patients, and the surgical procedure is easier in case of partial sternotomy, too