Friday, August 19, 2011
Electrical stimulation outside the heart
"In the previous paragraphs, we have discussed the application of electrical stimulation on the heart, which has the advantage of avoiding possible adverse side-effects as regularly encountered with pharmacological therapies. The therapies discussed below are applied outside the heart and usually are applied continuously throughout the cardiac cycle (see Fig. 1). Their benefit may be that the stimulation is affecting a much more integrated system. Studies of these therapies clearly show cardiac benefit, but in most cases, the exact mechanism is unknown. This is likely due to multi-organ and central nervous system pathways.
Vagal nerve stimulation
There has been extensive research demonstrating that acute vagus nerve stimulation results in a decrease in various measures of ventricular function including contractility. Lewis et al. showed that in the human and pig heart, stimulation of the left vagus nerve can profoundly decrease contractility of the left ventricular myocardium, independent of its braducardic effect . This decrease in ventricular contractility during vagal stimulation (VNS) appears to be mediated by the parasympathetic ganglia located in the cranial medial ventricular fat pad [55, 56]. However, at low sympathetic tone, the negative inotropic effect of vagal stimulation is attributable primarily to its negative chronotropic effect . This suggests that the effect of VNS on contractility is mediated via an interaction with the sympathetic system.
It may seem counterintuitive that a reduction in contractility by VNS may be beneficial to patients with heart failure. However, several pre-clinical studies have shown benefit in chronic vagus nerve stimulation in models of systolic heart failure . Recently, Zhang et al. evaluated VNS in a canine high-rate pacing-induced model of heart failure. VNS at an intensity that reduced sinus rate by approximately 20 bpm was delivered in the VNS group. After 4 and 8 weeks, both left ventricular end-diastolic and end-systolic volumes were lower, and left ventricular EF was higher in the VNS group than in the control group . Li et al. showed that VNS markedly improved the long-term survival of chronic heart failure rats through the prevention of pumping failure, remodeling, and increasing contractility . Very recently, the same group showed that VNS applied immediately after MI attenuated LV remodeling, which may be related to the decreased acute inflammatory response or to the reduction in infarct size induced by VNS , since the remodeling process increases with a larger infarct."