Influencing the macro- and microcirculatory complications of nonocclusive mesenteric ischemia by complement C5a inhibitor treatments

Nonocclusive mesenteric ischemia (NOMI) can develop in the absence of apparent anatomical obstruction of the mesenteric circulation in a variety of low flow states. The pathophysiology of NOMI is unexplored, the early diagnosis is challenging and the available treatments are of questionable effectiveness. In this respect, new experimental models are sought to clarify the exact pathomechanisms and new, effective therapeutic ways are needed to reduce the increasingly high mortality. Our first aim was to develop clinically relevant in vivo models to investigate the macro- and microcirculatory effects of NOMI. Also, we hypothesized the role of complement activation in the acute and subacute consequences of NOMI and our objectives were to characterize the effects of the inhibition of complement protein known as C5a during this condition. Acetyl-peptide-A (AcPepA) is an antisense-homology box-derived peptide, which is capable to inhibit the C5a effects by binding directly to the anaphylatoxin. We hypothesized that the inhibition of C5a can decrease the intensity of inflammatory reactions and in parallel, to normalize the impaired mesenteric circulation. Acute experimental pericardial tamponade (PT) was established in anesthetized minipigs, while partial aorta occlusion (PAO) was induced in rats to investigate the circulatory and inflammatory changes of NOMI in clinically relevant time frames. After the relief of PT, elevated levels of oxidative stress markers and inflammatory mediators were detected in association with the signs of diminished splanchnic microcirculation. 24 hours after PAO the macrocirculatory parameters improved significantly, while the intramural microcirculation was significantly impaired and accompanied by increased leukocyte infiltration. The in vivo histology confirmed the structural and microvascular damage of the mucosa. In both animal models of NOMI, the administration of AcPepA moderated the hemodynamic changes, improved the intramural microcirculation, reduced the inflammatory activations and the histological signs of mucosal damage. In conclusion we can say that our newly developed animal models provide a cross section for events in the short and long time frames and proved to be suitable for the investigations of the pathophysiology of NOMI. The hemodynamic changes in the acute PT together with those observed after PAO suggest that complement activation plays central role in the early and late macro- and microcirculatory disturbances during NOMI. The results suggest that C5a inhibitor treatment influences favourably the hemodynamic effects and reduces the potentially harmful inflammatory activation after experimental NOMI as well

Examination of the vascularization of fetal kidney with three-dimensional power Doppler technique in pregnancies complicated by increased maternal blood pressure

The goal of this study was to investigate the fetal renal vascularization during the third trimester of gestation and the perinatal outcome in pregnancies diagnosed with hypertension. Depending on the medical history, the cases were divided into two groups: chronic hypertension group and gestational hypertension group. The vascularization and the volume of kidneys were observed in prenatal period by three-dimensional ultrasound. We monitored gestations and perinatal complications. Renal volume and vascularization were detected in 45 cases complicated by gestational hypertension and 21 cases with chronic hypertension during the 20-month study period. The alteration in fetal renal volume and vascularization may be an in utero cause of subsequent intrauterine and neonatal complications, such as Cesarean section because of fetal distress (36%), perinatal infection (24%), treatment in neonatal intensive care unit (39%), or increased perinatal mortality (1%) in affected cases. The results demonstrate that fetuses with depressed vascularization of medullae had 1.5 times the risk of an abnormal outcome compared to the control group. The volume of kidneys had a strong correlation with their vascularization. Detailed ultrasound examinations of renal parenchyma appear to be useful for the prenatal diagnosis of intrauterine hypoxia, allowing the detection of potential pathological fetal conditions in utero

A gyermek 3 (1909) 06

A gyermek A Magyar Gyermektanulmányi Társaság közlönye 3. évfolyam, 06. szám Budapest, 1909. A folyóirat 1908-ig a Gyermekvédelmi lap mellékleteként, 1909-től mint önálló lap jelent meg

A gyermek 20 (1927) 04-07

A gyermek 20. évfolyam , 4-7. szám Budapest, 1927. A folyóirat 1908-ig a Gyermekvédelmi lap mellékleteként, 1909-től mint önálló lap jelent meg

Complement C5a inhibition improves late hemodynamic and inflammatory changes in a rat model of nonocclusive mesenteric ischemia

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) can evolve in a variety of low-flow states. Although the mechanisms leading to NOMI-related intestinal necrosis are largely unknown, circumstantial evidence suggests that excessive vasoconstriction and complement activation both play important roles in this process. Because targeting of the circulatory malfunction of the splanchnic area could be of therapeutic relevance, we set out to investigate the long-term effects of treatment with a complement C5a antagonist in a rat model of partial aortic occlusion (PAO)-induced transient mesenteric hypoperfusion. METHODS: The mean arterial pressure of the splanchnic area was kept between 30 and 40 mm Hg by 60 minutes of PAO in anesthetized male Sprague-Dawley rats. C5a inhibitor acetyl-peptide-A (AcPepA; 4 mg kg-1 intravenously) or vehicle administration was initiated at the 45th minute of PAO. After 24 hours, the animals were reanesthetized to record the macrohemodynamics and ileal microcirculation, and plasma and tissue samples were taken for determination of high-mobility group box protein-1 (HMGB-1), endothelin-1, tumor necrosis factor (TNF)-alpha levels, and small intestinal leukocyte infiltration. Epithelial structural changes were visualized by in vivo confocal laser scanning endomicroscopy. RESULTS: At 24 hours after PAO, mean arterial pressure, heart rate, and cardiac output were significantly greater, the intestinal intramural microcirculation was significantly impaired, and plasma HMGB-1, endothelin-1, TNF-alpha levels, the degree of epithelial damage and leukocyte infiltration was increased. The AcPepA treatment moderated the hemodynamic and microcirculatory changes, and decreased inflammatory activation and histologic signs of mucosal damage. CONCLUSION: C5a inhibition ameliorated the potentially harmful local mesenteric hypoperfusion and global long-term inflammatory consequences of PAO. This approach is of promise for use in NOMI-associated situations

A gyermek 19 (1926) 05-10

A gyermek 19. évfolyam , 5-10. szám Budapest, 1926. A folyóirat 1908-ig a Gyermekvédelmi lap mellékleteként, 1909-től mint önálló lap jelent meg