Acute antiischaemic properties of high dosages of intravenous diltiazem in humans in relation to its coronary and systemic haemodynamic effects.

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The antiischaemic properties of intravenous diltiazem in recommended therapeutic doses are disputed. In 17 patients with coronary artery disease the systemic and coronary haemodynamic effects of diltiazem were assessed during a high-dose infusion (0.4 mg kg-1 per 5 min, followed by 0.4 mg kg-1 per 10 min). In addition, its potential antiischaemic properties were investigated during identical pacing stress tests, 30 minutes before (P1) and immediately after diltiazem administration (P2). Diltiazem reduced left ventricular systolic pressure from 133 +/- 5 to 116 +/- 5 mmHg (P less than 0.005, means +/- SEM), persisting until after P2. It decreased systemic and coronary resistance by 32% (P less than 0.001) and 29% (P less than 0.005), respectively, with a sustained increase in cardiac output from 5.9 +/- 0.4 to 7.3 +/- 0.6 l min-1 (P less than 0.01), but a brief 20% rise in coronary flow (P less than 0.05), after the bolus infusion only. Heart rate, contractility, left ventricular filling pressure and myocardial O2 consumption remained unchanged. Despite high plasma levels (673 +/- 81 micrograms l-1) diltiazem was well tolerated. During identical maximal pacing rates diltiazem considerably reduced myocardial O2 demand (double product: 16.3 +/- 0.8 (P2) vs 21.1 +/- 1.1 (P1), P less than 0.005), due to an 18% decrease in left ventricular systolic pressure, resulting in diminished coronary flow and myocardial O2 consumption during P2 (14% and 15%, respectively, P less than 0.05 vs P1). Diltiazem also significantly reduced pacing-induced ischaemia, indicated by normalization of myocardial lactate extraction (1 +/- 8% (P2) vs -41 +/- 12% (P1), P less than 0.05), and left ventricular filling pressure (13 +/- 2 (P2) vs 27 +/- 3 mmHg (P1), P less than 0.01), less ST-segment depression (0.12 +/- 0.01 (P2) vs 0.24 +/- 0.02 mV (P1), P less than 0.01) and improved contractility (Vmax 59 +/- 5 (P2) vs 48 +/- 3 s-1 (P1), P less than 0.05). Angina was absent or less in 15 patients during pacing after diltiazem. Thus, diltiazem, in high dosages, induces continuing systemic but short lasting coronary vasodilation, improves pump function without negative chronotropic and inotropic effects and has pronounced antiischaemic properties, predominantly due to diminished myocardial O2 demand.