title: High doses of ketamine-xylazine anesthesia reduce cardiac ischemia-reperfusion injury in guinea pigs.
abstract: Choosing an appropriate anesthetic protocol that will have minimal effect on experimental design can be difficult. Guinea pigs have highly variable responses to a variety of injectable anesthetics, including ketamine-xylazine (KX). Because of this variability, supplemental doses often are required to obtain an adequate plane of anesthesia. Our group studies the isolated guinea pig heart, and we must anesthetize guinea pigs prior to harvesting this organ. In this study, we sought to determine whether a higher dose of KX protected isolated guinea pig hearts against myocardial ischemia-reperfusion injury. Male Hartley guinea pigs (Crl:HA; 275 to 300 g; n = 14) were anesthetized with either of 2 doses of KX (K: 85 mg/kg, X: 15 mg/kg; or K: 200 mg/kg, X: 60 mg/kg). After thoracotomy, hearts underwent 20 min of ischemia followed by 2 h of reperfusion. The high dose of KX significantly reduced myocardial infarct size as compared with the low dose (36% ± 3% and 51% ± 6%, respectively). Furthermore, the high dose of KX improved hemodynamic function over that associated with the low dose as measured by increases in both left ventricular developed pressure (49 ± 4 and 30 ± 8 mm Hg, respectively) and maximal rate of left ventricular relaxation (-876 ± 70 and -576 ± 120 mm Hg/s, respectively). However, the high dose of KX did not alter the maximal rate of left ventricular contraction or coronary flow. These results suggest that supplementation of KX to ensure an adequate anesthetic plane may introduce unwanted variability in ischemia-reperfusion studies.
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Sloan
authors.forename: Matthew
authors.initials: M
authors.lastname: Rosenbaum
authors.forename: Dorcas
authors.initials: D
authors.lastname: O'Rourke
authors.forename: Karen
authors.initials: K
authors.lastname: Oppelt
authors.forename: Chad R
authors.initials: CR
authors.lastname: Frasier
authors.forename: Corinne A
authors.initials: CA
authors.lastname: Waston
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Allan
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D000777:Anesthetics / Q000494:pharmacology / Q000627:therapeutic use*; D019162:Anesthetics, Combined / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000830:Animals, Laboratory / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006168:Guinea Pigs / Q000502:physiology*; D007649:Ketamine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D020858:Tissue and Organ Harvesting / Q000379:methods / Q000662:veterinary; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D014991:Xylazine / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000777:Anesthetics; D019162:Anesthetics, Combined; D014991:Xylazine; D007649:Ketamine