Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A Na(+)-HCO3- coinflux carrier and the Na(+)-H+ antiport have both been shown to contribute to recovery from intracellular acidosis in cardiac tissue. We have investigated the participation of these mechanisms as well as metabolite (lactate and CO2) washout in the recovery of pHi after myocardial ischemia. Isovolumic ferret hearts were Langendorff-perfused with either HCO3(-)-buffered or nominally HCO3(-)-free (HEPES-buffered) medium at 30 degrees C. pHi was estimated from the chemical shift of the 31P-nuclear magnetic resonance signal of intracellular PO4-, and net H+ efflux rates were calculated at pHi 6.80. The H+ efflux rate during reperfusion, after 10 minutes of global ischemia, was 15.5 +/- 1.9 mmol.l-1 x min-1 (n = 10) in hearts perfused with HCO3(-)-buffered medium and 8.2 +/- 1.5 mmol.l-1 x min-1 (n = 9, p < 0.01) in hearts perfused with HEPES-buffered medium. HCO3- influx, assessed either by inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (20 microM) or by initially perfusing hearts with HEPES-buffered medium but reperfusing with HCO3(-)-buffered medium, accounted for 3.5-4.9 mmol.l-1 x min-1, and CO2 efflux accounted for 3.8-6.2 mmol.l-1 x min-1 of the additional H+ efflux in HCO3(-)-buffered medium. H(+)-coupled lactate efflux, measured by NAD(+)-linked spectrophotometric assay and inhibited by the sarcolemmal monocarboxylate transport inhibitor 4,4'-dibenzamidostilbene-2,2'-disulfonate (0.25 mM), contributed 3.7-6.2 mmol.l-1 x min-1. H+ efflux via the 5-(N-ethyl-N-isopropyl)amiloride-sensitive Na(+)-H+ antiport was 1.0-2.9 mmol.l-1 x min-1. pHi recovery after ischemia is therefore principally mediated by metabolite (lactate and CO2) washout. Na(+)-coupled acid extrusion contributed approximately 35% of total H+ efflux in this system. However, the associated Na+ entry (approximately 5 mmol.l-1 x min-1) may contribute to Ca2+ overload after reperfusion.
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PMID:Mechanisms of pHi recovery after global ischemia in the perfused heart. 838 98

Acidosis elicited during myocardial ischemia is a significant pathophysiological condition markedly affecting the electrical and contractile properties of heart muscle. We examined the effects of protons on K channel activity in rat ventricular myocytes by recording transient outward (Ito) and inward rectifier (IKl) K+ currents using the whole cell, voltage clamp technique. Proton concentration was controlled by independently varying the pH of HEPES-buffered external (pHo) or pipette (pHp) solutions. Mean Ito density in myocytes preconditioned in acidic external solution (pHo 6.0) for 15-20 min was significantly less than control cells equilibrated at physiological pHo. In contrast, IKl was not changed during this period of acidosis. External acidification did not decrease Ito when initiated after intracellular dialysis with standard pHp 7.2. However, when myocytes were dialyzed with acidic pHp, Ito density was significantly less than control, while alkaline pHp had little effect. Despite marked reduction in current density produced by low pHp solutions, steady-state activation and inactivation parameters of Ito were not significantly altered. In addition, the reversal potential of this current, kinetics of inactivation, and recovery from inactivation were not significantly affected by acidic or alkaline pHp solutions. Acidic pHp alone did not change IKl density compared with control, but when combined with Na+/H+ exchange blockade with 5-(N,N-dimethyl)-amiloride or Na(+)-free external solution, IKl density was significantly reduced. Our data suggest that protons inhibit Ito predominantly from the intracellular side of the channel, possibly by altering its conductance or gating properties. Moreover, intracellular protons differentially affect Ito and IKl channels, with the former exhibiting greater sensitivity for a given level of acidosis.
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PMID:Proton inhibition of transient outward potassium current in rat ventricular myocytes. 914 Aug 8

To study the effects of different pH HEPES-KH reperfusate solution on immature myocardial protection, isolated perfused Langendorff model from immature rabbit hearts were developed formed. Control group (C) was perfused only with pH 7.4 HEPES-KH solution for 90 min. Ischemia/reperfusion group (group I/R) was perfused with pH 7.4 HEPES-KH solution before ischemia or after ischemia. Experimental group (group E), after ischemia, was perfused with pH 6.8, pH 7.1 and pH 7.4 HEPES-KH solutions for 5 min, 5 min, and 20 min, respectively. The left ventricular function recovery, MWC, LDH and CK leakage, MDA, ATP content, and SOD activity were determined. Our results showed that the left ventricular function recovery, ATP content and SOD activity in group E were higher than those of group I/R (P < 0.05). MWC, MDA content, LDH and CK leakage in group E were lower than those of group I/R (P < 0.05). These findings suggested that pH paradox might be one of important mechanisms for immature myocardial ischemia-reperfusion injury, and acidic perfusate, at the beginning of reperfusion, might attenuate pH paradox and ameliorate functional recovery in isolated perfused immature rabbit hearts.
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PMID:Acidic HEPES-KH reperfusion enhances myocardial protection in immature rabbits. 1265 46