Diltiazem (0.5 mg/l) decreases coronary vascular resistance during reperfusion, but not during low flow ischemia, in the isolated perfused rat heart.
Isolated rat hearts underwent low flow perfusion with a perfusion pressure of 15 mmHg for two hours followed by reperfusion at a perfusion pressure of 80 mmHg for two hours. In these severely damaged hearts we tested whether diltiazem (0.5 mg/l) administered during ischemia or during reperfusion had vasodilatory effects. Ischemia-induced progressive vasoconstriction was not influenced by the presence of diltiazem: during ischemia coronary vascular resistance (CVR) rose from 3.3 +/- 0.1 to 46.4 +/- 17.6 mmHg.ml-1.min in the diltiazem group and from 3.5 +/- 0.1 to 42.4 +/- 5.3 mmHg.ml-1.min in the control group (n.s.). If diltiazem was administered during reperfusion only CVR dropped from 45.7 +/- 9.2 to 4.4 +/- 1.1 mmHg.ml-1.min in the presence of diltiazem, and from 47.1 +/- 11.6 to 9.3 +/- 1.5 mmHg.ml-1.min in the control group (P less than 0.025). The disparity between diltiazem's effects during ischemia and reperfusion suggests a different mechanism of Ca2+-influx in vascular smooth muscle cells in ischemic and reperfused hearts: in reperfusion through the Ca2+-channels which are sensitive to calcium antagonists, and in ischemia through other channels, like the Na+/Ca2+ exchanger, or from intracellular calcium stores.
Mohanlal
R W
RW
Dept. Cardiology, University Hospital Leiden, The Netherlands.
Wijnmaalen
P
P
Mauve
I
I
Zeeuwe
P
P
van der Laarse
A
A
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology*; D008297:Male; D015425:Myocardial Reperfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D004110:Diltiazem