Importance of heart rate in determining the effects of sympathomimetic amines on regional myocardial function and blood flow in conscious dogs with acute myocardial ischemia.

Abstract

We examined the effects of dopamine (DP), dobutamine (DB), and isoproterenol (ISO) in 38 conscious dogs after coronary artery occlusion on measurements of overall left ventricular (LV) function (i.e., LV pressure, dP/dt, mean arterial pressure, and heart rate), while regional myocardial function was assessed, using an ultrasonic gauge to measure segment length (SL) in normal and ischemic areas of myocardium. We measured regional myocardial blood flow, using the radioactive microsphere technique. Coronary occlusion resulted in graded reductions of blood flow and function from the normal to severely ischemic zones. DP and DB, 4.0 pg/kg per min, and ISO, 0.03 fig/kg per rain, iv, increased LV dP/dt similarly; i.e., by 20%, and increased blood flow and systolic SL shortening in the normal zone. ISO increased heart rate (29.9 ± 4.6%) and decreased SL shortening and blood flow (32.9 ± 6.1%) in the severely ischemic zone. In contrast, we observed significantly different (P < 0.01) effects with these doses of DP and DB, which caused no increases in heart rate or decreases in blood flow or contractile function in the ischemic zone. DP and DB, 10 pg/kg per min, iv, increased LV dP/dt 3-to 4-fold more than with the lower dose, but still failed to elicit reductions in contractile function or blood flow in the severely ischemic zone when heart rate did not rise. In contrast, when the same doses of DP and DB increased heart rate in another group of dogs, blood flow and contractile function fell in the ischemic zone. Thus, /J-adrenergic agents do not always elicit a "coronary steal" or deleterious effects on ischemic myocardial function, despite coronary dilation in the normal zone. However, when inotropic stimulation is coupled with tachycardia, blood flow falls and contractile function deteriorates in the ischemic myocardium. Circ Res 45: 793-803, 1979

Influence of heart rate on the effects of prenalterol on regional myocardial blood flow and function during coronary stenosis in dogs

“…This phenomenon probably also occurred in our experiments with prenalterol and may have limited its beneficial effects. Second, it has been shown that dobutamine does not affect left ventricular end-diastolic pressure in conscious dogs (Vatner & Baig, 1979;Liang et al, 1981) while it reduces this parameter in anaesthetized dogs (Tuttle et al, 1977). Similarly, prenalterol does not affect left ventricular end-diastolic pressure in conscious dogs (Manders et al, 1980) but reduced it in our experiments, which may have enhanced the drug's beneficial effects on ischaemic flow and function.…”

“…With prenalterol, 20 jig kg-', both RMBF and regional contractility were decreased, a picture similar to that observed with atrial pacing at 175 beats min-'. These results must be considered in the light of those previously reported in anaesthetized (Marshall & Parratt, 1976;Willerson et al, 1976;Warltier et al, 1981;Rude etal., 1982Rude etal., , 1983 or in conscious dogs (Vatner & Baig, 1979;Liang et al, 1981) treated with dobutamine or dopamine during coronary artery occlusion or stenosis. Despite some differences, all these studies concluded that P-adrenoceptor agonists that induce coronary vasodilatation do not always cause a 'coronary steal phenomenon' nor necessarily enhance myocardial injury providing that coronary perfusion pressure is maintained and above all that tachycardia remains limited.…”

“…For instance, after coronary occlusion in dogs, low doses of dopamine or dobutamine can decrease intramyocardial Pco2 (Rude et al, 1983), improve the regional contractility of the ischaemic zone (Vatner & Baig, 1979) and even reduce the ultimate infarct size (Liang et al, 1981) providing that heart rate remains unchanged. These results tend to support the view that the increase in heart rate induced by P-adrenoceptor stimulation is more deleterious for the ischaemic myocardium than the concomitant increase in cardiac contractility, the latter being possibly associated with a lesser myocardial oxygen cost than the former.…”

Cardiovascular Effects of Dihydroergotamine during Epidural Anaesthesia in Dogs

“…As opposed to catecholamines which have been recommended to increase blood pressure in epidural anaesthesia [2], DHE caused a de crease in heart rate. In this connection it is important to note that the Pi component of adrenergic sympathomimetic amines is thought to be deleterious in the presence of myocardial ischaemia since, by increasing myocardial metabolic demands in the face of a limited oxygen supply, the ischaemia may be intensified [14]. The pj-adrcnergic effects may lead to a dilatation of blood vessels which are compensatorily constricted in epi dural anaesthesia [3].…”

La découverte de l’ivabradine (Procoralan®), inhibiteur sélectif du courantpacemakerIf: Une nouvelle approche thérapeutique des cardiopathies ischémiques

“…L'accélération de la fréquence cardiaque contribue au déclenchement ou à l'aggravation de la plupart des épisodes d'ischémie myocardique en augmentant la consommation d'O 2 et en réduisant le temps de perfusion myocardiques, voire en induisant une vasoconstriction coronaire aggravant les conséquences hémodynamiques d'une sténose athéromateuse, comme cela a été montré chez des patients coronariens soumis à une stimulation auriculaire rapide [9]. De plus, la tachycardie est le facteur le plus délétère d'une stimulation sympathique sur le coeur ischémique [10]. Inversement, on peut attendre une puissante activité anti-ischémique d'une réduction sélec-tive de la fréquence cardiaque, capable de diminuer la consommation d'O 2 myocardique, d'augmenter le temps de perfusion diastolique et de prévenir la survenue d'une vasoconstriction coronaire dépendante de la fréquence.…”