Amiloride enhances postischemic ventricular recovery: possible role of Na+-H+ exchange.
Amiloride (40 micrograms/ml) was studied in the isolated rat heart subjected to low-flow ischemia followed by reperfusion. Reperfusion after 30 min of ischemia produced recoveries of force, rate of force development (+dF/dt), and rate of relaxation (-dF/dt) of 42, 82, and 71%, respectively, in control hearts. Amiloride did not enhance the maximum degree of recovery, although, when present during ischemia, it markedly shortened the time required for peak recovery. Reperfusion after 60 min of ischemia resulted in 18, 43, and 34% recovery of force, +dF/dt, and -dF/dt, respectively. Amiloride significantly enhanced recovery to a maximum of 39, 88, and 78% for force, +dF/dt, and -dF/dt, respectively. The improved contractile recovery was accompanied with substantial reductions in the release of creatine kinase (CK) and 6-ketoprostaglandin F1 alpha. Coronary perfusion pressure and resting tension were generally unaffected by amiloride, although there was a moderate tendency to attenuate these parameters after reperfusion. The salutary effects of amiloride were dependent on the drug's presence during ischemia with maximum protection when it was administered during both ischemia and reperfusion and no benefit when added at the time of reperfusion. Because of amiloride's well-documented property in inhibiting Na+-H+ exchange, it is possible that this process plays an important role in modulating the cardiac response to reperfusion.
Karmazyn
M
M
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
D000584:Amiloride / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D013997:Time Factors
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D012964:Sodium