[Enhancement of susceptibility to ouabain in ischemic rat heart].
During 10 mins of reperfusion after 25 mins global ischemia, subtoxic doses of ouabain (50, 100 microM) were used and followed by 20 mins reperfusion with standard buffer. At these doses ouabain had no harmful effects with 29% and 45% increase in developed pressure in aerobic hearts. Intracellular Na+ (Nai), 45Ca2+ uptake and recovery of ventricular function were measured. Nai increased from 15 to 64 mumol/g dw with no increase in 45Ca2+ uptake during ischemia. Upon reperfusion with standard buffer, additional gain in Nai at 2 mins (73 mumol/g dw) was followed by a rapid decline (at 10 mins: 48 mumol/g dw). 45Ca2+ uptake increased from 0.8 to 7.5 mumol/g dw after 30 mins reperfusion with decreased recovery of function (45%) and increased LVEDP (29 mmHg). Reperfusion with ouabain accelerated initial rise in Nai (2 mins: 79 and 83 mumol/g dw) and decline of Nai was retarded (10 mins: 65 and 83 mumol/g dw). Consequently, 45Ca2+ uptake and depression of function were augmented (Ca: 10.0, 11.5 mumol/g dw; function: 27%, 18%; LVEDP: 47, 48 mmHg) even when hearts were switched back to standard buffer. Combination of high K+ (20mM) reversed the effect of ouabain. The results suggested increased susceptibility to ouabain was caused by inhibited outward Na+ transport resulting in enhanced Ca2+ influx through Na+/Ca2+ exchange.
Tani
M
M
Department of Geriatrics, Keio University School of Medicine.
Neely
J R
JR
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology*; D004070:Digitalis; D006439:Hemodynamics / Q000187:drug effects*; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000009:adverse effects*; D010946:Plants, Medicinal; D010947:Plants, Toxic; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D007473:Ion Channels; D010042:Ouabain; D012964:Sodium; D011188:Potassium