Experimentally observed steady-state pO2 profiles in tissue slices can be described by a Michaelis-Menten oxygen consumption model. Calculated values for Km = 0., torr in brain tissue, and Km = 2.2 torr in liver tissue are two orders of magnitude higher than Km values determined from mitochondrial suspensions. Brain tissue has a higher metabolic rate and higher affinity for oxygen than liver tissue.

Animals↗

PubMedDate not supplied

Perceptual contributions to optimization of breathing.

Besides regulating the energetic cost of breathing, optimization of breathing may involve the alleviation of an uncomfortable breathing sensation. In this article, we consider perceptual contributions to the optimization of breathing. Just as the cost function proposed by Poon depends on ventilation and arterial PCO2 so does the sense of dyspnea. Consequently, we examined the relationship between breathing discomfort and Poon's cost function. Based on our model and psychophysical studies, it appears that breathing discomfort, which can integrate chemical and mechanical inputs to the respiratory controller, may not operate simply as an estimate of a cost function. We explain how our reflex control model can dynamically minimize a cost function such as Poon's. Also, we consider the influence of willful adjustments of ventilation on breathing discomfort. From this we infer that ventilatory optimization may emerge from automatic reflexes and behavioral responses that involve excitatory chemical and inhibitory neuromechanical feedbacks.

Dyspnea↗

PubMedDate not supplied

Dynamic model of oxygen transport for transcutaneous PO2 analysis.

A dynamic model of oxygen transport through the outer skin layers and a polarographic sensor was developed for the analysis of transcutaneous oxygen tension (tcPO2). It provides a basis for quantifying the factors that determine the relationship between tcPO2 and arterial oxygen tension (PaO2). Model simulations show the importance of stratum papillare metabolic oxygen consumption; the oxygen permeability of the skin relative to that of the sensor membrane and electrolyte; and temperature and the oxyhemoglobin dissociation curve. These simulations were consistent with experimental data obtained by using microcathode transcutaneous oxygen sensors, which were placed on the skin of 10 healthy adults. Furthermore, the model indicates that accurate evaluation of arterial oxygen tension by using transcutaneous measurements requires continuous estimation of skin perfusion. On the basis of tcPO2 measurements made during arterial occlusion, simulations indicate that quantitative evaluation of the metabolic oxygen consumption of the viable skin tissues is possible only when the oxygen permeabilities of the skin and sensor are known.

Adult↗

PubMedDate not supplied

Multimolecular process in a packed-bed immobilized enzyme reactor: numerical simulation and back-mixing effects.

In a previous report, we presented a new analytical model describing the performance of a packed-bed catalytic unit, where the reaction between two cosubstrates is catalyzed by an enzyme immobilized on a porous carrier. The model explicitly takes into account the changes in concentrations of both cosubstrates along the reactor, as well as the hydrodynamic regimen (i.e., back-mixing) prevailing in the packed bed. In the present report, and on the basis of the procedures developed, we present a detailed analysis of the performance of the reactor. With numerical simulations, the effects of internal diffusion limitations, the depth of the pores, the substrates' concentration in the feed, and kinetic parameters are evaluated. Particular attention is also given here to the back-mixing effects prevailing in the reactor. An experimental procedure for assessing their extent is described.

Catalysis↗

PubMedDate not supplied

Single cell model for simultaneous drug delivery and efflux.

Multidrug resistance (MDR) of some cancer cells is a major challenge for chemotherapy of systemic cancers to overcome. To experimentally uncover the cellular mechanisms leading to MDR, it is necessary to quantitatively assess both drug influx into, and efflux from, the cells exposed to drug treatment. By using a novel molecular microdelivery system to enforce continuous and adjustable drug influx into single cells by controlled diffusion through a gel plug in a micropipet tip, drug resistance studies can now be performed on the single cell level. Our dynamic model of this scheme incorporates drug delivery, diffusive mixing, and accumulation inside the cytoplasm, and efflux by both passive and active membrane transport. Model simulations using available experimental information on these processes can assist in the design of MDR related experiments on single cancer cells which are expected to lead to a quantitative evaluation of mechanisms. Simulations indicate that drug resistance of a cancer cell can be quantified better by its dynamic response than by steady-state analysis.

Animals↗

PubMedDate not supplied

Role of O2 in regulation of lactate dynamics during hypoxia: mathematical model and analysis.

The mechanistic basis of the relationship between O2 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 O2 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, O2, 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 in the 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 O2 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 O2 concentration, without affecting muscle respiration (Um,O2) significantly. However, a small decrease in Um,O2 (1%-2%) can result in a large increase in LA production (50%-100%). The cellular rate of oxygen consumption, Um,O2, which is coupled 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 O2 concentration, it is indirectly affected by Um,O2, through changes in ADP/ATP, and NADH/NAD. Arterial LA concentration (Ca,LA) follows the pattern of change of muscle LA concentration (Cm,LA). Nevertheless, changes in Ca,LA, due to Cm,LA, are unlikely to be detected experimentally because changes in Cm,LA are small relative to the total LA concentrations in other tissues.

Adenosine Triphosphate↗

PubMedDate not supplied

A theoretical basis for assessing pulmonary membrane transport. Continuous CO monitoring during a single-breath maneuver.

Explore the source record for details and available documents.

Carbon Monoxide↗