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Biomedical subjects

S N Heyman

Publications and source records attributed to S N Heyman.

At least 37 records · Page 2Linked to original sources
PubMed1995

The role of medullary ischemia in acute renal failure.

The introduction of new techniques for the determination of renal parenchymal oxygenation and intrarenal microcirculation has elucidated some important aspects in the pathophysiology of acute renal failure (ARF). Data accumulated over the last decade with these techniques, together with improved morphologic evaluation of the kidney, indicate that medullary damage may play a pivotal role in various forms of acute and chronic renal hypoxic and toxic insults. The outer medulla functions normally under hypoxic conditions, as a result of limited regional oxygen supply and high oxygen consumption for urinary concentration. Outer medullary oxygenation is critically balanced by mechanisms designed to adjust oxygen demand and supply, and their insufficiency may lead to ARF with hypoxic medullary damage. In this article, we outline our current concept of the physiologic control of medullary oxygenation and review the clinical conditions that predispose to hypoxic medullary damage, including rhabdomyolysis, hypercalcemia, or the exposure to endotoxin, nonsteroidal anti-inflammatory drugs, radiologic contrast agents, cyclosporine, FK506, and amphothericin. We shall indicate a possible role for medullary oxygen insufficiency in clinical conditions known to predispose to ARF, such as preexisting renal disease, diabetes mellitus, hypertension, atherosclerosis, effective volume depletion, urinary obstruction, or aging, and suggest potential strategies to preserve medullary oxygenation and integrity.

Acute Kidney Injury↗
PubMed1995

Emphysematous complications in dentistry, 1960-1993: an illustrative case and review of the literature.

Seventy-four reports of emphysematous complications in ambulatory dental patients, published in the English literature between the years 1960 and 1993, are reviewed, and an additional case of subcutaneous, retropharyngeal, and mediastinal emphysema following an impression-taking procedure for a crown preparation is presented. This rare complication occurred mainly in patients in the third and fifth decades of life, after dental procedures on the third molar, in particular during mandibular extractions and treatment on the right side. The use of an air syringe, high-speed handpieces, or their combination was reported in 71% of cases. Centripetal air dissection, with retropharyngeal and mediastinal emphysema, occurred in 35% of the patients, especially following extractions.

Adolescent↗
PubMed1994

Loop diuretics reduce hypoxic damage to proximal tubules of the isolated perfused rat kidney.

The straight portion (S3) of the proximal tubule lies in close proximity to the thick ascending limbs (TALs) at the cortico-medullary junction. Since a delicate balance exists between oxygen demand and the limited oxygen supply in this region, we hypothesized that reduction of thick limb metabolic activity might augment oxygen availability to S3 segments, which depend heavily upon aerobic metabolism, and prevent hypoxic damage. The degree of functional deterioration and morphological damage to S3 was assessed in isolated rat kidneys perfused with an erythrocyte-free medium. Bumetanide (10(-5) M) and furosemide (10(-4) M) reduced S3 fragmentation from 9.8 +/- 3.9% of tubules in controls to 0 and 1.4 +/- 0.9%, respectively (P < 0.0005). Tubular glucose reabsorption was better preserved in kidneys exposed to loop diuretics than in control kidneys (P < 0.01), and urinary alkaline phosphatase (P < 0.05) and the total amount of LDH released into the perfusate and urine (P < 0.01) were lower in the treatment groups. Morphological damage to S3 was closely correlated with medullary TAL necrosis (r = 0.66, P < 0.001), urinary alkaline phosphatase excretion (r = 0.89, P < 0.001) and glycosuria (r = 0.83, P < 0.001). We conclude that under hypoxic conditions TALs and S3 segments may compete with each other for a limited oxygen supply. Reduction of active transport in the mTAL might augment oxygen availability to S3 segments and improve their survival.

Alkaline Phosphatase↗
PubMed1994

Determinants of intrarenal oxygenation. II. Hemodynamic effects.

To study hemodynamic effects on intrarenal oxygenation, O2 microelectrodes were inserted into rat kidneys. In a previous study [M. Brezis, Y. Agmon, and F. H. Epstein. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36): F1059-F1062, 1994], we showed that tubular metabolism is a major determinant of intrarenal oxygenation, in part responsible for medullary hypoxia observed under basal conditions. Acute hypotension (by controlled hemorrhage, aortic ligation, or nitroprusside infusion) paradoxically increased medullary PO2 (from 21 +/- 2 to 39 +/- 2 mmHg, P < 0.001) while decreasing cortical PO2 (from 46 +/- 2 to 32 +/- 3 mmHg, P < 0.001), abolishing corticomedullary gradients of oxygen. Laser-Doppler studies indicated that, while cortical blood flow was reduced during hypotension, medullary blood flow was unchanged or increased. The increase in medullary PO2 induced by hypotension was abolished by prior administration of furosemide, suggesting that during hypotension, reduced glomerular filtration rate (GFR), distal delivery, and reabsorption result in decreased oxygen utilization. Acute infusions of atriopeptin III (0.1-1 microgram.kg-1.min-1) decreased both cortical PO2 (from 61 +/- 2 to 55 +/- 2 mmHg, P < 0.001) and medullary PO2 (from 15 +/- 1 to 7 +/- 1 mmHg, P < 0.001), consistent with atriopeptin-induced increases in GFR and tubular reabsorptive work. These data suggest that medullary oxygen availability increases during renal hypoperfusion and may decrease during renal vasodilation.

Animals↗
PubMed1994

Effects of salt depletion on the kidney: changes in medullary oxygenation and thick ascending limb size.

Previous studies have shown that salt depletion enhances the susceptibility of the kidney to nephrotoxins (amphotericin, cyclosporine, and contrast). To study the renal response to salt depletion, Sprague-Dawley rats were fed a sodium-deficient diet (N = 12) with pair-fed controls (N = 13) for 4 wk. In addition, rats from each group underwent 24-h water deprivation studies (N = 9; four salt deprived, five normal). Plastic 1-micron horizontal sections of mid-inner stripe were examined, and cross-sectional areas of the medullary thick ascending limb (mTAL) were analyzed. The mTAL of the salt-deprived rats were smaller (P = 0.04) and showed greater variance in size (P = 0.02) than control (618 +/- 106 versus 693 +/- 50 microns2). However, mean glomerular and collecting duct cross-sectional areas were unaffected by salt intake. Cross-sectional areas of long- and short-loop mTAL were significantly different, regardless of group (518 +/- 78 versus 732 +/- 92 microns2). Maximal urinary concentrating ability was found to correlate with mTAL cross-sectional area (r = 0.85; P = 0.004) and with long-loop mTAL size (r = 0.77; P = 0.016). However, it did not significantly correlate with short loop mTAL size (r = 0.53; P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[The osmolar gap and the diagnosis of severe alcohol intoxication].

The calculated osmolar gap is a useful diagnostic tool in clinical toxicology whenever toxicologic screens are not available. In a case of severe intoxication with ethyl alcohol there was deep coma and a calculated osmolar gap of 208 mOsm, consistent with an ethanol plasma level of 958 mg/dl. The diagnosis of severe ethanol intoxication was confirmed later. Serial calculations of the osmolar gap served to assess the clinical course.

Alcoholic Intoxication↗
PubMed1993

Glycine reduces early renal parenchymal uptake of cisplatin.

We evaluated the effect of glycine infusions on the early renal uptake of cisplatin, measured one hour after cisplatin was injected, as well as five days following cisplatin administration. Glycine (1.25 mmol per 100 g body wt) markedly attenuated the early uptake of platinum by the kidney, an effect not observed with control infusions of saline or of L-alanine. The kidney content of platinum at five days, on the other hand, was similar in glycine-treated animals and saline controls. Early inhibition of renal uptake of platinum may be responsible for glycine's protective action in experimental cisplatin nephrotoxicity.

Animals↗
PubMed1993

Effects of ioversol versus iothalamate on endothelin release and radiocontrast nephropathy.

RATIONALE AND OBJECTIVES: Certain radiocontrast agents, including iothalamate, iohexol, and ioxaglate, release the renal vasoconstrictor peptide endothelin from vascular endothelium in a way that might contribute to radiocontrast nephropathy. The effects of the nonionic, low osmolar agent, ioversol, on endothelin release and renal function are investigated. METHODS: Effects of ioversol were compared with equi-iodine doses of iothalamate when applied to cultured bovine aortic endothelial cells or injected into normal rats and rats preconditioned by uninephrectomy, salt depletion, and indomethacin (USIC) to develop radiocontrast nephropathy. RESULTS: In comparison with iothalamate, ioversol had a greatly reduced propensity to stimulate the release of endothelin, from cultured cells and when injected into anesthetized rats. Ioversol produced less renal vasoconstriction than did iothalamate, in control and in USIC rats, and the development of radiocontrast nephropathy, assessed by creatinine clearance and morphologic damage to the renal medulla, was largely avoided. CONCLUSIONS: These results strengthen the hypothesis that endothelin release induced by radiocontrast agents is correlated with their renal toxicity and therefore, may play a role in radiocontrast nephropathy.

Animals↗
PubMed1993

Chronic amphotericin nephropathy: morphometric, electron microscopic, and functional studies.

The two major hypotheses for the pathogenesis of amphotericin nephrotoxicity are direct interaction with epithelial cell membranes and vasoconstriction. Studies indicating the special vulnerability of the medullary ray and medulla to hypoxia led to a reexamination of amphotericin nephrotoxicity. Twenty-four rats were divided into four groups: amphotericin injection (5 mg/kg daily for 3 wk), amphotericin plus salt depletion, vehicle, and salt depletion and vehicle. The amphotericin group had polyuria (P < 0.01) but normal serum creatinine. In contrast, amphotericin plus salt depletion rats exhibited renal failure (creatinine of 1.49 +/- 0.05 versus amphotericin alone 0.98 +/- 0.01; P < 0.01). Semiquantitative histologic analysis of cortical and medullary injury correlated with functional impairment. Cortical changes in the amphotericin group were largely restricted to the medullary ray, where focal rupture and calcification of thick ascending limbs were noted. The S2/S3 tubules in the medullary rays showed focally diminished cell complexity with histiocytic/lymphocytic infiltration. However, calcification was also seen in the area of the macula densa. Morphometry revealed that the thick ascending limbs in the medulla were hypertrophied (1,420 +/- 63 versus 1,195 +/- 48 microns 2 for vehicle; P < 0.05). In contrast, in the amphotericin and salt depletion group, the changes in the medullary ray extended to the labyrinth and the thick ascending limbs in the inner stripe showed atrophic changes (772 +/- 23 microns 2; P < 0.01 versus vehicle). Thus, changes as a result of amphotericin toxicity take place both in areas known to be most vulnerable to hypoxia (medullary ray and medulla), and in areas rich in oxygen (adjacent to glomerulus). Salt depletion potentiates the cortical changes and converts medullary hypertrophy to atrophy. These findings support a dual pathogenesis for amphotericin nephropathy (direct toxicity and vasoconstriction).

Amphotericin B↗
PubMed1993

Reduced amphotericin toxicity in an albumin vehicle.

Amphotericin B systemically infused into anesthetized rats at the rate of 0.4 mg/kg body weight over 20 min reproducibly induced renal vasoconstriction and renal cortical hypoxemia. By contrast, when infused with albumin (3 g/dl), amphotericin B did not reduce renal blood flow and did not affect renal cortical oxygenation. In vitro, hemolysis induced by amphotericin was also markedly reduced in the presence of albumin. Albumin did not appear to reduce the antibiotic effect of amphotericin in vitro. It was concluded that amphotericin B toxicity may be considerably reduced if administered in an albumin vehicle.

Albumins↗
PubMed1992

Cyclosporine nephropathy: morphometric analysis of the medullary thick ascending limb.

The effects of cyclosporine A (CsA) (12.5 mg/kg/d) on the medullary thick ascending limb (mTAL) were studied in five experimental groups: vehicle-treated control (C), salt depletion (SD), cyclosporine (CsA), and the combination of both salt depletion and cyclosporine for 3 (CsA-SD:S) and 8 (CsA-SD:L) weeks. Evaluation was performed on 1-micron plastic horizontal sections. mTALs were classified as either atrophic or nonatrophic by assessing mitochondrial density. The mean cross-sectional area of atrophic mTALs was found to be significantly smaller than the mean of nonatrophic mTALs in all treatment groups. The percentage of atrophic tubules was found to be significantly increased in both CsA-SD groups as compared with the other three treatment groups (P less than 0.01). Regression analysis indicated a rectangular hyperbolic relationship between the percentage of atrophic tubules and mean nonatrophic tubule cross-sectional area (P less than 0.0001). Thus, low levels of injury are associated with a rapid increase in cross-sectional tubular area (hypertrophy), and this response plateaued with increasing degrees of injury. Terminal plasma creatinine correlated with nonatrophic tubular cross-section area (r = 0.52, P less than 0.003). These studies indicate that CsA induces mTAL atrophy, which is more extensive with salt depletion. With limited injury, hypertrophy develops. However, the hypertrophic response cannot be sustained with increasing degrees of injury. The phenomenon of mTAL atrophy and hypertrophy is particularly important, since hypertrophy itself is a known risk factor for mTAL injury.

Animals↗
PubMed1992

Effect of glycine and hypertrophy on renal outer medullary hypoxic injury in ischemia reflow and contrast nephropathy.

Glycine preserves tubular cell integrity under hypoxic and toxic conditions in vitro. It also ameliorates cisplatin nephrotoxicity in vivo. We studied the effect of glycine on tubular necrosis from ischemia reflow and on inner stripe injury in an animal model of radiocontrast nephropathy. In all experiments, glycine (75 mg/100 g/h) increased tubular damage in the inner stripe. In the model of radiocontrast nephropathy, the percentage of medullary thick ascending limb (mTAL) necrosis at 24 hours increased from 22% +/- 6% to 41% +/- 9% or 55% +/- 7% with glycine infusion of 75 or 135 minutes, respectively (mean +/- SE, P less than 0.05, analysis of variance [ANOVA]). Renal function was not significantly affected. In rat kidneys subjected to ischemia reflow, mTAL injury following glycine increased from 1% +/- 0% to 12% +/- 6% (P less than 0.05) and from 8% +/- 5% to 49% +/- 8% (P less than 0.01) 24 hours after 30 minutes and 45 minutes ischemia, respectively. Tubular injury in the inner stripe was maximal in the deep interbundle zone, typical of hypoxic, rather than reperfusion, injury. Prior uninephrectomy increased inner stripe damage, but protected the proximal tubules. Both uninephrectomy and glycine infusion were found to contribute to mTAL necrosis. The infusion of glycine for 1 hour in intact rats increased renal blood flow by 44% and tripled urine volume (P less than 0.01). A parallel increase in glomerular filtration rate GFR; by 22% over 90 minutes) fell short of statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗