Ex vivo rat heart normothermic perfusion with intermittent low flow and triiodothyronine

Ischemia-reperfusion injury remains the main constraint of normothermic perfusion. The present study investigated the potential of therapies targeting reperfusion injury such as triiodothyronine and interventions mimicking ischemic preconditioning (PC) to optimize normothermic crystalloid perfusion.

Rat hearts were perfused for 6 h with constant flow, in a Langendorff mode and Krebs-Henseleit as perfusate with glucose being the only metabolic substrate, (NP, n = 9). PC treated hearts were subjected to 5 cycles of 40 min low flow perfusion followed by 20 min normal flow perfusion with either vehicle (PC, n = 11) or 60nM T3 (PC + T3, n = 10). Left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), perfusion pressure (PP), and percentage of change of these parameters from baseline values were measured. The ratio of LV weight to body weight was calculated as index of tissue edema.

Baseline parameters were similar between groups. At the end of perfusion, no difference in LVDP was observed, LVEDP was significantly lower in PC and PC + T3 vs. NP, p < 0.05. PP was significantly lower in both PC and PC + T3 vs. NP hearts. p < 0.05. Both PC and PC + T3 significantly reduced tissue edema.

Intermittent low flow mimicking ischemic preconditioning (PC) appears to optimize crystalloid based normothermic rat heart perfusion by limiting tissue edema and diastolic and vascular dysfunction.