Observations on autoregulation in skeletal muscle: the effects of arterial hypoxia.

Autoregulation of blood flow in skeletal muscle, as manifested by steady-state resistance changes, has been shown to be present in the low range of perfusion pressure but has been demonstrated by some observers to be lacking at higher perfusion pressures. Transient responses have often been neglected or observed only qualitatively in analyses of autoregulation. The present study was undertaken (1) to determine the relative importance of steady-state and transient responses in flow in demonstrating autoregulation of blood flow over a broad range of perfusion pressures, (2) to establish a means of quantitating autoregulation, and (3) to observe the effect of hypoxia on autoregulation. In isolated, perfused canine gracilis muscle, perfusion pressure was increased and subsequently returned to baseline (9.7 +/- 0.13 kPa [73 +/- 1 mmHg]) during perfusion with normally oxygenated blood (PO2 = 9.3-13.3 kPa [70-100 mmHg]), and mildly (PO2 = 6.1-9.2 kPa [46-69 mmHg]), moderately (PO2 = 4.5-6.0 kPa [34-45 mmHg]), or severely (PO2 = 2.7-4.4kPa [20-33 mmHg]) hypoxic blood. Consistent with other studies canine gracilis muscle was often found to possess passive vascular responses when only steady-state parameters were considered. However, quantitation of the transient response in flow with step increases in perfusion pressure demonstrated substantial transient responses under conditions of normal oxygenation, and progressive attenuation of flow transients with increasing hypoxia.

The neurogenic vasoconstrictor effect of digitalis on coronary vascular resistance.

The coronary vasoconstrictor properties of digitals were evaluated in 61 anesthetized, openchest dogs after coronary sinus cannulation and under conditions of a constant heart rate (atrioventricular pacing) and near-constant blood pressure. The contribution of alpha adrenergic receptor stimulation to the digitalis-induced increase in coronary vascular resistance (CVR) was examined. With Na pentobarbital anesthesia (16 dogs), intravenous acetylstrophanthidin (0.5 mg) caused a significant (P<0.05) rise in CVR from 1 through 9 min after injection. The peak increase was +11+/-2% SE of the control of 1.8+/-0.2 mm Hg/cm(3)/min. The mean time to peak effect was 3 min, and to recovery was 21 min. Prior alpha adrenergic receptor blockade with phenoxybenzamine in 11 animals reduced (P<0.05) the acetylstrophanthidin-induced peak of CVR and substantially decreased (P<0.05) the time to recovery (5 min). Intravenous digoxin (1.0 mg) with Na pentobarbital anesthesia (five dogs) had no significant effect on CVR. However, with chloralose and urethane anesthesia (nine dogs) the same dose of digoxin produced a significant rise in CVR from 3 through 30 min. The peak increase was +20+/-3% of control (1.4+/-0.1 mm Hg/cm(3)/min). One-third the dose of intravenous digoxin (0.35 mg) produced a 9.5+/-1.0% increase in CVR (five additional dogs). Myocardial oxygen consumption did not change significantly in nine dogs after intravenous digoxin. In 10 additional dogs pretreated with phenoxy-benzamine and in 7 dogs pretreated with mecamylamine, the increase in CVR did not occur after 1.0 mg of intravenous digoxin. Thus there is a coronary vasoconstrictor effect of intravenous acetylstrophanthidin and digoxin, of rapid onset, which is mediated through alpha adrenergic receptor stimulation.