Mechanisms of reduced reperfusion injury by low Ca2+ and/or high K+.
Mechanisms of the protective effects of low Ca2+ (0.15 mM) and/or high K+ (20 mM) concentrations in the buffer on reperfusion injury were investigated. Intracellular Na+ (Nai+) increased fourfold during 25 min of ischemia. When hearts were reperfused with the standard buffer (1.25 mM Ca2+, 5.9 mM K+), Nai+ increased further during the 1st 2 min (5-fold) and then declined by 30% at 10 min of reperfusion. Ca2+ uptake increased 6- and 12-fold at 10 and 30 min of reperfusion, respectively. Function, which was assessed as the product of developed pressure and heart rate, recovered to 45% of the preischemic value and end-diastolic pressure was elevated (EDP: 31 mmHg). Reperfusion for 10 min with low Ca2+ buffer abolished the increase in Ca2+ uptake during this period, but it increased 10-fold when the perfusate was switched back to the standard buffer. Accelerated Ca2+ influx at this time was probably through Na(+)-Ca2+ exchange because Nai+ did not decline during low Ca2+ reperfusion. Elevation of EDP was suppressed (12 mmHg), but development of pressure did not increase. Reperfusion for 10 min with high K+ buffer accelerated the decline in Nai+ by 70% and reduced the increase in Ca2+ uptake (8-fold). Recovery of function improved (67%, EDP: 18 mmHg). Further improvement in function (78%, EDP: 10 mmHg) was obtained along with less Ca2+ uptake (7-fold) when low Ca2+ and high K+ were combined. Recovery of energy metabolites at 10 and 30 min of reperfusion was not different among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Tani
M
M
Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822.
Neely
J R
JR
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000494:pharmacology*; D003327:Coronary Disease / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D008297:Male; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D004573:Electrolytes; D011188:Potassium; D002118:Calcium