The sensory-cardiac interface in heart failure – A therapeutic target

      Background: Cardiac sensory nerves that traverse anatomically defined sympathetic pathways (“cardiac sympathetic afferents”) have been traditionally thought to convey the sensation of pain during coronary ischemia. They also have been shown to mediate sympatho-excitation. Previous studies from our laboratory have shown that the afferent discharge and the reflex effects upon stimulation of these afferents with either bradykinin or capsaicin evoke increased responses in the setting of chronic heart failure (CHF). More recently, we demonstrated that cardiac sympathetic afferents also participate in the cardiac remodeling process following a myocardial infarction (MI). Results: Epicardial application of the ultra-potent capsaicin analog resiniferitoxin (RTX) at the time of coronary ligation significantly reduced both cardiac and renal sympathetic nerve activity as well as norepinephrine excretion 12 weeks after MI. Furthermore, several markers of the remodeling process were also abrogated in RTX treated animals. This included collagen, fibronectin, and TGFβ receptor expression in the remote left ventricular myocardium. RTX reduced tissue cytokine expression. While cardiac systolic function was not improved there was a marked increase in diastolic function as measured by pressure-volume loop analyses. Cardiac reserve (response to isoproterenol) was also enhanced in the RTX treated group. Most importantly the 6 month survival curves were markedly enhanced for both epicardial and epidural application of RTX. Conclusion: Cardiac sympathetic afferent ablation may have important therapeutic benefits in the setting of CHF.
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