Accuracy of gated equilibrium radioventriculography in measuring left ventricular function in dogs.

To assess the precision of gated equilibrium radioventriculography in measuring changes in left ventricular stroke volume (LVSV), we studied five dogs each with a chronically implanted electromagnetic flowmeter on the ascending aorta. Per cent changes in left ventricular stroke counts (LVSC) were compared to those in LVSV following acute changes induced by positive end respiratory pressure. We have compared LVSCs calculated in five different ways: (1) Manual outlining of LV region of interest (LVROI), either single fixed enddiastolic (ED) ROI or ED and endsystolic (ES) ROIs with the aid of functional images (first harmonic of Fourier analysis); (2-5) automatic outlining of LV ROI (the algorithm generated 30 profiles on which the maximum of second derivative delineated the LV edges) was performed either on ED image or both ED and ES images. For these four methods a crescent-shaped ROI for background correction was manually drawn at the border of the LV ROI. The fifth method used an automatically drawn single fixed LVED ROI with interpolative background substraction (IBS) between LV and RV edges. LVSC changes, calculated with the IBS method correlated better with LVSV changes than the other four methods. Thus assessment of small LVSC changes is highly processing-dependent.

Effect of bepridil on metabolic control and insulin secretion in diabetics.

In a double-blind cross-over study bepridil 900 mg followed by 300 mg daily for 11 days was given to 37 insulin (Type I) or non-insulin (Type II)-dependent diabetic patients. It did not modify the metabolic control of the patients as levels of glucose in blood and urine, doses of insulin and oral hypoglycaemic drugs, energy intake, and the number of hypoglycaemic attacks during therapy were unchanged. The serum concentration of C-peptide was not modified in either type of diabetic patient, and serum insulin in the Type I but not in the Type II patients was slightly higher during active drug treatment. No adverse organotoxic or arrhythmogenic effects or changes in possible atherogenic lipid fractions in serum could be demonstrated during bepridil therapy.

Comparison of short-term efficacy of diltiazem and propranolol in unstable angina at rest--a randomized trial in 70 patients.

The short-term efficacy of diltiazem (D) has been compared to that of propranolol (P), in a group of 70 patients hospitalized in the Coronary Care Unit for unstable angina, defined as recent (less than one month) appearance or aggravation of spontaneous chest pains. Among the 70 patients, 24 had angina only at rest. The patients have been divided into two groups according to ST-T changes during chest pain: 29 with ST elevation (group A) and 41 with other repolarization abnormalities (group B). Treatment was then randomized in each group. Treatment Treatment was considered successful only if spontaneous chest pains disappeared completely. Thirty-four patients were treated with D (282 +/- 102 mg/day) and 36 with P (158 +/- 81 mg/day). In the whole group and in groups A and B considered individually, responses to D and P did not differ. Among the 24 patients with angina exclusively at rest, nine successes and four failures were observed with D. There was no symptomatic relief among the 11 patients treated by P (P = 0.001). Moreover, the number of episodes of angina was decreased by D and unchanged by P, while eight out of the 11 failures with P were immediate successes when treatment was replaced with D. These results suggest that D is preferable to P for management of unstable angina in patients with angina which is exclusively spontaneous.

Effects of intravenous diltiazem on sinus node function and atrioventricular conduction in patients.

We studied the electrophysiologic effects of injectable diltiazem (dosage: bolus of 0.15 mg/kg, maintenance infusion of 0.3 mg/kg/h for 20 min) on sinus node function and atrioventricular function in 33 patients (22 men and 11 women, mean age 63.6 +/- 15.8 years). Seventeen patients had an electrophysiological exploration considered as normal, eight had sinus node dysfunction (corrected sinus recovery time greater than 525 ms), and eight had AV nodal block (PH greater than 160 ms and/or a Wenckebach point less than 125/min). Effects of the drug were assessed 20 min after the beginning of the infusion, which was continued until the end of examination. In normal subjects diltiazem lengthened corrected sinus node recovery time (305 +/- 115 ms leads to 451 +/- 283 ms) and slightly depressed AV nodal conduction (Wenckebach point: 163 +/- 23 leads to 147 +/- 25). In patients with sinus node dysfunction diltiazem provoked a bradycardia without significant changes in corrected sinus node recovery time or in estimated atrio-sino-atrial conduction time. In patients with AV nodal block diltiazem provoked a lowering of the Wenckebach point (137 +/- 47 leads to 122 +/- 38). There was no effect on hissian or infrahissian conduction, even when this was abnormal in the basal state. These data suggest that diltiazem must be utilized with caution in patients with sinus node dysfunction and AV nodal block.

Acute haemodynamic effects of a single intravenous dose of piretanide in congestive heart failure.

The haemodynamic effect of a single 12 mg intravenous dose of piretanide was assessed in 11 patients with congestive heart failure. It did not cause any change in cardiac output, heart rate or systemic vascular resistance, whereas the pulmonary wedge, mean pulmonary and right atrial pressures and pulmonary blood volume fell progressively, the difference from the control values being significant 5 minutes after the injection. The temporal evolution of the ratios pulmonary wedge pressure/total blood volume, pulmonary blood volume/total blood volume, right atrial pressure/total blood volume was chiefly determined by the numerator, which in all cases showed a more rapid decrease than total blood volume. Serum electrolytes remained unchanged 1 hour after the injection of the drug, except for potassium which fell from 4.9 to 4.1 mEq/l, while urinary sodium and potassium excretion were greatly increased. This high ceiling diuretic appears to have renal and venodilator properties close to those of furosemide.

Pharmacokinetics of diltiazem in severe renal failure.

The acute effects of a single dose of diltiazem (Tildiem), a calcium antagonist, were studied in 9 patients with severely impaired renal function (GFR between 0.03 and 0.87 ml/s/1.73 m2). Control measurements were made of inulin and PAH clearance, creatinine, blood pressure, heart rate and ECG. Following administration of diltiazem 120 mg, 7 blood samples were collected in the first 12 h and after 24 h, 32 h, 48 h; urine was collected for the first 12 h, 12-24 h and 24-48 h, and blood pressure, heart rate and ECG were recorded after 6 h. Diltiazem and its main metabolite, desacetyldiltiazem, had a pharmacokinetic profile similar to that in patients with normal renal function (peak plasma concentration, half-life and urinary excretion). Diltiazem is normally eliminated in the urine to a small extent, because it is metabolized, and this also applies to desacetyldiltiazem, which is probably further metabolized.

[Effects of diltiazem on cardiac and coronary circulation, at rest and during rapid auricular electric stimulation]. / Effets du diltiazem sur les circulations cardiaque et coronaire, au repos et au cours de la stimulation électrique auriculaire rapide.

The effects on cardiac performance and systemic and coronary blood flow of rapid atrial pacing alone and associated with an intravenous infusion of a slow calcium channel inhibitor, diltiazem, at a dose of 20 mg/kg were studied in 20 patients with chronic coronary artery disease. Atrial pacing increased coronary flow and myocardial oxygen consumption: it decreased coronary arterial resistance and the coronary arteriovenous difference in lactates. Left ventricular end diastolic pressure rose significantly compared to the basal state in the period following pacing. The administration of diltiazem was associated with a significant fall of femoral arterial pressure, of coronary arteriovenous difference and myocardial consumption of oxygen, and an increase in the coronary arteriovenous difference in lactate. Left ventricular end diastolic pressure did not differ significantly from the basal values recorded after terminating atrial pacing. Left ventricular end diastolic volume decreased. Diltiazem opposed or cancelled the undesirable effects of rapid atrial pacing with respect to coronary arteriovenous difference in lactate content. The beneficial action of diltiazem does not seem to be closely related to its hemodynamic effects. It could be related to a reduction in myocardial oxygen demands due to a decrease in systolic ventricular strain and the specific metabolic effects of the drug, and also to an increase in myocardial oxygen supply due to the reduction in left ventricular end diastolic stress and the coronary vasodilation caused by the drug.

Comparison of hemodynamic effects of furosemide and piretanide in normovolemic patients.

The effects of furosemide and piretanide (Hoe 118) on the pulmonary hemodynamics in 20 patients recovering from uncomplicated myocardial infarctions were compared in a double-blind study. The diuretic effects and half-lives of the two drugs were not significantly different, so that their hemodynamic actions could be compared directly. Both drugs progressively reduced cardiac output and pressures in the pulmonary circulation, whereas systemic vascular resistance increased significantly. Both drugs slightly increased pulmonary blood volume but not significantly. Total blood volume decreased less rapidly than cardiac output, so that the ratio of cardiac output to total blood volume decreased with time. We conclude that both drugs increase venous compliance in normovolemic subjects and probably increase the compliance of pulmonary vessels.

[Arrhythmias following closure of atrial septal defects. Apropos of 300 cases]. / Les troubles du rythme après fermeture des communications inter-auriculaires. A propos de 300 cas.

In a series of 300 cases whose atrial septal defects were closed (268 with ostium secundum, 27 with ostium primum, and 5 cases with both), arrhythmias were found in 60%. These were usually slow supraventricular arrhythmias caused by substitution (51%), and less commonly rapid supraventricular arrhythmias (27%), extra-systoles (16%), disorders of atrio-ventricular conduction of second and third degree and disorders of the auricle (6%). Conduction disorders were significantly more common (p less than 0.001) after closure of ostium primum (37%) than after closure of an ostium secundum (4.5%). Arrhythmias are most common during the first week (56%), and are usually of the slow type, and during the three succeeding weeks are markedly less frequent (31%) with a higher proportion (p less than 0.001) of the rapid type. No one anatomical type of ASD was complicated with arrhythmia more than the others. The slow type of arrhythmias occurred in the high ASDs, and the fast type especially amongst elderly patients. Longterm follow-up showed arrhythmias in 28% of patients with an ostium secundum defect. The factors influencing arrhythmias were age, cardiac enlargement, and the mean pulmonary arterial pressure. Arrhythmias were just as common in cases with a small shunt.