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Biomedical subjects

M Epstein

Publications and source records attributed to M Epstein.

At least 199 records · Page 11Linked to original sources
PubMed1990

Effects of calcium antagonists on renal hemodynamics.

Recent attention has been 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 actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do markedly alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment the glomerular filtration rate but produce only a modest improvement in renal perfusion. Studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, have demonstrated that the augmentation of the glomerular filtration rate is attributable to a preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations are not fully delineated, preliminary studies in experimental animal models indicate that calcium antagonists might exert salutary effects on renal function in clinical settings characterized by an acute impairment of renal hemodynamics. It is apparent, however, that the renal hemodynamic effects of calcium antagonists commend their use in the management of essential hypertension.

Animals↗
PubMed1990

Diclofenac induced immune thrombocytopenia.

We describe a patient with scleroderma who developed immune thrombocytopenia secondary to diclofenac on 2 occasions. Platelet count returned to normal with cessation of diclofenac and institution of prednisone.

Diclofenac↗
PubMed1989

Effects of amlodipine on renal hemodynamics.

Recently, 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 the kidney to vasoconstrictor agents. This study examined the effects of the novel dihydropyridine amlodipine on the hemodynamic response of the isolated perfused kidney to angiotensin II. Amlodipine completely reversed the angiotensin II-induced decrement in glomerular filtration rate of this model (0.72 +/- 0.15, 0.26 +/- 0.10 and 0.73 +/- 0.12 ml/min/g for control, angiotensin II and angiotensin II plus 0.1 microM amlodipine respectively). In contrast, amlodipine only partially restored renal perfusate flow (35.8 +/- 2.7, 14.7 +/- 1.9 and 23.7 +/- 2.5 ml/min/g for control, angiotensin II and angiotensin II plus amlodipine), thereby increasing filtration fraction. These findings are consistent with previous observations from this laboratory indicating that dihydropyridines predominantly vasodilate preglomerular renal resistance vessels and through this mechanism exert a preferential augmentation of glomerular filtration rate.

Amlodipine↗
PubMed1989

Renal hemodynamic effects of calcium antagonists.

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit predictable actions allowing for characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney; however, they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment the glomerular filtration rate but produce only a modest improvement in renal perfusion. A study using the postischemic hydronephrotic rat kidney model that permits direct visualization of afferent and efferent arterioles, this study demonstrated that this preferential augmentation of the glomerular filtration rate is primarily attributable to a selective vasodilation of pre-glomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies in experimental animal models indicate that calcium antagonists might exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics. The possible benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients in whom there is increased risk of acute renal insufficiency remain to be evaluated.

Animals↗
PubMed1989

Maternal and fetal sequelae of anticoagulation during pregnancy in patients with mechanical heart valve prostheses.

Previous reports indicate an increased risk of thrombotic and embolic events in patients with mechanical heart valve prostheses during pregnancy. We prospectively followed 50 pregnancies in 49 patients with 62 cardiac prostheses from presentation at the antenatal clinic through the remainder of the pregnancy. Of the 60 mechanical prostheses, 39 were Medtronic-Hall, 7 St. Jude Medical, 7 Starr-Edwards and 7 Björk-Shiley. Forty-three patients were in New York Heart Association functional class I or II and 6 were in functional class III or IV. Forty-five patients were in sinus rhythm and 4 had chronic atrial fibrillation. All patients received warfarin during the first and second trimesters. Forty-one pregnancies proceeded beyond 28 weeks. In 23 of these (group I) warfarin was replaced with heparin at 36 weeks gestation. In the remaining 18 (group II) warfarin was not substituted owing to premature onset of labor. The target prothrombin ratio (international normalized ratio) in patients receiving warfarin was 2.0 to 2.5. The partial thromboplastin time was maintained at 1.5 to 2.5 times the control value in patients receiving heparin. Eleven patients received dipyridamole plus warfarin for the duration of pregnancy. There were no maternal thromboembolic complications or deaths associated with pregnancy. Antepartum hemorrhage occurred in 1 patient at 35 weeks gestation. One patient (group I) experienced peripartum hemorrhage. All patients were hemodynamically stable before delivery, but 2 developed pulmonary edema during labor. The mean fetal birth weight was low (2.54 +/- 0.98 kg). There were 9 abortions (18%), 7 stillbirths (14%), 2 neonatal deaths (4%) and 2 instances of warfarin embryopathy (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

The hepatorenal syndrome.

A new appreciation of the hemodynamic, hormonal, and neural derangements associated with unexplained renal failure in patients with severe liver disease has led to a reappraisal of the limited therapeutic approaches to the hepatorenal syndrome. Although the prognosis generally remains dismal, specific supportive measures are now available for the management of selected patients.

Atrial Natriuretic Factor↗
PubMed1989

Interactions of low density lipoprotein with rat mesangial cells.

Hyperlipidemia may contribute to the pathogenesis of glomerular sclerosis. We therefore studied binding and uptake of low density lipoprotein (LDL) by cultured rat mesangial cells. In addition effects of LDL on PGE2 synthesis and cell proliferation were determined. At 4 degrees C mesangial cells bound [125I] LDL in a time- and concentration-dependent manner with half-maximal binding observed at 5 micrograms/ml of LDL protein. Binding was blocked by excess unlabeled LDL and by heparin. Uptake (binding plus internalization) of LDL at 37 degrees C markedly exceeded binding at 4 degrees C, continued to increase even with longer periods of incubation, and showed no saturability, consistent with uptake of LDL by mesangial cells. Further evidence for LDL uptake by mesangial cells was obtained by use of the fluorescent probe 1,1'-dioactadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate-labeled LDL (Dil-LDL). Incubation of mesangial cells with Dil-LDL at 37 degrees C showed positive fluorescence for all mesangial cells, indicating uptake of the Dil-LDL. LDL had a biphasic effect on mesangial cell proliferation as determined by [3H] thymidine incorporation. LDL at 10 micrograms/ml enhanced [3H] thymidine uptake modestly, but significantly, whereas a progressive and marked inhibition occurred at LDL concentration from 100 to 500 micrograms/ml. While LDL at 10 and 100 micrograms/ml significantly stimulated PGE2 production, inhibition of PGE2 by meclofenamate did not influence the effects of LDL on [3H] thymidine incorporation. We conclude that mesangial cells show specific binding and uptake of LDL and that high concentrations of LDL markedly decrease mesangial cell proliferation. These findings may pertain to the pathogenesis of glomerular lesions in hyperlipidemia of renal disease.

Animals↗
PubMed1989

Calcium antagonists and the kidney.

Recently, 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 the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment the glomerular filtration rate, but produce only a modest improvement in renal perfusion. By use of the postischemic, hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, it can be demonstrated that the above-mentioned preferential augmentation of glomerular filtration rate may be attributable to a selective vasodilation of preglomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies in experimental animal models indicate that calcium antagonists might exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics. There is a need to carry out prospective studies to determine the benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients at risk of acute renal insufficiency.

Animals↗
PubMed1989

Divergent effects of KCl-induced depolarization on afferent and efferent arterioles.

We have previously proposed that renal microvessels exhibit a unique regional heterogeneity. Studies with calcium channel agonists and antagonists suggest that potential-dependent calcium channels may play a more prominent role in the activation of the afferent arteriole than the efferent arteriole. Because KCl-induced depolarization elicits vasoconstriction exclusively by the activation of potential-dependent calcium channels, we tested this postulate directly by ascertaining the vasoconstrictor effects of KCl and countervailing effects of a calcium channel blocker on the afferent and efferent arteriole of isolated perfused hydronephrotic kidneys. Increasing media potassium concentration from 5 to 30 mM resulted in a marked renal vasoconstriction decreasing renal perfusate flow by 61 +/- 4%. An examination of the microvascular response to KCl revealed a predominant response of the afferent arteriole. Thus afferent arteriolar diameter decreased by 38 +/- 6% (i.e., from 20.7 +/- 1.5 to 13.0 +/- 1.8 microns, P less than 0.005), whereas efferent arteriolar diameter decreased by only 12 +/- 4% (i.e., from 15.8 +/- 1.6 to 13.8 +/- 1.4 microns, P = 0.05). Nifedipine completely returned afferent arteriolar diameter to control levels with a mean effective dose of 41 +/- 2 nM. These findings indicate that the afferent arteriole is more responsive to depolarization-induced vasoconstrictor stimuli than is the efferent arteriole and suggest a greater prevalence of potential-dependent calcium channels in this vessel.

Animals↗
PubMed1989

Lidocaine pharmacokinetics during water immersion in normal humans.

Water immersion produces a marked diuresis, natriuresis, and kaliuresis in association with suppression of the renin-aldosterone system. These effects are mediated primarily by an increase in central blood volume. Consequently, this redistribution and the resultant marked increase in cardiac output is associated with alterations in the circulating levels of several volume regulatory hormones, including plasma renin activity and plasma aldosterone. Although the changes in these blood hormonal levels probably reflect perturbation of hormonal release, it is conceivable that the above-mentioned central hemodynamic modifications result in an altered splanchnic blood flow, thereby modulating hormonal clearances. We assessed the effects of immersion on hepatic blood flow by determining the pharmacokinetics of single doses of lidocaine administered intravenously. Seven normal male subjects were studied during a time-control period and during water immersion to the neck. The clearance of lidocaine was unaltered by immersion, suggesting that the presumed marked central hypervolemia and increased cardiac output was not associated with changes in splanchnic blood flow.

Adult↗
PubMed1989

Effects of water immersion on atrial natriuretic peptide release in humans.

Water immersion (WI) to the neck induces prompt increases in central blood volume, central venous pressure, and atrial distension. Since atrial distension is a major stimulus for atrial natriuretic peptide (ANP) release, WI constitutes a unique model to investigate the physiological importance of ANP in humans. All studies to date demonstrate that ANP increases during the 1st h of WI in hydrated subjects, rising 2.5- to 3-fold by the end of the 2nd or 3rd h. During recovery from WI, ANP returns promptly to prestudy levels. Although distension of the atria probably constitutes the major stimulus for ANP release during WI, other mechanisms may coexist. In normal hydrated subjects undergoing WI, the increases in ANP correlate with the magnitude of the natriuresis, suggesting that ANP constitutes an important determinant of renal sodium handling in humans. It is simplistic, however, to consider the WI-induced augmentation of ANP to be the sole, or even the prepotent, mediator of the resultant natriuresis. Rather ANP should be considered as one of several hormonal, neural, and hemodynamic factors acting in concert in an integrated matrix to modulate volume homeostasis. Clearly, the results of several recent studies utilizing WI demonstrate that this maneuver constitutes an important investigative model to delineate further the role of ANP in subserving volume homeostasis in normal humans and in disorders of deranged volume regulation.

Animals↗
PubMed1989

Relationship between plasma ANF responsiveness and renal sodium handling in cirrhotic humans.

The responsiveness of atrial natriuretic factor (ANF) to central volume expansion and its role as a determinant of the natriuretic and diuretic responses of cirrhotic patients was evaluated utilizing water immersion (WI). Following equilibration on a 10-mEq sodium diet, 9 seated cirrhotic patients were studied during 3 h of WI. Before WI, plasma ANF levels (10.9 +/- 2.4 fmol/ml) were similar to those previously observed in normal sodium-replete subjects (7.7 +/- 0.9 fmol/ml). Five of the 9 cirrhotic subjects manifested an exaggerated peak ANF response, whereas the remaining 4 manifested increases similar to those of normals. The concomitant natriuretic response varied widely, ranging from absent to markedly exaggerated responses. The peak urinary sodium excretion varied independently of peak plasma levels of ANF and peak change of ANF from the prestudy hour (r = 0.36, p greater than 0.20, and r = 0.46, p greater than 0.20, respectively). Thus, in contrast to normal subjects, in whom the immersion-induced natriuresis correlated closely with the changes in ANF, the natriuretic responses of cirrhotic patients were dissociated from the concomitant increases in ANF. These observations indicate that sodium retention in cirrhosis is not attributable to impaired ANF release.

Adult↗
PubMed1989

Pressure-induced vasoconstriction of renal microvessels in normotensive and hypertensive rats. Studies in the isolated perfused hydronephrotic kidney.

The capacity of small arteries to respond to increased intravascular pressure may be altered in hypertension. In the kidney, hypertension is associated with a compensatory shift in the autoregulatory response to pressure. To directly determine the effects of established hypertension on the renal microvascular response to changes of perfusion pressure, we evaluated pressure-induced vasoconstriction in hydronephrotic kidneys isolated from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Vessel diameters of interlobular arteries (ILAs) and afferent and efferent arterioles were determined by computer-assisted videomicroscopy during alterations in renal arterial pressure (RAP) from 80 to 180 mm Hg. Increased RAP induced a pressure-dependent vasoconstriction in preglomerular vessels (afferent arterioles and ILAs), but not in postglomerular vessels (efferent arterioles). The calcium antagonist nifedipine prevented pressure-induced afferent arteriolar vasoconstriction with a similar half-maximal inhibitory concentration (IC50) (WKY, 63 +/- 27 vs. SHR, 60 +/- 32 nM). The pressure-activation curves for ILAs in SHR and WKY were similar. In contrast, the pressure-activation curve for afferent arterioles in SHR kidneys exhibited a rightward shift, which was observed at every segment of the afferent arteriole (i.e., near ILA, at midportion, and near glomerulus). These findings demonstrate that the ILA and the afferent arteriole both possess the ability to constrict in response to increased pressure, whereas this property is lacking in the efferent arteriole. Hypertension was associated with a compensatory shift in the pressure response of the afferent arteriole, such that higher RAPs were required to elicit vasoconstriction in this vessel.

Animals↗
PubMed1989

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

The role of peptides from the N terminus and C terminus of the 126 amino acid atrial natriuretic factor (ANF) prohormone in modulating renal sodium and water handling has not been defined. Since water immersion to the neck (NI) provides an acute central volume expansion identical to that produced by 2 liters of saline but without plasma compositional change, immersion to the neck was used to assess the N-terminal and C-terminal portions of the ANF prohormone response to acute central blood volume expansion in seven seated sodium-replete normal subjects. Both the C terminus, which contains amino acids 99-126 and is identical to ANF, and the whole N terminus (i.e., amino acids 1-98) increased promptly with NI and peaked after 1 hr of immersion. A Mr 3900 peptide from the midportion of the N terminus consistent with amino acids 31-67 (i.e., pro-ANF-31-67) also increased with NI and followed a pattern of increasing circulating concentration nearly identical to that of the whole N terminus of the prohormone, except that its maximal concentration was at the second hour of the 3 hr of NI. With cessation of immersion, ANF decreased to preimmersion levels within 1 hr whereas the N terminus and pro-ANF-31-67, although their circulating concentrations were decreasing, were still significantly elevated at 1 hr. These findings suggest that the increase in plasma ANF, the N terminus of the ANF prohormone, and pro-ANF-31-67 from the midportion of the N terminus, with natriuretic properties similar to ANF, contribute to the natriuretic response to NI, implying a physiologic role for these atrial peptides in modulating volume homeostasis in humans.

Adult↗