Microvascular Responses Following 5‐Fluoruracil Chemotherapy Administration

Abstract

BACKGROUNDThe pyrimidine antimetabolite 5‐Fluorouracil (5‐FU) is implicated with the second highest rate of cardiotoxicity among cancer chemotherapies, manifesting as vascular vasospasms. Despite this, the pathophysiological mechanisms in which 5‐FU‐induced vasospasms occur is not well understood, but alterations in microvascular endothelial‐dependent and ‐independent pathways have been implicated. This is critical given that decrements in microvascular function are known to occur early in the development of overt cardiovascular disease and like measurements have previously been used to asses pathophysiological mechanisms in numerous patient populations. However, to date, no study has investigated the microvascular function in cancer patients actively receiving 5‐FU chemotherapy. Therefore, we hypothesized that cancer patients treated with 5‐FU would exhibit lower measurements of cutaneous blood flow (CBF) and cutaneous vascular conductance (CVC) following iontophoresis of ACh to that of healthy non‐treated controls.METHODS9 5‐FU treated cancer patients (7 M, 2 F; age 62.8 ± 11.1 yr) and 9 healthy controls (6 M, 3 F; age 56.62 ± 9.9 yr) were recruited for this study. Red blood cell flux was measured non‐invasively in the right forearm via Laser Doppler Flowmetry (LDF) and used as an index of CBF. Endothelial‐dependent vasodilation was elicited via iontophoresis of acetylcholine (ACh). Baseline to peak changes CBF and CVC, derived from CBF and mean arterial pressure were calculated.RESULTSNo significant differences for CBF [5‐FU: 792.78 ± 476.3%, control: 973 ± 682.77%, p = .26] or CVC [5‐FU: 796.76 ± 472.99 %, control: 918.33 ± 638.01.3%, p = .32] were found between groups.CONCLUSIONTo date, our data suggests 5‐FU does not alter Ach‐mediated endothelial‐dependent vasodilation within the cutaneous microcirculation. These findings suggest that endothelial‐independent mechanisms may be linked to 5‐FU cardiotoxicity. Future directions will include a focus on smooth muscle function and vasoconstrictor responses of patients undergoing 5‐FU chemotherapy.