Propofol improves recovery of the isolated working hypertrophic heart from ischaemia–reperfusion

Abstract

The general anaesthetic propofol shows promise in protecting normal hearts against various cardiac insults, but little is known about its cardioprotective potential in hypertrophic hearts. This study tested the hypothesis that propofol at a clinically relevant dose would enhance functional recovery in hypertrophic hearts following ischaemia. Hypertrophic hearts from spontaneously hypertensive rats and hearts from their normotensive controls, Wistar Kyoto Rats, were equilibrated in the working mode prior to global normothermic ischaemia. Reperfusion commenced with 10min in Langendorff mode, followed by 30-min working reperfusion. Functional performance was measured throughout the working mode, whilst reperfusion damage was assessed from myocardial troponin I release during Langendorff reperfusion. Where used, 4μg/ml propofol was added 10min before ischaemia and was washed out 10min into working reperfusion. An additional protocol investigated recovery of hearts protected by normothermic hyperkalaemic cardioplegic arrest. Following 20-min ischaemia, reperfusion damage was significantly worse in hypertrophic hearts compared to normal hearts, whilst addition of propofol to hypertrophic hearts significantly improved the aortic flow (31 ± 5.8 vs. 11.6 ± 2.0ml/min, n = 6-7 ± SE, p < 0.05). Propofol also conferred significant protection following 30-min ischaemia where the recovery of cardiac output and stroke volume was similar to that for cardioplegia alone. Incubation with propofol improved the NADH/NAD(+) ratio in freshly isolated cardiomyocytes from hypertrophic hearts, suggesting possible improvements in metabolic flux. These findings suggest that propofol at the clinically relevant dose of 4μg/ml is as effective as cardioplegic arrest in protecting hypertrophic hearts against ischaemia-reperfusion.