Cardioprotection evoked by remote ischaemic preconditioning is critically dependent on the activity of vagal pre-ganglionic neurones

Autor: Stefan Trapp, Michael P. Gilbey, Sergey Kasparov, Anja G. Teschemacher, Svetlana Mastitskaya, Nephtali Marina, Gareth L. Ackland, Alexander V. Gourine, Andrey Gourine, K. Michael Spyer
Rok vydání: 2012
Předmět:
Atropine
Male
Receptors
Neuropeptide
Time Factors
Physiology
Myocardial Infarction
Action Potentials
030204 cardiovascular system & hematology
Receptors
G-Protein-Coupled
Rats
Sprague-Dawley
0302 clinical medicine
Transduction
Genetic
Neural Pathways
Drosophila Proteins
Medicine
Cardioprotection
education.field_of_study
Brain
Heart
Constriction
Hindlimb
Anesthesia
Ischemic Preconditioning
Myocardial
Cardiology and Cardiovascular Medicine
Ischaemia/reperfusion injury
Rhodopsin
Autonomic Fibers
Preganglionic
Recombinant Fusion Proteins
Genetic Vectors
Population
Myocardial Reperfusion Injury
Preconditioning
Muscarinic Antagonists
Vagus nerve
Adenoviridae
03 medical and health sciences
Reperfusion therapy
Physiology (medical)
Animals
Muscle
Skeletal
education
business.industry
Myocardium
Lentivirus
Neuropeptides
Original Articles
medicine.disease
Rats
Disease Models
Animal
Autonomic nervous system
Dorsal motor nucleus
Ischemic preconditioning
sense organs
business
Reperfusion injury
Neuroscience
030217 neurology & neurosurgery
Brain Stem
Zdroj: Cardiovascular Research
ISSN: 1755-3245
0008-6363
Popis: Aims 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). Methods and results 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. Conclusion 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.
Databáze: OpenAIRE
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