Roger W. Sevy

N-acetylprocainamide: an active metabolite of procainamide.

Summary N-Acetylprocainamide has been detected in the plasma samples of each of four patients receiving procainamide. The metabolite was identified from tlc data and its identity confirmed by gas chomatographic-mass spectroscopic analysis. The metabolite was also detected in the whole blood of Sprague-Dawley rats after administration of PA. NAPA · HCI when injected ip into 42- to 49- day-old ICR male mice prevented coarse ventricular fibrillation caused by deep chloroform anesthesia and resultant hypoxia. NAPA · HCl reduced aconitine-induced arrhythmia to atrial flutter or atrial tachycardia with varying degrees of A-V block in three dogs. Analysis by tlc indicated that the mice, dogs, and rats did not deacetylate NAPA during the period of pharmacologic testing. NAPA was found to cause less ferrihemoglobin in Sprague-Dawley rats than did PA.

Gatecholamine Content and Response to Norepinephrine of Middle Cerebral Artery

Summary The norepinephrine (NE) and epinephrine (E) contents of bovine middle cerebral (MCA) and lingual (LA) arteries were determined fluorometrically. Although the amount of E was almost identical in the 2 vessels, the MCA contained almost four times as much NE as the LA. Cumulative NE dose-response curves revealed a much greater reactivity of the LA than the MCA. An inverse relationship is demonstrated between NE content and vascular reactivity to this agent, and a similar relationship is suggested between NE content and the degree of functional innervation in some vascular beds. The technical assistance of Mrs. Olha Holo-wecky is gratefully acknowledged.

Complexometric Titrations Using Calcium Specific Electrodes.

Summary This new technique is valuable in 3 different areas: the quantitative determination of calcium ion concentration, unequivocal determination of the stoichiometry of a complex, and determination of stability constants for complexes of various ligands with calcium ion. These cation specific electrodes are extremely useful in the study of chelation phenomena in biochemical reactions.

Renal Hemodynamic Responses to Stress in Normotensive and Hypertensive Subjects

Renal responses to stress were studied in 28 normotensive and 51 hypertensive patients. Renal clearances of inulin and PAH, filtration fraction, arterial blood pressure, and renal vascular resistance were determined in each patient immediately before, during, and after exercise (sit-ups), or the cold pressor test. In the control periods immediately before stress the majority of patients with essential hypertension displayed reduced values for inulin clearance (Cin) and clearance of paraaminohippurate (Cpah) and increased values for filtration fraction and renal vascular resistance, when compared with normotensive groups. These abnormalities were more severe in malignant hypertension than in benign essential hypertension. The pattern of response to stress was similar in normotensive and untreated hypertensive patients: reduction in Cin and Cpah, and increases in filtration fraction, blood pressure, and renal vascular resistance. These responses were more marked with exercise than with the cold pressor test. These responses to stress were also quantitatively similar in normotensive and untreated hypertensive subjects, except for renal vascular resistance, which was increased more in the hypertensive groups. Hyperreactivity in terms of vascular resistance, however, is not necessarily indicative of vascular smooth muscle hyperreactivity. The renal responses to exercise or the cold pressor test were reduced or abolished in hypertensive subjects by sympathectomy, and were diminished, in the majority of patients, by therapy with reserpine. Neither sympathectomy nor reserpine affected control (prestress) values for renal clearances or renal vascular resistance, however. The majority of patients with malignant hypertension, though showing severely reduced values for Cin and Cpah, and marked elevations in renal vascular resistance initially, showed minimal renal responses to exercise or the cold pressor test.

Renal and Hemodynamic Effects of Combination Therapy in Hypertension

in arterial blood pressure, to therapy with a combination of antihypertensive drugs rather than to therapy with a single drugt3 The knowledge of the pharmacodynamic effects of drug combinations is very inadequate in comparison with that for single antihypertensive drugs. This report summarizes our results on the acute and chronic renal and hemodynamic effects of reserpine, hydrochlorothiazide, and hydralazine in combination. Combinations of these three drugs, with only minor dosage adjustments of each, have been reported to provide satisfactory management in the majority of patients with moderate or severe hypertension

Catecholamine content of the sinoatrial node and common right atrial tissue.

Summary The NE and E content of the SA node region and right atrium of the dog was determined fluorometrically. The NE concentration of the SA node region was found to be significantly greater than in the right atrium. No difference in the epinephrine content could be demonstrated between the two regions.

Hypercalciuria during Acidosis in Hypoparathyroidism

Summary Both normal intact and hypocalcemic thyroparathyroidectomized rats developed hypercalciuria when made acidotic by NH4Cl plus acetazolamide administration. One hypoparathyroid patient developed hypercalciuria and hypocalcemia when given NH4Cl. This demonstrates that the hypercalciuria of acidosis can occur in the absence of parathyroid hormone and thyrocalcitonin.

Vascular Responses to Norepinephrine in Adrenal Insufficiency.

Summary Femoral vascular resistance as calculated from pressure/flow ratios was used as an index of vascular responsiveness to norepinephrine in control and adrenalectomized dogs. As indicated by changes produced by small intra-arterial doses of norepinephrine, there was no impairment in vascular responses of adrenalectomized animals when compared to controls.

Cardiovascular responses to norepinephrine in acute adrenal insufficiency.

Summary Cardiovascular responses to norepinephrine have been studied in adrenalectomized and control dogs. The initial mean systolic and diastolic blood pressures of the adrenalectomized group in both femoral and pulmonary arteries were lower than those of the control group. There was no significant difference between the 2 groups in ability to respond to intravenously injected norepinephrine by an increase in force of cardiac contraction or by an increase in systemic or pulmonary blood pressure. Myocardial or coronary artery lesions did not occur in the 2 adrenalectomized animals examined.

Theoretical basis for the determination of the molecularity of drug-receptor reactions and affinity of agonists.

Abstract According to tue occupation theory of drug-receptor reactions the biological response is a function of the number of receptors occupied by drug molecules. It is generally assumed that the reaction is a bi-molecular one involving one molecule of drug and one molecule of receptor. In the present paper this assumption regarding the stoichiometry is generalized to n molecule; of drug reacting with m molecules of receptor. The method is derived for the determination of m and n and the consequences examined as related to the major theories of receptor occupation theory. It is shown that the value of m significancy alters the estimation of both the affinity constant of the drug-receptor complex and the number of ‘spare’ receptors. The significance of independent and dependent effects is also discussed.