title: Experimental antifibrillatory effects of calcium channel blockade with diltiazem: comparison with beta-blockade and nitroglycerin.
abstract: Calcium channel blockade appears to be at least as effective as beta-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), beta-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 less than .01) and nonischemic (by 5.5-5.8 mA, p less than .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 less than 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.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D004110:Diltiazem / Q000097:blood / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D008297:Male; D005996:Nitroglycerin / Q000627:therapeutic use*; D013999:Timolol / Q000627:therapeutic use; D014693:Ventricular Fibrillation / Q000517:prevention & control*
chemical_list: D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D002121:Calcium Channel Blockers; D013999:Timolol; D004110:Diltiazem; D005996:Nitroglycerin