Activated matrix metalloproteinase and disrupted myocardial collagen matrix in increased sympathetic activity following stimulation of dorsal medulla in the vagotomized feline model

Sympathetic hyperactivation in many kinds of neurocardiogenic injury can result in obvious heart failure. We generated a vagotomized feline model in which sympathetic hyperactivation was induced by electrical stimulation of dorsal medulla (ESDM) of brain stem to investigate the relationship between disruption of extracellular collagen matrix (ECM) and activation of matrix metalloproteinases (MMPs) in myocardium in the sympathetic hyperactivity. Mean blood pressure, heart rate and plasma norepinephrine were all significantly increased from baseline to a peak at 5 min after ESDM. Echocardiographic study showed significant left ventricular dilatation and hypokinesia (ejection fraction: from 87.7 +/- 6.3% to 39.4 +/- 7.8%) from baseline to 180 mm after ESDM. Histopathological finding revealed significant overstretching or spring-like disappearance and disruption of ECM. MMP-2 expression was significantly increased in left ventricular myocardium as compared to sham. These results suggest that ESDM-induced sympathetic hyperactivity causes the expression of MMP-2 that disrupts myocardial ECM, contributing to the development of cardiac dysfunction.