Vmax of the action potential upstroke in canine cardiac Purkinje fibers was studied in the presence of seven class I antiarrhythmic drugs--lidocaine (4 micrograms/ml), mexiletine (4 micrograms/ml), propranolol (0.9 micrograms/ml), procainamide (30 micrograms/ml), quinidine (5 micrograms/ml), flecainide (4 micrograms/ml), and disopyramide (3.1 micrograms/ml)--at constant cycle lengths (CCL) and after abrupt changes in cycle length (ACCL). The time constant of Vmax recovery after ACCL at a basic cycle length of 500 ms was 0.09 +/- 0.01 s for lidocaine, 0.18 +/- 0.03 s for mexiletine, 1.35 +/- 0.20 s for propranolol, 4.4 +/- 0.8 s for procainamide, 8.3 +/- 1.2 s for quinidine, 11.0 +/- 0.9 s for flecainide, and 37.9 +/- 9.4 s for disopyramide. These values were similar to those reported by others in guinea pig papillary muscle, and, with the exception of flecainide, conformed to the scheme proposed by Courtney (J Mol Cell Cardiol 1980; 12:1273-86) based on the molecular weight and lipid solubility hypothesis. Each drug altered the Vmax differently at CCL from after ACCL at the same diastolic intervals. The magnitude of these differences and the range of diastolic intervals at which they were present varied among different drugs. These observations explain differences in the drug effects on the Vmax of the regularly and prematurely occurring depolarizations. In the presence of lidocaine and mexiletine, the recovery kinetics of Vmax were not altered by CCL within the 300-1,500-ms range, and the magnitude of Vmax depression was not influenced by action potential duration within the 200-270-ms range.

Action Potentials↗

PubMedDate not supplied

Effect of antiarrhythmic drugs on the cycle length-dependent action potential duration in dog Purkinje and ventricular muscle fibers.

We examined the steady-state action potential duration (APD) within a wide range of cycle lengths (CL) in cardiac dog Purkinje (P) and ventricular (V) muscle fibers in the presence of: lidocaine (L) 4 and 8 micrograms/ml, mexiletine (M) 4 and 8 micrograms/ml, flecainide (F) 1 and 4 micrograms/ml, disopyramide (D) 3.1 and 10 micrograms/ml, quinidine (Q) 2.5, 5, and 10 micrograms/ml, bretylium tosylate (B) 5 and 10 micrograms/ml, and sotalol (S) 5 micrograms/ml. In the P fibers, all drugs except for B and S shortened plateau duration, increased slope of phase 2 and decreased slope of phase 3 repolarization, and either shortened (L, M, Q, F) or prolonged (D) APD. B and S lengthened APD and did not change significantly the slopes of phase 2 and 3 of repolarization. Each drug altered the relation between APD and Cl according to one of the following three patterns: (a) L, M, Q, and F shortened APD more at long than at short CL; (b) D lengthened APD more at short than at long CL; (c) B and S lengthened APD more at long that at short CL. In the V fibers, APD was lengthened by F, Q, and B, and shortened by L and M. The drug-induced changes in the relation between APD and CL were as in the P fibers. The results suggest that the drug-induced changes in the relation between APD and CL can be predicted from the drug effects on the course of repolarization.

Action Potentials↗

PubMedDate not supplied

Noninvasive assessment of ventricular arrhythmias in clinical practice: prognostic implications.

Frequency and complexity of ventricular arrhythmias increases with age and increasing severity of heart disease. However, fatal ventricular fibrillation occurs frequently in the absence of symptomatic warning arrhythmias. Several classifications of ventricular arrhythmias are discussed. The morphology of ventricular premature complexes (VPC), their frequency and complexity at rest, during ordinary activity, or after exercise do not influence life expectancy of subjects without heart disease, nor in those with coronary artery disease with no history of myocardial infarction. In the survivors of myocardial infarction, the frequency and "complexity" of ventricular arrhythmias appears to be an independent risk factor for sudden and nonsudden cardiac death. However, the low specificity and predictive value of ventricular arrhythmias makes their assessment difficult for practical purposes. The prognosis of most patients with ventricular arrhythmias is determined predominantly by the condition of the heart. "Complex" arrhythmias at rest and during exercise do not appear to worsen prognosis and life expectancy in individuals without heart disease. Ambulatory electrocardiographic monitoring has serious limitations as a guide for clinical decision making. Ventricular tachycardias in patients with coronary artery disease are not strictly related to the frequency and "complexity" of ventricular premature complex, but correlate with the presence of ventricular aneurysms, poor ventricular function and late potentials in the signal-averaged high frequency electrocardiogram. Recording of such late potentials is a new and promising noninvasive technique for identification of patients with serious arrhythmias but the sensitivity and specificity of this method remains to be established.

Arrhythmias, Cardiac↗

PubMedDate not supplied

Symposium: sudden cardiac death.

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Coronary Care Units↗