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Correspondence  |   September 2006
Nitrous Oxide and Preconditioning
Author Affiliations & Notes
  • Paul S. Pagel, M.D., Ph.D.
    *
  • *Medical College of Wisconsin, Milwaukee, Wisconsin.
Article Information
Correspondence
Correspondence   |   September 2006
Nitrous Oxide and Preconditioning
Anesthesiology 9 2006, Vol.105, 630. doi:
Anesthesiology 9 2006, Vol.105, 630. doi:
To the Editor:—
We read with interest the recent report by Weber et al.  1 demonstrating that brief, repetitive administration of 60% nitrous oxide before prolonged coronary artery occlusion and reperfusion did not protect myocardium against infarction in rats. These findings concur with previous results from our laboratory indicating that administration of 70% nitrous oxide before and during a 15-min coronary artery occlusion failed to improve and, in fact, exacerbated the functional recovery of postischemic, reperfused (“stunned”) myocardium as compared with 70% nitrogen in barbiturate-anesthetized, acutely instrumented dogs.2 The results of Weber et al.  further demonstrated that nitrous oxide exposure did not produce phosphorylation of ϵ isoform of protein kinase C (PKC-ϵ) and Src protein tyrosine kinase or cause sarcolemmal translocation of PKC-ϵ. Our investigation was conducted several years before the prosurvival signaling mechanisms responsible for anesthetic-induced myocardial protection against reversible and irreversible ischemic injury were discovered. Myocardial stunning and infarction most likely represent a continuum of ischemic damage, and it is clear that activation of PKC-ϵ plays a central role in volatile anesthetic–induced preservation of myocardial function and integrity during these processes, respectively.3–7 Src protein tyrosine kinase has also been implicated in anesthetic-induced preconditioning against infarction,1,6 but whether this enzyme also mediates the beneficial actions of volatile agents in stunned myocardium is unknown. The current results1 indicating that a clinically relevant concentration of nitrous oxide does not cause preconditioning are not entirely unexpected based on our previous findings,2 but they nevertheless provide new molecular insight into the observation that this anesthetic gas does not produce cardioprotection in ischemic myocardium.
Nitrous oxide may also fail to produce preconditioning as a result of adverse effects on myocardial oxygen supply versus  demand relations. Nitrous oxide was previously shown to produce epicardial coronary artery vasoconstriction as assessed using angiography.8 These data suggested that nitrous oxide may theoretically compromise perfusion of ischemic myocardium.9 We demonstrated that 70% nitrous oxide did not affect coronary collateral perfusion or alter the ratio of endocardial to epicardial blood flow measured using radioactive microspheres in a canine model of ischemia and reperfusion, but we did not specifically examine the influence of nitrous oxide on epicardial coronary artery diameter in our investigation.2 Rats have been shown to possess little if any coronary collateral blood flow,10 but the actions of nitrous oxide on transmural myocardial perfusion and epicardial coronary dimension were not quantified, nor was the potential impact of the anesthetic gas on myocardial oxygen supply considered in the current study.1 Nitrous oxide has been shown to directly activate the sympathetic nervous system11 and stimulate the release of norepinephrine from sympathetic efferents innervating vascular smooth muscle.12 These actions increase left ventricular afterload,13 an important determinant of myocardial oxygen consumption. As a consequence, nitrous oxide may precipitate a relatively greater ischemic burden by increasing myocardial oxygen consumption before the onset of coronary artery occlusion. Heart rate and mean aortic blood pressure remained unchanged during nitrous oxide preconditioning, suggesting that alterations in myocardial oxygen consumption did not occur during administration of the anesthetic gas in rats.1 Nevertheless, the current results should also be qualified because other hemodynamic determinants of myocardial oxygen consumption were not evaluated (e.g.  , myocardial contractility, left ventricular preload), nor was myocardial oxygen consumption directly calculated by measurement of arterial and coronary venous oxygen tensions.
*Medical College of Wisconsin, Milwaukee, Wisconsin.
References
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