title: Heparin-mediated reductions of the toxic effects of protamine sulfate on rabbit myocardium.
abstract: Protamine sulfate causes direct myocardial suppression when used to reverse heparin anticoagulation. Protamine's excessive positive charge accompanying its surface arginine groups appears to be responsible for this toxicity. This study was designed to assess the hypothesis that negatively charged heparin given after protamine exposure may enhance the recovery of protamine-induced myocardial dysfunction. Isolated rabbit hearts (n = 20) were perfused with physiologic saline solution at 80 to 90 mm Hg containing high dose protamine, 250 micrograms/ml, until heart contraction essentially ceased (baseline). Hearts were then randomly reperfused for 15 minutes with either physiologic saline solution (group I, n = 10) or heparin plus physiologic saline solution (group II, n = 10) at a dose of 0.1 IU/1.0 microgram of previously administered protamine. Developed left ventricular blood pressure, heart rate, pulmonary artery PaO2, contractility (+dp/dt), oxygen extraction (AvO2), oxygen consumption (VO2), and rate x pressure product were assessed. A protective, beneficial response accompanied heparin administration (group II) in all functions assessed except blood pressure. Maximum changes, comparing group I with II, were heart rate (beats/min) -72 versus -1, p less than 0.001; +dp/dt -64% versus -51%, p less than 0.01; PaO2 +86% versus +9%, p less than 0.001; AvO2 -37% versus -4%, p less than 0.001; VO2 -50% versus -28%, p less than 0.008; and rate x pressure product -73% versus -51%, p less than 0.001. These data suggest a separation of protamine's hemodynamic effects (blood pressure) and metabolic effects (VO2). Furthermore, these data support the tenet that heparin is able to markedly lessen the toxic myocardial effects of protamine.
authors.affiliation: Jobst Vascular Research Laboratories, Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0329.
authors.forename: T W
authors.initials: TW
authors.lastname: Wakefield
authors.forename: S K
authors.initials: SK
authors.lastname: Wrobleski
authors.forename: B J
authors.initials: BJ
authors.lastname: Nichol
authors.forename: A M
authors.initials: AM
authors.lastname: Kadell
authors.forename: J C
authors.initials: JC
authors.lastname: Stanley
mesh_terms: D000818:Animals; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008660:Metabolism / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D011479:Protamines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011817:Rabbits
chemical_list: D011479:Protamines; D006493:Heparin