Calcium Channel Blockers and Cardiac Surgery

Abstract

Calcium channel blockers have an important role in the pharmacotherapy of cardiovascular disorders. These agents act by inhibiting the slow inward current into excitable cells, exert direct negative inotropic, chronotropic, and dromotropic activity, and are potent vasodilators. These direct effects are modified by reflex autonomic stimulation and by pathologic states. Serious adverse effects of the calcium channel blockers are most frequently observed in patients with ventricular dysfunction, conduction system disease, or concomitant beta blockade. Calcium channel blockers are indicated in the treatment of angina pectoris, supraventricular arrhythmias, and hypertension. The use of these agents in patients with hypertrophic cardiomyopathy, congestive heart failure, and pulmonary hypertension is investigational. The calcium channel blockers are gaining increased importance in the management of patients undergoing cardiac surgery. Verapamil is indicated for the treatment of post-cardiac-surgical atrial flutter and fibrillation; however, the calcium antagonists are not effective as prophylaxis against postoperative supraventricular arrhythmias. Laboratory studies have shown that drug interactions exist between calcium channel blockers and inhalational anesthetics and nondepolarizing neuromuscular blocking agents; clinical studies have demonstrated that these interactions are rarely significant. Perioperative coronary spasm can be effectively treated with the calcium channel blockers. The timing of calcium antagonist withdrawal prior to surgery is controversial, but continuation of therapy until surgery is usually safe. The clinical significance of platelet function inhibition by the calcium antagonists is unknown. Protection of ischemic myocardium by calcium channel blockers has been demonstrated. Important interactions between the calcium antagonists, hypothermia, and the ionic constituents of cardioplegia require further study before the role of these agents as adjuncts to clinical cardioplegia is defined. Expanded indications and the introduction of new calcium channel blockers will result in increased use of these agents in the future.

Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection

“…When administrated before reperfusion, this cardioprotective effect of nifedipine was lower in comparison to administration before ischemia [81,82]. This result is due to cytosolic Ca 2+ overload generated during ischemia and increased depolarization of cardiomyocytes at the onset of reperfusion, which reduces the cardioprotective efficacy of nifedipine [81,82,83,84,85]. Clinical studies suggest that post-ischemia treatment with nifedipine in patients with acute myocardial infarction reduced the incidence of ventricular arrhythmias, but was unable to reduce lethality [86,87,88,89,90,91].…”

Cardioprotective effects of 5‐hydroxymethylfurfural mediated by inhibition of L‐type Ca2+ currents

“…Work is ongoing in our laboratories to confirm the beneficial effects of the drug in a clinical setting of cardiac I/R. Ca 2+ channel blockers were extensively tested as additives to cardioplegic solutions to reduce myocardial injury, and divergent results were obtained,depending on experimental study parameters (Murphy and Wechsler, 1987). Although clinical studies have failed to demonstrate convincing benefits of Ca 2+ channel blockers in cardioplegic solutions so far (Christakis et al, 1986;Flameng et al, 1986), these drugs have remained attractive candidates as constituents of new cardioplegic formulations despite adverse effects, like depressed systolic function and atrioventricular block (Fallouh et al, 2009).…”