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To investigate primary graft function of hearts from circulatory dead donors (DCD) preserved with oxygenated hypothermic machine perfusion (oHMP) (XVIVO Heart preservation system) following either direct procurement and perfusion (DPP) or normothermic regional perfusion (NRP) with subsequent transplantation and correlate graft function to oHMP perfusion parameters. In a porcine model, DCD was instituted with circulatory arrest of 15 min, followed by preservation with either DPP and oHMP or NRP and oHMP. After 180 min preservation, orthotopic heart transplantation (HTX) was performed. Dobutamine and norepinephrine were titrated for inotropic and vasoconstrictive support. After weaning from cardiopulmonary bypass, ventricular function was assessed by pressure-volume admittance and Swan-Ganz catheters. Left ventricular contractility was correlated to available HMP parameters using spearman rank correlation. Functional warm ischemic time (FWIT) was similar between groups (DPP 19±1 and NRP 18±1 min, p = 0.23), while time from withdrawal to oxygenated reperfusion was significantly longer in the DPP group (DPP 39±6 and NRP 21±1 min, p < 0.001). End-oHMP coronary flow was negatively correlated to contractile function, while oxygen uptake was positive correlated contractile function. Delta values of perfusion parameters did not correlate to contractile function. Coronary flow and oxygen extraction during oHMP may be important predictors of early graft contractile function post-HTX from DCD donors. [ABSTRACT FROM AUTHOR]

Background: Thoracoabdominal normothermic regional perfusion (NRP) is a new method for in situ reperfusion and reanimation of potential donor organs in donation after circulatory death by reperfusion of the thoracic and abdominal organs with oxygenated blood. We investigated effects of high oxygenation (HOX) versus low oxygenation (LOX) during NRP on donor heart function in a porcine model., Methods: Pigs (80 kg) underwent a 15-min anoxic cardiac arrest followed by cardiac reanimation on NRP using a heart-lung bypass machine with subsequent assessment 180 min post-NRP. The animals were randomized to HOX (FiO2 1.0) or LOX (FiO2 0.21 increased to 0.40 during NRP). Hemodynamic data were obtained by invasive blood pressure and biventricular pressure-volume measurements. Blood gases, biomarkers of inflammation, and oxidative stress were measured., Results: Eight of 9 animals in the HOX group and 7 of 10 in the LOX group were successfully weaned from NRP. Right ventricular end-systole elastance was significantly improved in the HOX group compared with the LOX group, whereas left ventricular end-systole elastance was preserved at baseline levels. Post-NRP cardiac output, mean arterial, central venous, and pulmonary capillary wedge pressure were all comparable to baseline. Creatinine kinase-MB increased more in the LOX group than the HOX group, whereas proinflammatory cytokines increased more in the HOX group than the LOX group. No difference was found in oxidative stress between groups., Conclusions: All hearts weaned from NRP showed acceptable hemodynamic function for transplantation. Hearts exposed to LOX showed more myocardial damage and showed poorer contractile performance than hearts reperfused with high oxygen., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Insulin-like growth factor-1 (IGF-1) is a pleiotropic molecule with neurotrophic and immunomodulatory functions. Knowing the capacity of chronically activated microglia to produce IGF-1 may therefore show essential to promote beneficial microglial functions in Alzheimer's disease (AD). Here, we investigated the expression of IGF-1 mRNA and IGF-1 along with the expression of tumor necrosis factor (TNF) mRNA, and the amyloid-β (Aβ) plaque load in the hippocampus of 3- to 24-month-old APP swe /PS1 ΔE9 transgenic (Tg) and wild-type (WT) mice. As IGF-1, in particular, is implicated in neurogenesis we also monitored the proliferation of cells in the subgranular zone (sgz) of the dentate gyrus. We found that the Aβ plaque load reached its maximum in aged 21- and 24-month-old APP swe /PS1 ΔE9 Tg mice, and that microglial reactivity and hippocampal IGF-1 and TNF mRNA levels were significantly elevated in aged APP swe /PS1 ΔE9 Tg mice. The sgz cell proliferation decreased with age, regardless of genotype and increased IGF-1/TNF mRNA levels. Interestingly, IGF-1 mRNA was expressed in subsets of sgz cells, likely neuroblasts, and neurons in both genotypes, regardless of age, as well as in glial-like cells. By double in situ hybridization these were shown to be IGF1 mRNA + CD11b mRNA + cells, i.e., IGF-1 mRNA-expressing microglia. Quantification showed a 2-fold increase in the number of microglia and IGF-1 mRNA-expressing microglia in the molecular layer of the dentate gyrus in aged APP swe /PS1 ΔE9 Tg mice. Double-immunofluorescence showed that IGF-1 was expressed in a subset of Aβ plaque-associated CD11b + microglia and in several subsets of neurons. Exposure of primary murine microglia and BV2 cells to Aβ 42 did not affect IGF-1 mRNA expression. IGF-1 mRNA levels remained constant in WT mice with aging, unlike TNF mRNA levels which increased with aging. In conclusion, our results suggest that the increased IGF-1 mRNA levels can be ascribed to a larger number of IGF-1 mRNA-expressing microglia in the aged APP swe /PS1 ΔE9 Tg mice. The finding that subsets of microglia retain the capacity to express IGF-1 mRNA and IGF-1 in the aged APP swe /PS1 ΔE9 Tg mice is encouraging, considering the beneficial therapeutic potential of modulating microglial production of IGF-1 in AD.

Neuroinflammation, characterized by chronic activation of the myeloid-derived microglia, is a hallmark of Alzheimer's disease (AD). Systemic inflammation, typically resulting from infection, has been linked to the progression of AD due to exacerbation of the chronic microglial reaction. However, the mechanism and the consequences of this exacerbation are largely unknown. Here, we mimicked systemic inflammation in AD with weekly intraperitoneal (i.p.) injections of APP SWE /PS1 ΔE9 transgenic mice with E. coli lipopolysaccharide (LPS) from 9 to 12 months of age, corresponding to the period with the steepest increase in amyloid pathology. We found that the repeated LPS injections ameliorated amyloid pathology in the neocortex while increasing the neuroinflammatory reaction. To elucidate mechanisms, we analyzed the proteome of the hippocampus from the same mice as well as in unique samples of CNS myeloid cells. The repeated LPS injections stimulated protein pathways of the complement system, retinoid receptor activation and oxidative stress. CNS myeloid cells from transgenic mice showed enrichment in pathways of amyloid-beta clearance and elevated levels of the lysosomal protease cathepsin Z, as well as amyloid precursor protein, apolipoprotein E and clusterin. These proteins were found elevated in the proteome of both LPS and vehicle injected transgenics, and co-localized to CD11b + microglia in transgenic mice and in primary murine microglia. Additionally, cathepsin Z, amyloid precursor protein, and apolipoprotein E appeared associated with amyloid plaques in neocortex of AD cases. Interestingly, cathepsin Z was expressed in microglial-like cells and co-localized to CD68 + microglial lysosomes in AD cases, and it was expressed in perivascular cells in AD and control cases. Taken together, our results implicate systemic LPS administration in ameliorating amyloid pathology in early-to-mid stage disease in the APP SWE /PS1 ΔE9 mouse and attract attention to the potential disease involvement of cathepsin Z expressed in CNS myeloid cells in AD.

Background: Although mood and sleep disturbances are nearly universal among patients with Alzheimer's disease (AD), brain structures involved in non-cognitive processing remain under characterized in terms of AD pathology., Objectives: This study was designed to evaluate hallmarks of AD pathology in the brainstem of the APPswe/PS1dE9 mouse model of familial AD., Methods: Fresh-frozen sections from female, 12 month old, transgenic and control B6C3 mice (n=6/genotype) were examined for amyloid burden and neurofibrillary alterations, by using 6E10 immunohistochemistry and the Gallyas silver stain, respectively. Serotonin transporter (SERT) densities in the dorsal and the median raphe were quantified by [3H]DASB autoradiography. SERT mRNA expression was measured by RT-PCR and visualized by in situ hybridization. Neuroinflammation was evaluated by immunohistochemical staining for microglia and astrocytes, and by measuring mRNA levels of the proinflammatory cytokines TNF-α, IL-1β and IL-6., Results: No amyloid- and tau-associated lesions were observed in the midbrain raphe of 12 month old APPswe/PS1dE9 mice. SERT binding levels were reduced in transgenic animals compared to age-matched controls, and SERT mRNA levels were decreased by at least 50% from control values. Intense microglial, but not astrocytic immunoreactivity was observed in APPswe/PS1dE9 vs. wild-type mice. Levels of TNF-α mRNA were two-fold higher than control and correlated positively with SERT mRNA expression levels in transgenic animals., Conclusions: There was no amyloid accumulation and tau-associated pathology in the midbrain raphe of 12 month old APPswe/PS1dE9 mice. However, there was a local neuroinflammatory response with loss of serotonergic markers, which may partially account for some of the behavioral symptoms of AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Beta-amyloid (Aβ) plaques and chronic neuroinflammation are significant neuropathological features of Alzheimer's disease. Microglial cells in aged brains have potential to produce cytokines such as TNF and IL-1 family members (IL-1α, IL-1β, and IL-1Ra) and to phagocytose Aβ in Alzheimer's disease, however the inter-relationship between these processes is poorly understood. Here we show that % Aβ plaque load followed a sigmoidal trajectory with age in the neocortex of APPswe/PS1ΔE9 Tg mice, and correlated positively with soluble Aβ40 and Aβ42. Aβ measures were moderately correlated with mRNA levels of CD11b, TNF, and IL-1Ra. Cytokine production and Aβ load were assessed in neocortical CD11b(+)(CD45(+)) microglia by flow cytometry. Whereas most microglia in aged mice produced IL-1Ra, relatively low proportions of microglia produced TNF, IL-1α, and IL-1β. However, microglial production of these latter cytokines was generally increased in APP/PS1 Tg mice. Microglia that phagocytosed endogenously-produced Aβ were only observed in APP/PS1 Tg mice. Differences in phagocytic index and total Aβ load were observed in microglia with specific cytokine profiles. Both phagocytic index and total Aβ load were higher in IL-1α(+) and IL-1Ra(+) microglia, than microglia that did not produce these cytokines. In contrast, total Aβ load was lower in IL-1β(+) and TNF(+) microglia, compared to IL-1β(-) and TNF(-) microglia, and TNF(+) microglia also had a lower phagocytic index. Using GFP bone marrow chimeric mice, we confirmed that the majority of neocortical CD11b(+)(CD45(+)) microglia were resident cells (GFP(-)) in APP/PS1 Tg mice, even after selectively analysing CD11b(+)CD45(high) cells, which are typically considered to be infiltrating cells. Together, our data demonstrate that cytokine expression is selectively correlated with age and Aβ pathology, and is associated with an altered Aβ load in phagocytic microglia from APP/PS1 Tg mice. These findings have implications for understanding the regulation of microglial cytokine production and phagocytosis of Aβ in Alzheimer's disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Survival after pulseless electrical activity cardiac arrest is poor. In this case report we describe a patient who had acute massive pulmonary embolism and was treated with thrombolysis and an automatic mechanical chest compression device, Lund University Cardiac Arrest System (LUCAS 2). Chest compressions were effectively provided for two hours during a prolonged resuscitation and transferral for pulmonary embolectomy. The patient was extubated one day after the operation and discharged with normal cerebral function nine days after the cardiac arrest.

Introduction: The St Jude standard aortic bi-leaflet disc valve is still the most widespread. With almost 20 years of follow-up, the present material may describe the quality profile of the valve and the relevant risk factors throughout the remainder of most patients' lives., Material and Methods: A 100% complete follow-up was conducted of 694 adult patients who had an aortic valve replacement with the St Jude valve during 1980-1993. The Cox regression analysis was used to identify independent risk factors., Results: Survival was 79%, 58%, 39%, and 37% at 5, 10, 15, and 18 years, respectively. Only 12% of the deaths (0.60%/patient-year) were valve-related with a 15-year freedom of 91%. Embolism (1.18%/patient-year) and anticoagulant-related bleeding (2.24%/patient-year) were the dominant complications with 15-year freedoms of 80% and 72%. Valve thrombosis was noted in two patients (0.04%/patient-year) who were off anticoagulation. Mechanical failure was not observed. Endocarditis (0.42%/patient-year) had a 15-year freedom of 92% compared with 72% and 54%, respectively, for major valve (2.33%/patient-year) and all valve-related complications together (4.33%/patient-year) and 96% for aortic valve reoperation (0.36%/patient-year). Age of the patient and heart-related variables were identified as independent risk factors for mortality and valve-related complications., Conclusion: With a follow-up of almost two decades showing a low incidence of valve-related deaths, acceptable thrombogenicity, and absence of mechanical failure, the St Jude bi-leaflet aortic disc valve sets the standard for contemporary mechanical valves.

Cardiac rupture following blunt trauma is usually fatal. Patients arriving alive at the hospital may be saved with prompt diagnosis and treatment. We report a case where a haemopericardium was diagnosed by ultrasonography in a 28-year-old man involved in a motor vehicle accident. A tear in the right atrial appendage was successfully repaired in the operating room at the Emergency Department without the use of a cardiopulmonary bypass.

Coronary complications caused by percutaneous transluminal coronary angioplasty (PTCA) may necessitate emergency coronary artery bypass grafting (CABG). In 1994-1998, 132 patients (1.5% of the patients registered in the Danish PTCA registry) underwent CABG within 24 h because of angioplasty complications. We reviewed the files of 86 patients who had emergency operations within 6 h and found that 35% suffered from 1-vessel disease. Fifty-eight percent were taken directly to the operating room from the cardiovascular laboratory, and 13% were given preoperative cardiovascular resuscitation. The vessels most frequently injured were the right coronary artery and the left anterior descending branch (LAD). The patients received a mean of 2.4 coronary bypasses each. Forty-three percent of the patients with lesions of the left main coronary artery and/or the LAD received a vein graft to the LAD. A perioperative Q-wave myocardial infarction developed in 51% of the patients. The in-hospital mortality rate was 12%. These results are inferior to those obtained after elective surgery. Local cardiothoracic backup is vital when PTCA is performed in an unselected patient group.

Background: The standard St. Jude disc valve has been in use for 20 years and remains the dominant mechanical valve of today. With nearly 19 years of follow-up, the present large series could indicate the performance profile and its determinants in the very long term., Methods: A detailed follow-up was performed to a maximum of 18.6 years in 694 patients aged 15 to 83 years who undervent aortic valve replacement (AVR) with the standard St. Jude valve during 1980 to 1993. The Cox regression analysis was used to identify independent determinants of outcome in the aortic stenosis (n = 490) and regurgitation (n = 204) groups., Results: Overall survival was 58%, 39%, and 37% at 10, 15, and 18 years, respectively. Only 12% of deaths (0.60%/ patient-year) were related to the valve with a 15-year freedom of 91%. Embolism (1.18%/patient-year) and anticoagulant-related bleeding (2.24%/patient-year) were the dominant complications with 10-year/15-year freedoms of 90%/80% and 85%/72%, respectively. Only 24% of bleeding events were classified as major. Valve thrombosis occurred in 2 patients (0.04%/patient-year): 1 did not receive vitamin K antagonist treatment and International Normalized Ratio was below target level in the other. There were no mechanical failures. Endocarditis (0.42%/patient-year) and paravalvular leak (0.42%/ patient-year) occurred with 15-year freedoms of 92% and 96%, respectively, with a relation between the latter (but not the former) and preoperative endocarditis in the regurgitation group. Freedom from serious complications (2.33%/patient-year) and all complications joined (4.33%/ patient-year) were 72% and 54%, respectively, at 15 years with a 96% freedom from redo AVR (0.36%/patient-year). Age- and heart-related variables were independent risk factors for mortality, thromboembolism, bleeding, serious complications, and all complications joined. Small valve (19 and 21 mm) adversely affected serious and all complications in the regurgitation group., Conclusions: With a follow-up approaching 2 decades and exhibiting a low rate of valve-related deaths, acceptable low thrombogenicity, and absence of mechanical failure, the standard aortic St. Jude disc valve sets the standard for contemporary mechanical valves.

Background: The purpose of the present study was to describe infarct size and platelet accumulation when reperfusion injury was combined with a thrombogenic lesion in the coronary artery. The left anterior descending artery was damaged in 11 pigs and subsequently occluded proximal to the lesion for 50 min, followed by 4 h of reperfusion., Results: The infarct size/area at risk was 40 (35 63)%. Infarct size correlated with troponin-T-3 h (p=0.85, p<0.002), but not with creatine kinase-3 h. Platelet aggregation decreased by 34% (p<0.01) at 15 min of reperfusion, but returned to baseline. Platelet accumulation in the left ventricle was significantly higher in the area at risk (194 (157-206)%) compared to the right ventricle (137 (120-142)%); p<0.05)., Conclusion: A decreased platelet reactivity and increased accumulation of platelets in the area at risk indicates that activated platelets become entrapped in the myocardium. Troponin-T was a better marker of myocardial damage than creatine kinase in this in vivo model with pigs.

Experimental studies have demonstrated that intravenous magnesium (Mg) can protect the ischemic myocardium and has an antithrombotic effect. In patients with myocardial infarction, the reperfusion injury is complicated by the presence of a thrombogenic area in the affected coronary artery that may cause repetitive thrombus formation and embolization. We investigated the effect of Mg on infarct size in a randomized study in pigs. Myocardial infarction was induced by a 50-minute mechanical occlusion of the left anterior descending artery combined with an arterial injury, which stimulated a dynamic thrombus formation with emboli shedding on reperfusion. Magnesium sulfate (6 mmol/20 min plus 3 mmol/h) or saline was started at 30 minutes after coronary occlusion. Real-time ventricular pressure-volume loops were generated from the left ventricle by using a microtip pressure manometer and a conductance catheter. Platelet accumulation in the myocardium was evaluated by using 111In-labeled platelets. After 4 hours of reperfusion, the infarct size/area at risk ratio in the placebo group was 46+/-0.06% (n=8) compared with 22+/-0.07% (n=6) in the Mg-treated animals (P=0. 03). Ejection fraction decreased significantly in the control group but not in the Mg-treated animals (P=0.03). Platelet accumulation in the myocardium did not change significantly between the Mg- and placebo-treated animals (placebo group, 191+/-19%; Mg group, 177+/-29%; NS). The present study demonstrates that intravenous Mg infusion is able to reduce infarct size by >50% and preserve the ejection fraction in this model where ischemia/reperfusion injury was evaluated in the presence of a thrombogenic area in the nutrient artery.

Two-hundred-and-twenty-nine men aged between 80 and 97 years (mean 83 years) underwent transurethral prostatectomy (TUR-P) for lower urinary tract symptoms (LUTS). All case records were reviewed. The follow-up period was 6-16 years. One-hundred-and-seven patients underwent operation because of acute urinary retention, and 122 because of chronic retention. The mean weight of tissue removed was 20 g (1-200 g). The perioperative mortality (< 1 month) was 2% (5 patients). Postoperative complications occurred in 21% (49 patients). Reoperation was performed in 11% (26 cases). The result was considered satisfactory in 196 patients (86%). The present data demonstrate that transurethral resection of the prostate in men over 80 years has a good outcome with an acceptable urological complication rate and mortality, and we therefore advocate surgery instead of watchful waiting in the fit patient.

An oesophageal perforation is a serious condition with high morbidity and mortality. During the latest decades an increased number of traumatic perforations as well as wide use of endoscopic procedures have increased the incidence of oesophageal perforation. An early diagnosis and treatment is important for the prognosis. Cervical and selected thoracic perforations can be treated conservatively although the majority should be operated. Primary closure can be performed if done before 24 hours have elapsed, while later treatment is controversial. Drainage of the mediastinum and pleural space, as well as diversion of saliva and gastric content is important. The literature is reviewed in relation to etiology, diagnosis, treatment and prognosis.

Between January 1, 1980 and December 31, 1994, 37 patients with benign oesophageal perforation underwent different kinds of treatment. The overall mortality was 30%. When diagnosed less than 12 hours after the perforation the mortality was 21%, between 12 and 24 hours. Reinforced primary repair gave the best results without any deaths in seven cases where it was performed. Oesophageal perforation is a serious condition, and it is important to know the symptoms. If there is any suspicion of the condition, an oesophageal X-ray with watersoluble contrast medium should be performed on liberal indication. When diagnosed the patient should be transferred to a Department of Thoracic Surgery immediately. Only few patients can be treated conservatively and most should be operated with reinforced primary suture and drainage.

A 72-year-old man developed a total atelectasis of the right lung six weeks after a blunt trauma in a motor vehicle accident. Bronchoscopy demonstrated a total fibrotic occlusion of the right main bronchus. By re-examination of earlier case sheets and chest x-rays it was suspected that the patient had suffered a partiel bronchial rupture from the accident. One and a half centimetres of the bronchus were resected with a good result. Findings and treatment of this rare complication are discussed.

The case of a 52-year-old woman with an oesophagobronchial fistula is presented. The diagnosis was not made preoperatively. The patient was operated twice, with resection of a diverticulum of the oesophagus at the last operation. The congenital or acquired origin of the fistula is discussed.