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.     

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.     

Segmental colonic transit studies: comparison of a radiological and a scintigraphic method

OBJECTIVE: Colonic transit studies are used to diagnose slow transit constipation (STC) and to evaluate segmental colonic transit before segmental or subtotal colectomy. The aim of the study was to compare a single X-ray radio-opaque marker method with a scintigraphic technique to assess total and segmental colonic transit in patients with STC. METHOD: Thirty-one female patients (median age 46 years) with severe constipation and a prolonged or borderline prolonged colonic transit time on radio-opaque marker study were included in the study. They were subsequently investigated with (111)Indium-DTPA colonic transit scintigraphy, with a median time between the investigations of 4(range 1-27) months. Normal values of healthy female controls were used for comparison. RESULTS: There was no difference between the two methods in terms of prolonged or normal total colonic transit time. Twenty-nine of 31 female patients had a prolonged transit time only in one or two segments on the marker study. On scintigraphy, the transit time was prolonged for patients in the left (P < 0.05 to P < 0.001), but not in the right colon. With respect to prolonged or normal segmental transit time, there was a significant difference between the two methods only in the descending colon (P = 0.02). However, the results varied considerably for individual patients. CONCLUSION: Segmental colonic delay was a common finding. The two methods gave similar results for groups of patients, except in the descending colon. The variation of the results for individuals suggests that a repeated transit test may improve the assessment of total and segmental transit.     

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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Effects of diltiazem in acute and long-term administration

In 16 patients with unstable angina pectoris haemodynamic and clinical effects of diltiazem were investigated. In a second group patients (n = 11) with unstable or therapy-refractory course the long-term effect was tested. The acute intervention with injected and infused diltiazem via an improved oxygen balance due to decreased minute work and reduced product of cardiac frequency and pressure stabilized the clinical picture from the haemodynamic aspect. The decreases of the ST segment were significantly lower. In the long-term use a significant influence on the frequency of angina pectoris with increase of the range of efficacy by one NYHA-state was the result. Diltiazem can be regarded as alternative medicament in unstable phases and in therapy-refractory courses of the chronic coronary heart disease.     

Peptide inhibitors of ADP-ribosylation by pertussis toxin are substrates with affinities comparable to those of the trimeric GTP-binding proteins.

Pertussis toxin (PTX) ADP-ribosylates alpha subunits of GTP-binding proteins (G proteins) when they are in association with beta gamma dimers, and free alpha subunits are thought not to be substrates under standard assay conditions. We now report the rather unexpected discovery that synthetic peptides encompassing the last 10-20 amino acids of alpha subunits of PTX-sensitive G proteins are substrates for PTX by themselves and in the absence of beta gamma dimers. As determined for G13, the Km of PTX for the 20-amino acid carboxyl-terminal peptide is 10-fold higher than that for the trimeric G protein. Interestingly, PTX ADP-ribosylates the free full length alpha 13 subunit with a Km not different from that of the trimer but with a Vmax that is only 1% of that with which it ADP-ribosylates the trimer. It follows that the primary role of beta gamma dimers in ADP-ribosylation of G proteins is one of increasing the Vmax of the reaction without affecting the Km of the substrate for the toxin. Mutant peptides lacking the ADP-ribose acceptor site act as competitive inhibitors.