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Am J Physiol Heart Circ Physiol 287: H1262-H1268, 2004. First published April 15, 2004; doi:10.1152/ajpheart.00153.2003
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Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia

Brian A. Mullan,1,2 Ciaran N. Ennis,1 Howard J. P. Fee,2 Ian S. Young,3 and David R. McCance1

1Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital; and 2Department of Anaesthesia and Intensive Care Medicine and 3Department of Medicine, Queen's University, Belfast BT12 6BA, Northern Ireland

Submitted 19 February 2003 ; accepted in final form 12 April 2004

Mortality increases when acute coronary syndromes are complicated by stress-induced hyperglycemia. Early pulse wave reflection can augment central aortic systolic blood pressure and increase left ventricular strain. Altered pulse wave reflection may contribute to the increase in cardiac risk during acute hyperglycemia. Chronic ascorbic acid (AA) supplementation has recently been shown to reduce pulse wave reflection in diabetes. We investigated the in vivo effects of acute hyperglycemia, with and without AA pretreatment, on pulse wave reflection and arterial hemodynamics. Healthy male volunteers were studied. Peripheral blood pressure (BP) was measured at the brachial artery, and the SphygmoCor pulse wave analysis system was used to derive central BP, the aortic augmentation index (AIx; measure of systemic arterial stiffness), and the time to pulse wave refection (Tr; measure of aortic distensibility) from noninvasively obtained radial artery pulse pressure (PP) waveforms. Hemodynamics were recorded at baseline and then every 30 min during a 120-min systemic hyperglycemic clamp (14 mmol/l). The subjects, studied on two separate occasions, were randomized in a double-blind, crossover manner to placebo or 2 g intravenous AA before the initiation of hyperglycemia. During hyperglycemia, AIx increased and Tr decreased. Hyperglycemia did not change peripheral PP but did magnify central aortic PP and diminished the normal physiological amplification of PP from the aorta to the periphery. Pulse wave reflection, as assessed from peripheral pulse wave analysis, is enhanced during acute hyperglycemia. Pretreatment with AA prevented the hyperglycemia-induced hemodynamic changes. By protecting hemodynamics during acute hyperglycemia, AA may have therapeutic use.

arterial stiffness; augmentation index; blood pressure; glucose



Address for correspondence: B. A. Mullan, Regional Intensive Care Unit, Royal Victoria Hospital, Grosvenor Rd., Belfast BT12 6BA, Northern Ireland (E-mail: brian{at}mullan99.fsnet.co.uk). Reprints will not be available from the authors.




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