The increased susceptibility to hydrogen peroxide of the (post)-ischemic rat heart is associated with the magnitude of the low molecular weight iron pool

Recently we have shown that intracellular low molecular weight (LMW) iron increases during ischemia. It is hypothesized that this increase in LMW iron during ischemia underlies the reported hydrogen peroxide toxicity toward ischemic hearts. To investigate this hypothesis, rat hearts were subjected to 15 min of no-flow ischemia and reperfused with buffer saturated against 95% N2 and 5% CO2 (anoxic reperfusuion) for 7 min. Hearts were then swithched to buffer saturated against 95% O2 and 5% CO2 (reoxygenation) to assess functional recovery. The cardiac function recovered to 80 ± 7% of the preischemic value. When the anoxic reperfusion was applied in the presence of 10 μM hydrogen peroxide, functional recovery after reoxygenation was 47 ± 7%. Hearts that were perfused with deferoxamine before ischemia and then subjected to ischemia and anoxic reperfusion in the presence of 10 μM hydrogen peroxide recovered to 78 ± 8%. Immediate reoxygenation after ischemia led to only 45 ± 6% recovery of function. During ischemia, LMW iron increased from 49 ± 45 to 183 ± 45 pmol/mg protein (p < .05) and decreasedto 58 ± 38 pmol/mg protein (p < .05) during the subsequent anoxic perfusion. Rat hearts preloaded with deferoxamine showed a slightly higher LMW iron content than normal (85 ± 23 and 49 ± 45 pmol/mg protein, respectively; n.s.), which showed a small, nonsignificant increase up to 136 ± 42 pmol/mg protein after 15 min of ischemia. No significant changes were found in reduced and oxidized glutathione content and glutathione peroxidase or catalase activities under those conditions. Our results indicate that hydrogen peroxide toxicity is determined by the amount of catalytic iron in the LMW pool and not by a decrease in antioxidant defense capacity to hydrogen peroxide

935-38 Restenosis After Coronary Angioplasty is Associated with the Activation Status of Circulating Phagocytes Before Treatment

BackgroundThe purpose of this study was to identify biological risk factors for restenosis after PTCA, in order to predict the long-term outcome of PTCA before treatment.Methods and ResultsTo investigate whether blood granulocytes and monocytes could determine luminal renarrowing after PTCA, several characteristics of these phagocytes were assessed before angioplasty in 32 patients who underwent PTCA of one coronary artery and who had repeat angiograms at six months follow-up. The plasma levels 1L-1β, TNF-α, IL-6, fibrinogen, C-reactive protein and LP(a) before angioplasty were assessed as well. We found that the expression of the membrane antigens CD64, CD66 and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at six months after PTCA. while the production of IL-1β by stimulated monocytes was positively associated with the relative loss. Next. these univariate predictors were corrected for the established clinical risk factors, dilation of the LAD, current smoking and angina class.Multiple linear regression analysis showed that luminal renarrowing could be predicted reliably (R2=0.65; P&lt;0.0001) in this patients group on the basis of the vessel dilated and only two biological risk factors that reflect the activation status of blood phagocytes, i.e., the expression of CD66 by granulocytes and the production of IL-lβ by stimulated monocytes.ConclusionsThe results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote restenosis. To validate this new finding further study in an independent patients group is required

Prenatal hormones alter antioxidant enzymes and lung histology in rats with congenital diaphragmatic hernia.

Prenatal administration of dexamethasone (Dex) and thyrotropin-releasing hormone (TRH) synergistically enhances lung maturity, but TRH suppresses the antioxidant enzyme activity. Prenatal hormonal therapy improves alveolar surfactant content and lung compliance in rats with congenital diaphragmatic hernia (CDH). In full term neonatal rats with CDH we studied the effects of prenatal Dex or Dex+TRH on antioxidant enzyme activity at birth, on survival, and on lung morphometry after 4 h of ventilation with 100% O2. CDH was induced by administration of 2,4-dichlorophenyl-p-nitro-phenylether (Nitrofen) on gestational day 10. Dex+TRH-treated CDH rats had lower activity of glutathione reductase after birth than did sham-treated CDH pups. Dex-treated and sham-treated pups had similar antioxidant enzyme activity. Hormonal treatment did not change survival during ventilation. The average airspace volume increased in Dex-treated CDH pups after ventilation, with a small synergistic effect after addition of TRH. On the basis of our findings, we speculate that prenatal administration of Dex is the best choice to improve lung maturity and airspace volume in CDH patients

Scavenging of reactive oxygen species leads to diminished peritoneal tumor recurrence

Previously, we demonstrated that RBCs inhibit the recurrence of perioperatively spilled tumor cells. The aim of this study was to identify on which RBC component(s) the inhibitory effect is based. By using a cell-seeding model in rats, the effect of RBC-related antioxidant scavengers [hemoglobin, catalase, and superoxide dismutase (SOD)] on peritoneal tumor recurrence was investigated. i.p. injection of hemoglobin caused 45% more tumor load (P < 0.0001). At least 40% inhibition of tumor recurrence was achieved with the use of catalase or SOD (P < 0.05). Combining SOD and catalase did not lead to additional inhibition of tumor recurrence. Inhibition of the overwhelmin

A comparison of balloon injury models of endovascular lesions in rat arteries

BACKGROUND: Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA. METHODS: Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared. RESULTS: In the BI-groups the area of IH increased to 0.14 ± 0.08 mm(2) (CCA), 0.14 ± 0.03 mm(2) (CIA) and 0.12 ± 0.04 mm(2) (AA) at 16 weeks (NS). The LD decreased with 0.49 ± 0.07 mm (CCA), compared to 0.22 ± 0.07 mm (CIA) and 0.07 ± 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive vascular remodelling (CVR = wall circumference loss combined with a decrease in LD) was -0.17 ± 0.05 mm in CIA but absent in CCA and AA. No IH, no decrease in LD and no CVR was seen in the control groups. CONCLUSIONS: BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI