New continuous-flow total artificial heart and vascular permeability

Abstract

Background We tested the short-term effects of completely non-pulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability. Methods Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10–25 mmHg) at a rate of 40 pulses per minute (PP). The remaining 5 calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (POD) 1, 7 and 14. Skeletal muscle tissue water content was measured and morphological alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin and CD31 were analyzed by immuno-histochemistry. Results There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, POD 1, 7 and 14, respectively. There were no significant alterations in the expression/distribution of VE-cadherin, phospho-VE cadherin and CD31 in skeletal muscle vasculature at baseline, POD 1, 7 and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histological damage scores at POD 7 and 14, it failed to reach statistical significance. Conclusions There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability.

Calpain inhibition decreases inflammatory protein expression in vessel walls in a model of chronic myocardial ischemia

“…[13–15] Briefly, to induce metabolic syndrome 25 Yorkshire Swine (E.M. Parsons and Sons, Hadley MA) were fed a high fat/ high cholesterol diet (4% cholesterol, 2.3% corn oil, 17.2% coconut oil, 1.5% sodium cholate and 75% regular chow) for four weeks (Sinclair Research, Columbia, MO). To induce chronic myocardial ischemia, the pigs then underwent a procedure to place an ameroid constrictor on their Left Circumflex artery to induce chronic coronary artery ischemia.…”

The ongoing quest for the first total artificial heart as destination therapy

“…Although LVADs were developed to assist the native left ventricle, these devices are powerful enough to take over the function of the native ventricle completely. Therefore, several research groups have investigated the efficacy of two commercially available LVADs (such as HeartMate II, Heartmate III, HeartWare HVAD, Jarvik 2000 and HeartAssist 5) combined into a TAH configuration after removing the native heart 85,86,87,88,89,90,91,92,93,94 . The configuration of two LVADs functioning as a TAH has been tested in animal studies and clinical trials 85,86,87,88,89,90,91,92,93,94 .…”

“…Therefore, several research groups have investigated the efficacy of two commercially available LVADs (such as HeartMate II, Heartmate III, HeartWare HVAD, Jarvik 2000 and HeartAssist 5) combined into a TAH configuration after removing the native heart 85,86,87,88,89,90,91,92,93,94 . The configuration of two LVADs functioning as a TAH has been tested in animal studies and clinical trials 85,86,87,88,89,90,91,92,93,94 . In this Review, we refer to the configuration of two commercially available LVADs functioning as a TAH as 'LVAD-TAH'.…”