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Biomedical subjects

F F Jöbsis

Publications and source records attributed to F F Jöbsis.

At least 19 recordsLinked to original sources
PubMed1986

Insufficient supply of reducing equivalents to the respiratory chain in cerebral cortex during severe insulin-induced hypoglycemia in cats.

The ability of endogenous substrates in brain to substitute for glucose as sources for energy metabolism during insulin-induced hypoglycemia was studied. The ratio of the arteriovenous difference of glucose to the arteriovenous difference of oxygen in the cerebral cortex was measured during progressive hypoglycemia in paralyzed, artificially ventilated cats that were anesthetized with pentobarbital sodium and nitrous oxide. The ratio did not change when blood glucose fell from a mean of 7.68 to approximately 2 mumol/ml. Below 2 mumol/ml the ratio decreased, indicating that substrates other than the glucose supplied by the blood were being utilized. In another series of experiments, changes in the redox state of respiratory chain NAD were monitored from the cerebral cortex using microfluorometry during the onset of hypoglycemia and the recovery. Hypoglycemia severe enough to produce isoelectric EEG was accompanied by an oxidation of NADH, demonstrating that the supply of reducing equivalents to the respiratory chain was decreased. Recovery from hypoglycemia, produced by intravenous glucose injections, was accompanied by an increase in blood glucose concentrations, the return of EEG activity, and a decrease in the NAD/NADH ratio. When blood glucose concentration reached 2.23 during the recovery, further increases in blood glucose had no effect on the redox state of NAD. Although alternative substrates appear to be utilized for energy metabolism during severe hypoglycemia, they cannot fully replace glucose as the source of reducing equivalent to the respiratory chain.

Animals↗
PubMed1983

In vivo comparison of cytochrome aa3 redox state and tissue PO2 in transient anoxia.

We have determined, in vivo and simultaneously, the tissue PO2 (Ptio2) and the oxidation-reduction (redox) state of cytochrome aa3 (cyt aa3) of cat cerebral cortex during and after a short period of N2 breathing. Thirteen cats were anesthetized, ventilated mechanically with room air, subjected to a limited bilateral craniotomy, and then injected with 25 mg/kg of pyrenebutyric acid (PBA) intravenously. Ptio2 was measured from PBA generated fluorescence, emitted by monitored cerebral cortical cells. The cyt aa3 redox state was measured from differential absorption of monochromatic light at 605 vs. 590 nm reflected from the same cortical cells. In response to a 1.5-min N2 ventilation (phase I) the increase in PBA fluorescence signal, indicating a decline in Ptio2, lagged behind the cyt aa3 reduction. When the animal was ventilated with room air (phase II), rapid reoxidation, followed by hyperoxidation of cyt aa3 occurred. The decrease in PBA fluorescence signal, indicating an increase in Ptio2, was seen to lag behind cyt aa3 reoxidation. These results indicate that hysteresis exists in the relation between Ptio2 and cyt aa3 redox state. This may be the result of the situation that 1) low tissue O2 concentration is partially compensated by accumulation of reduced cyt aa3, and 2) following brief periods of anoxia, the affinity of cyt aa3 to O2 is increased.

Animals↗
PubMed1983

Cytochrome a,a3 reoxidation. Early indicator of metabolic recovery from hemorrhagic shock in rats.

To assess the metabolic recovery of mitochondria after injury, we have monitored, in vivo and noninvasively, changes in the redox state of cytochrome (cyt) a,a3 in 35 rats after tissue hypoxia induced by rapid exsanguination to a mean arterial pressure of 30-35 mmHg. This level of mean arterial pressure was maintained for a shorter period of time in group I (n = 17) and a longer period of time in group II (n = 18), then the shed blood was returned by infusion. The surviving animals were observed for 2 more h before terminating the experiments. During exsanguination, reinfusion and recovery intervals brain tissue parameters of blood oxygenation, relative blood volume, and cyt a,a3 redox state were monitored continuously by spectrophotometry through the closed skull and intact skin. Group I had a high survival rate while group II had a very low survival rate. In both groups, with the onset of hypotension, there was a prompt rapid shift, followed by a slow continued progressive shift, of cyt a,a3 toward a more reduced state. The extent of recovery of cyt a,a3 following reinfusion was different in each group. In group I there was a rapid reoxidation of cyt a,a3 to a level above the base line (16 +/- 12%, mean +/- SEM). In contrast, the extent of reoxidation of cyt a,a3 in group II was significantly lower and stayed 31 +/- 6% below the base-line level. To further evaluate the mechanisms responsible for these observations, another related experiment was performed. 12 rats were subjected to shock and resuscitation as outlined for groups I and II. After death or killing of the animal, we measured, in vitro, oxygen consumption of cerebral cortical slices. Oxygen consumption of cortical tissue slices in subgroup I was significantly higher than in subgroup II. We conclude that, under these experimental conditions, the oxidative response of cyt a,a3 correlates closely with survival or death in the two groups. If in group I animals the greater oxidation of cyt a,a3, in vivo after resuscitation, reflects greater oxygen utilization, as is suggested by the in vitro observations in subgroup I, then we may be observing a useful adaptive response to tissue injury leading to preserved organ function and enhanced survival. Therefore, noninvasively measured cyt a,a3 redox state, reflecting intracellular metabolic activity, seems to indicate both the overall cerebral cellular response to injury and the likelihood of survival.

Animals↗
PubMed1983

Cyanide-induced cytochrome a,a3 oxidation-reduction responses in rat brain in vivo.

The sensitivity of the brain to cyanide-induced histotoxic hypoxia and the protective effects of known cyanide antagonists, have been assessed in vivo by reflectance spectrophotometry. Cyanide-related changes in cytochrome a,a3 (cytochrome c oxidase) oxidation-reduction (redox) state, tissue hemoglobin saturation, and local blood volume were continuously monitored in cerebral cortex of rats. Noncumulative, dose-dependent inhibition of the in situ mitochondrial respiratory chain was evaluated directly by measuring increases in reduction levels of the terminal oxidase. These transient cytochrome a,a3 reductions were accompanied by increases in regional cerebral hemoglobin saturation and blood volume. Cytochrome redox responses were not altered either in magnitude or kinetics by hyperoxia; however, the cyanide-cytochrome dose-response curve was greatly shifted to the right by pretreatment with sodium nitrite, and the recovery rate of cytochrome a,a3 from cyanide-induced reduction was enhanced fourfold by pretreatment with sodium thiosulfate.

Animals↗
PubMed1982

Exchange transfusion with Fluosol 43: in vivo assessment of cerebral cytochrome c oxidase redox state.

Rats were serially exchange transfused to hematocrits less than 2% (50-cc exchange) with either Krebs-Henseleit-albumin (KHA) solution or Fluosol-43 (F-43). Reflectance spectrophotometry was employed to monitor cerebral cytochrome c oxidase redox states. Determination of mean arterial pressure (MAP), arterial and venous oxygen content difference (A-VO2), and cerebral cortical ATP and lactate concentrations were also made. As hemodilution progressed, neither solution provided normal quantities of oxygen as evaluated by the cytochrome c oxidase redox state and a decrease in A-VO2 difference, although F-43 was significantly (p less than 0.01) better than KHA in terms of cytochrome c oxidase redox state as well as maintenance of MAP. There was no significant difference between the two test solutions in terms of cortical ATP and lactate.

Adenosine Triphosphate↗
PubMed1981

Infra-red technique for cerebral blood flow: comparison with 133Xenon clearance.

A rapid infra-red optical technique has been developed for the measurement of cerebral blood flow. The method measures optical density changes across the intact skull during the passage of a bolus of the dye. Cardio-Green (CG). The clearance curves obtained for CG boluses are very short (less than 30 sec) in comparison with those obtained with tracers such as 133Xenon (10-30 min) that distribute into cerebral tissue. The volume of distribution of CG is totally intravascular, and the dye is relatively slowly cleared from the body. The important advantages of this spectrophotometric technique are its speed, versatility, and the avoidance of radioactive materials. The differential spectrophotometer used in this study, with trivial modifications, has been used to monitor changes in brain blood volume, oxygen saturation of hemoglobin, and cortical mitochondrial respiratory function, which illustrate the versatility of the technique for neurological assessments.

Animals↗
PubMed1981

In vivo comparison of cerebral tissue PO2 and cytochrome aa3 reduction-oxidation state in cats during hemorrhagic shock.

To assess the adequacy of oxygen availability and utilization within the cerebral cortex in vivo, we have measured the partial pressure of oxygen in tissue (PtO2), as well as the reduction oxidation state of cytochrome c oxidase (cyt aa3) during shock induced by slow or rapid hemorrhage in anesthetized cats. PtO2 was measured with pyrenebutyric acid-generated fluorescence in cerebral cortical cells. Cyt aa3 redox state was measured by the absorption of monochromatic light at 605 nm absorption peak of the enzyme reflected from the same cortical field. The PtO2 remained within the normal range until either 30 +/- 1.5 ml blood/kg was removed or the mean arterial pressure fell by 70 +/- 5% of base line. Beyond either point, the PtO2 fell rapidly to a low value approximating zero. By contrast, the reduction of cyt aa3 began early when as little as 5 ml blood/kg was removed. Thereafter, the shift toward reduction was progressive and continuous with a slow rate at first and a rapid rate later. This accelerated rate of cyt aa3 reduction preceded the rapid fall of PtO2. We concluded that, under these experimental conditions, cyt aa3 reduction is a much earlier and more sensitive indicator of perturbed intracellular aerobic metabolism due to hemorrhage that is PtO2.

Animals↗
PubMed1980

Temperature coefficients for the oxidative metabolic responses to electrical stimulation in cerebral cortex.

Temperature coefficients of both cat and toad brain have been calculated for the active metabolic state induced by electrical stimulation. Values are higher than most of the values previously reported for "rest" metabolism, whether calculated from Arrhenius plots or from linear graphs. Relative rates of oxidative metabolism were obtained by measuring the time course of the transient changes in NADH fluorescence and cytochrome aa3 absorption by reflectance techniques directly from the surface of the exposed cat cerebral cortex in vivo and from the isolated intact toad brain mounted in a cuvet. These findings demonstrate that such optical methods accurately record metabolic processes.

Animals↗
PubMed1978

Simultaneous monitoring by optical techniques of respiratory chain and intracellular pH in toad ventricle strip.

Intracellular pH and oxidative metabolism can be measured in toad ventricle strips simultaneously by the use of the pH indicator dye, neutral red, and a rapid scanning spectrophotometer. The effects of hypoxia and acidification on mechanical function are approximately additive. The decrease in tension due to slight acidification is probably through an effect on the portion of the twitch tension supported by anaerobic metabolism.

Anaerobiosis↗
PubMed1978

Behaviour of the mitochondrial respiratory chain in vivo.

The interrelation of neuronal function and oxidative metabolism of the brain is most incisively studied by optical techniques in vivo. When O2 becomes limited the respiratory chain becomes reduced, extracellular potassium activity is increased, the EEG is depressed and excitability declines, all as expected. Under mildly hyperoxic conditions however, the opposite responses occur, which indicate an absence of a critical tissue Po2 and a continuum of dependence on the O2 concentration, including levels well above the limits for maximal activity of the respiratory chain in isolated mitochondria in vivo. The unexpectedly high steady state of reduction of cytochrome a, a3 provides the basis for a new hypothesis of an extra energy conservation site between cytochrome a3 and O2 and leads to a consideration of a reaction mechanism of O2 with four electrons and four H+ ions occurring at an enzymically active centre of cytochrome a, a3. A special function of the cytochrome a, a3 complex is implied in regulating cellular K+ transport and thus excitability.

Animals↗
PubMed1977

Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters.

The relatively good transparency of biological materials in the near infrared region of the spectrum permits sufficient photon transmission through organs in situ for the monitoring of cellular events. Observations by infrared transillumination in the exposed heart and in the brain in cephalo without surgical intervention show that oxygen sufficiency for cytochrome a,a3, function, changes in tissue blood volume, and the average hemoglobin-oxyhemoglobin equilibrium can be recorded effectively and in continuous fashion for research and clinical purposes. The copper atom associated with heme a3 did not respond to anoxia and may be reduced under normoxic conditions, whereas the heme-a copper was at least partially reducible.

Animals↗
PubMed1977

A fluorometric study of oxidative metabolism in the in vivo canine heart during acute ischemia and hypoxia.

Optical techniques for monitoring the fluorescence of intramitochondrial nicotinamide adenine dinucleotide (NADH) were employed to allow an on-line, non-invasive study of the metabolic state of healthy and ischemic cardiac tissue in the intact dog. Acute interruption of blood flow to the area of myocardium studied resulted in an immediate rise in NADH, indicating impairment of oxidative metabolism due to limitation of oxygen availability. Release of the coronary artery occlusion resulted in an oxidation of NADH to preocclusion baseline and signaled repayment of incurred O2 debt. Collateral flow produced a spontaneous fall in NADH levels towards preocclusion baseline. Hypoxic tissue was recognized by an oxidation of NADH on ventilation with 100 per cent O2, while in normal hearts no oxidation indicated the O2 was not rate limiting. Ischemic NADH increases preceded the onset of epicardial EKG changes, suggesting that an inability to rephosphorylate ADP to ATP is the primary cause of the EKG changes. Fluorometry of the in vivo heart provides a sensitive, continuous technique of monitoring cardiac cellular mitochondrial NAD;NADH redox levels and, therefore, the adequacy of high energy phosphate production and allows localization of cardiac tissue with marginal oxygen supply.

Animals↗