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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Magnetic resonance (MR) images obtained in 15 patients with delayed encephalopathy after acute carbon monoxide (CO) intoxication were reviewed. Images had been obtained 4-9 weeks after exposure to CO, during the relapse of neuropsychiatric symptoms after initial recovery. Bilateral symmetric confluent high signal intensity in the periventricular white matter and centrum semiovale was seen on long-repetition-time images (n = 15). The high intensity extended into the corpus callosum (n = 11), subcortical U fibers (n = 12), and external (n = 9) and internal (n = 7) capsules. Bilateral diffuse low-intensity signal in the thalamus and putamen on T2-weighted images, suggesting iron deposition, was demonstrated in 10 patients. Bilateral ischemia or necrosis of the globus pallidus was seen in nine patients. In three of four patients with follow-up MR imaging studies, a decrease in extent and signal intensity of white matter lesions accompanied lessening of clinical symptoms. These results suggest that the main pathologic feature of delayed encephalopathy associated with CO intoxication is a reversible demyelinating process of the cerebral white matter.
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PMID:Delayed encephalopathy after acute carbon monoxide intoxication: MR imaging features and distribution of cerebral white matter lesions. 160 67

We characterized the release of arachidonic acid (AA) metabolites in lung effluent following lung ischemia-reperfusion since they may contribute to the pathophysiology of reperfusion lung injury. The left pulmonary artery of rabbits (N = 5) was occluded for 24 hrs with a surgically implanted vascular clip. At 24 hrs, the heart and lungs were removed en bloc and perfused with Ringers-albumin (0.5 gm%) at 60 ml/min while statically inflated with 95% O2-5% CO2. The lipid fraction of the lung effluent was concentrated using the Bligh-Dyer extraction and analyzed by gradient RP-HPLC. Samples obtained in the first minute of reperfusion showed significant increases in LTB4 (+180%), LTC4 (+3600%), 15-HETE (+370%), 5-HPETE (+270%), PGE2 (+140%), 6-keto-PGF1 alpha (+110%) and 12-HHT (+160%) compared to the effluent from the right control lung. The reperfusion-induced increases in LTB4, LTC4, LTD4 and 15-HETE were inhibited greater than or equal to 70% by pretreatment with the 5-LO inhibitors L663,536 or L651,392. The increases in lipid concentrations corresponded to significantly increased pulmonary arterial pressure from a baseline value of 9.5 +/- 0.3 to 29.3 +/- 2.9 (cmH2O) during the first min of reperfusion. The pulmonary arterial pressure remained elevated for at least 20 min of reperfusion. Reperfusion also resulted in PMN uptake (assessed by lung tissue myeloperoxidase content) in the reperfused lung versus control lung (25.0 +/- 2.4 vs. 10.5 +/- 2.5 units). The generation of lipoxygenase metabolites during the initial phase of reperfusion may contribute to post-reperfusion PMN uptake and pulmonary vasoconstriction.
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PMID:Generation of 5-lipoxygenase metabolites following pulmonary reperfusion in isolated rabbit lungs. 160 20

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

To test the hypothesis that O2 chemoreception in the carotid body (CB) is mediated by cellular acidosis, we simultaneously measured responses of the chemosensory and intracellular pH (pHi) to agents that are known to change pHi and studied the effects of hypoxia and ischemia on these variables in the cat CB. The CB was perfused and superfused in vitro with a modified Tyrode's solution at 36.0 +/- 0.5 degrees C with or without CO2-HCO3- (pH 7.40) and equilibrated at a given PO2. Chemosensory discharges were recorded from the whole carotid sinus nerve. To measure pHi changes, the CB was loaded with the pH-sensitive indicator 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, and the fluorescence (excitation 420-490 nm, emission greater than 515 nm) was detected by an intensified charged coupled device camera with an epifluorescence macroscope. Boluses of Tyrode's solution (0.5 ml, free of CO2-HCO3-) containing sodium acetate or NH4Cl prolonged perfusion of acid Tyrode's solution (pH 7.20-6.50), and boluses of Tyrode's solution with CO2-HCO3- were used. A decrease of fluorescence indicated pHi turning acid, and an increase of fluorescence indicated a change in alkaline pHi. Chemosensory activity varied inversely with the fluorescence change after application of these agents. Interruption of perfusate flow or application of hypoxic perfusate resulted in large increases in chemosensory discharge without any change in the fluorescence. The results indicated that chemosensory responses to brief ischemia and hypoxia were not mediated by a fall of pHi of CB cells, whereas those to CO2 and extracellular acidity were associated with decreases in pHi.
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PMID:Intracellular pH and oxygen chemoreception in the cat carotid body in vitro. 162 81

In order to understand the pathophysiology of myocardial stunning, reversibility, accumulation and continuity of ischemic myocardial damage after reperfusion should be studied. Then, to analyze these three factors, myocardial function, metabolism and morphology under ischemia and reperfusion were studied in anesthetized, open-chest dogs. When myocardial ischemia was induced by occlusion of the left anterior descending coronary artery, percentage regional systolic shortening (%SS) of ischemic myocardium sharply decreased and became stable 10 min after occlusion. After reperfusion, ischemic myocardium showed active shortening after within 30-min occlusion, but did not after more than 60-min occlusion. During 90-min of ischemia, extracellular K+ concentration (Ke) steeply increased for first 10 min and was almost stable for next 10 min. Then, Ke straightly increased till 90 min. Metabolic rates, calculated from myocardial tissue CO2 and pH, steeply increased for first 20 min and sharply decreased for next 10 min. After 30 min, these two variables were almost stable, near zero. By electron-microscopy with cytochemistry, distribution of Na/K ATPase to myocardial cell membrane was observed to be almost after 15-min occlusion but distinctly sparse with destruction of cell membrane after 30-min occlusion. Therefore, irreversible myocardial damage appears after about 20-min ischemia and is almost complete after 60 min. Reversibility of damage to ischemic myocardium after reperfusion may mainly occur within 60-min ischemia. Although stunned myocardium in a narrow sense is may appear after reperfusion within less than 20-min of ischemia, stunned myocardium in a broad sense may appear within less than 60-min ischemia. When reversible myocardial ischemia (4- or 15-min occlusion) was repeated after short time intervals (20-min reperfusion), %SS of ischemic myocardium was gradually decreased with each ischemic episode. Active shortening of ischemic myocardium disappeared after more than two episodes of 15-min occlusion. Fluctuation of PCO2, pH and Ke of ischemic myocardium was gradually depressed with each occlusion. Metabolic viability of ischemic myocardium was cumulatively depressed by repeated brief occlusion. Naturally, myocardial damage was more severe after repeated 15-min occlusion than after 4-min occlusion. Accumulation of ischemic myocardial damage may arise as brief ischemia, which only induces reversible damage, is repeated. At last, continuity of ischemic myocardial damage was studied. The effect of 5-min occlusion to %SS of ischemic myocardium was apparently reversed after 90-min reperfusion. Early contractile failure was advanced even after very short duration of ischemia. Thus, myocardial function will be latently damaged.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pathophysiology of myocardial stunning: reversibility, accumulation and continuity of the ischemic myocardial damage after reperfusion. 165 10

We investigated in the isolated rat heart the influence of the gas surrounding the globally ischemic heart on transmural inhomogeneity of energy metabolism, extracellular K+ accumulation, and change of extracellular pH. Hearts were made ischemic in 100% N2 (N2-ischemia), 100% O2 (O2-ischemia) or 100% CO2 (CO2-ischemia). We measured: 1) Midmural, subepicardial, and epicardial changes of extracellular [K+] and pH during successive 6-min periods of global ischemia, and 2) content of creatinephosphate (CrP) in consecutive tissue sections of 100 microns, from the subepicardium after 10 min of ischemia. A) During O2-ischemia both extracellular [K+] and change of pH in the subepicardium are significantly less than in the midmyocardium. During N2-ischemia only minor differences exist in [K+] and pH between the subepicardium and the midmyocardium. During CO2-ischemia midmural and subepicardial [K+] are similar to those during N2-ischemia. The midmural change of pH resembles that during N2-ischemia; subepicardial change of pH, however, was slightly larger. Midmural changes in [K+] and pH were not influenced by the nature of the surrounding gas. B) After 10 min of O2-ischemia a gradient of tissue content of CrP extends from the epicardium (CrP about 30 mumoles/g dry weight) to a distance of about 1000 microns (CrP 1 mumoles/g dry weight). In N2- and CO2-ischemia a CrP gradient is absent; CrP is appreciably less than 1 mumoles/g dry weight at any distances from the epicardium. C) We conclude that diffusion of O2 into the myocardium and of CO2 from the myocardium affects transmural gradients of [K+], pH, and energy metabolism during ischemia. Local availability of O2 increases the capacity of the ischemic tissue to generate high energy phosphates and mitigates ischemia-induced changes of transsarcolemmal ion gradients.
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PMID:Transmural inhomogeneity of extracellular [K+] and pH and myocardial energy metabolism in the isolated rat heart during acute global ischemia; dependence on gaseous environment. 169 28

The role of local accumulation and diffusion of CO2 to modify cellular loss and extracellular accumulation of K+ during the initial, reversible phase of myocardial ischemia was investigated in isolated, cylindrical papillary muscles of the rabbit. The muscles were blood-perfused through their vascular tree and placed in a (permanently flowing) humidified gas mixture with predetermined partial pressures of N2, O2, and CO2. Ischemia was produced by total arrest of perfusion and O2 withdrawal from the gas mixture. With surface PCO2 kept constant during ischemia, [K+]o varied markedly with muscle geometry. After 10 minutes of ischemia, K+ accumulation was approximately 2.5 mM in muscles with a radius of 0.35 mm and approximately 14 mM in muscles with a radius of 0.9 mm, indicating that a large fraction of K+ accumulation was dependent on diffusion of a volatile metabolite. Computer simulation of CO2 accumulation and diffusion within a tissue cylinder suggested a close phenomenological relation between PCO2 and [K+]o in ischemia. This was confirmed by the finding that an increase of tissue PCO2 in small cylinders before or during ischemia by externally applied CO2 produced an increase in K+ accumulation. The importance of CO2 diffusion for local inhomogeneities in K+ within the same preparation was demonstrated by showing [K+]o gradients with simultaneous or consecutive measurements between the papillary muscle cylinders and the adjacent septum and within 300 microns from the surface of the papillary muscle cylinders. These gradients predict an inhomogeneity of impulse conduction that might contribute to the genesis of ventricular arrhythmias. Besides the demonstration that accumulation and diffusion introduce inhomogeneities of [K+]o in ischemia, our results suggest that a significant component of cellular ischemic K+ loss is associated with production and extrusion of metabolic acid. On the basis of previous measurements of pHo and pHi in identical conditions, possible mechanisms of ischemic cellular K+ loss are discussed.
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PMID:Early changes in extracellular potassium in ischemic rabbit myocardium. The role of extracellular carbon dioxide accumulation and diffusion. 173 38

The quantification of adenine nucleotides released from the heart is hampered by their rapid dephosphorylation to adenosine in the extracellular space catalyzed by highly active ectonucleotidases. To determine the total release of adenine nucleotides from isolated Langendorff-perfused guinea pig hearts, ecto 5'-nucleotidase was effectively blocked by infusion of alpha, beta-methylene-ADP (AOPCP, 50 microM). Adenine nucleotides were measured in the coronary venous effluent by the luciferin-luciferase method after enzymatic rephosphorylation to ATP. In hearts perfused at a constant flow rate (10 ml/min) with normoxic buffer (95% O2, 5% CO2) the release +/- SEM of adenine nucleotides and adenosine was 0.06 +/- 0.01 (n = 11) and 0.04 +/- 0.01 (n = 13) nmol/min. In the presence of AOPCP, the release of adenine nucleotides increased to 0.43 +/- 0.04 nmol/min (n = 9; p less than 0.05), whereas adenosine remained unchanged. Hypoxic perfusion (10% O2, 85% N2, 5% CO2) caused a threefold increase in adenine nucleotide release but a 40-fold increase in adenosine. In contrast, global ischemia (30 seconds) caused adenine nucleotide and adenosine release to rise to similar values of 1.06 +/- 0.10 and 0.80 +/- 0.14 nmol/min (n = 9). Stimulation of hearts with isoproterenol (4 nM) likewise increased the release of adenine nucleotides (0.50 +/- 0.04 nmol/min) and adenosine (0.87 +/- 0.21 nmol/min) (n = 6). To determine the cellular source of adenine nucleotides released from the heart, the coronary endothelial adenine nucleotide pool was selectively prelabeled by [3H]adenosine. Global ischemia increased the specific radioactivity of released adenine nucleotides by 57%. The findings indicate that 1) adenine nucleotides and adenosine are released at the same order of magnitude from the well-oxygenated heart; 2) beta-adrenergic stimulation and ischemia stimulate the release of adenine nucleotides and adenosine, both purines reaching vasoactive concentrations in the effluent perfusate; 3) during hypoxic perfusion only the release of adenosine is greatly enhanced; and 4) the coronary endothelium preferentially contributes to the ischemia-induced adenine nucleotide release.
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PMID:Adenine nucleotide release from isolated perfused guinea pig hearts and extracellular formation of adenosine. 174 67

Multiple measurements of pulmonary function were performed during exercise testing in 29 patients with coronary artery disease (CAD) before and after exercise training. Following training, significant increases in oxygen consumption (VO2), carbon dioxide production (VCO2), and peak flow at maximal exercise were seen as compared with pretraining values (p less than .01), but not in any other respiratory variables. Only the peak respiratory exchange ratio (RER) achieved during pretraining exercise testing and peak values of minute ventilation (VT), respiratory rate, and VCO2 during a posttraining exercise test showed significant correlations with the change in maximum VO2 following exercise training (p less than .05). Significant correlations were also found among VT, VCO2, and peak flow at peak exercise following exercise training and the change in exercise duration between pretraining and posttraining stress tests. Of 22 patients evaluated with thallium 201 scintigraphy during their pretraining exercise test, 11 developed ischemic ST depression or a reversible perfusion defect. No significant differences in pulmonary function measurements during exercise testing were seen between patients who developed ischemia and those who did not. However, the change in peak metabolic equivalents (METS) achieved between pretraining and posttraining exercise was significantly greater in patients who developed ischemia (.836 +/- 1.003 versus .091 +/- .481, p less than .05). These results indicate that exercise training in patients with CAD is not associated with significant changes in most measurements of pulmonary function and, with the exception of RER at peak exercise, pretraining measurements do no show a significant correlation with changes in exercise capacity.
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PMID:Effect of exercise training on multiple respiratory variables in patients with coronary artery disease: correlation with change in exercise capacity. 176 28

A comparison of the respiratory responses of jogging in place, an alternative exercise test we recently proposed, was made with those of the Bruce exercise test. We obtained on-line measurements of heart rate, ventilation, oxygen uptake, and carbon dioxide production from 9 healthy subjects of mean age 25 years. There was a higher heart rate and ventilatory response with jogging than with the Bruce test, but by 10 minutes the responses of the two tests were similar. Oxygen consumption, while higher with jogging, rose in parallel with that of the Bruce test from the second to the seventh min, and the change of the ratio of minute ventilation to oxygen consumption indicated that the anaerobic threshold occurred earlier during jogging. These results show that jogging in place is more vigorous than the graded exercise test and may produce ischemia earlier.
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PMID:Comparison of respiratory response of jogging in place and Bruce treadmill exercise test. 176 28


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