HISTAMINE-RELEASE AND ITS EFFECTS IN ISCHEMIA-REPERFUSION INJURY OF THE ISOLATED RAT-HEART

Histamine is released from the heart during ischaemia-reperfusion inju ry. As histamine has cardiac effects, are investigated the role of his tamine in ischaemia-reperfusion injury of isolated rat hearts. A Lange ndorff-model with 30 min global (37 degrees C) ischaemia followed by 6 0 min reperfusion was employed. The effects of ischaemia alone (n = 10 , group 1.1 + n = 10, group 2.1, 2 different series), and ischaemia wi th H-1- and H-2-receptor blockade with cimetidine (10 mu M, n = 10), c hlorpheniramine (10 mu M, n = 8), terfenadine (10 mu M, n = 8), and pr omethazin (10 mu M, n = 9), or both cimetidine and chlorpheniramine (n = 8), were studied. Histamine was measured in the coronary effluent a nd cardiac tissue of group 1.1. Release of histamine increased from 6. 5 +/- 1 pmol min(-1) before ischaemia to 19 +/- 3 pmol min(-1) at the start of reperfusion. Ischaemia decreased left ventricular developed p ressure to 18 +/- 11% (1.1) and 50 +/- 11 % (2.1) of initial value (me an +/- SEM) at the start of reperfusion. Left ventricular end-diastoli c pressure increased from 0 to 79 + 8 mmHg (1.1) and 39 + 9 (2.1) mmHg , while left ventricular systolic pressure was unchanged (101 +/- 12% in 1.1 and 101 +/- 10% in 2.1). Severe arrhythmias were induced in 90 (1.1) and 30 (2.1)% of the hearts, while coronary flow decreased durin g reperfusion. H-2-blockade did not modify the changes in left ventric ular pressures, coronary how, or heart rate induced by ischaemia. Thre e different H-1-blockers increased left ventricular systolic pressure, inhibited the decrease of developed pressure, attenuated the increase of end-diastolic pressure, and totally inhibited reperfusion arrhythm ias. The effect of both blockers together was similar to that of H-1-b lockers alone. Coronary flow was increased during reperfusion in two o f the groups with H-1-blocker compared with ischaemic controls. Increa sed release of histamine from ischaemic-reperfused rat hearts concurre d with depression of left ventricular function and arrhythmias during early reperfusion. Cardiac dysfunction during reperfusion was attenuat ed by three different H-1-receptor blockers.