Effect of low perfusate [Ca2+] and diltiazem on cardiac sarcoplasmic reticulum in myocardial stunning.
The ability of low perfusate Ca2+ concentration ([Ca2+]) or diltiazem to improve sarcoplasmic reticulum (SR) function and mechanical performance after ischemia-reperfusion was investigated using an isovolumic Langendorff preparation. SR function was evaluated by the oxalate-supported Ca2+ uptake rates of ventricular homogenates. Influx of Ca2+ was estimated from the rate of Ca2+ uptake in the presence of high concentrations of ryanodine (500 microM) to close the Ca2+ efflux channel. Ca2+ efflux under the assay conditions was estimated as the difference in Ca2+ uptake rate in the presence and absence of ryanodine. Ten and fifteen min of global, normothermic ischemia decreased the Ca2+ uptake rate in the presence of ryanodine, suggesting that Ca2+ influx was decreased. The effect of ischemia on Ca2+ influx was not altered by preperfusion with low [Ca2+] (0.2 mM) or with 1.0 microM diltiazem. Ischemia decreased SR Ca2+ uptake rate twice as much in the absence of ryanodine as in its presence, indicating an increased efflux of Ca2+. This increased efflux was reduced by preperfusion with either low [Ca2+] or diltiazem. The decreased Ca2+ influx was completely reversed by 15 min of reperfusion, whereas the increased Ca2+ efflux was only partially reversed. These results indicate that ischemia exerts independent effects on the SR Ca2+ influx and efflux pathways. The results also suggest that one site of cardiac protection by low [Ca2+] or diltiazem is the ryanodine-sensitive Ca2+ efflux pathway of the SR, rather than the Ca2+ influx pathway.
Abdelmeguid
A E
AE
Department of Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Feher
J J
JJ
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D004110:Diltiazem; D002118:Calcium