Effect of pretreatment with diltiazem on left ventricular function and intracellular calcium distribution in postischemic reperfused guinea-pig hearts.
BACKGROUND
It has been previously demonstrated that pretreatment with diltiazem preserves mitochondrial function during postischemic reperfusion.


OBJECTIVE
The purpose of this study was to perform cytochemical and hemodynamical assessment to confirm this demonstration.


METHODS
Isolated Langendorff-perfused guinea-pig hearts received 10 min of diltiazem (7.5 microM) treatment, were subjected to 10 min of global ischemia and to 20 min of reperfusion. Left ventricular function was monitored by connecting a balloon to a pressure transducer. Intracellular calcium was precipitated with potassium pyroantimonate and examined with a transmission electron microscope.


RESULTS
Compared with the control and the ischemic hearts, the diltiazem-pretreated hearts showed a significant increase in the left ventricular developed pressure (LVDP), dP/dtmax (P < 0.01), and recovery rates of the LVDP (P < 0.01 versus ischemic hearts) and dP/dtmax (P < 0.05), and a decrease in the heart rate (P < 0.01). The left ventricular end-diastolic pressure (LVEDP) and leakage of creatine kinase were not significantly different. Calcium deposits were seen along the inner aspects of the sarcolemma and t-tubule membranes, and in the mitochondria of the control hearts. The number of these deposits was considerably reduced after ischemia. They reappeared principally in the mitochondria by reperfusion. In contrast, the calcium deposits reappeared along the sarcolemma, t-tubule membranes, and cell junctions, and in the mitochondria in the diltiazem-pretreated hearts.


CONCLUSIONS
These results suggest that pretreatment with diltiazem may improve cardiac function during postischemic reperfusion, probably in part by maintenance of sarcolemmal integrity rather than by mitochondrial buffering function.
Rah
B J
BJ
Department of Histology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Kim
H O
HO
Park
Y W
YW
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D004110:Diltiazem / Q000627:therapeutic use*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*; D010477:Perfusion; D011292:Premedication; D016277:Ventricular Function, Left / Q000187:drug effects*
D003402:Creatine Kinase; D004110:Diltiazem; D002118:Calcium