No abstract

Thirty-eight patients with refractory supraventricular and ventricular tachyarrhythmias were administered a mean oral dosage of 400 mg amiodarone daily (200-600 mg). A high-pressure liquid chromatography method was used to measure serum concentrations of amiodarone and its metabolite desethylamiodarone after one week, one month, three months, and then at 6-month intervals. In 24 patients subcutaneous fatty tissue concentrations were also measured. The mean follow-up was 9 months (4 days to 29 months). A linear correlation was found between amiodarone and its metabolite in serum (r = 0.56, p less than 0.001) as well as in subcutaneous fatty tissue (r = 0.67, p less than 0.001). While serum concentrations were dose dependent, tissue concentrations accumulated during chronic therapy (p less than 0.01, both). Clinical efficacy was achieved in 84% of the patients. No statistically significant difference was found between responders and non-responders as regards serum and subcutaneous fatty tissue concentrations. Side effects of amiodarone occurred in 63%. The incidence of adverse effects was related to significantly higher serum and subcutaneous fatty tissue concentrations of amiodarone and its metabolite (p less than 0.001, both). Thus, although the determination of serum and subcutaneous fatty tissue concentrations does not seem to be helpful for assessing clinical efficacy of this antiarrhythmic drug, these values may predict the occurrence of adverse effects.

Catheter ablation by radiofrequency energy was carried out in 10 patients with one type of recurrent monomorphic sustained ventricular tachycardia resistant to medical antiarrhythmic management. Electrophysiological studies before ablation included activation and pace-mapping. In all patients, the origin of the tachycardia was localized in the left ventricle: in the septum in six, at the posterolateral wall in three and anterobasal in one. The earliest onset of endocardia! activation preceding the QRS complex during ventricular tachycardia ranged between-45 and-90 ms. Transcatheter ablation was performed with a bipolar or quadripolar catheter using a radiofrequency generator (HA T100, Osypka). No complications occurred during the ablation procedure. Thereafter, in all patients, the clinical tachycardia was no longer inducible by programmed stimulation. During a follow-up period of 22 to 32 months including eight patients, the tachycardia recurred in two; one of these patients subsequently died suddenly. A third patient had one episode of a new type of sustained ventricular tachycardia some hours after catheter ablation. In the remaining patients, there was no recurrence of symptomatic tachycardia under maintainance of the antiarrhythmic management which, prior to ablation had been ineffective. Thus, our preliminary results suggest that radiofrequency catheter ablation might be beneficial for these high risk patients.

The modulation of the high-voltage-activated calcium current (ICa) by external ATP was examined in single ventricular cardiomyocytes of the hamster using the whole-cell configuration of the patch-clamp technique. Extracellular application of ATP (0.1-100 microM) was found to inhibit ICa reversibly. The inhibition followed a slow time course (half time approximately 25 s) and was accompanied by very small changes of the holding current and no shift in the current-voltage relationship. With 100 microM ATP, peak ICa was reduced by approximately 30%. This response was not blocked by the P1 inhibitor 8-cyclopentyl-1,3-dipropylxanthine. The nonhydrolyzable ATP analogs adenosine 5'-O-(3-thiotriphosphate) and AMP-adenosine 5'-[beta,gamma-imido]triphosphate also reduced ICa. The ATP analog alpha,beta-methylene-ATP was about equipotent with ATP at 50 microM. Internal guanosine 5'-O-(3-thiotriphosphate) (200 microM) rendered the ATP-mediated inhibition of ICa poorly reversible, whereas internal guanosine 5'-O-(2-thiodiphosphate) (200-500 microM) had no effect. Holding the intracellular adenosine 3',5'-cyclic monophosphate concentration at a constant high level did not alter the ATP response. We conclude that external ATP inhibits ICa via a P2 purinergic receptor in hamster ventricular myocytes. Our results suggest the involvement of a G protein not coupled to adenylate cyclase. The inhibition of ICa by extracellular ATP might have pathophysiological relevance under conditions of myocardial injury.

Summary: In a prospective study, 100 patients with various cardiac diseases not selected on the basis of previous ventricular arrhythmias underwent left ventricular endocardial mapping. With 10 different positions of the quadripolar catheter per patient, 90 of the 100 patients showed late potentials. These findings were documented in 50 of 52 patients with coronary heart disease compared to 26 of 34 patients with dilative cardiomyopathy (p ~0 . 0 2 5 ) .Late potentials in diastole were the most frequent type of abnormal electrogram, found in 82 patients. Fractionated electrograms were documented in 43 patients. They were seen in 27 (52%) coronary patients more often than in 8 (24 %) patients with dilative cardiomyopathy (p <0.025). Onset of fractionated electrograms in coronary patients was somewhat later (301 f 177 ms after the QRS) than in the cardiomyopathy group (263 * 141 ms).The duration was longer (189f 114 ms) in the former group than in the latter (148 f 87 ms). Thus, endocardial late potentials are not uncommon in patients with various cardiac diseases. The more frequent occurrence in coronary heart disease and the higher frequency of fractionated electrograms may indicate a more inhomogeneous, patchy type of fibrosis in the ischemically diseased myocardium.