Allometric scaling of the parameters characterizing venous return surface in the generalized framework of circulatory equilibrium

Abstract

Study objective: In the generalized framework of circulatory equilibrium (GCE), the integrated cardiac output (CO) curve characterizes the pumping abilities of the left and right hearts, whereas the venous return (VR) surface characterizes the preloading properties of the systemic and pulmonary circuits. Equilibrium CO (= VR), left (PLA) and right (PRA) atrial pressures are predicted from the intersection between the CO curve and VR surface. In VR surface, VR is theoretically related with stressed blood volume (V), PLA and PRA as: VR =V/W − Gs × PRA − Gp × PLA, where Gs and Gp is a ratio of systemic (Cs) and pulmonary (Cp) vascular compliance to W (time constant of the systemic and pulmonary circuits), respectively. However, there was a concern whether the standard parameters can be applicable to animals with different body size including human. The objective of this study is to experimentally investigate whether an allometric scaling of the parameters (Gs, Gp, W, Cs, Cp) of the VR surface is feasible. Hypothesis: Kleiber’s law indicates that an animal's metabolic rate scales to the 3⁄4 power of the animal's body weight (BW). Based on this, we hypothesize that Cs and Cp may be proportionate to BW, W may be proportionate to BW1/4. Hence, Gs and Gp may be proportionate to BW3/4. Methodology: Seven mongrel dogs (BW 26±2.8 kg) and 4 beagles (BW 9±0.5 kg) were anesthetized, and their left and right hearts were replaced by dual mechanical pumps. While V was kept constant, by controlling the speed of the fluid pumps, VR (ml/min), PLA and PRA (mmHg) were changed variably over a wide range to obtain six sets of VR, PLA and PRA. After the change of a known amount of V (4 mL/kg), six sets of VR, PLA and PRA were obtained in a similar manner. Using 12 sets of VR, PLA and PRA, we obtained Gs, Gp, W, Cs, and Cp using regression analysis in each animal. Finally, we analyzed relations between BW and all these parameters using regression analysis over the 11 animals. Data: Gs (r2=0.73, p value for independent variable piv<0.01; p value for intercept, pi=0.57) and Gp (r2=0.81, piv<0.01, pi=0.64) were proportionate to BW3/4. Cs (r2=0.37, piv=0.027, pi=0.40) and Cp (r2=0.61, piv<0.01, pi=0.48) were proportionate to BW. However, W (r2=-0.11, piv=0.90, pi=0.17) was not associated with BW1/4. Summary of results: All parameters characterizing VR surface except for W were significantly associated with BW. W did not show a significant association with BW, potentially due to the low variations of BW. Conclusions: Allometric scaling of VR surface may be feasible and effective in future clinical application of GCE. NTT Research, Inc. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.