Dissertation (MD)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: Acute renal failure still is, with the exception of cardiac deaths, the most important pathological process associated with perioperative mortality in patients operated for abdominal aortic aneurysms. The intraoperative change in renal blood flow (RBF) and glomerular function have been investigated in human and animal models, particularly over the past 15 years. Despite large variation in study populations, measurement techniques and study designs in general, a significant body of evidence has developed which suggests infrarenal aortic clamp-induced renal ischemia to be the cause of postoperative acute renal failure when this complication does occur. It is rather surprizing then that, despite some recent studies which have reported on various pharmacological interventions to prevent intraoperative renal ischemia (with variable success), very little has apparently been done to unravel the pathogenesis and exact pathophysiology of this potentially lethal complication. Although a number of investigators suggest the possibility of hormonal involvement (particularly reninangiotensin, antidiuretic hormone (ADH) and catecholamines) in the process, the exact role of these mediators have not been explored (or reported) in a structured fashion. In an initial human study, renal hemodynamics and function were measured from the preoperative period, during the intraoperative phase and at least until 4 hours after aortic unclamping. To investigate the possibility of a temporal relationship between renal changes and fluctuations in hormonal concentrations, plasma concentrations of relevant hormones were determined at every sampling period where renal parameters were measured. The decrease in RBF and glomerular filtration rate (GFR) which we demonstrated to coincide with infrarenal aortic cross clamping, is consistent with results previously published. We demonstrated persistence of the impairment of these parameters as long as 4 hours into the postoperative phase; which has previously only been reported for the period until immediately after aortic unclamping with the abdomen still open. The persistence of a depressed GFR until the time of discharge of patients is cause for concern, particularly in patients with compromised renal function prior to surgery. Of the measured hormones with a potential influence on RBF and nephron function, renin was the only mediator where changes in plasma concentrations coincided with the depression of RBF and GFR after aortic cross clamping. The design of our study did not allow us to conclude whether the concomitant increase in angiotensin II was primarily responsible for the change in renal hemodynamics, or whether the raised renin (and angiotensin) levels were stimulated by the decrease in RBF induced by another mechanism. In another patient group, we demonstrated that the combination of mannitol and dopamine provided no protection against the deleterious effects of aortic cross clamping. In fact, the high urine volumes produced under the influence of these agents (which did not correlate with RBF at the corresponding periods), is likely to prompt a false sense of security. Given the lack of any objective benefit afforded by these agents, their use in these clinical circumstances should be discouraged. The animal studies were aimed at elucidation of the exact role of angiotensin in the pathogenesis and pathophysiology of the renal changes associated with infrarenal aortic clamping, as well as the interaction of angiotensin with other modulators for which an interactive relationship had been described previously under other experimental and/or clinical circumstances. The first study showed that, although renin (and thus angiotensin) concentrations were high after aortic unclamping, the hormone had no pathogenic or pathophysiological role of significance in the observed renal changes during this period (since blocking angiotensin II activation by the prevention of renin release, or by inhibiting the conversion enzyme, did not prevent a substantial decrease in RBF or GFR during that period). Preventing angiotensin II activation did, however, prevent renal changes during aortic clamping. This beneficial effect did not establish a primary role for angiotensin during that period, since the favourable influence could also (at least partially) be explained by prevention of the permissive influence of angiotensin on other vasoconstrictors and/or other vasodilatory influences of ACE inhibition and [1- blockade which are unrelated to angiotensin. This study did indicate that (at least partially) different mechanisms are responsible for the renal changes seen during aortic clamping, and after aortic unclamping. The second study explored the role of calcium in the renal pathophysiological changes during aortic clamping and after unclamping. The protective influence effected by the administration of a Ca2 + -blocker suggest the dependence of the renal vasoconstrictive and glomerular pathophysiological process( es) on the cellular influx of Ca2 + through voltage-gated channels. It unfortunately provides no definitive insight into the primary instigators of these processes. However, it does offer a clinically useful method of preventing these changes and protecting the kidney against ischemic injury during abdominal aortic surgery. The third component of the animal studies demonstrates the importance of the protective effect of renal prostaglandins during the specific experimental (and probably also the clinical) circumstances. Again, it does not provide definitive information on the mediators responsible for the renal changes, since the deleterious effects of numerous endogenous substances have previously been shown to be counterbalanced by intrarenal synthesis of prostaglandins under various experimental and clinical circumstances. The extent of the pathophysiological and ultrastructural changes which occurred under the influence of a NSAID does, however, suggest that these drugs should not be used under these clinical circumstances. The last component of the study provides evidence that angiotensin only plays a secondary/supplementary role in the renal pathophysiological process even during aortic clamping. This may explain the contradictory evidence regarding the potential beneficial effect of ACE inhibition (on renal hemodynamics and glomerular function) during abdominal aortic surgery (Licker et al. 1996, Colson et al. 1992a). Based on our studies, ACE inhibition can not be supported for this purpose. / AFRIKAANSE OPSOMMING: Akute nierversaking is met die uitsondering van kardiale sterftes, steeds die belangrikste patologiese proses wat geassosieer is met perioperatiewe mortaliteit in pasiënte wat opereer word vir abdominale aorta aneurismes. Die intraoperatiewe veranderinge in renale bloedvloei (NBV) en glomerulêre funksie is die afgelope 15 jaar ondersoek en gerapporteer in pasiënte- sowel as diere-modelle. Ten spyte van groot variasies in studie-populasies, meettegnieke en ontwerp van studies in die algemeen, dui 'n wesenlike hoeveelheid getuienis daarop dat infrarenale klemming van die aorta renale isgemie induseer, wat die oorsaak is van postoperatiewe akute nierversaking wanneer hierdie komplikasie voorkom. Dit is verbasend dat, ten spyte van sommige onlangse studies wat rapporteer oor 'n verskeidenheid farmakologiese ingrepe om intraoperatiewe renale isgemie te voorkom (met wisselende sukses), baie min oënskynlik gedoen is om die patogenese en die presiese patofisiologie van hierdie potensieel dodelike komplikasie te ontrafel. Hoewel verskeie outeurs die moontlikheid van hormonale betrokkenheid (veral renienangiotensien, antidiuretiese hormoon en katekolamiene) in hierdie proses suggereer, is die presiese rol van hierdie mediators nog nie op 'n gestruktureerde wyse ondersoek (of rapporteer) nie. In ons aanvanklike pasiënte-studie is renale hemodinamika en -funksie gemeet vanaf die preoperatiewe periode, gedurende die intra-operatiewe fase en tot minstens vier uur na ontklemming van die aorta. Serumkonsentrasies van relevante hormone is bepaal tydens elke metingsperiode waar renale parameters gemeet is, ten einde die moontlikheid van 'n temporale verwantskap tussen renale veranderinge en variasies in hormoonkonsentrasies te ondersoek. Die vermindering in NBV en glomerulêre filtrasiespoed (GFS) wat ons aangetoon het om saam te val met infrarenale aortaklemming, stem ooreen met resultate wat tevore deur ander navorsers publiseer is. Ons het aangetoon dat die inkorting van hierdie parameters voortduur tot minstens vier uur na aorta-ontklemming. Hierdie veranderinge is tevore slegs rapporteer vir periodes tot kort na aorta-ontklemming voor sluiting van die buikwond. Die feit dat die GFS steeds verlaag is met ontslag van hierdie pasiënte, skep rede tot kommer, veral in pasiënte wat alreeds ingekorte nierfunksie het voor die chirurgiese prosedure. Van die gemete hormone wat moontlik 'n invloed sou kon uitoefen op NBV eh nefronfunksie, was renien die enigste waarvan verandering in plasmakonsentrasies saamgeval het met die onderdrukking van NBV en GFS na aortaklemming. Die ontwerp van ons studie het ons nie toegelaat om 'n besliste uitspraak te maak of die geassosieerde verhoging in angiotensien II primêr verantwoordelik was vir die verandering in renale hemodinamika, of dat die verhoogde renien (en angiotensien) bloedvlakke moontlik sekondêr stimuleer is deur die verandering in NBV wat deur 'n ander meganisme induseer is. In 'n ander pasiëntegroep het ons aangetoon dat die kombinasie van mannitol en dopamien geen beskerming verleen het teen die nadelige effekte van aorta-klemming nie. Die groot volumes uriene wat uitgeskei is onder die invloed van hierdie middels (wat nie korreleer het met NBV tydens ooreenstemmende periodes nie), het inderwaarheid 'n ontoepaslike gerustheid uitgelok. Weens die ooglopende gebrek aan objektiewe voordeel wat verleen word deur hierdie middels, behoort hulle gebruik tydens hierdie kliniese omstandighede ontmoedig te word. Die doel van die diere studies was die identifisering van die presiese rol van angiotensien in die patogenese en patofisiologie van die renale veranderinge geassosieer met infrarenale aortaklemming, sowel as die interaksie van angiotensien met ander modulators waarvoor 'n interaktiewe verwantskap voorheen beskryf is onder eksperimentele en/of kliniese omstandighede. Die eerste studie het getoon dat alhoewel renien (en dus angiotensien) konsentrasies hoog was na aorta-ontklemming, die hormone geen betekenisvolle patogenetiese of patofisiologiese rol in die waargenome renale veranderinge gedurende hierdie periode het nie (aangesien blokkade van angiotensien aktivering deur voorkoming van renien vrystelling, of deur inhibisie van angiotensien omsettingsensiem (AOE), nie 'n daling in NBV of GFS kon voorkom nie). Voorkoming van angiotensien II aktivering het egter wel renale verandering voorkom gedurende aortaklemming. Dié voordelige effek het nie 'n primêre rol vir angiotensien gedurende die periode bevestig nie, aangesien die gunstige invloed ook (ten minste gedeeltelik) verduidelik kon word deur die voorkoming van die fassiliterende invloed van angiotensien op ander vasokonstriktore en/of ander vasodilator-invloede van die onderdrukking van AOE en ïs-blokkers (wat geen verband het met angiotensien of die blokkade daarvan nie). Die studie het aangetoon dat (ten minste gedeeltelik) verskillende meganismes verantwoordelik is vir renale veranderinge wat gesien is gedurende aortaklemming en na -ontklemming. Die tweede studie het die rol van kalsium in die renale patofisiologiese veranderinge gedurende aortaklemming en na ontklemming ondersoek. Die beskermende invloed wat deur die toediening van Ca2 + -blokkers bewerkstellig is, het bevestig dat die renale vasokonstriktoriese en glomerulêre patofisiologiese prosesse afhanklik is van sellulêre influks van kalsium deur spannings-afhanklike kannale. Dit het ongelukkig geen definitiewe insig verleen ten opsigte van die primêre inisieerders van die proses nie. Dit verskaf nogtans 'n bruikbare kliniese metode om daardie veranderinge te voorkom en die niere teen isgemiese besering gedurende abdominale aorta-chirurgie te beskerm. Die derde komponent van die diere-studies demonstreer die belangrikheid van die beskermende effek van renale prostaglandiene tydens die spesifieke eksperimentele (en waarskynlik ook die kliniese) omstandighede. Weereens gee dit nie definitiewe inligting oor die bemiddelaars wat verantwoordelik is vir die renale veranderinge nie, aangesien die skadelike effekte van verskeie endogene stowwe voorheen aangetoon is om beperk of voorkom te word deur die intrarenale vrystelling van prostaglandiene. Die omvang van die patofisiologiese en ultrastrukturele veranderinge wat ontstaan het onder die invloed van nie-steroïed anti-inflammatoriese middels (wat gebruik is om prostaglandien sintese te inhibeer), dui aan dat hierdie middels vermy moet word onder soortelyke kliniese omstandighede. Die laaste komponent van die studie verskaf 'n sterk aanduiding dat angiotensien slegs 'n sekondêre/aanvullende rol speel in die renale patofisiologiese proses, selfs gedurende aortaklemming. Dit mag die weersprekende getuienis oor die potensiële voordeel van AOE onderdrukking (op renale hemodinamika en glomerulêre funksie) gedurende abdominale aortachirurgie (Licker et al. 1996, Colson et al. 1992a) verklaar. Gebaseer op ons studies, kan AOE onderdrukking nie ondersteun word vir hierdie doel nie.

A necessidade de cirurgia para substituição da aorta ascendente e valva aórtica com reimplante coronariano em grupos especiais de pacientes onde a anticoagulação é indesejável, como nos idosos, é crescente nos últimos anos. Este estudo objetiva desenvolver e avaliar em modelo animal o comportamento de um conduto valvado aórtico feito com pericárdio bovino tratado pelo glutaraldeído (CVAP). Para tanto, CVAPs foram implantados em 8 ovinos jovens e explantados após serem sacrificados com 150 dias de pós-operatório. Realizou-se estudo angiográfico e hemodinâmico no préoperatório e antes do explante. Ecodopplercardiogramas foram realizados nos dias 30 e 150 de pós-operatório (teste) e também em 5 ovinos não operados (controle). Após explantados, submetemos os CVAPs à avaliação macroscópica, radiológica e histológica por microscopia óptica e eletrônica de transmissão. A análise estatística foi feita com teste não-paramétrico de Mann-Whitney, teste não-paramétrico de Wilcoxon e teste exato de Fisher. O nível de significância utilizado foi 5%. Na análise hemodinâmica houve acréscimo (p>0,05) das pressões arterial e capilar pulmonar entre os dias 0 e 150. Na análise ecodopplercardiográfica, o grupo teste apresentou valores maiores (p>0,05) dos diâmetros diastólicos e sistólicos do ventrículo esquerdo. No grupo teste entre os dias 30 e 150 houve acréscimo (p>0,05) de: peso, espessura das paredes do ventrículo esquerdo, gradiente transvalvar máximo, gradiente transvalvar médio, diâmetro diastólico do ventrículo esquerdo e decréscimo da fração de ejeção. Dois animais com endocardite podem explicar essas diferenças. A macroscopia demonstrou calcificação de grau variável, além de abaulamento na região dos seios em todos os CVAPs, sem aumento de diâmetro. A microscopia óptica revelou dados similares ao da literatura com o uso do pericárdio bovino tratado pelo glutaraldeído. A quantificação realizada com a microscopia eletrônica de transmissão mostrou percentual maior (p>0,05) de colágeno nos seios e nas cúspides e maior conteúdo hídrico na porção mais distal do CVAP. Estes dados indicam que a bioprótese aqui estudada permite a realização desse tipo de experimento no modelo proposto e que os resultados hemodinâmicos encontrados se assemelham aos parâmetros fisiológicos. / The need for replacement surgery of the ascending aorta and aortic valve with coronary reimplantation in special patient groups where anti-coagulation in undesirable, such as elderly, is increasing in the past years. This study aims to develop and evaluate the performance of an aortic valved conduit made with glutaraldehyde treated bovine pericardium (AVCP) in an animal model. Therefore, AVCPs were implanted in 8 young ovine and explanted after being euthanized at 150 days of the post-operative period. An angiographic and hemodynamic study was performed at pre-operative and prior the explant. EchoDoppercardiograms were performed at day 30 and 150 of post-operative (test) as well as in 5 non-operated on ovines (control). Following the explant, AVCPs were submitted to a macroscopical, radiological and histological evaluation by optic and electronic transmission microscopy. A statistics analysis was performed with a Mann-Whitneys nonparametric test, Wilcoxons non-parametric test and Fishers exact test. The significance level used was 5%. In the hemodynamic analysis an increase (p>0,05) of arterial and pulmonary capillary pressure occurred between day 0 and 150. In the echoDoppercardiographic analysis, the test group presented higher values (p>0,05) in the diastolic and systolic diameters of the left ventricle. In the test group, between day 30 and 150, occurred an increase (p>0,05) of weight, thickness of the left ventricle walls, maximum transvalvar gradient, medium transvalvar gradient, left ventricle diastolic diameter and a decrease in the ejection function. Two animals with endocarditis could explain those differences. Macroscopy showed a calcification in variable degrees besides a bulging of the sinus region in all AVCPs, without an increase of diameter. Optic microscopy revealed data similar to literature with the use of glutaraldehyde treated bovine pericadium. The quantification performed by electronic transmission microscopy showed a higher percentage (p>0,05) of collagen in sinus and cusps, and a higher watery content in the most distal portion of the AVCP. These data indicate that the bioprosthesis hereby studied allows the performance of this kind of experiment in the proposed model and that the hemodynamic outcomes found are similar to physiological parameters.

A necessidade de cirurgia para substituição da aorta ascendente e valva aórtica com reimplante coronariano em grupos especiais de pacientes onde a anticoagulação é indesejável, como nos idosos, é crescente nos últimos anos. Este estudo objetiva desenvolver e avaliar em modelo animal o comportamento de um conduto valvado aórtico feito com pericárdio bovino tratado pelo glutaraldeído (CVAP). Para tanto, CVAPs foram implantados em 8 ovinos jovens e explantados após serem sacrificados com 150 dias de pós-operatório. Realizou-se estudo angiográfico e hemodinâmico no préoperatório e antes do explante. Ecodopplercardiogramas foram realizados nos dias 30 e 150 de pós-operatório (teste) e também em 5 ovinos não operados (controle). Após explantados, submetemos os CVAPs à avaliação macroscópica, radiológica e histológica por microscopia óptica e eletrônica de transmissão. A análise estatística foi feita com teste não-paramétrico de Mann-Whitney, teste não-paramétrico de Wilcoxon e teste exato de Fisher. O nível de significância utilizado foi 5%. Na análise hemodinâmica houve acréscimo (p>0,05) das pressões arterial e capilar pulmonar entre os dias 0 e 150. Na análise ecodopplercardiográfica, o grupo teste apresentou valores maiores (p>0,05) dos diâmetros diastólicos e sistólicos do ventrículo esquerdo. No grupo teste entre os dias 30 e 150 houve acréscimo (p>0,05) de: peso, espessura das paredes do ventrículo esquerdo, gradiente transvalvar máximo, gradiente transvalvar médio, diâmetro diastólico do ventrículo esquerdo e decréscimo da fração de ejeção. Dois animais com endocardite podem explicar essas diferenças. A macroscopia demonstrou calcificação de grau variável, além de abaulamento na região dos seios em todos os CVAPs, sem aumento de diâmetro. A microscopia óptica revelou dados similares ao da literatura com o uso do pericárdio bovino tratado pelo glutaraldeído. A quantificação realizada com a microscopia eletrônica de transmissão mostrou percentual maior (p>0,05) de colágeno nos seios e nas cúspides e maior conteúdo hídrico na porção mais distal do CVAP. Estes dados indicam que a bioprótese aqui estudada permite a realização desse tipo de experimento no modelo proposto e que os resultados hemodinâmicos encontrados se assemelham aos parâmetros fisiológicos. / The need for replacement surgery of the ascending aorta and aortic valve with coronary reimplantation in special patient groups where anti-coagulation in undesirable, such as elderly, is increasing in the past years. This study aims to develop and evaluate the performance of an aortic valved conduit made with glutaraldehyde treated bovine pericardium (AVCP) in an animal model. Therefore, AVCPs were implanted in 8 young ovine and explanted after being euthanized at 150 days of the post-operative period. An angiographic and hemodynamic study was performed at pre-operative and prior the explant. EchoDoppercardiograms were performed at day 30 and 150 of post-operative (test) as well as in 5 non-operated on ovines (control). Following the explant, AVCPs were submitted to a macroscopical, radiological and histological evaluation by optic and electronic transmission microscopy. A statistics analysis was performed with a Mann-Whitneys nonparametric test, Wilcoxons non-parametric test and Fishers exact test. The significance level used was 5%. In the hemodynamic analysis an increase (p>0,05) of arterial and pulmonary capillary pressure occurred between day 0 and 150. In the echoDoppercardiographic analysis, the test group presented higher values (p>0,05) in the diastolic and systolic diameters of the left ventricle. In the test group, between day 30 and 150, occurred an increase (p>0,05) of weight, thickness of the left ventricle walls, maximum transvalvar gradient, medium transvalvar gradient, left ventricle diastolic diameter and a decrease in the ejection function. Two animals with endocarditis could explain those differences. Macroscopy showed a calcification in variable degrees besides a bulging of the sinus region in all AVCPs, without an increase of diameter. Optic microscopy revealed data similar to literature with the use of glutaraldehyde treated bovine pericadium. The quantification performed by electronic transmission microscopy showed a higher percentage (p>0,05) of collagen in sinus and cusps, and a higher watery content in the most distal portion of the AVCP. These data indicate that the bioprosthesis hereby studied allows the performance of this kind of experiment in the proposed model and that the hemodynamic outcomes found are similar to physiological parameters.

Η νευρολογικές διαταραχές και κυρίως η παραπληγία, αποτελούν τις πιο καταστροφικές επιπλοκές των επεμβάσεων στη θωρακο-κοιλιακή αορτή. Η διαδικασία ισχαιμίας/επαναιμάτωσης κατά τις επεμβάσεις αυτές λόγω του αποκλεισμού της αορτής, προκαλεί την ανάπτυξη τοξικών ελεύθερων ριζών οξυγόνου φαινόμενο που ορίζει το οξειδωτικό stress. Ο σκοπός της παρούσας μελέτης είναι ο καθορισμός και η ανίχνευση των ελευθέρων ριζών, αλλά και η επίδραση της Αμιφοστίνης, ενός αντιοξειδωτικού παράγοντα της κατηγορίας των θειολών. Μέθοδος: Η μέθοδος αφορά δεκαοκτώ αρσενικούς κονίκλους που υποβάλλονται σε ισχαιμία του νωτιαίου μυελού με αποκλεισμό της αορτής με τη χρήση ενδο-αορτικού ασκού. Ο ασκός προωθείται μέσω της μηριαίας αρτηρίας σε επίπεδο αμέσως κάτωθεν της αριστεράς υποκλειδίου αρτηρίας. Τα ζώα αποτελούσαν τρείς ομάδες. Η Ομάδα Ι αποτέλεσε την ομάδα ελέγχου. Στην Ομάδα ΙΙ η αορτή αποκλείσθηκε για 30΄και ακολούθησε επαναιμάτωση για 75΄. Στην Ομάδα ΙΙΙ χορηγήθηκε Αμιφοστίνη μέσω του καθετήρα αποκλεισμού κατά το δεύτερο ήμισυ της περιόδου αποκλεισμού (των 30΄). Στο τέλος της επαναιμάτωσης δείγματα νωτιαίου μυελού υποβλήθηκαν σε ανάλογη επεξεργασία για την ανίχνευση ελευθέρων ριζών οξυγόνου με τη χρήση υδροεθιδίνης και παραγώγων λιπιδικής υπεροξείδωσης με ιδιαίτερα ευαίσθητη μέθοδο φθορισμού. Αποτελέσματα: Τα αποτελέσματα των μετρήσεων έδειξαν αύξηση του υπεροξειδίου του οξυγόνου στην Ομάδα ΙΙ κατά 27.43% σχετικά με την Ομάδα Ι για να ακολουθήσει μείωση στην Ομάδα ΙΙΙ κατά 42.55% σε σχέση με την Ομάδα ΙΙ και κατά 15.25% από την Ομάδα ΙΙΙ. Η μέτρηση ενώσεων λιπιδικής υπεροξείδωσης που αντιδρούν με θειοβαρβιτουρικό οξύ (TBARSassay) έδειξε αύξηση κατά 55.3% στην Ομάδα ΙΙ σε σχέση με την Ομάδα Ι και μείωση κατά 30.3% στην Ομάδα ΙΙΙ σε σχέση με την Ομάδα ΙΙ. Η στατιστική ανάλυση και των δύο μεθόδων ανέδειξε σημαντική διαφορά με ( p<0.05). Συμπεράσματα: Ο αποκλεισμός της κατιούσας αορτής σε επίπεδο αμέσως κάτωθεν της αριστεράς υποκλειδίου αρτηρίας, προκαλεί αναμφισβήτητα ισχαιμία του νωτιαίου μυελού. Η ανάπτυξη οξειδωτικού stressως αποτέλεσμα της διαδικασίας ισχαιμία/επαναιμάτωση ανιχνεύεται μέσω των ριζών υπεροξειδίου και παραγώγων λιπιδικής υπεροξείδωσης. Η έγχυση Αμιφοστίνης προτείνεται ως αντιοξειδωτικός παράγων που μπορεί να ανιχνεύσει και να δεσμεύσει τις ελεύθερες ρίζες οξυγόνου κατά το οξειδωτικό stress που προκαλεί η ισχαιμία /επαναιμάτωση του νωτιαίου μυελού. / Paraplegia is the most devastating complication of thoraco-abdominal aortic procedures. An ischemia-reperfusion procedure is known to elevate free radicals causing oxidative stress. The aim of this study is to determine and to detect the free radical products and to examine the influence of Amifostine, a triphosphate agent, on oxidative stress of spinal cord ischemia-reperfusion in rabbits. Methods: Eighteen male, New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by inflation of a coronary artery balloon catheter, advanced to descending thoracic aorta through the femoral artery. The animals were randomly divided into 3 groups. Group I functioned as control. In group II the aorta was occluded for 30 minutes and then re-perfused for 75 min. In group III, 500mg Amifostine was infused into the distal aorta during the second half-time of ischemia period. At the end of reperfusion all animals were sacrificed and spinal cord specimens were examined for superoxide radicals by an ultra sensitive fluorescent assay. Results: Superoxide radical levels ranged, in group I between 1.52 and 1.76 (1.64±0.10), in group II between 1.96 and 2.50 (2.10±0.21), and in group III (amifostine) between 1.21 and 1.60 (1.40±0.13) (p=0.00), showing a decrease of 43% in the Group of Amifostine. A lipid peroxidation marker measurement ranged, in group I between 0.28 and 0.31 (0.30±0.01), in group II between 0.427 and 0.497 (0.466±0.024), and in group III (amifostine) between 0.343 and 0.357 (0.36±0.005) (p<0.00), showing a decrease of 38% after Amifostine administration. Conclusions: Occlusion of aorta below left subclavian artery causes spinal cause ischemia without the interference of collateral perfusion. Modified use of hydrο-ethidine is a useful assay for the detection of superoxide radicals. By direct and indirect methods of measuring the oxidative stress of spinal cord after ischemia/reperfusion, it is suggested that intra-aortic Amifostine infusion significantly attenuated the spinal cord oxidative injury.

Σκοπός: Διεξάγαμε την παρούσα μελέτη για να καταδείξουμε την ύπαρξη των βρογχικο-στεφανιαίων αναστομώσεων στο πειραματικό μοντέλο του χοίρου. Επιπλέον διερευνήσαμε την επίπτωση της αρτηριοσκλήρυνσης στις βρογχικές αρτηρίες. Υλικό – Μέθοδος: Χρησιμοποιήθηκαν τα παρασκευάσματα καρδιάς και πνευμόνων από 6 χοίρους. Επιπλέον, δείγματα βρογχικών αρτηριών ελήφθησαν από 40 ασθενείς που υποβάλλονταν σε θωρακοτομή. Σημειώθηκαν αναλυτικά οι κλινικοί και εργαστηριακοί παράγοντες κινδύνου για ανάπτυξη αρτηριοσκλήρυνσης. Αποτελέσματα: Με υπολογιστική τομογραφία, ψηφιακή αγγειογραφία και χορήγηση χρωστικής ρητίνης καταδείξαμε το αναστομωτικό δίκτυο μεταξύ των βρογχικών και κυρίως των αριστερών στεφανιαίων αρτηριών σε 5 από τα 6 παρασκευάσματα. Η μικροσκοπική εξέταση των δειγμάτων δεν στοιχειοθέτησε ύπαρξη αθηροσκλήρυνσης, παρά μόνο ύπαρξη ασβεστοποιού σκλήρυνσης του μέσου χιτώνα σε ποσοστό 2.5%, που δεν συσχετίστηκε με τους παράγοντες κινδύνου αρτηριοσκλήρυνσης. Συμπεράσματα: Με δεδομένο ότι βρογχικές αρτηρίες παρουσιάζουν ελάχιστο βαθμό ασβεστοποιού σκλήρυνσης του μέσου χιτώνα., υποθέτουμε ότι θα μπορούσαν να συνδράμουν στη στεφανιαία κυκλοφορία μέσω των προαναφερθεισών αναστομώσεων σε καταστάσεις εκσεσημασμένης στεφανιαίας νόσου. Η μελέτη μας υπογραμμίζει την σπουδαιότητα των βρογχικών αρτηριών και των βρογχικο-στεφανιαίων αναστομώσεων σε περιπτώσεις εμβολισμού των βρογχικών αρτηριών, μεταμοσχεύσεων καρδιάς-πνευμόνων και αντιμετώπισης ανευρυσμάτων θωρακικής αορτής. / Aim of the study: We conducted this study to demonstrate the coronary-bronchial anastomotic routes in a porcine model. Additionally, we estimated the incidence of bronchial arteries arteriosclerosis. Material and Methods: Six heart-lung porcine blocks were used. Furthermore, 40 bronchial arteries were obtained from patients who underwent thoracotomy. Detailed clinical and laboratory atherosclerotic risk factors of the patients were documented. Results: Using CT-scan, Digital Subtraction Angiography and colored latex, we demonstrated communications between the bronchial and coronary circulation in 5 of 6 subjects. Histology revealed no established atherosclerotic lesion and narrowing of the lumen, but medial calcific sclerosis in 2.5%, that was independent from the arteriosclerotic risk factors. Conclusions: As evidence suggests that bronchial arteries only exhibit medial calcific sclerosis, we hypothesize that bronchial arteries can contribute to the coronary flow through the broncho-coronary anastomoses in cases of severe coronary artery disease. Our study emphasizes their importance and their anastomoses to coronaries in cases of embolization, heart-lung transplantation and thoracic aorta aneurysms repair.

Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)