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Titolo:
ROLE OF O-2 IN REGULATION OF LACTATE DYNAMICS DURING HYPOXIA - MATHEMATICAL-MODEL AND ANALYSIS
Autore:
CABRERA ME; SAIDEL GM; KALHAN SC;
Indirizzi:
RAINBOW BABIES & CHILDRENS HOSP,RBC-380N,11100 EUCLID AVE CLEVELAND OH 44106 CASE WESTERN RESERVE UNIV,DEPT BIOMED ENGN CLEVELAND OH 44106 CASE WESTERN RESERVE UNIV,DEPT PEDIAT CLEVELAND OH 44106
Titolo Testata:
Annals of biomedical engineering
fascicolo: 1, volume: 26, anno: 1998,
pagine: 1 - 27
SICI:
0090-6964(1998)26:1<1:ROOIRO>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELLULAR-ENERGY METABOLISM; CRITICALLY ILL PATIENTS; HUMAN SKELETAL-MUSCLE; OXIDATIVE-PHOSPHORYLATION; QUANTITATIVE-EVALUATION; ANAEROBIC THRESHOLD; HUMAN BIOENERGETICS; LACTIC-ACIDOSIS; LIVER-GLYCOGEN; LEG EXERCISE;
Keywords:
HYPOXIA; METABOLIC CONTROL; ENERGY METABOLISM; CRITICAL O-2; O-2 SENSITIVITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
48
Recensione:
Indirizzi per estratti:
Citazione:
M.E. Cabrera et al., "ROLE OF O-2 IN REGULATION OF LACTATE DYNAMICS DURING HYPOXIA - MATHEMATICAL-MODEL AND ANALYSIS", Annals of biomedical engineering, 26(1), 1998, pp. 1-27

Abstract

The mechanistic basis of the relationship between O-2 and lactate concentration in muscle is not fully understood. Although hypoxia can cause lactate (LA) accumulation, it is possible for LA accumulation to occur without hypoxia. Nevertheless, during conditions of low O-2 availability, blood and tissue LA accumulation are used as indicators of hypoxia. To provide a framework for analyzing changes in energy metabolism and its regulation, we developed a mathematical model of human bioenergetics that links cellular metabolic processes to whole-body responses. Our model is based on dynamic mass balances and mechanistic kinetics in muscle, splanchnic and other body tissues for many substrates (glycogen, glucose, pyruvate, LA, O-2, CO2, etc.) and control metabolites (e.g., ATP) through coupled reaction processes. Normal substrate concentrations in blood and tissues as well as model parameters are obtained directly or estimated indirectly from physiological observation inthe literature. The model equations are solved numerically to simulate substrate concentration changes in tissues in response to disturbances. One key objective is to examine and quantify the mechanisms that control LA accumulation when O-2 availability to the muscle is lowered. Another objective is to quantify the contribution of different tissues to an observed increase in blood lactate concentration. Simulations of system responses to respiratory hypoxia were examined and compared to physiological observations. Model simulations show patterns of change for substrates and control metabolites that behave similarly to those found experimentally. From the simulations, it is evident that a large decrease can occur in muscle O-2 concentration, without affecting muscle respiration (U-m,U-O2) significantly. However, a small decreasein U-m,U-O2 (1%-2%) can result in a large increase in LA production (50%-100%). The cellular rate of oxygen consumption, U-m,U-O2, which iscoupled to ATP formation and NADH oxidation, can regulate other processes (e.g., glycolysis, pyruvate reduction) with high sensitivity through its effects on ADP/ATP and NADH/NAD. Thus, although LA metabolism does not depend directly on O-2 concentration, it is indirectly affected by U-m,U-O2, through changes in ADP/ATP, and NADH/NAD. Arterial LA concentration (C-a,C-LA) follows the pattern of change of muscle LA concentration (C-a,C-LA). Nevertheless, changes in C-a,C-LA, due to C-m,C-LA, are unlikely to be detected experimentally because changes in C-m,C-LA are small relative to the total LA concentrations in other tissues. (C) 1998 Biomedical Engineering Society. [S0090-6964(98)00201-X].

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Documento generato il 01/04/20 alle ore 11:27:46