title: Histamine release and its effects in ischaemia-reperfusion injury of the isolated rat heart.
abstract: Histamine is released from the heart during ischaemia-reperfusion injury. As histamine has cardiac effects, we investigated the role of histamine in ischaemia-reperfusion injury of isolated rat hearts. A Langendorff-model with 30 min global (37 degrees C) ischaemia followed by 60 min reperfusion was employed. The effects of ischaemia alone (n = 10, group 1.1 + n = 10, group 2.1, 2 different series), and ischaemia with H1- and H2-receptor blockade with cimetidine (10 microM, n = 10), chlorpheniramine (10 microM, n = 8), terfenadine (10 microM, n = 8), and promethazin (10 microM, n = 9), or both cimetidine and chlorpheniramine (n = 8), were studied. Histamine was measured in the coronary effluent and 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 pressure to 18 +/- 11% (1.1) and 50 +/- 11% (2.1) of initial value (mean +/- SEM) at the start of reperfusion. Left ventricular end-diastolic 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 during reperfusion. H2-blockade did not modify the changes in left ventricular pressures, coronary flow, or heart rate induced by ischaemia. Three different H1-blockers increased left ventricular systolic pressure, inhibited the decrease of developed pressure, attenuated the increase of end-diastolic pressure, and totally inhibited reperfusion arrhythmias. The effect of both blockers together was similar to that of H1-blockers alone. Coronary flow was increased during reperfusion in two of the groups with H1-blocker compared with ischaemic controls. Increased release of histamine from ischaemic-reperfused rat hearts concurred with depression of left ventricular function and arrhythmias during early reperfusion. Cardiac dysfunction during reperfusion was attenuated by three different H1-receptor blockers.
authors.affiliation: Department of Surgery, University of Tromsø, Norway.
authors.forename: G
authors.initials: G
authors.lastname: Valen
authors.forename: J
authors.initials: J
authors.lastname: Kaszaki
authors.forename: I
authors.initials: I
authors.lastname: Szabo
authors.forename: S
authors.initials: S
authors.lastname: Nagy
authors.forename: J
authors.initials: J
authors.lastname: Vaage
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D003326:Coronary Circulation; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D006439:Hemodynamics; D006636:Histamine Release; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000502:physiology