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Biomedical subjects

F M Fouad

Publications and source records attributed to F M Fouad.

At least 73 records · Page 4Linked to original sources

Hyperkalemia in azotemic patients during angiotensin-converting enzyme inhibition and aldosterone reduction with captopril.

Thirty-three hypertensive patients with a wide range of renal function were studied during initiation of angiotensin-converting enzyme inhibition with captopril to evaluate changes in potassium levels concomitant with reduction of aldosterone excretion. Ten patients (Group I) with low levels of plasma renin activity had no change in either aldosterone excretion or potassium during the first week of therapy. Twenty-three other patients (Group II) had decreased aldosterone excretion of an average of 63 percent, often reversing secondary hyperaldosteronism. This was associated with a rise in serum potassium from 3.6 +/- 0.1 to 4.4 +/- 0.1 mEq/liter (p less than 0.001). Serum potassium levels during captopril therapy were inversely related to glomerular filtration rate (creatinine clearance) and transiently exceeded 6.0 mEq/liter in markedly azotemic subjects. Despite rising potassium levels, nine patients had reduced aldosterone excretion to subnormal levels, sometimes for many months. During initiation of converting-enzyme inhibition, potassium-sparing agents and supplements should be discontinued and serum potassium levels should be monitored closely, particularly in patients with imparied renal function.

Adolescent↗

Heterogeneity of systemic hemodynamic response to a new calcium entry blocker, nitrendipine.

The hemodynamic effects of nitrendipine, a new calcium entry blocker, have been evaluated both experimentally and in hypertensive patients. The acute hemodynamic effects (left atrial injection of radioactive microspheres) were studied in normotensive and hypertensive (2K-1 Clip, Goldblatt) Sprague-Dawley rats; two dose levels were used intravenously: 0.3 and 3.0 mg/kg body weight. Arterial blood pressure was reduced in both groups in a dose dependent manner. Cardiac output increased with the higher dose but was reduced with the smaller dose. In humans, nitrendipine was given in a dose of 20 mg b.i.d. for 2 weeks to nine hypertensive patients. The reduction in blood pressure was due to a decrease in systemic resistance (52 +/- 9.7 (SD) to 39 +/- 5.4 u X M2, p less than 0.05); both cardiac output and heart rate response varied among patients (+ 2.1 to -0.97 L/min and + 19 to 4 bpm, respectively). Vasodilators have been previously classified according to predominance of their effects on venous or arterial system. Results of this study suggested that the same vasodilator could fall in one or the other subdivision depending on the dose used and possibly on individual responses.

Animals↗

Cardiovascular reflexes during long-term converting enzyme inhibition and sodium depletion. The response to tilt in hypertensive patients.

The reflex hemodynamic and humoral response to postural change during long-term renin-angiotensin blockade (captopril) was assessed in sodium-depleted hypertensive patients. Orthostatic hypotension was not observed with head-up tilt or repeated pressure recordings. During tilt, a reflex increase of heart rate occurred (76 +/- 2 to 98 +/- 4 bpm, p less than 0.001). Home recordings demonstrated only minor changes in blood pressure with standing. To evaluate these observations, hemodynamic studies were performed during tilt at three stages of therapy: control, administration of captopril, and administration of captopril plus diuretic. With tilt, no orthostatic hypotension was noted at all three stages of therapy, despite similar peripheral pooling (-22 percent cardiac index). Maintenance of blood pressure was due to reflex increase of heart rate (44, 45 and 38 percent) and systemic resistance (34, 38 and 37 percent). The response to tilt of plasma renin activity was modified by drug therapy, but not completely blocked. This study indicated that long-term converting enzyme inhibition and sodium depletion were safe and did not appreciably blunt the cardiovascular reflexes responsible for prevention of orthostatic hypotension.

Blood Pressure↗

Dihydroergotamine in idiopathic orthostatic hypotension: short-term intramuscular and long-term oral therapy.

The efficacy of dihydroergotamine (DHE-45) in the treatment of orthostatic hypotension due to deficient circulatory reflexes was investigated in 10 patients. Over the short term, intramuscular DHE-45 induced an increase (P less than 0.005) in supine blood pressure (137 +/- 8.9 to 158 +/- 8.1 mm Hg 15 min after DHE-45 and 142 +/- 9.9 to 183 +/- 7.5 mm Hg 60 min after DHE-45) associated with an increase in total peripheral resistance (TPR) (37 +/- 1.9 to 41 +/- 2.8 U . m2 and 34 +/- 2.2 to 41 +/- 2.3) and no change in cardiac output (CO), plasma renin activity (PRA), or plasma norepinephrine. Eight patients tolerated head-up tilt to a higher angle--the drop of mean arterial pressure at equivalent angles of tilt (pre- and post-DHE-45) was less. The other two patients did not improve. On the other hand, oral DHE-45 (1-mo therapy) did not induce a change in mean arterial pressure, heart rate, CO, or TPR; the only significant hemodynamic change was an increase in the ratio cardiopulmonary volume/total blood volume (12 +/- 1.9% to 16 +/- 0.7%, P less than 0.025). Changes in PRA, plasma aldosterone, and plasma catecholamines were not significant. Response to head-up tilt was variable after the first week of therapy. Blood level 2 hr after an oral dose was one order of magnitude lower (0.1 to 0.2 ng/ml) than after intramuscular injection (1.2 to 3.2 ng/ml). The discrepancy between the effects of intramuscular and oral DHE-45 for treatment of idiopathic orthostatic hypotension in this group of patients might be related to the nature of the disease (autonomic insufficiency) or to low bioavailability, suggesting that either another formulation of the drug or methods to improve absorption are needed for long-term therapy.

Administration, Oral↗

Early hemodynamic and humoral effects of lofexidine.

Hemodynamic and humoral effects of lofexidine were assessed in 11 patients with essential hypertension after a total of 1.5 mg were given orally over 24 hr. Heart rate (bpm) slowed (-12 +/- 6 [SEM], p less than 0.05) and cardiac output (liters per minute) was reduced (-0.78 +/-0.18, p less than 0.01) irrespective of blood pressure response; the latter was related to changes in systemic resistance (TPR) (r = 0.72, p less than 0.01). Cardiac performance judged from ejection fraction (0.61 +/- 0.03 to 0.59 +/- 0.03, NS) and mean transit time (8.73 +/- 0.53 sec to 9.20 +/- 0.35, NS) were not altered. Plasma volume was expanded more than 10% in two patients but not changed in the others. Supine plasma catecholamines determined in five patients were reduced in all but one with no correlation to changes in either TPR or diastolic blood pressure. On the other hand, there was an increase in plasma catecholamines during head-up tilt in four of five patients, indicating normal catecholamines release. Orthostatic hypotension occurred de novo in three patients; two of them had simultaneous slowing of heart rate (vasovagal attack). Results suggested that reduction of blood pressure by lofexidine depended on lack of increase in TPR in response to reduction of cardiac output; the hemodynamic pattern of this centrally acting adrenergic blocker closely resembled that reported for beta blockers.

Adolescent↗

Kinetics of the acute-phase reaction in rats after tumor transplantation.

Transplantation of Yoshida sarcoma (solid type) and Zajdela ascites hepatoma tumors in rats induces a biphasic change in the concentration of the following five acute-phase proteins: alpha-1-acid glycoprotein; alpha-1-antitrypsin; haptoglobin; hemopexin; and ceruloplasmin. These proteins and other plasma proteins were quantitated by two-dimensional immunoelectrophoresis relative to normal serum concentrations. The elevation of most of these acute-phase proteins was greater in the second phase, during which serum levels increased continuously as the tumor burden increased until the animals died. The increase in haptoglobin concentration during the second phase was much higher in rats bearing Yoshida sarcoma than in rats bearing Zajdela tumors. Rats receiving irradiated tumor cells showed neither tumor growth nor second-phase protein changes. Significant increases in uptake of 3H-amino acids by isolated perfused livers of tumor-bearing rats provided evidence for an increase in the hepatic synthesis rates of the acute-phase proteins. Removal of the solid tumor resulted in a gradual decrease of acute-phase protein concentrations with concomitant increase in serum albumin concentration. These alterations in serum acute-phase proteins during tumor growth and after removal of the tumor may make their use attractive as biological markers of the response of the tumor-bearing animal to its tumor.

Animals↗

Noninvasive measurement of cardiopulmonary blood volume. Evaluation of the centroid method.

Cardiopulmonary blood volume (CPV) and mean pulmonary transit time (MTT) determined by radionuclide measurements (Tc-99m HSA) were compared with values obtained from simultaneous dye-dilution (DD) studies (indocyanine green). The mean transit time was obtained from radionuclide curves by two methods: the "peak-to-peak" time and the interval between the two centroids determined from the right and left-ventricular time-concentration curves. Correlation of dye-dilution MTT and "peak-to-peak" time was significant (r = 0.79, p less than 0.001), but its correlation with centroid-derived values was better (r = 0.86, p less than 0.001). CPV values (using the centroid method for radionuclide technique) correlated significantly with values derived from dye-dilution curves (r = 0.74, p less than 0.001). Discrepancies between the two were greater the more rapid the circulation (r = 0.61, p less than 0.01), suggesting that minor inaccuracies of dye-dilution methods, due to positioning or delay of the system, can become magnified in hyperkinetic conditions. The radionuclide method is simple, repeatable, and noninvasive, and it provides simultaneous evaluation of pulmonary and systemic hemodynamics. Further, calculation of the ratio of cardiopulmonary to total blood volume can be used as an index of overall venous distensibility and relocation of intravascular blood volume.

Adolescent↗

Abnormal left ventricular relaxation in hypertensive patients.

1. The maximum rates of left ventricular ejection and filling were derived (Fourier analysis) from the left ventricular volume curve (99m technetium-human serum albumin gated blood pool studies) in 12 normotensive subjects and 15 hypertensive patients of matched age groups. 2. Average values of cardiac output, ejection fraction, heart rate and left ventricular ejection rate were not significantly different in the two groups. 3. Hypertensive patients had a slower rate of left ventricular filling (P < 0.05), suggesting diminished left ventricular compliance in hypertension.

Adult↗

Constrasts and similarities of acute hemodynamic responses to specific antagonism of angiotensin II ([Sar1, Thr8] A II) and to inhibition of converting enzyme (captopril).

The early blood pressure and hemodynamic effects of the converting enzyme inhibitor (CEI), captopril, were compared in 23 hypertensive patients with those of a specific angiotensin II antagonist (AA), [Sar1, Thr8] A II. AA reduced mean arterial pressure (MAP) greater than 10 mm Hg only in seven of 23 patients vs 15 of 23 who responded to CEI (p less than 0.02). With both drugs, changes in MAP were not associated with significant changes in cardiac output (p greater than 0.10 for both drugs), but correlated with changes in systemic resistance (TPR); r = 0.84, p less than 0.001 for AA and r = 0.71, p less than 0.001 for CEI. Changes in TPR and MAP correlated significantly and inversely with log plasma renin activity in both instances; for AA, r = 0.829 and for CEI, r = -0.737; p less than 0.001 for both. The slopes of the two regression lines were not significantly different but the intercepts were +8.47 mm Hg for AA vs -10.17 mm Hg for CEI (p less than 0.001). This quantitative difference in response could be attributed either to an agonistic effect of [Sar1, Thr8] A II or to an additional vasodilator effect of captopril.

Adult↗

Isolation and characterization of human and canine gastric mucosal glycoproteins and their degradation by proteases and acid hydrolases.

High molecular weight glycoproteins were isolated and purified from canine antral and fundic mucosal tissue by means of non-degrading techniques. The results disclosed the advantage of urea extraction technique over the culture method in isolating the native glycoproteins. The glycoproteins were susceptible to degradation by protease, thus yielding low molecular weight glycopeptides. Chemical analysis of these glycopeptides and their parent macromolecules revealed that the oligosaccharide residues are attached to threonine, serine and proline residues of the protein chains. Similarly, high molecular weight glycoproteins isolated from human gastric gel mucin showed the same characteristics of canine gastric glycoproteins. Canine fundic glycoprotein or glycopeptide released their prosthetic carbohydrate groups under the lytic effect of fundic acid hydrolases.

Animals↗

Biosynthesis of plasma proteins in serum-free medium by primary monolayer culture of rat hepatocytes.

Morphologically intact rat hepatocytes separated by collagenase perfusion were cultured in L-15/fetal calf serum medium to form a monolayer. Thereafter the hepatocytes were grown in serum-free L-15 medium in which they produced and continuously released plasma proteins. The secreted plasma proteins were collected, separated and characterized by crossed immunoelectrophoresis. Most of the newly biosynthesized plasma proteins secreted into the medium during incubation for thirty hours had the same electrophoretic mobility, antigenicity and staining characteristics as their counterparts in rat serum. The addition of tritium labelled amino acid mixture to the culture medium revealed that the release of radioactively labelled plasma proteins into the culture medium was essentially linear during the thirty hour incubation period. However, saturation of the intracellular pool took place after ca. ten hours of incubation. Addition of leukocytic endogenous mediator, LEM, to cultures of rat hepatocytes caused a profound increase in the relative concentration of acute-phase proteins secreted into the culture medium.

Amino Acids↗