The cardiac output - cerebral blood flow relation is abnormal in most ME/CFS patients with a normal heart rate and blood pressure response during a tilt test.

Abstract

**Introduction** Orthostatic intolerance is highly prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HC) regulation of CBF is complex and involves multiple mechanisms including cardiac output (CO), cerebral perfusion pressure, PO2 and PCO2, flow-metabolism coupling, and innervation of cerebral vessels. In ME/CFS multiple other mechanisms have also been identified. **Aim of the study** We previously found that both CBF and CO were reduced in ME/CFS patients during tilt testing, and we hypothesized that the relation between CBF and CO is abnormal and different from HC. In this retrospective study we analyzed this relation in a large group of patients. To compare the patient data with those of HC, we focused on patients with a normal heart rate (HR) and blood pressure (BP) response to upright tilt. Also, the influence of clinical data was analyzed. **Methods** A total of 534 ME/CFS patients and 49 HC underwent tilt testing with measurements of HR, BP, CBF, and CO. In 46 (9%) patients CO and CBF changes were in the normal range of HC, and in 488 (91%) an abnormal CO and CBF reduction was found. **Results** patients with a CO and CBF reduction in the range of HC had less severe disease and were more likely to be male. In patients with an abnormal CO and CBF reduction the slope of the regression line of CO versus CBF reduction was almost 1. A multiple regression analysis of the latter group, including patients with PetCO2 measurements (440/488: 90%) showed that the CO reduction for the major part predicted the CBF reduction, with a limited role for the PetCO2 reduction and the tilt duration. Other data did not add to the model. **Conclusions** Two different patient groups with a normal HR and BP response during the tilt were identified: those with a CO and CBF in the normal range of HC and those with an abnormal CO and CBF reduction during the tilt (91% of patients). The former group had milder disease and included more men. In the largest group of patients there was an almost 1:1 relation between the CO and CBF reduction, suggesting absence of compensatory vasodilation in the cerebral vasculature. This may be an appropriate target for clinical and therapeutic interventions.