Comparative study on the effects of intracoronary nicorandil and nitroglycerin in ischaemic, reperfused porcine hearts.
The direct cardioprotective properties of nitroglycerin and nicorandil were compared in regionally ischaemic (45 min), reperfused (24 h) porcine hearts. Intracoronary treatments, which were started 15 min prior to occlusion of the distal left anterior descending coronary artery (LAD), were continuously administered for 105 min. The following equi-hypotensive drug dosages were used in nine pigs each; nitroglycerin 6 micrograms.kg-1 x min before ischaemia and during 45 min of reperfusion, 0.6 microgram.kg-1 x min during ischaemia; nicorandil 5 micrograms.kg-1 x min before ischaemia and during 45 min of reperfusion, and 0.5 microgram.kg-1 x min during ischaemia. Nine control animals were treated with isotonic sodium hydrochloride solution (1 ml.min-1). Despite comparable effects on blood pressure, intracoronary nicorandil, in contrast to intracoronary nitroglycerin, did not increase heart rate. Although neither drug affected coronary blood flow significantly, nicorandil substantially reduced regional myocardial oxygen consumption before coronary artery occlusion (-37 +/- 22%, P = 0.003 vs control group, P = 0.01 vs nitroglycerin treatment). Infarct sizes (tetrazolium method) after 45 min of ischaemia and 24 h of reperfusion were significantly decreased by nicorandil (control group 76.9 +/- 19%, nicorandil group 49.3 +/- 24%, P = 0.012) whereas nitroglycerin exhibited a borderline effect (62.5 +/- 15%, P = 0.054). Both treatments resulted in improved regional systolic shortening of the reperfused segment at the end of the experiments but this was not significant. At these drug dosages the direct cardioprotective action of nicorandil is slightly superior to nitroglycerin. This may be ascribed to its K-channel opening property associated with reduced regional myocardial oxygen consumption before the onset of ischaemia.
Klein
H H
HH
Department of Cardiology, University of Marburg, Germany.
Pich
S
S
Lindert-Heimberg
S
S
Schade-Brittinger
C
C
Maisch
B
B
Nebendahl
K
K
D000818:Animals; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007269:Injections, Intra-Arterial; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020108:Nicorandil; D005996:Nitroglycerin / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013552:Swine; D014665:Vasodilator Agents / Q000627:therapeutic use*
D015221:Potassium Channels; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D005996:Nitroglycerin