A Systems Model of the Effects of Pathological Alterations in Circulatory Dynamics on VO2 Kinetics

Abstract

Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are associated with slow pulmonary O2 uptake (VO2p) kinetics. Another feature of CHF is a long time-constant (t) for cardiac output (Qt) on transition to moderate exercise (Kemps et al. J Appl Physiol 105:1822-, 2008). In contrast, a high thoracic pressure during exercise in COPD constrains the Qt amplitude (ΔQt/ΔVO2p; Aliverti et al. Eur J Appl Physiol 95:229-, 2005). The influence of these pathological circulatory dynamics on muscle O2 consumption (VO2m) and its coupling to VO2p is not well known. PURPOSE: To develop a computational model to assess the influence of time- and amplitude-based alterations in Qt on gas exchange kinetics in health, CHF, and COPD. METHODS: Algorithms representing muscle and rest-of-body compartments were connected in parallel by arterial and venous circulations to a pulmonary compartment and a pump. Exercise-induced increases in VO2m (0.5-1.0 L.min-1) and Qt were confined to the muscle compartment. Starting values for tQt, tVO2m, and ΔQt/ΔVO2p in health (20s, 30s, 5), CHF (60s, 60s, 5) and COPD (50s, 60s, 4.5) were varied independently by ±5s, ±5s and ±0.5, respectively. Outputs were analysed for the minimum muscle-venous O2 content (CvO2m) and phase II tVO2p. RESULTS: A 0.5 L.min-1 increase in metabolic rate resulted in better tVO2p-tVO2m matching and higher CvO2m in health than in CHF (p<0.05) [mean, range]: 0.1 [-3.4, 4.6] vs -3.9 [-5.0, -2.6] s; and 30.4 [30.4, 30.4] vs 30.3 [27.9, 30.7] mL.L-1, respectively. In COPD, tVO2p-tVO2m matching was improved (-2.5 [-3.9, -0.8] s) but CvO2m reduced (15.1 [14.9, 15.3] mL.L-1) compared to CHF (p<0.05); differences that were widened at higher metabolic rates. CONCLUSIONS: Using available estimates for circulatory dynamics in CHF this model suggests that VO2m kinetics are slower than VO2p. This implies a close matching of tQt-to-tVO2m that helps to support CvO2m and capillary PO2 in the transient. In COPD, however, the low Qt amplitude exposes VO2m to kinetic limitation with only minor increments in tQt, metabolic rate or arterial hypoxemia. As such, VO2m appears more vulnerable to an O2 delivery limitation in COPD than CHF. This model predicts that, unlike in health, pathological alterations in circulatory adjustments modulate both muscle and pulmonary gas exchange kinetics.