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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this survey, the effect of fentanyl, a potent morphinomimetic, on myocardial metabolism and some hemodynamic variables during ischemia is described. The data presented were derived from open-chest experiments on dogs. Ischemia was induced by partial occlusion (stenosis) of a coronary artery. Inducing the stenosis twice in the same animal after a certain interval made it possible to use the animal as its own control. Control and compound series are discussed. In the compound series, fentanyl (25 microgram/kg-1) was injected IV 5 minutes before induction of the second stenosis. Fentanyl decreased the oxygen demand of the ischemic myocardium, mainly due to a reduction in heart rate, which resulted in a decrease in the breakdown of energy-rich phosphates and in the anaerobic breakdown of glucose. The latter resulted in a less pronounced production of lactate by the ischemic myocardium and hence in a diminished acidity of this tissue. The release of potassium ions during ischemia was reduced after fentanyl. The uptake of glucose by the ischemic myocardium was not affected by fentanyl, but the uptake of free fatty acids was diminished. During ischemia, the arterial free fatty acid concentration decreased after fentanyl, indicating that the compound may suppress stress responses. Although extrapolation to clinical anesthesia should be handled with care, the described findings suggest that the use of fentanyl may benefit patients with coronary artery disease during anesthesia.
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PMID:Effect of fentanyl on myocardial metabolism during ischemia. 705 56

A subpopulation of pain fibers are activated by capsaicin, the ingredient in red peppers that produces a burning sensation when eaten or placed on skin. Previous studies on dorsal root ganglion neurons indicated that capsaicin activates sensory nerves via a single slowly activating and inactivating inward current. In rat trigeminal neurons, we identified a second capsaicin-activated inward current. This current can be distinguished from the slow one in that it rapidly activates and inactivates, requires Ca2+ for activation, and is insensitive to the potent capsaicin agonist resiniferatoxin. The rapid current, like the slower one, is inhibited by ruthenium red and capsazepine. The two capsaicin-activated inward currents share many similarities with the two inward currents activated by lowering the pH to 6.0. These similarities include kinetics, reversal potentials, responses to Ca2+, and inhibition by ruthenium red and capsazepine. These results suggest that acidic stimuli may be an endogenous activator of capsaicin-gated currents and therefore may rationalize why pain is produced when the plasma acidity is increased, as occurs during ischemia and inflammation.
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PMID:A rapid capsaicin-activated current in rat trigeminal ganglion neurons. 829 May 92

Glutamate antagonists protect neurons from hypoxic injury both in vivo and in vitro, but in vitro studies have not been done under the acidic conditions typical of hypoxia-ischemia in vivo. Consistent with glutamate receptor antagonism, extracellular acidity reduced neuronal death in murine cortical cultures that were deprived of oxygen and glucose. Under these acid conditions, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-kainate antagonists further reduced neuronal death, such that some neurons tolerated prolonged oxygen and glucose deprivation almost as well as did astrocytes. Neuroprotection induced by this combination exceeded that induced by glutamate antagonists alone, suggesting that extracellular acidity has beneficial effects beyond the attenuation of ionotropic glutamate receptor activation.
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PMID:Neuroprotective effects of glutamate antagonists and extracellular acidity. 838 56

The three-compartment model of brain acid-base regulation postulates that under circumstances of changing function or disease, hydrogen ion concentrations may differ considerably in the interstitial space (ISS), the neurons and the glial cells. During hyperglycemia plus profound ischemia, for example, direct measurements by microelectrodes followed by intracellular HRP staining show that intraglial pH can fall transiently as low as 3.9, although more often the nadir drops to the 4.5-5.5 range. Concurrently, ISS-pH and, by calculation, neuronal pH fails to and remains constant (but not necessarily the same) at pH 6.2. By contrast, during spreading depression, ISS and intraglial pH at first move rapidly and transiently in opposite directions, ISS [H+] rising, intraglial falling. These two then gradually stabilize, whereas neuronal pH remains substantially more steady and near normal, shifting only minimally from resting baseline levels over several minutes' time. Similar but less pronounced effects follow direct electrical stimulation. The net change represents complex biophysical transmembrane and buffering mechanisms that appear to guard neuronal homeostasis. Studies carried out on embryonic rat forebrain neurons and glia show that these cells have considerably different vulnerabilities to extracellular acidity depending on the anionic nature of the acid in the bathing medium. In cultures to which HCI was added to the medium, neurons and neuronal processes almost all survived ten minute exposures to pH 3.8, whereas glial cells succumbed after ten minute exposures at pH not lower than 4.2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo and in vitro control of acid-base regulation of brain cells during ischemic and selective acidic exposure. 842 56

This isolated working rat heart study was designed to investigate the effect of duration of reperfusion and degree of acidity of the reperfusate on myocardial protection. The experimental time course was as follows: 20 minutes of perfusion with the heart working, 3 minutes of infusion with the St. Thomas' Hospital cardioplegic solution followed by global ischemia for 33 minutes at 37 degrees C, and 20 minutes of Langendorff reperfusion followed by 20 minutes of working perfusion. During the initial 3 minutes of Langendorff reperfusion, the pH of the reperfusate was changed to 5.6, 6.8, and 7.5 by addition of sodium hydroxide into Krebs-Henseleit nonbicarbonate HEPES buffer. A respiratory acidic reperfusate was used for the initial 0.5, 1, 2, 3, 5, and 15 minutes during reperfusion. The results were as follows: (1) Reperfusion with a mildly acidic solution (i.e., pH 6.8) yielded better recovery than reperfusion with solutions having pH levels of 5.8 or 7.5. (2) Reperfusion for less than 3 minutes with a reperfusate having a pH level of 6.8 provided better recovery, although reperfusion for longer than 3 minutes exacerbated reperfusion injury. In conclusion, the effects of reperfusion with acidic solution were influenced by degree and duration with biphasic response characteristics.
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PMID:Transient reperfusion with acidic solution affects postischemic functional recovery: studies in the isolated working rat heart. 860 76

The role of endogenous acid was evaluated in a rat model of gastric epithelial damage induced by local ischemia-reperfusion (IR). Because no gross lesion was induced in this model, the damage was quantified by measuring the blood-to-lumen [51Cr]EDTA clearance. A proton pump inhibitor (omeprazole) or an H2-receptor antagonist (T-593) was used to suppress luminal acidity from pH 5 to pH 6.3-7.0. Both drugs significantly attenuated the increase in clearance induced by IR, indicating an important role for endogenous acid. A second series of experiments was performed to confirm whether the change in pH from around 5 to 7 was sufficient to reduce IR-induced gastric mucosal damage. Phosphate-buffered saline was perfused into the gastric lumen to neutralize the endogenous luminal acid. Although the luminal acid was completely neutralized, no reduction in clearance was observed. These data indicate that endogenous luminal acid does not play an important role in gastric injury induced by local IR stress and that a proton pump inhibitor or H2-receptor antagonist may suppress IR injury by a mechanism other than reducing luminal acidity, i.e., reducing consumption of ATP needed for acid secretion, thereby improving gastric mucosal energy metabolism.
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PMID:Role of endogenous acid in gastric mucosal injury induced by local ischemia-reperfusion in the rat. 877 1

Acidosis has traditionally been considered to mediate certain types of hypoxic-ischemic injury to the brain. However, the recent demonstration that moderate acidosis will reduce NMDA-mediated currents suggested that acidity could actually protect against types of ischemia and excitotoxicity, and in vitro studies now support this idea. Prompted by this, we have utilized the silicon microphysiometer, a recently-developed instrument that allows for indirect real-time measurement of metabolic rate by detecting proton efflux from small numbers of cultured cells, to determine whether acidity has protective effects upon cellular metabolism. Reducing extracellular pH from 7.4 to as low as 6.0 caused prompt, step-wise, and reversible inhibition of proton efflux rate in cortical and hippocampal cultures both normally and restricted to either glycolysis or oxidative metabolism. Approximately half of the inhibition was due to acidotic effects of NMDA-mediated currents, as demonstrated with NMDA receptor antagonists. Such an inhibition of this indirect metabolic measure could be associated with constant or increased ATP concentrations and represent a beneficial decrease in energy demands upon a neuron. Alternatively, an inhibition of proton efflux rate could be associated with ATP depletion and reflect impaired energy production. We observed a complex interplay between these opposing patterns. Reducing pH to 6.7 for 20 min caused significantly increased ATP concentrations, and prevented excitotoxin-induced ATP depletion. These effects of acidosis involved both NMDA-dependent and- independent actions. More severe (less than pH 6.7) acidosis did not cause ATP concentrations to rise, and if sustained for more than an hour caused a significant decline in ATP concentrations. Thus, despite the recent emphasis on the surprising neuroprotective potential of acidosis, a drop in pH is still likely to have complex and mixed consequences for brain tissue.
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PMID:Salutary and deleterious effects of acidity on an indirect measure of metabolic rate and ATP concentrations in CNS cultures. 888 62

Acidosis is a well established concomitant of tissue ischemia. Acidosis in the pH range 6.0-7.0 is seen in cerebral ischemia and within solid tumors. Extracellular acidosis of pH 6.0 and 6.4 provided essentially complete protection from 48 h serum deprivation induced apoptotic death of cultured primary murine neurons. We tested the effect of p53 using transformed mouse embryo fibroblasts of either p53+/+ or p53-/- genotype. Both were markedly protected from serum deprivation by acidity. Hypoxia induced fibroblast injury was also reduced at pH 6.8. Lower pH resulted in a shift from apoptotic to necrotic morphology after 42 h hypoxia. Acidosis reduces apoptosis of both normal and transformed cells, irrespective of p53 status.
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PMID:Acidosis reduces neuronal apoptosis. 957 83

Mucosal pH abnormalities are associated with anastomotic dehiscence, ischemia, and malignancy. We postulated that intraluminal pH influences intestinal epithelial motility, proliferation, and differentiation and studied extracellular pHo (7.0-8.5) effects on human (Caco-2) intestinal epithelial motility, proliferation, and differentiation. Mucosal healing was modeled by sheet migration and differentiation by alkaline phosphatase and dipeptidyl dipeptidase specific activity. In parallel differentiation and motility studies, we inhibited proliferation with mitomycin to dissociate indirect mitogenic effects. Intracellular pHi was quantitated using BCECF/AM at varying extracellular pHo and in migrating cells. Motility was maximal at pHo 7.6 and proliferation at 7.2. Each decreased with acidity and alkalinity. By contrast, brush border enzyme activity was lowest at pHo 7.0 and highest at pHo 8.5. pHi was highest at pHo 8.5. Migrating cell pHi was higher than static cell pHi. Thus, extracellular pHo deviations perturb Caco-2 pHi homeostasis and motility. Alkalinity promotes differentiation while acidity induces proliferation and limits differentiation.
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PMID:Differential effects of mucosal pH on human (Caco-2) intestinal epithelial cell motility, proliferation, and differentiation. 969 Mar 92

The extracellular acidity that accompanies brain hypoxia-ischemia is known to reduce both NMDA and AMPA-kainate receptor-mediated currents and NMDA receptor-mediated neurotoxicity. Although a protective effect of acidic pH on AMPA-kainate receptor-mediated excitotoxicity has been assumed, such has not been demonstrated. Paradoxically, we found that lowering extracellular pH selectively increased AMPA-kainate receptor-mediated neurotoxicity in neocortical cell cultures, despite reducing peak elevations in intracellular free Ca2+. This injury potentiation may, at least in part, be related to a slowed recovery of intracellular Ca2+ homeostasis, observed after AMPA-kainate receptor activation, but not after NMDA receptor activation or exposure to high K+. The ability of acidic pH to selectively augment AMPA-kainate receptor-mediated excitotoxicity may contribute to the prominent role that these receptors play in selective neuronal death after transient global ischemia.
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PMID:Extracellular acidity potentiates AMPA receptor-mediated cortical neuronal death. 969 21


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