Long-term follow-up of patients receiving aprindine. Safety and efficacy.

Aprindine hydrochloride is an antiarrhythmic agent presently undergoing clinical trials in the United States. Because of the narrow therapeutic-toxic ratio observed for aprindine, the long-term follow-up of these patients is important in determining the potential clinical effectiveness of this drug. In this report we examine our experience with 30 patients with drug-resistant arrhythmias who were discharged receiving aprindine and who were followed up for a mean period of 25 months.

Ventricular tachycardia: prediction of response to oral aprindine with intravenous aprindine.

Aprindine was administered both intravenously and orally to 25 patients with ventricular tachycardia refractory to conventional antiarrhythmic agents to test the hypothesis that the response to intravenous aprindine predicts the response to oral aprindine. Ten patients had incessant ventricular tachycardia and 15 had paroxysmal sustained inducible ventricular tachycardia. Eleven patients (43 percent) had conversion to sinus rhythm with intravenous aprindine (nine with incessant and two with paroxysmal sustained ventricular tachycardia). Thirteen patients (all with paroxysmal sustained ventricular tachycardia) manifested slowing of the tachycardia without conversion, whereas in one patient with incessant ventricular tachycardia, the tachycardia became less frequent and nonsustained after intravenous aprindine. All 11 patients who had conversion to sinus rhythm with intravenous aprindine remained free of ventricular tachycardia during oral treatment with aprindine (at 2 weeks) and for a follow-up period of 2 to 38 months (mean 16 +/- 13). Of the 14 patients who did not have conversion to sinus rhythm with intravenous aprindine, 12 had spontaneous or inducible ventricular tachycardia, or both, at evaluation 1 to 2 weeks after initiation of oral aprindine. In conclusion, administration of intravenous aprindine to patients with ventricular tachycardia is helpful in predicting the subsequent response to oral aprindine. In addition, the pattern of ventricular tachycardia predicted the response to aprindine; patients with incessant ventricular tachycardia tended to respond, and those with paroxysmal sustained ventricular tachycardia tended not to respond.

Bethanidine sulfate in paroxysmal ventricular tachycardia: toxicity and antifibrillatory actions.

Programmed ventricular stimulation was used to test oral bethanidine sulfate in 10 patients with life-threatening ventricular arrhythmias. These patients had previously documented, recurrent, sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) complicating stable heart disease. During control electrophysiologic studies, VT could be induced in all 10 patients: 6 with nonsustained VT, 3 with sustained VT, and 1 with VT/VF. After control, bethanidine 20-30 mg/kg was administered orally and beginning 60 minutes later, programmed ventricular stimulation was repeated. After bethanidine administration, VT could be induced in nine patients; in four, the VT was essentially unchanged from that induced during control studies. In four others, worse VT was induced after bethanidine. The remaining two patients had a potentially beneficial response to the drug. Bethanidine was poorly tolerated: seven patients had symptomatic orthostatic hypotension that persisted for several days despite concurrent protriptyline therapy. Furthermore, in four patients, spontaneous VT or VT/VF occurred 3-8 hours after the last dose. Nausea, vomiting, flushing, and blood pressure elevation were also noted. Bethanidine sulfate in the dosages used usually does not prevent the induction of VT by programmed ventricular stimulation and frequently causes serious toxicity. These findings suggest that the drug would be ineffective and poorly tolerated for long-term therapy in patients with serious ventricular arrhythmias.

The effects of miracidal aging and dilution of snail-conditioned water on responses of miracidia of Megalodiscus temperatus.

Miracidia of Megalodiscus temperatus from newly hatched until 10 hr old were tested for their ability to react to Helisoma trivolvis snail-conditioned water (SCW) by contact with return (CR) to agar blocks and by percentage of miracidia reacting to a point inoculation of SCW as determined by a photographic time exposure method. CR to agar blocks containing 1:50 SCW was greatest during the first 6 hr after hatching but declined thereafter. The reaction during the first hour to a point inoculation was lower than during the 2nd and 3rd hr. Results were variable from 4 to 10 hr after hatching with the lowest response recorded from 9 to 10 hr. Miracidial responses to dilutions of SCW were assessed by the same two methods. CR to agar blocks containing decreasing concentrations of SCW declined until at a dilution of 1:500 CR was only slightly above the controls. On the other hand, miracidial reactions to point inoculations of SCW as determined by the photographic method were still apparent at a dilution of 1:25,000, when 12% of the miracidia tested reacted. Thus, the photographic time exposure method gives a sensitive means for detecting altered miracidial behavior to various intrinsic and extrinsic factors.

Responses of Megalodiscus temperatus miracidia to amino and sialic acids found in snail-conditioned water.

Analysis of snail-conditioned water (SCW) from Helisoma trivolvis revealed 17 free amino acids. Those in great concentration were glycine, serine, and alanine. The concentration of sialic acid was found to be twice that of the most abundant amino acid. The behavior of miracidia of Megalodiscus temperatus, measured by the contact with return method, to agar cylinders containing single amino acids and sialic acid indicated greater responses to polar molecules charged either positively or negatively at neutral pH. The molecules elicting the greatest response were aspartic, glutamic, and sialic acid. No correlation was found between concentration of amino acids in H. trivolvis SCW and response of M. temperatus miracidia.

Ventricular tachycardia in a young population without overt heart disease.

Since 1974, 24 young patients presenting with ventricular tachycardia and without clinical evidence of heart disease were evaluated and followed. Sixteen patients (67%) were symptomatic. Clinical episodes of ventricular tachycardia were sustained in 18, incessant in four, and nonsustained in two patients. The rate of tachycardia ranged from 130 to 300 beats/min (mean = 200 beats/min). Subtle abnormalities of cardiac size or function were present at cardiac catheterization in 16 of 23 patients (70%). During electrophysiologic studies, spontaneous ventricular tachycardia was present in six patients. The clinical ventricular tachycardia was inducible by programmed stimulation in 13 of 18 patients. The site of origin of tachycardia based on endocardial mapping in 17 patients was the right ventricle in 14, the ventricular septum in one, and indeterminate in two patients. Seventeen patients were treated based on results of short-term drug testing. During a mean follow-up period of 7.5 years, three patients died suddenly; none of these patients were receiving antiarrhythmic medication at the time of death. We conclude that in a young population without clinical evidence of heart disease, ventricular tachycardia may be the first manifestation of cardiomyopathy, since at least two-thirds of these patients have abnormalities at cardiac catheterization. Without treatment mortality in this population may be as high as 13% over an 8 year period. Presently we recommend treatment of ventricular tachycardia in any symptomatic patient, with therapy guided by electrophysiologic and treadmill testing. In addition, we recommend treatment for any asymptomatic patient with exercise-related tachycardia, since this group appears to be at increased risk for sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneity of reperfusion after reversible regional myocardial ischemia in a canine model.

Variability of regional myocardial blood flow (RMBF) during reflow after 20 minutes of left anterior descending (LAD) coronary occlusion was measured by the radioactive microsphere technique in nine open-chest dogs. Preocclusion RMBF in the LAD territory was 0.89 +/- 0.27 ml/min/gm. Twenty minutes of LAD occlusion resulted in uniform and severe ischemia (RMBF < or = 0.25 ml/min/gm). After 1 minute of reperfusion, RMBF in the LAD territory rose to 3.48 +/- 1.88 ml/min/gm, and declined to 1.06 +/- 0.29 ml/min/gm after 20 minutes of reperfusion. RMBF variance increased significantly from 0.046 preocclusion to 0.2857 after 1 minute of reperfusion (p < 0.01) and declining to 0.086 after 20 minutes of reperfusion. By contrast, RMBF variance analysis of myocardial segments from the nonischemic left circumflex territory exhibited no significant change throughout the experiment. In any given dog this heterogeneous reperfusion of previously ischemic tissue resulted in a disorganized topography of blood flow rates. Myocardium with relatively high regional flow was intermingled with islands of tissue with relatively low blood flow. In conclusion, despite a relatively uniform and severe myocardial ischemic insult, the subsequent initial hyperemic response during reperfusion exhibits marked spatial heterogeneity. The juxtaposition of myocardial regions exposed to vastly differing rates of oxygen delivery and washout of toxic metabolites may set the stage for nonuniform recovery of myocardial function.