Phosphorus nuclear magnetic resonance of perfused working rat hearts

Jacobus, William E.; Th, Goodin; Hollis, Donald P.; Nunnally, Ray L.

doi:10.1038/265756a0

Cited by 271 publications

(85 citation statements)

References 4 publications

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“…However, in the present study, intracellular acidification induced by simulated ischemia was greater than that reported by previous authors (32). At this moment, we have no explanation for the discrepancy between the present results and theirs, but the magnitude of intracellular acidification observed in the present study was within the range reported for ischemic myocardium from the normal values of around 7.2 to values as low as 6.3 (41) or even 5.7 (42). Thus, although we are aware of the technical limitation of the present method to simulate myocardial ischemia occurring in situ, the method adopted in the present study is considered to reflect, at least in part, some aspects of pathophysiological changes occurring in cardiac ischemia in situ.…”

Section: Simulated Ischemiacontrasting

confidence: 55%

Effects of Stilbene Derivatives SITS and DIDS on Development of Intracellular Acidosis during Ischemia in Isolated Guinea Pig Ventricular Papillary Muscle In Vitro

Lai

Liu

Nishi

1996

Japanese Journal of Pharmacology

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ABSTRACT-Using ion-selective microelectrode techniques, we investigated the effects of 4-acetamido-4'-isothiocyanatostilbene-2,2 disulfonic acid (SITS) and 4,4' -diisothiocyanostilbene-2,2 disulfonic acid (DIDS), which are known as Cl--HCO3-exchange blockers, on action potentials and intracellular pH (pH;) in guinea pig ventricular papillary muscles subjected to simulated ischemia. Simulated ischemia was produced by stopping the flow of superfusing solution and then covering the preparations with mineral oil. Simulated ischemia induced a progressive decrease in the maximum upstroke rate and resting membrane potentials, shortened action potential duration, and resulted in cessation of action potentials within 10-12 min after the onset of simulated ischemia. The pH;-measurements revealed progressive intracellular acidosis during the period of simulated ischemia. SITS (0.5 mM) or DIDS (0.1 mM) delayed the onset of ischemiainduced deterioration of action potentials and prolonged the time to cessation of action potentials. SITS or DIDS (0.1-0.5 mM) induced an increase in pH, in HCO3--buffered solution and suppressed the development of intracellular acidosis during ischemia. Under the external Cl--free condition, the time to cessation of action potentials caused by ischemia was significantly delayed, and the development of intracellular acidosis during ischemia was attenuated. The present results indicate that activation of the Cl--HC03-exchange system would be involved, in part, in the development of intracellular acidosis during cardiac ischemia.

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Section: Simulated Ischemiacontrasting

confidence: 55%

Effects of Stilbene Derivatives SITS and DIDS on Development of Intracellular Acidosis during Ischemia in Isolated Guinea Pig Ventricular Papillary Muscle In Vitro

Lai

Liu

Nishi

1996

Japanese Journal of Pharmacology

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“…To our knowledge, there are no reports in the literature showing reductions in extracellular pH following muscle inflammation. However, reduction in pH in ischemic tissues, arthritic joints, and incisional wounds have been reported in humans and animals (Jacobus et al, 1977;Andersson et al, 1999;Woo et al, 2004), including in exudates from patients with inflammatory conditions, such as arthritis, mastitis, and bursitis (Hä bler, 1929(Hä bler, , 1930Cummings and Nordby, 1966;Geborek et al, 1989). Furthermore, there is a wide range of pH decreases observed in the literature with reductions ranging from 0.1 pH unit in inflamed tissue (Andersson et al, 1999) to as great as 2.0 pH units in exudate (Hä bler, 1929).…”

mentioning

confidence: 99%

“…Extracellular tissue pH is reduced in an isolated perfused heart preparation during ischemia (Jacobus et al, 1977) in the paw or gastrocnemius muscle after incision (Woo et al, 2004) in periarticular soft tissue during different phases of antigen-induced arthritis (Andersson et al, 1999) and in exudates from inflammatory conditions (Hä bler, 1929(Hä bler, , 1930Cummings and Nordby, 1966). One of the major biochemical reactions involved in proton generation in tissues at rest is through reversible hydration of carbon dioxide, mediated by carbonic anhydrase (CA) enzymes (Chen and Chesler, 1992).…”

mentioning

confidence: 99%

Acetazolamide, a Carbonic Anhydrase Inhibitor, Reverses Inflammation-Induced Thermal Hyperalgesia in Rats

Radhakrishnan

Sluka²

2005

J Pharmacol Exp Ther

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Inflammatory pain is linked to reduction in tissue pH. Tissue proton generation is mainly mediated by carbonic anhydrases (CAs). We therefore hypothesized that inhibition of CAs with acetazolamide (ACTZ) increases the tissue pH and reverses inflammation-induced pain. CAs are also present in the central nervous system and control anion concentrations. Furthermore, ACTZ has direct effects on ion channels involved in nociception. In the current study, responses to heat and mechanical stimuli (von Frey filaments) of the paw were assessed before and after carrageenan-induced muscle inflammation and after treatment with ACTZ in rats. ACTZ was administered systemically, locally, or intrathecally 24 h after the induction of inflammation. In separate studies, pH was measured in the inflamed and noninflamed muscles and after administration of ACTZ. Carrageenan injection to the gastrocnemius muscle produced heat hyperalgesia and mechanical allodynia of the paw. Systemic ACTZ reversed the heat hyperalgesia but not mechanical allodynia. Similarly, injections of ACTZ into the inflamed muscle or intrathecally reversed the heat hyperalgesia but not mechanical allodynia. Surprisingly, the pH in the inflamed muscle was not reduced compared with noninflamed muscle. Thus, the current data do not support our hypothesis that ACTZ reduces inflammatory hyperalgesia by raising the reduced pH in muscle. Although the possibility of pH changes and the role of CAs in the microenvironment cannot be ruled out, the mechanism of ACTZ-induced antihyperalgesia is not clear from this study. It is possible that the inhibition of ion channels and/or the inhibition of spinally located CAs contribute to the observed antihyperalgesia.

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“…This enabled the measurement of intracellular pH (1) as well as of concentration changes of several metabolites including 2,3-diphosphoglycerate and ATP (2). The technique has been applied to various tissues (3)(4)(5)(6)(7)(8)(9)(10) and cells (11)(12)(13) and recently to Ehrlich ascites tumor cells (11). We report here the application of 31P NMR at 40 MHz to the analysis of human cancer cells (HeLa) grown from tissue culture.…”

mentioning

confidence: 99%

³¹ P nuclear magnetic resonance studies of HeLa cells

Evans

Kaplan

1977

Proc. Natl. Acad. Sci. U.S.A.

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A survey of phosphorus compounds present in HeLa cells and their acid extracts-has been carried out by 31p nuclear magnetic resonance spectroscopy at 40 MHz. The proton decoupled 31p spectrum of the neutralized extract had resolution adequate to enable the identification of the main phosphate compounds. The spectral intensities were converted to concentrations. The lower detection limit with extensive signal averaging was 0.02 Mmol for the extract. The composition, listed in order of decreasing concentration, was: inorganic phosphate, ATP, phosphorylcholine, creatine phosphate, UTP, NAD+, glucose 6-phosphate, fl-D-fructose 1,6-bisphosphate, a-

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Phosphorus nuclear magnetic resonance of perfused working rat hearts

Cited by 271 publications

References 4 publications

Effects of Stilbene Derivatives SITS and DIDS on Development of Intracellular Acidosis during Ischemia in Isolated Guinea Pig Ventricular Papillary Muscle In Vitro

Effects of Stilbene Derivatives SITS and DIDS on Development of Intracellular Acidosis during Ischemia in Isolated Guinea Pig Ventricular Papillary Muscle In Vitro

Acetazolamide, a Carbonic Anhydrase Inhibitor, Reverses Inflammation-Induced Thermal Hyperalgesia in Rats

³¹ P nuclear magnetic resonance studies of HeLa cells

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Phosphorus nuclear magnetic resonance of perfused working rat hearts

Cited by 271 publications

References 4 publications

Effects of Stilbene Derivatives SITS and DIDS on Development of Intracellular Acidosis during Ischemia in Isolated Guinea Pig Ventricular Papillary Muscle In Vitro

Effects of Stilbene Derivatives SITS and DIDS on Development of Intracellular Acidosis during Ischemia in Isolated Guinea Pig Ventricular Papillary Muscle In Vitro

Acetazolamide, a Carbonic Anhydrase Inhibitor, Reverses Inflammation-Induced Thermal Hyperalgesia in Rats

31 P nuclear magnetic resonance studies of HeLa cells

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³¹ P nuclear magnetic resonance studies of HeLa cells