title: Diphenhydramine protection of the failing myocardium during gram-negative endotoxemia.
abstract: Gram-negative endotoxin (Escherichia coli, 4 mg/kg) was found to produce a sustained fall in systemic arterial pressure, left ventricular pressure, and cardiac output that could be blocked by the histamine antagonist diphenhydramine. Histamine infusion was found to produce a parallel depression of systemic arterial pressure. Further, endotoxemia was found to produce a significant depression of myocardial contractility (dP/dt max) that could also be blocked by diphenhydramine. Cardiac myofibrillar adenosine triphosphatase (ATPase) activity from endotoxin-shocked hearts was found to be depressed, ATPase activity from subendocardial myofibrils being more depressed than that from subepicardial myofibrils. Myofibrillar ATPase activity was significantly protected by pretreating the animals with diphenhydramine. It is concluded that the initial hemodynamic phase of endotoxin shock is histamine-mediated and that this hemodynamic depression can be blocked with diphenhydramine. Further, it appears that endotoxin is capable of depressing myocardial contractility by depressing contractile protein function (myofibrillar ATPase activity)--the subendocardial surface more so than the subepicardial surface--and this depression of myocardial contractility can be blocked with diphenhydramine.
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004155:Diphenhydramine / Q000494:pharmacology*; D004285:Dogs; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology; D004926:Escherichia coli; D005260:Female; D006321:Heart / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology
chemical_list: D004731:Endotoxins; D006632:Histamine; D004155:Diphenhydramine; D000251:Adenosine Triphosphatases