N-dimethylisopropyl propranolol. Effects on myocardial oxygen demands.

Abstract

N-Dimethylisopropyl propranolol (DMP) is a quaternary derivative which lacks significant beta-adrenergic blocking and local anesthetic effects. It has been reported, nonetheless, to be effective in treating experimental arrhythmias and in limiting the extent of ST-segment elevations following experimental coronary occlusion. The present study examined the effects of DMP on the hemodynamics and myocardial oxygen demands of anesthetized dogs. After a single dose of 3 mg/kg, heart rate fell from 146 +/- 8 to 124 +/- 6 beats/min (P less than 0.0025), and aortic systolic pressure fell from 151 +/- 11 to 141 +/- 9 mm Hg (0.05 less than P less than 0.10), resulting in a 16.8% reduction in the tension-time index. Stroke volume was reduced by 10% despite a 54% increase in left ventricular end-diastolic pressure, suggesting a negative inotropic effect. This was supported by a decrease in maximum extrapolated contractile element velocity from 9.10 +/- 1.05 to 6.61 +/- 65 units/sec (P less than 0.0025). Myocardial oxygen consumption was reduced from 12.0 +/- 1.4 to 9.9 +/- 1.5 ml/min/100 g tissue (P less than 0.05). Myocardial oxygen extraction was unchanged, indicating that the decrease in oxygen consumption resulted from a reduction in myocardial oxygen demand. When heart rate and systolic pressure were artificially restored to control levels, after the administration of DMP, myocardial oxygen consumption remained significantly below the control level. DMP, therefore, appeared to reduce myocardial oxygen demands primarily by its negative inotropic effect. This drug may have application in the treatment of ischemic heart disease.

Ventricular fibrillation in a conscious canine model - Its prevention by UM-272

“…We cannot eliminate the actions of UM-272 upon the ischemic process as a mechanism for its protective effect. UM-272 has been shown to reduce myocardial oxygen consumption and the ultimate extent of irreversible injury produced by regional myocardial ischemia (Kniffen et al, 1975;Lucchesi et al, 1976;Ku and Lucchesi, 1978;Olson et al, 1976;Warltier et al, 1978). These actions could be beneficial in limiting the extent of ischemic injury and thereby prevent ventricular fibrillation.…”

Pranolium

“…Pranolium significantly reduces heart rate, cardiac output (871, and blood pressure in anesthetized dogs (57). A decrease in heart rate and cardiac output was seen with an increasing cumulative dose (1 to 3 mg/kg).…”

“…Pranolium decreases myocardial oxygen consumption in both the open-chest (33) or closed-chest (57,87) anesthetized dog and in the isolated perfused heart in siru (33,82). Pranolium, 10 mg/kg, has been shown to decrease myocardial oxygen consumption in anesthetized, open-chest dogs (Fig.…”

“…22) with only minimal changes in cardiac force and heart rate (33). In the closed-chest anesthetized dog (57) pranolium decreases myocardial oxygen consumption by decreasing heart rate and force, which also results in a decrease in cardiac output and tension-time index. In isolated, blood perfused canine hearts ( Fig.…”

Disposition of pranolium chloride in dogs, baboons and monkeys

“…In a variety of animal model test systems pranolium has been shown to possess potent anti-fibrillatory and anti-arrhythmic properties but to be without the~-blocking and local anaesthetic properties of propranolol (1-4). Pranolium improves the relationship between myocardial oxygen supply and demand by increasing subendocardial perfusion (5) and decreasing oxygen consumption (6,7) and so, may protect against ischemic injury (6)(7)(8).…”