Carbamylated erythropoietin prevents cardio-respiratory dysfunctions induced by chronic intermittent hypoxia

Abstract

Erythropoietin (EPO) has protective effects in several tissues and could be used for therapeutic purposes. However, EPO-induced erythropoiesis could be detrimental in treated patients. Carbamylation of erythropoietin maintains the tissue-protective effects of EPO but without erythropoietic effects. Here, we assume that carbamylated erythropoietin (cEPO) prevents the cardiorespiratory deleterious effects induced by chronic intermittent hypoxia. Indeed, Obstructive Sleep Apnoea (OSA) is characterised by Chronic Intermittent Hypoxia (CIH) that leads to an increase in oxidative stress, responsible for cardiorespiratory disorders. To test our hypothesis, Sprague-Dawley male rats (around 300g) were exposed to CIH for 1 month (8 h/days; 12 cycles per hour; FiO2 nadir: 5% O2). cEpo was administrated during the last week of CIH exposure and cardiorespiratory variables as well as chemoreflex function were evaluated in control conditions (Sham), after 3 weeks of CIH and then 1 week after and cEPO treatment (CIH-Epo). As expected, cEPO had no effect on haematocrit. CIH increased mean arterial pressure, frequency of apnea/hypopnea and hypoxic and hypercapnic ventilatory responses. cEPO treatment prevented CIH-induced hypertension, reduced the Apnea-Hypopnea index and improved the stability of breathing pattern after CIH exposure. Furthermore, cEpo reduced the increase in chemoreflex function observed during exposure to CIH. In conclusion, cEpo prevented cardiorespiratory disorders induced by CIH. These results suggest that cEpo could be considered as a treatment for patients with OSA-induced cardio-respiratory disorders.