Deceasing sarcoplasmic reticular (SR)
calcium may contribute to the myocardiac protection against
ischemia and reperfusion-induced injury. Therefore, using the isolated working rat heart model, we investigated the effect of
Thapsigargin (TH)-induced SR
calcium diminution on the myocardial protection when added either before onset of
ischemia or at time of reperfusion under conditions of normothermic
ischemia. Hearts (n = 6/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with
bicarbonate buffer. In the experimental protocol A, this was followed by a 3 min infusion of
St. Thomas' Hospital cardioplegic solution No. 2 (STS) containing various concentrations of TH. Hearts were then subjected to 34 min of normothermic (37 degrees C) global
ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). Reperfusion cardiac functions at 20 min of working perfusion was measured and compared with the preischemia values. STS added to 0.1 and 0.25 mumol/L TH improved recovery of aortic flow after 20 min reperfusion from 47 +/- 3% in the TH free controls to 62 +/- 3, 63 +/- 2% (n = 6) (p < 0.05). There was no difference in
creatine kinase (CK) leakage during Langendorff reperfusion between the TH treated groups and the control group. In the experimental protocol
B, 3 min of
cardioplegia without TH and 34 min of
ischemia (37 degrees C) were followed by
a 10 min Langendorff reperfusion with various concentrations of TH, then 10 min Langendroff reperfusion for washing out, and 20 min working reperfusion. When TH was added to reperfusate the recovery of aortic flow did not change, 0.5 mumol/L TH group had the detelious effect. Thus, TH, when added to the
cardioplegia, enhanced myocardial protection. We conclude that lessened uptake of Ca2+ into sarcoplasmic reticulum by inhibitors of the Ca(2+)-
ATPase pump can decrease
ischemia and reperfusion-induced injury.