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Biomedical subjects

G Deray

Publications and source records attributed to G Deray.

At least 91 records · Page 5Linked to original sources
PubMed1997

Role of endothelium-derived nitric oxide-endothelin balance in contrast medium-induced acute renal vasoconstriction in dogs.

RATIONALE AND OBJECTIVES: The authors evaluated the involvement of nitric oxide and endothelin in radiographic contrast medium-induced changes in renal hemodynamics. METHODS: Eleven anesthetized healthy dogs were each studied during three periods. Thirty minutes before the first, second, and third periods, the dogs received 1 mL per kilogram of body weight of isotonic saline, L-N-nitro-L-arginine-methyl-ester (L-Name, 10 mg/kg intravenously), and L-arginine (500 mg/ kg intravenously), respectively. Renal blood flow (RBF) and mean arterial blood pressure were continuously monitored. The glomerular filtration rate (GFR) was evaluated by means of polyfructosan clearance. RESULTS: Contrast medium induced a significant (P < .05) decrease in RBF and GFR and a significant (P < .05) increase in urinary endothelin excretion. L-Name enhanced the effect of contrast media on RBF and GFR. L-arginine attenuated the effect of L-Name on the contrast medium-induced reduction of GFR. CONCLUSION: These findings support the hypothesis that acute contrast medium-induced intrarenal vasoconstriction may involve an imbalance of endothelial vasoactive agents, nitric oxide, and endothelin, and they confirm the involvement of hemodynamic changes in contrast medium-induced nephropathy.

Animals↗
PubMed1997

Neuromuscular blockade with acute respiratory failure in a patient receiving cibenzoline.

Cibenzoline is a class Ic antiarrhythmic agent that can be used to treat supraventricular arrhythmias. A case is reported of cibenzoline overdose in a patient with impaired renal function, leading not only to the usual cardiac and metabolic symptoms (bradycardia and hypoglycaemia), but also to a myastheniform syndrome with acute respiratory failure. Neuromuscular blockade was demonstrated by repetitive supramaximal stimulation of the median nerve, and diaphragmatic involvement was evidenced by applying the same protocol to the phrenic nerve. Muscle strength recovered as serum cibenzoline levels decreased, allowing the patient to be weaned from the ventilator. This observation suggests that cibenzoline, like other antiarrhythmic agents, can be responsible for neuromuscular blockade, and should therefore be used with caution in patients with neuromuscular and respiratory diseases or with impaired renal function.

Acute Disease↗
PubMed1997

Comparative acute nephrotoxicity of FK-506 and ciclosporin in an isolated in situ autoperfused rat kidney model.

The acute hemodynamic effects of ciclosporin A (Cs-A; 40 and 20 mg/kg), FK506 (1.5 and 0.4 mg/kg), and their vehicles were studied in an in situ autoperfused rat kidney model. Cs-A (60 +/- 7 and 66 +/- 5% of the initial value, respectively; p < 0.05 vs. control group) and FK506 (89 +/- 3 and 77 +/- 3% of the initial value respectively; p < 0.05 vs. control group) induced a significant fall in renal blood flow. Cs-A significantly increased the renal vascular resistance, whereas FK506 had no effect. The glomerular filtration rate (inulin clearance) declined significantly in all groups. Cremophore and FK506 vehicle had no hemodynamic effect on the glomerular filtration rate. In our model, FK506 had less vasoactive effects on the renal hemodynamics than Cs-A.

Animals↗
PubMed1997

No need to adjust the dose of 311C90 (zolmitriptan), a novel anti-migraine treatment, in patients with renal failure not requiring dialysis.

311C90 ("Zomig", zolmitriptan), is a novel and selective, centrally and peripherally acting 5 HT1B/1D receptor agonist in development for the acute, oral treatment of migraine. We have conducted a parallel group study in patients with moderate/severe renal impairment (creatinine clearance < or = 40 ml/min) and age- and sex-matched healthy volunteers (creatinine clearance > or = 60 ml/min). All subjects received a single, 10 mg dose of 311C90. Mean peak concentrations of 311C90 and its pharmacologically active N-desmethyl metabolite (183C91) were similar in both groups although AUC0-infinity for 183C91 was increased by 35% in the renally impaired patients. Other pharmacokinetic parameters were little changed apart from the expected reduction in CLR and urinary recovery and a small increase of 0.9 and 1.0 h, respectively, in the mean half-lives of 311C90 and 183C91. For the 2 inactive metabolites, the N-oxide (1652W92) and the indolacetic acid (2161W92), mean peak concentrations were approximately 3 times higher in renally impaired patients than in healthy volunteers and AUC0-infinity was 6-7.5 times higher. CLR for these metabolites was approximately 90% lower in renal impairment and half-life of both was increased approximately 3-fold. Baseline blood pressures were higher in the renally impaired group. After 311C90 there was a transient, small increase in blood pressure in both groups. There was little difference in the increase in diastolic blood pressure between the groups (16 mmHg in both) but the rise in systolic blood pressure was greater in the renally impaired group (23 mmHg vs 16 mmHg in healthy subjects). The lack of substantial changes in the plasma concentrations of both parent compound and 183C91, and the similarity of the changes in blood pressure, in renally impaired subjects compared to healthy volunteers suggest that there is no reason to adjust the dose of 311C90 in patients with renal impairment.

Adult↗
PubMed1996

Chronic effects of endothelin-3 on blood pressure and renal haemodynamics in rats.

BACKGROUND: Renal vasoconstriction and systemic hypertension are well-known effects of bolus or short-term endothelin administration. However, the role of endothelin as a circulating hormone remains largely unknown. METHODS: The present study explores the effects of endothelin-3 (ET-3) on renal haemodynamics and systemic blood pressure during a 3-h and a 3-day intravenous infusion in rats. Male Sprague-Dawley (SD) rats were infused with vehicle (group 1) or ET-3 (group 2), 10 ng/kg per min; group 3, 50 ng/kg per min) delivered via osmotic minipumps into the right jugular vein for 3 days. On day 3 after pump implantation, rats were anaesthetized with Inactin and surgically prepared for assessment of mean arterial blood pressure (MABP), renal plasma flow (RPF), glomerular filtration rate (GFR), and renal vascular resistance (RVR). The same parameters were assessed during a 3-h ET-3 infusion study in SD rats (group 4, vehicle; group 5, ET-3, 10 ng/kg per min; group 6, ET-3, 50 ng/kg per min). RESULTS: In 3-day infused rats, ET-3 induced a significant decrease in RPF (-22+/-7% and -26+/-8% for group 2 and group 3 respectively, P<0.05 vs group 1) and an increase in RVR (+40+/-11% for groups 2 and 3; P<0.05 vs group 1); 50 ng/kg per min ET-3 significantly decreased GFR (-17%, P<0.05 vs group 1). MABP was not significantly affected by endothelin infusion. In acute infusion studies a decrease of the same magnitude was seen for the renal haemodynamics values. 50 ng/kg per min ET-3 increased MABP; a systemic effect that disappeared after the 3-day infusion. CONCLUSIONS: This study suggests that intravenously administered ET-3 in the rat has only a transient effect on systemic blood pressure, whereas it induces alterations in renal haemodynamics after both acute and chronic perfusions.

Animals↗
PubMed1996

Prevention of cyclosporin nephrotoxicity with a platelet-activating factor (PAF) antagonist.

BACKGROUND: Cyclosporin (CsA) is a potent immunosuppressive drug whose main side-effect is nephrotoxicity. In the kidney, CsA induces vasoconstriction with a decrease in renal blood flow (RBF) and glomerular filtration rate (GFR) and a significant increase in renal vascular resistance (RVR). CsA enhances platelet-activating factor (PAF) synthesis in mesangial cells in vitro. PAF, a secondary mediator of anaphylaxis and inflammation, exhibits vasoactive properties in the kidney similar to those of CsA. METHODS: The in situ autoperfused rat kidney model was used to investigate whether PAF plays a role in the haemodynamic injury induced by CsA. RESULTS: In this model, CsA (40 mg/kg and 20 mg/kg i.v.) induced a significant decrease in RBF and in GFR and an increase in RVR. BN 52021, a potent and specific PAF antagonist (20 mg/kg i.v. bolus dose) induced a significant increase in GFR (137 +/- 32% of initial value, P < 0.05). BN 52021 (20 and 10 mg/kg) also significantly prevented the decline in RBF and GFR induced by CsA. CONCLUSIONS: We have demonstrated that the PAF antagonist BN 52021 can minimize the alteration of renal function induced by CsA.

Animals↗
PubMed1996

[Treatment of cardiac failure with angiotensin-converting enzyme inhibitors and diuretics].

Congestive cardiac failure is characterised by redistribution of blood flow to the brain and the heart at the expense of the kidneys. The prognosis of this condition at its most advanced stage (stage IV) is poor with a mortality of about 50% at 5 years. The reduction of renal perfusion will lead to stimulation of all vasoconstrictor and anti-natiuretic mechanisms, and to a parallel activation of vasodilator and natiuretic systems. There is, therefore, a clear conflict of interest between the heart, which attempts to preserve its perfusion and function, and the kidneys which aggravate the haemodynamic disturbances by salt and water overload and the risk of arrhythmias due to hypokalaemia and hypomagnesaemia. The diuretics and ACE inhibitors are essential therapeutic classes for the treatment of congestive cardiac failure. The prevention of the secondary effects of diuretics and ACE inhibitors on renal function, serum sodium, potassium and magnesium concentrations, is based on an initial low dose prescription, the detection and correction of risk factors and strict clinical and biological surveillance. In order to avoid the risks of hyperkalaemia during the association of ACE inhibitor and diuretic therapy with a potassium sparing agent, the initial dose of these two drugs should be as low as possible.

Aged↗