Letters to the Editor: Letter to the Editor
To the Editor
In a recent paper, Bulte et al.1 described studies in healthy humans to determine the effect of general anesthesia with sevoflurane on the myocardial hyperemia (an index of coronary flow reserve [CFR]) induced by an IV infusion of adenosine. The authors reported that sevoflurane anesthesia caused a 36% decrease in the myocardial hyperemia. An analysis of their data indicates that the decrease in the hyperemic response can be entirely explained by a proportional decrease in mean arterial blood pressure, i.e., perfusion pressure, which was caused by adenosine during sevoflurane anesthesia. It is standard to evaluate CFR using an intracoronary infusion of a vasodilating drug such as papaverine or the reactive hyperemic response (the transient increase in blood flow that follows an interval of arterial occlusion) to avoid systemic hemodynamic effects.2,3 If either of these approaches was used by Bulte et al.,1 no change in the hyperemic response would have been evident. Bulte et al.1 also reported that sevoflurane was a coronary vasodilator in the human subjects of their study which confirmed previous findings in canine models.4,5
The physiological significance of a reduced CFR was not addressed by Bulte et al.1 and requires comment. Myocardial oxygen uptake is determined by coronary blood flow and myocardial oxygen extraction. Since oxygen extraction is nearly maximum at rest, increases in myocardial oxygen uptake are dependent on essentially proportional increases in coronary blood flow.6 Thus, one might conclude that a reduced CFR would necessarily render the myocardium more vulnerable to ischemia when faced with an augmented cardiac workload. This is the case when the reduced CFR is due to the metabolic vasodilation that accompanies a coronary stenosis or a reduced arterial oxygen (O2) content, e.g., hypoxemia or hemodilution.2,3 However, it would not be the case when the reduced CFR is the result of pharmacological vasodilation. This situation is characterized by “luxuriant perfusion” leading to a concomitant reduction in O2 extraction.7 A consequence is the establishment of an O2 extraction reserve that can offset a blunted blood flow response during an increased myocardial O2 demand.
Studies in animal models have demonstrated that a decreased CFR can have important adverse effects on the regional distribution of myocardial blood flow.8 For example, when the CFR is normal, severe tachycardia is accompanied by a transmurally uniform increase in myocardial blood flow, but when CFR is limited, only mild tachycardia may produce subendocardial ischemia. This effect would be relevant regardless of the etiology of the decreased CFR.
Bulte et al.1 obtained measurements of myocardial blood flow using myocardial contrast echocardiography. They validated this technique in a previous study by demonstrating a good correlation to results obtained with positron emission tomography.9
Although the myocardial contrast echocardiography technique would appear to have clinical value in the diagnosis and management of coronary artery disease, its investigatory potential will be realized only if it is applied to thoughtfully conceived and well-designed studies of coronary physiology, pathophysiology, and pharmacology.
George J. Crystal PhD, FAHA
Department of Anesthesiology
Advocate Illinois Masonic Medical Center
1. Bulte CS, Slikkerveer J, Kamp O, Heymans MW, Loer SA, de Marchi SF, Vogel R, Boer C, Bouwman RA. General anesthesia with sevoflurane decreases myocardial blood volume and hyperemic blood flow in healthy humans. Anesth Analg. 2013;116:767–74
2. Bradley AJ, Alpert JS. Coronary flow reserve. Am Heart J. 1991;122:1116–28
3. Crystal GJ, Kim SJ, Salem MR. Right and left ventricular O2
uptake during hemodilution and beta-adrenergic stimulation. Am J Physiol. 1993;265:H1769–77
4. Bernard JM, Wouters PF, Doursout MF, Florence B, Chelly JE, Merin RG. Effects of sevoflurane and isoflurane on cardiac and coronary dynamics in chronically instrumented dogs. Anesthesiology. 1990;72:659–62
5. Crystal GJ, Zhou X, Gurevicius J, Czinn EA, Salem MR, Alam S, Piotrowski A, Hu G. Direct coronary vasomotor effects of sevoflurane and desflurane in in situ canine hearts. Anesthesiology. 2000;92:1103–13
6. Feigl EO. Coronary physiology. Physiol Rev. 1983;63:1–205
7. Crystal GJ, Downey HF, Bashour FA. Small vessel and total coronary blood volume during intracoronary adenosine. Am J Physiol. 1981;241:H194–201
8. Marcus ML. Transmural distribution of myocardial perfusion. The Coronary Circulation in Health and Disease. 1983 New York, NY McGraw-Hill:337–47
9. Vogel R, Indermühle A, Reinhardt J, Meier P, Siegrist PT, Namdar M, Kaufmann PA, Seiler C. The quantification of absolute myocardial perfusion in humans by contrast echocardiography: algorithm and validation. J Am Coll Cardiol. 2005;45:754–62