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 H1 blocking agent had a significant reduction in morphological injury which was scored as follows: grade 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 H1 receptor blockade, p less than 0.05). Animals pretreated with H2 receptor blockade (mean pathology score = 1.2 +/- 0.49) were not protected against morphological injury. Coronary blood flow decreased in animals that received histamine alone: control = 2.61 +/- 0.38 vs. 1.80 +/- 0.30 ml/min/g (p less than 0.05), and in animals pretreated with H1 blockade; control = 3.29 +/- 0.34 vs. 1.91 +/- 0.28 ml/min/g (p less than 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.
Department of Pathology, Stanford University Medical Center, California.
N E
NE
Kantrowitz
A K
AK
Ellis
M R
MR
Bristow
W
W
Minobe
M E
ME
Billingham
D C
DC
Harrison
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004155:Diphenhydramine / Q000494:pharmacology; D005260:Female; D006331:Heart Diseases / Q000503:physiopathology*; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008863:Microspheres; D011817:Rabbits
D006634:Histamine H1 Antagonists; D006632:Histamine; D004155:Diphenhydramine