End-organ function during chronic nonpulsatile circulation

Background. Evolving blood pump technology has produced user-friendly continuous flow left ventricular assist devices, but uncertainty exists about the safety of chronic nonpulsatile circulation. We established consistently nonpulsatile blood flow in a sheep model using the Terumo magnetically suspended centrifugal pump. We then compared end-organ function between pulseless and control animals. Methods. Fifteen healthy sheep (65 to 85 kg) were allocated to either left ventricular assist device (n = 9) or control (n = 6) groups. We implanted the device through a left thoracotomy and determined the flow rate at which pulse pressure was absent. The flow rate was then adjusted to exceed that rate (4.2 ± 1.5 L/min), and all variables of pump function were continuously monitored by computer. Blood tests were taken serially for hepatic and renal function and plasma renin levels. The sheep were sacrificed electively at 30 (n = 3), 90 (n = 4), 180 (n = 1), and 340 (n = 1) days. Detailed histologic examination was made of the brain, liver, kidney, myocardium, and major arteries. Results. All animals remained in good condition until sacrifice. All measures of end-organ function remained within normal limits for both groups. There were no histologic differences between the organs of pulsatile and nonpulsatile animals. Although there was no significant difference in mean blood pressure, plasma renin levels were substantially elevated in pulseless animals (1.4 ± 0.3 pg/mL versus 2.9 ± 0.3 pg/mL; p< 0.05). We also identified thinning of the medial layer of the ascending aorta in nonpulsatile sheep (1.8 ± 0.4 mm in left ventricular assist device animals versus 2.6 ± 0.6 mm in control sheep; p< 0.05). Conclusions. Chronic nonpulsatile circulation was well tolerated, and we found neither functional nor histologic changes in major end organs. The renin-angiotensin system was upregulated, but this did not provide a significant rise in blood pressure. The changes in the aortic wall merit further investigation. As a result of these findings, we consider that nonpulsatile devices can be used safely for long-term circulatory support.