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

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

The pathogenesis of vertebrobasilar ischemia (VBI) is still uncertain. Embolism and systemic hypotension have been discussed as possible causes. We evaluated the basilar arteries of 35 VBI-patients by transcranial Doppler-sonography at rest and under hypercapnic conditions and compared these findings with the basilar flow velocities in 10 healthy volunteers matched by age. We found no difference between the controls and the VBI-patients for the basilar flow velocities at rest. Under hypercapnia (end-tidal CO2-concentration 8.5%), the basilar blood flow velocities in the healthy controls increased by an average of 53.0% but only by 32.3% in the VBI-patients (p less than 0.005). The reduction of CO2 dependent vasomotor reactivity was observed in all VBI-patients, except in patients with infarction in the posterior cerebral artery area, possibly indicating a different pathogenic mechanism of stroke. The results in all other patients revealed no obvious correlation to the clinical course or angiographic or dopplersonographic findings. As CO2 dependent vasomotor reactivity and brain perfusion pressure dependent cerebral autoregulation have similar mechanisms, we conclude that systemic hypotension might play an important part in VBI.
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PMID:Doppler CO2-test in patients with vertebrobasilar ischemia. 179 55

Experiments were undertaken to test the comparability of changes in respiratory frequency and tidal volume during hypoxia and hypercapnia in rats with and without intact peripheral chemoreceptors and with intact vagi. Neural organisation of respiratory control was perturbed by anemic decerebration, achieved by ligation of the common carotid and basilar arteries. Ischemia of the brain was produced as far candal as the rostral pontine nuclei involved in respiratory control but left the medulla well perfused. The dominant respiratory effect in animals breathing air or oxygen was polypnea with hypocapnia (mean PaCO2 when breathing air 24.7 mmHg, when breathing oxygen 29.6 mmHg). After decerebration the increase of ventilation produced by breathing 10% O2 in N2 was reduced compared with responses in the intact state but levels of ventilation (V1) in hypoxia were similar to those before decerebration. After decerebration, the increase of ventilation produced by breathing 5% CO2 was greatly reduced and the level of V1 in animals breathing CO2 was significantly less than in the intact state. Intermediate changes were seen in animals breathing 2-3% CO2 which converted the hypocapnia (PaCO2 30.9 mmHg) to eucapnia (PaCO2 46.4 mmHg). In the intact state, hypoxia dominantly caused increased frequency (f) and hypercapnia caused increased tidal volume (VT); after decerebration, hypoxia produced reduction of VT while hypercapnia produced reduction of f. Bilateral carotid sinus nerve section in decerebrate animals eliminated the ventilatory response to hypoxia but left the responses to hypercapnia unaltered. The results point to differences in the mechanisms by which hypoxia and hypercapnia influence respiration in both intact and decerebrate animals with carotid sinus and vagus nerves functional. The differences can now be interpreted in terms of specific neural features of respiratory control.
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PMID:Respiratory patterns in anesthetised rats before and after anemic decerebration. 185 90

The effect of alveolar oxygen tension on lung lipid peroxidation during lung ischemia was evaluated by using isolated rat lungs perfused with synthetic medium. After a 5-min equilibration period, global ischemia was produced by discontinuing perfusion while ventilation continued with gas mixtures containing 5% CO2 and a fixed oxygen concentration between 0 and 95%. Lipid peroxidation was assessed by measurement of tissue thiobarbituric acid-reactive products and conjugated dienes. Control studies (no ischemia) showed no change in parameters of lipid peroxidation during 1 h of perfusion and ventilation with 20% or 95% O2. With 60 min of ischemia, there was increased lipid peroxidation which varied with oxygen content of the ventilating gas and was markedly inhibited by ventilation with N2. Perfusion with 5-, 8-, 11-, 14-eicosatetraynoic acid indicated that generation of eicosanoids during ischemia accounted for approximately 40-50% of lung lipid peroxide production. Changes of CO2 content of the ventilating gas (to alter tissue pH) or of perfusate glucose concentration had no effect on lipid peroxidation during ischemia, but perfusion at 8% of the normal flow rate prevented lipid peroxidation. Lung dry/wet weight measured after 3 min of reperfusion showed good correlation between lung fluid accumulation and lipid peroxidation. These results indicate that reperfusion is not necessary for lipid peroxidation with ischemic insult of the lung and provide evidence that elevated PO2 during ischemia accelerates the rate of tissue injury.
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PMID:Oxygen-dependent lipid peroxidation during lung ischemia. 186 76

The effects of ethanol on gastric vasculature in isolated vascularly perfused rabbit stomach was investigated. The isolated stomach was perfused with Krebs-Henseleit solution containing 3% dextran bubbled with 95% O2 and 5% CO2 at a rate of 12 ml/min. After mixture and perfusion of 10 mM to 400 mM of ethanol, perfusion pressure and endothelin-1 concentration in effluent from gastric vasculature were measured. Perfusion pressure and endothelin-1 concentration in effluent increased in a dose-dependent manner with increasing ethanol concentrations. In conclusion, the data suggest that ethanol may stimulate the release of endothelin from gastric vasculature and may cause gastric ischemia due to vasoconstriction resulting in acute gastric mucosal injury.
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PMID:Effect of ethanol on endothelin-1 release from gastric vasculature. 188 67

To evaluate the changes in cerebral blood flow (CBF) that occur immediately after head injury and the effects of different posttraumatic lesions on CBF, 61 CBF studies were obtained using the xenon-computerized tomography method in 32 severely head-injured adults (Glasgow Coma Scale score (GCS) less than or equal to 7). The measurements were made within 7 days after injury, 43% in the first 24 hours. During the 1st day, patients with an initial GCS score of 3 or 4 and no surgical mass had significantly lower flows than did those with a higher GCS score or mass lesions (p less than 0.05): in the first 1 to 4 hours, those without surgical mass lesions had a mean CBF of 27 cc/100 gm/min, which rose to 44 cc/100 gm/min by 24 hours. Patients without surgical mass lesions who died tended to have a lower global CBF than did those with better outcomes. Mass lesions were associated with a high global CBF and bihemispheric contusions with the lowest flows. By 24 hours after injury, global blood flow increased in groups that originally had low flows and decreased in those with very high initial flows, such that by 36 to 48 hours, most patients had CBF values between 32 and 55 cc/100 gm/min. Lobar, basal ganglion, and brain-stem blood flow values frequently differed by 25% or more from global averages. Brain-stem CBF varied the most but did not correlate with clinical signs of brain-stem dysfunction. Double studies were performed at two different pCO2 values in 10 patients with various posttraumatic lesions, and the CO2 vasoresponsivity was calculated. Abnormal CO2 vasoresponsivity was found with acute subdural hematomas and defuse cerebral swelling but not with epidural hematomas. In patients without surgical mass lesions, the findings suggest that CBF in the first few hours after injury is often low, followed by a hyperemic phase that peaks at 24 hours. Global CBF values vary widely depending on the type of traumatic brain injury, and brain-stem flow is often not accurately reflected by global CBF values. These findings underscore the need to define regional CBF abnormalities in victims of severe head injury if treatment is intended to prevent regional ischemia.
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PMID:Acute regional cerebral blood flow changes caused by severe head injuries. 189 94

We tested the hypothesis that cerebral blood flow (CBF) reactivity to CO2 after global ischemia takes longer to recover in 1- to 2-wk-old piglets than in 6- to 10-mo-old pigs. All animals were sedated with ketamine and anesthetized with pentobarbital sodium. Cerebral ischemia was produced by sequentially tightening ligatures around the inferior vena cava and ascending aorta for 10 min. The microsphere-determined CBF response to hypercapnia (arterial PCO2 approximately 65 mmHg) was depressed at 60 min of reperfusion (9 +/- 6% of preischemia; means +/- SE) and remained depressed at 120 min (33 +/- 23% of preischemia, means +/- SE) in young pigs. In older pigs, the response was also depressed at 60 min of reperfusion (21 +/- 9% of preischemia) but was not depressed at 120 min. The pattern for recovery of hypercapnic reactivity was present in most brain regions except cerebellum, where CO2 reactivity returned to control in young animals by 120 min of reperfusion. The response to hypocapnia (arterial PCO2 approximately 25 mmHg) was also better preserved in older pigs. In older pigs recovery of CO2 reactivity during reperfusion paralleled recovery of cerebral O2 consumption over time. We conclude that older pigs have quicker return of CBF CO2 reactivity following transient global ischemia, which may be due to age-related differences in mechanisms of vascular reactivity.
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PMID:Age-related cerebrovascular reactivity to CO2 after cerebral ischemia in swine. 190 1

The cheek pouch was prepared as a single layer and attached to a two-piece Lucite chamber that was filled with bicarbonate buffer (pH 7.35, equilibrated with 95% N2-5% CO2). Two microcirculatory areas were circumscribed in the cheek pouch by equilateral triangular chambers. Each chamber was made of 90-microns thick Mylar sheet (2 mm wide, 18 mm long). A cover slip was used as the chamber top. Ischemia was induced by applying pressure to the cover slip. The experimental area was reperfused after 1 h of ischemia by releasing the pressure. The other area served as control. One hour of reperfusion after 1 h of ischemia caused a significant increase in the number of leukocytes adhering to postcapillary venules (PCVs) per 100 microns vessel length in the ischemic area relative to the values in the control area (7.8 +/- 2.5 vs. 3.7 +/- 1.3, respectively, for PCVs 10-19.9 microns diam; and 10.9 +/- 2.8 vs. 6.2 +/- 1.8 for PCVs 20-29.9 microns diam; P less than 0.01 for both comparisons). The results demonstrate the adequacy of the model to investigate leukocyte adhesion to endothelium in ischemia-reperfusion. Because blood flow is maintained in most of the pouch, our model should also be useful for identifying possible interactions between ischemic and nonischemic areas in the microcirculation.
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PMID:A new model for studying ischemia-reperfusion injury in hamster cheek pouch. 195 48

The authors sought to determine how hypoperfusion influences acid-base balance in arterial and mixed venous blood. In anesthetized, ventilated pigs (n = 12), we determined hemodynamics, O2 uptake, CO2 output, dead-space ventilation, arterial and mixed venous blood acid-base balances, and lactate concentrations during graded reductions in cardiac output by incremental positive end-expiratory pressure (PEEP, 0-20 cm H2O). Cardiac output decreased from 3.2 +/- 0.2 (mean +/- SEM) to 1.2 +/- 0.1 L/min at 20 cm H2O PEEP. Oxygen delivery declined more than O2 uptake did by 60% +/- 2% and 27% +/- 2%, respectively. The decrease in CO2 output (by 21% +/- 2%) was less than that in O2 uptake. Fractional dead-space ventilation increased. At a slight increase in carbon dioxide tension (PCO2) of 4 +/- 1 mm Hg, pH decreased in arterial blood from 7.54 +/- 0.01 to 7.47 +/- 0.02 mmol/L, and standard bicarbonate decreased from 30.3 +/- 0.5 to 27.5 +/- 0.6 mmol/L. The decrease in standard bicarbonate exceeded the increase in blood lactate concentrations. At a similar decrease in standard bicarbonate, the decrease in pH was larger (P less than 0.005) in mixed venous blood than in arterial blood owing to a larger increase in PCO2 (from 40 +/- 2 to 50 +/- 2 mm Hg, P less than 0.005). The changes were reversed after discontinuing PEEP. The authors conclude that ischemia after incremental PEEP results in tissue metabolic acidosis with superimposed respiratory acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arterial and mixed venous blood acid-base balance during hypoperfusion with incremental positive end-expiratory pressure in the pig. 195 38


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