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Biomedical subjects

M Epstein

Publications and source records attributed to M Epstein.

At least 37 records · Page 2Linked to original sources
PubMed1991

Characterization of the renal microvascular effects of angiotensin II antagonist, DuP 753: studies in isolated perfused hydronephrotic kidneys.

The renal microvascular effects of DuP 753, an orally active imidazole angiotensin II (ANG II) receptor antagonist were assessed directly in isolated perfused hydronephrotic rat kidneys. Unilateral hydronephrosis was induced to facilitate direct visualization of renal microvessels. Hydronephrotic kidneys were perfused in vitro and microvessel diameters were measured by automated computer-assisted image processing. The administration of 0.3 nmol/L ANG II decreased afferent arteriolar (AA) and efferent arteriolar (EA) diameters by 34 +/- 3% (from 17.9 +/- 0.6 to 11.9 +/- 0.6 microns, P less than .001, n = 11) and 28 +/- 3% (from 17.1 +/- 1.3 to 12.3 +/- 1.3 microns, P less than .001, n = 11), respectively. The subsequent administration of 0.1, 1.0, and 10 mumols/L DuP 753 reversed ANG II-induced vasoconstriction of the AA by 39 +/- 10%, 81 +/- 8%, and 103 +/- 9%, and of the EA by 22 +/- 7%, 51 +/- 6%, and 87 +/- 13%, respectively. These observations indicate that DuP 753 completely blocks both the renal afferent and efferent arteriolar actions of ANG II. In light of the pathogenetic role of ANG II in mediating the deranged renal hemodynamics associated with hypertension, congestive heart failure, and some forms of renal insufficiency, our findings provide a theoretical framework for future studies assessing the potential therapeutic applicability of DuP 753 in reversing ANG II-mediated renal vasoconstriction.

Angiotensin II↗
PubMed1991

Calcium antagonists and the kidney. Implications for renal protection.

During the past decade, attention has been focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney (IPK), calcium antagonists exhibit consistent actions, permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated IPK, but do dramatically alter the hemodynamic response of the kidney to vasoconstrictor agents. Our recent studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, demonstrate that the preferential augmentation of glomerular filtration rate (GFR) observed in the IPK is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, recent studies indicate that calcium antagonists exert salutary effects on renal function in clinical settings, characterized by impaired renal hemodynamics such as radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the salutary effects of calcium antagonists on renal hemodynamics recommend their use in the management of essential hypertension.

Acute Kidney Injury↗
PubMed1991

Increased release of the N-terminal and C-terminal portions of the atrial natriuretic factor prohormone during immersion-induced central hypervolemia in cirrhotic humans.

The role of peptides from the N-terminus and C-terminus of the 126 amino acid (a.a.) atrial natriuretic factors (ANF) prohormone in modulating renal sodium and water handling in cirrhotic patients has not been defined. Eight cirrhotic individuals were evaluated; their mean basal circulating concentration of the C-terminus (a.a. 99-126; i.e., ANF) was 25 +/- 2 fmol/ml, not different from the 22 +/- 1 fmol/ml value found in 54 normal volunteers. On the other hand, the basal circulating concentrations of the whole N-terminus (a.a. 1-98) and the midportion of the N-terminus (namely a.a. 31-67; pro ANF 31-67) of the ANF prohormone in these cirrhotic subjects of 704 +/- 52 and 654 +/- 83 fmol/ml were significantly elevated (p less than 0.05; ANOVA) in comparison to control values (531 +/- 25, 317 +/- 22 fmol/ml, respectively). Following equilibration on a 10 mmol/day sodium diet, the responsiveness of the N-terminus and C-terminus of ANF prohormone to 3 h of water immersion, which induces marked acute central volume expansion, was evaluated in these 8 seated cirrhotic patients. There was a prompt increase in the circulating concentrations of immunoreactive (ir) pro ANF 1-98 (whole N-terminus), ir pro ANF 31-67, and ir ANF (C-terminus) within 15 min of immersion (p less than 0.05; ANOVA) compared to their preimmersion values. The response of circulating ir pro ANF 1-98, pro ANF 31-67, and ANF concentrations in these 8 cirrhotic subjects to immersion was significantly greater (p less than 0.05; ANOVA) than that of 7 healthy volunteers undergoing an identical 3-hour immersion study. With cessation of immersion, the C-terminus decreased within 30 min to a concentration not significantly different from preimmersion values, whereas the N-terminus and pro ANF 31-67 remained significantly elevated after 1 h.

Adult↗
PubMed1991

Right and left ventricular function after cardiac transplantation. Changes during and after rejection.

BACKGROUND: Attempts to identify noninvasive markers of ventricular dysfunction accompanying acute rejection have been hampered by a lack of detailed simultaneous hemodynamic data. Therefore, we prospectively performed serial monitoring of detailed left and right heart hemodynamic parameters in cardiac transplant recipients at the time of routine endomyocardial biopsy to better define the physiology of the allograft heart during and after acute rejection. METHODS AND RESULTS: To better assess the pathophysiology of the rejection process, 18 cardiac transplant patients were prospectively studied by serial right heart micromanometer catheterization and digital image processing at the time of routine endomyocardial biopsy. Eleven patients had 18 episodes of rejection. Studies of baseline (negative biopsy preceding rejection), rejection (acute moderate rejection), and resolved (first negative biopsy after rejection) states were compared. Seven patients who did not experience an episode of rejection served as the control group. Right ventricular minimum and end-diastolic pressures increased from baseline values of 0.9 +/- 3.2 and 6.9 +/- 3.7 mm Hg, respectively, to 3.2 +/- 5.5 and 9.9 +/- 6.6 mm Hg, respectively, with rejection (both variables, p less than 0.05) and remained elevated despite histological resolution of rejection (4.3 +/- 5.5 and 10.0 +/- 7.1 mm Hg, respectively; p less than 0.05 for both variables compared with baseline values). Concurrently, right ventricular end-diastolic volumes (133 +/- 29, 119 +/- 27, and 114 +/- 30 ml; baseline, rejection, and resolved, respectively) and left ventricular end-diastolic volumes (133 +/- 24, 117 +/- 20, and 113 +/- 30 ml; baseline, rejection, and resolved, respectively) significantly decreased during rejection and remained decreased after resolution of rejection (rejection and resolved compared with baseline values, p less than 0.05). Right ventricular chamber stiffness (0.055 +/- 0.035, 0.085 +/- 0.057, and 0.092 +/- 0.076 mm Hg/ml; baseline, rejection, and resolution, respectively; rejection and resolved compared with baseline values, p less than 0.05) increased with rejection and remained elevated after resolution of rejection. Right ventricular peak filling rate also increased from a baseline value of 2.48 +/- 0.45 to 2.76 +/- 0.63 ml end-diastolic volumes per second with rejection (p less than 0.05). Elevation of right ventricular filling pressures, peak filling rate, and chamber stiffness with a concomitant decrease in end-diastolic volume is consistent with a restrictive/constrictive physiology. Mean arterial blood pressure and systemic vascular resistance were elevated after the resolution of rejection (compared with either rejection or baseline values, p less than 0.05) associated with a higher mean daily dose of prednisone (resolved compared with either baseline or rejection values, p less than 0.05). The control group experienced a time-dependent increase in mean and diastolic systemic arterial pressures (both comparisons, p less than 0.05) without detectable diastolic dysfunction. CONCLUSIONS: Persistence of biventricular diastolic dysfunction may be due to an irreversible effect of rejection, although multifactorial changes in left ventricular afterload occur that may complicate serial assessment of ventricular function.

Adult↗
PubMed1991

Calcium antagonists and renal hemodynamics: implications for renal protection.

During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of this preparation to vasoconstrictor agents. Our recent studies with the isolated perfused hydronephrotic rat kidney model, which permits visualization of afferent and efferent arterioles, have demonstrated that the augmentation of glomerular filtration rate observed in the isolated perfused kidney is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in patients with impaired renal hemodynamics. Such disorders include radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the effects of calcium antagonists on renal blood flow commend their use in the management of essential hypertension.

Animals↗
PubMed1991

Reduction of high-risk sexual behavior among heterosexuals undergoing HIV antibody testing: a randomized clinical trial.

BACKGROUND: We evaluated the effect of HIV antibody testing on sexual behavior and communication with sexual partners about AIDS risk among heterosexual adults at a clinic for sexually transmitted diseases. METHODS: We randomized 186 subjects to receive either AIDS education alone (the control group) or AIDS education, an HIV antibody test, and the test results (the intervention group). These subjects were then followed up 8 weeks later. RESULTS: At follow-up, mean number of sexual partners decreased, but not differently between groups. However, compared with controls, HIV antibody test intervention subjects, all of whom tested negative, questioned their most recent sexual partner more about HIV antibody status (P less than 0.01), worried more about getting AIDS (P less than 0.03), and tended to use a condom more often with their last sexual partner (P = 0.05): 40% of intervention subjects vs 20% of controls used condoms, avoided genital intercourse, or knew their last partner had a negative HIV antibody test (P less than 0.005). CONCLUSION: HIV antibody testing combined with AIDS education increases concern about HIV and, at least in the short term, may promote safer sexual behaviors. Additional strategies will be necessary if behaviors risky for HIV transmission are to be further reduced.

AIDS Serodiagnosis↗
PubMed1991

Calcium antagonists and the kidney: implications for renal protection.

During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney (IPK), but they do dramatically alter the response of this preparation to vasoconstrictor agents. Our recent studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that the preferential augmentation of the glomerular filtration rate observed in the IPK is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in patients with impaired renal hemodynamics. Such disorders include radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the effects of calcium antagonists on renal blood flow commend their use in the management of essential hypertension.

Animals↗
PubMed1991

Diltiazem and renal hemodynamics: implications for renal protection.

During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists (including diltiazem) do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of this preparation to vasoconstrictor agents. Our recent studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that the preferential augmentation of glomerular filtration rate induced by calcium antagonists in the isolated perfused kidney is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in patients with impaired renal hemodynamics, such as radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency.

Animals↗
PubMed1991

Calcium antagonists and renal hemodynamics: implications for renal protection.

Recently, attention has focussed on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal hemodynamic effects. Calcium antagonists do not affect the vascular tone of the vasodilated isolated perfused kidney, but they do dramatically reverse the response of this preparation to vasoconstrictor agents. Studies using the isolated hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that calcium antagonists selectively vasodilate preglomerular vessels. The clinical implications of such observations are still being delineated. Nevertheless, the results of preliminary studies in experimental animal models and in human transplant recipients suggest that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics. Furthermore, a case can be made that these salutary renal hemodynamic effects of calcium antagonists commend their use in the management of essential hypertension.

Calcium Channel Blockers↗
PubMed1991

Use of centrally acting sympatholytic agents in the management of hypertension.

Considerable evidence suggests that hyperactivity of the sympathetic nervous system is implicated not only in the pathogenesis of essential hypertension but also in several blood pressure-independent complications of essential hypertension. Even with the advent of newer antihypertensive agents, including angiotensin-converting enzyme inhibitors and calcium antagonists, the centrally acting sympatholytics (alpha 2-adrenoceptor agonists) remain a valuable group of medications for the management of hypertension of all grades of severity. Their advantages include efficacy; rarity of contraindication; absence of most metabolic and serious side effects; favorable effects on systemic hemodynamics; lack of true tolerance and infrequency of volume expansion-related pseudotolerance; suitability in the elderly, in isolated systolic hypertension, and in patients with various concomitant conditions, such as diabetes mellitus; ability to reverse left ventricular hypertrophy; and relative low cost. The long duration of action of guanfacine hydrochloride, the most recently marketed agent, and of the transdermal formulation of clonidine is an especially commendable feature. The principal disadvantages of this class of medications are an overlap between the therapeutic dosage and that producing sedation and dry mouth and the potential to cause the discontinuation syndrome and sexual dysfunction.

Aged↗
PubMed1990

[Right ventricular dysplasia].

Right ventricular dysplasia (RVD) is characterized by partial or total replacement of part of the right ventricular musculature by fatty and fibrous tissue. In its typical form it presents with ventricular tachycardia, usually in the fourth decade of life. 6 men and 2 women (mean age 55.6 years), referred for evaluation of arrhythmias or other cardiac symptoms, were diagnosed as having RVD on echocardiography after other causes of right ventricular enlargement were excluded. The mean age was 55.6 years, older than originally reported. 5 presented with supraventricular arrhythmias, including atrial flutter, atrial fibrillation, supraventricular tachycardia and sick-sinus syndrome. Only 2 had ventricular tachycardia; in 1 patient no arrhythmia was found. We conclude that RVD includes a wide spectrum of arrhythmias, of which ventricular tachycardia is probably not the most common. The incidence of RVD in the older population may be greater than originally reported, and may include a slowly developing form of the disease. In some cases RVD may be the pathophysiological basis of lone atrial fibrillation and sick-sinus syndrome.

Adult↗
PubMed1990

Direct visualization of effects of endothelin on the renal microvasculature.

The renal microvascular and hemodynamic actions of endothelin were assessed directly in isolated perfused hydronephrotic (HYD) and normal kidneys, respectively. In HYD kidneys endothelin was a potent vasoconstrictor of the afferent arteriole (AA), eliciting a threshold vasoconstrictor response at 0.01 nM (P less than 0.05). At 0.1 and 0.3 nM, endothelin reduced AA diameter by 22 +/- 6 (P less than 0.025) and 41 +/- 4% (P less than 0.001), respectively. Furthermore, endothelin provoked oscillatory vasomotion in the AA. In contrast, endothelin had less effect on the efferent arteriole (EA), reducing EA diameter by only 7 +/- 4 (P greater than 0.20) and 13 +/- 4% (P less than 0.05), at 0.1 and 0.3 nM, respectively. In normal kidneys endothelin elicited a long-lasting vasoconstriction with a dose dependency similar to that observed in the AA of HYD kidneys. Furthermore, endothelin reduced glomerular filtration rate (GFR) from 0.58 +/- 0.04 to 0.09 +/- 0.05 ml.min-1.g-1 (P less than 0.001) in this model. Both the AA vasoconstriction and reduction in GFR were completely reversed by nifedipine. These findings indicate that endothelin is a potent renal vasoconstrictor that decreases GFR by a predominant vasoconstriction of the AA. Our observations are consistent with the postulate that endothelin elicits renal vasoconstriction via a mechanism involving dihydropyridine-sensitive calcium channels and that such calcium channels play a prominent role in the activation of the AA.

Animals↗
PubMed1990

Determinants of renal actions of atrial natriuretic peptide. Lack of effect of atrial natriuretic peptide on pressure-induced vasoconstriction.

We have previously demonstrated that atrial natriuretic peptide (ANP) completely reverses norepinephrine-induced afferent arteriolar (AA) vasoconstriction. In the present study we characterized the effects of ANP on pressure-induced vasoconstriction of AA. Chronic unilateral hydronephrosis was induced to facilitate direct visualization of the renal microcirculation. Hydronephrotic kidneys were perfused in vitro, and AA diameters were measured during stepwise alterations in renal arterial pressure. Increasing renal arterial pressure from 80 to 180 mm Hg decreased AA diameter by 22 +/- 2% (from 18.5 +/- 1.0 to 14.4 +/- 1.0 microns, p less than 0.005). In the presence of 100 nM ANP [human ANP-(4-28)], AA vasoconstricted by 23 +/- 4%, indicating that ANP failed to modify the pressure-induced AA vasoconstriction. Furthermore, both nitroprusside (10 microM) and 8-bromoguanosine 3':5'-cyclic monophosphate (30 microM) only partially inhibited pressure-induced AA vasoconstriction (31 +/- 5% and 47 +/- 7%, respectively), whereas these vasodilators completely abolished norepinephrine-induced AA vasoconstriction. In contrast, nifedipine completely inhibited pressure-induced AA vasoconstriction. In summary, pressure-induced AA vasoconstriction is insensitive to the action of ANP, is relatively refractory to cyclic GMP-mediated vasorelaxation, but is completely inhibited by calcium channel blockade. Furthermore, since ANP completely abolishes norepinephrine-induced vasoconstriction but fails to affect pressure-induced vasoconstriction, it is apparent that the type of underlying vasoconstrictor stimuli constitutes a major determinant of the renal microvascular response to ANP.

Animals↗