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

Abstract

1 The effects of prenalterol, a selective 31-adrenoceptor agonist with potent cardiac positive inotropic properties have been investigated on regional myocardial blood flow (RMBF) (microspheres) and contractile function (ultrasonic crystals) during partial circumflex coronary artery stenosis in 8 open-chest anaesthetized dogs. 2 Prenalterol was investigated at two intravenous doses: 5 gg kg-', which increased myocardial contractility (dP/dt max: +29%) more than heart rate (+12%, up to 150 beatsmin-') and 20 jig kg-1 which induced almost similar increases in contractility (+35%) and heart rate (+ 31% up to 175 beats min-1). The induced modifications of regional flow and function were then compared to those produced in another series of 6 dogs by atrial pacing at 150 and 175 beats min-1 respectively. 3 Prenalterol significantly increased RMBF and segment length (SL)-shortening in a dosedependent manner in the nonischaemic zone. In the ischaemic zone, RMBF was maintained and SL-shortening increased with prenalterol, 5 gig kg-' whereas both RMBF and contractile function were severely decreased with prenalterol, 20 gg kg-'. 4 Atrial pacing had almost no effect on RMBF and SL-shortening in the nonischaemic zone. In the ischaemic zone, atrial pacing rate-dependently decreased both RMBF and SL-shortening. 5 Thus, a significant increase in contractility, associated with little tachycardia (prenalterol, 5 fig kg-), induces beneficial effects on RMBF and function in both the nonischaemic and ischaemic myocardium. In contrast, a strong tachycardia, whether accompanied by positive inotropic effects (prenalterol, 20 gig kg-') or not (atrial pacing at 175 beats min-1) induces deleterious effects on RMBF and cardiac function in the ischaemic myocardium.

Effects of nipradilol on myocardial ischaemia produced by coronary stenosis in dogs

“…Improvement by nipradilol of ischaemic segment function was almost abolished after atrial pacing, with little change in the other haemodynamic variables. These results may be consistent with the view that slowing of heart rate is of importance in the mechanisms related to the restoration of regional function in the ischaemic area distal to a coronary stenosis (Schamhardt et al, 1981;Gross et al, 1984;Berdeaux et al, 1984).…”

Nisoldipine and perfusion of post‐stenotic myocardium in conscious pigs with different degrees of concentric stenosis

“…Nisoldipine might have decreased oxygen demand of the post-stenotic area, although the increase in heart rate suggests an increase in oxygen demand rather than a reduction. Another possibility arises from the investigation of Berdeaux et al (1984) who observed an increase in wall function of severely ischaemic myocardium after a low dose of prenalterol, a ,B-adrenoceptor agonist, causing an increase in heart rate of 15 beats min-1, while after a high dose of prenalterol an increase in heart rate of 40 beats min 1 was accompanied by an unchanged wall function. This suggests that the reflex-mediated increase in sympathetic activity can cause an increase in wall function even in severely ischaemic myocardium, provided that the increase in heart rate is minimal.…”