The Isolated Post Ischaemic Rat Heart is More Vulnerable to Protamine Sulphate Than the Non-Ischaemic Heart

Abstract

Protamine sulphate is currently used for the reversal of heparin anticoagulation but is known to cause direct myocardial depression. The purpose of this study was to compare the effects of protamine sulphate on the isolated heart with and without cardioplegic ischaemia. Isolated rat hearts (Langendorff preparation) were electrically paced at 300 beats/min and perfused with Krebs—Henseleit solution. Five groups were tested: (1) control: no ischaemia, no protamine; (2) no ischaemia, protamine; (3) no ischaemia, protamine (time-matched control to groups 4 and 5): (4) control: ischaemia, no protamine; and (5) ischaemia, protamine. Protamine sulphate was infused for 15 min at 10 μg/ml. In groups 4 and 5, cardioplegic ischemia was maintained for 30 min at 30°C before protamine exposure. Protamine decreased myocardial performance in a time- and dose-dependent manner. Protamine depressed mean (s.d.) myocardial left ventricular pressure in both non-ischaemic hearts (groups 2 and 3, to 49(4)% and 50(4)% from baseline, respectively) and post ischaemic hearts (group 5, to 28(8%). Mean (s.d.) left ventricular-developed pressure only partially recovered after protamine in post-ischaemic hearts (to 55(13)% of baseline) compared with full recovery of the non-ischaemic group. Protamine depressed coronary flow to 70(5)% and 74(8)% in non-ischaemic hearts (groups 2 and 3, respectively) and to 58(7)% in group 5. Coronary flow recovered completely at the end of the experiments in all protamine-treated groups. In conclusion, isolated rat hearts subjected to cardioplegic ischaemia are more vulnerable to protamine than are non-ischaemic hearts.