To evaluate whether cervical spinal neurons can influence cardiac indices and myocyte viability in the acutely ischemic heart, the hearts of anesthetized rabbits subjected to 30 min of LAD (left anterior descending) coronary arterial occlusion (CAO) were studied 3h after reperfusion.
Control animals were compared to those exposed to pre-emptive high cervical cord stimulation (SCS; the dorsal aspect of the C1-C2 spinal cord was stimulated electrically at 50 Hz; 0.2 ms; 90% of motor threshold, starting 15 min prior to and continuing throughout CAO).
Four groups of animals were so tested: 1) neuroaxis intact; 2) prior cervical vagotomy; 3) prior transection of the dorsal spinal columns at C6; and 4) following pharmacological treatment [muscarinic (atropine) or adrenergic (atenolol, prazosin or yohimbine) receptor blockade].
Infarct size (IS) was measured by tetrazolium, expressed as percentage of risk zone. C1-C2 SCS reduced acute ischemia induced IS by 43%, without changing the incidence of sudden cardiac death (SCD). While SCS-induced reduction in IS was unaffected by vagotomy, it was no longer evident following transection of C6 dorsal columns or atropinization. Beta-adrenoceptor blockade eliminated ischemia induced SCD, while alpha-receptor blockade doubled its incidence. During SCS, myocardial ischemia induced SCD was eliminated following vagotomy while remaining unaffected by atropinization.
These data indicate that, in contrast to thoracic spinal neurons, i)cranial cervical spinal neurons affect both adrenergic and cholinergic motor outflows to the heart such that ii) their activation modifies ventricular infarctsize and lethal arrhythmogenesis.
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While presenting the paper, Shivaji added that clinical usage of spinal cord stimulation is on an "intent to treat" basis when the heart is not considered fit for a cardiac procedure (eg - when the arteries are too calcified and a stent cannot be used) and is done via an implantable device post laminectomy at the thoracic level. While this procedure was used as early as 2002, it has not gained much traction.
The mechanisms of SCS action in improving heart function has been discussed by Armour etal and Wu etal. Wu etal suggest that the improved cardiac response could be due to regulation of the intrinsic cardiac nervous system (the so called 'brain in the heart' per Armour), redistribution of blood flow, release of catecholamines (via the alpha and beta adrenergic pathways) and the suppression of nociceptive transmission (the severity of pain during a myocardial infarct is in itself is an intense stressor).
There was a discussion regarding reperfusion. Here is Shivaji's update, post the journal club:
There are many way of looking at what the SCS did in the experiment. The SCS could not have affected perfusion during the actual occlusion period because the artery was mechanically fully closed and the rabbit heart doesn't have collateral circulation. So we can conclude that the effects on actual reperfusion happen post removal of occlusion on the artery.
Note that other mechanisms relying on neural mechanisms eg the alpha and beta adrenergic receptor cascades occur during the artery occlusion as well. The other mechanisms which would work during occlusion also include the stabilisation of intrinsic cardiac nervous system.
The redistribution of blood flow within the coronary vascular bed has only weak evidence in the literature with contradictory results. Though tissue blood flow in vivo diseased hearts consistently showed such an effect, the in vitro results were not convincing. In a way this shows SCS perhaps works where it counts, ie, in diseased hearts.
That blood flow is maintained later is obvious. Once the occlusion is removed the arterial flow is restored. The thing to note here is that the occlusion was acute and reversible. No peripheral vascular bed pathology was present. Ie., once the occlusion was removed, there was no impediment to blood flow.
In reperfusion injury to the heart, one of the mechanisms is the larger production of free radical peroxynitrite. This is produced from NO that is locally produced due to a variety of factors. This includes local tissue reflexes and cholinergic innervation. This combines with superoxide released by wbc which come in post reperfusion.
(The last paragraph is speculative)The paper showed a balance change in favor of sympathetic system. So the beneficial effect of NO is preserved while reducing the deleterious effects post reperfusion. This could be a way in which reperfusion injury is reduced by SCS.
The evidence here is primarily neural, I feel, and their downstream effects on cardiac cells. Far lesser evidence on any vascular mechanisms.