Summary of poster session I, ISOTT symposium

MKROVASCULAR

RESEARCH

Summary

(1977)

13,421X24

of Poster

Current

Session

Problems

I, ISOTT

in Tissue

Symposium’

Oxygenation

JOSE STRAUSS* AND LEENA MELA? *Department of Pediatrics, University of Miami School of Medicine, Miami, Florida 33152, and 7Harrison Department of Surgical Research, University of Pennsylvania Medical School, Philadelphia, Pennsylvania 19104

Received October 22, 1976

This summary highlights papers about five major areas which were presented and discussedin ISOTT Poster Session 1: efficiency of hemoglobin and other O,-carrying systems,organ blood flow and its regulation, techniques for determination of tissue oxygenation, enzyme adaptation in systemic hypoxia, and prevention or decreaseof the detrimental tissue effectsof ischemia. 1.

EFFICIENCY

OF

HEMOGLOBIN

AND OTHER O,-CARRYING SYSTEMS

The capacity of red blood cells to release 0, was studied in nonacidotic diabetic patients (Ditzel et al., Aalborg, Denmark, Abstract 1768).Despite increased 2,3-DPG levels, the PsO of the oxyhemoglobin dissociation curve was found to be decreased when compared with controls. Plasma inorganic phosphate and P,, were increased after the oral administration of disodium ethane-1-hydroxy- 1,I-diphosphonate (EHDP). Since the level of plasma inorganic phosphate was found to be markedly elevated after administration of EHDP, it was concluded that this elevation improves the defect in the O,-release capacity of red blood cells in diabetic patients. The effect of chronic administration of sodium cyanate on 0, releaseto tissue was studied in rats (Turek et al., Nijmegen, The Netherlands, Abstract 1764).A shift to the left in the oxyhemoglobin dissociation curve was induced by this procedure; in addition, venous blood PO,, A - Vo, difference, and arterial and venous pH all were higher in the hypoxic cyanate-treated animals than in the hypoxic controls. It was concluded that artificial left-shifting of the oxyhemoglobin dissociation curve seemsto be desirable under conditions of severehypoxia. Advantages of blood substitutes over that of whole blood, under certain conditions, were reported by two groups. One (Messmer et al., Munich, Germany, Abstract 1763) presented evidence for improved muscle oxygenation and O,-extraction ratio from RBC-Hb by pyridoxylation of stroma-free hemoglobin. The other (Doss et al., Little Rock, Ark., and New Orleans, La., Abstract 1751) evaluated the effect of replacing 5 ml of CSF with oxygenated fluorocarbon emulsion in hypoxic cats; it was concluded that the presenceof oxygenated fluorocarbons reduced the fall in cerebral TPo2. 1 Anaheim Symposium, International Society on Oxygen Transport to Tissue, April 1I-16,1976. 421 ISSN 0026-2862

Copyright 0 1977 by Academic Press, Inc. All rights of reproduction in any form reserved. Printed in Great Britain

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2. ORGAN BLOOD FLOW AND ITS REGULATION

Histograms of both microflow (hydrogen gasclearance)and tissuePO, were evaluated (Skolasinska et al., Dortmund, Germany, Abstract 1754) as indicators of beating cat heart microflow and 0, supply, respectively, under hyperoxic and hypoxic conditions. Both histograms were found to be reliable methods for assessmentof regulation of microflow and tissue 0, supply. The carotid body tissue PO, during high arterial blood PO, was studied (Acker and Lubbers, Dortmund, Germany, Abstract 1769) for its meaning as the autoregulator of the carotid body; it was shown that the main factor is the local distribution of microcirculatory flow. Autoregulation of coronary flow was dealt with (Schubert and Whalen, Cleveland, Ohio, Abstract 1759)by a mathematical model which led to the postulate that 0, distribution is under active control and that , 5 mm Hg) are an essentialfeature of this system. local hypoxic areas(P,,, < Redistribution of microcirculation was reviewed (Krumme and Kessler, Dortmund, Germany, Abstract 1771)and evaluated as a new and meaningful principle of regulation. Studies in rat liver suggestedthat a nonhomogeneous distribution of capillary length may induce a nonhomogeneous pattern of microcirculation. Further, the studies suggestedthat hypoxic hypoxia may causea redistribution of microcirculation in an attempt to improve the 0, utilization from the high venous reserve found normally. There was a decreasemainly at sitesof high microflow; this decreasewas accompanied by an increasein the areasof low microflow when norepinephrine was added to hypoxic hypoxia. Redistribution of microcirculation seemsto be a well-documented principle of regulation. The role of local hyperemia and metabolic demands as factors controlling tissue oxygenation in the cat brain (Dorson and Bogue, Tempe, Ariz., Abstract 1776) and cat intestine (Mortillaro and Granger, Mobile, Ala. and Jackson, Miss., Abstract 1767)was emphasized.Rapidly changing arterial blood PO, elicited tissue adjustments including rapid diffusional transfer, local hyperemia, and metabolic conservation of Po2. Under certain conditions, duration of local arterial occlusion in the cat intestine correlated well with intensity and duration of the reactive hyperemia. Venous occlusion was followed only by weak reactive hyperemia. Intercapillary distance in the left ventricle of the cat and dog heart was found to be shorter and 0, consumption was higher than in the right ventricle (Honig and Henquell, Rochester, N.Y., Abstract 1765). Sinceintracellular PO, seemsto be the samein both ventricles, it was suggestedthat local tissue PO, controls precapillary sphincters and that intracellular PO, is a regulated variable. 3. TECHNIQUES FOR DETERMINATION OF TISSUE OXYGENATION

Continuous measurement of 0, availability by O2 wire electrodes in rabbit brain during acute hypoxia, cat brain during chronic hypoxia, and rabbit kidney during hemorrhagic shock did not correlate well with changes in central arterial or venous blood pressure, or with arterial blood PO, (Baker et al., Miami, Fla, and Irvine, Calif., Abstract 1750). The role of local homeostatic adjustments witheither increasedblood flow or oxygen release,or decreasedO2 utilization was emphasized.Thus, the importance of direct 0, tissue measurementsis obvious.

ISOTT POSTER SESSION 1

423

The fluorescence enhancement of pyridine nucleotide signals and of flavoprotein signals at low temperatures (<-loo”) was utilized (Chance et al., Philadelphia, Pa., Abstract 1757) as a ratio method in brain and heart. The absenceof blood flow in the frozen tissue made the ffuorometric determination of trapped mitochondrial redox states free of the corrections needed at room temperature with circulating blood. Calibration for extremes of oxidized and reduced states of intact tissues was possible. The in situ fluorescencephotography of heart pyridine nucleotides was used (Barlow, Philadelphia, Pa., Abstract 1752) to determine the size of the ischemic area following occlusion of a coronary artery. A well-defined area of the myocardium distal to the silk ligature increased its fluorescence emission due to the higher NAD(P)H levels with local ischemia than with controls (anoxia, amytal infusion, or pentachlorophenol). Local brain surface fluorometry and uv reflectometry were measured in parallel (Gyulai et al., Budapest, Hungary, Abstract 1749)to record changesin pyridine nucleotide redox state and brain blood content. Electrical stimulation of the brain cortex induced an increasein tissue blood content greater than that of hypercapnia. The small vesselsseemedto be controlled mainly by changesin cortical neuronal activity and not by arterial blood Pco,. Contrary to other reports, no oxidation of NADH was observed during increased neuronal activity. Pyrenebutyric acid was usedasa fluorescent probe for intracellularP,,, determination in the cat cerebral cortex (Mitnick and Jobsis,Durham, N.C., Abstract 1756).Contrary to reports by several investigators using O2 electrodes, no values approaching zero were found. Much discussion was devoted to this point without satisfactory explanation as to the causeof these discrepancies. Oxygen-sensitive recessedmicroelectrodes were used in brain and liver slices to evaluate a classical passive diffusion model (Buerk and Longmuir, Cleveland, Ohio, and Raleigh, N.C., Abstract 1770).It was concluded that the observedgradients could not be explained by the classical respiratory model; also, that either a MichaelisMenten “saturation” model or a model incorporating a chemical reaction at low PO, would have to be present to explain the findings. Platinum microelectrodes were placed stereotactically in the globus pallidus and the globus striatum of rats exposed to hyperbaric O2 (Ogilvie et al., Charleston, SC., Abstract 1761).The Pazof globus pallidus readily rose while that of the globus striatum remained unchanged. After pretreatment with dibenzylene both areas’ PO, increased markedly. These findings led the authors to the conclusion that the differences in Po, are due to differencesin blood flow. Multiple 25-pm diameter platinum cathodes were used to measure surface hepatic PO, in rats with lethal intraabdominal sepsis (Rink et al., Louisville, KY., Abstract 1758). Hepatic oxygenation showed a consistent decreasewhich was initially gradual and precipitous after 2 hr of sepsis. Changes in the waveform of the evoked cortical somatosensory potential in the unrestrained rabbit was used to evaluate local cortical ischemia @ourgain et al., Brussels, Belgium, Abstract 1748). The first component of the wave (a subcortical component) was not affected while others disappeared completely or were decreased in size.

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4. ENZYME ADAPTATION IN SYSTEMIC HYPOXIA Further evidence for the adaptive enhancement of mitochondrial respiratory chain activity in hypoxia was presented(Mela et al., Philadelphia, Pa., Abstract 1755).These studies involved acute hypoxia in the rat and assaysin liver and heart mitochondria. The data suggeststhat the enhancementis controlled by dehydrogenaseactivity; more specifically, by succinic dehydrogenase. The level of P-450 in the endoplasmic reticulum of experimental animals’ hepatocytes was doubled after 2-3 hr at a simulated altitude of 12,000 ft (Longmuir and Pashko, Raleigh, N.C., Abstract 1753).Sincethe levels of P-450 correlate well with the levels of cytochrome P-450 it was assumed that the level of cytochrome P-450 also doubled. This finding supports the contention that cytochrome P-450 facilitates the diffusion of 02, especially during hypoxia. 5. PREVENTION OF DECREASE OF THE DETRIMENTAL TISSUE EFFECTS OF ISCHEMIA Oxidoreduction state, hemoglobin content, and blood flow after phenoxybenzamine treatment were evaluated in cat brain cortex during and after hemorrhagic shock and in controls (Kovach et al., Budapest, Hungary, Abstract 1762). Phenoxybenzaminetreated animals did not show the arterial blood pressure-dependentdecreasein brain blood flow or the reduction in brain NAD. The preservation of tissue oxygenation, seemedto be a direct result of pretreatment with phenoxybenzamine. The effect of intraluminal pressure and of administration of dextran 40 on bowel microcirculation and O2 supply was studied in rabbits (Thermann et al., Marburg/ Lahu, Germany, Abstract 1760). Increasing the intraluminal pressure significantly decreasedthe bowel surface PO*.Administration of dextran 40 basically reversed the decreasein local PO,. Since dextran 40 improved the 0, supply of distended bowel, it. was suggestedthat dextran 40 may be helpful in the treatment of ileus.