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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 68 (1990), S. 223-236 
    ISSN: 1432-1440
    Keywords: Diagnosis ; HTK solution ; Heterogeneity ; Ischemia ; Kidney ; Lithium ; Magnesium ; Potassium ; Proximal tubule ; Organ protection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Several functional parameters were applied in an experimental model of ischemia to test the ability to localize the distribution of tubular lesions. Canine kidneys were perfused with protective solutions and rendered ischemic for definite periods. Renal function was determined during a subsequent 3-h reperfusion. The pattern and the extent of renal injury were influenced by varying the duration of ischemia and by modifying the protective solution used. The results suggest that by employing an appropriate selection of parameters it is possible to allocate renal injury to definite sections of the tubules. According to such an evaluation, under protection with HTK-solution, the proximal tubule limits the tolerance of renal ischemia. The thick ascending limb shows some vulnerability that is aggravated by disadvantageous modifications of the protective solution and that may become more pronounced in the course of reperfusion. In contrast, more distal parts of the nephron retain a remarkable reserve transport capacity after a tolerable level of ischemia.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2307
    Keywords: AV nodal cells ; Working myocardium ; Cardiac arrest and global ischaemia ; HTK cardioplegia ; Qualitative and quantitative ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The cardiac conduction system is considered to be particularly resistant to ischaemia. Nevertheless, following open heart surgery with short periods of ischaemia disturbances in AV conduction or ventricular arrhythmia have been reported. We compared the ultrastructure of AV node and working myocardium following 30 min global ischaemia at 25° C, during pure ischaemia and with HTK cardioplegia qualitatively and morphometrically. After 30 min of pure ischaemia, interstitial and intracellular oedema together with considerable changes in organelles in AV nodes predominate over mainly cellular oedema in working myocardium. Sometimes irregular overcontractions of sarcomeres occur in the AV node, though very seldom in working myocardium. In pure ischaemia, mitochondrial swelling is comparable in both types of tissue. Following HTK cardioplegia and 30 min ischaemia, cellular oedema and mitochondrial swelling are significantly reduced in AV nodal cells and working myocardium, but remain more extensive in the AV nodes. Irregularities in the contractile state of sarcomeres are not observed. The extent of the ultrastructural alterations corresponds to the degree of metabolic change in the working myocardium. Thus, despite considerable differences during pure ischaemia and HTK cardioplegia, ultrastructurally the AV nodal cells do not display a greater resistance to ischaemia than working myocardium.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2307
    Keywords: Purkinje fibres ; Ischaemia tolerance ; Qualitative and quantitative ultrastructure ; Cardioplegia ; Arrhythmias
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary During open heart surgery, reperfusion-induced arrhythmias arising after short periods of ischaemia may originate from subendocardial Purkinje fibres. We investigated the ultrastructure of these fibres during 30 min of global ischaemia at 25° C. The effects both with myocardial protection (HTK cardioplegia) and without it (pure ischaemia) were compared qualitatively and morphometrically. After 30 min pure ischaemia overcontraction of sarcomeres, hypercontraction and contraction bands, together with considerable changes in organelles, predominate over cellular oedema. In Purkinje fibres, both cellular and mitochondrial swelling were significantly increased within this 30-min time period from the onset of pure ischaemia. In contrast, following HTK cardioplegia and 30 min ischaemia, cellular and mitochondrial swelling remain moderate and over-contractions are almost entirely lacking. This means that despite remarkable differences between pure ischaemia and HTK cardioplegia in the degree of protection attained it is clear that, compared with the working myocardium, subendocardial Purkinje fibres do not display a higher resistance to early global ischaemia. Further investigations of this sensitivity of Purkinje fibres to global ischaemia and certain drugs may bring about new insights into myocardial protection and pharmacotherapy of arrhythmias.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2307
    Keywords: Purkinje fibres ; Transitional cells ; Working myocardium ; Global ischaemia ; Ultrastructure ; Contraction state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Contraction bands usually occur in the intramural working myocardium following post-ischaemic reperfusion. In the subendocardium, however, they are found during ischaemia. Thus, we ascertained the contraction states of Purkinje fibres, transitional cells, subendocardial and intramural parts of the working myocardium during 30 min global ischaemia at 25° C. The effects with and without myocardial protection were compared. At the onset of pure ischaemia contraction bands are completely lacking in all cell types. During pure ischaemia contraction bands are found in all subendocardial cell types but not in the intramural working myocardium. A peak of pathological contraction states is found in the intramural working myocardium at the onset (0 min), in the subendocardial working myocardium at 10 min, in the transitional cells and Purkinje fibres at 30 min of pure ischaemia. Histidine-, tryptophan-, ketoglutarate-enriched (HTK) cardioplegia prevents contraction bands completely at the onset of ischaemia and prevents both contraction bands and pathological contraction states during ischaemia almost completely. Striking differences in the physiological contraction states are seen only in the working myocardium: HTK cardioplegia brings about dominance of relaxation during ischaemia. These findings may be due mainly to the effects of global ischaemia on the one hand and to catecholamines, calcium and oxygen on the other.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2307
    Keywords: Myocardial ultrastructure ; Mitochondrial swelling ; Stereology ; Correlations of structural parameters ; Cardiac arrest and global ischaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cellular changes occuring in the left ventricular myocardium during ischaemia after different methods of cardiac arrest have been evaluated by morphological and morphometric parameters: volume densities of mitochondria (VVMi), sarcoplasm (VVSp), myofibrils (VVMf), surface densities of mitochondria (SVMi). The surface to volume ratio of mitochondria (SVratioMi) has been used as an independent parameter of mitochondrial swelling. Since ischaemic swelling of myocardial cells increases the volume of the reference space and ischaemic swelling of mitochondria decreases the free sarcoplasm, VVMi and VVSp cannot be considered as reliable indicators of the degree of oedema. SVMi/VVMf remains nearly constant after different forms of cardiac arrest, demonstrating the integrity of mitochondrial outer membranes. The inverse linear ratio between SVratioMi and the mean mitochondrial volume indicates that the increase in mitochondrial volume is achieved by surface smoothing. Loss of matrix structure and fragmentation of cristae occur at an SVratioMi of about 5.8, cristolysis at 5.5 to 5.6 and amorphous matrix densities at an SVratioMi of less than 5.5 μm2/μm3. The SVratioMi is a suitable parameter for evaluating mitochondrial swelling both at the onset and during global myocardial ischaemia, independent of the method of cardiac arrest used. It serves as an indicator of the state of structural preservation of mitochondria during ischaemia.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2277
    Keywords: HTK solution ; UW solution, liver preservation ; Liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Over a 30-month period, 60 patients (30 in each group) suffering from end-stage liver disease or primary hepatic malignancy and scheduled for liver transplantation were enrolled in a prospective, randomized study to compare two methods of liver preservation: histidinetryptophan-ketoglutarate (HTK) solution versus University of Wisconsin (UW) solution. Entry criteria for both groups were: age (18–65 years), elective surgery (transplantable or urgent category of the recipients), first transplantations and harvesting procedure performed by the same team. The parameters under investigation were the clinical and laboratory data preand post-transplantation, as well as follow-up data such as complications and survival. There were no significant differences in the two groups as far as the evaluation criteria were concerned, even when cold ischemia time was more than 15h (n=7). A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group. Hepatocellular injury (SGOT, SGPT, GLDH, lactate) appeared to be more marked in the HTK group. These results suggest that both HTK and UW solutions are appropriate for clinical use in liver transplantation, even if cold ischemia time is more than 15h.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-2451
    Keywords: Lebertransplantation ; Ischämiezeit ; Perfusionslösung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The cardioplegic HTK-solution (Bretschneider) has not been used in human liver transplantation as yet. Herein the first results obtained from 14 patients with HTK-preserved liver grafts are presented. The suitability of HTK-solution could be shown. All grafts functioned primarily except one, where initial non-function was obviously due to donor reasons. The early postoperative peak values of transaminases as a sign of ischemic damage were average and similar to the values of other flushout solutions. Using HTK primary function could be achieved even in livers prospectively assessed as only of fair quality, and livers with poor donor function tests (MegX) functioned from the beginning. HTK-solution therefore seems to allow widening of the acceptance criteria for donor livers. It was not the aim of this trial to extend cold ischemic time, but 3 livers with 11 h and 12 h 25 showed immediate function. How far cold ischemic time can be extended is a still open question. All livers were rapidly cooled and homogeneously flushed out due to the low viscosity of HTK-solution. All livers had a soft consistency after perfusion indicating a low degree of cell edema. HTK therefore is an effective solution for liver preservation.
    Notes: Zusammenfassung Die kardioplegische Lösung HTK nach Bretschneider ist bisher noch nicht im Bereich der klinischen Lebertransplantation verwendet worden. Hier werden die ersten Ergebnisse von 14 Patienten vorgestellt, denen eine mit HTK-Lösung protektionierte Leber transplantiert wurde. Die Eignung der HTK-Lösung konnte gezeigt werden. Alle Transplantate zeigten eine Primärfunktion mit Ausnahme eines Transplantates, bei dem die initiale Nichtfunktion zweifelsfrei spenderbedingt war. Die höchsten friihpostoperativen Werte der Transaminasen, die als Zeichen des Ischämieschadens herangezogen wurden, waren durchschnittlich und vergleichbar mit den Transaminasenausschüttungen nach anderen Lösungen. Unter Verwendung der HTK-Lösung konnte eine Primarfunktion selbst bei solchen Transplantaten erzielt werden, die prospektiv als solche von problematischer oder geringer Qualität eingeschätzt worden waren, and Lebern mit schlechten Funktionstesten (MegX) funktionierten von Beginn an. Deshalb scheint die HTK-L6sung die Ausweitung der Akzeptanzkriterien für Spenderlebern zu ermöglichen. Es war nicht das Ziel dieser Studie, die kalte Ischämiezeit zu verlängern, aber drei Transplantate mit 11 h and 12 h 25 min nahmen unmittelbar nach Reperfusion ihre Funktion auf. Wie weft die kalte Ischämiezeit ausgedehnt werden kann, ist noch eine offene Frage. Alle Spenderlebern wurden aufgrund der geringen Viskosität der HTK-Lösung schlagartig gekühlt und homogen perfundiert. Alle Lebern hatten eine weiche Konsistenz nach der Perfusion, was kein oder nur ein geringes Zellödem bedeutet. Aus diesen Gründen ist HTK eine effektive Lösung für die Leberkonservierung.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1435-2451
    Keywords: Nierenperfusion ; Renale Ischämie ; HTK-Protektion ; Tumorexzision ; Nierenfunktion ; Intrarenaler pH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary So far two methods for prolonging the tolerance of renal ischemia are available: 1) surface cooling with crushed ice and 2) perfusion cooling with an extracellular-like solution. Both methods use only the principle of reducing metabolism through cooling. While rewarming during surgery the ischemic protection is lost, or the kidney must be cooled once again. Therefore, a new preservation solution should reduce energy consumption due to its composition in addition to cooling. For open heart surgery, the HTK solution by Bretschneider is already used clinically. In 71 dog kidney experiments, the ischemic time kidneys could tolerate was prolonged by this solution from 15 to 120 min at 35°C and from 45 to 360 min at 25°C. After 2h of ischemia at 30°C glomerular filtration rate was about 20 ml/min · 100 gww within 3 h of reperfusion. After six postoperative days the filtration rate was 40 ml/min · 100 gww. No ischemic damage could be recognized by histological investigations. The clinical effectiveness of this method was shown in 7 clinical applications. Ischemic duration lasted up to 113 min, and blood creatinine was between 0.8 and 2.4 mg% at the 6th postoperative day. Use of this preservation technique thus leads to improved kidney function immediately following operation. Longer ischemia can be tolerated by a kidney thus protected, and using this technique excellent visibility can be achieved during intrarenal surgery, simplifying, for example, tumor extirpation.
    Notes: Zusammenfassung Zur Verlängerung der renalen Ischämie stehen bisher zwei Verfahren zur Verfügung: 1) eine Oberflächenkilhlüng mit Eis and 2) eine Perfusionskühlung mit einer extrazellulären Losung. Beide Methoden nutzen nur das Prinzip der Stoffwechselsenkung durch Kühlung. Während der Wiedererwärmung bei der Operation geht der Ischämieschutz verloren oder die Niere muß erneut gekiihlt werden. Deshalb sollte eine neue Protektionslösung den Energieverbrauch zusätzlich zur Kühlung auch durch ihre Zusammensetzung senken. Bei offenen Herzoperationen wird die HTK-Lösung nach Bretschneider bereits klinisch angewendet. In 71 Experimenten an Hundenieren wurde die Ischämiezeit durch diese Lösung von 15 auf 120 min bei 35°C and von 45 auf 360 min bei 25°C. verlängert. Nach 120 min Ischämie bei 30°C betrug die glomeruläre Filtrationsrate ca. 20 ml/min 100gFG innerhalb von 3 h Reperfusion. Nach 6 Tagen postoperativ war die GFR wieder 40 ml/min 100gFG. Es konnte kein ischämischer Schaden durch histologische Untersuchungen mehr festgestellt werden. Der klinische Nutzen dieser Methode konnte in 7 klinischen Anwendungen gezeigt werden. Die Ischamiezeit betrug bis zu 113 min and das Kreatinin lag zwischen 0,8 and 2,4 mg% am 6. postoperativen Tag. Dieses Protektionsverfahren führt also zu einer verbesserten Nierenfunktion in der postoperativen Phase. Eine längere Ischämiezeit wird von der Niere vertragen, and unter Anwendung dieser Technik wird eine ausgezeichnete Übersichtlichkeit während der Nierenoperation erreicht, was eine radikale Tumorexzision erleichtert.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-2451
    Keywords: Electrical impedance ; Liver ischemia ; Liver transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 22 Lebern, die zur Transplantation beim Menschen perfundiert und entnommen wurden, wurde das Verfahren der nichtinvasiven Messung der bioelektrischen Impedanz prospektiv angewendet. Im Verlauf der Messung sollten Rückschlüsse auf einen möglichen Ischamieschaden der Organe gezogen wurden. Die Meßwerte wurden zur Funktion der Lebern, den Ischämiezeiten und den Konservierungsverfahren in Beziehung gesetzt. Für die Impedanz ergaben sich in vivo bei 192 Hz im Mittel 620 Ohm, für den Phasenwinkel bei 5 kHz −7,4°. Diese Werte entsprachen denen eines Kollektivs von 72 lebergesunden Patienten (mittels Multivarianz aus einem untersuchten Kollektiv von 132 Patienten ermittelt), die intraoperativ durchgeführt wurden. Die 22 Transplantatlebern wurden in den Ischämiephasen mit jeweils mindestens 5 Meßpunkten weiterverfolgt. Das Verfahren wurde als geeignet befunden, schwere hepatozelluläre Schäden im Verlauf der Kaltischämie zu erfassen.
    Notes: Abstract In 22 human donor livers the measurement of the non-invasive bioelectrical impedance was performed prospectively to evaluate the degree of tissue damage sustained during cold ischemia. The results of the measurement were correlated with liver function, the method of organ preservation and the period of ischemia. The impedance was measured in vivo as 620 ohm (at 192 Hz), the phase angle as −7.4° (at 5 kHz). The results were compared with the data obtained from 72 patients who underwent elective laparotomies. The 22 donor livers were studied further during ischemia. The method was found to be a reliable way of detecting severe damage to the hepatocytes during the cold ischemia.
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  • 10
    ISSN: 1435-2451
    Keywords: Morphologie ; Ischämie ; Leber ; Organkonservierung ; Transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In order to study perfusion effects of different liver preservation methods on liver structure, porcine livers were perfused with either Bretschneider's HTK (Histidine Tryptophane Ketoglutarat) solution, Euro-Collins (EC) solution or University of Wisconsin solution (UW) according to the respective recommended protocols. Subsequently, together with a group of unprotected livers, all organs were examined by light and electron microscopy including computer assisted morphometry. The width of the space of Disse, the continuity of endothelial cells and the ultrastructure of the hepatocytes were not impaired after cold perfusion with any of the 3 solutions. However, we found considerable differences between the groups with respect to removal of blood cells from liver sinusoids. Livers flushed according to the HTK-protocol had the lowest residual blood cell content followed by the livers of the EC- and the UW-group. Centrilobular regions of the liver lobules were generally better washed free of blood than periportal zones. Computer assisted morphometry did not reveal any significant difference. between the size of hepatocytes of EC-, UW- and HTK livers. Only the hepatocytes of normothermic control livers (biopsy samples) were 10% larger than hepatocytes of cold flushed groups. None of the protective perfusion protocols showed structural signs of perfusion injury.
    Notes: Zusammenfassung Zur Klärung der Frage, ob unter der Anwendung verschiedener Verfahren zur Leberkonservierung strukturell nachweisbare perfusionsbedingte Schäden auftreten können, wurden Lebern von Schweinen mit a) HTK-Lösung nach Bretschneider (Histidin-Tryptophan-Ketoglutarat), b) Euro-Collins-Lösung (EC), c) “University of Wisconsin”-Lösung (UW) entsprechend den Anweisungen des Herstellers perfundiert. Anschließend wurden alle Organe zusammen mit unprotelctionierten Lebern licht- und elektronenmikroskopisch unter Einschluß computergestutzter morphometrischer Analysen untersucht. Die Kontinuität der Sinusendothelzellen, die Weite des Disseschen Raumes sowie die Ultrastruktur der Hepatozyten wurden primär durch keines der protektiven Verfahren beeintrdchtigt. Beträchtliche Unterschiede wurden aber hinsichtlich der Ausspülung des Blutes festgestellt. Die mit der HTK-Lösung perfundierten lebern waren mit Abstand am besten von korpuskulären Blutbestandteilen befreit, gefolgt von EC-und UW-Lebern. Mittels eines computerunterstützten Morphometrieverfahrens konnten keine signifikanten Größenunterschiede zwischen den Hepatozyten der EC-, UW- and HTK-Gruppe festgestellt wurden. Lediglich die Hepatozyten der normothermen Kontrollebern waren um 10% größer als diejenigen in den mit den 3 protektiven Lösungen perfundierten Organen. Es ergaben sich unter keinem der drei Protektionsverfahren strukturelle Anhaltspunkte für einen Perfusionsschaden.
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