Reply to “Letter to the editor: When what you see may not be what you get: prudent considerations of anesthetics for murine echocardiography”

reply: We thank Wu et al. (9) for an interesting and important letter, raising considerations for future directions for this work. We agree that you correctly point out that understanding the effects of anesthetics is a complex issue and simply analyzing left ventricular (LV) systolic function is not sufficient for a full understanding of this complex subject. In fact, the senior author on the current letter has been describing the effects on anesthetics on autonomic control as well as direct effects on LV function for over 40 years (1, 3–8) and the importance of studying cardiovascular control mechanisms in the conscious state not only because of the profound effects of anesthetics on LV function (1, 3, 6, 8) but also because of their profound effects on autonomic control (3–5, 7).

However, we respectfully disagree with one of the conclusions of the letter by Wu et al., i.e., that our “findings allow alternative interpretations.” It would be more correct to state that the current investigation is an important first step but that there is considerable further work required to understand the best anesthesia for more complicated experiments and surgeries and how autonomic mechanisms contribute to or modify the cardiac depression observed with anesthetic agents. This, however, does not mean that our study can be interpreted differently, since the goal of our study was simply to determine which anesthetics for routine echocardiographic studies in mice have the least negative effects on LV function, using echocardiography, compared with studies in the conscious state. It is well recognized that there are complex autonomic mechanisms that are elicited by all anesthetics, as noted above (1, 3–8), or that if an experiment calls for more measurements or surgery, other factors must be considered. Moreover, whether or not autonomic effects contribute to the overall effect of each anesthetic on LV function is important scientifically and a valid direction for future work. Therefore, any effect on mechanism of anesthetic effects on LV function does not affect the conclusions of our study, which simply defined the extent to which each anesthetic actually depresses LV function.

In summary, we believe that Wu et al. (9) correctly point out that anesthesia induces complex effects on the heart and circulation (1, 3–8) and that considerably more work is required to examine and quantitate all the mechanisms that contribute to the overall effect on LV function. However, these complex effects do not alter the conclusions of our study (2), which are based on the extent to which commonly used anesthetics for echocardiographic studies in mice depress LV function, as compared with data obtained on LV function in conscious, unanesthetized mice.

GRANTS

This work was supported by National Institutes of Health Grants 5P01AG027211, 1R01HL102472, 5T32HL069752, 5R01HL095888, 5P01HL069020, R01HL106511, R01HL093481, and 1R01HL119464.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the author(s).

AUTHOR CONTRIBUTIONS

R.E.P. drafted manuscript; S.F.V. and D.E.V. edited and revised manuscript; S.F.V., D.E.V., and R.E.P. approved final version of manuscript.