We thank the authors for their thoughtful letter and informative review regarding the effects of anesthesia on the cardiovascular system.  This previous work using animal models has been foundational in framing our understanding of arterial physiology and the effects of anesthetic agents. Our omission of these previous works in our recently published review on aortic biomechanics was not meant to diminish their importance.  Rather, the purpose of our review was to focus on concepts related to the material properties of the aorta itself in health, disease, surgery, and anesthesia, and to propose that local aortic changes may have both physiologic and clinical ramifications through the aorta’s relationship with the heart and distal arteries.

Certainly, the previous studies highlighted by Dr. Pagel et al., using a three-element Windkessel model in animals, have provided important details on the effects of anesthesia on aortic biomechanics. But we respectfully submit that it may not tell the whole story. First, compliance, as calculated in the Windkessel model, is total arterial compliance, not exclusively aortic.  The contribution of small arteries to compliance is considerable and, in humans, increases with age-related aortic stiffening, thereby “blurring the distinction between large and small artery function.”  As such, the described changes to compliance from the Windkessel model likely cannot be attributed to the aortic biomechanical properties alone. Second, we disagree with the contention that characteristic aortic impedance is “the resistance of the aorta itself.” Although aortic impedance has the units of resistance, it exists only with pulsatile flow and pressure and is a function of the modulus of elasticity and radius.3  Similar to compliance, there is no exact anatomical aortic correlate to aortic impedance, although it characterizes the vessel in close proximity to the measurement. Therefore, although we agree that left ventricular afterload can be modeled using the Windkessel, we believe that aortic biomechanics as defined by the authors is only partly responsible.

Aortic biomechanics, at the level of local aortic microstructure and mechanical behavior, has until now been limited to bench-top testing on excised tissue. With recent advancements in imaging technology, there are new opportunities to explore the aorta in vivo and hopefully gain new insights into local aortic biomechanical properties in the clinical anesthesia environment. As we assert in our review, this work has yet to be done.

Our understanding of cardiovascular physiology has greatly benefitted from the previous scientific work of Dr. Pagel and others who have published using similar arterial system models. They have put together much of the puzzle as it pertains to anesthesia and cardiovascular physiology. We believe that the additional perspectives on aortic biomechanics described in our review hold potential to add a piece to said puzzle, not replace it altogether.