Protective Effects of Nigella sativa Oil in Hyperoxia-Induced Lung Injury

BackgroundOxygen-induced lung injury is believed to lead to the development of bronchopulmonary dysplasia in premature infants. We have evaluated the beneficial effects of Nigella sativa oil (NSO) on rats with hyperoxia-induced lung injury.MethodsThirty newborn Sprague-Dawley rats were randomly divided into 3 groups as hyperoxia (95% O₂), hyperoxia+NSO and control (21% O₂). Pups in the hyperoxia+NSO group were administered intraperitoneal NSO at a dose of 4 ml/kg daily during the study period. Histopathologic, immunochemical, and biochemical evaluations (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malonaldehyde [MDA] and myeloperoxidase [MPO]) were performed.ResultsIn the histopathologic and immunochemical evaluation, severity of lung damage was significantly lower in the hyperoxia+NOS group (P<.05). Tissue GSH-Px and SOD levels were significantly preserved, and MDA, MPO levels were significantly lower in the hyperoxia+NSO group (P<.05).ConclusionNSO significantly reduced the severity of lung damage due to hyperoxia.     

TNF-α Blockade Efficiently Reduced Severe Intestinal Damage in Necrotizing Enterocolitis

Objectives: To ascertain the beneficial effects of infliximab an inhibitor of tumor necrosis factor alpha (TNF-α) on the development of NEC in an experimental NEC rat model. Material and Methods: Thirty newborn Sprague-Dawley rats were randomly divided into three groups as NEC, NEC+ infliximab, and control. NEC was induced by enteral formula feeding, exposure to hypoxia-hyperoxia and cold stress. Pups in the NEC+ infliximab group were administered infliximab at a dose of 10 mg/kg daily by intraperitoneal route from the first day until the end of the study. All pups were sacrificed on the 5th day. Proximal colon and ileum were excised for histopathologic, immunohistochemical (TUNEL and caspase-3), and biochemical evaluation, including, total antioxidant status (TAS), total oxidant status (TOS), malonaldehyde (MDA), and myeloperoxdase (MPO) and TNF-α activities. Results: We observed better clinical sickness scores, weight gain, and survival rate in the NEC+ infliximab group compared to the NEC group (p < .05). Histopathological and apoptosis examination (TUNEL and immunohistochemical evaluation for caspase-3) revealed lower damage in the NEC+ infliximab group compared to the damage in the NEC group (p < .01). Tissue MDA, MPO, TNF-α levels, and TOS were significantly decreased in the NEC+infliximab group, whereas TAS was significantly increased in the NEC + infliximab group (p < .01). Conclusion: TNF-α blockade with infliximab efficiently reduced the intestinal injury and preserve the intestinal tissues from severe intestinal damage by its complex mechanisms on NEC. Therefore, it may be an alternative option for the treatment of NEC.     

N-acetylcysteine may prevent severe intestinal damage in necrotizing enterocolitis

ObjectiveThe aim of this study was to evaluate the preventive effect of N-acetylcysteine (NAC) on the development of necrotizing enterocolitis (NEC) in an experimental rat model.Material and MethodsThirty newborn Sprague-Dawley rats were randomly divided into 3 groups: NEC, NEC + NAC, and control. Necrotizing enterocolitis was induced by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. Pups in the NEC + NAC group were administered NAC at a dose of 150 mg/kg daily by intraperitoneal route from the first day until the last day of the study. All pups were killed on the fifth day. Proximal colon and ileum were excised for histopathologic, immunohistochemical (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick end-labeling and caspase-3, caspase-8, caspase-9), and biochemical evaluation, including xanthine oxidase, total antioxidant status, total oxidant status, malondialdehyde, and myeloperoxidase activities.ResultsThe pups in the NEC + NAC group had better clinical sickness scores compared with those in the NEC group (P < .05). In histopathologic and apoptosis evaluations (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate–biotin nick end-labeling and immunohistochemical evaluation for caspase-3 and caspase-9), the severity of bowel damage was significantly less in the NEC + NAC group compared with the NEC group (P < .01). Tissue malondialdehyde, myeloperoxidase, xanthine oxidase levels, and total oxidant status were significantly decreased in the NEC + NAC group, whereas total antioxidant status (TAS) was significantly increased in the NEC + NAC group (P < .01).ConclusionN-acetylcysteine therapy significantly reduced the severity of intestinal damage in NEC.     

The Effect of Erythropoietin on Anastomotic Healing of Irradiated Rats

ABSTRACT

Aim: The aim of the present study is to evaluate the possible protective effects of erythropoietin (EPO) on anastomotic wound healing after preoperative radiotherapy according to its pleiotropic mechanism of action. Methods: Thirty-two male Wistar albino rats were randomized into four groups containing eight rats each: ANAS group, standard resection plus anastomosis; RT+ANAS group, radiation plus standard resection plus anastomosis; ANAS+EPO group, standard resection plus anastomosis plus EPO; RT+ANAS+EPO, radiation plus standard resection plus anastomosis plus EPO. All animals were sacrificed by cardiac puncture, and anastomotic healing was measured by bursting pressure, hydroxyproline (OHP) levels, myeloperoxidase (MPO) activity and histopathological evaluations. Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) were also measured in serum specimens. Results: OHP levels in the RT+ANAS + EPO group were significantly increased compared with other groups (p < .05). In contrast, MPO activity in the RT+ANAS+EPO group was significantly decreased compared with other groups (p < .05). Serum MDA levels were found to be decreased in the ANAS+EPO and RT+ANAS+EPO groups (p < .05). Group comparisons demonstrated that bursting pressure was significantly higher in EPO treated rats (p < .05). The histopathology results revealed that EPO treatment improves anastomotic wound healing though decreased necrosis and inflammatory cell infiltration and increased fibroblast activity. Conclusion: The findings of the present study indicate that EPO contributes to wound healing and the strength of colon anastomosis following radiation due to its antioxidant and anti-inflammatory effects, but further studies are needed to explore the significance of these effects.     

Dynamic p53 protein expression and phosphorylation in the kidneys of rats that experienced intrauterine growth restriction

Abstract

Aim: This study investigated the mechanisms involved in intrauterine growth restriction (IUGR). Methods: The IUGR model was established by feeding pregnant SD rats a low-protein diet. Protein expression and phosphorylation were detected using Western blot and/or immunohistochemistry. Cell apoptosis was detected by TUNEL staining. The MDM2 mRNA expression was measured by real-time PCR. Results: Pups from the IUGR group had significantly lower body (7th day, 2 months) and kidney weights (1st day, 7th day, 2 months) compared to pups from the control group (p?<?0.01). The glomeruli number in IUGR pups was significantly less than that in the control pups at 2 and 3 months after birth (p?<?0.01). p53 protein level and p53 phosphorylation at Ser¹⁵ were time-dependently decreased in the kidney at 1st day, 7th day, 21st day, 2 months and 3 months, but their levels in the kidney of the IUGR pups was significantly higher than that in control pups at each time point (p?<?0.05, p?<?0.01, or p?<?0.001). Significantly more positive p21 staining was observed in IUGR pups than in control pups at each time point. Real-time PCR of MDM2 mRNA expression showed no significant difference between IUGR and control pups (p?>?0.05). Significant apoptosis was observed in the kidneys of IUGR pups compared to control pups. Conclusion: Malnutrition-induced IUGR may be associated with the activation of p53–p21 signaling in the kidney.     

Protective Effect of Infliximab on Ischemia/Reperfusion-Induced Damage in Rat Kidney

Objective: To investigate the protective effect of infliximab on ischemia–reperfusion (I/R) injury of the rat kidney. Methods: Twenty-eight male Wistar albino rats were divided into four groups: sham-operated, I/R, I/R with infliximab administered before ischemia [I/R + infliximab (bi)], and I/R with infliximab administered before reperfusion [I/R + infliximab (br)]. After a right nephrectomy to produce damage, the left renal vessels were occluded for 60 min, followed by 24-h reperfusion in rats. Changes in the rat kidney were observed by measuring the tissue levels of malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), and superoxide dismutase (SOD) and by evaluating hematoxylin–eosin (H&E)-stained and periodic acid–Schiff (PAS) sections. Results: The MDA and MPO levels in the I/R group were significantly higher than in the other groups (p < 0.05), and the SOD and GSH levels in the I/R + infliximab (bi) and I/R + infliximab (br) groups were significantly higher than in the I/R group (p < 0.05). However, histological examination revealed that the I/R + infliximab (bi) group and the I/R + infliximab (br) group had significantly fewer tubular changes and interstitial inflammatory cell infiltration than the I/R group. Conclusion: These results show that infliximab may protect against I/R injury in the rat I/R model.     

Heparin-binding epidermal growth factor-like growth factor reduces intestinal apoptosis in neonatal rats with necrotizing enterocolitis

Purpose

We have previously demonstrated that enterally administered heparin-binding epidermal growth factor-like growth factor (HB-EGF) decreases the incidence and severity of necrotizing enterocolitis (NEC) in a neonatal rat model. Because apoptosis contributes to gut barrier failure in this model, the aim of this study was to investigate the effect of HB-EGF on apoptosis during the development of NEC.

Methods

NEC was induced in neonatal rats by exposure to hypoxia, hypothermia, hypertonic formula feeding (HHHTF) plus enteral administration of lipopolysaccharide (LPS). Fifty-one neonatal rats were randomly divided into the following groups: (1) breast-fed (BF), (2) HHHTF + LPS, and (3) HHHTF + LPS with HB-EGF (600 μg/kg) added to the formula. NEC was evaluated using a standard histological scoring system. Apoptotic cells in intestinal tissues were detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and by active caspase 3 immunohistochemical staining.

Results

The incidence of NEC in the HHHTF + LPS group was higher than that in the BF group (65% vs 0%, P < .05). With administration of HB-EGF, the incidence of NEC significantly decreased to 23.8% (P < .05). The median TUNEL and active caspase 3 scores in the HHHTF + LPS group were higher than those in the BF group (1.9 vs 0.9 and 1.75 vs 0.6, respectively, P < .05). The median TUNEL and active caspase 3 scores were significantly decreased in the HHHTF + LPS + HB-EGF group compared with the HHHTF + LPS group (1.24 vs 1.9 and 1.0 vs 1.75, respectively, P < .05).

Conclusion

HB-EGF reduces the incidence of NEC in a neonatal rat model in part by decreasing apoptosis. These results support the use of HB-EGF-based clinical regimens for the treatment of NEC.     

The effect of prostate cancer and antianrogenic therapy on lipid peroxidation and antioxidant systems

In living organism, excessive free radicals oroxidative damage which occur as a result of deficient antioxidant defensive mechanisms by the effect of endogenous and exogenous factors, influences especially developmental steps of chemically induced cancers [1, 2]. In our study, plasma malondialdehyde level (MDA) as an indicator of lipid peroxidation, erythrocyte glutathione (GSH) level as an indicator of antioxidant state, glutathione reductase (GSH-Red), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) as an antioxidant enzymes and plasma vitamin E level were detected in patients with prostate cancer (21 males; age, 69.4 ± 4.8 years) before and after three months of antiandrogenic therapy with goserelin acetate as luteinizing hormone releasing hormone (LHRH) analogue. Healthy people evaluated as a control group (20 males; age, 63.7 ± 3.9). Erythrocyte GSH levels, the activities of GSH-Red and GSH-Px and plasma vitamin E levels were found significantly low in patients with prostate cancer when compared with the healthy subjects (p < 0.01, p < 0.05, p ≤ 0.001 and p ≤ 0.001 respectively). Plasma MDA level and erythrocyte GST activity of patient group were significantly higher than the levels of control group (p ≤ 0.001 and p ≤ 0.001 respectively). After antiandrogenic therapy erythrocyte GSH level, GSH-Red, GSH-Px activity and plasma vitamin E level were found unchanged. Significant decrease in plasma MDA level and significant increase in erythrocyte GST activity were detected in patient group (p < 0.05 and p ≤ 0.01 respectively). The study has revealed the shift in the oxidant-antioxidant balance towards oxidative state in patients with metastatic prostate cancer. Our results showed that antiandrogenic therapy increased in GST activity, decreased in lipid peroxidation. This revised version was published online in August 2006 with corrections to the Cover Date.     

Experimental Studies on the Effect of Lidocaine on Wound Healing

p = 0.120). Important statistical differences were observed in vascularity ( p < 0.003) and morphometric results ( p < 0.001), where collagen was found in small amounts in the lidocaine group. The results of this study suggest that local infiltration of lidocaine produces significant histopathologic changes, but it does not substantially alter wound healing as there were no differences in the breaking strength of the wounds.     

Impact of endogenous hydrogen sulfide on toll-like receptor pathway in renal ischemia/reperfusion injury in rats

Abstract

In this study, we investigated the impact of endogenous hydrogen sulfide (H₂S) on toll-like receptors (TLRs)-mediated inflammatory response and apoptosis in renal ischemia–reperfusion injury (IRI). Twenty-four male Wistar rats were randomly divided into four groups: sham, IR, IR?+?propargylglycine (PAG) and IR?+?hydroxylamine (HA). After right nephrectomy, rats were given saline for the sham and IR group, PAG for the IR?+?PAG group and HA for the IR?+?HA group, through the left renal artery for 20?min. Five minutes after drug administration, all rats except sham underwent 45?min of left renal ischemia followed by 24?h of reperfusion. Kidneys were harvested for histological and biochemical evaluation. Levels of TLRs, downstream signaling molecules and pro-inflammatory cytokines were determined by Western blot or immunohistochemistry. Hematoxylin and eosin (H&E) stained renal sections were used for histological grading of renal injury. Apoptotic cells were detected by TUNEL assay. Compared to the sham group, rats in the IR group showed higher renal levels of TLR-2, TLR-4, nuclear NF-κB p65, phosphorylated ASK1, phosphorylated TRAF2, IL-1β, IL-6, IL-18 and TNF-α (p?<?0.05), and exhibited acute kidney injury (p?<?0.05) and apoptosis (p?<?0.05). Compared to the IR group, rats receiving PAG or HA showed significantly higher levels of TLR-2, TLR-4, nuclear NF-κB p65, phosphorylated ASK1, phosphorylated TRAF2, IL-1β, IL-6, IL-18 and TNF-α (p?<?0.01), more severe acute kidney injury (p?<?0.05) and increased apoptosis (p?<?0.01). Thus, inflammatory response and apoptosis mediated by TLRs are involved in renal IRI. Inhibition of endogenous H₂S significantly activated inflammatory response and apoptosis, and thus promoted renal IRI.     

The Evaluation of Protective Effects of FK-506 on Neural Ischemic-Reperfusion Injury: an Experimental Study

Abstract Objective: In this study, we aimed to delineate the mode of neuroprotective action of FK-506, and demonstrated that FK-506 could decrease oxidative stress and apoptotic cell death in an in vivo rat model of neural ischemia-reperfusion after hemorrhagic shock. Methods: Thirty rats were used as experimental subjects and divided into five equal groups. Group A rats (sham group, n = 6) were anesthetized and craniotomies were performed for collecting brain tissue samples. In group B ischemia-reperfusion (I/R + 1 h, n = 6), group C (I/R + 24 h, n = 6), group D (I/ R + 1 h FK-506, n = 6) and group E (I/R + 24 h FK-506, n = 6), systolic blood pressure of the rats decreased to 40–50% of the normal level via bleeding from the femoral vein. Thus, a hemorrhagic shock and ischemic neural tissue model was formed. The bloodwas retained and given to the remaining animals in groups B, C,Dand E via femoral vein for reperfusion 20 min after the procedure. In group D and E, 1 mg/kg FK-506 in 0.5 ml isotonic solution was administered to the rats 5 min before reperfusion. Group B and D rats were sacrificed after 1 h and group Cand E rats were sacrificed 24 h after reperfusion; the rats were sacrificed via bleeding associated with intracardiac puncture. Craniotomy was also performed in groups B, C, D and E and brain tissue samples were fixed using neutral buffered 10% formaldehyde solution for immunohistopathological examination as in group A. Brain tissue superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, tissue myeloperoxydase (MPO) activities and apoptotic cell analyses with Apo 2.7 immunohistochemically were also performed in all groups. Results: The result of the study revealed that the SOD activities were lower for groups B (I/R + 1 h) and C (I/ R + 24 h) than for group A (sham group) (p < 0.05). In addition, SOD activities were higher in groups D (I/ R + 1 h FK-506) and E (I/R + 24 h FK-506) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). MDA levels, MPO activities and the number of apoptotic cells were lower in group A (sham group) than in groups B (I/R + 1 h) and C (I/R + 24 h) (p < 0.05). In addition to these MDA levels, MPO activities and the number of apoptotic cells were higher in groups B (I/R + 1 h) and C (I/R + 24 h) as compared to groups D (I/R + 1 h FK-506) and E (I/R + 24 h FK-506) (p < 0.05). Conclusion: The results suggest that the prophylactic use of FK-506 in an in situ ischemic neural tissue may prevent reperfusion injury.     

The antioxidant role of oral administration of garlic oil on renal ischemia–reperfusion injury

Aim: In this study we examined the effect of oral application of garlic form [garlic oil (GO)] on rats after renal ischemia–reperfusion (I/R) injury. Materials and methods: Forty male Wistar albino rats were divided into four groups: control, sham-operated, I/R, and I/R + GO. GO was diluted in water and administered by oral intubation three times each week for 6 weeks. All rats except sham-operated underwent 45 min of bilateral renal ischemia followed by 6 hr of reperfusion. Blood samples and kidney tissues were harvested from the rats, and then rats were killed. Serum urea, creatinine, and cystatin C levels were determined. Total antioxidant capacity (TAC), catalase (CAT), total oxidant status (TOS), oxidative stress index (OSI), myeloperoxidase (MPO), nitrite oxide (NO), and protein carbonyl (PC) levels in kidney tissue and blood were measured. In addition, kidney tissue histopathology was evaluated. Results: The serum urea, creatinine, and cystatin C levels were significantly higher in I/R group compared to I/R + GO group (p < 0.01). The serum and tissue antioxidant markers (TAC, CAT) were significantly lower in I/R group than I/R + GO group (p < 0.01). The serum oxidant markers (TOS, MPO, NO, and PC) were significantly higher in I/R group than I/R + GO group (p < 0.01). Also oral application of GO was effective in decreasing of tubular necrosis score. Conclusion: Based on the present data, we conclude that increased antioxidants and decreased oxidants modulated by oral application of GO attenuated the renal I/R injury.     

Effects of Surgical Sympathectomy on Skin Blood Flow in a Rat Model of Chronic Limb Ischemia

p < 0.05), NSBF ( p < 0.05), and SO ( p < 0.05) were found to be drastically reduced at day 2 after ligation compared to preligation values. This reduction partially recovered during the following weeks. TSBF ( p < 0.05) and NSBF ( p < 0.05), however were still reduced at day 28 after ligation compared to preligation values, whereas the SO at this time tended to be lower ( p = 0.11). In the sympathectomy group the TSBF was found to be increased at day 2 ( p < 0.05) and day 28 ( p < 0.05) after sympathectomy, both compared to values obtained at day 28 after ligation. Sympathectomy did not have an effect on NSBF and SO. The sham procedure had no effect on the TSBF, NSBF, or SO. These results indicate that in case of lower limb ischemia, sympathectomy improves skin blood flow at the thermoregulatory but not the nutritive level of skin microcirculation. This may be related to the fact that the thermoregulatory vessels are mainly sympathetically controlled, whereas the nutritive capillaries are mainly controlled by local (nonneural) factors.     

Effects of Polyglycolic Acid and Polypropylene Meshes on Postoperative Adhesion Formation in Mice

p > 0.05). Adhesion degree and tissue OHP levels as determinants of adhesion severity were higher in the PGA mesh group than the control group and the PP mesh group on day 90 ( p < 0.001). There was no difference between the control group and the PP mesh groups ( p > 0.05). Adhesion degree was higher on day 90 than on day 5 in the control group and the PGA mesh group ( p < 0.05), whereas tissue OHP level was higher on day 90 than on day 5 in all three groups ( p < 0.001). Also there was linear correlation between adhesion degree and tissue OHP levels ( r = 0.86, p < 0.001). The study demonstrates that ABS PGA mesh has higher potential for adhesion formation than the NA PP mesh, probably related to the increased foreign body and inflammatory reactions during the absorption process of the mesh.     

Inhibiting hydrogen sulfide production in umbilical stem cells reduces their protective effects during experimental necrotizing enterocolitis

IntroductionUmbilical mesenchymal stem cells (USC) have been shown to reduce illness in animal models of necrotizing enterocolitis (NEC), possibly through the paracrine release of hydrogen sulfide (H₂S). We hypothesized that animals treated with USCs with inhibited H₂S synthesis would exhibit more severe disease.MethodsNEC was induced in five-day-old mouse pups by formula feeding and hypoxic and hypothermic stress. Experimental groups received intraperitoneal injection of either saline vehicle or 80,000cells/gram of one of the following cell types: USC, USCs with negative-control siRNA, or USCs with targeted siRNA inhibition of the H₂S-producing enzymes. Pups were monitored by clinical assessment and after euthanasia, intestine and lung histologic injury were scored. Tissue was homogenized, and concentrations of IL-6, IL-10, and VEGF were determined by ELISA. For statistical analysis, p < 0.05 was considered significant.ResultsAnimals treated with negative-control siRNA USCs were significantly improved compared to vehicle. Clinical sickness scores as well as intestinal and lung histologic injury scores in the targeted siRNA groups were significantly worse when compared to the negative-control siRNA group. IL-6, IL-10, and VEGF had varying patterns of expression in the different groups.ConclusionInhibition of H₂S production in USCs reduces the beneficial effects of these cells during therapy in experimental NEC.Level of evidenceAnimal studies are typically described as “foundational evidence” without a true level assigned.Type of studyAnimal Study.     

Protective effect of tumor necrosis factor alpha antibody on experimental necrotizing enterocolitis in the rat

Background

Necrotizing enterocolitis (NEC) is a common and devastating disorder of premature infants. Elevated proinflammatory cytokines, especially tumor necrosis factor α (TNF-α), have been implicated in the pathogenesis of NEC. The aim of this study was to evaluate the effects of TNF-α on the inflammatory response in NEC by immunoneutralizing TNF-α with a selective antibody.

Methods

Neonatal Sprague-Dawley rats were divided in 3 groups: group 1 (n = 20), a NEC-like enterocolitis was induced by formula feeding, asphyxia, and cold exposure; group 2 (n = 9), animals were treated like in group 1 and additionally received TNF-α antibody intraperitoneally; and group 3 (n = 17), animals were dam-fed (controls). Animals were killed in case of imminent death or after 96 hours. Specimens from small bowel were processed for blinded histologic (H&E) and immunhistologic (myeloperoxidase [MPO]) analysis.

Results

In group 1, animals developed severe NEC (mean NEC score, 3.28 ± 0.32; mean MPO, 65.85 ± 9.46). In group 2, animals developed mild NEC (mean NEC score, 1.72 ± 0.41; mean MPO, 34.33 ± 9.69; P < .05). In group 3, no NEC was induced (mean NEC score, 0.0 ± 0; mean MPO, 6 ± 1.32; P < .05).

Conclusion

Tumor necrosis factor α antibody may have an attenuating effect on experimental NEC in rats.     

Recombinant Human Erythropoietin and Hemoglobin Concentration at Operation and during the Postoperative Period: Reduced Need for Blood Transfusions in Patients Undergoing Colorectal Surgery—Prospective Double-blind Placebo-controlled Study

p < 0.05). On postoperative days 3 and 7 the values were 7.2 (5.3–8.2) and 7.5 (5.4–9.4) mmol/L, respectively, in the erythropoietin group compared to 6.7 (5.2–7.8) and 6.9 (5.1–8.6) mmol/L in the placebo group ( p < 0.01). At discharge the hemoglobin concentration was 7.8 (5.9–8.8) mmol/L in the erythropoietin group and 7.2 (5.4–8.6) mmol/L in the placebo group ( p < 0.002). The blood loss during operation was similar in the two groups. In the erythropoietin group the median value was 280 ml (range 25–2000 ml), with the lower and upper quartiles 150 and 500 ml, respectively. In the placebo group the blood loss was median 300 ml (range 50–1800 ml), with the lower and upper quartiles 200 and 750 ml, respectively. The number of blood transfusions given was significantly lower in the erythropoietin group, with a mean of 0.3 (range 0–6) units compared to 1.6 (0–9) units in the control group ( p < 0.05). In conclusion, the hemoglobin concentration at the time of surgery and during the week following surgery was significantly higher in the group of patients receiving r-HuEPO perioperatively compared to the placebo group together with a significant lower use of blood transfusions in the r-HuEPO group. However, the clinical implications of these findings has yet to be proven.RID=" ID=" <E5>Correspondence to:</E5> N. Qvist, M.D., D.Sci.     

l-Arginine: Effect on Reperfusion Injury after Heart Transplantation

n = 12) or l-arginine (l-Arg 40 mg/kg, n = 12), a substrate of NO synthesis. Myocardial blood flow (MBF) was assessed by the hydrogen clearance method. An implanted balloon was used to obtain pressure–volume relations of the transplanted heart. Left ventricular developed pressure (LVDP), rate of pressure development (dP/dt), end-diastolic pressure (LVEDP), isovolumic relaxation constant (T _E ), and MBF were measured after 60 minutes and 24 hours of reperfusion. Endothelium-dependent vasodilatation in response to acetylcholine (ACh) and endothelium-independent vasodilatation in response to sodium nitroprusside (SNP) were also determined. After 1 hour the MBF was significantly higher in the l-Arg group (3.6 ± 0.6 vs. 1.9 ± 0.2 ml/min/g, p < 0.05). The l-Arg group showed better recovery of systolic function and myocardial relaxation (LVDP 106 ± 6 vs. 70 ± 7 mmHg, p < 0.05; maximal dP/dt 5145 ± 498 vs. 3410 ± 257 mmHg/s, p < 0.05; T _E 12.1 ± 0.9 vs. 16.1 ± 1.5 ms, p < 0.05, at an intraventricular volume of 80 μl). LVEDP was similar in the two groups. After 24 hours no difference was found between the groups for basal MBF, LVP, dP/dt, T _E , LVEDP, or the response of MBF to SNP. However, ACh led to a significantly higher increase in MBF in the l-Arg group (52 ± 8% vs. 29 ± 7%, p < 0.05). These results indicate that (1) NO donation improves myocardial and endothelial functional recovery during early reperfusion after heart transplantation; and (2) initial treatment with l-Arg has a persisting beneficial effect against reperfusion-induced graft coronary endothelial dysfunction during late reperfusion.     

Morbidity associated with laparotomy-confirmed spontaneous intestinal perforation: A prospective multicenter analysis

BackgroundDifferences in morbidities between spontaneous intestinal perforation (SIP) and necrotizing enterocolitis (NEC) are unknown.MethodsProspectively collected multicenter data regarding very low birth weight (VLBW) infants 2015–2019 were analyzed. Diagnosis of SIP or NEC was laparotomy-confirmed in all patients. Multivariable regression modeling was used to assess adjusted length of stay (LOS; primary outcome) and adjusted risk ratios (ARR) for weight <10th percentile at discharge, and supplemental oxygen requirement at discharge.ResultsOf 201,300 VLBW infants at 790 hospitals, 1523 had SIP and 2601 had NEC. Adjusted LOS was similar for SIP and NEC (92 vs 88 days, p = 0.08561), but significantly higher than seen without SIP or NEC (68 days, p<0.0001). The risk of growth morbidity at discharge was similar between SIP and NEC (74.2% vs 75.3%; ARR:1.00;0.94,1.06), but higher than infants without SIP or NEC (47.7%; ARR:0.50;0.47,0.53). Infants with NEC were less likely to require supplemental oxygen at discharge than infants with SIP (24.4% vs 34.9%; ARR:0.80; 0.71,0.89).ConclusionsAlthough mortality is known to be lower in VLBW infants with SIP than NEC, this study highlights the similarly high morbidity experienced by both groups of infants. These benchmark data can help align counseling of families with expected outcomes.Level of evidenceLevel II.Type of StudyPrognosis study (Cohort Study).     

Intestinal perfusion assessed by quantitative fluorescence angiography in piglets with necrotizing enterocolitis

BackgroundReduced intestinal perfusion is thought to be a part of the pathogenesis in necrotizing enterocolitis (NEC). This study aims to evaluate the intestinal perfusion assessment in NEC-lesions by quantitative fluorescence angiography with indocyanine green (q-ICG) during laparoscopy and open surgery.MethodsThirty-four premature piglets were delivered by cesarean section and fed with parenteral nutrition and increasing infant formula volumes to induce NEC. During surgery, macroscopic NEC-lesions were evaluated using a validated macroscopic scoring system (1–6 for increasing NEC severity). The intestinal perfusion was assessed by q-ICG and quantified with a validated pixel intensity computer algorithm.ResultsSignificantly higher perfusion values were found in healthy areas of the colon (score 1) compared to those with NEC scores of 4, 5, and 6 (p < 0.05). Similarly, in the small intestine, perfusion was higher in the intestine with areas scored 1 compared to scores of 3 and 4 (p < 0.05). A cut-off value was found between NEC score of 1–2 vs. 3–4 for the small intestine at 117 and for colon at 107 between NEC scores 12 vs. scores of 36 with an area less than the curve value at 0.9 (p < 0.05).Conclusionsq-ICG seems to be a feasible and valuable technique to evaluate the perfusion of tissue with NEC-lesions. We found a cut-off between intestine with scores 1-2 and intestine with NEC scores 3-6 in colon, and NEC score 3–4 in the small intestine.Level of evidenceII.