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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Experimental antifibrillatory effects of calcium channel blockade with diltiazem: comparison with beta-blockade and
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.
Insights
Beta-blockade (timolol) significantly increased ventricular fibrillation thresholds more than calcium channel blockade (diltiazem) in dogs. Nitroglycerin had no effect, highlighting the need for clinical trials on mortality reduction in ischemic heart disease.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Calcium channel blockers and beta-blockers are used for angina.
- Their effectiveness against sudden cardiac death remains unclear.
Purpose of the Study:
- To compare the antifibrillatory effects of diltiazem, timolol, and nitroglycerin.
- To assess their impact on ventricular fibrillation thresholds during ischemia.
Main Methods:
- Anesthetized dogs underwent coronary ischemia.
- Ventricular fibrillation thresholds were measured before and after drug administration (diltiazem, timolol, nitroglycerin, or saline).
Main Results:
- Timolol significantly increased ventricular fibrillation thresholds under both ischemic and non-ischemic conditions.
- Diltiazem also increased thresholds, but to a lesser extent than timolol.
- Nitroglycerin did not alter ventricular fibrillation thresholds.
Conclusions:
- Beta-blockade (timolol) demonstrated stronger antifibrillatory effects than calcium channel blockade (diltiazem) in this experimental model.
- Further clinical studies are required to determine the comparative efficacy of these agents in reducing mortality in ischemic heart disease.
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