Outcomes of Atrioseptostomy with Stenting in Patients with Pulmonary Arterial Hypertension from a Large Single-Institution Cohort.

The aim of this study was to analyze results of stenting atrioseptostomy in patients with pulmonary arterial hypertension and a different level of risk for one-year mortality that is not well described. Patients that underwent atrioseptostomy with stenting were retrospectively divided in two groups: "intermediate" (n = 55) or "high" risk (n = 13), according to the 2015 ESC/ESR guideline. Results of atrioseptostomy were assessed during hospital period and at follow-up. Patients from "intermediate" risk group demonstrated lower mortality rate (10/55, vs. 6/13) during the course of the study period, as well as higher freedom from lung transplantation or Potts shunt. At discharge, patients of both groups presented improvement in functional class and mobility. Patients from "intermediate" risk group showed longer 6-min walking distance, and lower levels of brain natriuretic peptide. At the latest follow-up, stable position and full patency of stents with right-to-left or bidirectional shunt at atrial level and absence of syncope was confirmed in patients of both groups. Patients from the "intermediate" risk group demonstrated higher functional class, better performance of walking test, and lower levels of brain natriuretic peptide. Stenting atrioseptostomy reliably secured interatrial communication and improved clinical condition in patients with idiopathic pulmonary arterial hypertension. Mid-term results were better in "intermediate" risk group.

Potts shunt in children with pulmonary arterial hypertension: institutional experience.

OBJECTIVES: Since 2004, different techniques for the Potts shunt have been used in patients with incurable pulmonary arterial hypertension. However, the experience with these interventions in a single institution is limited. We present our series of Potts shunts in children with pulmonary arterial hypertension. METHODS: Eight patients with suprasystemic pulmonary arterial hypertension (pulmonary artery-to-aorta mean pressure ratio of 1.39 ± 0.30) had a Potts shunt at the median age of 13.5 months. Six patients were followed up for 2-32 (median 17) months after the operation. RESULTS: In all cases, the Potts shunt caused a decrease in arterial blood oxygen saturation at the lower extremities and was the genesis of the arterial blood oxygen saturation gradient between the upper and lower extremities (10.5 ± 1.8% at discharge). Postoperative echocardiography revealed flattening of the ventricular septum as well as a decrease in the right ventricle-to-left ventricle end-diastolic diameter ratio from 1.36 ± 0.14 preoperatively to 0.99 ± 0.22 at discharge (P = 0.010). The 2 patients with the highest preoperative pulmonary artery-to-aorta mean pressure ratio (1.79-1.86) died during the early postoperative period from repeated pulmonary hypertension crises and uncontrolled hypoxaemia. There were no deaths during the follow-up period. The paediatric functional class of the patients improved from IIIb-IV to I-II, syncopal episodes no longer persisted and the weight deficit decreased from 21.8 ± 7.5% preoperatively to 11.5 ± 5.9% at the latest follow-up examination (P = 0.004). The arterial blood oxygen saturation gradient between the upper and lower extremities and the right ventricle-to-left ventricle end-diastolic diameter ratio were the same as they were while the patients were in the hospital. CONCLUSIONS: Our limited experience demonstrates that the Potts shunt lowers suprasystemic pulmonary hypertension to the systemic level, limits manifestations of right-sided heart failure and improves the overall functional status of the patients.

Repair of isolated partial anomalous pulmonary venous connection of the right upper pulmonary veins to the left vertical vein.

The most common form of partial anomalous pulmonary venous connection is drainage of the right pulmonary veins to the superior vena cava. On the contrary, partial anomalous venous connection of right pulmonary veins to the left vertical vein is described in few reports. The goal of this publication is to present the case of diagnosis and surgical repair of this extremely rare pathology in a 19-year old female. Methods of preoperative examination included but were not limited to spiral computed tomography and angiocardiography. Intraoperative examination confirmed that the collector of right upper pulmonary veins was connected to the vertical vein that continued to the innominate vein and then to the superior vena cava draining into the right atrium. During surgical intervention, the vertical vein was transected in the area of connection to the innominate vein with the suturing of inlet area. The collector of the right upper pulmonary veins was then anastomosed with the left atrial appendage. Postoperative course was uneventful. In conclusion, isolated partial anomalous pulmonary venous connection of the right upper pulmonary veins to the left vertical vein is a very rare congenital defect. Existing modern techniques contribute to the precise and timely diagnosis of this anomaly.

Poor Left Ventricular Performance in a Child With Coronary Sinus Stenosis: Successful Surgical Repair.

Atresia or stenosis of the coronary sinus is a rare congenital defect that can cause marked clinical manifestations, depending on the presence of concomitant anomalies securing adequate coronary venous outflow. We describe a 4.5-year-old boy admitted to the clinic with signs of congestive heart failure (left ventricular ejection fraction, 29%). His condition had deteriorated during the previous 4 months. The examination revealed stenosis of the coronary sinus ostium, coronary sinus-to-left atrium fistula, mitral regurgitation of the second grade, and moderate pulmonary hypertension. The surgical intervention consisted of enlargement and plastic reconstruction of the coronary sinus as well as closure of the coronary sinus-to-left atrium fistula. The hospital period was uneventful. The left ventricular ejection fraction at discharge increased up to 50%.

Stroke education in an emergency department waiting room: a comparison of methods.

BACKGROUND: Since the emergency department (ED) waiting room hosts a large, captive audience of patients and visitors, it may be an ideal location for conducting focused stroke education. The aim of this study was to assess the effectiveness of various stroke education methods. METHODS: Patients and visitors of an urban ED waiting room were randomized into one of the following groups: video, brochure, one-to-one teaching, combination of these three methods, or control group. We administered a 13-question multiple-choice test to assess stroke knowledge prior to, immediately after, and at 1 month post-education to patients and visitors in the ED waiting room. RESULTS: Of 4 groups receiving education, all significantly improved their test scores immediately post intervention (test scores 9.4±2.5-10.3±2.0, P<0.01). At 1 month, the combination group retained the most knowledge (9.4±2.4) exceeding pre-intervention and control scores (both 6.7±2.6, P<0.01). CONCLUSION: Among the various stroke education methods delivered in the ED waiting room, the combination method resulted in the highest knowledge retention at 1-month post intervention.

Results of Fontan operation in patients with atrioventricular valve regurgitation.

OBJECTIVES: The influence of concomitant atrioventricular valve regurgitation on the results of Fontan operation remains disputable. The goal of this study was to compare early and late results of Fontan operation performed in patients with mild or moderate-to-severe atrioventricular valve regurgitation. METHODS: For retrospective analysis, patients with atrioventricular valve insufficiency assessed by echocardiography were divided into three groups based on the severity of regurgitation and its repair or non-repair during Fontan operation: Group 1: unrepaired regurgitation 1-2+ (n = 33); Group 2: unrepaired regurgitation 3-4+ (n = 11); Group 3: repaired regurgitation 3-4+ (n = 35). Actuarial survival was estimated by the Kaplan-Meier method, followed by the log-rank test to compare survival curves between groups. RESULTS: Hospital mortality rates in Groups 1 through 3 reached 3, 27 and 14%, respectively (P = 0.015, Group 1 vs Group 2). The frequency of non-lethal complications did not significantly differ between groups. However, patients from Group 2 required significantly more intensive inotropic support, longer mechanical ventilation and had larger pleural effusion. Predicted survival after Fontan operation was the worst in Group 2 (P = 0.016, Group 2 vs Group 1). The frequency of non-lethal late complications was also the highest in Group 2 (50 vs 17 or 11%); however, the difference did not reach statistical significance (P = 0.13 and 0.069, respectively). The severity of atrioventricular valve regurgitation during the follow-up did not significantly change when compared with discharge after the repair in Group 2 or Group 3 (P = 0.19 and 0.52, respectively), and significantly increased in Group 1 (P = 0.003). However, this increase did not have clinical significance during the reported period of follow-up. CONCLUSIONS: If unrepaired, concomitant moderate-to-severe atrioventricular valve regurgitation significantly worsens the results of the Fontan procedure. Longer observation is needed to define the strategy in patients with mild atrioventricular valve regurgitation that remained unrepaired during Fontan operation.

Repair of congenital heart defects associated with single pulmonary artery.

BACKGROUND: Experience with complete repair of congenital heart defects associated with unilateral absence of a pulmonary artery is limited. The aim of this retrospective study was to present our surgical experience of this complex category of patients, to analyze immediate results of surgical interventions, and to suggest a rational surgical strategy. METHODS: Of 37 patients with a single pulmonary artery who underwent complete repair of associated heart defects, the left or right pulmonary artery was absent in 32 and 5, respectively. The most frequent heart defects were tetralogy of Fallot (n = 25) and ventricular septal defect (n = 8). The median age of these patients was 7.1 years. Preoperative examinations included echocardiography, cardiac catheterization and angiocardiography, with quantitative assessment of the single pulmonary artery. In-hospital parameters of surgical outcome were analyzed. RESULTS: Recorded hospital mortality was 2.7% (1/37). The single death was in a patient with tetralogy of Fallot, agenesis of the left pulmonary artery, and a small diameter of the contralateral pulmonary artery (Nakata index 174 mm(2)·m(-2)). The right-to-left ventricular systolic pressure ratio after complete tetralogy of Fallot repair in patients who survived the operation was 0.58 ± 0.11. CONCLUSIONS: Complete repair of congenital heart defects in patients with unilateral absence of a pulmonary artery is associated with a relatively low risk. If the hilar artery is of adequate size, surgical intervention should attempt restoration of the communication between the disconnected hilar artery and the pulmonary trunk, in addition to repairing the heart defects.

Dynamics of factor XIII levels after open heart surgery for congenital heart defects: do cyanotic and acyanotic patients differ?

Cardiopulmonary bypass (CPB) reduces coagulation factor levels through hemodilution and consumption. Differences in CPB-induced alterations of factor XIII (FXIII) levels in children with cyanotic and acyanotic congenital heart defects (CHDs) are not well characterized. FXIII activity (determined by Berichrom assay), prothrombin index, activated partial thromboplastin time, and fibrinogen were measured before open heart surgery with CPB and 5 days postoperatively for children older than 3 years with acyanotic (n = 30) and cyanotic (n = 30) CHDs. The preoperative FXIII levels did not differ significantly among the children of the compared groups. The cyanotic patients showed a significantly longer duration of CPB (111.4 ± 45.8 vs 71.5 ± 33.6 min; p = 0.026) and aortic cross-clamp (68.0 ± 27.1 vs 45.4 ± 31.4 min; p = 0.034). The drop in FXIII levels after termination of CPB was more profound for the children with cyanotic CHDs (87.1 ± 13.4 to 49.1 ± 13.2 vs 81.5 ± 12.6 to 58.6 ± 11.1 %, respectively; p = 0.018). The cyanotc patients also were restored to their baseline FXIII levels later than the children with acyanotic CHDs (at 48 vs 24 h). The post-CPB dynamics of the majority of the other coagulation parameters in the compared groups of patients were similar. The cyanotic patients experienced significantly greater postoperative blood loss than the acyanotic patients (12.6 ± 4.9 vs 5.0 ± 2.1 mL/kg; p < 0.001) and were transfused with larger volumes of red blood cells (10.4 ± 6.5 vs 4.2 ± 2.5 mL/kg; p = 0.007). The decrease in FXIII levels after CPB is more profound and lasts longer in children with cyanotic CHDs than in acyanotic patients. The rational strategy of postoperative FXIII replacement therapy for these categories of patients needs to be determined.

Does recombinant factor XIII eliminate early manifestations of multiple-organ injury after experimental burn similarly to gut ischemia-reperfusion injury or trauma-hemorrhagic shock?

The authors have previously shown that recombinant factor XIII (rFXIII) eliminates early manifestations of multiple-organ injury caused by experimental superior mesenteric artery occlusion or trauma-hemorrhagic shock. The aim of the present study was to test the hypothesis that rFXIII provides similar protective effect in experimental burn injury. Rats were randomly divided into five groups (eight animals per group): group 1: burn + placebo treatment; group 2: burn + rFXIII pretreatment; group 3: burn + rFXIII treatment; group 4: sham burn + placebo treatment, and group 5: sham burn + rFXIII treatment. Burn (40% of TBSA) was achieved by immersing the back and abdomen of a rat into 97°C water for 10 and 5 seconds, respectively. Infusion of rFXIII (1 mg/kg) or placebo was performed immediately after burn/sham burn in treatment groups or 24 hours before burn and repeated immediately after it in pretreatment group. Endpoint parameters measured 3 hours after burn/sham burn included muscle blood flow and PO2, lung permeability, gut histology, lung and gut myeloperoxidase activity, neutrophil respiratory burst, and FXIII activity. Both treatment and pretreatment with rFXIII partially preserved microvascular blood flow in the muscle. Muscle PO2 in pretreated rats did not differ from that in shams. Pretreatment but not treatment with rFXIII preserved lung permeability. rFXIII did not have any protective effect on other endpoint parameters. In contrast to superior mesenteric artery occlusion and trauma-hemorrhagic shock experimental models, rFXIII at the doses tested has a limited effect on preventing early manifestations of multiple-organ injury after experimental burn.

Palliative surgical treatment of congenital heart defects associated with unilateral absence of the pulmonary artery.

OBJECTIVES: Experience with the palliative treatment of congenital heart defects (CHDs) associated with unilateral absence of the pulmonary artery (UAPA) is limited. There is a description of 32 interventions in the available literature. The aim of this retrospective study was to present our experience with palliative interventions in patients with cyanotic CHDs associated with UAPA and to suggest a rational surgical strategy. METHODS: Twenty-nine patients were subjected to palliative interventions. All of them had the following cyanotic CHDs with agenesis of the left pulmonary artery: tetralogy of Fallot (n = 26) or double outlet right ventricle (n = 3). Twenty patients were subjected to a single and 9 to multiple staged palliative operations. Patients were grouped according to the type of initial palliation to assess the clinical and haemodynamic results of each surgical intervention: Group 1: systemic-to-pulmonary shunts (n = 13); Group 2: transluminal balloon pulmonary valvuloplasty (n = 5); Group 3: palliative reconstruction of the right ventricular outflow tract (n = 11). The median age of patients at the initial palliative intervention was 2.6 years. Twenty-three of 27 discharged patients were followed up for a median period of 3 years. RESULTS: Hospital mortality in our series reached 7% (2 of 29 patients). Both lethal outcomes occurred after palliative reconstruction of the right ventricular outflow tract was performed as a sole intervention. The assessment of angiographic parameters has shown that palliative reconstruction of the right ventricular outflow tract provided more significant and uniform enlargement of the pulmonary artery than systemic-to-pulmonary shunts or transluminal balloon pulmonary valvuloplasty. Fifty-nine percent of patients (17 of 29 patients) were subjected to complete repair of CHDs during the follow-up. CONCLUSIONS: Palliative surgical treatment of CHDs associated with UAPA can be performed with a relatively low risk. Systemic-to-pulmonary artery shunt and transluminal balloon pulmonary valvuloplasty are methods of choice in patients with non-severe hypoplasia of the single pulmonary artery. The intravascular intervention is indicated more in patients with a prevailing valvular component of the pulmonary stenosis. Palliative reconstruction of the right ventricular outflow tract is a more favourable procedure for patients with a severe hypoplasia of the single pulmonary artery.

Recombinant factor XIII mitigates hemorrhagic shock-induced organ dysfunction.

BACKGROUND: Plasma factor XIII (FXIII) is responsible for stabilization of fibrin clot at the final stage of blood coagulation. Since FXIII has also been shown to modulate inflammation, endothelial permeability, as well as diminish multiple organ dysfunction (MOD) after gut ischemia-reperfusion injury, we hypothesized that FXIII would reduce MOD caused by trauma-hemorrhagic shock (THS). MATERIALS AND METHODS: Rats were subjected to a 90 min THS or trauma sham shock (TSS) and treated with either recombinant human FXIII A(2) subunit (rFXIII) or placebo immediately after resuscitation with shed blood or at the end of the TSS period. Lung permeability, lung and gut myeloperoxidase (MPO) activity, gut histology, neutrophil respiratory burst, microvascular blood flow in the liver and muscles, and cytokine levels were measured 3 h after the THS or TSS. FXIII levels were measured before THS or TSS and after the 3-h post-shock period. RESULTS: THS-induced lung permeability as well as lung and gut MPO activity was significantly lower in rFXIII-treated than in placebo-treated animals. Similarly, rFXIII-treated rats had lower neutrophil respiratory burst activity and less ileal mucosal injury. rFXIII-treated rats also had a higher liver microvascular blood flow compared with the placebo group. Cytokine response was more favorable in rFXIII-treated animals. Trauma-hemorrhagic shock did not cause a drop in FXIII activity during the study period. CONCLUSIONS: Administration of rFXIII diminishes THS-induced MOD in rats, presumably by preservation of the gut barrier function, limitation of polymorphonuclear leukocyte (PMN) activation, and modulation of the cytokine response.

Experience with bidirectional cavopulmonary anastomosis and modified Fontan operation in patients with single ventricle and concomitant visceral heterotaxy.

The object of our study was to analyze the results of bidirectional cavopulmonary anastomosis (BCPA) and modified Fontan operations (MFO) in patients with a functionally single ventricle and heterotaxy syndrome and to reveal risk factors for these surgical interventions. During 1983-2010, 681 patients underwent BCPA or MFO. Thirty-nine had heterotaxy syndrome. The median follow-up period after BCPA and MFO was nine and 1.5 years, respectively. Risk factors for lethal outcomes were determined by logistic regression analysis. Hospital mortality after BCPA and MFO was 7.9% and 12.5%, respectively and did not significantly differ from patients without heterotaxy. The most frequent hospital complications were heart failure, pleural effusions, and arrhythmias. Late mortality after BCPA and MFO was 8.7% and did not significantly differ from patients without heterotaxy. Late deaths were caused by congestive heart failure or pulmonary thromboembolism. The main non-lethal complication was arrhythmia. Patients have significantly improved their functional class at follow-up. The independent risk factor for lethal outcomes after BCPA and MFO was preoperative regurgitation at atrioventricular valves (P=0.012). BCPA and MFO in patients with a functionally single ventricle and heterotaxy syndrome allow to significantly improves their quality of life. Preoperative regurgitation at atrioventricular valves worsens surgical results.

Immediate results of bidirectional cavopulmonary anastomosis and Fontan operations in adults.

The purpose of this study is to analyze the immediate results of bidirectional cavopulmonary anastomosis (BCPA) and Fontan operations performed in adults, and to reveal the risk factors. During the years 1983-2010, 681 consecutive patients underwent BCPA or a Fontan operation. Fifty-three of 681 patients were more than 18 years of age. Twenty-nine adults underwent BCPA and 24 underwent a Fontan operation. Immediate results of surgical treatment were followed during the hospital period. The average number of exceeded 'operability' criteria by Choussat et al. [Choussat A, Fontan F, Besse P, Vallot F, Chauve A, Bricaud H. Selection criteria for Fontan procedure. In: Anderson RH, Shinebourne EA, editors. Pediatric Cardiology. Edinburgh: Churchhill Livingstone, 1977:559-566] was significantly higher in patients from the BCPA group compared to the Fontan group (1.3±0.8 vs. 0.9±0.7, P=0.034). Hospital mortality after BCPA in adults was 6.9% (2/29) and did not differ from children (7.1%, 19/268), P=0.634. Hospital mortality after Fontan operation in adults was 8.3% (2/24) and did not differ from children (11.9%, 43/360), P=0.419. The frequency of non-lethal hospital complications was higher in patients after a Fontan operation. Patients from the Fontan group more frequently developed arrhythmias and prolonged pleural effusions. Preoperative regurgitation at atrioventricular valves was an independent risk factor for hospital mortality and morbidity after a Fontan operation. BCPA and Fontan operations performed in adults are accompanied by good immediate results and considerably improves patients' condition.

Effectiveness of stroke education in the emergency department waiting room.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of stroke education provided to patients and their significant others in the emergency department (ED) waiting area. Our focus was on the 4 main aspects of stroke: signs and symptoms, risk factors, behavior modification, and the urgency to seek medical attention. We hypothesized that showing educational videos, providing one-on-one counseling, and distributing literature would result in greater stroke knowledge and positive behavioral modification. METHODS: In this pilot, randomized controlled trial, our research team enrolled patients and visitors in the fast-track waiting area of the ED. After obtaining informed written consent, participants were randomly assigned to the control group or to the intervention group. The intervention group received an educational video program, one-on-one counseling, and stroke education materials, and completed a 13-question test after receiving the education. The control group completed the same test without receiving any education. Both groups completed the same test again at 1 and 3 months to assess stroke knowledge retention. RESULTS: There were a total of 329 participants: 151 in the control group and 178 in the intervention group. Gender, age, and educational level of participants did not differ between groups. At all time points of the study, participants receiving stroke education demonstrated better test scores than those in the control group. However, knowledge retention in the intervention group gradually declined during the follow-up. Individuals enrolled in the intervention group appeared to be more motivated to reduce their smoking habits, compared with control subjects; however, the number of cigarettes they smoked per day did not dramatically decrease in comparison with their own baseline. Receiving the education session did not result in positive diet or physical activity changes. CONCLUSIONS: ED stroke education, which includes video program, one-on-one counseling, and written educational materials, is able to significantly increase stroke knowledge. Modification and reinforcement of education is needed to achieve better knowledge retention and favorable lifestyle modifications.

Augmenting regional cerebral blood flow using external-to-internal carotid artery flow diversion method.

The objective of this study was to assess the effect of flow diversion by external carotid artery (ECA) occlusion on ipsilateral regional cerebral blood flow (rCBF). Local cerebral hyperperfusion in rats (n = 12) was induced by ligating the right ECA. Ipsilateral rCBF was determined pre- and post-ligation for 120 min using a laser Doppler flow meter. Sham animals (n = 6) were subjected to the craniotomy without ligation of the right ECA. In a separate series of rats (n = 5), brain tissue oxygen levels (pO(2)) in the right and left brain hemispheres were determined before and 90 min after ligation of the right ECA using a tissue oxygenation monitoring unit. We investigated the effect of ECA occlusion hemispheric changes in rCBF in one clinical case as a proof of concept. Ligation of ECA resulted in a statistically significant increase in rCBF on the ipsilateral side compared to the sham-operated rats (p < 0.0001). On average we observed a 34% increase (95% CI: 24-45%) in rCBF in the ipsilateral territory in the treated group compared with sham-operated rats. There was no significant variation in MAP for the treated animals. Vascular permeability and cerebral water content in the right hemisphere after ligation of ECA did not significantly differ from the contralateral hemisphere. Ipsilateral hemisphere tissue pO(2) was significantly higher compared to the contralateral area (p < 0.002) post-ligation or to the ipsilateral area (p < 0.001) prior to ligation. In the clinical case, occlusion of ECA resulted in 3.6% and 12.1% increase in peak value and rise-time of the time-density curves. Flow diversion by temporary occlusion of the ECA can result in increased rCBF and cerebral pO(2) on the ipsilateral side. The strategy may represent a viable option to augment rCBF in focal cerebral ischemia.

Trauma-hemorrhagic shock-induced red blood cell damage leads to decreased microcirculatory blood flow.

OBJECTIVE: To test the hypothesis that trauma-hemorrhagic shock (T/HS)-induced changes in red blood cells (RBC) contribute to the reduction of blood flow in distant organs. DESIGN: Laboratory study. SETTING: Academic medical center laboratory. SUBJECTS: Specific pathogen-free male Sprague-Dawley rats weighing between 250 and 350 g. INTERVENTIONS: Rats were transfused with trauma-sham shock (T/SS), or T/HS whole blood, or RBC-depleted blood (blood with the RBC removed and consisting of white blood cells and plasma). MEASUREMENTS AND MAIN RESULTS: Cardiac output and organ blood flow were measured by the radioactive microsphere technique. RBC tissue trapping, deformability, and RBC aggregation and adhesion were studied. Measurements of RBC adenosine triphosphate (ATP) and plasma fibrinogen were performed. Exchange transfusion with T/SS blood did not alter cardiac output or organ blood flow. However, cardiac output and blood flow in several organs were decreased when T/HS whole blood was used and RBCs were trapped in the organs that evidenced decreased blood flow. T/HS also increased RBC aggregation and adhesion, and decreased deformability. The ability of T/HS exchange transfusion to decrease microcirculatory blood flow did not appear to be due to plasma factors or non-RBC elements (i.e., white blood cell), because organ blood flow was not reduced after exchange transfusion with T/HS RBC-depleted blood. Likewise, neither decreased RBC ATP nor increased plasma fibrinogen explained the T/HS-induced changes that were observed. There was no change in fibrinogen levels during or after shock. Although there was a transient decrease in T/HS erythrocyte ATP levels during the early shock period, in contrast to RBC function, the ATP levels had returned to normal with resuscitation. CONCLUSIONS: T/HS induces significant changes in RBC functions and the injection of T/HS, but not T/SS, RBC leads to decreased organ blood flow. These findings confirm the hypothesis that T/HS-induced RBC alterations will directly cause organ hypoperfusion and suggest that T/HS-induced RBC damage contributes to this process. Thus, T/HS-induced changes in RBC function may contribute to the development of shock-induced multiple organ failure.

Elimination of C5aR prevents intestinal mucosal damage and attenuates neutrophil infiltration in local and remote organs.

The complement C5a pathway has been shown to be an important mediator of inflammation and tissue injury. To further understand the role of C5a receptor (C5aR) pathway in ischemia/reperfusion (I/R) injury, and to evaluate the potential of antagonizing C5aR to protect from I/R injury, we tested the effect of eliminating C5aR using C5aR knockout (KO) mice and their wild-type (WT) littermates in a superior mesenteric artery occlusion (SMAO) intestinal I/R injury model. C5aR KO and WT mice were subjected to SMAO or sham for 45 min. After 3 h of reperfusion, the percentage of injured ileal villi was twice as high in WT mice subjected to SMAO as compared with the C5aR KO mice. In addition, the number of neutrophils was 34% higher in WT mice subjected to SMAO as compared with the C5aR KO mice. Moreover, ileum and lung myeloperoxidase activities after SMAO were significantly higher in WT than C5aR KO mice. Apoptotic cell death was induced after reperfusion in WT-SMAO and was reduced by more than 50% in C5aR KO mice. The plasma level of TNF-alpha was increased approximately 3.74-fold in WT subjected to SMAO compared with sham. In contrast, the level was increased only approximately 1.18-fold in the C5aR KO mice subjected to SMAO. In conclusion, this study demonstrates that elimination of the C5aR pathway protects the intestine from I/R injury and diminishes intestine-derived pulmonary neutrophil sequestration. Blocking C5aR may be considered as a potential therapeutic intervention for I/R injury.

Recombinant factor XIII diminishes multiple organ dysfunction in rats caused by gut ischemia-reperfusion injury.

Plasma factor XIII (FXIII) is responsible for stabilization of fibrin clot at the final stage of blood coagulation. Because FXIII has also been shown to modulate inflammation and endothelial permeability, we hypothesized that FXIII diminishes multiple organ dysfunction caused by gut I/R injury. A model of superior mesenteric artery occlusion (SMAO) was used to induce gut I/R injury. Rats were subjected to 45-min SMAO or sham SMAO and treated with recombinant human FXIII A2 subunit (rFXIII) or placebo at the beginning of the reperfusion period. Lung permeability, lung and gut myeloperoxidase activity, gut histology, neutrophil respiratory burst, and microvascular blood flow in the liver and muscles were measured after a 3-h reperfusion period. The effect of activated rFXIII on transendothelial resistance of human umbilical vein endothelial cells was tested in vitro. Superior mesenteric artery occlusion-induced lung permeability as well as lung and gut myeloperoxidase activity was significantly lower in rFXIII-treated versus untreated animals. Similarly, rFXIII-treated rats had lower neutrophil respiratory burst activity and ileal mucosal injury. Rats treated with rFXIII also had higher liver microvascular blood flow compared with the placebo group. Superior mesenteric artery occlusion did not cause FXIII consumption during the study period. In vitro, activated rFXIII caused a dose-dependent increase in human umbilical vein endothelial cell monolayer resistance to thrombin-induced injury. Thus, administration of rFXIII diminishes SMAO-induced multiple organ dysfunction in rats, presumably by preservation of endothelial barrier function and the limitation of polymorphonuclear leukocyte activation.

The influence of the type of resuscitation fluid on gut injury and distant organ injury in a rat model of trauma/hemorrhagic shock.

BACKGROUND: Recognition that resuscitation with Ringers lactate (RL) potentiates trauma-hemorrhagic shock (T/HS)-induced organ injury and systemic inflammation has led to a search for improved initial fluid resuscitation regimens. However, one relatively neglected component in the search for new and novel resuscitation strategies is a determination of what fluid resuscitation therapy (i.e., control group) the new experimental regimen of interest should be tested against. Thus, we tested the effects of three commonly used resuscitation strategies on trauma-shock-induced gut and lung injury, as well as neutrophil activation and red blood cell (RBC) function. METHODS: Male Sprague Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of sham shock (trauma-sham shock [T/SS]) or a laparotomy plus hemorrhagic shock (T/HS), followed by a reperfusion period of 3 hours. The T/HS groups were resuscitated either with their shed blood (SB), or half the SB and 1.5 times the SB volume as RL (SB/RL), or 3 times the SB volume as RL (3RL). The T/SS groups received either no resuscitation or RL at 1.5 times the SB volume of the T/HS rats. Gut injury was quantified by measuring intestinal permeability to flourescein dextran (FD-4), as well as by histologic analysis of the terminal ileum. Lung injury was assessed histologically and by the magnitude of neutrophil sequestration as reflected in myeloperoxidase levels. Neutrophil activation was measured by quantitating the level of CD11b expression using flow cytometry. RBC injury was analyzed by measuring the RBC deformability. RESULTS: As compared with the T/SS groups, all three T/HS resuscitation regimens were associated with morphologic evidence of gut and lung injury, increased gut permeability, pulmonary leukosequestration, systemic neutrophil activation, and decreased RBC deformability (p < 0.05). However, the effect of the resuscitation regimens varied based on the tissues and cells tested. Morphologically, gut and lung injury as well as pulmonary neutrophil sequestration was worse in the 3RL T/HS group than the other two T/HS groups. As compared with the other two T/HS resuscitation regimens, resuscitation with the SB/RL combination was associated with less of an increase in gut permeability, systemic neutrophil activation, and RBC rigidification (p < 0.05). CONCLUSIONS: The type of resuscitation regimen used influenced the extent of organ injury and cellular activation or dysfunction observed after T/HS with different resuscitation regimens showing varying effects depending on the cell or organ tested. Thus, when testing novel fluid resuscitation regimen, attention must be paid to the control resuscitation regimen used.

Double outlet right ventricle with anomalous left pulmonary artery.

We describe a rare case of anomalous origin of the left pulmonary artery from the ascending aorta with concomitant double-outlet right ventricle in a 2-year-old boy. He underwent successful 2-stage surgical treatment with transluminal balloon pulmonary valvuloplasty, followed by complete repair. A follow-up examination at 4 years after the operation showed good results.