摘要:

ABSTRACT—The nuclear enzyme poly (ADP ribose) synthetase (PARS) has been shown to play an important role in the pathogenesis of various forms of ischemia or reperfusion injury and circulatory shock. Recent studies demonstrated that inhibition or genetic inactivation of PARS is beneficial in the early phase of myocardial reperfusion injury. The aim of the present study was to investigate whether inactivation of PARS influences the delayed myocardial necrosis and the production of the proinflammatory cytokine tumor necrosis factor&agr; (TNF&agr;), the anti‐inflammatory cytokine interleukin‐10 (IL‐10), and the free radical nitric oxide in the late stage of myocardial reperfusion injury. The results demonstrate that genetic disruption of PARS provides marked protection against the delayed myocardial ischemia and reperfusion injury. In addition, in the absence of functional PARS, a suppression of TNF&agr;, IL‐10, and nitric oxide production was found. These findings provide direct evidence that PARS activation participates in the development of delayed cell injury and delayed mediator production in myocardial reperfusion injury.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ABSTRACT—Neutrophil accumulation in the first hour of myocardial reperfusion was assessed in dog hearts submitted to ischemia with and without necrosis. In anesthetized dogs, the left anterior descending coronary artery was occluded for 20 min (group IS‐20 n = 7) and for 90 min (group IS‐90 n = 6). Immediately after reperfusion,99mTc‐Ceretec (Exametazime‐Amersham) labeled neutrophils were injected into a central vein and 60 min later the dogs were killed. The left ventricle was isolated, weighed, and sliced. Six sections, 3 from normal and 3 from reperfused regions, were divided into endocardial and epicardial layers. Myocardial and blood radiometry were used to evaluate the neutrophil accumulation during reperfusion.The differences between leukocyte accumulation in both groups were assessed comparing the ischemic/normal relations in the endocardial and epicardial layers. A second comparison considered myocardium/blood relations to allow the evaluation of differences between remote normal myocardial areas of the two experimental groups.In dogs submitted to 20 min of ischemia, leukocytes accumulated significantly more (P< 0.01) in the reperfused myocardium as compared with the non‐ischemic region. The increase occurred both in the endocardial (1.49 ± 0.20) and epicardial (1.48 ± 0.29) regions. After 90 min ischemia, leukocyte accumulation was more intense and predominant in endocardium where there was a 4‐fold (3.97 ± 1.28) increase over the non‐ischemic region, while in the epicardium this relation was only 2.5‐fold (2.56 ± 0.98).In the remote non‐ischemic myocardium, leukocyte accumulation was greater in dogs submitted to 90 min of ischemia compared to the 20 min group (P< 0.01), without distinction between endocardial and epicardial layers. This accumulation in territories of non‐culprit coronary arteries may be related to the blood flow abnormalities and matrix structure changes that occur in these regions during the development of an acute myocardial infarction and its natural repair.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ABSTRACT—This study was performed to determine whether ischemia/reperfusion (I/R) injury in rat liver results in alterations in endothelin receptor expression. Hepatic ischemia was produced in rats for 60 min followed by 6 or 24 h reperfusion. Portal inflow pressure was increased (7.38 ± 0.60 mmHg) at 24 hours after reperfusion. Serum ALT increased significantly at both 6 and 24 h (6 h; 258.3 ± 74.3, 24 h; 243.1 ± 74.8 IU/L). Portal vascular response to an endothelin‐B receptor agonist (IRL 1620) was significantly increased in the I/R livers compared to control and this was potentiated by L‐NAME. IRL 1620 also caused LDH release from I/R livers but not controls. LDH release after IRL 1620 in I/R livers correlated with increased portal pressure response. To determine whether the altered response might be the result of altered endothelin receptor expression, livers were harvested after reperfusion and total endothelin binding sites were determined by competitive binding with ET‐1. Proportion of endothelin receptor subtypes (ETA/ETB) was determined using the ETAantagonist BQ‐610 (1 &mgr;M) and ETBagonist IRL‐1620 (100 nM). There were no significant changes in Kd but Bmax for endothelin‐1 was decreased in I/R group especially non‐ischemic lobe at 24 h. ETAreceptors were significantly decreased whereas ETBreceptors were increased. These changes were more pronounced at 24 h after reperfusion than at 6 h. Interestingly, the changes in ET receptors was observed identically both in ischemic and non‐ischemic lobes (ischemic lobe ETA41.9%, ETB51%; non‐ischemic lobe ETA 38.8%, ETB49.5%). These results indicate that the major functional endothelin receptor subtype upregulated in I/R is the ETBreceptor and that this upregulation may contribute to microvascular dysregulation and hepatic injury.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ABSTRACT—It has been postulated that in severely ill patients splanchnic hypoperfusion may cause endotoxin release from the gut, and this leakage of endotoxin into the circulation can trigger the cascade of inflammatory cytokines. We tested this hypothesis in 9 patients with acute severe pancreatitis by monitoring gastric intramucosal pH (pHi) as measure of splanchnic hypoperfusion at 12‐h intervals trying to correlate it to endotoxin and cytokine release. Only 3 of 59 samples, obtained from 3 patients contained circulating endotoxin. Thirteen of 15 plasma samples drawn at pHi <7.20 did not contain endotoxin. The pHi was significantly lower in patients who subsequently developed 3 or more organ failures (P= 0.0017, analysis of variance). Although endotoxemia was only occasionally found, most patients had measurable interleukin 1&bgr; (IL‐1&bgr;), interleukin 6 (IL‐6), interleukin 8 (IL‐8), and interleukin 10 (IL‐10) in their plasma. Concentrations of IL‐6, IL‐8, and IL‐10 on admission correlated to degree of organ dysfunction as measured by the multiple organ system failure score (P= 0.035,r= 0.74;P= 0.010,r= 0.91;P= 0.021,r= 0.82, respectively). In conclusion, patients with acute, severe pancreatitis often have splanchnic hypoperfusion and produce a wide array of cytokines despite a rare occurrence of endotoxemia.

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1073-2322    

出版商:OVID    

年代:2000

数据来源: OVID