Effects of Cardiac Rehabilitation on High Mobility Group Box-1 Levels After Acute Myocardial Infarction

Effects of Cardiac Rehabilitation on High Mobility Group Box-1 Levels After Acute Myocardial Infarction

Effects of Cardiac Rehabilitation on High Mobility Group Box-1 Levels After Acute Myocardial Infarction

This purpose of this study is to examine the relationship between HMGB-1 and postinfarction predictors of outcome such as cardiopulmonary and echocardiographic parameters before and after a 6-month exercise-based cardiac rehabilitation program.

Exercise-based Cardiac Rehabilitation after acute myocardial infarction (AMI) has beneficial effects on cardiovascular functional capacity, quality of life, risk factors modification, and morbidity and mortality. Mounting evidences suggest that inflammation plays a key role both on initiation and progression of atherosclerosis. Several markers of systemic inflammation appear to be active effectors in the pathophysiology of athero-thrombotic disease leading to the occurrence of AMI. The high mobility group box 1 (HMGB-1) is a ubiquitous nuclear protein constitutively expressed in quiescent cells, and it has been implicated in several cellular functions, including determination of nucleosomal structure and stability, and binding of transcription factors to DNA sequences. HMGB-1 has been recently recognized as a critical mediator of inflammatory diseases. In fact, the passive release of this protein from necrotic or damaged cells represents an effective stimulus triggering the inflammatory response. Specifically, HMGB-1 binds to the receptor for advanced glycation end products (RAGE) and, in turns, it activates mitogen-activated protein-kinase (MAPK) and nuclear factor-κB (NF-κB). This intracellular pathway leads to the production of several pro-inflammatory cytokines. Interestingly, increased levels of HMGB-1 have been observed in atherosclerotic lesions, suggesting that HMGB-1 might be involved in the pathophysiology of atherosclerosis. This study was designed to investigate the relationship between HMGB-1 and strong postinfarction predictors of outcome such as cardiopulmonary and echocardiographic parameters before and after a 6-month exercise-based Cardiac Rehabilitation program.

Cardiac Rehabilitation, High Mobility Group Box proteins, Inflammatory markers, Cardiopulmonary Functional Capacity, Maximal Oxygen Consumption, Echocardiography, Left Ventricular Ejection Fraction, Left Ventricular Chambers Dilation, Left Ventricular Remodeling, Left Atrium Remodeling, Cardiac Remodeling, Exercise Training

Trained patients attend the exercise training protocol for 6 months on hospital ambulatory-based regimen 3 times/week. Training sessions are supervised under continuous electrocardiography monitoring by a cardiologist, a physiotherapist and a graduate nurse. Each session is preceded by a 5-min warming-up and followed by a 5-min cooling-down. Exercise is performed for 30 min on a bicycle ergometer with the target of 60-70% of the peak oxygen consumption achieved at the initial symptom-limited cardiopulmonary exercise test. Exercise protocol is performed with a gradual increase in exercise workload until the achievement of the predefined target.

High mobility group box-1 (HMGB1) is a ubiquitous nuclear protein, constitutively expressed in quiescent cells, where it is involved in several cellular functions, including determination of nucleosomal structure and stability, and binding of transcription factors to DNA sequences. HMGB1 has been recently recognized as a critical mediator of inflammatory processes: the passive release of this protein from necrotic or damaged cells represents an effective stimulus triggering the inflammatory response.

Oxygen consumption at peak exercise stress testing (VO2peak) was obtained breath-by-breath with use of a computerized metabolic cart. VO2peak was recorded as the mean value of VO2 during the last 20 s of the test and expressed in millilitres per kilogram per minute.

The autonomic nervous system (ANS) is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. It is subdivided into two subsystems: the parasympathetic (vagal) and sympathetic nervous system. Sympatho-vagal imbalance is evaluated by post-exercise Heart Rate Recovery (HRR), defined as the fall in heart rate during the first minute after exercise (beats/min). HRR is a marker of vagal tone which is a powerful predictor of all-cause mortality in patients with coronary artery disease.

Inclusion Criteria: Acute Myocardial Infarction Exclusion Criteria: BMI higher than 30 and lower than 18 Residual myocardial ischemia Severe ventricular arrhythmias IIb or III degree atrio-ventricular block Valvular disease requiring surgery Pericarditis Severe renal dysfunction (i.e. creatinine >2.5 mg/dl) Severe concomitant non-cardiac disease such as cancer Liver dysfunction (alanine aminotransferase/aspartate aminotransferase level >1.5 times the upper normal limit) Dementia Any systemic disease limiting exercise Inability to participate in a prospective study for any logistic reason

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