Comparative cardiac effects of intravenous bolus of ipratropium bromide (itrop) and atropine sulfate in 22 patients.

At the present time, there is no satisfactory pharmacological treatment for arrhythmia or conduction disorders induced by or aggravated by vagal hypertonia. The limited duration of action of the atropine derivatives currently available justifies the development of new compounds with expected longer acting duration. The aim of this study was to compare the effects of a single blind intravenous injection of ipratropium bromide to those of atropine sulfate in 22 patients. These patients were studied with continuous Holter recordings for three days. During the second and the third nights (patient sleeping), boluses of atropine (0.03 mg/kg) and of ipratropium bromide (0.03 mg/kg), respectively, were added to a continuous saline intravenous infusion. Accurate ECG analysis allowed determination of maximal heart rate peak, timing of maximal heart rate, variations in sinus cycle length, atrioventricular conduction, and durations of drug action. A nonsuggestive questionnaire was presented to patients to detect possible occurrence of side effects. The mean maximal heart rate rose significantly (p less than 0.001) for atropine (+46.2%) and for ipratropium bromide (+57.4%). The effects obtained with ipratropium bromide on the heart rate lasted nearly twice as long as those obtained with atropine (respectively, 120 +/- 38.4 min and 70 +/- 30 min- for the pharmacological half-life). Common minor muscarinic side effects (dryness of the mouth) were noted with the two drugs. In conclusion, this comparative intraindividual study confirmed the prolonged vagolytic effects of intravenous ipratropium bromide, which may be valuable in the treatment of patients with vagally mediated automaticity and conduction disturbances.

Electrophysiological effects of intravenous nicaïnoprol, a new antiarrhythmic agent, in 11 patients.

Nicaïnoprol, a new class 1 antiarrhythmic drug was given intravenously in a dose of 2 mg kg-1 of body weight (two patients) and 3 mg kg-1 of body weight (nine patients), and the clinical, electrocardiographic and electrophysiological effects were studied. Fifteen minutes after the end of drug administration, the PR interval was prolonged by 24.4% (P less than 0.001), and the QTc by 3.9% (P less than 0.01). The prolongation of QRS duration (+6%) was not significant. There was a slight (-3.9%) but non-significant decrease of the heart rate, with no alteration in sinus node function. Alteration of atrial conduction and atrioventricular (AV) conduction were due to an increase in the PA interval (+57.4%, P less than 0.05), the AH interval (+10.9%, NS) and the HV interval (+43.8%, P less than 0.01). The anterograde Wenckebach cycle length increased by 11% (P less than 0.01). The effective and functional atrial refractory periods increased respectively by 4.5% and 11.4% (P less than 0.05), and the effective refractory period of the AV node increased by 11.2% (P less than 0.05). None of the other electrophysiological variables changed significantly. A non-significant drop in blood pressure was noted between the second minute following injection (-9.4%) and the 15th minute (-3.4%), and two patients complained of dizziness; one of these two patients reported a heat flush with an oral burning. In conclusion, nicaïnoprol seems to possess the electrophysiological properties of some other class I antiarrhythmic drugs, and is clinically well tolerated.

Electrophysiological effects of encainide and its metabolites in 11 patients.

Encainide is a new antiarrhythmic class IC agent. Eleven patients were given 1 mg/kg of encainide i.v. over a 15-min period. Electrophysiological studies were done before and l h after drug administration. Blood levels of encainide and its principle metabolites O-demethyl-encainide, 3 metoxy-O-demetyl-encainide and N-demethyl-encainide were measured serially after drug administration. Heart rate, blood pressure, and conduction intervals were monitored. Sixty minutes after drug administration there was a marked increase of the QRS, PA, AH, and HV intervals of 28.1% (p less than 0.01), 17.2% (p less than 0.01), 22.4% (p less than 0.01), and 32.2% (p less than 0.01), respectively, and a slight increase of the Wenckebach cycle length of 8% (p less than 0.05). BP, RR, QT, CSNRT, ESACT, ERP, and FRP did not vary significantly. The HV interval already was increased significantly 2 min after drug administration, while AH was not increased until 15 min after drug administration. The average blood levels of encainide and ODE 60 min after drug administration were 0.410 +/- 0.12 and 0.176 +/- 0.09 microgram/ml, respectively (mean +/- SE of the mean). There was a positive correlation between the increase of the AH and the blood level of ODE, which points out the importance of prolonged electrophysiological studies when testing drug with possibly active metabolites.

Comparative study of encainide and disopyramide in chronic ventricular arrhythmias: a double-blind placebo-controlled crossover study.

Ten patients suffering from chronic premature ventricular complexes (greater than 60/h) were treated orally in a double-blind crossover study with encainide (50 mg three times a day) and disopyramide (200 mg three times a day), with five 7 day study periods: survey, placebo, encainide or disopyramide, washout placebo and disopyramide or encainide. At the end of each 7 day period, a 12 lead electrocardiogram, a 48 hour ambulatory electrocardiogram and a treadmill exercise test were performed. Blood levels of encainide and its metabolites and of disopyramide were measured at the end of each treatment (steady state). Drug efficacy was assessed by: 1) more than 80% reduction in the number of premature ventricular complexes per 24 hours, and 2) absence of ventricular tachycardia. Encainide was effective in four patients (complete suppression of premature ventricular complexes) and ineffective in five. One patient who showed a 92% reduction in the number of premature ventricular complexes developed sustained ventricular tachycardia after 24 hours of treatment. Disopyramide was effective in three patients (greater than 80% reduction in the number of premature ventricular complexes) and ineffective in seven patients. With encainide, the percent increase in PR, QRS and QT interval duration was, respectively: 32.7 (p less than 0.001), 30.8 (p less than 0.001) and 10.6% (p less than 0.01). With disopyramide this increase was not significant. Despite the variability of drug blood levels, a relation between blood levels and suppression of premature ventricular complexes on the 48 hour ambulatory electrocardiogram was found with encainide, but not with disopyramide.(ABSTRACT TRUNCATED AT 250 WORDS)

[Acute hemodynamic effects of betaxolol in uncomplicated arterial hypertension in young persons]. / Effets hémodynamiques aigus du bétaxolol dans l'hypertension artérielle essentielle non compliquée du sujet jeune.

Acute hemodynamic changes induced by Betaxolol (B.) were studied in 10 patients (7 men, 3 women, mean age: 36 years), with uncomplicated essential hypertension. The brachial artery was cannulated with a short Teflon catheter and Swan-Ganz catheter was introduced into the pulmonary artery. Brachial (BAP) and Pulmonary arterial pressures (PAP), cardiac output (dye dilution) were recorded before (To) and after intravenous infusion of B. (0.2 mg/kg) during 5 minutes (T1), followed by the infusion of B. at a rate of 0.4 mg/kg during 15 minutes (T2). Cardiac index (C.I.), Stroke index (S.I.), Systemic Vascular (SVR) and Pulmonary Vascular Resistances (PVR), Left Ventricular Stroke Work Index (LVSWI) were calculated. C.I. declined significantly. This resulted from a significant decrease of heart rate, since S.I. was unsignificantly changed. BAP (systolic and mean) decreased significantly, since unsignificant changes of PAP were noted. SVR and PVR were significantly increased and LVSWI was significantly decreased. Plasmatic Renin Activity was unsignificantly decreased.

[Detection of coronary artery spasm by the methylergometrin test. Technic. Results. Indications]. / La détection du spasme des artères coronaires par le test à la méthylergométrine. Technique. Résultats. Indications.

Methylergometrine (Methergin) was given intravenously (0.4 mg) to 118 patients undergoing coronary arteriography. The electrocardiogramme and intraaortic pressure was continuously monitored whilst coronary arteriography was performed, 1,3, and 5 minutes after the injection of the ergot alkaloid. The test was positive if: 1) coronary spasm was observed; 2) if ST segment elevation was recorded with or without pain. Positive tests were obtained in 13 out of 14 patients with Prinzmetal angina. The test was negative in the other patients. However in 3 patients with Prinzmetal angina, the test produced typical coronary spasm without electrocardiographic changes. In Prinzmetal angina the sensitivity of this test was 93 p. 100 with a high specificity: 96-100 p. 100 depending on whether or not electrocardiographical changes associated with spasm are considered. Taking into account current therapeutic methods of treating Prinzmetal angina the indications of this test of coronary spasm are: 1) patients presenting with resting angina whatever the state of their coronary arteries; 2) patients with documented Prinzmetal angina with "angiographically normal" coronary arteries.

Coronary arteriography in acute transmural myocardial infarction.

Coronary arteriography was performed 16 +/- 3 days (range 7 to 21 days) in 106 patients with acute transmural myocardial infarction (61 posterior infarct, 45 anterior infarct). Coronary arteriography was performed without serious complications. Only 44% of patients with anterior infarct had total occlusion of the left anterior descending artery while a significant stenosis of the vessel was observed in the others -27% had a single vessel disease, 49% had two lesions and 22% had three lesions; one patient had angiographically normal coronary arteries. Among the patients with posterior infarction, 21% had one vessel disease and double or triple lesions accounted for 39% of each. Sixty per cent of patients with anterior infarction and 45% with posterior infarction had no collateral vessels. In the others patients collateral circulation had a protective effect only in anterior infarction. Age has no effect on the distribution and number of lesions nor on the development of a collateral circulation. The location and severity of the lesions were not different in patients who presented with arrythmias and those who did not.

Left ventricular compliance in acute transmural myocardial infarction in man.

130 patients with recent transmural myocardial infarction were studied in order to evaluate changes in left ventricular compliance. Left heart catheterization and cineangiographic left ventriculography were performed. The modulus of chamber stiffness (K) was determined from the slope of the linear relation between volume stiffness (dP/dv) and pressure; the modulus of muscle stiffness was evaluated by the Laird index (asymptotic slope of logP vs log V). Patients were divided in 3 groups: Group A included 5 patients studied before and after myocardial infarction who experienced an increase in the modulus of chamber and muscle stiffness after infarction. Group B included 10 patients who were studied at the onset of infarct and 15 days later: this group demonstrated changes in LV compliance with, most often a rightwardshift of P-V curve in anterior infarct and inversely a leftward shift in posterior infarction. The 115 patients of Group B are roughly equally distributed in the areas of normal, increased or decreased compliance. Any correlation was found between the extent of asynergy and changes in modulus of chamber stiffness. However, ejection fraction or VCF were higher in patients with a reduction of compliance than in patients with an increase of compliance.