Abnormal lanthanum accumulation due to ischemia in isolated myocardium: effect of chlorpromazine

The progression of functional, structural, and membrane permeability alterations in the isolated, perfused rabbit interventricular septal preparation was examined at 1, 1.5 or 2 h of ischemia and during 1 h of postischemic reflow. Two other groups of rabbits were pretreated with chlorpromazine (15 and 25 mg/kg), a drug with inhibitory effects on Ca influx and phospholipase activation. The ability of the septa to contract decreased markedly during the ischemic period, but a graded recovery response in physiological contractile parameters was observed upon reperfusion. In septa with comparable preischemic contractile function, pretreatment with chlorpromazine resulted in better functional recovery than that of nontreated septa. Ultrastructural examination showed more extensive and severe damage with increasing periods of ischemia. Ionic La-probe studies of altered membrane integrity showed extensive abnormal intracellular La deposition with ischemic periods of 1.5 h or longer followed by reperfusion. Septa pretreated with chlorpromazine showed better preservation of cell integrity and less intracellular lanthanum deposition. Thus, in this model, a good correlation was found between the extent of functional, structural, and membrane permeability alterations caused by ischemia, and a protective effect of chlorpromazine was shown.