A novel miniature ventricular assist device for hemodynamic support

The HemoDynamics Systems enabler is a new cardiac assist pump that can expel blood from the left ventricle and provide pulsatile flow in the aorta. We evaluated the efficacy of the 18 Fr enabler. The enabler was inserted from the left ventricular apex into the ascending aorta in eight sheep. Heart failure (mild, moderate, and severe) was induced by microsphere injection into the coronary arteries to reduce cardiac output by 10-30%, 31-50%, and more than 50% from baseline, respectively. The enabler was activated, and its flow was increased to approximately 2.0 L/min. Hemodynamic variables were recorded before and after activation. In moderate heart failure, cardiac output and mean aortic pressure increased from 2.3 +/- 0.6 L/min and 59 +/- 12 mm Hg before assist to 2.8 +/- 0.6 L/min and 70 +/- 8 mm Hg at 30 minutes after activation, respectively (p < 0.01). Left atrial pressure decreased from 17 +/- 3 to 13 +/- 4 mm Hg (p < 0.05). Similar findings were observed in mild and severe heart failure. Despite its small diameter, the enabler significantly improved the hemodynamics of failing hearts and may potentially serve as a means of peripheral left ventricular support. Further study is warranted.     

急性肺栓塞时左右心室压力容量关系变化的实验研究

目的: 建立急性肺栓塞（APE）动物模型，探讨急性肺栓塞时左右心室压力容量关系变化。方法: 成年杂种犬7只，依据动物模型建立过程中不同时段和压力负荷程度分为肺栓塞前组、中度肺栓塞和重度肺栓塞3组，采用漂浮导管经肺动脉内注射缝线线段的方法建立中度APE和重度APE动物模型，并测量心导管压力指标；使用超声心动图声学定量技术获得同步容量指标；两者结合建立左右心室简易压力容量关系。结果: 中度APE时，右室压力容量关系图明显向右上移位，面积扩大明显，环的形态由近似三角形向矩型转变；左室压力容量关系图则小幅度左下移位，形态无明显变化；重度APE时，右室压力容量关系图右上移位且面积缩小，形态不规则。左室压力容量关系图则较大幅度左下移位，面积缩小，形态不规则。结论： 急性肺栓塞时左右心室压力容量关系变化是APE血流动力学变化和临床预后的理论基础，是探讨APE血流动力学变化的实用、简便、直观方法。     

Biventricular support with the Jarvik 2000 ventricular assist device in a calf model of pulmonary hypertension

The Jarvik 2000 ventricular assist device (VAD) is clinically efficacious for treating end-stage left ventricular failure. Because simultaneous right ventricular support is also occasionally necessary, we developed a biventricular Jarvik 2000 technique and tested it in a calf model. One VAD was implanted in the left ventricle with outflow-graft anastomosis to the descending aorta. The other VAD was implanted in the right ventricle with outflow-graft anastomosis to the pulmonary artery. Throughout the 30 day study, hemodynamic values were continuously monitored. On day 30, both pumps were evaluated at different speeds, under various hemodynamic conditions. By gradually occluding the pulmonary artery proximally or distally, we simulated varying degrees of high pulmonary vascular resistance, right ventricular hypertension, global heart failure, or ventricular fibrillation. The two VADs maintained biventricular support even during pulmonary artery occlusion and ventricular fibrillation, yielding a cardiac output of 3-11 L/min, left ventricular end-diastolic pressure of 11-24 mm Hg, and central venous pressure of 9-25 mm Hg. End-organ function was unimpaired, and no major adverse events occurred. The dual VADs offered safe, effective biventricular assistance in the calf. Additional studies are needed to assess the effects of lowered pulse pressure upon the pulmonary circulation and to develop a single pump speed controller.     

Experimental and clinical evaluation of a counterpulsation device

The counterpulsation technique has been widely used for the assistance of the acutely failing left ventricle utilizing the intraaortic balloon pump. However, a variety of other counterpulsation devices are available. To evaluate a counterpulsation device several variables need to be considered: (1) experimental and clinical determination of the salutary effects of the device on the left ventricular ejection fraction, cardiac output, aortic pressures, left ventricular end-diastolic pressure, tension-time index, diastolic pressure-time index and endocardial viability ratio; (2) experimental and clinical estimation of the device biocompatibility, and (3) the clinical improvement of the assisted patients.     

Changes in the sensitivity of left atrial receptors following reversal of heart failure.

Recordings were made from left atrial type B receptors in six mongrel dogs after recovery from the cardiac effects of a chronic AV fistula. All animals showed hemodynamic and clinical signs of congestive heart failure after 44.5 +/- 3.6 days with a patent Dacron shunt between the aorta and inferior vena cava below the level of the renal arteries. The stimulus-response curves of the left atrial stretch receptors (change in spikes/cardiac cycle or in spikes/minute vs. change in left atrial pressure) after 45.2 +/- 7.2 days of shunt closure were similar to those seen in sham-operated dogs from a previous study. However, the slope of the stimulus-response curve of the dogs in which the AV fistula was closed was significantly greater than the slope of the curve from the AV fistula dogs with heart failure. Radiographs indicated that after shunt closure, cardiac dilatation had regressed. This study incidates that a decrease in the sensitivity of left atrial receptors in dogs with congestive heart failure is a reversible phenomenon and that the initial depression is most likely related to the concomitant cardiac dilatation that accompanies the failure state.     

Assessment of synchronized direct mechanical ventricular actuation in a canine model of left ventricular dysfunction

Direct mechanical ventricular actuation (DMVA) is an experimental procedure that provides biventricular cardiac assistance by intracorporeal pneumatic compression of the heart. The advantages this technique has over other assist devices are biventricular assistance, no direct blood contact, pulsatile blood flow, and rapid, less complicated application. Prior studies of nonsynchronized DMVA support have demonstrated that a subject can be maintained for up to 7 days. The purpose of this study was to determine the acute hemodynamic effects of cardiac synchronized, partial DMVA support in a canine model (RVP) of left ventricular (LV) dysfunction. The study consisted of rapidly pacing seven dogs for 4 weeks to create LV dysfunction. At the conclusion of the pacing period, the DMVA device was positioned around the heart by means of a median sternotomy. The animals were then imaged in a 1.5 T whole body high speed clinical MR system, with simultaneous LV pressure recording. Left ventricular pressure-volume (PV) loops of the nonassisted and DMVA assisted heart were generated and demonstrated that DMVA assist shifted the loops leftward. In addition, assist significantly improved pressure dependent LV systolic parameters (left ventricular peak pressure and dp/dt max, p < 0.05), with no diastolic impairment. This study demonstrates that DMVA can provide synchronized partial assist, resulting in a decrease in the workload of the native heart, thus having a potential application for heart failure patients.     

Mechanical support of the left ventricle in ischemia induced left ventricular failure: an experimental study.

OBJECTIVE: this study compares the hemodynamic effects of intra-aortic balloon pumping (IABP), left ventricular assist device (LVAD), and extracorporeal membrane oxygenation (ECMO) in left ventricular failure in pigs. METHODS: In 29 pigs weighing 12 +/- 0.7 kg left ventricular failure was induced by ligating the left anterior descending coronary artery. Eight animals served as controls. Eight pigs were treated by IABP, seven by LVAD, and six by ECMO. The study period lasted four hours. Hemodynamic and oxygen transport/uptake parameters were measured continuously or intermittently. RESULTS: Six animals of the ECMO and LVAD groups survived the 4 hour period, but only 3 and 4 animals of the IABP and control groups survived (p less than 0.05). Cardiac index decreased about 48% and 22% in the control and IABP groups (p less than 0.05), whereas there was only a slight decrease in the ECMO (9%) and LVAD (14%) groups. Oxygen delivery fell significantly in the control and IABP groups (p less than 0.05), compared with only a slight change in the LVAD and ECMO groups. CONCLUSION: ECMO is the most effective system for temporary circulatory support in severe ventricular failure. LVAD maintains cardiac output when pulmonary blood flow is provided. IABP is less efficient in supporting the failing heart, especially in the presence of severe ventricular arrhythmias.     

Hyperfunction with normal inotropic state of the hypertrophied left ventricle.

Conscious dogs were instrumented with an inflatable cuff around the ascending aorta, a high-fidelity micromanometer in the left ventricle (LV), and pairs of ultrasonic crystals for measurements of LV wall thickness and internal LV diameter. Wall stress (WSt) and mean velocity of wall shortening (VCF) were calculated. Mean force-velocity relations and WSt-diameter loops in single contractions were then analyzed over a range of matched systolic pressures during acute aortic constrictions both before and after induction of chronic hypertrophy by sustained aortic constriction. At normal LV systolic pressures and at each matched level of systolic LV pressure, wall shortening velocity was increased in the hypertrophied ventricle. However, force-velocity relations obtained by relating mean VCF to mean WSt at various stress levels fell on the same relation as during control. The linear relation between LV diameter and pressure at the end of ventricular ejection was shifted to the left in the hypertrophied ventricle, indicating enhanced shortening. However, linear WSt-diameter relations at end-ejection were not different in control and hypertrophied hearts. These findings indicate that the ventricle hypertrophied by pressure overload exhibited hyperfunction as a pump but that its myocardium had a normal level of inotropic state.     

A wireless and battery-less miniature intracardiac pressure sensor: early implantation studies

Permanently implantable hemodynamic monitors show great promise in providing personalized and cost-efficient care to heart failure patients by providing timely intracardiac pressure data under ambulatory conditions. The data may be used to titrate maintenance therapies and to monitor health status so that more intensive interventions can be planned and performed under optimal conditions. In this pilot study, we present the results of the implantation of a novel wireless, battery-less pressure sensor into the apex of the left ventricle of four dogs for a period of 8 weeks. All animals recovered to a normal state and did not show any clinical signs of cardiac insufficiency or any complications suggestive of thromboembolism. All sensors functioned throughout the implantation period and provided detailed waveforms of ventricular pressure.     

压力超负荷对大鼠左室心肌肌型LIM蛋白mRNA和蛋白表达的影响

目的:了解压力超负荷大鼠左室肥厚心肌肌型LIM蛋白(MLP)mRNA和蛋白水平的变化, 探讨病理性左室肥厚心肌是否存在细胞骨架蛋白的缺失。方法:观察大鼠腹主动脉缩窄术后1、4、8、16周各组血流动力学参数、心室肥厚指数、MLPmRNA表达和蛋白水平的变化。结果:腹主动脉缩窄术后4周左室肥厚指数较术后1周组明显增加(P＜0.05), 术后8周组左室心肌MLPmRNA的表达较术后1、4周组明显下降(P＜0.05), 但各组左室心肌MLP蛋白水平差异无显著(P＞0.05)。结论:在病理性左室肥厚心肌出现明显心力衰竭前, MLP转录水平下调, 而MLP蛋白水平无明显改变。提示MLP作为心肌细胞骨架的基础, 对维持肥厚左室心肌的收缩功能起重要作用。     

The enabler cannula pump: a novel circulatory support system.

BACKGROUND: The enabler circulatory support system is a catheter pump which expels blood from the left or right ventricular cavity and provides pulsatile flow in the ascending aorta or pulmonary artery. It is driven by a bedside installed pulsatile driving console. The device can easily be implanted by a minimal invasive approach, similar to the Hemopump. PURPOSE: To demonstrate the hemodynamic performance of this new intracardiac support system. METHODS: In a series of 9 sheep, hemodynamic evolutions were recorded in various conditions of myocardial contractility (the non-failing, the moderately failing and the severely failing heart). Heart failure was induced by injection of microspheres in the coronary arteries. RESULTS: Introduction of the cannula through the aortic valve was feasible in all cases. Pump flow by the enabler was gradually increased to a maximum of 3.5 L/min. Diastolic (and mean) aortic blood pressure is significantly increased in the non-failing and moderately failing condition (counterpulsation mode). In heart failure, cardiac output is significantly increased by the pump (p < 0.0001). A drop in left atrial pressure (indicating unloading) is achieved in all conditions but reaches significant levels only during heart failure (p=0.0068). CONCLUSIONS: This new circulatory support system contributes to stabilization of the circulation in the presence of cardiac unloading. In heart failure it actually supports the circulation by increasing cardiac output and perfusion pressure.     

Cardiac assistance with electrically stimulated skeletal muscle

This study examined the ability of a skeletal muscle-powered assist ventricle (SMV) to augment cardiac output in ten dogs with pharmacologically induced heart failure under acute conditions. An SMV was surgically constructed in each dog by wrapping the untrained rectus abdominis muscle around a compressible pouch that was inserted into a left ventricular apex-to-aortic vascular conduit. The multiple motor nerves to the rectus muscle were then stimulated during ventricular diastole at a rate which equalled a ratio of 1:2, 1:3, or 1:4 with the natural ventricular beat. There was an increased cardiac output during SMV assistance compared with preassistance values in all ten dogs at each stimulation ratio with a mean increase of 46 +/- 4 per cent with a ratio of 1:2, 25 +/- 4 per cent with a ratio of 1:3, and 31 +/- 7 per cent with a ratio of 1:4 (p less than 0.01 for all values). The diastolic blood pressure and mean blood pressure were both increased (p less than 0.01 and p less than 0.05, respectively) during SMV stimulation at ratios of 1:2 and 1:3, but not 1:4. We have shown that untrained rectus abdominis muscle, when used as the power supply for a SMV in an apico-aortic conduit, can temporarily augment cardiac output in dogs with pharmacologically induced heart failure.     

A reproducible model of moderate to severe concentric left ventricular hypertrophy.

A reproducible model for the production of moderate to severe concentric left ventricular hypertrophy has been developed in this laboratory. Coarctation-banding of the ascending aorta was performed successfully in 10 puppies. There were no late deaths related to aortic rupture, and in the dogs surviving for 1 yr no evidence of congestive heart failure was present. A second operative procedure was performed in seven dogs for chronic instrumentation, and all survived. Severe supravalvular aortic stenosis with a marked peak systolic pressure gradient was noted in each dog. Postmortem examination revealed a substantial increase in left ventricular mass and in the ratio of left ventricular to body weight.     

Left ventricular afterload and systemic hydraulic power during in-series cardiac assistance: Studies using intraaortic balloon pumping in dogs

The effects of in-series mechanical assistance on left ventricular (LV) afterload and aortic power dissipation were studied in four groups of open chest mongrel dogs: control, acute myocardial ischemia, cholinergic and beta-adrenergic blockade, and combined ischemia and blockade. Aortic root pressure, flow, power, and impedance and LV pressure and power were obtained. Assistance was provided by intraaortic balloon pumping. Times of inflation and deflation of the balloon were controlled to maintain a phase difference of 180° between the fundamental components of aortic root pressure and flow. Differences in hemodynamic parameters before and after 2–5 min of cardiac assistance were calculated. The results confirm other observations regarding effects of in-series assistance on LV and aortic pressure, cardiac output, and peripheral resistance. No consistent changes were obtained in the pulsatile components of aortic input impedance. A significant decrease (14–20%) was observed in the dc component of the impedance in all animals. The results reported here contradict previous reports regarding decreased LV power generation. It was found that LV power generation and aortic power dissipation increased significantly during assistance (LV, 3–17%; aortic, 4–19%). The results of this investigation also appear to conflict with previous reports regarding the role of cardiovascular control in “counteracting” the effects of assistance in the normal experimental preparation. They suggest that the short term effects are attributable directly to the device and are not mediated by the autonomic nervous system. This work was supported in part by SUPHS Grant HL-13737 to Sinai Hospital and by NSF Grant ENG 74-21085 to the University of Rhode Island. Portions of this investigation were performed while D. Jaron was Director of the Surgical Research Laboratory at Sinai Hospital of Detroit.     

主动脉转流对腹主动脉阻断所致血液动力学等改变的影响

目的:探讨不同流量主动脉转流对腹主动脉暂时性阻断时全身血液动力学等改变的影响。方法:实验建立在小猪腹腔动脉开口以上阻断腹主动脉1h和同时应用辅助主动脉转流的模型,监测血液动力学的变化,并观察组织学的改变。结果:阻断组发生了明显的血液动力学紊乱,尿量明显减少,代谢性酸中毒也极为明显,肝、肾和小肠组织及超微结构均发生了明显的病变。在主动脉转流组血液动力学的紊乱得到明显改善。结论:腹主动脉阻断1h将造成严重的全身血液动力学紊乱,当转流量达到原腹主动脉血流量的70%时主动脉转流能较好地防止这一损伤改变。     

牙髓牙本质复合体中VIP阳性神经纤维的研究

目的:研究血管活性肠肽(VIP)在牙髓牙本质复合体中的表达,探讨其功能。方法:收集人前磨牙,石蜡包埋切片,作免疫组织化学和图象定量分析。结果:VIP阳性神经纤维自根尖孔呈束状进入牙髓,至颈部扇形分开,在冠髓大量分支,部分围绕在血管周围,部分终止于牙髓基质,部分参与形成成牙本质细胞层下Raschkow神经丛,然后发出分支伸入成牙本质细胞层和前期牙本质,但不进入成熟牙本质。VIP阳性神经纤维在冠髓的积分光密度为12.74±1.807,体密度为0.0192±0.0127,线密度为0.0046±0.0029,在前期牙本质的积分光密度为13.07±1.927,线段长度为(19.60±8.597)mm。结论:VIP阳性神经纤维存在于人牙髓牙本质复合体,部分纤维围绕血管,部分纤维止于牙髓基质和前期牙本质,这种分布提示该纤维除与血管运动有关外,可能还与感觉有关,在痛觉传导、血管调节等方面发挥重要作用。     

Theoretical estimation of cannulation methods for left ventricular assist device support as a bridge to recovery

Left ventricular assist device (LVAD) support under cannulation connected from the left atrium to the aorta (LA-AA) is used as a bridge to recovery in heart failure patients because it is non-invasive to ventricular muscle. However, it has serious problems, such as valve stenosis and blood thrombosis due to the low ejection fraction of the ventricle. We theoretically estimated the effect of the in-series cannulation, connected from ascending aorta to descending aorta (AA-DA), on ventricular unloading as an alternative to the LA-AA method. We developed a theoretical model of a LVAD-implanted cardiovascular system that included coronary circulation. Using this model, we compared hemodynamic responses according to various cannulation methods such as LA-AA, AA-DA, and a cannulation connected from the left ventricle to ascending aorta (LV-AA), under continuous and pulsatile LVAD supports. The AA-DA method provided 14% and 18% less left ventricular peak pressure than the LA-AA method under continuous and pulsatile LVAD conditions, respectively. The LA-AA method demonstrated higher coronary flow than AA-DA method. Therefore, the LA-AA method is more advantageous in increasing ventricular unloading whereas the AA-DA method is a better choice to increase coronary perfusion.     

Measurement of hemodynamic changes with the axial flow blood pump installed in descending aorta

We have developed various axial flow blood pumps to realize the concept of the Valvo pump, and we have studied hemodynamic changes under cardiac assistance using an axial flow blood pump in series with the natural heart. In this study, we measured hemodynamic changes of not only systemic circulation but also cerebral circulation and coronary circulation under cardiac support using our latest axial flow blood pump placed in the descending aorta in an acute animal experiment. The axial flow blood pump was installed at the thoracic descending aorta through a left thoracotomy of a goat (43.8 kg, female). When the pump was on, the aortic pressure and aortic flow downstream of the pump increased with preservation of pulsatilities. The pressure drop upstream of the pump caused reduction of afterload pressure, and it may lead to reduction of left ventricular wall stress. However, cerebral blood flow and coronary blood flow were decreased when the pump was on. The axial flow blood pump enables more effective blood perfusion into systemic circulation, but it has the potential risk of blood perfusion disturbance into cerebral circulation and coronary circulation. The results indicate that the position before the coronary ostia might be suitable for implantation of the axial flow blood pump in series with the natural heart to avoid blood perfusion disturbances.     

Effect of pump flow mode of novel left ventricular assist device upon end organ perfusion in dogs with doxorubicin induced heart failure

End organ effects of nonpulsatile (NP) and pulsatile (P) left ventricular assist device (LVAD) flow were compared in a canine model of doxorubicin-induced heart failure. After heart failure induction, a prototype bimodal LVAD was implanted. Hemodynamics, cardiac dimensions, and myocardial metabolism were monitored with the LVAD off (baseline) and on (in NP and P modes at 70% or 100% power). End organ perfusion was assessed by colored microsphere analysis. Seven dogs were used: two died before pump implantation and were excluded from analysis, and the remaining five survived to study termination. At 70% NP, ascending aortic flow and myocardial oxygen consumption (MVO2) decreased significantly. At 100% NP, LV dimensions decreased, aortic systolic, pulse, and LV pressures decreased but not significantly, and ascending aorta flow reversed. At 100% NP, coronary blood flow, MVO2, and LV free wall subepicardial and subendocardial blood flows decreased significantly. However, as NP support increased, the subepicardial/subendocardial blood flow ratio remained near baseline. At 100% NP, right ventricular perfusion decreased but not significantly, cerebral perfusion decreased significantly, and renal perfusion stayed constant. P mode results were similar, except that ascending aorta flow decreased significantly at 100% P instead of reversing as at 100% NP. These results suggest that end organ perfusion is not differentially affected by LVAD flow mode during chronic heart failure.     

Left ventricular pressure transmission to myocardial lymph vessels is different during systole and diastole

In six open-thorax-anaesthetized dogs with paced hearts and a retrogradely cannulated epicardial lymph vessel, the sensitivity of myocardial lymph pressure to left ventricular pressure during systole and during diastole was determined. The lymph vessels were cannulated using PE-90 tubing, and lymph pressure was measured by connecting the cannula to a microtip pressure transducer. To obtain the systolic sensitivity, left ventricular pressure was changed by clamping the descending aorta, which caused left ventricular pressure to increase. The diastolic sensitivity was obtained from natural variation to left ventricular pressure caused by atrial contractions during induced long diastoles. The mean ratio of the pulse in lymph pressure to the pulse in left ventricular pressure was determined: systole: 0.069±0.013, n=213, diastole: 0.76±0.16, n=249 and, if possible, linear regression analysis between lymph and left ventricular pressure was performed. The systolic regression coefficients could be determined in six dogs and the diastolic coefficients in three dogs. During long diastoles lymph pressure variations are on average 76 per cent of those in the left ventricle. However, during systole, the sensitivity of lymph pressure to left ventricular pressure is more than ten times lower. It is not unlikely that the structural embedment of lymph vessels within the myocardium is such that volume variations by cardiac contraction are limited.