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)

Ischemic preconditioning (IP) has been proposed as an endogenous form of protection against ischemia reperfusion injury. IP, however, does not prevent post-ischemic dysfunction in the aging heart but may be partially corrected by exercise training and food restriction. We investigated the role of exercise training combined with food restriction on restoring IP in the aging heart. Effects of IP against ischemia-reperfusion injury in isolated hearts from adult (A, 6 months old), sedentary 'ad libitum' fed (SL), trained ad libitum fed (TL), sedentary food-restricted (SR), trained- and food-restricted senescent rats (TR) (24 months old) were investigated. Norepinephrine release in coronary effluent was determined by high performance liquid cromatography. IP significantly improved final recovery of percent developed pressure in hearts from A (p<0.01) but not in those from SL (p=NS) vs unconditioned controls. Developed pressure recovery was partial in hearts from TL and SR (64.3 and 67.3%, respectively; p<0.05 vs controls) but it was total in those from TR (82.3%, p=NS vs A; p<0.05 vs hearts from TL and SR). Similarly, IP determined a similar increase of norepinephrine release in A (p<0.001) and in TR (p<0.001, p=NS vs adult). IP was abolished by depletion of myocardial norepinephrine stores by reserpine in all groups. Thus, IP reduces post-ischemic dysfunction in A but not in SL. Moreover, IP was preserved partially in TR and SR and totally in TR. Complete IP maybe due to full restoration of norepinephrine release in response to IP stimulus.
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PMID:Tandem action of exercise training and food restriction completely preserves ischemic preconditioning in the aging heart. 1566 31

We investigated the role of endothelin-A (ETA) and endothelin-B (ETB) receptors in ischemia/reperfusion-induced cardiac dysfunction and norepinephrine overflow using isolated rat hearts. According to the Langendorff technique, isolated hearts were subjected to 40 minutes of global ischemia followed by 30 minutes of reperfusion. Ischemia/reperfusion led to decreases in left ventricular developed pressure and coronary flow, and an increase in left ventricular end-diastolic pressure compared with pre-ischemic basal levels. An ETB receptor antagonist A-192621 at 1 microM worsened ischemia/reperfusion-induced cardiac dysfunction. In contrast, an ETA receptor antagonist ABT-627 at 5 microM with or without A-192621 improved the aforementioned cardiac dysfunction, to the same extent. Norepinephrine was massively released in coronary effluent from the hearts exposed to ischemia/ reperfusion. Treatment with ABT-627 significantly suppressed the norepinephrine overflow induced by the ischemia/reperfusion whereas A-192621 further enhanced it, which was completely abolished by the concomitant treatment with ABT-627. These results suggest that the detrimental effect of ETB receptor blockade on post-ischemic cardiac function is mediated by the ETA receptor-related action and that norepinephrine overflow from sympathetic nerve endings is closely related to the antagonist-induced functional changes of post-ischemic hearts.
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PMID:Effects of ET(A) and ET(B) receptor blockade on post-ischemic cardiac dysfunction and norepinephrine overflow in isolated rat hearts. 1583 30

Acute renal failure (ARF) induced by sepsis has a high mortality but lacks effective treatments. To develop novel therapies we must diagnose renal injury early and accurately in septic patients and identify any additional insults such as nephrotoxic drugs and ischemia. In this short review we describe our experience using MRI with dendrimer-based contrast agents in mouse models of ARF. This technique can diagnose early renal injury before serum creatinine is elevated, distinguish different ARF etiologies, track drug therapy and predict outcome. As an ARF biomarker, MRI with dendrimer-based contrast is a promising technique deserving further development.
Nephron Clin Pract 2006
PMID:Imaging acute renal failure with polyamine dendrimer-based MRI contrast agents. 1654 55

The importance of analyzing the kinetics of reactive oxygen species or related substances in vivo is increasing. Electron paramagnetic resonance (EPR) is currently a powerful method for in vivo, non-invasive analysis of oxidative stress. We have applied EPR imaging for murine renal ischemia-reperfusion injury, as a model of acute renal damage, and NF-E2-related factor 2 (Nrf2)-deficient mice, a model for chronic progressive renal disease. In the ischemia-reperfusion model, EPR imaging revealed that the renal radical-reducing activity showed only partial recovery when serum creatinine and BUN have recovered. In the Nrf2-deficient mice, we have revealed that the impaired antioxidant activity is brought by both Nrf2 deficiency and the aging process and may play a key role in the onset of autoimmune nephritis in this model. In addition, EPR imaging is recently being applied to the redox analysis of several nephrosis models, hypertensive rats and streptozotocin-induced diabetic rats. This article summarizes the nephrological application of EPR imaging and in vivo EPR.
Nephron Clin Pract 2006
PMID:Electron paramagnetic resonance imaging of oxidative stress in renal disease. 1654 59

Heme oxygenase (HO) isoforms catalyze the conversion of heme to carbon monoxide (CO) and biliverdin/bilirubin with a concurrent release of iron. There is strong evidence that HO activity and products play a major role in renoprotection, however the exact molecular mechanisms underlying the beneficial effects exerted by this pathway are not fully understood. This review is aimed at illustrating the possible mechanism/s by which HO is renoprotective in the context of ischemia/reperfusion. We will first analyze the effects of exogenous administration of bilirubin/biliverdin and CO and then describe their biological activities once generated endogenously following stimulation of the HO pathway by either pharmacological means or gene targeting-mediated approaches.
Nephron Exp Nephrol 2006
PMID:Role of carbon monoxide and biliverdin in renal ischemia/reperfusion injury. 1690 17

Mitochondria are intracellular organelles with a variety of vital functions, including the provision of energy in the form of adenosine 5'-triphosphate. Increasingly, we are becoming more aware of the importance of mitochondrial dysfunction in a number of common medical conditions. In this review and overview, we focus on the growing evidence that mitochondrial dysfunction is involved in either the etiology or underlying pathophysiology of a broad spectrum of renal diseases, including acute renal injury due to ischemia-reperfusion injury, renal Fanconi syndrome, and glomerular disorders such as focal segmental glomerulosclerosis. In addition, mitochondrial dysfunction may also contribute to the growing burden of chronic kidney disease seen in our aging population, which is still largely unexplained. Unfortunately, at present, our ability to diagnose and treat renal disorders related to mitochondrial dysfunction is limited, and further work in this field is needed.
Nephron Physiol 2007
PMID:The not so 'mighty chondrion': emergence of renal diseases due to mitochondrial dysfunction. 1709 76

During myocardial ischemia, a substantial accumulation of norepinephrine occurs in the ischemic zone due to a local nonexocytotic release of norepinephrine. Norepinephrine release is driven by the neuronal monoamine transporter (NET), which reverses its usual transmembrane transport direction. We investigated whether this local accumulation of norepinephrine contributes to irreversible myocardial injury in an in vivo model of myocardial infarction. Male, anaesthetized Wistar rats were subjected to 30 min coronary occlusion and subsequent 120 min reperfusion. Five minutes prior to coronary occlusion, the NET inhibitor desipramine was administered intravenously. Infarct size (IS) was determined by TTC-staining and was related to the area at risk (AAR). The influence of desipramine on cardiac norepinephrine release was investigated in isolated perfused hearts with 30 min of regional ischemia. Norepinephrine was measured in the effluent from the hearts by HPLC and electrochemical detection. Desipramine (0.1-0.8 mg/kg) dose-dependently reduced infarct size (IS/AAR) from 0.54 to 0.21 and suppressed postischemic norepinephrine release from 245 to 108 pg/mL. In summary, the data indicate that nonexocytotic release of norepinephrine in myocardial ischemia exaggerates acute ischemic damage, because suppression of ischemia-induced release of norepinephrine by the tricyclic antidepressant desipramine effectively reduces infarct size in an in vivo model of myocardial ischemia.
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PMID:Inhibition of nonexocytotic norepinephrine release by desipramine reduces myocardial infarction size. 1721 83

The peripheral benzodiazepine receptor (PBR) is located mainly in the outer mitochondrial membrane and many functions are associated directly or indirectly with the PBR. We have studied the influence of different durations of warm ischemia (WI) on renal function, tissue damage and PBR expression in a Large Whitepig model. After a midline incision, the renal pedicle was clamped for 10 (WI10), 30 (WI30), 45 (WI45), 60 (WI60) or 90 min (WI90), and blood and renal tissue samples were collected between 1 day and 2 weeks after reperfusion for assessment of renal function. Metabolite excretion associated with renal ischemia reperfusion injury such as trimethylamine-N-oxide (TMAO) was quantified in blood by magnetic resonance spectroscopy. PBR mRNA and protein expression were determined in renal tissue. TMAO levels rose progressively and significantly with increasing duration of WI. PBR mRNA expression was upregulated between 3 h and 1 day after reperfusion in WI30, WI45 and WI60. Its upregulation was noted 3 days after reperfusion in WI90. At day 14, PBR transcript expression was not different from basal level in any group. PBR protein followed the same pattern. These findings suggest a new role for PBR which could be a major target in the regeneration process during ischemia reperfusion.
Nephron Exp Nephrol 2007
PMID:Influence of warm ischemia time on peripheral-type benzodiazepine receptor: a new aspect of the role of mitochondria. 1762 71

The aim of this study was to investigate the role of adrenergic activity in patients with slow coronary flow (SCF) and its relationship to TIMI frame count on the pathogenesis of SCF. Plasma noradrenalin and adrenalin concentrations at rest were compared in 51 patients diagnosed with SCF through coronary angiography and TIMI frame count; and 44 healthy controls with normal coronary flow (NCF). Furthermore, the relationship between TIMI frame count and noradrenalin and adrenalin levels was investigated. Plasma noradrenalin (127.9 +/-9.2 and 79.3 +/- 7.3 ng/mL, p < 0.0001) and adrenalin levels (63.9 +/- 2.6 and 44.7 +/- 2.8 ng/mL, p < 0.0001) were higher in patients with SCF when compared to patients with NCF. Noradrenalin and adrenalin levels were effected with SCF-dominant vessels with respect to TIMI frame count (p = 0.012 and p < 0.0001). Patients with SCF in 1, 2, or 3 vessels had different noradrenalin and adrenalin levels (p <0.003 and p < 0.0001). Patients with TIMI frame count above the 75th percentile had significantly higher noradrenalin and adrenalin levels when compared with those between the 25th-50th percentiles and below (p < 0.001 and p = 0.011, respectively). Correlation analysis established that both adrenalin and noradrenalin levels were correlated with TIMI frame counts of left anterior descending (LAD) and circumflex (Cx) arteries. Exercise testing revealed ischemia in 6 patients. Their TIMI frame counts were above the 75th percentile, and they had higher noradrenalin and adrenalin levels when compared with those without ischemia (p = 0.029, p = 0.045). Higher noradrenalin and adrenalin levels and correlation between TIMI frame count and ischemia in patients with SCF suggest that increased adrenergic activity may be the manifestation of slow coronary flow.
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PMID:The role of adrenergic activity in slow coronary flow and its relationship to TIMI frame count. 1765 27

Ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI) and evidence supporting the involvement of both innate and adaptive immunity in renal IRI has accumulated in recent years. In addition to leukocytes, kidney endothelial cells promote inflammation after IRI by increasing adhesion molecule expression and vascular permeability. Kidney tubular epithelial cells increase complement binding and upregulate toll-like receptors, both of which lead to cytokine/chemokine production in IRI. Activation of kidney resident dendritic cells, interferon-gamma-producing neutrophils, infiltrating macrophages, CD4+ T cells, B cells and invariant natural killer T cells are all implicated in the pathogenesis of AKI. The complex interplay between innate and adaptive immunity in renal IRI is still not completely understood, but major advances have been made. This review summarizes these recent advances to further our understanding of the immune mechanisms of acute kidney injury.
Nephron Exp Nephrol 2008
PMID:Inflammation in acute kidney injury. 1880 72


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