Theoretical analysis of effects of blood substitute affinity and cooperativity on organ oxygen transport

2002 ◽  
Vol 93 (6) ◽  
pp. 2122-2128 ◽  
Author(s):  
Mahendra Kavdia ◽  
Roland N. Pittman ◽  
Aleksander S. Popel

Hemoglobin-based O2carriers (HBOCs), which are developed as an alternative to blood transfusion, provide O2 delivery. At present, there is no model to predict the O2 transport for a red blood cell-HBOC mixture on a whole organ basis. On the basis of the first principles of mass balance, a model of O2 transport for an organ was derived to calculate venous Po 2(PvO2 ) for a given inlet arterial Po 2 (PaO2 ), blood flow, and oxygen consumption. The model was validated by using several in vivo animal studies on HBOC administration for a wide range of HBOC oxygen-binding parameters and predicted PvO2 for various PaO2 in the same species. The model was also used to predict the effect of HBOC affinity and cooperativity on PvO2 for humans. The results indicate that PvO2 can be increased at a constant blood flow-to-oxygen consumption ratio by reducing the affinity of HBOC for normoxia and mild hypoxia; however, a high-affinity HBOC would be more efficient in maintaining higher PvO2 for severe hypoxia (PaO2 < 40 Torr).

2004 ◽  
Vol 286 (2) ◽  
pp. C457-C463 ◽  
Author(s):  
David J. Marcinek ◽  
Kenneth A. Schenkman ◽  
Wayne A. Ciesielski ◽  
Kevin E. Conley

The coupling of mitochondrial ATP synthesis and oxygen consumption (ratio of ATP and oxygen fluxes, P/O) plays a central role in cellular bioenergetics. Reduced P/O values are associated with mitochondrial pathologies that can lead to reduced capacity for ATP synthesis and tissue degeneration. Previous work found a wide range of values for P/O in normal mitochondria. To measure mitochondrial coupling under physiological conditions, we have developed a procedure for determining the P/O of skeletal muscle in vivo. This technique measures ATPase and oxygen consumption rates during ischemia with 31P magnetic resonance and optical spectroscopy, respectively. This novel approach allows the independent quantitative measurement of ATPase and oxygen flux rates in intact tissue. The quantitative measurement of oxygen consumption is made possible by our ability to independently measure the saturations of hemoglobin (Hb) and myoglobin (Mb) from optical spectra. Our results indicate that the P/O in skeletal muscle of the mouse hindlimb measured in vivo is 2.16 ± 0.24. The theoretical P/O for resting muscle is 2.33. Systemic treatment with 2,4-dinitrophenol to partially uncouple mitochondria does not affect the ATPase rate in the mouse hindlimb but nearly doubles the rate of oxygen consumption, reducing in vivo P/O to 1.37 ± 0.22. These results indicate that only a small fraction of the oxygen consumption in resting mouse skeletal muscle is nonphosphorylating under physiological conditions, suggesting that mitochondria are more tightly coupled than previously thought.


1992 ◽  
Vol 3 (4) ◽  
pp. 193-201 ◽  
Author(s):  
George G Zhanel ◽  
Daryl J Hoban ◽  
Godfrey KM Harding

Antimicrobial activity is not an ‘all or none’ effect. An increase in the rate and extent of antimicrobial action is usually observed over a wide range of antimicrobial concentrations. Subinhibitory antimicrobial concentrations are well known to produce significant antibacterial effects, and various antimicrobials at subinhibitory concentrations have been reported to inhibit the rate of bacterial growth. Bacterial virulence may be increased or decreased by subinhibitory antimicrobial concentrations by changes in the ability of bacteria to adhere to epithelial cells or by alterations in bacterial susceptibility to host immune defences. Animal studies performed in rats, hamsters and rabbits demonstrate decreased bacterial adherence, reduced infectivity and increased survival of animals treated with subinhibitory antimicrobial concentrations compared to untreated controls. The major future role of investigation of subinhibitory antimicrobial concentrations will be to define more fully, at a molecular level, how antimicrobials exert their antibacterial effects.


1982 ◽  
Vol 2 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Myron D. Ginsberg ◽  
Alan H. Lockwood ◽  
Raul Busto ◽  
Ronald D. Finn ◽  
Cathy M. Butler ◽  
...  

A simplified mathematical model is described for the measurement of regional cerebral blood flow by positron emission tomography in man, based on a modification of the autoradiographic strategy originally developed for experimental animal studies. A modified ramp intravenous infusion of radiolabeled tracer is used; this results in a monotonically increasing curvilinear arterial activity curve that may be accurately described by a polynomial of low degree (= z). Integrated cranial activity C̄ B is measured in regions of interest during the latter portion of the tracer infusion period (times T1 to T2). It is shown that [Formula: see text] where each of the terms A x is a readily evaluated function of the blood flow rate constant k, the brain:blood partition coefficient for the tracer, the cranial activity integration limits T1 and T2, the coefficients of the polynomial describing the arterial curve, and an iteration factor n that is chosen to yield the desired degree of precision. This relationship permits generation of a table of C̄ B vs. k, thus facilitating on-line computer solution for blood flow. This in vivo autoradiographic paradigm was validated in a series of rats by comparing it to the classical autoradiographic strategy developed by Kety and associates. Excellent agreement was demonstrated between blood flow values obtained by the two methods: CBF in vivo = CBFclassical X 0.99 − 0.02 (units in ml g−1 min−1; correlation coefficient r = 0.966).


Zygote ◽  
2021 ◽  
pp. 1-7
Author(s):  
Maryam Mahaldashtian ◽  
Mohammad Ali Khalili ◽  
Fatemeh Anbari ◽  
Mohammad Seify ◽  
Manuel Belli

Summary Cell phones operate with a wide range of frequency bands and emit radiofrequency-electromagnetic radiation (RF-EMR). Concern on the possible health hazards of RF-EMR has been growing in many countries because these RF-EMR pulses may be absorbed into the body cells, directly affecting them. There are some in vitro and in vivo animal studies related to the consequences of RF-EMR exposure from cell phones on embryo development and offspring. In addition, some studies have revealed that RF-EMR from cellular phone may lead to decrease in the rates of fertilization and embryo development, as well as the risk of the developmental anomalies, other studies have reported that it does not interfere with in vitro fertilization or intracytoplasmic sperm injection success rates, or the chromosomal aberration rate. Of course, it is unethical to study the effect of waves generated from cell phones on the forming human embryos. Conversely, other mammals have many similarities to humans in terms of anatomy, physiology and genetics. Therefore, in this review we focused on the existing literature evaluating the potential effects of RF-EMR on mammalian embryonic and fetal development.


1998 ◽  
Vol 88 (3) ◽  
pp. 735-743 ◽  
Author(s):  
George J. Crystal ◽  
Xiping Zhou ◽  
Ramez M. Salem

Background Calcium produces constriction in isolated coronary vessels and in the coronary circulation of isolated hearts, but the importance of this mechanism in vivo remains controversial. Methods The left anterior descending coronary arteries of 20 anesthetized dogs whose chests had been opened were perfused at 80 mmHg. Myocardial segmental shortening was measured with ultrasonic crystals and coronary blood flow with a Doppler flow transducer. The coronary arteriovenous oxygen difference was determined and used to calculate myocardial oxygen consumption and the myocardial oxygen extraction ratio. The myocardial oxygen extraction ratio served as an index of effectiveness of metabolic vasodilation. Data were obtained during intracoronary infusions of CaCl2 (5, 10, and 15 mg/min) and compared with those during intracoronary infusions of dobutamine (2.5, 5.0, and 10.0 microg/min). Results CaCl2 caused dose-dependent increases in segmental shortening, accompanied by proportional increases in myocardial oxygen consumption. Although CaCl2 also increased coronary blood flow, these increases were less than proportional to those in myocardial oxygen consumption, and therefore the myocardial oxygen extraction ratio increased. Dobutamine caused dose-dependent increases in segmental shortening and myocardial oxygen consumption that were similar in magnitude to those caused by CaCl2. In contrast to CaCl2, however, the accompanying increases in coronary blood flow were proportional to the increases in myocardial oxygen consumption, with the result that the myocardial oxygen extraction ratio remained constant. Conclusions Calcium has a coronary vasoconstricting effect and a positive inotropic effect in vivo. This vasoconstricting effect impairs coupling of coronary blood flow to the augmented myocardial oxygen demand by metabolic vascular control mechanisms. Dobutamine is an inotropic agent with no apparent direct action on coronary resistance vessels in vivo.


1991 ◽  
Vol 179 (2) ◽  
pp. 954-961 ◽  
Author(s):  
Toshiyuki Arai ◽  
Kenjiro Mori ◽  
Shin-ichi Nakao ◽  
Koji Watanabe ◽  
Koichi Kito ◽  
...  

1981 ◽  
Vol 45 (1) ◽  
pp. 188-191 ◽  
Author(s):  
K.R Thulborn ◽  
J.C Waterton ◽  
G.K Radda

2021 ◽  
Vol 11 ◽  
Author(s):  
Ofentse Mazimba ◽  
Tebogo E. Kwape ◽  
Goabaone Gaobotse

: Indigenous and medicinal plants have proven crucial to the health of mankind for a very long time. Dichrostachys cinerea is a traditional herb used in the treatment of a variety of human diseases in African and Indian traditional medicine. This paper reviews the ethnomedicinal uses, phytochemical constituents, pharmacology and toxicity of D. cinerea, in order to provide scientific consensus for further research and exploitation of its therapeutic potential of this plant. Information was accessed by literature searches in different sources including Science direct, PubMed and Google Scholar. The findings of this review paper highlight D. Cinerea as an important component of African and Indian traditional medicine. D. cinerea is traditionally used in the treatment of rheumatism, diabetes, coughs, asthma, kidney disorders, gonorrhea, syphilis, malaria, tuberculosis, epilepsy, snake bites, pains, wounds, boils, burns, toothache, headache, and scabies. D. cinerea displays a diverse phytochemistry, with a wide range of isolated compounds that have well documented biological activities. D. cinerea has demonstrated both in vitro and in vivo biological activities. In vitro biological activities exhibited include enzyme inhibition, antibacterial, anti-fungal and anti-malarial activities. In vivo activities demonstrated by D. cinerea include anti-inflammatory, anti-diarrheal, anti-analgesic, hepatoprotective, anti-uro lithiatic, anti-lice, anti-dandruff and neuropharmacological activities. Animal studies have elucidated non-toxicity of D. cinerea for the ethanol root extract and methanol and water leaf extracts. It is vital that future studies on D. cinerea focus on the mechanisms of action behind these biological activities for both the crude extract and its individual chemical compounds. These studies could possibly lead to clinical trials to confirm biological activities found in animal studies. Further studies on multi-target network pharmacology, and molecular docking technology of D. cinerea sub fractions for enzyme inhibitions and neuropharmacological activities are of great importance and could accelerate the process of pharmaceutical development of this plant.


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