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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Action Potentials, Adenoviridae, Animals, Atropine, Autonomic Fibers, Preganglionic, Brain Stem, Constriction, Disease Models, Animal, Drosophila Proteins, Genetic Vectors, Heart, Hindlimb, Ischemic Preconditioning, Myocardial, Lentivirus, Male, Muscarinic Antagonists, Muscle, Skeletal, Myocardial Infarction, Myocardial Reperfusion Injury, Myocardium, Neural Pathways, Neuropeptides, Rats, Rats, Sprague-Dawley, Receptors, G-Protein-Coupled, Receptors, Neuropeptide, Recombinant Fusion Proteins, Rhodopsin, Time Factors, Transduction, Genetic, Vagus Nerve.
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Is cardioprotection evoked by remote ischaemic preconditioning critically dependent on the activity of vagal pre-ganglionic neurones? Context: Innate mechanisms of inter-organ protection underlie the phenomenon of remote ischaemic preconditioning (RPc) in which episode(s) of ischaemia and reperfusion in tissues remote from the heart reduce myocardial ischaemia/reperfusion injury. The uncertainty surrounding the mechanism(s) underlying RPc centres on whether humoral factor(s) produced during ischaemia/reperfusion of remote tissue and released into the systemic circulation mediate RPc, or whether a neural signal is required. While these two hypotheses may not be incompatible, one approach to clarify the potential role of a neural pathway requires targeted disruption or activation of discrete central nervous substrate(s). Using a rat model of myocardial ischaemia/reperfusion injury in combination with viral gene transfer, pharmaco-, and optogenetics, we tested the hypothesis that RPc cardioprotection depends on the activity of vagal pre-ganglionic neurones and consequently an intact parasympathetic drive. For cell-specific silencing or activation, neurones of the brainstem dorsal motor nucleus of the vagus nerve (DVMN) were targeted using viral vectors to express a Drosophila allatostatin receptor (AlstR) or light-sensitive fast channelrhodopsin variant (ChIEF), respectively. RPc cardioprotection, elicited by ischaemia/reperfusion of the limbs, was abolished when DVMN neurones transduced to express AlstR were silenced by selective ligand allatostatin or in conditions of systemic muscarinic receptor blockade with atropine. In the absence of remote ischaemia/reperfusion, optogenetic activation of DVMN neurones transduced to express ChIEF reduced infarct size, mimicking the effect of RPc.
assistant
These data indicate a crucial dependence of RPc cardioprotection against ischaemia/reperfusion injury upon the activity of a distinct population of vagal pre-ganglionic neurones. Final Decision: yes