Tissue Pco<sub>2</sub>in Brain Ischemia Related to Lactate Content in Normo- and Hypercapnic Rats

Katsura, Ken‐ichiro; Ekholm, Anders; Siesjö, Bo K.

doi:10.1038/jcbfm.1992.37

Cited by 37 publications

(26 citation statements)

References 21 publications

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“…Using the established pH i /lactate interrelationship (22), the lactate values corresponded to pH i of 6.5, 6.3, and 6.0 for hypo‐, normo‐, and hyperglycemic animals, respectively. These values are close to those reported in rat with similar preischemic blood glucose levels (26).…”

Section: Resultssupporting

confidence: 91%

Cerebral T_1ρ relaxation time increases immediately upon global ischemia in the rat independently of blood glucose and anoxic depolarization

Kettunen¹,

Gröhn²,

Penttonen

et al. 2001

Magnetic Resonance in Med

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Time-dependent changes of T 1 in the rotating frame (T 1 ), diffusion, T 2 , and magnetization transfer contrast on cardiac arrest-induced global ischemia in rat were investigated. T 1 , as acquired with spin lock amplitudes >0.6 G, started to increase 10 -20 sec after cardiac arrest followed by an increase within 3-4 min to a level that was 6 -8% greater than in normal brain. The ischemic T 1 response coincided with the drop of water diffusion coefficient in normoglycemic animals. However, unlike the rate of diffusion, the kinetics of T 1 were not affected by either preischemic hypoglycemia or hyperglycemia. Similar to diffusion, the kinetics of anoxic depolarization were dependent on preischemic blood glucose levels. Ischemia caused a reduction in the Hahn spin echo T 2 as a result of blood oxygenation level-dependent (BOLD) effect; maximal negative BOLD seen by 40 sec. In the animals injected with an ironoxide particle contrast agent, AMI-227, prior to the insult, both T 1 and T 2 immediately increased in concert on induction of ischemia. In contrast to the T 1 and diffusion changes, a much slower change in magnetization transfer contrast was evident over the first 20 min of ischemia. These data demonstrate that T 1 immediately increases following ischemia and that the pathophysio- Cerebral ischemia results in a number of immediate tissue perturbations that makes it a perfect target to be monitored by NMR methods in vivo. Subtle changes in a number of cerebral metabolites and pH have extensively been exploited for neurochemical assessment of ischemia by 31 P, 1 H, and 13 C NMR spectroscopy (1). In fact, as far as the primary consequences of ischemia are concerned 31 P NMR spectroscopy can be regarded as a "diagnostic" means of the condition owing to its ability to directly probe cellular energy metabolites. However, due to the low spatial and temporal resolutions of spectroscopy methods relative to the rates of metabolic perturbations, its applicability in detection of acute brain tissue changes following ischemia is limited.Direct and early demonstration of ischemia in the brain tissue is crucial both from experimental and clinical points of view. Therefore, the observations that apparent diffusion coefficient (ADC) of water and exhaustion of ATP proceed in parallel upon ischemia (2) and that the cerebral blood flow (CBF) thresholds for extensive reduction of ADC and ATP are very similar (3) were of pivotal importance. These data showed that energy failure is the key factor causing the drop of ADC water (3,4), rendering acute cerebral ischemia detectable at the spatial resolution of MRI. High-speed MRI studies have shown that in normoglycemic animals a large drop of tissue water ADC starts at about 1-2 min of ischemia (2,5) and that hyperglycemia delays the onset of ADC drop (6). Diffusion MRI has provided unique opportunities for investigating the tissue pathophysiology of cerebral ischemia (3,7), assessing the efficacy of antiischemic drugs (8) as well as enabling the accurate diagnosis of acute ischemic s...

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Section: Resultssupporting

confidence: 91%

Cerebral T_1ρ relaxation time increases immediately upon global ischemia in the rat independently of blood glucose and anoxic depolarization

Kettunen¹,

Gröhn²,

Penttonen

et al. 2001

Magnetic Resonance in Med

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“…It is unlikely a living mammal would have a blood pH of 6.9 unless it is in extremis . In the case of a pure respiratory acidosis, the PCO 2 would have to rise above 100 mmHg in order for the pH to drop below 7.1 (Katsura et al 1992a, Katsura et al 1992b), which greatly surpasses the range of 50-70 mmHg that might occur in a critically ill patient with chronic obstructive pulmonary disease, and would likely only occur when a patient goes into respiratory failure, cardiopulmonary arrest or other medical emergency (Koo et al 1975). When studying putative chemoreceptors, it is imperative to keep in vitro experimental conditions within a physiological range.…”

Section: Unraveling the Apparent Contradictionsmentioning

confidence: 99%

Serotonin Neurons and Central Respiratory Chemoreception

Teran

Massey

Richerson

2014

Progress in Brain Research

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Serotonin (5-hydroxytryptamine; 5-HT) neurons are widely considered to play an important role in central respiratory chemoreception. Although many studies in the past decades have supported this hypothesis, there had been concerns about its validity until recently. One recurring claim had been that 5-HT neurons are not consistently sensitive to hypercapnia in vivo. Another belief was that 5-HT neurons do not stimulate breathing; instead, they inhibit or modulate respiratory output. It was also believed by some that 5-HT neuron chemosensitivity is dependent on TASK channels, but mice with genetic deletion of TASK-1 & TASK-3 have a normal hypercapnic ventilatory response (HCVR). This review explains why these principal arguments against the hypothesis are not supported by existing data. Despite repeated challenges, a large body of evidence now supports the conclusion that at least a subset of 5-HT neurons are central chemoreceptors.

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“…The value obtained was close to 30 mmol a kg-' pH unit-'. This represents total buffer capacity (0, Katsura et al (1991Katsura et al ( , 1992.…”

Section: Steady-state Intra-and Extra-cellular Ph Changesmentioning

confidence: 99%

Coupling among changes in energy metabolism, acid-base homeostasis, and ion fluxes in ischemia

Katsura

Ekholm²,

Siesjö³

1992

Can. J. Physiol. Pharmacol.

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This article attempts correlating changes in cellular energy metabolism, acid-base alterations, and ion homeostasis in ischemia and other conditions. It is emphasized that loss of ion homeostasis, with thermodynamically downhill fluxes of K+, Ca2+, Na+, Cl-, and H+, occurs because energy production fails and (or) ion conductances are increased. In ischemia, energy failure is the leading event but, in hypoglycemia, activation of ion conductances is what precipitates energy failure. The initial event is a rise in K+ e, at least in part caused by activation of K+ conductances modulated by Ca2+ or ATP/ADP ratio. Secondarily, this leads to release of excitatory amino acids and massive activation of unspecific cation (and anion) conductances. Production of H+ occurs in states characterized by energy failure (ischemia and hypoxia) or by alkalosis (hypocapnia and ammonia accumulation). H+ equilibrates between intra- and extra-cellular fluid via nonionic diffusion of lactic acid, and transmembrane fluxes of H+ or HCO3- via ion channels. Since the relationship between lactate and either pHi or pHe is linear, there are no abrupt pH shifts explaining why hyperglycemia worsens ischemic damage. The reversible insults seem to induce a sustained stimulation of H+ extrusion from cells giving rise to intracellular alkalosis and extracellular acidosis.

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Tissue Pco₂in Brain Ischemia Related to Lactate Content in Normo- and Hypercapnic Rats

Cited by 37 publications

References 21 publications

Cerebral T_1ρ relaxation time increases immediately upon global ischemia in the rat independently of blood glucose and anoxic depolarization

Cerebral T_1ρ relaxation time increases immediately upon global ischemia in the rat independently of blood glucose and anoxic depolarization

Serotonin Neurons and Central Respiratory Chemoreception

Coupling among changes in energy metabolism, acid-base homeostasis, and ion fluxes in ischemia

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Tissue Pco2in Brain Ischemia Related to Lactate Content in Normo- and Hypercapnic Rats

Cited by 37 publications

References 21 publications

Cerebral T1ρ relaxation time increases immediately upon global ischemia in the rat independently of blood glucose and anoxic depolarization

Cerebral T1ρ relaxation time increases immediately upon global ischemia in the rat independently of blood glucose and anoxic depolarization

Serotonin Neurons and Central Respiratory Chemoreception

Coupling among changes in energy metabolism, acid-base homeostasis, and ion fluxes in ischemia

Contact Info

Product

Resources

About

Tissue Pco₂in Brain Ischemia Related to Lactate Content in Normo- and Hypercapnic Rats

Cerebral T_1ρ relaxation time increases immediately upon global ischemia in the rat independently of blood glucose and anoxic depolarization

Cerebral T_1ρ relaxation time increases immediately upon global ischemia in the rat independently of blood glucose and anoxic depolarization