Experimental Antifibrillatory Effects of Calcium Channel Blockade with Diltiazem

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Abstract
Calcium channel blockade appears to be at least as effective as β-blockade in the treatment of anginal syndromes, but whether a similar protective effect is afforded against sudden death is unknown. In order to compare experimental antifibrillatory effects of calcium channel blockade (diltiazem), β-adrenoceptor blockade (timolol), and nitroglycerin, we measured ventricular fibrillation (VF) thresholds in anesthetized, open-chest dogs before and after 3 min of coronary ischemia before and after i.v. administration of each of these drugs or saline. In control studies, VF occurred after delivery of 11.8 ± 5.3 mA (x ± SD) in the nonischemic state and 9.4 ± 4.6 mA during ischemia (n = 25). During saline administration, no significant change in VF threshold occurred during ischemia, and a minimal increase over time occurred in the nonischemic state. Diltiazem (0.04–0.08 mg/kg/min; n = 10) increased VF thresholds under both ischemic (by 7.7 mA, p < .01) and nonischemic (by 5.5–5.8 mA, p < .05) conditions. Timolol (0.03 mg/kg; n = 8) caused substantially greater increases in VFT during nonischemia and ischemia: 11.2 ± 2.8 mA to 51.6 ± 38.5 mA (nonischemia) and 8.4 ± 3.8 mA to 28.7 ± 16.4 mA (ischemia), both p < 0.02. VF thresholds were not changed after nitroglycerin (n = 8). Differing experimental effects of these drugs emphasize the need for clinical studies to establish the relative potential of calcium channel blockade and nitroglycerin to reduce mortality in ischemic heart disease.