Haemodynamics at rest and under effort in chronic arteriovenous fistulae (AVFs).

Latero-lateral femoro-femoral arteriovenous fistulae (AVFs) were surgically created in mongrel dogs. After 7-9 months during which the dogs were trained on a treadmill, devices suitable for recording arterial pressure and aortic and coronary flow were chronically implanted. Haemodynamic parameters of the dogs were controlled either at rest or after effort, keeping AVFs open or manually closed. The results, when statistically processed, showed that haemodynamic changes induced by occlusion of AVFs at rest and under effort are similar from a qualitative point of view, but considerably more marked after muscular exercise. Under effort the shunt index calculated rose to a higher extent than cardiac output. The decrease in heart rate after AVFs occlusion was significantly correlated with flow in the fistulae. However, the Nicoladoni-Branham phenomenon ought to be used for indirect evaluation of the shunt flow.

Coronary blood flow and myocardial O2 consumption in hypertrophied cardiac muscle in dogs.

In dogs with experimental cardiac hypertrophy in resting conditions, coronary blood flow and myocardial O2 consumption increased proportionately to the cardiac mass; coronary flow and O2 consumption per gram of myocardium, therefore, ranged within normal values. The coronary reserve, neasured as the percentage increase in the coronary blood flow from rest till peak flow during reactive hyperaemia, was noticeably reduced, because it was partially utilized, even at rest, and consequently the possibility of an increase in flow after exercise or stress was diminished.

Pharmacological profile of ibopamine. A summary of experiments on anaesthesized dogs.

This review summarizes the results obtained with ibopamine on anaesthesized dogs. Ibopamine is a dopamine-related drug active by oral route, namely the diisobutyric ester of N-methyl-dopamine. Ibopamine is able to activate dopamine specific and adrenergic receptors in the heart and circulation, inducing a vasodilating activity together with a mild positive inotropic effect without increasing heart rate and myocardial O2 consumption. The activation of dopamine and adrenergic receptors mediates a direct vasodilation postjunctional DA1 and beta 2 receptors and an indirect vasodilation (presynaptic DA2 and alpha 2-receptors) through the inhibition of the release in norepinephrine, the renin-angiotensin system, and the secretion of aldosterone and vasopressin, thus antagonizing the neurohormonal alterations in congestive heart failure through a receptor mechanism. Ibopamine can also activate beta 1- and beta 2 and very modestly vascular synaptic alpha 1- and alpha 2-receptors, thus inducing a mild positive inotropic activity and avoiding a drop in arterial pressure which might take place in presence of the intense vasodilation induced by the drug. There is some difference in potency between dopamine and epinine. Epinine is the active metabolite of ibopamine and is more active than dopamine on DA1, DA2, alpha 1, alpha 2 and beta 1 and beta 2 receptors. Ibopamine can be safely associated with captopril and digoxin but not with nifedipine.

Treatment of heart failure following chronic cor pulmonale with ibopamine.

A group of 36 patients with cor pulmonale chronicum were treated for 12 months with ibopamine, a dopamine-related drug, orally active, suitable for the long-term therapy of congestive heart failure. In heart failure due to chronic pulmonary disease other drugs such as digitalis are hardly effective. The results obtained indicate that ibopamine, given alone or associated to other drugs, is clinically efficient in the treatment of cor pulmonale chronicum while very few side effects definitely related to ibopamine were reported. In particular no increase in arrhythmias or significant augmentation of anginal episodes was noted.

Absence of proarrhythmic effects of ibopamine in patients with congestive heart failure.

Ibopamine, the di-isobutyric ester of N-methyldopamine, is an orally effective dopamine-related drug. Ibopamine acts mainly through the stimulation of beta 1- and beta 2-adrenergic and dopaminic DA1 and DA2 receptors. Cardiac beta 1 activation may facilitate the occurrence of arrhythmias, by reducing the mean refractory period. The aim of this multicenter investigation was to ascertain whether the administration of ibopamine can induce any rhythm disorder or increase pre-existing arrhythmias. In the first part of the investigation, after a washout period 20 patients were treated randomly under double-blind conditions with ibopamine (100 mg t.i.d.) or placebo for 7 days. In the second part of the study, 25 patients were treated with placebo for 7 days, and then with ibopamine (100 mg t.i.d. and 200 mg t.i.d.) for another two 7-day periods. The results did not show any increase in arrhythmias during the two ibopamine periods, in comparison with the data collected under placebo treatment. Ibopamine did not affect heart rate and blood pressure. The number of SVPBs and VPBs decreased considerably in several patients and also the Lown classification improved after ibopamine treatment, even after the 200 mg t.i.d. dose. It can be concluded that ibopamine does not seem to elicit any significant proarrhythmic property.

Long-term therapy of chronic congestive heart failure with ibopamine: a multicenter trial.

The present multicenter open investigation was designed to provide information on the adverse reaction rate, drug interaction, and survival in a group of 544 cardiac patients treated for 1 year with ibopamine either alone or in association with digitalis, diuretics, and other drugs. Some efficacy parameters were also considered. Heart failure was due to idiopathic dilated cardiomyopathy (21%), ischemic heart disease (32%), hypertensive heart disease (31%), and others (16%). Ibopamine was given alone to 39 patients; the others were given the drug in association with digitalis, diuretics, and vasodilators. One hundred forty patients did not complete the trial (25.7%). The most common causes of discontinuation were death (12.5%), noncompliance with the protocol (5%), and adverse events (3.9%). The clinical conditions and NYHA functional class improved in most patients. The cardiothoracic ratio decreased on average. The 1-year mortality rates associated with NYHA class II, III, and IV were 4.4, 13.8, and 37.2%, respectively. Survival tended to be shorter in a small group of 22 patients with hyponatremia, thus confirming some previous reports. Adverse experiences were mainly related to cardiovascular and gastrointestinal systems; the symptoms were considered severe only in 1 of 544 patients enrolled. Ibopamine seems not to induce dangerous arrhythmias. Blood pressure and heart rate did not change over time during ibopamine treatment. Laboratory tests were not significantly affected; fluctuations observed in some tests were related to concomitant variations in the severity of the primary disease. No tolerance to ibopamine seems to be observed during this long-term therapeutic trial.

Long-term treatment of congestive heart failure with oral ibopamine. Effects of rhythm disorders and neurohormonal alterations.

A group of 30 patients with II-III NYHA class cardiac insufficiency was treated with ibopamine in association with other drugs for a 6-month period. The patients were submitted to a 24-h ambulatory ECG Holter monitoring, chest X-ray, Doppler echocardiography in order to calculate total peripheral vascular resistance. Blood levels of aldosterone and renin-angiotensin activity in plasma were also measured, together with norepinephrine excretion. The measurements and recordings were performed in basal conditions before the trial, and were repeated after the first, second, third and sixth month. Laboratory tests were performed at the baseline and after 6 months. The results showed a significant decline in the number of ventricular and supraventricular ectopic beats after treatment. Heart rate did not change. Cardio-thoracic ratio decreased significantly along with peripheral vascular resistance. A very noticeable decline in all three neurohormonal parameters, i.e. norepinephrine excretion, blood level of aldosterone and renin activity in plasma was observed after 1 month's treatment, and this reduction was still present without any attenuation after 6 months. No significant changes were observed in routine laboratory tests.