Synthesis of 3-Amino-2-(3-indolyl)propanol and Propanoate Derivatives and Preliminary Cardiovascular Evaluation in Rats

A series of tryptamine analogues has been prepared and tested for their 5-HT₁ receptor agonist properties. The incorporation of an alkoxy group at the C-5 position of the indole nucleus resulted in a short-lived and dose-dependent immediate antihypertensive and bradycardic response in anaesthetized spontaneously hypertensive rats (SHR). In addition, a carbomethoxy function at the β-position of the side-chain of the tryptamines significantly increased the mean resting arterial blood pressure (MAP) in pithed rats and also produced contraction of the canine basilar artery in a dose-dependent fashion. Structure-activity relationships (SAR) suggest that the 5-alkoxy group is an important pharmacophore in the production of the antihypertensive effect and that the introduction of a hydroxymethylene group on the side-chain, instead of the carbomethoxy group, changed the receptor affinity profile.     

Identical QRS Complexes during Atrial Fibrillation with Aberrant Conduction and Ventricular Tachycardia. The Value of a His Bundle Recording

In a patient with chronic congestive heart failure, right bundle branch block-shaped QRS complexes occurred in salvos during atrial fibrillation. The site of origin of these complexes could not be determined from the 12-lead ECG alone. Recording of a His bundle electrogram showed that both intraventricular aberrant conduction and ventricular tachycardia were responsible for salvos having the same QRS complexes in the 12-lead ECG.     

At what time are implantable defibrillator shocks delivered?: Evidence for individual circadian variance in sudden cardiac death

Background: As in myocardial infarction and transient ischaemia,out-of-hospital sudden cardiac death has an increased morningincidence. However, sudden death occurring in hospital is evenlydistributed over the 24 h period suggesting that there mightbe subgroups of patients with atypial circadian patterns ofsudden death. Patients who received an implantable defibrillatorconstitute an ideal group for studies of circadian patternsof sudden death since this generation of devices are able tostore the exact time when defibrillation occurred Methods: The distribution of sudden death aborted by the implantabledefibrillator was analysed during the 24 h period for 87 presumedappropriate shocks delivered in a group of 22 patients, 18 menand four women, 58.7 ± 11.9 years old and with a meanleft ventricular ejection fraction of 39.4 ± 17.6%. Results: Each patient received an average of 4.42 ± 3.04shocks during a mean follow-up of 9.4 ± 5.6 months. Apartfrom a clear tendency for shocks to occur during the morninghours (42% of total shocks), five of 16 patients who receivedmultiple shocks also showed a trend to repeat the shocks aroundthe same period during the day. Conclusion: Our results support the accepted view that changesin autonomic tone in the early morning play a role in the circadianvariations of sudden death. Sudden death not only occurs morefrequently in the morning hours, but it also clusters in certainperiods for individual patients.     

The Implantable Cardioverter-Defibrillator: Clinical Results

To evaluate the effectiveness of the automatic implantable cardioverter-defibrillator (AICD), a 7-year experience, from 1983–1990, was reviewed. A total of 111 patients received an AICD device. Their ages ranged between 8 and 83 years. Mean age was 63.9 years. There were 91 men and 20 women. Eighty of the patients received the AICD following an out-of-hospital cardiac arrest, white 32 were suffering from intermittent symptomatic ventricular tachycardia. The underlying etiology in 97 patients (87%) was ischemic coronary artery disease, in 11 patients (10%) dilated cardiomyopathy, and in 3 patients (3%) idiopathic ventricular fibrillation. Mean ejection fraction was 33.2%. Implantation of the AICD was performed via a left thoracotomy in 39 patients, median sternotomy in 49 patients and subxiphoidsubcostal approach in 23 patients. In-hospital mortality occurred in one patient who suffered an acute myocardial infarction 4 hours postoperatively. Out-of-hospital mortality was observed in 19 patients. There were two arrhythmic deaths. Follow-up was available for 107 patients. Mean follow-up was 33.1 months. Sixty-six patients (62%) had AICD shocks. The initial appropriate shocks occurred during the first postimplantation year in 91% of the patients. In 53 of the survivors, initial AICD shocks took place within 4.4 ± 4.7 months from implantation. Thirteen of the 20 patients who died had received appropriate AICD shocks. In these patients, the time between implantation and first shock was 2.7 ± 3.6 months whereas the time between implantation and death was 11.3 ± 10.3 months (NS). We conclude that the AICD is effective in converting ventricular tachyarrhythmias and prolongs survival.     

Initial Clinical Experience with a New Small Sized Third-Generation Implantable Cardioverter Defibrillator: Results of a Multicenter Study

This study reports the acute clinical experience with the new CPI VENTAK MINI: a small sized (68 cc), implantable cardioverter defibrillator (ICD) with 33 J stored energy. Implantation of the device was attempted in 113 patients (90 men, mean age 57 ± 16 years, 64 with coronary artery disease, mean left ventricular ejection fraction 41%) with ventricular tachycardia or ventricular fibrillation (VF). All 113 patients (100%) were ultimately implanted, 12% of them for ICD replacement. Transvenous lead implantation was accomplished in all 104 patients (100%) receiving new leads, 95% of them with a single lead configuration. The safety criteria for implantation (2 consecutive VF conversions at 15 J or 3 at 20 J. in both cases without failures to convert) were demonstrated in all but 7 patients (6%). In 6 of these, safety criteria were not fully assessed while in the last patient defibriliation efficacy was not determined. Of the 104 patients with new leads, 90% underwent pectoral implantation. Of the 9 patients (9%) abdominally implanted, only 4 (4%) (3 children) were judged small sized for pectoral implant. At predischarge testing, reliable VF detection and conversion were noted in 96 of 97 patients tested. There was no perioperative mortality. At a 3.6 ± 1.3 months follow-up, 34% of the patients had a spontaneous arrhythmic event, and 24% of the patients received shocks. Clinically inappropriate therapies occurred in 8% of the episodes in which any kind of therapy was delivered. This study demonstrates the short-term clinical efficacy and safety of the new device, and that pectoral implantation can be performed in the large majority of patients.