23. september 2003 Prolonged acetylcholine-induced vasodilatation in the peripheral microcirculation of patients with chronic fatigue syndrome Clin Physiol Funct Imaging 2003; 23(5): 282-285 Institution: Faisel Khan, Vance Spence, Gwen Kennedy and Jill J. F. Belch, Vascular Diseases Research Unit, Department of Medicine, University of Dundee, Dundee, UK. This new scientific paper in Clinical Physiology and Functional Imaging publishes research that shows prolonged vasodilatation in response to acetylcholine delivered to skin blood vessels. These results represent a further step in the MERGE-funded investigations of disturbances to cholinergic pathways and the vascular endothelium of patients with ME/CFS. Background: Although the aetiology of chronic fatigue syndrome (CFS) is unknown, there have been a number of reports of blood flow abnormalities within the cerebral circulation and systemic blood pressure defects manifesting as orthostatic intolerance. Neither of these phenomena has been explained adequately, but recent reports have linked cerebral hypoperfusion to abnormalities in cholinergic metabolism. Our group has previously reported enhanced skin vasodilatation in response to cumulative doses of transdermally applied acetylcholine (ACh), implying an alteration of peripheral cholinergic function. Methods and Results: To investigate this further, we studied the time course of Ach-induced vasodilatation following a single dose of ACh in 30 patients with CFS and 30 age and gender-matched healthy control subjects. No differences in peak blood flow were seen between patients and controls, but the time taken for the ACh response to recover to baseline was significantly longer in the CFS patients than in control subjects. The time taken to decay to 75% of the peak response in patients and controls was 13.7±11.3 vs. 8.9±3.7 min (P=0.03), respectively, and the time taken to decay to 50% of the peak response was 24.5±18.8 vs. 15.1±8.9 min (P=0,03), respectively. Conclusions: Prolongation of ACh-induced vasodilatation is suggestive of a disturbance to cholinergic pathways, perhaps within the vascular endothelium of patients with CFS, and might be related to some of the unusual vascular symptoms, such as hypotension and orthostatic intolerance, which are characteristic of the condition.