Involvement of capsaicin-sensitive sensory nerves in early and delayed cardioprotection induced by a brief ischaemia of the small intestine

Abstract

Early cardioprotection can be achieved by a brief ischaemia of noncardiac tissues. Our study examined whether a brief ischaemia of the small intestine induces both early and delayed cardioprotection in the rabbit and assessed the possible mechanism involved in the activation of capsaicin-sensitive sensory nerves. The plasma concentration of creatine kinase (CK) and infarct size (necrotic zone/left ventricular zone) after 30 min coronary artery occlusion and 180 min reperfusion were determined in rabbits. Infarct size was 35.5+/-6.8% in the control non-preconditioned group. Preconditioning induced by a brief period of 10-min small intestine ischaemia significantly reduced infarct size (6.5+/-1.9%, P<0.01 vs. the control non-preconditioned group) and decreased CK release (3092+/-236 and 1094+/-117 U/l for myocardial ischaemia-reperfusion and preconditioning plus myocardial ischemia-reperfusion, respectively, P<0.01), and the protection was partly abolished by pretreatment with capsaicin (50 mg/kg, s.c.) 4 days before the experiments. A brief period of anterior mesenteric artery occlusion caused an increase in the plasma level of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI), an effect which was abolished by pretreatment with capsaicin. Similar protection was shown in the animals subjected to a brief period of anterior mesenteric artery occlusion 24 h before coronary artery occlusion, and this delayed protection was also abolished partly by pretreatment with capsaicin. Capsaicin treatment (50 mg/kg, s.c.) alone also protected the ischaemic myocardium. The results suggest that brief ischaemia of the small intestine induces both early and delayed protection against reperfusion-induced myocardial injury, and the effects are, at least partly, related to the activation of capsaicin-sensitive sensory nerves.

Cardiac Remote Ischemic Preconditioning Prior to Elective Major Vascular Surgery (CRIPES): Study Design and Rationale

“…Supporting a neuronal pathway, studies have shown that cardioprotection can be abolished by the ganglionic blocker hexamethonium [19,20] or by pretreatment sensory nerves with capsaicin [21]. It is unclear whether the humoral mediators associated with ischemic preconditioning, which include adenosine, bradykinin, and opioids, are released into the bloodstream or locally in response to neural activation [22,23].…”

Cardioprotection Techniques: Preconditioning, Postconditioning and Remote Con-ditioning (Basic Science)

“…A similar type of study was conducted by Kristiansen and colleagues [169] who demonstrated that hearts excised from a rat that had been remote limb preconditioned experienced a smaller infarct size, when subjected to IRI. Other studies have investigated whether endogenous substances such as adenosine [170], bradykinin [171], opioids [172], CGRP [173], and endocannabinoids [174], are released from the remote organ during the preconditioning ischemia and are carried to the heart in the blood stream where they then activate intracellular pathways of cardioprotection. Alternatively, the endogenous mediator may activate afferent neural pathways within the remote preconditioned organ to confer cardioprotection, as is the case with adenosine, bradykinin and CGRP.…”

“…Gho and colleagues [10] demonstrated that the reduction in myocardial infarct size induced by brief ischemia and reperfusion of the anterior mesenteric artery could be reversed in the presence of the ganglion blocker, hexamethonium. The hypothesis for a neural pathway was further developed with the proposition that endogenous substances such as adenosine [170], bradykinin [171], calcitonin gene-related peptide (CGRP) [173], released by the remote preconditioned organ, stimulated afferent nerve fibres, which then relayed to efferent nerve fibres terminating on the myocardium to confer cardioprotection.…”

“…Several experimental studies have implicated calcitonin-gene related peptide (CGRP), a neurotransmitter released from capsaicinsensitive sensory nerves, as a potential mediator of both ischemic preconditioning [185] and RIPC [173,186]. These can be summarized as follows: remote intestinal preconditioning generates nitric oxide which stimulates capsaicin-sensitive sensory nerves in the intestinal vasculature, releasing CGRP into the blood-stream (where levels have reported to be increased by RIPC), which is then carried to the heart where it activates myocardial PKC-.…”

Chronobiological Aspects of the Heart Rhythm Disorders at the Change of Pulmonary Ventilation in Rat Model

“…It is now apparent that protection from IPC spreads from distant organs to the heart (Pell et al, 1998;Wolfrum et al, 2002) possibly via activation of the autonomic nervous system (Gho et al, 1996;Schoemaker & Van Heijningen, 2000;Liem et al, 2002;Wolfrum et al, 2002). It is possible that the release of local triggers of IPC activates the autonomic nervous system either directly (Schoemaker & Van Heijningen, 2000;Liem et al, 2002) or via sensory nerves (Tang et al, 1999;Xiao et al, 2001;Hu et al, 2002), and transfers the signal to the myocardium or other remote tissues. Evidence exists that sympathovagal regulation might be related to the protective mechanism of IPC (Loukogeorgakis et al, 2005;Wu et al, 2005).…”