Calypso Mathieu1,2, Martine Desrois2, Frank Kober2, Nathalie Lalevée3, Carole Lan2, Natacha Fourny2, Magali Iché-Torres3, Thi Thom Tran3, Linh Thuy Lê3, Mervyn Singer4, Jean-Louis Mège5, Monique Bernard2, Marc Leone1,5. 1. Aix Marseille University, Service d'anesthésie et de réanimation, Hôpital Nord, Assistance Publique Hôpitaux de Marseille, Marseille, France. 2. Aix-Marseille University, CNRS, CRMBM, Marseille, France. 3. Aix-Marseille University, INSERM, TAGC, UMR 1090, Marseille, France. 4. University College London, 4919, Bloomsbury Institute of Intensive Care Medicine, London, United Kingdom. 5. Aix-Marseille University, CNRS UMR 7278, IRD198, INSERM U1095, Institut Hospitalier Universitaire Méditerranée-Infection, Marseille, France.
Abstract
OBJECTIVES: To investigate any gender effect of the beta-1 adrenergic blocker, landiolol, on cardiac performance and energy metabolism in septic rats, and to explore the expression of genes and proteins involved in this process. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female Wistar rats. INTERVENTIONS: One hour after cecal ligation and puncture, male and female rats were randomly allocated to the following groups: sham male, cecal ligation and puncture male, cecal ligation and puncture + landiolol male, sham female, cecal ligation and puncture female, and cecal ligation and puncture + landiolol female. Cardiac MRI was carried out 18 hours after cecal ligation and puncture to assess in vivo cardiac function. Ex vivo cardiac function measurement and P magnetic resonance spectroscopy were subsequently performed using an isovolumic isolated heart preparation. Finally, we assessed cardiac gene and protein expression. MEASUREMENTS AND MAIN RESULTS: In males, landiolol increased indexed stroke volume by reversing the indexed end-diastolic volume reduction without affecting left ventricle ejection fraction. In females, landiolol did not increase indexed stroke volume and indexed end-diastolic volume but decreased left ventricle ejection fraction. Landiolol had no effect on ex vivo cardiac function and on high-energy phosphate compounds. The effect of landiolol on the gene expression of natriuretic peptide receptor 3 and on protein expression of phosphorylated-AKT:AKT ratio and endothelial nitric oxide synthase was different in males and females. CONCLUSIONS: Landiolol improved the in vivo cardiac performance of septic male rats while deleterious effects were reported in females. Expression of natriuretic peptide receptor 3, phosphorylated-AKT:AKT, and endothelial nitric oxide synthase are signaling pathways to investigate to better understand the sex differences in sepsis.
OBJECTIVES: To investigate any gender effect of the beta-1 adrenergic blocker, landiolol, on cardiac performance and energy metabolism in septic rats, and to explore the expression of genes and proteins involved in this process. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male and female Wistar rats. INTERVENTIONS: One hour after cecal ligation and puncture, male and female rats were randomly allocated to the following groups: sham male, cecal ligation and puncture male, cecal ligation and puncture + landiolol male, sham female, cecal ligation and puncture female, and cecal ligation and puncture + landiolol female. Cardiac MRI was carried out 18 hours after cecal ligation and puncture to assess in vivo cardiac function. Ex vivo cardiac function measurement and P magnetic resonance spectroscopy were subsequently performed using an isovolumic isolated heart preparation. Finally, we assessed cardiac gene and protein expression. MEASUREMENTS AND MAIN RESULTS: In males, landiolol increased indexed stroke volume by reversing the indexed end-diastolic volume reduction without affecting left ventricle ejection fraction. In females, landiolol did not increase indexed stroke volume and indexed end-diastolic volume but decreased left ventricle ejection fraction. Landiolol had no effect on ex vivo cardiac function and on high-energy phosphate compounds. The effect of landiolol on the gene expression of natriuretic peptide receptor 3 and on protein expression of phosphorylated-AKT:AKT ratio and endothelial nitric oxide synthase was different in males and females. CONCLUSIONS:Landiolol improved the in vivo cardiac performance of septic male rats while deleterious effects were reported in females. Expression of natriuretic peptide receptor 3, phosphorylated-AKT:AKT, and endothelial nitric oxide synthase are signaling pathways to investigate to better understand the sex differences in sepsis.
Authors: MengQi Zhang; Joshua Montroy; Rahul Sharma; Dean A Fergusson; Asher A Mendelson; Kimberly F Macala; Stephane L Bourque; Jared M Schlechte; Mikaela K Eng; Braedon McDonald; Sean E Gill; Kirsten M Fiest; Patricia C Liaw; Alison Fox-Robichaud; Manoj M Lalu Journal: Crit Care Explor Date: 2021-06-14