The goal of this project is to study the effects of exercise on the lung circulation. Maximal exercise makes extraordinary demands on the lung, including more than 5-fold increases in blood flow, 20-fold increases in ventilation, and concomitant increases in pulmonary vascular pressure and fluid filtration. Despite these demands, the normal lung continues to exchange gas, stay dry, and permit flow at pressure attainable by the right ventricle. On the other hand, in the presence of heart disease and some lung diseases, and in normals at high altitude or at maximal exhaustive effort, exertion can be associated with pressure and flow exceeding cardiopulmonary capacity, resulting in pulmonary edema. Thus the study of exercise is pertinent to the understanding of cardiopulmonary function both in health and disease. The general hypotheses to be tested are that capillary pressure is higher than previously suspected during exercise, that the hyperpnea of exercise causes extraordinarily fast clearance of filtered microvascular fluid, that surface area, the bronchial circulation, and augmented lymphatic function contribute to the high flow of lung lymph in exercise. Sheep will be instrumented for on-line measurement of pulmonary arterial, balloon occlusion, wedge, microwedge, and left atrial pressures and lung lymph flow, and will be trained to trot to maximal effort on a treadmill. Some sheep will have left atrial balloon catheters placed in order to vary pulmonary microvascular pressure and some will have pleural balloons and have endotracheal tubes to alter and measure ventilation. Preliminary studies have shown the feasibility of these methods in both transient and steady-state exercise, during hypoxic vasoconstriction and with infusion of PGH2 analog and isoproterenol. In paired studies, each important variable influencing pressure, flow, and lymph clearance will be measured in exercise and then altered to determine its relative role in the marked changes in lung function that occur with exercise. The hypotheses to be tested represent a departure from current concepts of the physiology of exercise and the resulting information should enlarge our understanding of how the lung circulation functions.
| Bjertnaes, L J; Koizumi, T; Newman, J H (1998) Inhaled nitric oxide reduces lung fluid filtration after endotoxin in awake sheep. Am J Respir Crit Care Med 158:1416-23 |
| Kane, D W; Tesauro, T; Koizumi, T et al. (1994) Exercise-induced pulmonary vasoconstriction during combined blockade of nitric oxide synthase and beta adrenergic receptors. J Clin Invest 93:677-83 |
| Newman, J H; Cochran, C P; Roselli, R J et al. (1993) Pressure and flow changes in the pulmonary circulation in exercising sheep: evidence for elevated microvascular pressure. Am Rev Respir Dis 147:921-6 |
| Kane, D W; Tesauro, T; Newman, J H (1993) Adrenergic modulation of the pulmonary circulation during strenuous exercise in sheep. Am Rev Respir Dis 147:1233-8 |
