Isoprenaline dose‐response curves plotting increases in heart rate before and after labetalol are suggestive of competitive antagonism at beta‐adrenoceptor sites. Phenylephrine dose‐response curves using increases in systolic pressure before and after labetalol are suggestive of competitive antagonism at alpha‐adrenoceptor sites. The ratio of alpha:beta‐adrenoceptor antagonism induced by labetalol is approximately 1:3. Peak pharmacological responses after a single oral dose of labetalol (400 mg) occurred between 90‐120 min after administration.
Many workers have shown that the cardiac output in normal man is less in the upright than in the recumbent position (McMichael and SharpeySchafer, 1944;Stead et al., 1945;Coe, Best, and Lawson, 1950;Wang, Marshall, and Shepherd, 1960;Chapman, Fisher, and Sproule, 1960;Reeves et al., 1961). The physiological events underlying this change are complex and depend on many variables, such as the angle of tilt and length of time the patient remains at a given angle and whether the change is from recumbency to an upright position or vice versa. Posture and its relation to cardiac output here becomes increasingly important with the introduction of hypotensive drugs. The purpose of this study was to determine the relation ofthe angle oftilting to the changes in cardiac output, blood pressure, and pulse rate in normal man. SUBJECTS AND METHODS Studies were carried out on 33 subjects: 28 women and 5 men, whose average age was 37 years.The observations were all made three hours after breakfast or lunch. The relative cardiac outputs were measured by the indicator dilution method from dye curves recorded by a photoelectric earpiece (Gabe, Tuckman, and Shillingford, 1962), chopper amplifier, and direct writer recording system. All subjects rested quietly in the supine position for 30 minutes before the first cardiac output determination. Coomassie blue dye was injected from a calibrated syringe through a three-way tap and eighteen-gauge needle into an antecubital vein, a 5 per cent dextrose-in-water drip keeping the system open between injections. In any one subject the injections of dye were of equal quantity and varied from 20 to 30 mg./injection in different subjects.
Labetalol 1.5 mg/kg administered intravenously to normal subjects in the supine position produced an immediate mean fall in systolic (16%) and diastolic (25%) blood pressure with a concomitant increase in heart rate (12%). After graded exercise, intravenous labetalol inhibited increases in heart rate and blood pressure.Isoprenaline log dose response curves of increase in heart rate and reduction in diastolic pressure after intravenous labetalol shifted to the right in a parallel manner compared with pre-labetalol response curves suggestive of competitive antagonism at beta-adrenoceptor sites. Similarly, phenylephrine dose response curves of increase in systolic pressure before and after intravenous labetalol were suggestive of competitive antagonism at alpha-adrenoceptor sites. The ratio of relative potency alpha: beta adrenoceptor antagonism after intravenous labetalol was approximately 1: 7, whereas in the same subjects after oral labetalol the ratio was approximately 1: 3 as previously reported.Using the inhibition of isoprenaline tachycardia to estimate the potency of the beta-adrenoceptor antagonism of labetalol relative to that of propranolol the potency ratio was 1: 6. However, using inhibition of Valsalva tachycardia as the index, the estimated ratio was approximately 1 :3. Estimates of relative potency using inhibition of tilt tachycardia were complicated by the additional effects upon blood pressure after labetalol not seen after propranolol.Labetalol produced adrenoceptor blockade at both alpha and beta sites in man sufficient to explain its therapeutic antihypertensive effect.Labetalol is a compound possessing combined alpha and beta adrenoceptor antagonist properties (Farmer et al., 1972). Consequently it has been assessed in clinical practice as an antihypertensive agent. Prichard et al. (1975) and Koch (1976)
The usual methods for the measurement of changes in cardiac output involve arterial puncture; it would be of value if a technique could be used without involving this procedure.Coomassie Blue dye and the photoelectric earpiece 1 " 3 make it comparatively simple to obtain successive dye-dilution curves without arterial puncture. If the response of the recording system is linear to blood dye concentration and the vascular content of the ear is constant, it should be possible to measure relative changes in cardiac output without calibrating the corves. The purpose of this paper is to investigate the validity of using noncalibrated earpiece dye-dilntion curves for such measurements in man. Arterial cuvette curves were used as the standard of comparison, and simultaneous earpiece curves were recorded during changes in posture, exercise, and intravenous administrations of an antihypertensive agent (guanethidine), sodium amobarbital, and norepinephrine. MethodsThe selenium photoelectric earpiece and cuvette, made by the Cambridge Instrument Company,* were used and were connected to similar chopper amplifiers.* Records were made on a twin-channel 1 ma. direct-writing recorder.! Linearity of the response of the two systems to concentration of
Skin breakdown lesions (SBLs) of the legs are common in spinal cord injury (SCI). It is assumed that the cause is deficient sensitivity and immobility of the limbs, which result in areas subjected to prolonged pressures. However, poor circulation may also be a significant factor. Indeed, strong reasons suggest that small vessel circulation is decreased in SCI because these patients have increased arteriosclerotic risk factors. Patients in the SCI population have advanced age, are sedentary, often have abnormal carbohydrate and lipid metabolism, and many use tobacco products. Total blood flow (TBF) to the legs and skin blood flows (SBFs) to 4 areas of the feet were measured simultaneously by duplex Doppler sonography and laser Doppler flowmetry in 10 healthy control and 10 chronic subjects with SCI when supine and during 30 minutes in a wheelchair. The average supine control TBF was 540 mL/minute, but greatly reduced between 24-76 mL/minute in 4 of the subjects. During sitting, the average TBF fell by 41% in the controls and increased by 6% in SCI. Nonetheless, in all control and SCI subjects the average sitting SBFs were severely decreased in all areas between 53-75%, similar to results found by others elsewhere in the foreleg. Ischemia of the skin and underlying muscles is important as a cause for the poor healing of SBLs in persons with SCI who daily spend many hours in a wheelchair.
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