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Renal/Inflammation/Protection

Methylprednisolone increases urinary nitrate/creatinine ratios in porcine infrarenal aortic ischaemia reperfusion: 066

Baker, R. C.1; Armstrong, M. A.2; Allen, S. J.3; Barros D'Sa, A. A.B.1; McBride, W. T.3

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European Journal of Anaesthesiology: June 2004 - Volume 21 - Issue - p 6-7

Introduction: Urinary nitrate mainly arises from systemic eNOS activation with a small contribution from intrarenal iNOS induction. Increased venous eNOS activity is a normal physiological response to proinflammatory mediators [1]. Methylprednisolone's anti-inflammatory effects in mice have recently been shown to depend on eNOS activation, whilst reducing inflammatory mediators [2]. We wondered if urinary nitrate excretion increases during porcine infrarenal aortic ischaemia reperfusion and investigated the hypothesis that methylprednisolone accentuates this response.

Method: Forty-two anaesthetized pigs underwent laparotomy, fluid resuscitation for 60min and then 150min of infra-renal aortic cross-clamping followed by 180min reperfusion. Urine samples were obtained for nitrate and creatinine measurement as follows: preoperative baseline (PB) and 30, 120, 220, 270, 330 and 390 min after induction of anaesthesia. Pigs were randomized to 2 groups. Group C received placebo and group MP received methylprednisolone 30mg/kg, after obtaining the 30 min sample. Analysis between groups - Mann-Whitney U; within groups - Friedman's test.

Results: Compared with PB there was a significant increase in urinary nitrate/creatinine ratios in both groups at 60 min (pre-cross clamp) which in group MP only, showed significant elevation thereafter (p < 0.05). In group MP urinary nitrate/creatinine ratios were significantly higher than placebo.

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Discussion: Perioperative rapid increases in urinary nitrate may reflect systemic eNOS activation and provide early evidence of an evolving inflammatory response. Since glucocorticoid beneficial anti-inflammatory effects appear to be eNOS dependent [2], urinary nitrate measurement may help determine the minimal steroid dose necessary for significant anti-inflammatory effects.

References:

1 Bhagat K, Hingorani AD, Palacios M, et al. Cytokine-induced venodilatation in humans in vivo: eNOS masquerading as iNOS. Cardiovasc Res 1999; 41(3): 754-764.
2 Hafezi-Moghadam A, Simoncini T, Yang E, et al. Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nat Med 2002; 8(5): 473-479.
© 2004 European Society of Anaesthesiology