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Cyclosporin A (CsA; 50, 100 or 150 mg/kg) was administered by gavage, daily for 4 days, to groups of normotensive rats. An additional group of animals received the drug vehicle. CsA-induced nephrotoxicity, characterized by reduced glomerular filtration rate (GFR) and urinary sodium flow, enzymuria and proximal tubular cell damage was accompanied by elevated plasma renin activity (PRA). These changes were dose-related at 50 and 100 mg/kg CsA, but were not increased by administration of 150 mg/kg. Circulating trough drug levels were related to dosage. Four days after CsA withdrawal in animals given 50 mg/kg, there was reduced nephrotoxicity and PRA had returned to normal, even though circulating CsA levels had not diminished. Rats given 100 and 150 mg/kg, however, showed no reduction in nephrotoxicity or in PRA. Hyperglycaemia was evident at 4 days in animals given 100 and 150 mg/kg CsA and persisted 4 days after drug withdrawal. There were no accompanying abnormalities in islet cell structure. Continuous administration of CsA (50 mg/kg) to rats for 14 days caused elevated PRA on day 4 but a return to normal levels by day 7. In contrast, significant GFR impairment was evident by day 7 whilst enzymuria was significantly increased from day 4 onwards. CsA nephrotoxicity in the rat is clearly associated with activation of the renin-angiotensin-aldosterone system. Possible mechanisms leading to increased renin release are discussed.

SummaryHeart failure is a major risk factor for adverse postoperative events following non-cardiac surgery. The use of transthoracic echocardiogram as a pre-operative investigation to assess cardiac dysfunction has limitations in this setting. The N-Terminal fragment of B-Type natriuretic peptide (NT proBNP) has been used in screening for heart failure. We have investigated the use of NT proBNP as a screening tool for left ventricular systolic dysfunction to reduce the requirement for preoperative echocardiograms. Ninety-eight pre-operative non-cardiac surgical patients scheduled to undergo echocardiography were assessed clinically and with an NT proBNP measurement. Echocardiogram was used to define two groups of patients depending on the presence or absence of abnormal left ventricular function and the NT proBNP level was compared between the groups using non-parametric and receiver-operator-characteristic (ROC) curve analysis. In terms of preoperative screening, a NT proBNP of <38.2 pmol.l )1 had a 100% negative predictive value in predicting patients with normal left ventricular systolic function and would have prevented the requirement for echocardiogram in 43% of pre-operative patients. NT proBNP was superior to electrocardiological and clinical criteria for detection of a normal echocardiogram. This may have significant impact in the pre-operative assessment of patients undergoing non-cardiac surgery. Heart failure involving left ventricular systolic dysfunction (LVSD) is a major risk factor for adverse peri-operative cardiovascular events [1]. Pre-operative recognition of LVSD is an important component of anaesthetic assessment. However, patients with cardiac dysfunction are often asymptomatic and where symptoms do exist they may be relatively non-specific. One investigational approach is to use indices determined by the use of resting transthoracic echocardiogram (TTE) for the assessment of cardiac dysfunction. In many centres this is seen as the 'gold standard' non-invasive pre-operative test. However, there are clinical and practical disadvantages associated with this simple investigational approach. The decision to obtain an echocardiogram is based on various pre-operative criteria which may vary between clinicians and are not consistently associated with subsequent abnormalities on echocardiogram. TTE is also relatively expensive and in many centres has a significant waiting list for its availability, since other specialties with more direct evidence for the use of TTE compete with pre-operative services for its availability.It follows that the ability of a biochemical marker to reliably and rapidly screen for cardiac dysfunction in patients presenting for major surgery would have considerable benefit both in reducing the requirement for preoperative TTE and assisting in the anaesthetic assessment of these patients.

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