Functional properties and responses to ischaemia-reperfusion in Langendorff perfused mouse heart

Despite minimal model characterisation Langendorff perfused murine hearts are increasingly employed in cardiovascular research, and particularly in studies of myocardial ischaemia and reperfusion. Reported contractility remains poor and ischaemic recoveries variable. We characterised function in C57/BL6 mouse hearts using a ventricular balloon or apicobasal displacement and assessed responses to 10-30 min global ischaemia. We examined the functional effects of pacing, ventricular balloon design, perfusate filtration, [Ca2+] and temperature. Contractility was high in isovolumically functioning mouse hearts (measured as the change in pressure with time (+dP/dt), 6000-7000 mmHg s(-1)) and was optimal at a heart rate of similar to 420 beats min(-1), with the vasculature sub-maximally dilated, and the cellular energy state high. Post-ischaemic recovery (after 40 min reperfusion) was related to the ischaemic duration: developed pressure recovered by 82 +/- 5 %, 73 +/- 4 %, 68 +/- 3 %, 57 +/- 2 % and 41 +/- 5 % after 10, 15, 20, 25 and 30 min ischaemia, respectively. Ventricular compliance and elastance were both reduced post-ischaemia. Post-ischaemic recoveries were lower in the apicobasal model (80 +/- 4 %, 58 +/- 7 %, 40 +/- 3 %, 32 +/- 7 % and 25 +/- 5 %) despite greater reflow and lower metabolic rate (pre-ischaemic myocardial O-2 consumption (Vo(2,myo)) 127 +/- 15 vs. 198 +/- 17 mul O-2 min(-1) g(-1)), contracture, enzyme and purine efflux. Electrical pacing slowed recovery in both models, small ventricular balloons (unpressurised volumes < 50-60 mul) artificially depressed ventricular function and recovery from ischaemia, and failure to filter the perfusion fluid to < 0.45 mum depressed pre- and post-ischaemic function. With attention to these various experimental factors, the buffer perfused isovolumically contracting mouse heart is shown to be stable and highly energised, and to possess a high level of contractility. The isovolumic model is more reliable in assessing ischaemic responses than the commonly employed apicobasal model.