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Comparative Effects of Diltiazem, Nifedipine, and Verapamil on Large and Small Coronary Artery Constriction Induced by Intracoronary Acetylcholine in Pigs

Summary: The in vivo protective effects of diltiazem, nifedipine, and verapamil on large and small coronary artery constriction induced by intracoronary injection of acetylcholine were compared by coronary arteriography in pigs. The percent narrowing of the epicardial major right coronary artery was used as an indicator of large coronary artery constriction, and the time required for contrast medium to reach the posterior descending coronary artery from the ostium of the right coronary artery was used as an indicator of small coronary artery constriction. Doses of 12.5, 25, 50, 100, and 200 μg of acetylcholine were administered into the right coronary artery under left ventricular pacing to keep the systemic hemodynamics constant. Marked prolongation of the flow time of contrast medium to ≥8.1 s (control of ≤1.8 s) with mild narrowing of the epicardial major right coronary artery (≤35%) was observed at doses of 12.5–50 μg of acetylcholine and was accompanied by myocardial ischemia. Over 50% narrowing of the epicardial major coronary artery plus markedly slow flow of contrast medium were induced in 12 of the 15 pigs by 100–200 μg of acetylcholine. Narrowing of the epicardial major coronary artery and the delay time of contrast medium flow induced by acetylcholine were both significantly reduced to 12–33% (control: 36–81%) and to 4.3–16.8 s (control: 16.2–37.7 s) after intracoronary injection of 100 μg of diltiazem. The changes were 15–28% vs. 40–79% and 2.7–11.3 s vs. 18.1–36.1 s after nifedipine injection (10 μg), as well as 19–48% vs. 44–82% and 1.5–9.3 s vs. 15.4–41.6 s after verapamil injection (100 μg). The percent of the control constriction (100%) of large and small coronary arteries was reduced to 36 ∼ 7 and 38 ∼ 9% with diltiazem, respectively, 37 ∼ 6 and 27 ∼ 11% with nifedipine, respectively, and 47 ∼ 9 and 13 ∼ 5% with verapamil, respectively. These data indicate that although diltiazem, nifedipine, and verapamil all protected large and small porcine coronary arteries from constriction induced by acetylcholine, the potency and selectivity of their vasodilatory effects showed some differences.