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Biomedical subjects

C Barlow

Publications and source records attributed to C Barlow.

63 records · Page 4Linked to original sources

Visualization of the distance between perfusion and anoxia along an ischemic border.

The distance between perfusion and anoxia was measured on the border of an experimental ischemic area in the rabbit heart. Reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography was used to detect myocardial anoxia. Fluorescein angiography marked areas of myocardial perfusion. The hearts were isolated, perfused with a hemoglobin-free solution and performed no external work. In all hearts there was a narrow band between areas of perfusion and anoxia that measured 329 +/- 42 mu (mean +/- SD). The transition from minimal to full NADH fluorescence was abrupt, less than 80 mu. We conclude that the normoxic/anoxic transition is sharp, and the gap between perfusion and anoxia is narrow along an ischemic border in the isolated heart performing no external work. These data suggest that in the vivo working heart the gap between perfusion and anoxia would be even narrower.

Animals↗

Heterogeneity of oxygen delivery in normoxic and hypoxic states: a fluorometer study.

An on-line, real-time histogram display of heterogeneity of oxygen delivery to perfused and in situ organs is afforded by a flying-spot fluorometer that provides excitation for either oxidized flavoprotein of the mitochondrial space or reduced pyridine nucleotide of mitochondrial and cytosolic spaces. Emission from the two fluorochromes is acquired at 10(4) to 10(5) data points/s and histograms of the fluorescence intensity versus the number of occurrences of that intensity are displayed at 1--10 times per second. The histograms show alterations of the intensity and of the degree of heterogeneity of the redox states of perfused heart with model coronary occlusion, of perfused and in situ rat liver, and of rat and gerbil models of stroke. The percentage change of oxygen delivery to the intracellular space can be calculated from the areas under the histogram.

Brain↗

Heterogeneity of the hypoxic state in perfused rat heart.

Tissue oxygen gradients were examined in the saline-perfused rat heart by NADH fluorescence photography. In high flow hypoxia, where the coronary flow was maintained and the arterial oxygen tension was gradually reduced, oxygen extraction was virtually complete before oxygen consumption was significantly diminished. Inadequate oxygen delivery resulted in a well defined pattern of anoxic zones. The anoxic zones were several hundred microns in width, an order of magnitude greater than intercapillary distances. In low flow hypoxia (ischemia), where the arterial oxygen tension remained at its control value and the coronary flow was diminished, anoxic zones also developed, following the same pattern as in high flow hypoxia. However, in ischemia, the anoxic areas developed while the effluent oxygen tesion was significantly greater than zero. Whereas respiratory acidosis between pH 7.3 and 6.9 resulted in vasodilation, below PH 6.8 there was a marked increase in vascular resistance. Anoxic zones appeared despite only a slight change in effluent oxygen tension from the control. In high flow hypoxia, ischemia, and acidosis-induced ischemia, the anoxic zones disappeared when control perfusion conditions were restored. The data demonstrate that tissue oxygen gradients are very steep in the hypoxic state, so that ischemia and hypoxia result in discrete heterogeneous areas of anoxic tissue bounded by sharp areas where the oxygen supply is sufficient to maintain normal mitochondrial oxidative function. In these states in which oxygen delivery is less than oxygen demand, coronary perfusion appears to be regulated at the level of the arterioles rather than the capillaries.

Animals↗

Phosphorus nuclear magnetic resonance studies on normoxic and ischemic cardiac tissue.

The intact heart of a young rat was excised rapidly and cooled to 0 degree C; its energy-rich compounds were examined by 31P Fourier Transform nuclear magnetic resonance. The heart showed the characteristic spectrum of sugar phosphates, inorganic phosphate, phosphocreatine, and magniesium phates, inorganic phosphate, phosphocreatine, and magnesium ATP, characteristics of the energizing state of the nonbeating tissue. Warming to 30 degrees C imposes an energy load upon the heart consistent with short-term resumption of beating, concomitant intracellular acidosis, and decomposition of all detectable energy-rich compounds. The intracellular acidity causes a shift from pH 7.0 to 6.0. The effects of possible interferences with this pH measurement are considered. The method appears to have wide usefulness in cardiac infarct models for detecting the fraction of the total volume occupied by the infarct and for studying the effect of various proposed therapies upon this infarcted volume.

Adenosine Triphosphate↗

A comparison of thyroid function in DBA/2J and C57BL/6J mice.

DBA/2J mice exhibit audiogenic seizure susceptibility (AGSS) and lower electroshock seizure thresholds compared with C57BL/6J mice. Thyroid function, including thyroxine (T4), 3,5,3'-triiodothyronine (T3), and thyrotropin (TSH) concentrations, T4/T3 ratio, and iodide uptake, of DBA and C57 mice were compared. Thyroid function was also assessed in relation to AGSS and severity in DBA mice. DBA mice have a larger thyroidal pool of iodide due to increased iodide uptake and possibly decreased release, but not to an increased organification rate. This increased iodide uptake exists until about 40 days of age. DBA mice also have a decreased radiochloride space and increased thyroid weight, indicative of enhanced TSH activity. The DBA mice show high T4 and TSH concentrations and a high T4/T3 ratio between the ages of 20 and 40 days. Beginning at 40 days of age the DBA mice have high T4, TSH, and T3 concentrations leading to a T4/T3 ratio approximating the C57 ratio. At any age, DBA mice demonstrating clonic/tonic seizures in response to auditory stimulation have hormone concentrations similar to their 21-day-old counterparts with seizures. Mice that show decreased response to auditory stimulation have hormone concentrations similar to the older age group. The increased thyroid activity of DBA mice is the result of enhanced TSH secretion. The increased TSH production is due to adaptations corresponding to the different age and AGSS. A decreased conversion of T4 to T3 by 3,3,5'-monodeiodinase, is responsible for the increase in TSH due to loss of T3 negative feedback on the anterior pituitary gland. By 40 days of age, the Type I 5'-deiodinase matures whereas the brain deiodinase activity remains subnormal.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Control of energy production in cardiac muscle: effects of ischemia in acidosis.

Evidence is summarized indicating that mitochondrial respiration and citric acid cycle activity in the intact heart are controlled by the cytosolic phosphate potential and mitochondrial NAD oxidation-reduction state. Data are presented showing that the effect of respiratory acidosis is greater than that of metabolic acidosis in inhibiting left ventricular pressure development in the perfused rat heart, because of a greater fall of intracellular pH under the former conditions. Respiratory acidosis is shown to be readily associated with tissue hypoxia as a result of an increased vascular resistance and diminished flow rate through the coronary circulation. In nonischemic respiratory acidosis, the rate of ATP production is well balanced by the rate of ATP utilization, and tissue ATP and creatine-P levels remain approximately normal. Partially ischemic respiratory acidosis was associated with low tissue levels of ATP and creatine-P and high tissue levels of lactate and NADH. Ischemic areas with sharp border zones were visualized during and after an abrupt decrease of perfusion fluid pH by directly photographing NADH fluorescence from the surface of perfused hearts. Reversal of the hypodynamic state with partially ischemic respiratory acidosis could not be achieved by augmenting the coronary flow by means of an external pump. The demonstration of the existence of sharp zones of high pyridine nucleotide fluorescence adjacent to normal zones indicates a great heterogeneity of coronary perfusion and the existence of steep oxygen gradients in the intact heart.

Acidosis↗