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Biomedical subjects

R G McAllister

Publications and source records attributed to R G McAllister.

8 recordsLinked to original sources

GLC assay of verapamil in plasma: identification of fluorescent metabolites after oral drug administration.

The fluorometric assay for verapamil in plasma is not useful after oral drug administration because of interference by inactive, but fluorescent, metabolites extracted along with the parent drug. A GLC method using a flame-ionization detector after silylation allows the separation of unchanged active verapamil from the metabolites and quantitation to a sensitivity of 0.025 microgram/ml. After a single oral dose of drug in dogs, up to 80% of "fluorescent verapamil" represented inactive metabolites.

Administration, Oral

Studies of experimental cervical spinal cord transection. Part II: Plasma norepinephrine levels after acute cervical spinal cord transection.

Plasma concentrations of norepinephrine (NE) were measured by a radioenzymatic assay technique before and serially after laminectomy at the C-6 level in 14 anesthetized dogs. In half the animals, no further procedures were carried out (control group); in the other dogs, cervical cord transection was performed in addition to laminectomy (experimental group). Mean plasma NE levels were similar in both groups after laminectomy and before cord interruption. In the control group, NE levels increased gradually for 2 hours after the procedure. In the group with cord transection, however, NE rose immediately after transection to 267% of the baseline value, then fell to 25% of the plasma NE level in the control group at 30 minutes, 29% at 60 minutes, and 15% at 120 minutes. Cervical spinal cord transection, therefore, results in an abrupt but short-lived increase in plasma NE concentrations. These changes in plasma NE levels may explain, at least in part, the hemodynamic alterations and the acute central hemorrhagic necrosis that occur after high spinal cord trauma.

Animals

Studies of experimental cervical spinal cord transection. Part III: Effects of acute cervical spinal cord transection on cerebral blood flow.

Regional cerebral blood flow (CBF) was measured by the microsphere technique in anesthetized, mechanically ventilated dogs before and after cervical laminectomy in four (control group), or cervical laminectomy followed by cervical cord transection (CCT) at the C-6 level in six (experimental group). No significant differences in arterial pH, pO2 or pCO2 were observed between control and experimental dogs. Baseline values for mean arterial pressure (MAP) were also similar in the two groups, but MAP fell in all experimental dogs after CCT (p less than 0.025). At 120 minutes after CCT, three of the six dogs had an MAP greater than 60 torr (66 +/- 4 torr), and in three the MAP was greater than 50 torr (45 +/- 3 torr). Regional CBF in cortical gray matter, white matter, and medulla did not change significantly after CCT in dogs with MAP greater than 60 torr. The CBF fell significantly at 120 minutes after CCT in all regions sampled in the dogs with MAP less than 50 torr (p less than 0.025). At 30 and 120 minutes after CCT, cerebellar blood flow fell significantly in all experimental animals (p less than 0.05). These findings indicate that, despite hypotension and sympathetic denervation of cerebral vessels, CBF in cortical gray matter, white matter, and medulla is maintained at normal levels after CCT by autoregulation as long as MAP exceeds 60 torr. Decreased cerebellar blood flow in the experimental group suggests redistribution of CBF after CCT with relative preservation of flow to gray matter, white matter, and medulla. Reduced CBF in the acutely cord-injured patient with significant hypotension (MAP less than 60 torr) may stimulate or complicate coexistent head injury.

Animals

Peripheral beta-receptor responsiveness in patients with essential hypertension.

Peripheral beta-adrenergic receptor sensitivity was characterized in 24 patients with essential hypertension and in 13 age-matched normotensive subjects using an isoproterenol hydrochloride bolus dose-response technique. Decreased beta-receptor responsiveness to this exogenously administered beta-agonist was observed in hypertensive patients; for an equivalent chronotropic effect, higher doses of isoproterenol were required in hypertensive subjects than in normal subjects. Among "normal-renin" hypertensive patients, beta-receptor responsiveness was directly related to furosemide-stimulated plasma renin activity (PRA), suggesting that independently stimulated PRA may provide an indirect estimate of endogenous beta-receptor sensitivity. Hypertensive patients whose mean arterial pressure fell at least 10 mm Hg after four weeks of treatment with hydrochlorothiazide had even further depression in beta-receptor responsiveness, whereas receptor sensitivity was unchanged in patients whose blood pressure was unaffected. Thus, it is unlikely that this decreased receptor responsiveness in patients with untreated essential hypertension is a direct consequence of elevated arterial pressure.

Adult

Effect of adrenergic receptor blockade on the responses to isometric handgrip: studies in normal and hypertensive subjects.

Heart rate and blood pressure (BP) responses to a standardized 3 min isometric handgrip (IHG) test were measured in 32 normotensive men and compared with those found in 35 age-matched, drug-free men with established essential hypertension (BP range: 140--170/90--110). IHG testing in the normal subjects induced significant increases in heart rate (mean +/- SE: 7.6 +/- 3.3 beats/min), systolic blood pressure (19.4 +/- 5.3 mm Hg), and diastolic blood pressure (15.6 +/- 4.6 mm Hg). Although beginning from higher resting levels the hypertensive patients had similar degrees of increase in all three parameters. After chronic treatment with propranolol, the heart rate increase with IHG was suppressed in both study groups, but blood pressure responses differed, with a diminished pressor response to IHG seen in normal subjects and augmented pressor effects in the hypertensive group. Intravenous administration of phentolamine and propranolol completely abolished the pressor effects of IHG. These observations suggest that the autonomic control mechanisms mediating the responses to isometric exercise function similarly in drug-free normal and hypertensive patients and that the responses to IHG, mediated largely by endogenous catecholamine release, can be prevented by peripheral sympathetic receptor blockade.

Adrenergic alpha-Antagonists