The proposed research will test the hypothesis that regulation of myocardial respiration in vivo is dependent on the developmental state of the heart. The existence of a maturational change in regulation is supported by published work from the principal investigator and others. However, the mechanisms through which oxidative phosphorylation are controlled remain undefined, and the developmental model will be useful in providing some clarifications.
Specific aims addressed are: 1. To test the hypothesis that regulation of myocardial respiration undergoes a maturational process that regulation is not dependent on the form of work stimulus in vivo. 2. To determine if maturation of respiratory control in vivo occurs at the level of coupling of the mitochondrial oxidation-reduction potential to phosphorylation of adenosine diphosphate. 3. To determine if developmental changes in regulation are due to maturational alterations in reducing equivalent delivery to the mitochondria. 4. To determine if the efficiency of oxidative phosphorylation is a function of the maturation. The primary tools of investigation will be 31phosphorous nuclear magnetic resonance spectroscopy with simultaneous measurement of oxygen consumption. In addition to providing some answers with regards to control of myocardial respiration, data provided in these studies should be applicable to the understanding and maintenance of developing myocardium.
| Portman, M A; Panos, A L; Xiao, Y et al. (1997) Influence of the pH of cardioplegic solutions on cellular energy metabolism and hydrogen ion flux during neonatal hypothermic circulatory arrest and reperfusion: a dynamic 31P nuclear magnetic resonance study in a pig model. J Thorac Cardiovasc Surg 114:601-8 |
| Portman, M A; Standaert, T A; Ning, X H (1996) Developmental changes in ATP utilization during graded hypoxia and reoxygenation in the heart in vivo. Am J Physiol 270:H216-23 |
| Portman, M A (1994) Measurement of unidirectional P(i)-->ATP flux in lamb myocardium in vivo. Biochim Biophys Acta 1185:221-7 |
| Portman, M A; Eyster, G E (1994) Myocardial buffering capacity and high-energy phosphate utilization during hypothermic circulatory arrest and recovery in the newborn lamb in vivo. J Thorac Cardiovasc Surg 108:946-52 |
