RESUMO
INTRODUCTION: This study explored how acute sleep deprivation (ASD) before myocardial ischemia influences oxytocin release from paraventricular (PVN) neurons and its correlation with sympathetic nervous system (SNS) activity post-acute sleep loss, impacting subsequent left ventricular (LV) remodeling following myocardial infarction (MI). METHODS: The study was conducted in two phases: induction of ASD, inducing MI, blood sampling, euthanizing animals and collecting their heart and brain for histological and gene expression evaluations. The animals in first and second phase were euthanized 24 h and 14 days after MI, respectively. RESULTS: Pre-MI ASD, accompanied by increased serum epinephrine levels within 24 h of MI, upregulated oxytocin and cFos expression in the PVN. Also, pre-MI ASD resulted in decreased serum PAB levels 14 days post-MI (P < 0.001). While notable echocardiographic changes were seen in MI versus sham groups, ASD demonstrated protective effects. This was evidenced by reduced infarct size, elevated TIMP1, MMP2, and MMP9 in the LV of SD + MI animals versus MI alone (P < 0.05). Additionally, histological analysis showed reduced LV fibrosis in pre-MI ASD subjects (P < 0.05). CONCLUSION: Our study supports the notion that activation of oxytocin neurons within the PVN subsequent to ASD interacts with autonomic centers in the central nervous system. This enhanced sympathetic outflow to the heart prior to MI triggers a preconditioning response, thereby mediating cardioprotection through decreased oxidative stress biomarkers and regulated extracellular matrix (ECM) turnover.
RESUMO
Disturbed sleep or sleep loss due to vocational or lifestyle changes following MI is a common problem that may affect many physiological processes involved in left ventricle (LV) remodeling. Herein, we proposed that experience of sleep disruption and/or restriction after myocardial infarction (MI) may aggravate cardiac extracellular matrix remodeling and induce apoptosis in the cardiomyocytes. MI was induced in adult male rats by permanent ligation of the left anterior descending coronary artery. Twenty-four hours after surgery, some animals experienced chronic sleep restriction (CSR) for 6 days. Serum levels of CK-MB, PAB, and TNF-α were evaluated at days 1, 8, and 21 postsurgery. Twenty-one days after surgery, hemodynamic parameters and expression of MMP-2, MMP-9, TIMP-1, and TNF-α, as well as myocardial fibrosis and apoptosis in the noninfarcted area of the LV were assessed. Our results showed a clear decrease in serum concentrations of CK-MB, PAB and TNF-α at day 21 postsurgery in the MI group as compared to MI+SR animals in which these markers remained at high levels. CSR following MI deteriorated LV hemodynamic indexes and also impaired the balance between MMPs and TIMP-1. Further, it yielded an increase in oxidant and inflammatory state which caused deleterious fibrotic and apoptotic effects on cardiomycytes. Our data suggest post-MI sleep loss may cause adverse LV remodeling due to increased inflammatory reactions as well as oxidative burden and/or anti-oxidative insufficiency that in turn impede the balance between MMPs and their inhibitors.
