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Correspondence  |   October 2004
Anesthesia and Multiorgan Protein Remodeling
Author Notes
  • Weill Medical College of Cornell University and Memorial Sloan-Kettering Cancer Center, New York, New York.
Article Information
Correspondence
Correspondence   |   October 2004
Anesthesia and Multiorgan Protein Remodeling
Anesthesiology 10 2004, Vol.101, 1040. doi:
Anesthesiology 10 2004, Vol.101, 1040. doi:
To the Editor:—
I read with particular interest the recent article by Fütterer et al.  1 describing both acute and relatively prolonged alteration in the expression of multiple proteins within the brains of rats anesthetized with desflurane. As both the authors and an accompanying editorial2 point out, although the functional significance of these observations remains uncertain, the data clearly challenge the common clinical perception that the global effects of volatile anesthetics are effervescent and rapidly reversible.
Although the brain is usually the target organ of clinical anesthesia, other organs are obviously exposed as well, which raises the prospect that persistent subcellular changes may be induced in structures other than the brain. Indeed, previous data indicating that even brief exposure to pentobarbital, propofol, or isoflurane alters immediate–early gene expression in multiple organs of the rat3 suggest that the secondary molecular responses to anesthetics may not be limited to the brain. In this vein, several years ago, we undertook a pilot project to assess whether volatile anesthetics alter expression of proteins regulating excitation–contraction coupling within the heart. Initially proposed as a means to shed light on whether aspects of perioperative management could have influenced results in our clinical study of myocardial remodeling in end-stage human heart failure,4 we decided to first examine effects of the prototypical potent volatile agent halothane in a rabbit model. As was previously reported,5 ventilation with 1% (0.7 minimum alveolar concentration) halothane in oxygen for 5 h produced a nearly twofold reduction in myocardial expression of the sarcoplasmic endoreticular calcium adenosine triphosphatase type 2a that was associated with a simultaneous time-dependent decrease in left ventricular contractility. In that sarcoplasmic endoreticular calcium adenosine triphosphatase type 2a is a major determinant of both diastolic and systolic function of the heart, molecular remodeling of the protein has been the focus of extensive research in the area of heart failure. In this setting, sarcoplasmic endoreticular calcium adenosine triphosphatase type 2a expression is also decreased, contributing, at least in part, to fundamental abnormalities in myocardial contraction and relaxation.4 Our preliminary observations with halothane and sarcoplasmic endoreticular calcium adenosine triphosphatase type 2a expression lead us to propose the idea that cardiac contractile reserve could be altered postoperatively through a process of “anesthetic-induced myocardial molecular remodeling,” a concept now seemingly supported in principal by the findings of Fütterer et al. 
As with the elegant work of Fütterer et al.  , our simple pilot study asked far more questions than it answered; multiple issues related to drug specificity and dose response, mechanisms, duration, and, most importantly, functional significance remain to be sorted out. Nonetheless, the fundamental knowledge that something may be happening within the heart and brain in response to anesthesia that can potentially persist beyond physical presence of the drug is both exciting and intimidating. Only time will tell whether we have entered a truly new era in our understanding of anesthetic pharmacology, but from my perspective, the future looks very intriguing.
Weill Medical College of Cornell University and Memorial Sloan-Kettering Cancer Center, New York, New York.
References
Fütterer CD, Maurer MH, Schmitt A, Feldmann RE Jr, Kuschinsky W, Waschke KF: Alterations in rat brain proteins after desflurane anesthesia. Anesthesiology 2004; 100:302–8Fütterer, CD Maurer, MH Schmitt, A Feldmann, RE Kuschinsky, W Waschke, KF
Hogan K: Long-lasting changes in brain protein expression after exposure to an anesthetic. Anesthesiology 2004; 100:209–12Hogan, K
Hamaya Y, Takeda T, Dohi S, Nakashima S, Nozawa Y: The effects of pentobarbital, isoflurane, and propofol on immediate-early gene expression in the vital organs of the rat. Anesth Analg 2000; 90:1177–83Hamaya, Y Takeda, T Dohi, S Nakashima, S Nozawa, Y
Heerdt PM, Holmes JW, Cai B, Barbone A, Madigan JD, Reiken SR, Lee DL, Oz MC, Marks AR, Burkhoff D: Chronic unloading by left ventricular assist device (LVAD) reverses abnormal contraction and alters gene expression in end-stage heart failure. Circulation 2000; 102:2577–82Heerdt, PM Holmes, JW Cai, B Barbone, A Madigan, JD Reiken, SR Lee, DL Oz, MC Marks, AR Burkhoff, D
Heerdt PM, Markov NP: Time dependence of halothane effects on left ventricular contractility: Evidence for anesthetic-induced myocardial remodeling (abstract). Anesthesiology 2003; 99:A-725Heerdt, PM Markov, NP