Abstract
RationalePatients with heart failure have an increased incidence of depression. Central and peripheral inflammation play a major role in the pathophysiology of both heart failure and depression.AimMinocycline is an antibiotic that inhibits microglia activation and release of pro-inflammatory cytokines. We assessed effects of minocycline on extent of heart failure and depression at 2 and 8 weeks post myocardial infarction.Methods/ResultsMale Wistar rats were randomly divided into 3 groups: (i) sham + vehicle; (ii) MI + vehicle; and (iii) MI + minocycline with n/group of 8, 9 and 9 at 2 weeks, and 10, 16, 8 at weeks, respectively. Oral minocycline (50 mg/kg/day) or vehicle started 2 days before surgery. Depression-like behaviour was assessed with sucrose preference and forced swim tests, and cardiac function with echo and hemodynamics. After myocardial infarction, microglia activation and plasma/brain pro-inflammatory cytokines increased, which were mostly prevented by minocycline. At 8 weeks, cardiac dysfunction was attenuated by minocycline: infarct size (MI + Vehicle 29±1, MI + Min 23±1%), ejection fraction (Sham 80±1, MI + Vehicle 48±2, MI + Min 58±2%) and end diastolic pressure (Sham 3.2±0.3, MI + Vehicle 18.2±1.1, MI + Min 8.5±0.9 mm Hg). Depression-like behaviour was significantly improved by minocycline in sucrose preference test (% Sucrose Intake: Sham 96±1, MI + Vehicle 78±2, MI + Min 87±2) and forced swim test (% Immobile: Sham 40±4, MI + Vehicle 61±3, MI + Min 37±6).ConclusionRats post myocardial infarction develop systemic inflammation, heart failure and depression-like behaviour that are all attenuated by minocycline. Targeting (neuro) inflammation may represent new therapeutic strategy for patients with heart failure and depression.
Highlights
Both heart failure (HF) and depression are very prevalent and major health concerns with tremendous consequences for quality of life, morbidity and mortality
Rats post myocardial infarction develop systemic inflammation, heart failure and depression-like behaviour that are all attenuated by minocycline
The results reveal that striking microglia and pro-inflammatory cytokines (PICs) activation and depression-like behaviour develop in the chronic phase of HF in rats post myocardial infarction (MI)
Summary
Both heart failure (HF) and depression are very prevalent and major health concerns with tremendous consequences for quality of life, morbidity and mortality. HF is associated with a high incidence of depression, and patients with both HF and depression have a poorer quality of life, and > 2-fold increased risk of further cardiac events and mortality than those with HF but not depressed [1,2,3,4]. There are currently no effective treatments to reduce depressive symptoms in patients with HF. Recent randomized clinical trials concluded that treatment of these patients with a selective serotonin-reuptake inhibitor compared to placebo does not cause a significant improvement in depression symptoms and does not improve cardiovascular event rates [1,2,3,4,5]. There is, a critical need to better understand the mechanisms contributing to this adverse interaction in order to develop new effective preventative/ therapeutic strategies
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