Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia-induced myocardial infarction via cardiac adrenergic neurons

Abstract

Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) mitigates transient ischemia-induced ventricular infarction and, if so, whether adrenergic neurons are involved in such cardioprotection. The hearts of anesthetized rabbits, subjected to 30 min of left anterior descending coronary arterial occlusion (CAO) followed by 3 h of reperfusion (control), were compared with those with preemptive SCS (starting 15 min before and continuing throughout the 30-min CAO) or reactive SCS (started at 1 or 28 min of CAO). For SCS, the dorsal C8-T2 segments of the spinal cord were stimulated electrically (50 Hz, 0.2 ms, 90% of motor threshold). For preemptive SCS, separate groups of animals were pretreated 15 min before SCS onset with 1) vehicle, 2) prazosin (alpha(1)-adrenoceptor blockade), or 3) timolol (beta-adrenoceptor blockade). Infarct size (IS), measured with tetrazolium, was expressed as a percentage of risk zone. In controls exposed to 30 min of CAO, IS was 36.4 +/- 9.5% (SD). Preemptive SCS reduced IS to 21.8 +/- 6.8% (P < 0.001). Preemptive SCS-mediated infarct reduction was eliminated by prazosin (36.6 +/- 8.8%) and blunted by timolol (29.4 +/- 7.5%). Reactive SCS did not reduce IS. SCS increased phosphorylation of cardiac PKC. SCS did not alter blood pressure or heart rate. We conclude that preemptive SCS reduces the size of infarcts induced by transient CAO; such cardioprotection involves cardiac adrenergic neurons.

Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies

“…Catecholamines have also been reported to protect heart from transient myocardial ischemia-induced apoptosis mediated by α 1 -PKC pathway and ß-PKA pathway (Broadley and Penson, 2004;). A recent study also reported that this cardioprotection was dependent on cardiac adrenergic efferent neurons (Southerland et al, 2006). Other neuropeptides, such as NO (Sanada and Kitakaze, 2004) and beta-endorphin are potentially released during SCS and also may prevent myocardial ischemia.…”

“…Recently, it was proposed that SCS stabilizes the intrinsic cardiac nervous system and improves cardiac function (Foreman et al, 2000;Armour et al, 2002;Cardinal et al, 2006). Pre-emptive SCS is likely to protect myocardium from effects of critical ischemia (Southerland et al, 2006). Importantly, there is no solid evidence that SCS has the capability to augment local blood flow in the heart, which is different from the SCS effects on the limbs and brain (Norrsell et al, 1998;Kingma et al 2001).…”

“…different coronary ischemic models have been established in order to study SCS effects on the heart (Kingma et al 2001;Cardinal et al, 2006;Southerland et al, 2006). Acute complete occlusion of the left anterior descending coronary artery (LAD) in dogs (Kingma et al 2001), rabbits (Southerland et al, 2006) or rats (Pirat et al, 2007) have been used as an acute ischemic model.…”

“…Acute complete occlusion of the left anterior descending coronary artery (LAD) in dogs (Kingma et al 2001), rabbits (Southerland et al, 2006) or rats (Pirat et al, 2007) have been used as an acute ischemic model. A chronic ischemic model has also been established by implanting an ameroid constrictor around proximal left circumflex coronary artery (Cardinal, et al, 2004).…”

“…T1-T2 spinal segments are the most common and optimal places to be stimulated and the electrode is placed slightly to the left of midline (Cardinal, et al, 2006). However, SCS applied at segments higher than the T1 level also provides some cardioprotection (Gonzalez-Darder et al, 1998;Southerland et al, 2006).…”