Histamine Mediates Myocardial Damage by an H1 Mechanism Independent of Coronary Blood Flow

Administration of histamine to rabbits may result in myocardial damage similar to that produced by catecholamines and the anthracycline antibiotics. To explore the mechanisms involved in histamine-mediated myocardial damage, conscious New Zealand white rabbits were pretreated with H1 and H2 receptor blocking agents, alone and in combination, and then administered histamine. Coronary artery blood flow was measured with radiolabeled microspheres in rabbits that received histamine alone, and in those that received an H1 blocking agent and histamine. Rabbits that received an H, blocking agent had a significant reduction in morphological injury which was scored as followsgrade 1, minimal or no injury; grade 2, moderate; and grade 3, severe injury (mean pathology score = 1.1 ± 0.28 for histamine alone vs. 0.06 ± 0.06 with H, receptor blockade, p < 0.05). Animals pretreated with H1 receptor blockade (mean pathology score = 1.2 ± 0.49) were not protected against morphological injury. Coronary blood flow de-creased in animals that received histamine alonecontrol = 2.61 ± 0.38 vs. 1.80 ± 0.30 ml/min/g (p < 0.05), and in animals pretreated with H, blockade; control = 3.29 ± 0.34 vs. 1.91 ± 0.28 ml/min/g (p < 0.01). We conclude that histamine-mediated myocardial damage appears to be mediated by the H1 receptor system and that this appears to be independent of initial changes in global coronary blood flow.