Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that angiotensin II-dependent hemodynamic effects are in part mediated by thromboxane A2 (TXA2). The present study investigates in 6 healthy normotensive men whether prostaglandin H2-TXA2 receptor blockade with 100 mg of linotroban (5(2-(phenylsulfonylamino)ethyl)-thienyloxy-acetic acid) p.o. influences angiotensin II-dependent peripheral regional vasoconstriction. Moreover, the regional balance of thromboxane B2 (TXB2), a stable metabolite of TXA2, across the leg vascular bed was assessed at baseline conditions as well as during exogenous infusion (0.2 microgram/min) of angiotensin II. Net transfemoral TXB2 balance was calculated from the respective arteriovenous plasma concentration differences and the corresponding regional plasma flow, the latter being determined by indocyanine-green dye, using appropriate catheterization techniques. Angiotensin II (0.2 microgram/min) induced a 66% increase in leg vascular resistance (p < 0.01) without affecting systemic hemodynamics. These regional hemodynamic effects of angiotensin II were not influenced by prostaglandin H2-TXA2 receptor blockade. Baseline TXB2 balance across the femoral vascular bed was equilibrated at slight extraction rates or around zero and remained unchanged during angiotensin II infusion. These results suggest that, in healthy man, angiotensin II-dependent, nonischemic peripheral vasoconstriction is not mediated by TXA2. Possible benefits of prostaglandin H2-TXA2 receptor blockade in pathological conditions with tissue malperfusion or ischemia are discussed.
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PMID:Thromboxane A2 does not mediate angiotensin II-dependent nonischemic peripheral vasoconstriction in healthy men: a pilot study. 914 8

We tested the hypothesis that heat-shock protected myocardial Ca2+-cycling by sarcoplasmic reticulum from ischemia and reperfusion (I/R) injury. Twenty-four hours after increasing body temperature to 42 degrees C for 15 min, rat hearts were isolated, Langendorff-perfused, and subjected to 30 min ischemia then 30 min reperfusion. Left ventricles were homogenized and their ionized Ca2+ concentration monitored with indo- during Ca2+-uptake in the presence and absence of the Ca2+-release channel (CRC) modulator ryanodine. Tissue content of heat-shock protein 72 (HSP 72) was analyzed. Exposure to I/R resulted in a 37% enhancement of CRC activity but no effect on Ca2+-pumping activity, resulting in 25% decreased net Ca2+-uptake activity. Pre-exposure to heat-shock resulted in a 10-fold increase in HSP 72, and a 25% enhancement of maximal Ca2+-pumping activity which counteracted the effect of I/R on CRC and net Ca2+-uptake activities. This protection of SR Ca2+-cycling was associated with partial protection of myocardial physiological performance. Net Ca2+-uptake activity was correlated with the left ventricular developed pressure and its rate of change. We conclude that one of the mechanisms by which heat-shock protects myocardium from I/R injury is to upregulate SR Ca2+-pumping activity to counteract the enhanced SR Ca2+-release produced by I/R.
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PMID:Compensatory up-regulation of cardiac SR Ca2+-pump by heat-shock counteracts SR Ca2+-channel activation by ischemia/reperfusion. 927 64

An in vivo model has been developed for chronic observation of the effects of ischemia on cortical bone remodeling and perfused vascularity. Diaphragm occluders were implanted around the right common iliac artery of four rabbits and inflated to produce 10 h of ischemia to the limb. Microcirculation was monitored with intravital microscopy of injected fluorescent microspheres and FITC-Dextran 70 through a bone window, the tibial bone chamber implant (BCI). Bone resorption and apposition in the BCI were indicated with mineralization dyes. Between 2 and 12 h following release of the occluder, secondary ischemia/no-reflow and other evidence of reperfusion injury were observed. Vessel damage was suggested by abnormally high leakage of FITC-D70 from the few vessels perfused during secondary ischemia. In the weeks following occluder release perfused vasculature increased beyond pre-occlusion levels. Net bone resorption reached a maximum when vascularity passed normal levels. In order to further validate the arterial occlusion model for osteonecrosis, techniques for (1) confirming bone death and (2) detecting increased leukocyte adherence to endothelial cells were added. The dead cell stain Ethidium homodimer-1 was used to tag dead osteocytes immediately after occlusion and produced a measure designated "osteonecrosis index." To detect leukocytes adhering to vessel walls, carboxyfluorescein diacetate, succinimidyl ester was injected at occluder release. An increase in the number of adherent leukocytes was detected.
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PMID:Model for intravital microscopic evaluation of the effects of arterial occlusion-caused ischemia in bone. 1046 35

We review the information obtained by 13C NMR methods on the metabolic compartmentation of the adult mammalian brain with emphasis on its quantitative aspects. Classical radiotracer evidence and more recent 13C NMR results support the presence in the brain of at least two glutamate pools, small and large, associated with two kinetically different tricarboxylic acid cycles localized in glia and neurons, respectively. Neuronal and glial cycles interact closely, utilizing common substrates like glucose and oxygen and exchanging a variety of metabolites including glutamate, glutamine and GABA. A model for the cerebral metabolism of (1,2-13C2) acetate has made it possible to calculate fluxes through both cycles and evaluate the exchanges of glutamate, glutamine and GABA under different physiopathological conditions. Calculated flux values through the neuronal and glial tricarboxylic acid cycles are 1.0 and 0.4 mumol/min g, respectively. In the adult normoxic brain, the small and large glutamate pools account for approximately 10% and 90% of cerebral glutamate with estimated turnover times of 1.25 and 5.8/min, respectively. Net transfers of neuronal glutamate and GABA to the glial compartment are calculated to be 0.1 and 0.04 mumol/min g while transfer of glial glutamine to the neuronal compartment is estimated as 0.1 mumol/min g. Pyruvate recycling in the adult brain occurs mainly in the synaptic terminals with a calculated flux of 0.3 mumol/min g. These flux values are altered severely in pathological states such as hypothyroidism or ischemia.
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PMID:Quantitative 13C NMR studies of metabolic compartmentation in the adult mammalian brain. 1065 92

We examined myocardial 5'-adenosine monophosphate (5'-AMP) catabolism, adenosine salvage and adenosine responses in perfused guinea pig, rat and mouse heart. MVO(2) increased from 71+/-8 microl O(2)/min per g in guinea pig to 138+/-17 and 221+/-15 microl O(2)/min per g in rat and mouse. VO(2)/beat was 0.42+/-0.03, 0.50+/-0.03 and 0.55+/-0.04 microl O(2)/g in guinea pig, rat and mouse, respectively. Resting and peak coronary flows were highest in mouse vs. rat and guinea pig, and peak ventricular pressures and Ca(2+) sensitivity declined as heart mass increased. Net myocardial 5'-AMP dephosphorylation increased significantly as mass declined (3.8+/-0.5, 9.0+/-1.4 and 11.0+/-1.6 nmol/min per g in guinea pig, rat and mouse, respectively). Despite increased 5'-AMP catabolism, coronary venous [adenosine] was similar in guinea pig, rat and mouse (45+/-8, 69+/-10 and 57+/-14 nM, respectively). Comparable venous [adenosine] was achieved by increased salvage vs. deamination: 64%, 41% and 39% of adenosine formed was rephosphorylated while 23%, 46%, and 50% was deaminated in mouse, rat and guinea pig, respectively. Moreover, only 35-45% of inosine and its catabolites derive from 5'-AMP (vs. IMP) dephosphorylation in all species. Although post-ischemic purine loss was low in mouse (due to these adaptations), functional tolerance to ischemia decreased with heart mass. Cardiovascular sensitivity to adenosine also differed between species, with A(1) receptor sensitivity being greatest in mouse while A(2) sensitivity was greatest in guinea pig. In summary: (i) cardiac 5'-AMP dephosphorylation, VO(2), contractility and Ca(2+) sensitivity all increase as heart mass falls; (ii) adaptations in adenosine salvage vs. deamination limit purine loss and yield similar adenosine levels across species; (iii) ischemic tolerance declines with heart mass; and (iv) cardiovascular sensitivity to adenosine varies, with increasing A(2) sensitivity relative to A(1) sensitivity in larger hearts.
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PMID:5'-Adenosine monophosphate and adenosine metabolism, and adenosine responses in mouse, rat and guinea pig heart. 1169 99

The mitochondrial K+ cycle consists of influx and efflux pathways for K+ and anions. Net movement of K+ salts across the inner membrane causes changes of matrix volume, so regulation of the cycle is vital for maintaining the structural integrity of the organelle. The mitochondrial K+ cycle also appears to play important roles in cellular pathophysiology in vivo. Opening the mitochondrial ATP-sensitive K+ channel (mitoK(ATP)) prior to ischemia protects the heart from ischemia-reperfusion injury. MitoK(ATP) is an important player in the cell signaling pathways for ischemic protection and also for gene transcription, roles that appear to depend on the ability of mitoK(ATP) opening to trigger increased mitochondrial production of reactive oxygen species. MitoK(ATP) opening during both ischemia and reperfusion and during the high work state is found to preserve the structure of the intermembrane space and thereby maintains the normally low outer membrane permeability to adenine nucleotides. This review discusses the properties of the mitochondrial K+ cycle that help to understand the basis of these effects.
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PMID:The mitochondrial potassium cycle. 1179 27

Net phosphocreatine (PCr) resynthesis during muscle contraction is a paradoxical phenomenon because it occurs under conditions of high energy demand. The metabolic underpinnings of this phenomenon were analyzed non-invasively using 31P-magnetic resonance spectroscopy in rat gastrocnemius muscle (n=11) electrically stimulated (7.6 Hz, 6 min duration) in situ under ischemic and normoxic conditions. During ischemic stimulation, [PCr] initially fell to a steady state (9+/-5% of resting concentration) which was maintained for the last 5 min of stimulation, whereas isometric force production decreased to a non-measurable level beyond 3 min. Throughout normoxic stimulation, [PCr] and force production declined to a steady state after respectively 1 min (5+/-3% of resting concentration) and 3.25 min (21+/-8% of initial value) of stimulation. Contrary to the observations under ischemia, a paradoxical net PCr resynthesis was recorded during the last 2 min of normoxic stimulation and was not accompanied by any improvement in force production. These results demonstrate that the paradoxical net PCr resynthesis recorded in contracting muscle relies exclusively on oxidative energy production and could occur in inactivated fibers, similarly to PCr resynthesis during post-exercise recovery.
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PMID:Metabolic underpinnings of the paradoxical net phosphocreatine resynthesis in contracting rat gastrocnemius muscle. 1199 31

Functional neurological outcome after transient ischemia might be improved by timely therapeutic intervention. To determine if restorative behavioral therapy influences damage, improves task learning, or alters astrocyte metabolic activity after ischemia, rats (food-restricted to 85% of free-feeding weight) were (a) first trained to respond on one of two levers under a fixed-ratio 20 schedule of food presentation (FR20), then (b) subjected to sham manipulation of carotid arteries or 10 min ischemia by four-vessel occlusion, followed by (c) 4 days of operant testing or inactivity, (d) then all rats were tested under a FR20 lever reversal task for 4 weeks, and (e) 3 days after the last behavioral session astrocyte metabolism was assayed by local uptake of [2-14C]acetate. Mild loss of hippocampal neurons occurred in ischemic rats with or without training after ischemia. Glial fibrillary acidic protein-positive astrocytes were present in similar numbers throughout brains of sham control and ischemic rats. Mild ischemia did not impair learning, and no changes in FR20 reversal learning were detected in sham vs. ischemic rats. Net [14C]acetate uptake was unaffected by ischemia but [14C]acetate uptake increased 15-24% (P<0.05; n=12-15/group) in specific structures (caudate, primary motor and sensorimotor cortex, CA1 hippocampus, subcortical white matter) in the pooled groups of rats that had 4 days FR20 testing vs. inactivity before reversal learning. 'Behavioral therapy' (operant testing on the 4 days immediately following either sham manipulation or ischemia) did not alter ischemic outcome, but was associated with higher acetate utilization in regions involved in motor activities.
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PMID:Behavioral training increases local astrocytic metabolic activity but does not alter outcome of mild transient ischemia. 1253 87

Ischemic acute renal failure (iARF) was described to reduce renal extraction of the organic anion para-aminohippurate (PAH) in humans. The rate-limiting step of renal organic anion secretion is its basolateral uptake into proximal tubular cells. This process is mediated by the organic anion transporters OAT1 and OAT3, which both have a broad spectrum of substrates including a variety of pharmaceutics and toxins. Using a rat model of iARF, we investigated whether impairing the secretion of the organic anion PAH might be associated with downregulation of OAT1 or OAT3. Inulin and PAH clearance was determined starting from 6 up to 336 h after ischemia-reperfusion (I/R) injury. Net secretion of PAH was calculated and OAT1 as well as OAT3 expression was analyzed by RT-PCR and Western blotting. Inulin and PAH clearance along with PAH net secretion were initially diminished after I/R injury with a gradual recovery during follow-up. This initial impairment after iARF was accompanied by decreased mRNA and protein levels of OAT1 and OAT3 in clamped animals compared with sham-operated controls. In correlation to the improvement of kidney function, both mRNA and protein levels of OAT1 and OAT3 were upregulated during the follow-up. Thus decreased expression of OAT1 and OAT3 is sufficient to explain the decline of PAH secretion after iARF. As a result, this may have substantial impact on excretion kinetics and half-life of organic anions. As a consequence, the biological effects of a variety of organic anions may be affected after iARF.
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PMID:Downregulation of organic anion transporters OAT1 and OAT3 correlates with impaired secretion of para-aminohippurate after ischemic acute renal failure in rats. 1724 91

Bivalirudin has been associated with decreased bleeding, with similar rates of ischemia in patients with stable angina, unstable angina, non-ST elevation myocardial infarction and elective percutaneous coronary intervention (PCI). The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial tested whether with primary PCI, bivalirudin--compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor--reduced bleeding and net clinical benefit (bleeding, death, reinfarction, target-vessel revascularization for ischemia or stroke). Bivalirudin reduced major bleeding by 40% (4.9 vs 8.3%; risk ratio [RR]: 0.60; 95% confidence interval [CI]: 0.46-0.77; p < 0.0001) as compared with unfractionated heparin and a IIb/IIIa antagonist. Net adverse clinical events were reduced (9.2 vs 12.1%; RR: 0.76: 95% CI: 0.63-0.92; p = 0.005). Cardiac death and total death at 30 days were reduced with bivalirudin (1.8 vs 2.9%; p = 0.03) and (2.1 vs 3.1%; p = 0.047), and at 12 months (2.1 vs 3.8%; p < 0.005) and (3.4 vs 4.8%; p = 0.029), respectively. Bivalirudin reduced bleeding and net adverse clinical events as well as mortality compared with unfractionated heparin and a glycoprotein IIb/IIIa inhibitor. Bivalirudin is an attractive antithrombotic choice in patients undergoing primary PCI.
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PMID:HORIZONS trial: a step forward for primary percutaneous coronary intervention. 1921 Feb 8


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