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(Circulation. 2000;102:994.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Acute Systemic Inflammation Impairs Endothelium-Dependent Dilatation in Humans

Aroon D. Hingorani, PhD, MRCP; Jenny Cross, BSc, MRCP; Rajesh K. Kharbanda, BSc, MRCP; Michael J. Mullen, MBBS, MRCP; Kiran Bhagat, PhD, MRCP; Mia Taylor, BSc; Ann E. Donald; Miriam Palacios, PhD; George E. Griffin, MD, FRCP; John E. Deanfield, MB, BChir, FRCP; Raymond J. MacAllister, MD, MRCP; Patrick Vallance, MD, FRCP

From the Centre for Clinical Pharmacology (A.D.H., J.C., R.K.K., K.B., R.J.M., P.V.) and Wolfson Institute for Biomedical Research (M.P.), University College London; Cardiothoracic Unit, Great Ormond Street Hospital for Children NHS Trust (M.J.M., M.T., A.E.D., J.E.D.); and Division of Infectious Diseases, School of Medicine, St George’s Hospital (G.E.G.), London, UK.

Correspondence to Dr A.D. Hingorani, Centre for Clinical Pharmacology, UCL, Rayne Institute, 5 University St, London WC1E 6JJ, UK. E-mail a.hingorani{at}ucl.ac.uk

Background—We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation.

Methods and Results—Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers. In 12 subjects, dilatation of the brachial artery to flow and to sublingual nitroglycerin (NTG) was recorded (conduit vessel response), and in 6 subjects, venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent dilators NTG and verapamil (resistance vessel response). Responses were assessed 16 hours before and 8 and 32 hours after vaccination. Vaccination resulted in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist. Eight hours after vaccination, resistance vessel responses to BK (P=0.0099) and ACh (P=0.0414) were markedly attenuated, and brachial artery flow-mediated dilatation was depressed. Resistance vessel responses to verapamil and NTG were unchanged, as was the conduit vessel response to NTG. Thirty-two hours after vaccination, resistance vessel responses to BK and ACh had returned to normal.

Conclusions—S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli. This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event.

Key Words: : endothelium • nitric oxide • coronary disease

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