L’interaction HMGB1/tétranectine: Une cible thérapeutique dans les états septiques ?

International audienc

The ratios of central venous to arterial carbon dioxide content and tension to arteriovenous oxygen content are not associated with overall anaerobic metabolism in postoperative cardiac surgery patients.

BACKGROUND:The aim of the present study was to evaluate the ability of the ratios of central venous to arterial carbon dioxide content and tension to arteriovenous oxygen content to predict an increase in oxygen consumption (VO2) upon fluid challenge (FC). METHODS AND RESULTS:110 patients admitted to cardiothoracic ICU and in whom the physician had decided to perform an FC (with 500 ml of Ringer's lactate solution) were included. The arterial pressure, cardiac index (Ci), and arterial and venous blood gas levels were measured before and after FC. VO2 and CO2-O2 derived variables were calculated. VO2 responders were defined as patients showing more than a 15% increase in VO2. Of the 92 FC responders, 43 (46%) were VO2 responders. At baseline, pCO2 gap, C(a-v)O2 were lower in VO2 responders than in VO2 non-responders, and central venous oxygen saturation (ScvO2) was higher in VO2 responders. FC was associated with an increase in MAP, SV, and CI in both groups. With regard to ScvO2, FC was associated with an increase in VO2 non-responders and a decrease in VO2 responders. FC was associated with a decrease in pvCO2 and pCO2 gap in VO2 non-responders only. The pCO2 gap/C(a-v)O2 ratio and C(a-v)CO2 content /C(a-v)O2 content ratio did not change with FC. The CO2 gap content/C(a-v)O2 content ratio and the C(a-v)CO2 content /C(a-v)O2 content ratio did not predict fluid-induced VO2 changes (area under the curve (AUC) [95% confidence interval (CI)] = 0.52 [0.39‒0.64] and 0.53 [0.4-0.65], respectively; p = 0.757 and 0.71, respectively). ScvO2 predicted an increase of more than 15% in the VO2 (AUC [95%CI] = 0.67 [0.55‒0.78]; p<0.0001). CONCLUSIONS:Our results showed that the ratios of central venous to arterial carbon dioxide content and tension to arteriovenous oxygen content were not predictive of VO2 changes following fluid challenge in postoperative cardiac surgery patients

JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.

JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development and complications remains unknown. In a cohort of patients with myeloproliferative neoplasm, JAK2V617F mutation was identified as an independent risk factor for dilation of both the ascending and descending thoracic aorta. Using single-cell RNA-seq, complementary genetically-modified mouse models, as well as pharmacological approaches, we found that JAK2V617F mutation was associated with a pathogenic pro-inflammatory phenotype of perivascular tissue-resident macrophages, which promoted deleterious aortic wall remodeling at early stages, and dissecting aneurysm through the recruitment of circulating monocytes at later stages. Finally, genetic manipulation of tissue-resident macrophages, or treatment with a Jak2 inhibitor, ruxolitinib, mitigated aortic wall inflammation and reduced aortic dilation and rupture. Overall, JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm