reply: We thank Dr. Munis for his letter (2) concerning interpreting Guyton's model of the circulation. In our opinion, when considering Guyton's model, it is useful to distinguish three types of questions: *1*) Are the statements concerning the model mathematically correct?, *2*) Are the interpretations of the model legitimate?, and *3*) Is the model adequate to represent the cardiovascular system during hemorrhage, exercise, heart failure, etc.? We agree with much of the content of Dr. Munis's analysis, particularly his clarifications that right atrial pressure does not act to impede cardiac output. However, we take issue with his application of the concept of mean systemic pressure (P_{MS}). This is a concept that is accurately defined by Guyton's model but was illegitimately interpreted by Guyton to represent a driving pressure for cardiac output.

In Guyton's model, P_{MS} is the imaginary constant pressure that would exist after cardiac pumping has ceased and flow becomes zero everywhere in the circulation without a change in resistance or capacitance anywhere in the circuit. When there is blood flow, the P_{MS} pressure cannot be measured and exists only as an artifact of a mathematical model. It is an indication of how tightly the blood volume fills the capacitance of the systemic circulation. Simple manipulations of its definition allow us to derive equally valid mathematical expressions where flow is proportional to either +P_{MS} or −P_{MS}. [See *Eqs. A2* and *A3* in Beard and Feigl (1)]. It therefore is an error to infer from either of these expressions that P_{MS} is a physical force driving or impeding flow in the circuit.

We agree with Dr. Munis when he writes “P_{MS} does not change in an isovolumic situation.” However, we find his statement, “Similarly, the locus of P_{MS} in the veins remains isometric during steady-state flow and is constrained from moving blood,” difficult to interpret. There is no locus of P_{MS} when blood is flowing. It cannot be associated with a physical entity or force when blood is flowing.

Remember that the Guyton model only pertains to the steady state when by definition venous return equals cardiac output. The famous Guyton equation for cardiac output flow (F) during steady state [*Eq. A2* in Beard and Feigl (1)]
_{50-RA} is the associated effective resistance. This statement is mathematically correct and serves as a definition for R_{50-RA}, just as *Eq. 1* serves as the definition of R_{VR}. However, neither *Eq. 1* nor *Eq. 2* illustrates the cause of cardiac output, which is determined by the pressure and flow the left ventricle develops that results in a cardiac output via the input impedance of the systemic circulation.

Dr. Munis equates peripheral venous pressure with P_{MS} in the last sentences of his letter (2) and in his *Eq. 2*. This is also the claim in his clinical paper where he suggests that venous pressure measured in the hand or arm is proposed as a substitute for P_{MS} [Munis et al. (3)]. For all the reasons given above, neither the Guyton nor the Munis model justifies equating peripheral venous pressure with P_{MS}. While it is true that clinicians may use the height of the jugular venous pulse as an indication of the blood volume status of the patient, this needs to be used with other observations and judgment. The height of the jugular pulse may vary without an alteration in blood volume, notably by a change in cardiac output. (An elevated jugular venous pulse is often an indication of low cardiac output).

In summary, most students, physiologists, and physicians intuitively understand that in heart failure, blood tends to dam up at the right atrial inlet side of the cardiac pump. It only takes a little more thought to recognize the opposite; that is, right atrial pressure will tend to fall if cardiac output increases. What actually happens during exercise, postural changes, heat stress, hemorrhage, etc., is more complicated than simple series models of the systemic circulation can reveal.

Many commentaries over several decades have demonstrated that the Guyton model generates more confusion than clarity. It is time to stop teaching the Guyton model with its associated misinterpretations.

## DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the author(s).

## AUTHOR CONTRIBUTIONS

D.A.B. and E.O.F. drafted, edited, and revised manuscript, and E.O.F. approved final version of manuscript.

- Copyright © 2013 the American Physiological Society