We thank Dr. Butterworth for his attention to our work.1He is correct: There is still confusion about the effects of α agonists on venous return. In fact, Dr. Butterworth’s letter is confusing. First, he refers to Yamazaki et al. ,2arguing that hypotension induced by spinal anesthesia and ganglionic blockade in dogs is “analogous to hypovolemia.” How could this be true? Clearly, the dogs are normovolemic; the arterial hypotension results mainly from vasodilation and redistribution of blood into the splanchnic vasculature. Hypovolemia, in contrast, empties the splanchnic reservoir. Yamazaki et al. 2show that α-adrenergic agonists increase venous return, which is exactly what we say in the sentence that Dr. Butterworth quotes from our article. He then refers to Supple et al. ,3whose study supports our viewpoint that α-adrenergic agonists can increase venous return. Indeed, the first two references offered by him to refute our position strongly support it.
Dr. Butterworth next cites Imai et al. ,4noting that α-adrenergic agonists decrease venous return, as is also stated in our article mentioning the same publication. The study by Imai et al. shows that methoxamine decreases venous return, but only at high doses. Dr. Butterworth does not mention that in dogs pretreated with a vasodilator, methoxamine increases venous return, ostensibly by reversing vasodilator-induced pooling of blood in the splanchnic vasculature, which again supports our position.
Then, Dr. Butterworth refers to his own study—and misquotes it.5In his letter, he writes, “we found that phenylephrine … decreased venous return.”5His article, however, states that phenylephrine “had no clear effect on reservoir volume.”5Besides, Dr. Butterworth et al. studied splenectomized dogs, which are likely to be hypovolemic because of the large blood volume removed with the spleen. They excluded two dogs because of “unexplained metabolic acidosis.” If splenectomy caused the hypovolemia, the “unexplained” becomes explicable, i.e. , metabolic acidosis from hypoperfusion. After reviewing Dr. Butterworth’s data, we understand a source of the confusion. Phenylephrine decreased mean reservoir volume in the highest-dose group but not in the lower-dose groups.5The difference was not statistically significant, in part because of the more variable responses among dogs given high-dose phenylephrine. Ironically, Dr. Butterworth’s data support our view that both the dose of α agonist and the degree of hypovolemia determine the net effect of α agonists on venous return.
Dr. Butterworth refers to three more studies6–8to prove that low doses of α-adrenergic agonists decrease venous return. However, in each study, the α agonist increased blood pressure and decreased heart rate, reflecting a baroreflex response. Baroreceptor activation itself dilates splanchnic veins, shifts blood into the splanchnic vasculature, and decreases venous return.9,10The authors of one study7admit that their observation “does not necessarily conflict with the findings that α-receptor stimulation can also result in increased venous return” (page 527). The final reference that Dr. Butterworth cites11shows that α agonists increase venous reservoir volume, reinforcing our position that α agonists can increase venous return.
References 27 and 33–35 in our original article1provide support for our opinion. Many other studies support our position that α agonists can increase venous return12–17; some focus on the matter in dispute. Stokland et al. ,12using a model in which preload was controllable, showed that two thirds of the phenylephrine-induced increase in blood pressure resulted from increased preload, whereas only one third was from increased peripheral vascular resistance. Richer et al. 13showed that low doses of α agonists increase venous return, whereas high doses decrease it, which directly conflicts with Dr. Butterworth’s viewpoint and affirms ours.
The basis for the confusion about α agonists lies in their abilities to constrict splanchnic preportal veins and hepatic resistance veins simultaneously. Constricting the former shifts splanchnic blood to the central circulation; constricting the latter impedes the shift. With high doses of α agonists, the effects on hepatic venous resistance can trap blood within the liver.4
Finally, we are happy to note that Dr. Butterworth’s letter closes by stressing a key message in our article, namely that “intense vasoconstriction can be detrimental … and should not be viewed as a substitute for the immediate replacement of blood volume.”1
* Brigham and Women’s Hospital, Boston, Massachusetts. email@example.com