Chlorpromazine inhibits loss of contractile function, compliance and ATP in ischemic rabbit heart

Using a modified Langendorff preparation, rabbit hearts were either continuously perfused at 37 degrees C for 150 min, in the presence of O2 and substrate, or after a 30 min equilibration period exposed to global ischemia followed by 30 min of reperfusion. Ischemia, for 90 min at 27 decrees C or for 60 min at 37 degrees C was compared. Perfusion pressure, heart rate, and ventricular volume were maintained constant. Contractile function and metabolic status were assessed. The effect of chlorpromazine, administered (30 mg/kg IP) 30 min prior to sacrifice, was compared to the untreated animal. (1) Chlorpromazine had little effect on the contractile function or metabolic status of hearts continuously perfused for 150 min in the presence of O2 and substrate. (2) The chloropromazine-treated hearts maintained contractile function and metabolic status at preischemic levels following exposure to 90 min of global ischemia at 27 degrees C and reperfusion at 37 degrees C. Untreated hearts exhibited a severe deterioration in both contractile and metabolic parameters under the same conditions. Both untreated and chlorpromazine-treated hearts exhibited loss of contractile function after 60 min ischemia at 37 degrees C; untreated hearts had undetectable ATP levels while chlorpromazine-treated hearts exhibited low levels of ATP. (3) Untreated hearts, exposed to 90 min of ischemia at 27 degrees C, exhibited a significant loss in compliance, while the compliance of chlorpromazine-treated hearts was unchanged from pre-ischemic levels.(ABSTRACT TRUNCATED AT 250 WORDS)