Companrson of Cardiac Output Responses to 2 , 4 - Dinitrophenol - Induced Hypermetabolism and Muscular Work

INTRODUCTION The principal factor initiating increased cardiac output during exercise, the "work stimulus," still is not fully understood (1). Both mechanical and metabolic factors have been identified with the "work stimulus." The former have been related to the stimulation of mechanical sensory receptors inside the muscles or tendons, and This work was presented in part at the Annual Meeting of the American Federation for Clinical Research in Atlantic City, N. J., 29 April 1973. Dr. Liang was a recipient of a National Institutes of Health Special Research Fellowship (1 F3 HL 52986). Received for publication 18 January 1973 and in revised form 5 April 1973. the latter to metabolic changes that occur in exercising muscles. In this study, dogs were infused with 2,4-dinitrophenol (DNP)1 to produce tissue hypermetabolic changes fundamentally like those that occur in exercise but not associated with muscular movement. The cardiac output responses to DNP infusion and exercise were compared to assess the relative contributions of mechanical and metabolic factors in the regulation of cardiac output. The rate of oxygen consumption was taken as the index of tissue metabolism. In addition, concentrations of lactate and pyruvate in arterial blood were measured. A change in the lactateto-pyruvate ratio indicates the presence or absence of tissue hypoxia (2), and its correlation with cardiac output provides an estimate of the role of anaerobic tissue metabolism in the cardiac output response to tissue hypermetabolism. METHODS Studies were performed on 22 healthy dogs of both sexes weighing between 14 and 33 kg. Anesthesia was induced with vaporized methoxyflurane, (Penthrane, Abbott Laboratories, North Chicago, Ill.) followed by intravenous chloralose (60 mg/kg). The trachea was cannulated with a T tube connected to a Benedict-Roth metabolic spirometer to record the rate of oxygen consumption. A femoral artery and the right ventricle were cannulated and connected to pressure transducers and a Sanborn 7700 recorder (HewlettPackard Co., Waltham Div., Waltham, Mass.) to measure blood pressures and heart rate. Another catheter was inserted into a carotid artery and connected to a Gilford Colson 103 densitometer (Gilford Instrument Laboratories, Inc., Oberlin, Ohio) to determine cardiac output (3) with indocyanine green (Cardio-Green, kindly supplied by Hynson, 1Abbreviations used in this paper: DNP, 2,4-dinitrophenol; LIP, lactate to pyrqva;e; PC, phosphorylcreatine; XL, excess lactate. The Journal of Clinical Investigation Volume 52 September 1973*2283-22922283 Downloaded from http://www.jci.org on October 21, 2017. https://doi.org/10.1172/JCI107416