Effect of heparin on myocardial contractility of the dog and on Na, K-ATPase.
It has recently been reported that heparin administration to rabbits is followed by an inhibition of the Na, K-ATPase of the myocardial sarcolemma. Further investigation of this phenomenon in an experimental animal which enables measurement of changes in myocardial contractility are presented here. The left ventricular pressure and the quotient of its first derivative to its total value (dp/dt/P) were followed for 60 min in 16 anesthetized dogs administered with heparin (700-5000 i.u./kg), as well as in 10 non treated animals. All animals were then sacrificed and myocardial Mg and Na, K-ATPase were assayed. The measured (dp/dt/P)max(Vpm) changes in the heparin treated animals at the 60th min of the experiment were positively correlated to the dose of heparin. A significant increase of Vpm values was observed only in the animals treated with doses of heparin higher than 2000 i.u./kg compared to non heparin group. A significant animals of the heparin group only, this decrease was not dose dependent. It is concluded that very large doses of heparin increase heart contractility by a mechanism probably not directly related to that which caused the Na, K-ATPase inhibition observed following heparin administration. Evidence is presented suggesting that lysophosphatidylcholine (LPC) is involved in the mechanism of this inhibition.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase; D004285:Dogs; D005260:Female; D006352:Heart Ventricles; D006493:Heparin / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D010042:Ouabain / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects* / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013268:Stimulation, Chemical
D008244:Lysophosphatidylcholines; D010042:Ouabain; D006493:Heparin; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase