Leukocyte-platelet aggregates and monocyte tissue factor expression in bovines implanted with ventricular assist devices.

Infection and thromboembolism remain significant complications associated with ventricular assist device (VAD) support, including the newer rotary VADs, limiting wider adoption of this promising technology. These complications persist in spite of extensive preclinical testing in large animal models. The amount of biocompatibility information collected during preclinical trials is limited due to a lack of available assays. We thus developed three flow cytometric assays to measure leukocyte-platelet aggregates and monocyte tissue factor expression and applied them to 26 bovines implanted with two types of rotary VADs. All animals displayed low levels of circulating aggregates and monocytes expressing tissue factor prior to device implant. The assay values significantly increased following VAD implant, then usually declined to a lower, yet significantly elevated versus baseline, level indicative of ongoing inflammation. The implementation of more robust biocompatibility assays for the evaluation of cardiovascular device performance and modification might ultimately contribute to the development of safer artificial organs.

Preclinical biocompatibility assessment of the EVAHEART ventricular assist device: coating comparison and platelet activation.

Thromboembolism and bleeding remain significant complications of ventricular assist device (VAD) support. Increasing the amount of biocompatibility data collected during preclinical studies can provide additional criteria to evaluate device refinements, while design changes may be implemented before entering clinical use. Twenty bovines were implanted with the EVAHEART centrifugal VAD for durations from 30 to 196 days. Titanium alloy pumps were coated with either diamond-like carbon or 2-methoxyethyloylphosphoryl choline (MPC). Activated platelets and platelet microaggregates were quantified by flow cytometry, including two new assays to quantify bovine platelets expressing CD62P and CD63. Temporally, all assays were low preoperatively, then significantly increased following VAD implantation, before declining to a lower, but still elevated level over 2-3 weeks. MPC-coated VADs produced significantly fewer activated platelets after implant trauma effects diminished. Three animals receiving no postoperative anticoagulation had similar amounts of circulating activated platelets and platelet microaggregates as animals receiving warfarin anticoagulation. Two new methods to quantify bovine activated platelets using antibodies to CD62P and CD63 were characterized and applied. These measures, along with previously described assays, were able to differentiate between two biocompatible coatings and assess effects of anticoagulation regimen in VAD preclinical testing.

Long-term results of modified Bentall procedure using flanged composite aortic prosthesis and separately interposed coronary graft technique.

We have selected the flanged composite aortic prosthesis and separately interposed coronary graft technique for the aortic root replacement over seven years. We sought to evaluate the long-term results of aortic root replacement with this technique. Between April 1996 and September 2003, 71 patients (mean age 46.1+/-12.9 years, 67.6% males) underwent aortic root replacement with this technique. Sixty-two patients had annuloaortic ectasia, and seven patients acute type A aortic dissection. Marfan syndrome was recognized in 35 patients. Two separate 8-10 mm knitted Dacron grafts were interposed between a valved composite graft and both coronary ostia to avoid kinking of coronary arteries. The early mortality rate was 4.2%. The actuarial survival rate was 93.9+/-3.0% at 5 years. The freedom from operation related complications was 86.7+/-4.1% at 5 years. No patients had anticoagulant-related hemorrhage, valve thrombosis, reoperation, graft thrombosis, or coronary pseudoaneurysm. The separately interposed coronary graft and the flanged composite graft technique is predictable and safe. Coronary pseudoaneurysm and graft thrombosis have been eliminated.

Effects of left ventricular assist device support and outflow graft location upon aortic blood flow.

Although continuous flow (CFVAD) and pulsatile (PVAD) ventricular assist devices (VADs) are being clinically used, their effects upon aortic blood flow as a measure of overall blood distribution remain unclear. The objective of this study was to compare the effects of CFVAD and PVAD support for ascending (AscA) and descending (DA) aorta outflow cannulation upon mean aortic blood flow and waveform morphology. Six experiments were conducted in a normal, acute calf model, in which an inflow cannula was implanted in the left ventricle apex and outflow cannulae were anastomosed to both the AscA and DA. Flow probes were placed around the pulmonary artery, pump outflow, brachiocephalic trunk, and aorta proximal and distal to the DA outflow. For each acute experiment, calves received randomly selected levels of VAD support (0-100% of cardiac output) and pump failure (VAD off and outflow cannula unclamped) for each of four randomly selected test conditions: (1) PVAD and AscA, (2) PVAD and DA, (3) CFVAD and AscA, and (4) CFVAD and DA. Regardless of pump type or support level, proximal and distal aorta mean flows were lower (p < 0.05) for DA compared with the AscA. No differences in mean aortic flows between pump types at either outflow graft location were discerned. Differences in morphologic features of blood flow waveforms between PVAD and CFVAD were observed. During simulated pump failure, retrograde aortic blood flow in both the aortic arch and DA was observed. Partial ventricular suction was also observed during the greatest levels of CFVAD support and suggested pronounced effects upon both the right and left ventricle. Collectively, these findings imply that VAD outflow location may have an important role in patient response and recovery. Investigation of the long-term pathophysiologic responses to pump type and outflow location is ongoing.

Distal thoracic aorta hemodynamics during exercise with continuous flow left ventricular assist system.

OBJECTIVES: Continuous flow left ventricular assist systems (LVAS) are being discussed as a destination therapy. LVAS patients will have expanded activity of daily life, including exercise. In this study, we analyzed the effects of exercise on blood flow in the distal thoracic aorta of LVAD implanted animals. METHODS: Five calves with a continuous flow LVAS exercised on treadmill at two different pump flow rates (PFR), 60-80% (high PFR) and 25-30% (low PFR) of pulmonary artery flow rate. Pump, pulmonary artery and descending thoracic aorta flow waves were recorded before, during and after exercise. Systolic and diastolic flow volume in each cardiac cycle in pump and descending thoracic aorta flow was calculated. RESULTS: (1) Average flow rates - Pulmonary artery and descending thoracic aorta flow rates increased with heart rate during exercise and there was no difference between groups. (2) Pump flow wave - Pump regurgitation increased temporally during exercise at both PFRs, but sustained incidences of regurgitation after exercise were only observed at low PFR. Systolic and diastolic pump flow volume decreased during exercise at both PFRs, but systolic volume increased and diastolic volume decreased significantly after exercise at low PFR. (3) Descending thoracic aorta flow wave - At high PFR, systolic volume of descending thoracic aorta increased but diastolic flow volume decreased during exercise. At low PFR, both systolic and diastolic volume of the descending thoracic aorta decreased during exercise, but systolic volume increased and diastolic volume decreased after exercise. Systolic volume of the descending thoracic aorta in low PFR was significantly greater and diastolic volume was less than those in high PFR during and after exercise. CONCLUSION: Exercise temporarily increases pump regurgitation with continuous flow LVAS support. Average flow rate of the descending thoracic aorta was maintained by compensation from increased heart rate, although the diastolic flow of the descending thoracic aorta decreased after exercise at the lower pump flow rate. Further study will be needed to evaluate whether or not this flow decrease causes hemodynamic and/or an oxygen delivery mismatch to peripheral tissue.

In vivo evaluation of a MPC polymer coated continuous flow left ventricular assist system.

The aim of this study was the evaluation of the thrombogenicity and the biocompatibility of the SunMedical EVAHEART left ventricular assist system (LVAS) coated with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer compared to a diamond-like carbon (DLC) coating. Four calves were implanted with the MPC polymer-coated LVAS. Eight calves were implanted with DLC coated LVAS. The thrombogenicity and biocompatibility of the pumps were evaluated. At explant, 60.0 +/- 37.2% (5-85%) of the pump surface area was still coated with MPC polymer after the duration of 45.0 +/- 32.0 days. In 1 out of 4 MPC and 2 out of 8 DLC coated pumps, there was a very small amount of thrombus around the seal ring; otherwise the blood contacting surfaces were free of thrombus. Major organs were normal except for a few lesions in kidneys from both groups. The MPC polymer coated EVAHEART LVAS seems to have low thrombogenicity and high biocompatibility similar to the DLC coated system. The current study demonstrated that the MPC polymer coating shows great promise for being used as an antithrombogenic substrate for the LVAS due to its ease of application, significant cost benefit, and reduction in anticoagulation therapy in acute postoperative period.

Effects of continuous flow left ventricular assist device support on skin tissue microcirculation and aortic hemodynamics.

Continuous flow ventricular assist devices (CFVADs) are thought to be the next generation of circulatory assist devices. With many now in various stages of development or clinical trial, it is important that the physiologic aspects of these pumps be critically analyzed. In this study, 15 calves were divided into two groups. One group received a CFVAD, and the other a sham implant. Two additional animals were used in an acute study to examine aortic blood flow patterns from a CFVAD. Tissue perfusion was measured on all animals before surgery and then weekly thereafter. Before surgery, there was no difference in hemodynamics or tissue perfusion between studied animals. Postoperatively, CFVAD animals had statistically significant increased diastolic pressure. Significantly decreased pulse pressure, pulse index, and tissue perfusion were also observed in CFVAD animals. Results from the flow pattern studies suggested that at moderate levels of pump support (40-75%), the amount of blood flow distal to the outflow graft anastomosis decreased approximately 25% because of increased regurgitant blood flow in the aorta. These results suggest that the diminished tissue perfusion is likely due to changes in aortic hemodynamics and provide some insight into the distribution of flow from CFVADs.

Smooth muscle cell hypertrophy of renal cortex arteries with chronic continuous flow left ventricular assist.

BACKGROUND: Pathophysiology of long-term continuous flow left ventricular assist is not well described. With many of these devices becoming available, it is important to examine for possible pathologic effects. In this study we examined the relationship between diminished pulsatility and pathologic changes in renal cortical arteries. METHODS: Twenty-nine calves were implanted with various continuous flow left ventricular assist systems in a left ventricle-descending thoracic aorta bypass configuration. Pulsatility was quantified by pulse pressure and pulsatility index. Pathologic changes of the renal cortex arteries were described and evaluated by medial thickness, medial/vascular cross-sectional area ratio, and smooth muscle cell count, to quantify hypertrophy or hyperplasia. Seven calves, which underwent a sham-implant, were used as controls. RESULTS: Systolic arterial pressure, pulse pressure, and pulsatility index were significantly lower and diastolic pressure was significantly higher than before implant in pump-implanted animals. Twenty-three of 29 pumpimplanted calves (79.3%) had medial smooth muscle cell hypertrophy in renal cortex arteries, whereas none of sham-implanted calves had any abnormal lesions. When the pump-implanted calves were grouped according to the presence of smooth muscle cell hypertrophy, there was a clear trend toward lower pump flow rate in calves with lesions. Renal function was within the normal range in all calves. CONCLUSIONS: There appears to be a relationship between smooth muscle cell hypertrophy in renal cortex arteries and continuous flow left ventricular assist. Furthermore, although the pathologic changes are likely multifactorial, these lesions appear to be related to lower pump assist rates.

Extracorporeal membrane oxygenation and left ventricular assist device: a case of double mechanical bridge.

A 14-year-old boy with dilated cardiomyopathy with cardiac arrest was successfully implanted with a left ventricular assist device (LVAD) after 6-day extracorporeal membrane oxygenation (ECMO). He had multiple organ failure at the initiation of ECMO, but the failed organs recovered during assisted circulation, leading to LVAD implantation. This case showed the advantages of the "double bridge" such as: (1) quick and easy installation for acute cardiogenic shock, (2) providing intervention time for complications refractory to LVAD implantation, and (3) providing evaluation time for potential LVAD implantation and transplant candidates.

Effects of milrinone for right ventricular failure after left ventricular assist device implantation.

Right ventricular failure after left ventricular assist device implantation sometimes requires additional mechanical right ventricular support. The effectiveness of nitrates, prostaglandin, or nitric oxide inhalation in such cases has already been reported. However, there are few reports on the administration of phosphodiesterase inhibitor for right ventricular failure after left ventricular assist device implantation. We report two patients with right ventricular failure after left ventricular assist device implantation successfully treated with milrinone. Both had residual pulmonary hypertension due to high pulmonary vascular resistance after left ventricular assist device implantation. However, intravenous milrinone caused a significant reduction in pulmonary vascular resistance and an increase in left ventricular assist device flow. Milrinone acts as both an inotropic agent and a direct vasodilator, and thus may avoid the need for mechanical support for right ventricular failure due to residual pulmonary hypertension after left ventricular assist device implantation.