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S N Heyman

Publications and source records attributed to S N Heyman.

At least 55 records · Page 3Linked to original sources
PubMed1992

In-vivo and in-vitro studies on the effect of amphotericin B on endothelin release.

Since amphotericin B nephrotoxicity is mediated, in part by hypoxic tubular injury, the role of endothelin in the renal vasoconstriction, characteristic of amphotericin toxicity has been studied. Intact and salt depleted rats were infused with amphotericin B (20 micrograms/kg per min) or 5% dextrose over 20 min. Plasma endothelin levels determined at the conclusion of the infusion period, did not differ between the experimental groups, despite a marked reduction in renal blood flow noted in rats infused with amphotericin B. Amphotericin B (10(-5)-10(-7) M) did not stimulate endothelin release from cultured bovine aortic endothelial cells. However, in a model of chronic amphotericin nephrotoxicity produced by repeated daily intraperitoneal injections of amphotericin B (5 mg/kg) to salt depleted rats, renal failure was associated with elevated plasma endothelin levels (29.3 +/- 4.4 fmol/mL, vs 10.8 +/- 1.2 fmol/mL in salt depleted controls, P less than 0.01). We conclude that while plasma endothelin may be increased in chronic amphotericin B nephropathy, this peptide does not mediate the acute renal vasoconstriction associated with the infusion of this drug.

Amphotericin B↗
PubMed1992

Radiocontrast agents induce endothelin release in vivo and in vitro.

The intravascular administration of the ionic radiocontrast agent sodium iothalamate (2.9 g of iodine/kg body wt) to rats induced an increase in plasma concentration of immunoreactive endothelin from 21.3 +/- 1.2 to 36 +/- 3 fmol/mL, preceded by a transient rise in the plasma level of atrial natriuretic peptide and associated with a fall in RBF. Equi-iodine amounts of the nonionic agents ioxaglate and iohexol elicited similar or more marked changes in plasma endothelin, but hypertonic solutions of NaCl, mannitol, or glucose did not. Comparable levels of endothelin produced by infusions of endothelin-1 induced a reduction of up to 29% in RBF. Iothalamate and iohexol stimulated endothelin release from cultured bovine endothelial cells, suggesting a direct effect of ionic and nonionic agents on vascular endothelium. The data invite speculation that under some circumstances endothelin release might play a role in the circulatory changes caused by these compounds and in the pathogenesis of radiocontrast nephropathy.

Animals↗
PubMed1991

Protective action of glycine in cisplatin nephrotoxicity.

Because glycine is cytoprotective for kidney cells in vitro, we investigated its possible action in vivo to protect rats against cisplatin nephrotoxicity, a well-established experimental model of renal tubular injury. Glycine was infused at a dose of 1 mmol per 100 g body weight per hour for 75 minutes, starting 15 minutes before cisplatin, 5 mg per kg, was injected intravenously. Plasma concentration of glycine rose to 3.5 mmol per liter at the time cisplatin was injected. These rats were compared with cisplatin-treated animals treated with L-alanine or with isotonic saline. After five days plasma creatinine of saline-treated rats given cisplatin had risen threefold to 2.6 +/- 1.5 mg per 100 ml (mean +/- SD), as creatinine clearance fell to 25% of baseline (0.14 +/- 0.05 ml/min/100 g). Morphological evaluation disclosed extensive damage involving all S3 segments in the outer medulla as well as the medullary rays of the cortex. In contrast, in rats treated with glycine, plasma creatinine rose only to 1.2 +/- 0.2 mg/100 ml and creatinine clearance was maintained at 75% of baseline (0.35 +/- 0.05 ml/min/100 g). Glycine also attenuated the weight loss, polyuria, increased fractional excretion of sodium and potassium, decreased urinary osmolality, and renal glycosuria observed in control, saline-treated rats after cisplatin, while substantially decreasing the percentage of S3 tubules with evident morphological injury. Renal platinum content was unaffected by glycine. The administration of L-alanine or the delayed infusion of glycine, starting one hour after cisplatin was given, did not prevent cisplatin toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Early renal medullary hypoxic injury from radiocontrast and indomethacin.

We evaluated the acute changes in cortical and outer medullary oxygen tension and the alterations in renal function and morphology within the first 90 minutes after the administration of indomethacin and iothalamate to anesthetized Sprague-Dawley rats. Both agents were found to produce marked and protracted outer medullary hypoxia averaging 12 +/- 4 and 9 +/- 2 mm Hg, respectively (mean +/- SE). Given together to salt depleted uninephrectomized rats they produced an early hypoxic injury localized selectively in the outer medulla. This lesion progressed from 3 +/- 1% of medullary thick ascending limbs (mTALs) at 15 minutes to 22 +/- 7% at 24 hours. Condensed "dark" cells were observed at 15 minutes, probably representing a type of early injury. Residual red cell mass, quantified in the outer medullary vasculature of perfusion-fixed kidneys and presumably reflecting stasis, was substantially increased in iothalamate treated rats. Red cell mass in the interbundle zone correlated with mTAL necrosis. Taken together, these results show an early period of medullary hypoxia, accompanied by a selective injury to mTALs in the central interbundle zone with apparent stasis. These findings contrast sharply with the ischemia-reflow pattern of renal damage and emphasize the important role of medullary hypoxia in the genesis of acute renal failure in this model.

Animals↗
PubMed1991

Experimental nephrotoxicity of the radiocontrast agents iohexol, ioxaglate, and iothalamate. An in vitro and in vivo study.

The authors compared the renal toxicity of the low osmolality radiocontrast agents, iohexol and ioxaglate, and the ionic agent, iothalamate, at equivalent iodine dose, using experimental models in vitro and in vivo. In isolated perfused rat kidneys, all agents induced comparable biphasic hemodynamic changes, associated with similar declines in glomerular filtration rate (GFR) and tubular necrosis. In two different in vivo models (using multiple insults combined with the administration of radiocontrast), iothalamate appeared to induce more severe morphologic injury. Despite similar nephrotoxic potential in vitro, the newer radiocontrast agents, iohexol and ioxaglate, cause in vivo less renal injury than iothalamate in the experimental models.

Angiotensin II↗
PubMed1991

Role of nitric oxide in renal medullary oxygenation. Studies in isolated and intact rat kidneys.

We investigated the role of the endothelial-derived relaxing factor nitric oxide (NO) in the homeostasis of O2 supply to the renal medulla, a region normally operating on the verge of hypoxia. Sensitive Clark-type O2 microelectrodes were inserted into renal cortex and medulla of anesthetized rats. The inhibitor of NO formation, L-NG-monomethylarginine (LNMMA), while increasing blood pressure and reducing renal blood flow, decreased medullary pO2 from 23 +/- 3 mmHg to 12 +/- 3 (P less than 0.001), with no change in the cortex. These responses were promptly reversed by L-arginine, which bypasses the LNMMA blockade. In isolated rat kidneys, LNMMA reduced perfusion flow without altering glomerular filtration rate, and augmented deep medullary hypoxic injury to thick ascending limbs from 68 to 90% of the tubules (P less than 0.02). These changes were prevented by L-arginine. Nitroprusside had a protective effect upon thick limb injury. Finally, in a previously reported model of radiocontrast nephropathy (1988. J. Clin. Invest. 82:401), LNMMA increased the severity of renal failure (final plasma creatinine from 2.3 +/- 2 mg% to 3.4 +/- 3, P less than 0.005) and the proportion of damaged thick limbs (from 24 +/- 6% to 53 +/- 9, P less than 0.01). Nitrovasodilatation may participate in the balance of renal medullary oxygenation and play an important role in the prevention of medullary hypoxic injury.

Acute Kidney Injury↗
PubMed1991

Hypertensive crisis from chronic intoxication with nasal decongestant and cough medications.

Cardiac hypertensive structural changes, catecholamine-related cardiomyopathy, and congestive heart failure (CHF) have been encountered in pheochromocytoma, as a result of prolonged exposure to high concentrations of endogenous catecholamines. A 34-year-old man presented with severe hypertension, cardiomegaly, and CHF, presumably as a result of continuous alpha-adrenergic intoxication with oxymetazoline hydrochloride, phenylephrine hydrochloride, and ephedrine hydrochloride, consumed in massive doses by an overuse of nasal decongestants and cough syrup (daily doses of 20, 100, and 300 mg, respectively). Coadministered chlorpromazine hydrochloride and trimeprazine tartrate may have also contributed to the clinical presentation through their anticholinergic and antihistaminic properties. The possibility of an overuse of these over-the-counter drugs should be considered in the differential diagnosis of hypertensive emergencies, especially with the simultaneous use of anticholinergic and antihistamine medications, beta-blocking agents, or monoamine oxidase inhibitors.

Adult↗
PubMed1991

Effect of indomethacin and salt depletion on renal proton MR imaging. An experimental study in the rat.

Blockade of the synthesis of vasodilating prostaglandins with non-steroidal anti-inflammatory drugs (NSAID) renders the renal medulla susceptible to hypoxic injury with reduced renal function, especially in clinical conditions characterized by volume depletion. Alterations in renal hemodynamics and urine production may affect renal MR imaging under these circumstances. We injected salt-depleted and control rats undergoing proton MR imaging with indomethacin 10 mg/kg. Indomethacin abolished the cortico-medullary T2-gradient and markedly diminished the overall renal signal in salt-depleted rats only. These changes, which progressed over a period of 40 min after indomethacin was injected, probably result from renal oligemia and decreased urine production, with an associated decrease in T2-values. We suggest that a history of consumption of non-steroidal anti-inflammatory drugs should be obtained and taken into account in the evaluation of renal proton MR imaging, especially in the presence of salt and volume depletion.

Animals↗
PubMed1989

[Bilateral hydronephrosis and erythrocytosis].

A 36-year-old woman who developed extreme erythrocytosis following partial correction of severe bilateral hydronephrosis by bilateral ureterolithotomy is presented. Hydronephrosis appears to stimulate renal synthesis and release of erythropoietin. The mechanism could involve increase in medullary hypoxia by increased pressure of the renal pelvis on the medullary vasculature. This might be especially marked when the renal blood supply is compromised by concomitant atherosclerosis, as in this case.

Adult↗
PubMed1989

Protective role of furosemide and saline in radiocontrast-induced acute renal failure in the rat.

Acute renal failure (ARF) can be produced in rats by a combination of insults which augment transport activity and blunt regulatory mechanisms designed to maintain medullary oxygen sufficiency. This type of ARF is characterized by necrosis of medullary thick ascending limbs (mTALs). Uninephrectomized, salt-depleted rats injected with indomethacin (10 mg/kg) develop ARF following the administration of the radiocontrast agent, iothalamate. Furosemide (20 mg/kg, intravenous), administered immediately before the contrast material, attenuated the severity of ARF and reduced mTAL necrosis. Treatment with furosemide and/or normal saline prevented both the decline in renal function and mTAL injury. It is concluded that furosemide and normal saline may ameliorate the course of ARF if administered before radiocontrast.

Acute Kidney Injury↗
PubMed1989

Diabetogenic effect of nifedipine.

This case report describes a 60-year-old diabetic patient whose daily insulin requirements increased by 30 percent following nifedipine administration. Glucagon and intravenous glucose tolerance tests were performed with and without nifedipine treatment, in order to evaluate the roles of decreased pancreatic beta islet cell function and augmented insulin peripheral resistance in the diabetogenic effect of nifedipine. Insulin and calculated glucose peripheral utilization extrapolated from the glucose concentration curves were not significantly different. C-peptide levels tended to be lower with nifedipine treatment at baseline and during the glucagon tests. This may suggest that the altered glycemic control associated with nifedipine was mediated by a suppressed islet beta cell function. The effect of calcium channel-blockers upon glycemic control and the possible mechanisms involved are discussed.

Blood Glucose↗
PubMed1988

Erythromycin-induced dynamic ileus?

A 39-year-old man and a 79-year-old woman developed dynamic ileus soon after erythromycin stearate was administered for a respiratory tract infection. Both had had prior uncomplicated abdominal operations: the man, vagotomy and pyloroplasty for bleeding duodenal ulcer, 3 years earlier; and the woman, an appendectomy some 44 years before. The temporal association with erythromycin therapy, resolution of signs and symptoms when the drug was stopped, an uneventful recovery, and the absence of other causes, suggest a possible role of erythromycin in the pathogenesis of dynamic ileus in these patients. Disturbed gastrointestinal motility patterns caused by erythromycin, in the presence of structural changes of the alimentary tract due to prior surgical procedures, may have contributed and we review these events.

Adult↗
PubMed1988

Acute renal failure with selective medullary injury in the rat.

Since human acute renal failure (ARF) is frequently the result of multiple rather than single insults, we used a combination of treatments to induce ARF in rats. Uninephrectomized, salt-depleted rats injected with indomethacin developed ARF after administration of radiocontrast. After 24 h, the plasma creatine rose from 103 +/- 3 to 211 +/- 22 mumol/liter (mean +/- SE) and the creatinine clearance dropped from 0.7 +/- 0.1 to 0.2 +/- 0.04 ml/min (P less than 0.001). Severe injury was confined to the outer medulla and comprised necrosis of medullary thick ascending limbs (mTALs), tubular collapse, and casts. Other nephron segments were free of damage except for the proximal convoluted tubules which showed vacuole formation originating from lateral limiting membranes that resembled changes reported in human contrast nephropathy. Cell damage to mTALs included mitochondrial swelling, nuclear pyknosis, and cytoplasmic disruption with superimposed calcification; these changes were most severe in the deepest areas of the outer medulla, away from vasa recta in zones remote from oxygen supply. The fraction of mTALs with severe damage was 30 +/- 7% (range 2-68) and the extent of injury was correlated with a rise in plasma creatinine (r = 0.8, P less than 0.001). Thus, the nature of mTAL injury was similar to the selective lesions observed in isolated kidneys perfused with cell-free medium and was shown to derive from an imbalance between high oxygen demand by actively transporting mTALs and the meager oxygen supply to the renal medulla. Combined multiple renal insults in the rat produce ARF that resembles the clinical syndrome of contrast nephropathy and is characterized by selective mTAL injury conditioned by medullary hypoxia.

Acute Kidney Injury↗
PubMed1986

Primary hyperparathyroidism presenting as cervical myelopathy.

Quadriplegia as a presenting syndrome in a case of primary hyperparathyroidism is reported. The clinical picture was misdiagnosed as a space-occupying lesion in the cervical spinal canal, for which an unnecessary laminectomy was performed. The neurologic deficits disappeared following the removal of a parathyroid adenoma. The neurologic presentations of hyperparathyroidism are reviewed and discussed.

Adenoma↗