To elucidate the mechanism of reduced exercise tolerance in the supine position, 14 patients with coronary artery disease were studied by both supine ergometer exercise and upright treadmill exercise. Maximal oxygen consumption in the supine position amounted to 80% of that in the upright position (1110 ± 453 vs 1387 ± 470 ml/min; p < 0.001). Maximal cardiac output was identical in both positions (12.07 ± 4.44 vs 12.55 ± 4.49 l/min; ns). Maximal arteriovenous oxygen difference in the supine position amounted to 83% of that in the upright position (9.22 ± 1.92 vs 11.14 ± 1.88 vol%; p < 0.01). thus, the lower maximal oxygen consumption in the supine position was not caused by the decreased cardiac output but by the impaired augmentation of arteriovenous oxygen difference. Lactate concentration at the same oxygen consumption was higher in the supine position, which means early augmentation of anaerobic metabolism. We concluded that the aerobic capacity in the supine position was significantly lower than that in the upright position in patients with coronary artery disease, and the impaired utilization of transported oxygen was considered to be one of the mechanisms of the decreased aerobic capacity in the supine position.
Addition of fibroblast growth factor (FGF) to quiescent cultures of Swiss 3T3 cells rapidly induced diacylglycerol formation, protein kinase C activation and Ca 2+ mobilization. Protein kinase C‐activating agents such as 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) and 1‐oleoyl‐2‐acetylglycerol (OAG) mimicked the action of FGF and stimulated DNA synthesis in the presence of insulin. Prolonged treatment of the cells with phorbol‐12,13‐dibutyrate (PDBu) led to the down‐regulation and complete disappearance of protein kinase C. In these cells, TPA and OAG did not induce DNA synthesis any more. FGF still elicited Ca 2+ mobilization and DNA synthesis, but the magnitude of DNA synthesis was reduced to almost half as compared with that in the control cells. These results clearly indicate that both diacylglycerol and Ca 2+ may serve as second messengers for FGF and suggest that these messengers may be involved in the mitogenic action of this growth factor.
To elucidate the effect of aging on respiratory muscle function, the authors performed respiratory muscle function tests in 116 normal subjects. Respiratory muscle function was evaluated with maximal expiratory mouth pressure at the TLC level (PEmax) and maximal inspiratory mouth pressure at the RV level (PImax). PEmax and PImax in both sexes showed significant correlations with age. PEmax in males was significantly higher than that in females (123.6 +/- 29.7 cmH2O and 79.0 +/- 21.1 cmH2O, p less than 0.01, respectively). PImax in males was also significantly higher than that in females (98.4 +/- 26.0 cmH2O and 71.9 +/- 26.4 cmH2O, p less than 0.01, respectively). PEmax correlated significantly with TLC, and PImax showed a significant inverse correlation with RV/TLC. Furthermore, there was a significant inverse correlation between RV/TLC and age. Our data suggest that inspiratory muscle weakness in aging may be responsible for the increase in RV/TLC.
Summary: To clarify the role of coronary responses to nitroglycerin (NTG) in relieving myocardial ischemia, we examined the effects of NTG in canine models of dynamic and fixed coronary stenoses. Application of coronary stenosis in the proximal left circumflex artery decreased resting coronary blood flow by ×40% and caused a significant depression of left ventricular (LV) dP/dt. During fixed coronary stenosis created with an externally applied constrictor device, intravenous NTG, 5 μg/kg, reduced mean aortic pressure by 12 ± 1.1 mm Hg (mean ± SEM, p < 0.01) and coronary blood flow by 9 ± 1.0% (p < 0.01) but did not affect stenosis resistance and LV dP/dt. During dynamic coronary stenosis produced with an intraluminal microballoon occluder, intravenous NTG caused a marked increase in coronary blood flow by 40 ± 8.3% (p < 0.01) and a decrease in stenosis resistance by 62 ± 9.3% (p < 0.01), as compared with postocclusion values, concomitant with a significant improvement in LV dP/dt. Intracoronary infusion of NTG, 1.0 μg/kg/min, had few systemic and coronary hemodynamic effects during fixed coronary stenosis, whereas intracoronary NTG increased coronary blood flow and reduced stenosis resistance, depending on its dose, during dynamic coronary stenosis. These results indicate that NTG is capable of increasing coronary blood flow and alleviating myocardial ischemia due to direct stenosis-dilating effects related to the vasomobility of the coronary stenosis.
