title: Thoracic spinal neuron responses to repeated myocardial ischemia and epicardial bradykinin.
abstract: Bradykinin has been strongly implicated as a mediator of cardiac nociception. During coronary artery occlusion, the content of bradykinin in coronary sinus blood increases. In non-cardiac tissues nociception to bradykinin exhibits tachyphylaxis, however, this phenomenon has not been rigorously studied in the heart. This raises the question that repeated coronary occlusions may also result in tachyphylaxis, thereby reducing cardiac sensation on subsequent ischemic stimulation. We therefore examined the hypothesis that repetitive episodes of myocardial ischemia and of epicardial application of bradykinin demonstrate tachyphylaxis. Mongrel cats were anesthetized with alpha-chloralose and heart rate, arterial pressure, and thoracic spinal neuron firing rate were recorded during 60 s of anterior descending coronary occlusion or local epicardial application of bradykinin (10 microM). Neurons were identified by cutaneous receptive fields in the left shoulder area. Sixty-one of 93 neurons tested responded with an increase in firing rate to coronary artery occlusion only (n=24), bradykinin only (n=19) or to both (n=18). On repetitive coronary occlusion, 14 of 25 neurons demonstrated tachyphylaxis compared to 12 of 15 tested with bradykinin (p<0.05). Similar responses were observed in thoracic spinal neurons that projected to the brain. In neurons demonstrating tachyphylaxis, dorsal cervical cold block partially restored the neuronal activation to coronary occlusion but not to bradykinin. We conclude, based on neuronal responses to repetitive stimuli, that afferent spinal responses to coronary occlusion and bradykinin are different. These data suggest that bradykinin is not the sole mediator of myocardial ischemic pain. The tachyphylaxis to repeated coronary artery occlusions may contribute to the clinical phenomenon of silent myocardial ischemia.
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Gutterman
authors.forename: P D
authors.initials: PD
authors.lastname: Pardubsky
authors.forename: M
authors.initials: M
authors.lastname: Pettersen
authors.forename: M L
authors.initials: ML
authors.lastname: Marcus
authors.forename: G F
authors.initials: GF
authors.lastname: Gebhart
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D002415:Cats; D003080:Cold Temperature; D003331:Coronary Vessels / Q000502:physiology; D004594:Electrophysiology; D006339:Heart Rate / Q000187:drug effects; D008026:Ligation; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D010496:Pericardium / Q000187:drug effects / Q000294:innervation; D011930:Reaction Time / Q000502:physiology; D012018:Reflex / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013618:Tachyphylaxis / Q000502:physiology
chemical_list: D001920:Bradykinin