From a cardio-vascular reserve hypothesis to a proposed measurable index: A pilot empirical validation

Background: Cardiovascular reserve index (CVRI) was previously proposed as an estimate of the assumed (momentary) cardiovascular reserve as a function of stroke volume (SV), systemic vascular resistance (SVR), respiratory rate (RR) and body surface area (BSA). Conversion through conventional hemodynamic equations reveals an equivalent, simpler, vital signs based function. We evaluated the association between CVRI and diverse conditions along the hemodynamic spectrum. Methods: CVRI was retrospectively computed for each subject of 3 existing patient databases. 1) Acute severe hospital admissions [N = 333] classified by disease course to: “shock on arrival”, “developing shock” and “non-shock”. 2) Heart failure (HF) patients [N = 71] classified by HF severity to: mild, moderate and severe HF. 3) Cardio-pulmonary exercise testing (CPX) [n = 387] classified by exercise capacity (EC) to: normal, mildly decrease, moderately decrease and severely decreased EC. CVRI association with these hemodynamic conditions was evaluated through ANOVA. Results: ‘Normal EC’ has the highest CVRI of 0.97 (0.88, 1.06), and in decreasing CVRI order ‘mildly decrease EC’, ‘moderately decrease EC’, ‘mild HF’ which was similar to ‘severely decrease EC’, ‘moderate HF’ which was similar to acute severe admission of ‘non-shock’, ‘severe heart failure’ which was similar to ‘developing shock’ and the lowest CVRI was observed in ‘shock on arrival’ with mean CVRI of 0.20 (0.19, 0.22), ANOVA p < 0.001. Conclusions: Mean CVRI exhibited consistent inverse association with the severity of the hemodynamic condition. However, CVRI clinical utility of an individual patient requires further studies

Effects of exercise training on quadriceps muscle gene expression in chronic obstructive pulmonary disease.

Exercise capacity and training response are limited in chronic obstructive pulmonary disease (COPD), but the extent to which this is related to altered skeletal muscle function is not fully understood. To test the hypothesis that muscle gene expression is altered in COPD, we performed needle biopsies from the vastus lateralis of six COPD patients and five sedentary age-matched healthy men, before and after 3 mo of exercise training. RNA was hybridized to Affymetrix U133A Genechip arrays. In addition, peak O(2) uptake and other functional parameters (e.g., 6-min walk) were measured before and after training. The 6-min walk test increased significantly following training in both groups (53.6 +/- 18.6 m in controls, P = 0.045; 37.1 +/- 6.7 m in COPD, P = 0.002), but peak O(2) uptake increased only in controls (19.4 +/- 4.5%, P = 0.011). Training significantly altered muscle gene expression in both groups, but the number of affected genes was lower in the COPD patients (231) compared with controls (573). Genes related to energy pathways had higher expression in trained controls. In contrast, oxidative stress, ubiquitin proteasome, and COX gene pathways had higher expression in trained COPD patients, and some genes (e.g., COX11, COX15, and MAPK-9) were upregulated by training only in COPD patients. We conclude that both COPD and control subjects demonstrated functional responses to training but with somewhat different patterns in muscle gene expression. The pathways that are uniquely induced by exercise in COPD (e.g., ubiquitin proteasome and COX) might indicate a greater degree of tissue stress (perhaps by altered O(2) and CO(2) dynamics) than in controls

Effects of exercise training on quadriceps muscle gene expression in chronic obstructive pulmonary disease

Exercise capacity and training response are limited in chronic obstructive pulmonary disease (COPD), but the extent to which this is related to altered skeletal muscle function is not fully understood. To test the hypothesis that muscle gene expression is altered in COPD, we performed needle biopsies from the vastus lateralis of six COPD patients and five sedentary age-matched healthy men, before and after 3 mo of exercise training. RNA was hybridized to Affymetrix U133A Genechip arrays. In addition, peak O(2) uptake and other functional parameters (e.g., 6-min walk) were measured before and after training. The 6-min walk test increased significantly following training in both groups (53.6 +/- 18.6 m in controls, P = 0.045; 37.1 +/- 6.7 m in COPD, P = 0.002), but peak O(2) uptake increased only in controls (19.4 +/- 4.5%, P = 0.011). Training significantly altered muscle gene expression in both groups, but the number of affected genes was lower in the COPD patients (231) compared with controls (573). Genes related to energy pathways had higher expression in trained controls. In contrast, oxidative stress, ubiquitin proteasome, and COX gene pathways had higher expression in trained COPD patients, and some genes (e.g., COX11, COX15, and MAPK-9) were upregulated by training only in COPD patients. We conclude that both COPD and control subjects demonstrated functional responses to training but with somewhat different patterns in muscle gene expression. The pathways that are uniquely induced by exercise in COPD (e.g., ubiquitin proteasome and COX) might indicate a greater degree of tissue stress (perhaps by altered O(2) and CO(2) dynamics) than in controls