title: Exogenous carbon monoxide does not affect cell membrane energy availability assessed by sarcolemmal calcium fluxes during myocardial ischaemia-reperfusion in the pig.
abstract: Carbon monoxide is thought to be cytoprotective and may hold therapeutic promise for mitigating ischaemic injury. The purpose of this study was to test low-dose carbon monoxide for protective effects in a porcine model of acute myocardial ischaemia and reperfusion. In acute open-thorax experiments in anaesthetised pigs, pretreatment with low-dose carbon monoxide (5% increase in carboxyhaemoglobin) was conducted for 120 min before localised ischaemia (45 min) and reperfusion (60 min) was performed using a coronary snare. Metabolic and injury markers were collected by microdialysis sampling in the ventricular wall. Recovery of radio-marked calcium delivered locally by microperfusate was measured to assess carbon monoxide treatment effects during ischaemia/reperfusion on the intracellular calcium pool. Coronary occlusion and ischaemia/reperfusion were analysed for 16 animals (eight in each group). Changes in glucose, lactate and pyruvate from the ischaemic area were observed during ischaemia and reperfusion interventions, though there was no difference between carbon monoxide-treated and control groups during ischaemia or reperfusion. Similar results were observed for glycerol and microdialysate ⁴⁵Ca(2+) recovery. These findings show that a relatively low and clinically relevant dose of carbon monoxide did not seem to provide acute protection as indicated by metabolic, energy-related and injury markers in a porcine myocardial ischaemia/reperfusion experimental model. We conclude that protective effects of carbon monoxide related to ischaemia/reperfusion either require higher doses of carbon monoxide or occur later after reperfusion than the immediate time frame studied here. More study is needed to characterise the mechanism and time frame of carbon monoxide-related cytoprotection.
authors.affiliation: Anesthesia and Intensive Care Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Ahlström
authors.forename: Björn
authors.initials: B
authors.lastname: Biber
authors.forename: Anna-Maja
authors.initials: AM
authors.lastname: Åberg
authors.forename: Pernilla
authors.initials: P
authors.lastname: Abrahamsson
authors.forename: Göran
authors.initials: G
authors.lastname: Johansson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Ronquist
authors.forename: Anders
authors.initials: A
authors.lastname: Waldenström
authors.forename: Michael F
authors.initials: MF
authors.lastname: Haney
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D054059:Coronary Occlusion / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D019344:Lactic Acid / Q000378:metabolism; D017551:Microdialysis; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D019289:Pyruvic Acid / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D013552:Swine
chemical_list: D019344:Lactic Acid; D002248:Carbon Monoxide; D019289:Pyruvic Acid; D005947:Glucose; D002118:Calcium