Effect of Anesthesia on Cerebral Tissue Oxygen and Cardiopulmonary Parameters in Rats

Liu, Ke Jian; Hoopes, P. Jack; Rolett, Ellis L.; Beerle, Brion J.; Azzawi, Ali; Goda, Fuminori; Dunn, Jeff F.; Swartz, Harold M.

doi:10.1007/978-1-4615-5865-1_5

Cited by 32 publications

(20 citation statements)

References 9 publications

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“…Alveolar air contains 14% O 2 , arterial O 2 concentration is 12%, venous O 2 levels are 5.3%, and mean tissue O 2 concentration is 3% (Guyton and Hall, 1996). In mammalian brain, interstitial tissue O 2 levels range from ϳ1 to 5% Liu et al, 1997;Tammela et al, 1997). Data gathered from extensive sampling suggest that mean brain O 2 levels in adult rat and fetal sheep are 1.6% (Koos and Power, 1987;Silver and Erecinska, 1988).…”

Section: Lowered Oxygen Cultures Favor Proliferation and Survival Of mentioning

confidence: 99%

Enhanced Proliferation, Survival, and Dopaminergic Differentiation of CNS Precursors in Lowered Oxygen

et al. 2000

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Standard cell culture systems impose environmental oxygen (O 2 ) levels of 20%, whereas actual tissue O 2 levels in both developing and adult brain are an order of magnitude lower. To address whether proliferation and differentiation of CNS precursors in vitro are influenced by the O 2 environment, we analyzed embryonic day 12 rat mesencephalic precursor cells in traditional cultures with 20% O 2 and in lowered O 2 (3 Ϯ 2%). Proliferation was promoted and apoptosis was reduced when cells were grown in lowered O 2 , yielding greater numbers of precursors. The differentiation of precursor cells into neurons with specific neurotransmitter phenotypes was also significantly altered. The percentage of neurons of dopaminergic phenotype increased to 56% in lowered O 2 compared with 18% in 20% O 2 . Together, the increases in total cell number and percentage of dopaminergic neurons resulted in a ninefold net increase in dopamine neuron yield. Differential gene expression analysis revealed more abundant messages for FGF8, engrailed-1, and erythropoietin in lowered O 2 . Erythropoietin supplementation of 20% O 2 cultures partially mimicked increased dopaminergic differentiation characteristic of CNS precursors cultured in lowered O 2 . These data demonstrate increased proliferation, reduced cell death, and enhanced dopamine neuron generation in lowered O 2 , making this method an important advance in the ex vivo generation of specific neurons for brain repair. Key words: CNS precursors; CNS stem cells; dopaminergic neurons; erythropoietin; oxygen; Parkinson's diseaseCultured CNS stem cells have proved useful in defining the pathways that lead to generation of neurons and glia (McKay, 1997). These cells self-renew, and after mitogen withdrawal, differentiate into neurons, astrocytes and oligodendrocytes in predictable proportions (Johe et al., 1996;McKay, 1997). Single extrinsic factors can shift the fate of CNS stem cells toward specific cell lineages (Johe et al., 1996;Panchision et al., 1998). The potential therapeutic application of CNS stem cells in common degenerative and ischemic diseases has become a major focus of research. The generation of dopaminergic neurons from CNS precursors is of special interest given the promising results of fetal cell transplantation in patients with Parkinson's disease (Olanow et al., 1996; Piccini at al., 1999;Freeman et al., 2000).In clinical settings, gases are appreciated as primary variables in organ survival, with O 2 as the critical gas parameter. However, traditional CNS stem cell culture (as well as virtually all other ex vivo cell culture) is performed in nonphysiologically high O 2 . Standard tissue culture incubator conditions are 5% CO 2 and 95% air, which exposes cells to a 20% O 2 environment. In mammalian brain, interstitial tissue O 2 levels range from ϳ1 to 5% (Table 1). We tested the effects of culturing CNS progenitor cells in physiological "lowered" (3 Ϯ 2%) O 2 , comparing the cultures with those grown in the usual 20% O 2 . Our results indicate that oxygen lowere...

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Section: Lowered Oxygen Cultures Favor Proliferation and Survival Of mentioning

confidence: 99%

Enhanced Proliferation, Survival, and Dopaminergic Differentiation of CNS Precursors in Lowered Oxygen

et al. 2000

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“…We anticipate that the full exploitation of this capability, however, will require the widespread availability of in vivo EPR in the clinical setting. In the meantime, of course, this technique is already being applied increasingly widely in vivo in experimental pharmacology for uses including: tracers of the distribution, metabolism, and excretion of paramagnetically tagged drugs 28,91 following the state of systems such as liposomes; 92 monitoring the distribution and status of NMR contrast agents; 21,[93][94][95][96] determining the occurrence of free radical intermediates of drugs and potential toxins; 97,98 determining the effects of anesthetics on pO 2 in the brain; [99][100][101] following the stability of spin traps and their adducts in vivo, 5,102 following the distribution and valence state of chromium in vivo, [103][104][105] and following the effect of drugs on the pH in the stomach. 106 …”

Section: Strategy For the Long-term Development Of Clinical Applicatimentioning

confidence: 99%

Clinical applications of EPR: overview and perspectives

et al. 2004

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The development and use of in vivo techniques for strictly experimental applications in animals has been very successful, and these results now have made possible some very attractive potential clinical applications. The area with the most obvious immediate, effective and widespread clinical use is oximetry, where EPR almost uniquely can make repeated and accurate measurements of pO 2 in tissues. Such measurements can provide clinicians with information that can impact directly on diagnosis and therapy, especially for oncology, peripheral vascular disease and wound healing. The other area of immediate and timely importance is the unique ability of in vivo EPR to measure clinically significant exposures to ionizing radiation 'after-the-fact', such as may occur due to accidents, terrorism or nuclear war. There are a number of other capabilities of in vivo EPR that also potentially could become extensively used in human subjects. In pharmacology the unique capabilities of in vivo EPR to detect and characterize free radicals could be applied to measure free radical intermediates from drugs and oxidative process. A closely related area of potential widespread applications is the use of EPR to measure nitric oxide. These often unique capabilities, combined with the sensitivity of EPR spectra to the immediate environment (e.g. pH, molecular motion, charge) have already resulted in some very productive applications in animals and these are likely to expand substantially in the near future. They should provide a continually developing base for extending clinical uses of in vivo EPR. The challenges for achieving full implementation include adapting the spectrometer for safe and comfortable measurements in human subjects, achieving sufficient sensitivity for measurements at the sites of the pathophysiological processes that are being measured, and establishing a consensus on the clinical value of the measurements.

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“…When no noise is present, the errors in linewidth are caused by the imperfections of the model (i.e., how rapidly the residual R, Eq. [9], approaches zero within the interval to be fit). Contributions of other factors, such as "wrap-around" effects discussed in (19), are negligible for the spectra shown in Fig.…”

Section: Effects Of Noise and The Interval To Be Fitmentioning

confidence: 95%

“…The estimate given by [9] shows that when the difference in linewidths between the "broadening" functions f (b) and f (a) is small, then the residual R is given by a convolution of the spectrum J…”

Section: Figmentioning

confidence: 99%

“…LiPc is a particularly attractive probe for EPR oximetry because its CW EPR spectrum is very narrow (with a peak-to-peak ∼30-mG linewidth in the absence of oxygen), the spectrum is modeled well by a Lorentzian function, and the response to oxygen is a linear function of pO 2 (3). In recent years EPR oximetry with LiPc has been applied to study the effects of various anesthetics on brain oxygenation (5,(9)(10)(11) and the effects of a hemoglobin shifter on cerebral pO 2 under baseline conditions and after acute hemorrhage (12,13). Recently this technique was utilized in the study of acute cerebral ischemia and reperfusion, induced by selective reversible unilateral occlusion of the middle cerebral artery of the rat brain.…”

Section: Introductionmentioning

confidence: 99%

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