Valen G, Kaszaki J, Szabo I, Nagy S, Vaage J
Department of Surgery, University of Tromsø, Norway.
Acta Physiol Scand. 1994 Apr;150(4):413-24. doi: 10.1111/j.1748-1716.1994.tb09706.x.
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.
在缺血-再灌注损伤期间，组胺从心脏释放。由于组胺具有心脏效应，我们研究了组胺在离体大鼠心脏缺血-再灌注损伤中的作用。采用Langendorff模型，进行30分钟的整体（37℃）缺血，随后再灌注60分钟。研究了单独缺血（n = 10，第1.1组 + n = 10，第2.1组，2个不同系列）以及用西咪替丁（10μM，n = 10）、氯苯那敏（10μM，n = 8）、特非那定（10μM，n = 8）和异丙嗪（10μM，n = 9）进行H1和H2受体阻断的缺血情况，或者同时使用西咪替丁和氯苯那敏（n = 8）的情况。在第1.1组的冠状动脉流出液和心脏组织中测量组胺。组胺释放从缺血前的6.5±1 pmol·min⁻¹增加到再灌注开始时的19±3 pmol·min⁻¹。在再灌注开始时，缺血使左心室舒张末压降至初始值的18±11%（第1.1组）和50±11%（第2.1组）（平均值±标准误）。左心室舒张末压从0升高到79±8 mmHg（第1.1组）和39±9（第2.1组）mmHg，而左心室收缩压未改变（第1.1组为101±12%，第2.1组为101±10%）。90%（第1.1组）和30%（第2.1组）的心脏诱发了严重心律失常，而再灌注期间冠状动脉血流量减少。H2受体阻断未改变缺血引起的左心室压力、冠状动脉血流量或心率的变化。三种不同的H1受体阻断剂增加了左心室收缩压，抑制了舒张末压的降低，减弱了舒张末压的升高，并完全抑制了再灌注心律失常。两种阻断剂联合使用的效果与单独使用H1受体阻断剂相似。与缺血对照组相比，在使用H1受体阻断剂的两组中，再灌注期间冠状动脉血流量增加。缺血-再灌注大鼠心脏中组胺释放增加与再灌注早期左心室功能抑制和心律失常同时出现。再灌注期间的心脏功能障碍被三种不同的H1受体阻断剂减轻。
