Letter Regarding Article by Kaufmann et al, “Systemic Inhibition of Nitric Oxide Synthase Unmasks Neural Constraint of Maximal Myocardial Blood Flow in Humans”

Abstract

To the Editor: Kaufmann et al1 suggest that augmented adenosine flow with N G-monomethyl-l-arginine (L-NMMA) requires inhibition of CNS neuronal nitric oxide synthase (nNOS), increased cardiac sympathetic nerve stimulation, and β2-agonism of coronary arterioles because (1) heart transplant patients (n=6), assumed to be denervated, did not show similar increase and (2) patients given phenylephrine to raise arterial pressure to levels equivalent to those given L-NMMA plus adenosine also did not show increased myocardial blood flow (MBF). Sympathetic reinnervation is not only a function of time after transplantation, however. Depending on definitions of “early” versus “late,” evidence of sympathetic innervation may be present by 12 months2 and possibly sooner because it occurs in <1 year in animals. Accordingly, the principal conclusion of the study rests on a small sample and an assumption that may not be warranted. Moreover, cardiac sympathetic reinnervation occurs first over the anterobasal region of the left ventricle. Thus, MBF data analysis might have been better focused on that region rather than on the whole heart. In addition, data from the phenylephrine group are difficult to interpret because the authors suggest that α-adrenergic constriction limits the MBF response to adenosine. Thus, the use of an α-agonist to raise arterial pressure may …