What determines systemic blood flow in vertebrates?

Abstract

In the 1950s, Arthur C. Guyton removed the heart from its pedestal in cardiovascular physiology by arguing that cardiac output is primarily regulated by the peripheral vasculature. This is counterintuitive, as modulating heart rate would appear to be the most obvious means of regulating cardiac output. In this Review, we visit recent and classic advances in comparative physiology in light of this concept. Although most vertebrates increase heart rate when oxygen demands rise (e.g. during activity or warming), experimental evidence suggests that this tachycardia is neither necessary nor sufficient to drive a change in cardiac output (i.e. systemic blood flow, Q̇sys) under most circumstances. Instead, Q̇sys is determined by the interplay between vascular conductance (resistance) and capacitance (which is mainly determined by the venous circulation), with a limited and variable contribution from heart function (myocardial inotropy). This pattern prevails across vertebrates; however, we also highlight the unique adaptations that have evolved in certain vertebrate groups to regulate venous return during diving bradycardia (i.e. inferior caval sphincters in diving mammals and atrial smooth muscle in turtles). Going forward, future investigation of cardiovascular responses to altered metabolic rate should pay equal consideration to the factors influencing venous return and cardiac filling as to the factors dictating cardiac function and heart rate.

Dehydration reduces stroke volume and cardiac output during exercise because of impaired cardiac filling and venous return, not left ventricular function

“…According to this view, the lower peripheral blood flow and venous return occurring during prolonged exercise with dehydration and hyperthermia might be simply a consequence of the lower Q . An alternative interpretation is based upon the theory proposed more than half a century ago by Guyton (Guyton, 1967) that Q is largely unaffected by the activity of the heart, as discussed above in regard to cardiac pacing (Bada et al, 2012;Munch et al, 2014;Parker et al, 1971;Ross et al, 1965;Stein et al, 1966), and that venous return plays a central role in control of Q (Joyce and Wang, 2020). Our findings of regional beat volumes provide insight into whether venous return is compromised when peripheral blood flow is reduced with dehydration and hyperthermia.…”

“…Granting the possibility that the lower venous return might be simply a consequence of the lower Q cannot be ruled out, evidence from studies manipulating peripheral blood flow provides crucial insight into the alternative view that factors controlling the peripheral circulation largely determine the output of the heart (Furst, 2020;Guyton, 1967;Joyce and Wang, 2020). Human investigations using pharmacologically-induced limb vasoconstriction (via intra-arterial infusion of adenosine and the sympathomimetic agent tyramine, or the combined blockade of prostaglandins and nitric oxide using N G -monomethyl-L-arginine F I G U R E 7 Relationships between stroke volume and LV end-diastolic volume (a) and between LV end-diastolic volume and blood volume (b), head and forearms beat volume (c), or LV filling time (d) during prolonged exercise in the progressive dehydration and euhydration control trials.…”

Exercise heat acclimation has minimal effects on left ventricular volumes, function and systemic hemodynamics in euhydrated and dehydrated trained humans

“…According to classic models of cardiovascular control, HA could modulate cardiac function during exercise by altering preload, afterload, and/or intrinsic cardiac function (23). However, evidence directly supporting these mechanisms is limited.…”

Regulation of splenic contraction persists as a vestigial trait in white‐blooded Antarctic fishes

“…It is unlikely that splenic constriction can appreciably affect blood volume; in a C. aceratus weighing 1 kg, the relatively large spleen would typically weigh 3.69 g (Holeton, 1976) whereas the expected blood volume is approximately 75 ml (Hemmingsen & Douglas, 1970). Compared with the potential to regulate stressed blood volume by other means, e.g ., adjusting venous capacitance (Joyce & Wang, 2020; Sandblom et al ., 2009), the change that could be achieved by maximal constriction of the spleen would appear to be minor. Nevertheless, it may be worthwhile to determine if there is an effect of splenectomy on cardiac performance in icefish.…”