Rescue of the Cold Preserved Rat Liver by Hypothermic Oxygenated Machine Perfusion

The aim of the study was to investigate whether hypothermic oxygenated liver perfusion after cold liver preservation resuscitated metabolic parameters and whether this treatment had a benefit for liver viability upon reperfusion.
We preserved rat livers either by cold storage (UW) for 10 h, or by perfusion for 3 h (oxygenated modified UW) after 10 h cold storage. We assessed viability of livers after preservation and after ischemic rewarming + normothermic reperfusion ex vivo . Ten hour cold storage reduced mitochondrial cytochrome oxidase and metabolically depleted the livers. Oxygenated perfusion after cold storage resulted in uploaded cellular energy charge and oxidized mitochondrial cytochrome oxidase. Reperfusion after 10 h cold storage increased formation of superoxid anions, release of cytosolic LDH, lipid peroxidation, caspase activities and led to disruption of sinusoidal endothelial cells. In contrast, reperfusion after 10 h cold storage + 3 h hypothermic oxygenated perfusion resulted in no changes of lipid peroxidation, bile flow, energy charge, total glutathione, LDH release and of caspase activation, as compared to fresh resected livers.
This study demonstrates, that a metabolically depleted liver due to cold storage can be energy recharged by short-termed cold machine perfusion. The machine perfused graft exhibited improved viability and functional integrity.     

Does prophylactic sotalol and magnesium decrease the incidence of atrial fibrillation following coronary artery bypass surgery: a propensity-matched analysis

Background  

Atrial fibrillation can occur in up to 40% of patients undergoing coronary surgery.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.     

Ischemia independent lesion evolution during focal stroke in rats

Lesion evolution during focal cerebral ischemia may depend on flow restrictions or on accumulation of toxic mediators within the infarct and expansion of these factors to the periinfarct region. So far, the precise contribution of flow dependent versus spreading-mediated impairment of viable periinfarct tissue has not been determined. Therefore, we measured lesion expansion, flow restrictions and glutamate distribution on serial brain sections at different time points after experimental focal ischemia.Permanent focal ischemia was induced by occlusion of the right middle cerebral artery in male rats and the flow reduction was subsequently measured at 1, 12 and 24 h using iodo[¹⁴C]antipyrine autoradiography. Additionally, the necrotic volume was determined on serial brain sections and the glutamate content was measured in tissue samples from adjacent microdissections.Twelve hours after focal ischemia no noteworthy viable areas with blood flow restrictions of 20-40 ml 100 g^− 1 min^− 1 existed but at 24 h the necrotic tissue exceeded the hemodynamically compromised region by 40 ± 21 mm³ (24%). Furthermore, at 12 and 24 h the glutamate content was elevated in areas surrounding the infarct.Relevant flow restrictions are detectable only during early stages of infarct maturation, whereas the propagation of secondary factors may be the predominant mechanism for delayed infarct evolution.     

The First‐Episode Psychosis Outcome Study: premorbid and baseline characteristics of an epidemiological cohort of 661 first‐episode psychosis patients

Aims: Studies conducted in first‐episode psychosis (FEP) samples avoid many biases. However, very few studies are based on epidemiological cohorts treated in specialized FEP services. The aim of this file audit study was to examine premorbid and baseline characteristics of a large epidemiological sample of FEP. Methods: File audit study of all patients admitted to the Early Psychosis Prevention and Intervention Centre between 1998 and 2000 using a specialized questionnaire. Results: There were 661 patient files included in the study. Premorbid evaluation revealed high rates of substance use disorder (74.1%), history of psychiatric disorder (47.5%), past traumatic events (82.7%) suicide attempts (14.3%) and family history of psychiatric illness (55.6%). Baseline characteristics revealed high intensity of illness (mean CGI 5.5), high prevalence of lack of insight (62%) and high rate of comorbidity (70%). Conclusion: High rates of traumatic events or episodes of mental illness before treatment for FEP must be considered when designing treatment approaches because a too narrow focus on positive psychotic symptoms will inevitably lead to incomplete treatment. Additionally, early intervention programmes need sufficient range of resources to address the multiple challenges presented by FEP patients such as high severity of illness, comorbidities and functional impairment. Finally, observation of an important degree of functional impairment despite short duration of untreated psychosis suggests that while early detection of FEP is a necessary step in early intervention, it may not be sufficient to improve functional recovery in psychosis and that efforts aimed at identifying people during the prodromal phase of psychotic disorders should be pursued.     

Self-expanding nitinol stents in canine vertebral arteries: hemodynamics and tissue response.

PURPOSETo evaluate the hemodynamics and tissue response associated with stent placement in low-flow-velocity arteries.METHODSSix self-expanding nitinol stents (5.5 mm caliber) were implanted transfemorally within the proximal segments of vertebral arteries (2.5 mm diameter) in six adult dogs during anticoagulative protection.RESULTSControl angiograms demonstrated patency and 20% dilatation of all stented arteries. One artery was partially thrombosed 1 week later and subsequently showed a 50% stenosis. Throughout the observation period (4 to 9 months after stenting), the other five arteries remained patent without significant narrowing (< or = 15%). Small cervical muscle branches originating from the vertebral arteries within the stented segments remained patent. No major branch occlusions of the vertebrobasilar system were detected. Stent migration or kinking did not occur. MR studies of the brain 4 months after implantation revealed no infarcted areas. These findings were confirmed with brain sections. Stented artery specimens showed delayed stent dilatation. A comparison of the total mean thickness of intima covering the five 30- to 40-mm stents removed at 4, 6, and 9 months showed no significant difference (338, 332, and 389 microns, respectively). Histologic findings verified the macroscopic impression of a thicker intima at the inner curve of the stented artery segments and at the junctions of the stent filaments. The shortest (10 mm) stent had the thinnest neointimal growth (155 microns). Stented vessels showed compression of the media with atrophy, but without necrosis or perforation. Scanning electron photomicrographs revealed intact endothelial cell linings with typical elongated cells.CONCLUSIONSNo significant risk of thromboembolic events exists after implanting these nitinol stents in nonatherosclerotic vertebral arteries in dogs. Thicker neointimal growth after stenting may result from either low wall shear stress with possible flow separation or from changes in the shape and size of the stent, or both.     

Pulmonary artery balloon counterpulsation for right ventricular failure after right ventriculotomy in the swine

To assess the efficacy of intrapulmonary balloon counterpulsation in the management of right ventricular failure after right ventriculotomy, we undertook an experimental study in a swine model. To mimic the clinical settings more closely, (1) we left the automatic control of the heart intact (2) did not use cardiopulmonary bypass to support the left side of the heart, and (3) induced right ventricular failure by means of a generous surgical incision (50% to 70% of the anterior wall) of the right ventricle. The criteria set for right ventricular failure were (1) 50% increase in right ventricular end-diastolic pressure, (2) 30% decrease in mean arterial pressure, and (3) 30% decrease in cardiac output. Right ventricular failure was attained in all animals studied: A 230% increase in right ventricular end-diastolic pressure, a 43% decrease in cardiac output, and a 34% decrease in mean arterial pressure were evident after the right ventriculotomy. A specially designed intrapulmonary balloon catheter (Datascope Corp., Oakland, N.J.) was placed into the left pulmonary artery through the right ventricular outflow tract. A Datascope console was used for counterpulsation. Effects of counterpulsation for 40 minutes in a 1:1 mode were assessed after surgical induction of right ventricular failure in 14 swine. Each animal served as its own control. The mean hemodynamic changes are outlined: Right ventricular end-diastolic pressure decreased by 48.9% (p = 0.01). Mean arterial pressure increased by 68.8% (p = 0.01) and cardiac output by 44.2% (p = 0.01). Histologic studies disclosed no morphologic damage to the pulmonary artery or valve in the specimens analyzed. In addition, these results were compared with those in a second group of seven swine in which right ventricular failure was induced by right ventriculotomy and a balloon was placed into the left pulmonary artery but not activated. These results of short-term counterpulsation should be evaluated in a longer term model so as to mimic more closely the clinical setting. If the hemodynamic benefits are duplicated, intrapulmonary balloon counterpulsation should be considered as a simple, effective device when right ventricular failure develops after right ventriculotomy. It effectively improves right ventricular function without damaging the pulmonary artery or valve.     

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