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

The fairly wide-ranging spectrum of tactics under investigation for ameliorating acute renal allograft dysfunction caused by harvest/preservation-related ischemia, acute CsA nephrotoxicity, and acute immunologic crises reflect the fact that no single approach has emerged as universally useful for mitigating the vasomotor nephropathy produced by the combined effects of each of these vectors of vasomotor renal allograft injury. Given the clinical heterogeneity of patients and allografts, it is the author's bias that, in addition to careful donor and recipient hemodynamic management, induction immunosuppressive regimens should be individualized on the basis of allograft function in the immediate postreperfusion period (judged by rate of diuresis, intraoperative parenchymal tone, renal scan profiles, and rate of decline of serum creatinine concentration) as well as patient-specific immunologic and general medical risk factors. Promising laboratory and clinical investigations of such agents as calcium channel blockers, substances promoting intrarenal vasodilator vs. vasoconstrictor prostaglandin formation, and atriopeptins have the potential to provide clinically helpful options with regard to adjunctive therapy for ameliorating acute renal allograft dysfunction associated with INF and ACR.
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PMID:Mechanisms and amelioration of acute renal allograft failure in the cyclosporine era. 138 38

To determine the evolutionary changes in right and left ventricular function in acute myocardial infarction, 3 serial gated blood pool scans were performed in 76 patients within 24 hours (24 H), at 10 days (10 D) and 3 months (3 M) following the onset of myocardial infarction. The patients were divided into 3 groups: ANT (anterior MI), INF (inferior MI without right ventricular dysfunction) and RVF (inferior MI with right ventricular dysfunction). LVEF in ANT was significantly lower than that of INF and RVF at 24 H, 10 D and 3 M. The ratio of right ventricular volume to LV volume (RVV/LVV) was compared among 3 groups. The mean values of RVV/LVV in RVF were 1.3 through 24 H and 3 M and they were significantly higher than the other two groups. The RVV/LVV in ANT and INF were around 1.0. LVEDVI in RVF was rather smaller than that of ANT and INF. LVESVI in ANT at 24 H was significantly larger than that of INF and RVF and the mean value of LVESVI in ANT were around 60 ml/M2 from 24 H to 3 M. LVEF in ANT, RVF and INF did not increase significantly during peak exercise at 3 M. However, quantitative regional wall motion analysis revealed that regional wall motion of R2 (posterolateral wall motion) in ANT and R5 (septal wall motion) in INF decreased significantly during peak exercise. These impairments in regional wall motion might be due to the exacerbation of ischemia of non-infarcted area.
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PMID:Evolutionary changes in left and right ventricular function in acute myocardial infarction. 327 98

Sixteen renal transplant (RT) patients (10 men, 6 women, aged 49 +/- 10 years) with chronic hepatitis C received alpha interferon (IFN alpha) therapy (Intron A, Schering Plough) at a dose of 3 x 10(6) units s.c. 3 times a week, scheduled for 24 consecutive weeks. At the beginning of the study all had a stable renal function since at least 12 months (mean serum creatinine -SCr- 121 +/- 38 mmol/l). Fourteen patients were receiving cyclosporin A (CsA) either alone (1) or in combination with steroids and/or azathioprine -AZA- (double therapy: 8; triple therapy: 5); two patients were on conventional therapy. The mean daily doses of CsA were 2.6 mg/kd i.e. a mean whole blood trough level of 104 ng/ml. Six patients experienced renal failure either acute (5) or subacute (1) within 7 to 24 weeks after the start of IFN alpha therapy. Their mean SCr increased from 105 +/- 31 mmol/l to 207 +/- 63 mmol/l (p = 0.02) with de-novo proteinuria in one case (1 g/d) and an increase in pre-existing proteinuria in 2; 3 remained without proteinuria. The histological study showed in all cases a diffuse interstitial edema associated with dilatation of peritubular capillaries; mild inflammatory infiltrates were present in only 3 cases; mild glomerular lesions were not always found (glomerular ischemia, mesangial hypertrophy). There was no vascular lesions IFN alpha was withdrawn in these 6 patients, associated with methylprednisolone pulses in 5 cases. Renal function improved in two cases, stabilized in one and progressed to end stage renal failure in 3 within 4 to 12 months. Four patients had iterative renal biopsies showing in all cases diffuse interstitial fibrosis. This subgroup of patients did not statistically differ at the start of the study from those who did not develop renal failure according to baseline immunosuppression, HLA matching, total peripheral blood lymphocyte (PBL) count. PBL subtypes. INF alpha therapy was associated with acute or subacute renal failure in 37% of patients. The most prominent histological finding was a diffuse interstitial edema of rapid onset, without signs of cellular or vascular rejection. Thus we do not recommend to use IFN alpha therapy in RT patients with chronic hepatitis C, until the mechanisms of the subsequent renal failure be more understood.
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PMID:[Acute renal insufficiency in renal transplants treated with interferon-alpha for chronic hepatitis C]. 876 57

In order to examine the relationship between local adenosine concentrations before, during, and after ischemia and the extent of ischemic myocardial damage, measurements of interstitial fluid (ISF) nucleosides were made using microdialysis probes implanted in the ischemic region of isoflurane anesthetized Micropigs undergoing 60' coronary artery occlusion (CAO) and 3 h of reperfusion (REP). Nucleoside concentrations in the dialysate collected from the microdialysis probes were used as an index of ISF levels. Dialysate nucleoside concentrations (ADO, inosine and hypoxanthine), myocardial infarct size, and myocardial blood flow (MBF) were determined in control animals (n = 6), animals preconditioned with a single 10' cycle of CAO and REP (PC, n = 6), and those treated with the adenosine deaminase inhibitor pentostatin (n = 6, 0.2 mg/Kg i.v. 30' prior to CAO). The brief PC occlusion resulted in a transient but significant increase in dialysate ADO (6.7 +/- 1.8 microM vs. 0.67 +/- 0.1 microM at baseline). Pentostatin administration had no significant effect on either dialysate nucleosides or MBF at baseline. During the 60' CAO, dialysate ADO increased in control animals. In PC animals, however, dialysate ADO during CAO was lower than control. Pretreatment with pentostatin resulted in a six-fold augmentation in dialysate ADO during the 60 min CAO when compared to the control values (110.62 +/- 30.2 microM vs. 16.31 +/- 2.1 microM at 60 min of ischemia). Pentostatin also resulted in a significant reduction in the accumulation of inosine and hypoxanthine, indicating inhibition of adenosine deaminase activity. There were no significant differences in MBF between groups at any time point. Following 3 h REP, infarct size was 35.4 +/- 5.5%, 8.1 +/- 1.5% and 8.3 +/- 1.8% of the region at risk in control, PC, and pentostatin groups, respectively. These data suggest that marked increase in ISF ADO during CAO, may be as effective in reducing INF as a modest increase in ISF ADO prior to prolonged CAO.
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PMID:Effects of ischemia, preconditioning, and adenosine deaminase inhibition on interstitial adenosine levels and infarct size. 934 31

The inducible nitric oxide synthase (iNOS) gene is expressed by hepatocytes in a number of physiologic and pathophysiologic conditions affecting the liver including septic and hemorrhagic shock. The molecular regulation of iNOS expression is complex and occurs at multiple levels in the gene expression pathway. The cytokines TNF-alpha, IL-1beta, and INF-gamma synergistically activate iNOS expression in the liver, and the human iNOS gene was first cloned from cytokine-stimulated hepatocytes. iNOS expression requires the transcription factor NF-kappaB and is down-regulated by steroids, TGF-beta, the heat shock response, p53, and nitric oxide (NO) itself. In vivo, hepatic iNOS induction is differentially regulated from the typical acute-phase reactants and is not expressed as a mandatory component of the acute phase response. Thus, numerous mechanisms have evolved to regulate iNOS expression during hepatocellular injury. Studies of the effects of NO in the liver demonstrate that induced NO synthesis plays an important role in hepatocyte function and protects the liver during sepsis and ischemia reperfusion. Its cytoprotective role is best exemplified in a rodent model of endotoxemia. Here the addition of the nonspecific NOS inhibitors significantly increased hepatic damage. NO exerts a protective effect through its ability to prevent intravascular thrombosis by inhibiting platelet adhesion and neutralizing toxic oxygen radicals. NO also exerts a protective effects both in vivo and in vitro by blocking TNF-alpha-induced apoptosis and hepatotoxicity, in part by a thiol-dependent inhibition of caspase-3-like protease activity. These studies demonstrate the cytoprotective effects of NO in the liver and suggest hepatic iNOS expression functions as an adaptive response to minimize inflammatory injury. In addition, NO has anti-tumor effects as well as known mutagenic effects, is involved in the systemic vasodilatation of cirrhosis, and has potent antimicrobial properties.
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PMID:Inducible nitric oxide synthase in the liver: regulation and function. 972 29

We examined the effect of adenovirus-mediated transtracheal transfer of the human interleukin 10 (hIL-10) gene on lung ischemia-reperfusion (IR) injury, which is the insult due to hypothermic preservation plus graft reperfusion, and posttransplant lung function in Lewis rat lungs. Thirty rats were divided into 6 groups (n = 5). Groups 1 and 4 received 5 x 10(9) PFU of Ad5E1RSVhIL-10, groups 2 and 5 received 5 x 10(9) PFU of Ad5BGL2 ("empty" vector), and groups 3 and 6 received 3% sucrose (diluent). After 24 hr of in vivo transfection, lungs were stored at 4 degrees C (cold ischemic time, CIT) for 6 hr (groups 1-3) or 24 hr (groups 4-6) before transplantation. After 2 hr of reperfusion, lung function was assessed by oxygenation (FIO2, 1.0), airway pressure (AwP), and wet-to-dry (W/D) weight ratios. Rat tumor necrosis factor alpha (rTNF-alpha), interferon gamma (IFN-gamma), IL-10, and hIL-10 were measured in graft tissue and recipient plasma by ELISA and detected by immunohistochemistry (IHC). Partial pressure of oxygen (PaO2) levels in the hIL-10 group (6 hr of CIT) were higher than in empty vector and diluent groups (PaO2, 530 +/- 23 vs. 387 +/- 31 and 439 +/- 27 mmHg, respectively, p < 0.05). IL-10 rats after 24 hr of CIT showed higher PaO2 levels (260 +/- 29 mmHg) than empty vector (96 +/- 24 mmHg) or diluent (133 +/- 10 mmHg) lungs (p < 0.05). AwP and W/D ratios were reduced in hIL10 lungs (p < 0.05) compared with the other groups. rTNF-alpha and INF-gamma were reduced in tissue and plasma in groups 1 and 4 (p < 0.05). rIL-10 was reduced in the tissue of hIL-10 lungs (p < 0.05). IHC showed equal distribution of cytokines in tissue and abundant transgene expression in large and small airway epithelium in hIL-10 lungs.
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PMID:In vivo transtracheal adenovirus-mediated transfer of human interleukin-10 gene to donor lungs ameliorates ischemia-reperfusion injury and improves early posttransplant graft function in the rat. 1150 94

Giant cell arteritis is a vasculitis of large and medium size arteries, especially those of the aortic arch with an extracranial distribution, but also the aorta and some of its larger branches. It is characterised by the presence of mononuclear inflammatory infiltrates close to the internal elastic lamina formed by lymphocytes and macrophages, which in slightly more than 50% of the cases contain multinucleate giant cells. The morbidity associated with this disease is related to phenomena of distal ischemia to the luminal stenosis of the inflamed arteries, and to a lesser extent to the formation of aneurisms due to the weakening of the arterial wall. With an unknown aetiology, its pathogenesis is immune through the migration and location of gamma-INF -producing T cells in the adventitia of the inflamed arteries, it being assumed that this is the place of immune stimulation by a still unidentified antigen. The recruitment and activation of macrophages by this cytokine is one of the most important points of its pathogenesis. The destruction by these of the arterial elastic tissue is a relevant phenomenon, as is the production of other factors promoting neoangiogenesis and a proliferation of neointime, responsible through obliterating light for the ischemic manifestations of the disease. The process is accompanied by an important systemic repercussion characterised by a strong reaction of acute phase and general but barely specific symptoms of disease. On the other hand, an important percentage of patients show a clinical picture of polymyalgia rheumatica, an entity that has a historical and controversial relationship to this arteritis. In recent years important contributions have been made to the understanding of the immune mechanisms involved in its pathogenesis.
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PMID:[Etiopathogenesis of giant cell arteritis]. 1275 11

Ischemia-reperfusion (I/R) injury occurs as a result of restoring blood flow to previously hypoperfused vessels or after tissue transplantation and is characterized by inflammation and microvascular occlusion. We report here that 4-[3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl]-cyclohexanecarboxylic acid methyl ester (ATL146e), a selective agonist of the A(2A) adenosine receptor (A(2A)AR), profoundly protects mouse liver from I/R injury when administered at the time of reperfusion, and protection is blocked by the antagonist ZM241385. ATL146e lowers liver damage by 90% as assessed by serum glutamyl pyruvic transaminase and reduces hepatic edema and MPO. Most protection remains if ATL146e treatment is delayed for 1 h but disappears when delayed for 4 h after the start of reperfusion. In mice lacking the A(2A)AR gene, protection by ATL1465e is lost and ischemic injury of short duration is exacerbated compared with wild-type mice, suggesting a protective role for endogenous adenosine. I/R injury causes induction of hepatic transcripts for IL-1alpha, IL-1beta, IL-1Ra, IL-6, IL-10, IL-18, INF-beta, INF-gamma, regulated on activation, normal T cell expressed, and presumably secreted (RANTES), major intrinsic protein (MIP)-1alpha, MIP-2, IFN-gamma-inducible protein (IP)-10, and monocyte chemotactic protein (MCP)-1 that are suppressed by administering ATL146e to wild-type but not to A(2A)AR knockout mice. RANTES, MCP-1, and IP-10 are notable as induced chemokines that are chemotactic to T lymphocytes. The induction of cytokines may contribute to transient lymphopenia and neutrophilia that occur after liver I/R injury. We conclude that most damage after hepatic ischemia occurs during reperfusion and can be blocked by A(2A)AR activation. We speculate that inhibition of chemokine and cytokine production limits inflammation and contributes to tissue protection by the A(2A)AR agonist ATL146e.
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PMID:Protection from ischemic liver injury by activation of A2A adenosine receptors during reperfusion: inhibition of chemokine induction. 1471 20

Complications of interferon (IFN) therapy include cardiac arrhythmias, impaired cardiac function and myocardial ischemia. Decreased heart rate variability (HRV) indices, impaired exercise tolerance and decreased left ventricular (LV) function are related to unfavorable outcome of heart disease. To investigate the effect of IFN therapy on HRV, exercise tolerance and cardiac function, 24-h ambulatory electrocardiographic monitoring (AECG), two-dimensional echocardiography, and exercise treadmill testing (ETT) was performed in 9 patients (age 56 +/- 9 years-old) with chronic hepatitis and without underlying heart disease before and after treatment with IFN (recombinant alpha 2b; 10 x 10(6) U/day for 4 weeks). HRV parameters consisted of standard deviation of RR interval (sdNN, ms), SDANN (ms), S.D. index (ms), rMSSD (ms), pNN50 (%) and frequency analysis of heart rate spectrum resulted in low (ms, 0.04-0.15 Hz), high (ms, 0.15-0.40 Hz) and total (ms, 0.01-1.00 Hz) frequency components. Ischemia was not detected by AECG or ETT, and LV function was normal after INF treatment in all patients. However, INF treatment resulted in a decrease in exercise tolerance time (449 +/- 94 s vs. 329 +/- 67 s, P < 0.05) and a decrease in several HRV parameters (S.D. index, 42 +/- 5 ms vs. 37 +/- 9 ms; rMSSD, 22 +/- 5 ms vs. 19 +/- 4 ms; pNN50, 4 +/- 3% vs. 2 +/- 1%; P < 0.05). Further, patients treated with INF tended to have a lower sdNN and total frequency spectra, although this difference did not reach the level of statistical significance. These data suggest that the arrhythmogenic effect of INF may be mediated by decreases in HRV and impairment of exercise tolerance even in patients without overt heart diseases. Further, INF therapy may be contraindicated in patients with predisposing severe cardiac disorders, including arrhythmias, ischemia and decreased LV function.
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PMID:Recombinant interferon alpha treatment decreases heart rate variability indices and impairs exercise tolerance in patients with chronic hepatitis. 1627 87

The aim of the study was to characterize the role of cold ischemia in the process of acute rejection using an experimental renal transplant model. Syngeneic renal transplants were performed between Wistar Agouti rats and allogeneic grafts using Wistar-Agouti rats as recipients of Brown-Norway kidneys. For cold ischemia (CI), kidneys were preserved in Euro-Collins (4 degrees C/ 2.5 hours). Rats were bilaterally nephrectomized at the moment of renal transplant and did not receive any immunosuppressant. The groups were NoAR (n = 6): immediate syngeneic transplant; CI-NoAR (n = 6): syngeneic transplant with CI; AR (n = 13): immediate allogeneic graft; CI-AR (n = 6): allogeneic graft with CI. Allogeneic rats were followed for the survival study. Syngeneic rats, with mean survival time beyond 6 months, were sacrificed on the day 7 to compare grafts with those in the allogeneic groups. H&E- and PAS-stained grafts were evaluated using the Banff criteria. Tissue INF-gamma and TNF-alpha were quantified by RT-real time-PCR on the kidney grafts. Renal insufficiency did not appear in the NoAR group, but it did from the posttransplant day 5 in both acute rejection groups. While NoAR kidneys showed well-conserved renal architecture, then AR group displayed variable degrees of tubular necrosis with scarce cellular infiltration, interstitial hemorrhage, vascular damage with fibrinoid necrosis, perivascular edema, and nuclear disruption. Cold ischemia in rejecting animals increased the mortality rate due to renal insufficiency and accelerated acute rejection. Independently of CI, the proinflammatory cytokines TNF-alpha and INF-gamma were increased in both rejection groups. In conclusion, addition of CI overactivates the acute rejection process via a humoral component.
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PMID:Role of cold ischemia in acute rejection: characterization of a humoral-like acute rejection in experimental renal transplantation. 1638 14


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