FATTY-ACIDS SUPPRESS RECOVERY OF HEART FUNCTION AFTER HYPOTHERMIC PERFUSION

Working rat hearts were perfused for 15 minutes at 37-degrees-C before switching to a Langendorff perfusion (60 mm Hg aortic pressure) at 10-degrees-C for 40 minutes of hypothermic arrest. Ventricular function was allowed to recover for 15 minutes at 37-degrees-C by reestablishing the prehypothermic conditions. The perfusate was Krebs-Henseleit bicarbonate buffer containing 3% bovine serum albumin and either glucose (11 mmol/L) or glucose (11 mmol/L) plus palmitate (1.2 mmol/L) and gassed with 95% O2 and 5% CO2. In hearts receiving glucose alone as substrate, coronary flow was maintained constant during the 40 minutes of hypothermic arrest and returned to prehypothermic rates with rewarming. Ventricular function, as estimated by peak systolic pressure and heart rate, recovered to the prehypothermic level. When palmitate was added, coronary flow decreased continuously throughout the hypothermic perfusion (22% decrease by 40 minutes), and ventricular pressure development was lower throughout the rewarming perfusion. Tissue levels of adenosine triphosphate and creatine phosphate were well maintained and long-chain acyl coenzyme A and acyl carnitine decreased during hypothermia regardless of the substrate provided. With rewarming, tissue levels of adenosine triphosphate and creatine phosphate decreased in those hearts receiving palmitate. Omission of fattY acid either during hypothermia or during the first 5 minutes of rewarming improved recovery of function. Addition of oxfenicine to inhibit fatty acid oxidation, or inhibition of Ca2+ overload by verapamil and low perfusate Ca2+, prevented the effects of palmitate on ventricular function. Suppressed recovery of ventricular function after hypothermic perfusion in the presence of palmitate did not consistently correlate with low energy levels or high levels of metabolic products. Altered energy metabolism did not appear to be responsible for the fatty acid effect.