Venous return and the physical connection between distribution of segmental pressures and volumes.

More than sixty years ago, Guyton and coworkers related their observations of venous return to a mathematical model. Showing steady-state flow (F) as proportional to the difference between mean systemic pressure (Pms) and right atrial pressure (Pra), the model fit their data. The parameter defined by the ratio (Pms - Pra)/F, first called an "impedance," came to be called the "resistance to venous return." The interpretation that Pra opposes Pms and that, to increase output, the heart must act to reduce back pressure at the right atrium was widely accepted. Today, the perceived importance of Pms is evident in the efforts to find reliable ways to estimate it in patients. This article reviews concepts about venous return, criticizing some as inconsistent with elementary physical principles. After review of basic background topics-the steady-state vascular compliance; stressed versus unstressed volume-simulations from a multicompartment model based on data and definitions from Rothe's classical review of the venous system are presented. They illustrate the obligatory connection between flow-dependent compartment pressures and the distribution of volume among vascular compartments. An appendix shows that the pressure profile can be expressed either as decrements relative to arterial pressure or as increments relative to Pra (the option taken in the original model). Conclusion: The (Pms - Pra)/F formulation was never about Pms physically driving venous return; it was about how intravascular volume distributes among compliant compartments in accordance with their flow-dependent distending pressures, arbitrarily expressed relative to Pra rather than arterial pressure.

Open-loop (feed-forward) and feedback control of coronary blood flow during exercise, cardiac pacing, and pressure changes.

A control system model was developed to analyze data on in vivo coronary blood flow regulation and to probe how different mechanisms work together to control coronary flow from rest to exercise, and under a variety of experimental conditions, including cardiac pacing and with changes in coronary arterial pressure (autoregulation). In the model coronary flow is determined by the combined action of a feedback pathway signal that is determined by the level of plasma ATP in coronary venous blood, an adrenergic open-loop (feed-forward) signal that increases with exercise, and a contribution of pressure-mediated myogenic control. The model was identified based on data from exercise experiments where myocardial oxygen extraction, coronary flow, cardiac interstitial norepinephrine concentration, and arterial and coronary venous plasma ATP concentrations were measured during control and during adrenergic and purinergic receptor blockade conditions. The identified model was used to quantify the relative contributions of open-loop and feedback pathways and to illustrate the degree of redundancy in the control of coronary flow. The results indicate that the adrenergic open-loop control component is responsible for most of the increase in coronary blood flow that occurs during high levels of exercise. However, the adenine nucleotide-mediated metabolic feedback control component is essential. The model was evaluated by predicting coronary flow in cardiac pacing and autoregulation experiments with reasonable fits to the data. The analysis shows that a model in which coronary venous plasma adenine nucleotides are a signal in local metabolic feedback control of coronary flow is consistent with the available data.

A critical analysis of the view that right atrial pressure determines venous return.

A. C. Guyton pioneered major advances in understanding cardiovascular equilibrium. He superimposed venous return curves on cardiac output curves to reveal their intersection at the one level of right atrial pressure (Pra) and flow simultaneously consistent with independent properties of the heart and vasculature. He showed how this point would change with altered properties of the heart (e.g., contractility, sensitivity to preload) and/or of the vasculature (e.g., resistance, total volume). In such graphical representations of negative feedback between two subdivisions of a system, one input/output relationship is necessarily plotted backward, i.e., with the input variable on the y-axis (here, the venous return curve). Unfortunately, this format encourages mistaken ideas about the role of Pra as a "back pressure," such as the assertion that elevating Pra to the level of mean systemic pressure would stop venous return. These concepts are reexamined through review of the original experiments on venous return, presentation of a hypothetical alternative way for obtaining the same data, and analysis of a simple model.