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)

Myocardial cell pH was measured with 5, 5 dimethyl-2, 4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular and water indicators were made into the left anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady state distribution of DMO between cells and plasma was calculated from the mean transit times of the indicator. Normal myocardial cell pH averaged 6.94 and changed by 58% of the concomitant alterations in plasma pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a balloon tip catheter in the left anterior descending coronary artery resulted in progressive decreases in cell pH to 6.59 by 1 hour. Infusions of sodium carbonate diminished intracellular acidosis. Hemodynamic studies during 4 hours of ischemia with blood pH at 7.55 to 7.60 indicated a significantly reduced left ventricular end-diastolic pressure and increased stroke volume by comparison with findings in animals given infusions of saline solution. Ventriculograms revealed improved wall motion in the ischemic segment after infusion of alkali. Precordial mapping showed a significant reduction in the number of leads with S-T segment elevation as well as in the sum of S-T segment elevations, but R wave amplitudes did not differ from those in control studies. Calculations of extracellular space, tissue water and cation content revealed a reduced gain of cell sodium ion and loss of cell potassium ion during ischemia after alkali treatment. The latter may account for the S-T segment responses, whereas enhanced ventricular performance may be related to reduced competition of hydrogen ion with calcium ion for binding sites on contractile protein.
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PMID:Myocardial ischemia and cell acidosis: Modification by alkali and the effects on ventricular function and cation composition. 0 59

The extracellular pH (pHo) and intracellular pH (pHi) were simultaneously measured with H(+)-sensitive microelectrodes in the rabbit papillary muscle during normal arterial perfusion and no-flow ischemia. The preparation was kept in an artificial gaseous atmosphere (N2 and CO2 during ischemia) without a surrounding fluid layer. Cylindrical muscles of small diameters (less than 1.0 mm) were selected to prevent major diffusion gradients of CO2 within the muscle cylinder during ischemia. In normal perfusion with CO2/HCO3(-)-buffered blood at PCO2 of 35 mm Hg, pHi was 7.03 +/- 0.03. During early ischemia, extracellular acidification was much more prominent than intracellular acidification. Consequently, the transmembrane pH gradient reversed (pHo less than pHi) at approximately 8 minutes. At 14 minutes of ischemia, pHo was 6.64 and pHi was 6.93. A moderate increase in PCO2 from 35 to 67 mm Hg before ischemia enhanced intracellular acidification in ischemia. Simulation of CO2 accumulation (increase of PCO2 in the surrounding atmosphere), as encountered in midmural ventricular layers during in vivo ischemia, produced a significant decrease of pHo (6.30 versus 6.64) and pHi (6.65 versus 6.93) at 14 minutes of ischemia. The presence of red blood cells in the intravascular space after arrest of coronary perfusion showed a pronounced effect on extracellular and intracellular acidosis. If the muscles were perfused with CO2/HCO3(-)-buffered perfusate in the absence of red blood cells, the changes of pHo and pHi were significantly larger (pHo, 6.00 versus 6.64; pHi, 6.46 versus 6.93 at 14 minutes) during ischemia. Actively developed force during ischemia was not significantly influenced by conditions modulating pHi. It decreased by 82% after 5 minutes, even when no significant change of pHi was recorded. By contrast, ischemic contracture was dependent on intracellular acidification. It developed earlier in the absence of red blood cells or with low extracellular buffer capacity. It is concluded that during acute myocardial ischemia 1) extracellular acidification exceeds intracellular acidification, 2) the decrease in pHi is inhomogeneous because of local variation in CO2 accumulation and diffusion, 3) the decrease in pHi is relatively small in the presence of red blood cells, and 4) the development of ischemic contracture but not the early decline in active tension is sensitive to changes in pHi.
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PMID:Changes in extracellular and intracellular pH in ischemic rabbit papillary muscle. 162

We have investigated (multivariate Cox's model) the relative risk of stable excitation-conduction block (ECB) in right ventricular myocardial strips (2 x 5 x 1 mm) from 26 female guinea-pigs, bathed in a 2-compartment chamber (3 ml) on the anterior side of which modified Tyrode's solution (K+ 12 mM, HCO3- 9 mM, pH 7 +/- 0.05, pO2 80 +/- 10 mmHg and absence of glucose) is supraperfused (stimulation rate: 450 ms; wire in the posterior compartment), thus enabling simulation of electrophysiologic changes seen during acute myocardial ischemia. Using glass microelectrodes, action potential amplitude (APA), durations (APD50 and 90%), resting membrane potential (RMP) and upstroke velocity (Vmax) are investigated. The hypothesis was tested of prostacyclin and histamine involvement in the genesis of ischemia-induced ECB in this model. Either a weak prostacyclin stimulator (cicletanine 10(-5) M, IPSEN, Paris, F, in DMSO 1:100; n = 16) or a potent prostacyclin generation blocker (indomethacin 10(-5) M, Sigma, in DMSO 1:100; n = 10) and either DMSO alone (1:100; n = 16) or a specific histaminergic H1 receptor antagonist (terfenadine 10(-5) M, Sigma, in DMSO 1:100; n = 10) were supraperfused using a randomization scheme. Each animal was used twice and either a first or a second occlusion (supraperfusing the modified Tyrode's solution for 30 min) period was performed and the randomized substances were supraperfused, thus enabling obtention of n = 52 experiments for analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The prevention of an excitation-conduction block during acute myocardial ischemia: is there a role for prostacyclin or for histamine?]. 172 7

This study was undertaken to assess the effect of a calcium antagonist, nicardipine (N), added in a cardioplegic solution on the ischemic myocardium. Isolated rat hearts were perfused with oxygenated Krebs Ringer Bicarbonate (KRB) solution by Langendorff's perfusion method and were subjected to 2 hours of ischemic arrest at 30 degrees C with multidose cardioplegia (every 30 min, for 5 min) and a subsequent 60 min of reperfusion. HR, LVP, coronary flow and oxygen tension of coronary effluent were monitored. Oxygen saturation of intracellular myoglobin and redox state of mitochondrial cytochrome aa3 in the myocardial cell were continuously measured throughout studies by a spectrophotometer. Oxygenated crystalloid cardioplegic solution (KRB) containing 25 mM of potassium was used. 40 rats were divided into 4 groups (10 rats each) according to the concentration of N (none, 0.5, 1 and 2 mg/L) in fully oxygenated potassium cardioplegic solution (PO2: 601 +/- 31 mmHg). The percent recovery of pressure-rate product after reperfusion was compared in each group and the optimal concentration of N was found to be 1 mg per liter of cardioplegic solution. No significant difference was found between Group Ia (N = 0 mg/L) and Group Ib (N = 1 mg/L) in metabolic or hemodynamic recovery after reperfusion. In other experiments, 40 rats in Group IIa (N = 0 mg/L, n = 20) and Group IIb (N = 1 mg/L, n = 20) received 10 ml of poorly oxygenated cardioplegic solution (PO2: 215 +/- 10 mmHg) on each reinfusion followed by a 25 min interval of ischemic arrest. The index of oxygen utilization, MVO2/pressure-rate product after reperfusion was significantly lower in Group IIb than in Group IIa (p less than 0.05). The results show that the addition of N (1 mg/L) to the cardioplegic solution preserved a more aerobic state (higher intracellular oxygen level) in the myocardium by further suppressing myocardial oxygen demand during the ischemic period which resulted in better myocardial protection. Therefore, it is concluded that the addition of N to the cardioplegic solution enhances myocardial preservation during myocardial ischemia.
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PMID:[Functional and metabolic effects of nicardipine on ischemic rat hearts with multidose potassium cardioplegia]. 237 97

The mechanism of myocardial revascularization was studied in 30 dogs with the aid of impulse carbonic acid laser after ligation of the anterior descending branch of the left coronary artery. In the control group, 4 dogs died of myocardial infarction. In 26 animals laser canals were formed. The walls of the canals comprised cardiomyocytes with the manifestations of a coagulation thermal necrosis. Morphological studies disclosed the aseptic productive nature of the inflammatory reaction and the absence of marked leukocytic infiltration of the tissues adjacent to the area of necrosis. The laser canals were lined with endothelium by the 10th-14th day after operation, they were not obliterated or sclerosed. Morphological, laboratory, and radionuclide studies attest to adequate perfusion of the myocardium with the aid of the laser canals preventing the development of myocardial ischemia and infarction.
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PMID:[Morphological bases of myocardial revascularization by laser radiation]. 650 10

In a study of regional variations in cardiovascular mortality in Great Britain during 1969-73 based on 253 towns the possible contributions of drinking water quality, climate, air pollution, blood groups, and socioeconomic factors were evaluated. A twofold range in mortality from stroke and ischaemic heart disease was apparent, the highest mortality being in the west of Scotland and the lowest in south-east England. A multifactorial approach identified five principal factors that substantially explained this geographic variation in cardiovascular mortality-namely, water hardness, rainfall, temperature, and two social factors (percentage of manual workers and car ownership). After adjustment for other factors cardiovascular mortality in areas with very soft water, around 0.25 mmol/l (calcium carbonate equivalent 25 mg/l), was estimated to be 10-15% higher than that in areas with medium-hard water, around 1.7 mmol/l (170 mg/l), while any further increase in hardness beyond 1.7 mmol/l did not additionally lower cardiovascular mortality.Thus a negative relation existed between water hardness and cardiovascular mortality, although climate and socioeconomic conditions also appeared to be important influences. Cross-sectional and prospective surveys of 7500 middle-aged men from 24 towns are in progress and will permit further exploration of these geographic differences, especially with regard to personal risk factors such as blood pressure, blood lipid concentrations, and cigarette smoking.
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PMID:British Regional Heart Study: geographic variations in cardiovascular mortality, and the role of water quality. 738 89

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

The Na+/H+ antiport and Na(+)-HCO3- coinflux carrier contribute to recovery from intracellular acidosis in cardiac tissue. The effects of angiotensin II (10(-12)-10(-6) M) on H+ fluxes after intracellular acid loading and during reperfusion after myocardial ischemia have been investigated in the isovolumic, Langendorff-perfused ferret heart. Intracellular pH (pHi) was estimated using 31P nuclear magnetic resonance (NMR) spectroscopy from the chemical shift of intracellular deoxyglucose-6-phosphate or inorganic phosphate. Angiotensin II produced concentration-dependent stimulation (maximum at 10(-6) M: 67%) of 5-(N-ethyl-N-isopropyl)amiloride (EIPA)-sensitive Na(+)-dependent of H+ efflux consistent with stimulation of the Na+/H+ antiport. Half-maximal stimulation of H+ efflux occurred at approximately 10(-9) M, which is close to the dissociation constant of the cardiac angiotensin AT1 receptor. Stimulation via this receptor was confirmed with the nonpeptide AT1 receptor blocker, GR-117289. Angiotensin II had less pronounced effects on HCO3(-)-dependent pHi recovery after acid loading with no effect on pHi recovery after intracellular alkalosis. During reperfusion, angiotensin II significantly increased H+ extrusion but impaired contractile recovery. The results support the hypothesis that angiotensin II facilitates H+ extrusion in the heart. This may help maintain physiological homeostasis, but the hypothesized obligated Na+ influx could exacerbate cellular dysfunction during reperfusion.
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PMID:Angiotensin II stimulates sodium-dependent proton extrusion in perfused ferret heart. 876 51

We investigated the effect of a newly synthesized compound, SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid] on Na+/H+ or Na+/Ca2+ exchange activity in rat cardiomyocytes, and on radioligand binding with several channels or receptors in membrane preparations, and ischemia/reperfusion injury in isolated perfused rat hearts. In myocytes, SM-20550 concentration-dependently inhibited the recovery from acidosis induced by an NH4Cl prepulse in HCO3(-)-free solution. Its IC50 was 10(-8) M, which was 10 times lower than that of ethylisopropyl amiloride (EIPA). SM-20550 (10(-6) M) did not affect the Na+-dependent Ca2+ influx (Na+/Ca2+ exchange activity) in cardiomyocytes. In the radioligand binding assay, SM-20550 did not have affinity for K+ channel, beta-adrenoceptor, adenosine, angiotensin, or endothelin receptors, and had low affinity for Na+ and Ca2+ channels and alpha-adrenoceptors, only at the concentrations of 10(-6)-10(-5) M. In perfused hearts exposed to 40 min of global ischemia and 20 min of reperfusion, SM-20550 (10(-8)-10(-7) M) significantly reduced the elevation of left ventricular end-diastolic pressure during reperfusion, improved the postischemic recovery of developed pressure, and prevented coronary perfusion pressure increase after reperfusion. Furthermore, SM-20550 reduced creatine phosphokinase release during reperfusion and prevented the abnormal gain of tissue Na+ and Ca2+ at the end of reperfusion. These results suggest that SM-20550 is a potent, highly specific Na+/H+ exchange inhibitor, which exerts a protective effect against myocardial ischemia/reperfusion injury. In addition, our data strongly support the hypothesis that Na+/H+ exchange plays an important role in the development of postischemic cardiac dysfunction, most likely by inducing Na+ and Ca2+ overload.
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PMID:SM-20550, a new Na+/H+ exchange inhibitor and its cardioprotective effect in ischemic/reperfused isolated rat hearts by preventing Ca2+-overload. 1083 18

We investigated the effects of simulated ischemia on intracellular Cl- concentration ([Cl-]i) in guinea pig ventricular myocardial cells and possible role of the [Cl-]i on the ischemia/reperfusion-induced arrhythmias in perfused rat hearts. Our results provided direct evidence that the [Cl-]i in ventricular muscle was increased under ischemic conditions, which suggested that activation of the Cl-(-)HCO3- exchanger by ischemia would partially contribute to the elevation of [Cl-]i. Application of stilbene derivatives or lowering Cl- concentration in perfusion solution delayed the onset of ischemia-induced deterioration in action potentials, pHi, [Cl-]i, and suppressed the incidence of ischemia/reperfusion-induced arrhythmias. The conclusion was made to emphasize the important role of intracellular Cl- homeostasis in cardiac physiology and pathogenesis of myocardial ischemia/reperfusion injury.
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PMID:[The relationship between intracellular chloride concentration and ischemia reperfusion-induced arrhythmias in myocardial cells]. 1290 2


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