Long-Term Ventricular Wall Actuation: Can and Should It Be Systematically Explored?

Abstract: Hearts fail because myocardial power fails. Assist, support, or replacement devices fail, at least in part, because their blood-contacting surfaces fail. Mechanical repowering of a failing heart might circumvent these difficulties by preserving a largely healthy endocardium while correcting the basic deficit, power. Any serious consideration of doing this though must confront some difficult requirements. Effective indefinite support must be coupled with preservation or restoration of valve competence, coronary flow, rapid low-impedance refilling and independent left and right pressures; the avoidance of wall coaptation; hardware that fits in the available space; and unless muscle powered, adaptability to a deliverable form of power. Despite earlier intense interest in acute mechanical devices and later empiric study of muscle wraps, little systematic methodical work has been done on elucidating and meeting these practical requirements. Concerted efforts toward developing research tools and techniques for their study and then finding mechanisms to meet them could well yield one or more effective modalities that circumvent a major obstacle to the indefinite mechanical treatment of heart failure     

Effects of direct mechanical ventricular assistance on regional myocardial function in an animal model of acute heart failure

Direct mechanical ventricular assistance (DMVA) improves hemodynamics in failing hearts without complications associated with a blood/device interface. Epicardial Doppler displacement transducers provide exact measurements of tissue displacement and regional myocardial function (RMF). An in vivo porcine model of acute heart failure was used to examine the effects of DMVA on RMF, which have not been reported before. In 8 anesthetized pigs cardiac output (CO), left ventricular pressure (LVP), aortic blood pressure (BP), systolic contractility (dp/dt max), and systolic wall thickening fraction (WT%) were measured. A multichamber pump system (IMPS) surrounding the left ventricle was implanted and the measurements were repeated. Then acute heart failure was induced by beta-blockade, resulting in a decline of all measured parameters to more than 30% compared to baseline values. In the further course of the experiment, repeated measurements were taken at several intervals with and without DMVA by the implanted device. The IMPS implantation caused no significant hemodynamic changes. Under conditions of acute heart failure DMVA improved LVP (46 +/- 7 to 81 +/- 9 mm Hg), dp/dt max (532 +/- 207 to 744 +/- 361 mm Hg/s), CO (1.5 +/- 0.1 to 1.9 +/- 0.5 L/min) and WT% (19 +/- 7% to 32 +/- 8%). Left ventricular myocardium not directly assisted by external pressure application showed improved regional myocardial function during DMVA. We conclude that DMVA is capable of improving hemodynamics due to extrinsic compression. It also enhances the remaining myocardial function of the failing heart, which might lead to myocardial recovery. These synergistic effects are considered responsible for the high efficiency shown by the IMPS in previous investigations.     

Heterotopic transplantation as a model to study functional recovery of unloaded failing hearts

OBJECTIVES: Recent studies have demonstrated cardiac improvement in patients supported with a ventricular assist device, suggesting that reverse remodeling and myocardial recovery are possible. We developed an animal model of cardiac unloading by adapting a heterotopic transplantation technique and used it to examine the pattern of functional recovery in the left ventricle of the failing heart. METHODS: Heart failure was induced in adult New Zealand rabbits by coronary artery ligation with subsequent myocardial infarction. Animals undergoing sham operation served as a control group. After 4 weeks or 3 months, failing hearts were transplanted into the necks of recipient rabbits. A left ventricular latex balloon connected to subcutaneous tubing allowed repeated physiologic analysis on days 1 and after transplantation and then every 5 days until day 30. RESULTS: Contractility (left ventricular dP/dt(max)) and relaxation (left ventricular dP/dt(min)) were significantly lower in transplanted postinfarction hearts as compared to control hearts immediately after transplantation. Both left ventricular dP/dt(max) and left ventricular dP/dt(min) responses to increased preload and to beta-adrenergic stimulation progressively improved to a significantly higher level after 30 days of left ventricular unloading for the hearts that were transplanted 4 weeks after myocardial infarction. However, this functional improvement was not detected in failing hearts transplanted 3 months after infarction. CONCLUSIONS: This model of cardiac unloading appears at least partially to mimic conditions of ventricular assist devices. If performed early in the development of heart failure, it permits improvement of contractile dysfunction and restoration of cardiac responsiveness to mechanical and beta-adrenergic stimulation. Therefore this model may constitute a novel alternative in the study of reverse remodeling in unloaded failing hearts.     

An artificial myocardium assist system: electrohydraulic ventricular actuation improves myocardial tissue perfusion in goats

Artificial hearts and ventricular assist devices have been widely used clinically to assist patients with severe heart failure. Unfortunately, direct contact between the device and the patient's blood leads to thromboembolic events, and then the need for anticoagulation and infections contribute significantly to complication and mortality. Compressing the dysfunctional heart from its epicardial surface, a nonblood-contacting method of direct mechanical ventricular actuation could provide ventricular support, pulsatile blood flow, and avoid interactions between blood and the surface of the artificial assistance system. An ElectroHydraulic Artificial Myocardial (EHAM) assist system that might assist heart muscle contraction has been developed. The purpose of this study is to determine the efficiency of the EHAM system in perfusing myocardial tissue in an acute animal experiment. METHOD: Healthy adult goats (n = 8) were used in acute animal experiments. A left lateral thoracotomy was done and the chest was opened through the 4th and 5th rib resection. Hemodynamic parameters were continuously monitored including ECG, aortic blood pressure, left ventricular pressure, and pulmonary artery pressure. Myocardial tissue perfusion was measured by using an Omega flow laser fiber attached on the surface of the heart. RESULTS: All the animals achieved significantly increased blood pressure, pulmonary artery flow, and myocardial tissue perfusion during the EHAM compression compared with the nondriving (pre-assisted) mode. CONCLUSIONS: The EHAM system can effectively improve myocardial tissue perfusion and increase blood pressure thus demonstrating a potential for treating failing cardiac performance.     

Restoration of left ventricular systolic performance after reattachment of the mitral chordae tendineae. The importance of valvular-ventricular interaction

Clinical studies suggest that chorda-sparing mitral valve replacement techniques are associated with superior postoperative outcome, and several animal experiments have shown that disruption of the mitral subvalvular apparatus is followed by deterioration of left ventricular systolic function. One essential element, however, underlying the importance of chordal integrity for left ventricular function remains unproved: All investigators heretofore have been unable to demonstrate that left ventricular systolic performance can be restored by chordal reattachment after disruption of annular-papillary continuity. Therefore, we studied the effects of chordal detachment and subsequent chordal reattachment on left ventricular systolic performance using an in situ, isovolumic heart preparation in 10 halothane-anesthetized swine. The slope and left ventricular volume intercept of the isovolumic peak pressure-volume relationship were measured to assess global left ventricular systolic performance independent of load. Coronary perfusion pressure was maintained constant (95 +/- 6 mm Hg [+/- standard deviation]), and heart rates were in the physiologic range (133 +/- 26 min-1). Slope changed significantly (repeated measures analysis of variance, p = 0.0002), decreasing by 29% (from 4.74 +/- 0.94 to 3.37 +/- 0.87 mm Hg/ml, p less than 0.001) after chordal detachment and then returning to baseline (6.05 +/- 2.38 mm Hg/ml, p = 0.001) after chordal reattachment. Slope after chordal reattachment was not significantly different from the baseline value (p = 0.074). Volume intercept did not change significantly (p = 0.44) at any time. We conclude that the acute decrease in left ventricular contractility associated with surgical interruption of annular-ventricular continuity can, in fact, be reversed by chordal reattachment in this experimental model (isovolumically contracting normal porcine hearts). These data provide concrete confirmation of the concept of valvular-ventricular interaction; if these findings can be corroborated in the dilated, human left ventricle, such would strongly support efforts to preserve the mitral chordae tendineae during clinical mitral valve replacement to optimize postoperative left ventricular function.     

Left ventricular systolic performance in failing heart improved acutely by left ventricular reshaping

OBJECTIVE: If the geometric distortion during dilated heart failure could be corrected, the tension on the myocytes would be decreased, thereby leading to an improvement in left ventricular systolic function. We tested the effects of the CardioClasp (CardioClasp Inc, Pine Brook, NJ), a left ventricular reshaping device, on the failing heart, and our empirical data were compared with computationally derived data. METHODS: Heart failure was induced by 4-week rapid cardiac pacing. At the terminal experiment, an isolated failing heart preparation (isovolumic contraction, n = 5) or an intact failing heart in vivo (n = 7) was used. The effects of the reshaping device on left ventricular performance were assessed by the slopes (Ees) of the left ventricular end-systolic pressure-volume relations, hemodynamics, and echocardiograph before and after placing the CardioClasp on the heart. The change in Ees as the result of left ventricular reshaping was also estimated from computed theoretical analysis and compared with empirical data. RESULTS: There was a significant change in left ventricular dimension after placing the CardioClasp on the heart. In isolated heart preparation, Ees significantly increased from 1.40 +/- 0.44 mm Hg/mL to 2.42 +/- 0.63 mm Hg/mL after placing the device on the heart but returned to the baseline level (1.46 +/- 0.27 mm Hg) after removing it. Left ventricular developed pressure and left ventricular fractional area shortening were significantly increased as the result of left ventricular reshaping. Ees derived from computed theoretical analysis was highly correlated with confirming empirical data. CONCLUSIONS: The CardioClasp can reshape the left ventricle and improve left ventricular systolic performance in failing hearts.     

Interaction of a Transapical Miniaturized Ventricular Assist Device With the Left Ventricle: Hemodynamic Evaluation and Visualization in an Isolated Heart Setup

New left ventricular assist devices (LVADs) offer both important advantages and potential hazards. VAD development requires better and expeditious ways to identify these advantages and hazards. We validated in an isolated working heart the hemodynamic performance of an intraventricular LVAD and investigated how its outflow cannula interacted with the aortic valve. Hearts from six pigs were explanted and connected to an isolated working heart setup. A miniaturized LVAD was implanted within the left ventricle (tMVAD, HeartWare Inc., Miami Lakes, FL, USA). In four experiments blood was used to investigate hemodynamics under various loading conditions. In two experiments crystalloid perfusate was used, allowing visualization of the outflow cannula within the aortic valve. In all hearts the transapical miniaturized ventricular assist device (tMVAD) implantation was successful. In the blood experiments hemodynamics similar to those observed clinically were achieved. Pump speeds ranged from 9 to 22 krpm with a maximum of 7.6 L/min against a pressure difference between ventricle and aorta of ～50 mm Hg. With crystalloid perfusate, central positioning of the outflow cannula in the aortic root was observed during full and partial support. With decreasing aortic pressures the cannula tended to drift toward the aortic root wall. The tMVAD could unload the ventricle similarly to LVADs under conventional cannulation. Aortic pressure influenced central positioning of the outflow cannula in the aortic root. The isolated heart is a simple, accessible evaluation platform unaffected by complex reactions within a whole, living animal. This platform allowed detection and visualization of potential hazards.     

Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm

Objectives: Brief episodes of myocardial ischemia-reperfusion employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of postconditioning on persistent reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart model. Methods: Isolated Langendorff-perfused rat hearts (n=46) were subjected to 30 min of regional ischemia and reperfusion. The hearts with persistent VF (n=11) present after 15 min of reperfusion were then randomly assigned into one of the two groups: (1) control hearts (n=6), in which perfusion was continued without intervention; (2) postconditioned hearts (n=5) subjected to 2 min of global ischemia followed by reperfusion. Left ventricular pressures, heart rate, coronary flow, and electrogram were monitored throughout the experiment. Results: Conversion of VF into regular rhythm was observed in all hearts subjected to postconditioning. Regular beating was maintained by all postconditioned hearts during the subsequent reperfusion. None of the hearts in the control group had normal rhythm at the end of the experiment. At the end of reperfusion, the left ventricular developed pressure was lower in beating postconditioned hearts compared to the hearts that did not develop persistent VF. Conclusions: Ischemic postconditioning possesses strong antiarrhythmic effect against persistent reperfusion-induced tachyarrhythmias. Postconditioning may be an interesting, novel adjunct strategy to protect the heart.     

Preexisting mitral valve prosthesis in patients undergoing left ventricular assist device implantation

Experience with patients undergoing left ventricular assist device (LVAD) implantation with preexisting mitral valve prostheses is limited. Patients with mechanical heart valves might have an increased risk of thromboembolism; in patients with biologic valves, there might be a risk of structural deterioration of the leaflets. Out of 597 patients supported with a LVAD system between 2000 and 2009, 18 patients had mitral valve surgery prior to implantation. We excluded all patients below 18 years of age, those with postcardiotomy failure, and patients who had had mitral valve reconstruction. Only 1% of the studied patient population (n= 6) had mitral valve replacement. The mitral valve implantation has been performed 7.4 ± 9.4 years prior to LVAD insertion. None of the valves (one biologic, five mechanical) were exchanged or explanted. LVAD implantation was done either with left lateral thoracotomy (n= 5) or with midline resternotomy (n= 1). Temporary right ventricular assist device support was necessary in one case (16.6%); 30-day mortality was 16.6% (n= 1). Median support time was 14 ± 15 months. Two patients received heart transplantation after 6 and 26 months on the device; four patients died on mechanical circulatory support after 1, 2, 5, and 40 months. No valve or pump thrombosis or other clinically relevant thromboembolic events were observed. Only a small number of patients (1%) had a preexisting mitral valve prosthesis prior to LVAD implantation. No severe adverse events were observed when the prosthesis was left in place. Attention should be paid to the anticoagulation regime.     

Functional recovery of the native heart after cardiomyoplasty in sheep with heart failure: passive and dynamic effects of volume loading

BACKGROUND: Dynamic cardiomyoplasty (d-CMP) encourages reverse remodeling and improved contractility and stroke work (SW) efficiency of the failing native heart. This contrasts with passive cardiomyoplasty (p-CMP), which provides "passive girdling." To further evaluate pump recovery we assessed native left ventricular performance (without assist) 6 months after dynamic and passive CMP in sheep with heart failure with acute volume loading. METHODS: Heart failure (left ventricular ejection fraction 26%+/-8%) induced by coronary microembolization was followed by CMP in 11 sheep. After 8 weeks of muscle "training," paced cardiac assist was undertaken in the d-CMP group (n = 6). Five sheep with heart failure served as controls. Six months later the pressure-volume relationship was derived before and after volume loading by colloid solution. Latissimus dorsi muscle pacing was previously ceased in the d-CMP group. RESULTS: Volume loading increased left ventricular end-diastolic volume and pressure in all groups. After volume loading in d-CMP, the SW and pressure-volume area were increased, and SW efficiency remained unchanged. In p-CMP neither variable changed, whereas in control heart failure SW efficiency decreased due to a rise in pressure-volume area with stable SW. CONCLUSIONS: Based on response to volume loading, the failing native heart after 6 months of d-CMP showed functional recovery from "active girdling," whereas p-CMP prevented functional deterioration through passive girdling. The failing control heart progressively deteriorated.     

Hypertrophied hearts: what of sevoflurane cardioprotection?

Background: Recent studies have demonstrated that inhalation anaesthetics, like sevoflurane, confer cardioprotection both experimentally and clinically. However, coexisting cardiac disease might diminish anaesthetic cardioprotection and could partly explain why the clinical results of cardioprotection with anaesthetics remain controversial – in contrast to solid experimental evidence. Concomitant left ventricular hypertrophy is found in some cardiac surgery patients and could change cardioprotection efficacy. Hypertrophy could potentially render the heart less susceptible to sevoflurane cardioprotection and more susceptible to ischaemic injury. We investigated whether hypertrophy blocks sevoflurane cardioprotection, and whether tolerance to ischaemia is altered by left ventricular hypertrophy, in an established experimental animal model of ischaemia–reperfusion.
Methods: Anaesthetized juvenile pigs ( n =7–12/group) were subjected to 45 min distal coronary artery balloon occlusion, followed by 120 min of reperfusion. Controls were given pentobarbital, while sevoflurane cardioprotection was achieved by 3.2% inhalation throughout the experiment. Chronic banding of the ascending aorta resulted in left ventricular hypertrophy development in two further groups and these animals underwent identical ischaemia–reperfusion protocols, with or without sevoflurane cardioprotection. Myocardial infarct sizes were compared post-mortem.
Results: The mean myocardial infarct size (% of area-at-risk) was reduced from mean 55.0 (13.6%) (±SD) in controls to 17.5 (13.2%) by sevoflurane ( P =0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) ( P =0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) ( P =0.001).
Conclusion: Sevoflurane abrogated ischaemic injury to similar levels in both normal and left ventricular hypertrophied hearts.     

Ventricular assist device in patients with prosthetic heart valves

Ventricular assist device (VAD) support inpatients with a prosthetic heart valve had previously been considered a relative contraindication due to an increased risk of thromboembolic complications. We report our clinical experience of VAD implantation in patients with prosthetic heart valves, including both mechanical and bioprosthetic valves. The clinical records of 133 consecutive patients who underwent VAD implantation at a single institution from January 2002 through June 2009 were retrospectively reviewed. Six of these patients had a prosthetic valve in place at the time of device implantation. Patient demographics,operative characteristics, and postoperative complications were reviewed.Of the six patients,four were male.The mean age was 57.8 years (range 35–66 years). The various prosthetic cardiac valves included a mechanical aortic valve (n = 2), a bioprosthetic aortic valve (n = 3), and a mechanical mitral valve (n = 1).The indications for VAD support included bridge to transplantation (n = 2), bridge to recovery (n = 1), and postcardiotomy ventricular failure(n = 3). Three patients underwent left ventricular assist device placement and three received a right ventricular assist device. Postoperatively, standard anticoagulation management began with a heparin infusion (if possible)followed by oral anticoagulation.The 30-day mortality was50% (3/6). The mean duration of support among survivors was 194.3 days (range 7–369 days) compared with 16.0 days(range 4–29 days) for nonsurvivors. Of the three survivors,two were successfully bridged to heart transplantation and one recovered native ventricular function.Among the three nonsurvivors,acute renal failure developed in each case, and two developed heparin-induced thrombocytopenia. This study suggests that VAD placement in patients with a prosthethic heart valve, either mechanical or bioprosthetic,appears to be a reasonable option.     

Ventricular remodeling after cardiomyoplasty in heart failure sheep: passive and dynamic effects

Background. Recent reports claim that cardiomyoplasty (CMP) has a girdling effect on the left ventricle, to prevent dilatation and functional deterioration, but the mechanism of its long-term effects on the native heart is not known. We compared the relative role of CMP’s active squeezing and passive girdling in chronically failing hearts.

Methods. After induction of stable heart failure (left ventricular ejection FRACTION = 27% ± 7%) by staged coronary microembolization, CMP was performed in 11 of 18 sheep. After 8 weeks pacing training of the latissimus dorsi muscle (LDM), cardiac assist was begun with 1:2 synchronous bursts in 6 sheep (d-CMP, N = 6), and the LDM in the passive group (p-CMP, N = 5) remained unstimulated. Four (base line) and 30 weeks after induction of heart failure, the pressure-volume relationship was derived.

Results. After 30 weeks in d-CMP the slope (E_max) of the end-systolic pressure-volume relationship increased by 66% ± 55% (p < 0.05) and external work efficiency by 48% ± 41% (p < 0.01). In the passive CMP and control groups, slope and external work efficiency were unchanged. Conversely, left ventricular end-diastolic volume decreased (−14% ± 12%, p < 0.05) in the dynamic CMP group compared with a static course in the passive CMP group (3% ± 10%, p > 0.05) and an increase (18% ± 15%, p < 0.05) in controls.

Conclusions. Dynamic CMP improved native heart’s contractility and external work efficiency. In addition, whereas passive CMP has simply a girdling effect, dynamic CMP also induces reverse left ventricular chamber remodeling.     

风湿性心脏病病人心包液中内皮素与心脏功能的关系

目的 探讨风湿性心脏病病人心包液中内皮素(ET)浓度与心脏功能的关系.方法 选取51例风湿性心脏病行心内直视术者,入院24 h内行经胸二维多普勒超声心动图检查,术中采集静脉血和心包液各4 ml、心包组织100～150 mg,利用放射免疫分析方法测定上述样本中内皮素的含量.结果 心包液中ET显著高于其在血浆中的水平[(128.79±43.58) pg/ml对(102.71±39.81) pg/ml,P=0.003).心包组织匀浆中也有较高浓度的ET.左室射血分数(LWF)小于0.50的病人心包液和心包组织中ET含量显著高于LV盯大于0.50,并与左室射血分数呈负相关,与左室收缩末内径和左室舒张末内径呈正相关.结论 风湿性心脏病病人心包液和心包组织中存在高浓度的内皮素,并可能参与风湿性心脏病者心脏功能的调节.     

Ascending aorta outflow graft location and pulsatile ventricular assist provide optimal hemodynamic support in an adult mock circulation

Although continuous flow (CF) and pulsatile flow (PF) ventricular assist devices (VADs) are being clinically used, their effects on aortic blood flow, as a measure of overall blood distribution, remain unclear. In acute VAD support animal experiments, our group has described a zone of turbulent mixing in the aortic arch. The objective of this study was to confirm this finding in the controlled setting of an adult mock circulation, simulating ventricular pathophysiologic states (normal and failing ventricle). CF and PF flow VADs were connected to ventricular apical inflow and ascending aorta (AA) or descending aorta (DA) outflow cannulae. Cardiovascular pressure and flow waveforms were recorded at varying levels of VAD bypass resulting in four test conditions: (i) CF-AA; (ii) CF-DA; (iii) PF-AA; and (iv) PF-DA. Confirming the animal data, no differences in mean aortic flow between CF and PF VADs were found, and significantly lower mean aortic arch flow with DA cannulation was noted. Mean aortic root flow decreased with increasing VAD bypass flow. As in the animal studies, despite similar mean flow rates, significant differences in waveform morphology were observed for AA and DA outflow graft locations and varying levels of VAD bypass. At 100% VAD support in the failing heart, PF restored waveform pulsatility to normal baseline while CF resulted in little pulsatility. These results confirm our earlier findings in the animal model, suggesting that outflow graft location may have a significant effect on aortic blood flow distribution. The long-term implications of these findings are being examined in ongoing studies.     

Levitronix CentriMag pump as perioperative left ventricular support in a patient with critical aortic stenosis, mitral regurgitation, and cardiogenic shock

Severe aortic stenosis (AS) has a poor prognosis when associated with left ventricular dysfunction and congestive heart failure. Despite a relatively high operative mortality, most patients with severe AS and a depressed left ventricular ejection fraction (LVEF) should be considered candidates for aortic valve replacement. The CentriMag left ventricular assist system (Levitronix) can be used for perioperative or postcardiotomy circulatory support for the failing heart. In this case report, we report the successful use of the Levitronix CentriMag device as perioperative support in a high-risk patient with severe AS, significant mitral insufficiency, and a poor LVEF with advanced organ failure.     

Disease-specific remodeling of cardiac mitochondria after a left ventricular assist device

BACKGROUND: Failing hearts can exhibit elements of structural and molecular "reverse remodeling" after support with a left ventricular assist device (LVAD). The present study examined LVAD-induced remodeling of cardiac mitochondria. METHODS: Left ventricular tissue from 20 failing and 21 LVAD-supported hearts, catagorized as ischemic (ICM) or dilated (DCM) cardiomyopathy and four nonfailing hearts were studied. Myocyte mitochondrial ultrastructure was assessed by high-performance liquid chromatography determination of cardiolipin, a specific lipid component of the inner membrane, and its three major molecular species: L4, L3O, and L2O2. RESULTS: Both failing and LVAD-supported hearts exhibited a reduction in cardiolipin content that was independent of the type of cardiomyopathy. However, in failing/ICM hearts, there was a 25% increase in the L4/L3O ratio and a 70% increase in the L4/L2O2 ratio, indicating a change in cardiolipin composition. These alterations were normalized by LVAD support. In sharp contrast, molecular species ratios in DCM hearts were the same as those in nonfailing hearts regardless of whether LVAD support had been used or not. CONCLUSIONS: These data demonstrate LVAD-induced reverse remodeling of myocyte cardiolipin composition in ICM but not DCM hearts.     

Effect of renal transplantation on left ventricular function in hemodialysis patients

The effect of renal transplantation on left ventricular function was evaluated in 14 patients with end-stage renal disease requiring maintenance hemodialysis. They had no apparent clinical evidence of heart disease. Ischemic heart disease was excluded by history, electrocardiography and radionuclide ventriculography. Echocardiography and radionuclide ventriculography were recorded in the interdialytic periods. Sixty-four per cent of the patients had abnormal left ventricular function despite adequate hemodialysis. Left ventricular function was reassessed within the first two months after successful renal transplantation. All parameters improved shortly after the transplantation. Cardiac index increased by an average of 0.76 +/- 0.11/min/m2 (P less than 0.001), stroke volume by 23.9 +/- 0.5 ml (P less than 0.001), ejection fraction by 9.7 +/- 1.9% (P less than 0.001), mean normalized posterior wall velocity by 0.17 +/- 0.06 second-1 (P less than 0.01), mean velocity of circumferential fiber shortening by 0.28 +/- 0.02 circle/second (P less than 0.001), and mitral valve diastolic closure rate by 17.2 +/- 2.3 mm/second (P less than 0.01). Our findings support the existence of a specific uremic cardiomyopathy which is a functional defect probably related to poorly dialyzed uremic toxins.     

Separate Origin of the Main Components of the Left Coronary Artery in Syrian Hamsters (Mesocricetus auratus)

This study describes a rare congenital coronary artery anomaly in the Syrian hamster; namely, the separate origin of the obtuse marginal and left circumflex arteries which are the main components of the left coronary artery. The hearts of nine affected animals were examined by means of a corrosion‐cast technique and histology. The hamsters belonged to a laboratory inbred family with a high incidence of coronary artery anomalies and bicuspid aortic valve. The aortic valve was tricuspid in three hamsters and bicuspid in the other six hamsters. In all cases, the right coronary artery was normal, whereas the left coronary artery main trunk was absent. The present anomalous coronary artery patterns could be classified into two main entities: (i) ectopic origin of the obtuse marginal artery from the right aortic sinus or from the right coronary artery, with the left circumflex artery arising from the left side of the aortic valve; and (ii) ectopic origin of both the obtuse marginal artery from the right aortic sinus or from the right coronary artery and left circumflex artery from the dorsal aortic sinus. In all cases, the obtuse marginal artery coursed to the right side of the heart through the ventral wall of the right ventricular outflow tract. When the left circumflex artery arose from the dorsal aortic sinus, it formed an acute angle with the aortic wall. This report seems to be the first to describe the separate origin of the main components of the left coronary artery in a non‐human mammalian species. In man, the congenital coronary artery and aortic valve defects reported herein may entail the risk of clinical complications. However, none of the affected hamsters showed signs of disease.     

Effects of the left ventricular assist device on right ventricular function

Right ventricular failure is a leading cause of death in patients who require the left ventricular assist device. Previous reports suggested right ventricular functional deterioration during left ventricular assist but lacked a method by which right ventricular function could be quantified adequately. This study examined the effects of left ventricular volume unloading on right ventricular systolic function by means of the stroke work/end-diastolic volume relationship, a load-insensitive index of myocardial performance. In 12 anesthetized open-chested dogs, right ventricular and left ventricular pressures were measured with micromanometers while ultrasonic dimension transducers measured left and right ventricular orthogonal diameters. Left ventricular unloading was accomplished with left atrial-to-femoral artery bypass with a centrifugal pump. Data were recorded during transient vena caval occlusion in the control state and with maximal left ventricular unloading by full support by the left ventricular assist device. Modified ellipsoidal geometry was used to calculate simultaneous biventricular volumes, and linear regression analysis of right ventricular stroke work versus end-diastolic volume was used to quantify right ventricular systolic function. Average slope and x intercept of this relationship under control conditions were 2.2 +/- 0.3 X 10(4) erg/ml and 10.7 +/- 5.0 ml, respectively. During full support by the left ventricular assist device (mean flow rate, 2.4 +/- 0.3 L/min), left ventricular end-diastolic volume decreased by 31% (p less than 0.01), left ventricular septal-free wall diameter decreased by 7% (p less than 0.001), and rate of rise of right ventricular peak positive pressure declined by 13% (p less than 0.05). The corresponding slope and x intercept of the right ventricular stroke work/end-diastolic volume relationship during full unloading of left ventricular assist device were 2.3 +/- 0.3 X 0.3 X 10(4) erg/ml and 14.3 +/- 4.8 ml, respectively; these values were not significantly different from control values (p greater than 0.5). Additionally, analysis of right ventricular end-diastolic pressure-volume relationships suggested improved right ventricular chamber compliance, although the effects were small and did not reach statistical significance (p = 0.10). These data imply that marked alterations in biventricular geometry accompanying left ventricular volume unloading by the left ventricular assist device in a normal heart do not significantly alter right ventricular performance characteristics.