The time course of haemodynamic, autonomic and skeletal muscle metabolic abnormalities following first extensive myocardial infarction in man
We investigate the time course of genesis of skeletal muscle dysfunction and sympatho-vagal imbalance after myocardial infarction. We studied 22 normal control, 22 patients with > 6 months stable chronic heart failure and 10 patients after a first massive myocardial infarction at 1-3 weeks (the 'eary' period), 6-8 weeks ('mid') and 6-9 months ('late') following their infarct. Four patients developed overt heart failure. Forearm muscle metabolism was stuided using 31P magnetic resonance spectroscopy (MRS). Sympatho-vagal balance was assess by heart rate variability and radiolabelled norepinephrine kinetics. Increased norepinephrine spillover (0.55 ± 0.02 v 0.27 ± 0.04 mg/min/m2; P < 0.01) and decreased heart rate variability were confined to those post-myocardial infarction patients who subsequently developed heart failure. Resting cardiac output was normal in all the post-myocardial infarction patients, although the reponse of cardiac output to supine bicycle exercise at the 'mid' study point was less in the group who subsequently developed heart failure (9 ± 1 v 41 ± 8%; P < 0.005). In the MRS studies, there were no detectable differences between those who did or did not develop heart failure. The initial rate of ATP turnover, calculated from initial-exercise changes in pH and phosphocreatine (PCr), was increased in established chronic heart failure, but in the post-myocardial infarction patients a numerically similar increase reached statistical significance only in the early group (19 ± 3 v 11 ± 1 mM/min; P < 0.005). The apparent maximum rate of oxidative ATP synthesis, calculated from post-exercise PCr recovery kinetics, was lower than control in the late post-myocardial infarction and established chronic heart failure groups 34 ± 5 v 55 ± 4 mM/min; P < 0.03 and 38 ± 3 v 55 ± 4 mM/min; P < 0.003, respectively). Skeletal muscle metabolism and autonomic function become abnormal after an extensive myocardial infarction. While skeletal muscle abnormalities are relatively slow to develop and unrelated to the degree of failure, excessive neurohormonal activation and impaired cardiac output response to exercise seem from an early stage to characterize patients who subsequently develop chronic heart failure.