Response to ‘What makes the blood go around?’

We thank Dr Dalmau (2020) for taking an interest in our review (Joyce and Wang, 2020). As we emphasised in our article, Guyton's model notoriously polarises opinion (e.g. Brengelmann, 2006; Magder, 2006), and we appreciate the correspondent’s eagerness to foster continued scientific debate on the topic (e.g. Dalmau, 2017, 2018, 2019).The relative contribution of central (cardiac) and peripheral (vascular) factors in determining systemic blood flow has been discussed for more than a century and we dispute that it can or should be dismissed as a ‘false dichotomy’, but rather that this discussion continues to provide fundamental insight into the mechanisms that dictate and regulate convective oxygen transport. We do not accuse the critics of the Guyton model of dismissing the role of the peripheral vasculature, but argue that ‘cardio-centrism’ is an innate predisposition to regard the heart as the primary regulator of blood flow as opposed to a staunchly guarded ideology.Dalmau invokes Brengelmann's criticisms of the Guyton model, which emphasise the importance of the heart as a pump and label the view of mean circulatory filling pressure being a central driver for the circulatory system as a ‘fallacy’ (Brengelmann, 2006, 2016). However, Brengelmann's standpoint is far from universally accepted (Berger et al., 2016; Magder, 2006, 2016). Mean circulatory filling pressure, a key component in the classic Guytonian view of the circulation, provides the pressure gradient for venous return, and the heart can only pump the blood it receives. Clearly, this does not dismiss the importance of the pump function of the heart, but the contribution of the heart should be viewed as a ‘restorative’ force that refills the systemic vasculature (Magder, 2016).What is more difficult to reconcile is Dalmau's insistence that heart rate determines cardiac output, which (in a physiological sense) is incompatible with the overwhelming experimental evidence from cardiac pacing studies demonstrating that cardiac output does not change when heart rate is altered (e.g. Bada et al., 2012; Joyce et al., 2018). The heart can only deliver flow on the arterial side at a rate that equals venous return, and venous return is predominantly determined by vascular components. In this regard, we hold no ‘ambiguity’, despite concurring that systemic blood flow obviously is the product of heart rate and stroke volume in an algebraic sense.In conclusion, we are grateful for being able to clarify that we do not believe that critics of the Guyton model disregard the role of the peripheral vasculature in general. However, we, like others, believe there is merit in the classical Guytonian model that mean circulatory filling pressure, as determined by blood volume and compliance of the blood vessels (i.e. vascular capacitance), is an important driver of venous return, which in turn determines cardiac output. We also take the opportunity to emphasise that experimental data suggest heart rate per se does not determine systemic blood flow (cardiac output). Of course, ultimately, the operating cardiovascular system involves both cardiac and venous return functions.

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