Pharmacologic Inhibition of Pain Response to Incomplete Vascular Occlusion Blunts Cardiovascular Preconditioning Response

• Published in: Cardiovascular toxicology Vol. 21; no. 11; pp. 889 - 900
• Main Authors: Kirschner, Akiva, Koch, Sheryl E., Robbins, Nathan, Karthik, Felix, Mudigonda, Parvathi, Ramasubramanian, Ranjani, Nieman, Michelle L., Lorenz, John N., Rubinstein, Jack
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2021; Springer; Springer Nature B.V
• Subjects: Anesthetics, Local - pharmacology; Animals; Biomedical and Life Sciences; Biomedicine; Cardiology; Cytokines - blood; Cytokines - genetics; Disease Models, Animal; Echocardiography; Ethylenediaminetetraacetic acid; Forelimb - blood supply; Inflammation; Ischemia; Ischemic Preconditioning - methods; Leather; Lidocaine; Lidocaine - pharmacology; Ligation; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction - blood; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - physiopathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - blood; Myocardial Reperfusion Injury - diagnostic imaging; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Occlusion; Pain; Pain perception; Pain Threshold - drug effects; Pharmacology/Toxicology; Radial Artery - diagnostic imaging; Radial Artery - physiology; Regional Blood Flow; Reperfusion; Time Factors; Vascular occlusion; IR; Pain; Cardioprotection; RIPC
• ISSN: 1530-7905; 1559-0259; 1559-0259
• DOI: 10.1007/s12012-021-09680-z

Complete vascular occlusion to distant tissue prior to an ischemic cardiac event can provide significant cardioprotection via remote ischemic preconditioning (RIPC). Despite understanding its mechanistic basis, its translation to clinical practice has been unsuccessful, likely secondary to the inherent impossibility of predicting (and therefore preconditioning) an ischemic event, as well as the discomfort that is associated with traditional, fully occlusive RIPC stimuli. Our laboratory has previously shown that non-occlusive banding (NOB) via wrapping of a leather band (similar to a traditional Jewish ritual) can elicit an RIPC response in healthy human subjects. This study sought to further the pain-mediated aspect of this observation in a mouse model of NOB with healthy mice that were exposed to treatment with and without lidocaine to inhibit pain sensation prior to ischemia/reperfusion injury. We demonstrated that NOB downregulates key inflammatory markers resulting in a preconditioning response that is partially mediated via pain sensation.