Section Review: Cardiovascular and Renal: Ion channel modulators in the treatment of congestive heart failure

Current therapy of heart failure is inadequate, relying on positive inotropic compoundsto increase force of contraction by the heart, diuretics to relieve oedema, vasodilators to decrease cardiac workload and, possibly, β-adrenoceptor antagonists to reverse compensatory responses. Since ion channels control the flux of Na+, K+, Ca2+, and Cl- across cardiac and vascular smooth muscle cell membranes, modification of the kinetics of these channels may attenuate disease-induced changes in the cardiovascular system.2. Na+ channel blockers are widely used as antiarrhythmics but produce negative inotropy. Newer compounds, such as BDF 9148, increase Na+ influx by inhibiting inactivation of Na+ channels, prolonging the action potential duration and inhibiting Na+/Ca2+ exchange. These compounds produce positive inotropy possibly with antiarrhythmic actions.3. Ca2+ channel blockers are widely used as vasodilators in hypertension yet may worsen heart failure. Compounds which selectively increase Ca2+ influx into cardiac cells (e.g., the dihydropyridine Bay Y 5959) may increase cardiac force without increasing vascular tone.4. K+ channels are the most diverse group with few truly selective pharmacological tools. In particular, compounds which block the delayed outward rectifier current in the heart, such as almokalant and dofetilide, lengthen the cardiac action potential thus increasing Ca2+ influx and force. These compounds may combine positive antiarrhythmic properties. KATP channel openers, such as pinacidil, are useful as vasodilators in hypertension.5. Thus, drugs which increase Na+ or Ca2+ influx or decrease K+ efflux represent exciting possibilities to increase cardiac contractility. In addition, these compounds may relax blood vessels or prevent cardiac arrhythmias. The potential of these compounds in the treatment of patients with heart failure needs to be fully evaluated.