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Bonvini, Stefano (2009) Temporary renal reperfusion to increase safe ischemic time. [Ph.D. thesis]

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Abstract (english)

The reported rate of acute renal failure from large series of patients undergoing Thoraco Abdominal Aortic Aneurysms (TAAA) repair ranges from 5% to 40% and is associated with mortality rates of 70%. Patients who develop acute renal failure also more frequently present a worse outcome and sustain non renal complications, such as respiratory failure, central nervous system dysfunction, sepsis, and gastrointestinal haemorrhage.
The factors contributing to renal dysfunction after TAAA repair include ischemia reperfusion injury, nonpulsatile flow in perfusion systems, transfusion of blood products, pre-operatory renal impairment etc.
Ischemia (cessation of blood flow), followed by reperfusion (re-establishment of blood flow), causes characteristic injury to organs and tissues. Ischemia compromises the continuous supply of oxygen required by tissues and organs to survive and maintain normal physiological function. A rapid return of oxygenated blood (reperfusion) is therefore essential for preventing ischemic and apoptotic cell death. However, reperfusion itself also contributes to cellular injury and death by the production of free oxygen radicals and the activation of a cytokine mediated inflammatory response that, on one side, through a pro-inflammatory component expression (IL1?, IL1?, IL,2, IL6, GM-CSF, TNF?, INF?) sustain cellular damage, and on the other side, through an anti inflammatory component expression (IL4, IL10) tends to limit it being therefore the prelude of the reestablishment of normal conditions.
The short term arterial blood reperfusion of renal arteries is one of the surgical techniques applied at the Vascular and Endovascular division of the University of Padova to prevent renal impairment. Renal blood reperfusion is obtained, once the proximal anastomosis between the proximal aorta and the Dacron graft is performed, by re-establishing pulsatile normothermic blood flow through a Pruitt-Inahara shunt. Application of the shunt may change in different surgical procedure. When the procedure requires more than 30 min to re-establish a normal flow in the renal artery, the proximal end of the shunt is distally inserted in the vascular graft. The proximal aortic clamp is released; the shunt is blood perfused and its distal end is inserted into the open end of the renal artery. After 3 min of blood reperfusion, the aorta and the renal artery are reclamped, the shunt is promptly removed and the renal artery reconstruction completed. The reperfusion is repeated every 30 min if necessary.
Aim of my PhD thesis was to evaluate on an animal model the possibility to increase the total time of clamping ischaemia by re-establishing blood flow into renal artery for 3 or 6 minutes leading to a total ischemic period of 90 minutes, evaluating functional, morphological damage and molecular processes involved in the pathophysiology of ischemia reperfusion injury.
27 Male Sprague-Dawley rats weighing 200 to 250 g, were used for the experiment. Through a midline laparotomy both renal arteries were dissected and clamped to obtain a bilateral ischemia followed by reperfusion in selected group of animals.The rats were allocated into one of the 4 experimental groups; control group, 18 rats with ischemia alone (with progressive clamping time of both renal arteries to assess organ damage at 30-45-60-90 min); group A, 4 rats (30 min of renal ischaemia followed by 3 min of reperfusion followed by other 30 min of ischemia for a total ischaemic time of 60 min), group B,4 rats (45 min of renal ischaemia followed by 3 min of reperfusion plus 45 minutes of ischemia for a total ischemic time of 90 min) and group C, 3 rats (30 min of renal ischaemia followed by 3 min of reperfusion repeated 3 times for a total ischemic time of 90min). A blood sample from inferior vena cava was drawn to evaluate serum creatinine level before the renal clamping. After 48 hours from the procedure the rats were sacrificed for kidney harvesting. Before kidney removal a blood sample from inferior vena cava was drawn to evaluate serum creatinine level.
Renal injury was assessed through evaluation of: a) renal functional parameters (serum level of creatinine at 0 and 48 hours after ischemia), b) morphological parameters on histological samples ( tubular necrosis, tubular dilatation, mitosis, apoptosis, haemorrhage infiltration interstitial leukocyte infiltration, and the proliferative index (Ki67), c) pro-inflammatory (IL1?, IL1?, IL,2, IL6, GM-CSF, TNF?, INF?) and anti-inflammatory (IL4, IL10) cytokine expression on tissue samples.
Animals that underwent renal ischemia with no reperfusion exhibited increase in the serum concentrations of creatinine when the clamping ischemia was more than 45 min, and this difference becomes statistically significant when the clamping time is more than 60 minutes suggesting glomerular dysfunction. In revascularized groups creatinine serum level demonstrates no significant changes compared to the base pre-ischemic value regardless the pattern of revascularization performed suggesting the lack of glomerular dysfunction also in these groups of animals.
Morphological damages were absent in the revascularized group if the total ischemic time is less than 60 minutes. When the total ischemic time was prolonged up to 90 minutes even if no functional alteration was present histopathological analysis demonstrated a moderate renal injury in terms of necrosis and apoptosis. However a higher proliferative index is present at 90 minutes in all revascularized group with the highest increase in double reperfusion. Pro inflammatory (IL-1?, IL-2, IL-6, GM-CSF, IFM-? ,TNF-?: ) and anti-inflammatory(IL-10, IL-4) cytokines are expressed in all the different groups of animals after ischemia and after ischemia and reperfusion. Both pro and anti inflammatory cytokines are over-expressed in animals that underwent a total ischemic time of 60 minutes with a single reperfusion (30+3+30 ), compared to the group without reperfusion and with those with ischemia of 90 min (30+3+30+3+30; 45+3+45). The cytokine evaluation showed a prevalence of anti-inflammatory cytokine expression in the revascularized group with a statistically significant difference for IL10 over-expression.
In the reperfusion at 90 minutes we observed a decrease in both pro-inflammatory and anti inflammatory cytokines. However with double reperfusion the decrease was more pronounced for the proinflammatory cytokines (TNF?) allowing the biological effect of IL10 to be more powerful (higher proliferative index).
The results of my PhD thesis showed that the functional, morphological and molecular results are congruent. At 60 min of ischemia there is an irreversible damage to the kidney with an increased creatinine level, necrosis and apoptosis, low proliferative response and increase in cytokines expression especially of pro-inflammatory cytokines (IL1?, IL2, IL6, TNF? and INF?). With ischemia-reperfusion (30-3-30) we obtain a less ischemic damage, a more pronounced proliferative response and anti-inflammatory cytokines over-expression (IL-10, IL-4) compared to ischemia alone. The balance was in favour of the protective role of reperfusion. With the ischemic-reperfusion model of 90 min of ischemia and 6 minutes reperfusion (30-3-30-3-30) we still observed the beneficial role of reperfusion since there is a reduction of necrosis, apoptosis and increasing in proliferation activity and at the end a positive ratio in favour of anti-inflammatory cytokines (IL-10). In the setting of 90 min ischemia and 3 min reperfusion, (45-3-45) we observed a similar ischemic damage in term of necrosis and less proliferative index and the ratio between pro and anti inflammatory was still in favour of anti inflammatory cytokines. However the decrease of pro inflammatory cytokine TNF? was less evident, thus counterbalancing more actively the protective role of anti inflammatory cytokine IL10.
We can state that according to our results the best model would be that of 30-3-30-3-30 which means less ischemic damage and more reperfusion benefits.

Abstract (italian)


L’incidenza di insufficienza renale (i.r.) post-operatoria in pazienti sottoposti a chirurgia dell’aorta toraco-addominale è riportata essere dal 5 al 40 % a seconda delle casistiche associata ad un tasso di mortalità intorno al 70%. I pazienti che sviluppano una insufficienza renale acuta post-operatoria sviluppano più frequentemente complicanze non renali come ad esempio insufficienza respiratoria, disfunzioni del sistema nervoso centrale, sepsi ed emorragie gastrointestinali.
I fattori che contribuiscono al danno renale dopo chirurgia aortica includono il danno da ischemia e riperfusione, il flusso non pulsato di alcuni sistemi di riperfusione, condizione renale preoperatoria, perdite ematiche etc.
L’ischemia (interruzione del flusso ematico a livello del parenchima renale), seguita dalla riperfusione (ripristino del flusso), provocano dei danni caratteristici ad organi e tessuti. L’ischemia compromette il continuo rifornimento di ossigeno ai tessuti necessario per il mantenimento delle normali funzioni fisiologiche. La riperfusione però, necessaria per il mantenimento della vitalità cellulare, è essa stessa causa di danno cellulare attraverso la produzione di radicali liberi dell’ossigeno e attivazione di una risposta infiammatoria mediata dalle citochine che da un lato, attraverso l’espressione della componente pro-infiammatoria (IL1?, IL1?, IL,2, IL6, GM-CSF, TNF?, INF?) sostiene il danno e dall’altro, attraverso l’espressione della sua componente anti-infiammatoria (IL4, IL10) tende ad arginarlo costituendo il preludio al ritorno alla condizione di normalità.
Attualmente la metodica chirurgica utilizzata presso la Clinica di Chirurgia Vascolare ed Endovascolare dell’Università degli studi di Padova nella prevenzione dell’insufficienza renale è rappresentata dall’utilizzo della riperfusione breve delle arterie renali che consiste nel riperfondere le arterie renali per 3 minuti, una volta completata l’anastomosi prossimale della ricostruzione aortica, attraverso degli shunt temporanei inseriti nella protesi. Tale riperfusione permette di poter clampare per ulteriori 30 minuti di ischemia le arterie renali permettendo di poter completare l’intervento. Qualora necessario è possibile inoltre riperfondere per ulteriori 3 minuti le arterie renali per ottenere ulteriori 30 minuti di ischemia.

Scopo di questo studio è dimostrare nel modello animale che è possibile incrementare il tempo di ischemia totale renale ristabilendo per 3 minuti un flusso pulsato all’interno dell’arteria renale, valutando i danni funzionali, morfologici ed i processi molecolari legati ad essi. La riperfusione breve delle arterie renali può essere ripetuta più volte raggiungendo un tempo di ischemia totale di 90 minuti.
Materiali e metodi
Lo studio è stato condotto su 27 ratti albini del ceppo Sprague-Dawley di sesso maschile e del peso di 250 gr circa .Dopo aver praticato una laparotomia mediana si è proceduto all’isolamento e al clampaggio dell’arteria renale bilateralmente ottenendo l’ischemia completa dei reni seguita da riperfusione secondo il protocollo. Gli animali sono stati suddivisi in 4 gruppi sperimentali; un gruppo di controllo, 18 ratti, (sottoposti ad un clampaggio di tempo crescente delle arterie renali per valutare la gravità del danno ischemico a tempi differenti pari a 30-35-40-45-50-55-60-75-90 minuti. Un gruppo A, 4 ratti (sottoposti a 30 minuti di ischemia seguiti da 3 minuti di riperfusione e successivi 30 minuti di ischemia per un totale di 60 minuti), un gruppo B, 4 ratti, (sottoposti a due periodi di ischemia di 45 minuti intervallati da 3 min di riperfusione per un totale di 90 minuti di ischemia); un gruppo C, 3 ratti, (sottoposti a tre periodi di ischemia di 30 minuti ognuno interrotti da 3 min di riperfusione per un totale di 90 minuti di ischemia). Prima dell’ischemia è stato eseguito un prelievo venoso dalla cava per il dosaggio della creatinina sierica. In seconda giornata post-operatoria i ratti sono stati sottoposti a riapertura della ferita chirurgica, con espianto di entrambi i reni e sacrificio dell’animale previo prelievo venoso dalla cava. Il materiale prelevato è stato inviato presso i laboratori di Anatomia Patologica per una valutazione mediante microscopia ottica.
La valutazione del danno renale è stata eseguita controllando i parametri di funzionalità renale (creatininemia a 0 e 48 ore dall’evento ischemico), i parametri morfologici di danno sugli esami istologici (la necrosi, la dilatazione tubuale, le mitosi, apoptosi, dimorfismi, stravasi ematici, infiltrato infiammatorio) e l’indice proliferativo (Ki67).
Inoltre è stata valutata l’espressione delle interleuchine pro-infiammatorie (IL1?, IL1?, IL,2, IL6, GM-CSF, TNF?, INF?) ed anti-infiammatorie (IL4, IL10)
La valutazione della creatinine mia a 0 e 48 ore ha evidenziato come la riperfusione temporanea sia in grado di proteggere funzionalmente il parenchima renale. A 90 minuti i ratti riperfusi mostrano valori di creatininemia sovrapponibili ai valori di base preischemici mentre i ratti non riperfusi a 90 minuti hanno un aumento significativo della creatininemia.
Da un punto di vista morfologico la valutazione a 60 minuti documenta l’assenza di lesioni. Quando il tempo di ischemia è prolungato a 90 minuti, anche se da un punto di vista funzionale non vi è evidenza di alterazioni, l’analisi istopatologica ha dimostrato un danno seppur lieve sia in termini di necrosi che di apoptosi. Tuttavia a 90 minuti si osserva un alto indice proliferativi in tutti gli animali sottoposti a riperfusione con il più alto valore che si riscontra nei ratti sottoposti a doppia riperfusione. Le citofhine pro-infiammatorie (IL-1?, IL-2, IL-6, GM-CSF, IFM-? ,TNF-?: ) ed antiinfiammatorie (IL-10, IL-4) sono espresse dai vari gruppi di animali dopo ischemia e dopo ischemia e riperfusione. Sia le citochine pro che antiinfiammatorie sono sovra espresse negli animali sottoposti ad una ischemia totale di 60 minuti con singola riperfusione confrontati con il gruppo senza riperfusione e con quelli con ischemia di 90 minuti. La valutazione delle citochine dimostra una prevalenza di citochine antinfiammatorie nel gruppo rivascolarizzato con una differenza statisticamente significativa per IL10.
Nelle riperfusioni a 90 minuti si è osservato un decremento sia per quel che riguarda le citochine pro che antinfiammatoria . Tuttavia con la doppia riperfusione il decremento era più marcato per le citochine proinfiammatorie (TNF?) permettendo l’esplicarsi dell’attività biologica della IL10.
I risultati della mia tesi di dottorato dimostrano come i risultati funzionali, morfologici e molecolari siano congrui. A 60 minuti di ischemia vi è la comparsa di un donno parenchimale irreversibile con incremento del dosaggio della creatininemia sierica, dei processi di apoptosi e necrosi cellulare, basso indice proliferatici ed un incremento del livello di espressione delle citochine. A tale riguardo tale incremento riguarda in particolar modo l’espressione delle citochine pro-infiammatorie (IL1?, IL1?, IL,2, IL6, GM-CSF, TNF?, INF?). Nel caso di ischemia e riperfusione con pattern 30-3-30 è stato osservato un minor danno ischemico accompagnato ad una risposta proliferativa pronunciata ed a una sovraespressione di citochine anti-infiammatorie (IL10, IL4). Il bilancio finale è in favore del ruolo protettivo della riperfusione. Con il modello di riperfusione di 90 minuti di ischemia e 6 di riperfusione (30-3-30-3-30) si osservano ancora i risultati positivi della riperfusione con una riduzione della necrosi, ed un incremento dell’attività proliferativi con un rapporto favorevole verso la produzione di citochine antinfiammatorie (IL10). Nel pattern dei 90 minuti di ischemia e 3 di riperfusione (45-3-45), abbiamo osservato un danno ischemico simile in termini di necrosi ed apoptosi ed un indice proliferativo più basso ed un rapporto tra citochine pro ed anti infiammatorie a favore di quelle antinfiammatorie. Tuttavia il decremento delle citochine pro-infiammatorie TNF è risultato essere meno evidente, contrastando così in maniera più attiva il ruolo antinfiammatorio di IL10.
Si può concludere,in accordo con i risultati presentati, che il miglior modello di riperfusione risulta essere quello di ischemia / riperfusione 30-3-30-3-30 accompagnato da meno danno ischemico associato ai benefici della riperfusione.

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EPrint type:Ph.D. thesis
Tutor:Deriu, Giovanni
Supervisor:Angelini , Annalisa
Data di deposito della tesi:02 February 2009
Anno di Pubblicazione:2009
Key Words:Renal, surgery, cytokine, aortic surgery, reperfusion
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/22 Chirurgia vascolare
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari
Codice ID:1954
Depositato il:02 Feb 2009
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Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

R.B. Griepp, M.A. Ergin and J.D. Galla et al., Natural history of descending thoracic and thoracoabdominal aneurysms, Ann Thorac Surg 67 (1999), pp. 1927–1930. Cerca con Google

L.G. Svensson, E.S. Crawford, K.R. Hess, J.S. Coselli and H.J. Safi, Experience with 1509 patients undergoing thoracoabdominal aortic operations, J Vasc Surg 17 (1993), pp. 357–370 Cerca con Google

J.S. Coselli, L.D. Conklin and S.A. LeMaire, Thoracoabdominal aortic aneurysm repair: review and update of current strategies, Ann Thorac Surg 74 (2002), pp. S1881–S1884 Cerca con Google

H.J. Safi, C.C. Miller 3rd and M.S. Subramaniam et al., Thoracic and thoracoabdominal aortic aneurysm repair using cardiopulmonary bypass, profound hypothermia, and circulatory arrest via left side of chest incision, J Vasc Surg 28 (1998), pp. 591–598 Cerca con Google

McCord JM. Oxigen-derived free radicals in post-ischemic tissue injury.N. Engl.Jour. Med.(1985);312:159-63 Cerca con Google

N. Singri, S.N. Ahya and M.L. Levin, Acute renal failure. JAMA 289 (2003), pp. 747–751. 7 C.A. Schmidt, M.N. Wood, K.A. Gan and A.J. Razzouk, Surgery for thoracoabdominal aortic aneurysms. Am Surg 56 (1990), pp. 745–748 Cerca con Google

L.M. Hollier, S. Monet, T. Naslund, D.C. Procter, W.C. Buhman and R.J. Marino, Risk of spinal cord dysfunction in patients undergoing thoracoabdominal aortic replacement. Am J Surg 164 (1992), pp. 210–214 Cerca con Google

V.S. Kashyap, R.P. Cambria, K. Davison and G.J. Renal failure after thoracoabdominal aortic surgery. J Vasc Surg 26 (1997), pp. 949–957 Cerca con Google

Kellen M, Aronson S, Roizen MF, Barnard J, Thisted RA. Predictive and diagnostic tests of renal failure: a review. Anesthesia and Analgesia (1994);78:134-42 Cerca con Google

Welch M, Newstead CG, Smyth JV, Dodd PD, Walker MG. Evaluation of dopexamine hydrochloride as a renoprotective agent during aortic surgery. Annals of Vascular Surgery (1995);9:488-92 Cerca con Google

Lassnigg A, Donner E, Grubhofer G, Presterl E, Drubl W, Hiesmayr M. Lack of renoprotective effects of dopamine and furosemide during cardiac surgery. Journal of American Society of Nephrology (2000);11:97-104. Cerca con Google

Wahbah AM, el-Hefny MO, Wafa EM, el-KharbotlyW, el-Enin AA, Zaglol, A, et al.Perioperative renal protection in patients with obstructive jaundice using drug combinations. Hepato-gastroenterology (2000);47:1691-4. Cerca con Google

J.S. Coselli and S.A. LeMaire, Left heart bypass reduces paraplegia rates after thoracoabdominal aortic aneurysm repair, Ann Thorac Surg 67 (1999), pp. 1931–1934 Cerca con Google

H.J. Soukiasian, S.S. Raissi and T. Kleisli et al., Total circulatory arrest for the replacement of the descending and thoracoabdominal aorta, Arch Surg 140 (2005), pp. 394–398. Cerca con Google

McCord JM, Oxygen-derived free radicals in post-ischemic tissue injury. N Engl J Med (1985) 312:159–163 Cerca con Google

Anaya-Prado R, Toledo-Pereyra LH, Lentsch AB, Ward PA Ischemia/reperfusion injury. J Surg Res (2002) 105:248–258 Cerca con Google

Grace PA Ischaemia-reperfusion injury. Br J Surg (1994) 81:637–647 Cerca con Google

Anaya-Prado R, Toledo-Pereyra LH, Lentsch AB, Ward PA Ischemia/reperfusion injury. J Surg Res (2002) 105:248–258 Cerca con Google

McCord JM Oxygen-derived free radicals in post-ischemic tissue injury. N Engl J Med (1985) 312:159–163 Cerca con Google

Zimmerman BJ, Granger DN Reperfusion injury. Surg Clin North Am(1992) 72:65–83 81 Cerca con Google

Ar’Rajab A, Dawidson I, Fabia R Reperfusion injury. New Horiz (1996) 4:224–234 Cerca con Google

Homer-Vanniasinkam S, Crinnion JN, Gough MJ Post-ischaemic organ dysfunction: a review. Eur J Vasc Endovasc Surg (1997) 14:195–203 Cerca con Google

Granger DN, Hollwarth MA, McCord JM Ischemia reperfusion injury: role of oxygenderived free radicals. Acta Physiol Scand (1986) 548:47–63 Cerca con Google

Bodwell W Ischemia, reperfusion and reperfusion injury: role of oxygen free radicals and oxygen free radical scavengers. J Cardiovasc Nurs (1989) 4:25–32 Cerca con Google

Kloner RA, Przyklenk K, Whittaker P Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation (1989) 80:1115–1127 Cerca con Google

Toledo-Pereyra LH, Lopez-Neblina F, Toledo AH Reactive oxygen species and molecular biology of ischemia/reperfusion. Ann Transplant (2004) 9:81–83 Cerca con Google

Bonventre JV Mechanisms of ischemic acute renal failure. Kidney Int (1993) 43:1160– 1178 Cerca con Google

Paller MS The cell biology of reperfusion injury in the kidney. J Invest Med (1994) 42:632–639 Cerca con Google

Weight SC, Bell PR, Nicholson ML Renal ischemia-reperfusion injury. Br J Surg (1996) 83:162–170 Cerca con Google

Versteilen AM, Di Maggio F, Leemreis JR, Groenveld AB, Musters RJ, Sipkema P Molecular mechanisms of acute renal failure following ischemia/reperfusion. Int J Artif Organs (2004) 27:1019–1029 Cerca con Google

Thadhani R, Pascual M, Bonventre JV Acute renal failure. N Engl J Med (1996) 334:1448–1460 Cerca con Google

Gilbert RE, Kelly DJ, Atkins RC Novel approaches to the treatment of progressive renal disease. Curr Opin Pharmacol (2001) 1:183–189 Cerca con Google

McCombs PR, Roberts B Acute renal failure following resection of abdominal aortic aneurysm. Surg Gynecol Obstet (1979) 148:175–178 Cerca con Google

Troppmann C, Gillingham KJ, Benedetti E, Almond PS, Gruessner RW, Najarian JS, Matas AJ Delayed graft function, acute rejection, and outcome after cadaver renal transplantation. The multivariate analysis. Transplantation (1995) 59:962–968 Cerca con Google

Aronson S, Blumenthal R Perioperative renal dysfunction and cardiovascular anesthesia: concerns and controversies. J Cardiothorac Vasc Anesth (1998) 12:567–586 Cerca con Google

Zanardo G, Michielon P, Paccagnella A, Rosi P, Calo M, Salandin V, Da Ros A, Michieletto F, Simini G Acute renal failure in the patient undergoing cardiac operation. J Thorac Cardiovasc Surg (1994) 107:1489–1495 Cerca con Google

Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J Independent association between ARF and mortality following cardiac surgery. Am J Med (1998) 104:343–348 Cerca con Google

Lameire N, Van Biesen W, Vanholder R Acute renal failure. Lancet (2005) 365:417–430 Cerca con Google

Gilbert RE, Kelly DJ, Atkins RC Novel approaches to the treatment of progressive renal disease. Curr Opin Pharmacol (2001) 1:183–189 Cerca con Google

Murphy TP, Rundback JH, Cooper C, Kiernan MS Chronic renal ischemia: implications for cardiovascular disease risk. J Vasc Interv Radiol (2002) 13:1187–1198 Cerca con Google

Rundback JH, Murphy TP, Cooper C, Weintraub JL Chronic renal ischemia: pathophysiologic mechanisms of cardiovascular and renal disease. J Vasc Interv Radiol (2002) 13:1085–1092 Cerca con Google

Venkatachalam MA, Bernard DB, Donohue JF, Levinsky NG Ischemic damage and repair Cerca con Google

in the rat proximal tubule. Differences among the S1, S2 and S3 segments. Kidney Int (1978) 14:31– Cerca con Google

49 Cerca con Google

Sheridan AM, Bonventre JV Cell biology and molecular mechanisms of injury in ischemic acute renal failure. Curr Opin Nephrol Hypertens (2000) 9:427–434 Cerca con Google

Masztalerz M, Wlodarczyk Z, Czuczejko J, Slupski M, Kedziora J Superoxide anion as a marker of ischemia-reperfusion injury of the transplanted kidney. Transplant Proc (2006) 38:46–48 Cerca con Google

Paller MS The cell biology of reperfusion injury in the kidney. J Invest Med (1994) 42:632–639 Cerca con Google

Weight SC, Bell PR, Nicholson ML Renal ischemia-reperfusion injury. Br J Surg (1996) 83:162–170 Cerca con Google

Cecka JM, Cho YW, Terasaki PI Analyses of the UNOS scientific renal transplant registry at 3 years—Early events affecting transplant success. Transplantation (1992) 53:59–64 Cerca con Google

Troppmann C, Gillingham KJ, Benedetti E, Almond PS, Gruessner RW, Najarian JS, Matas AJ Delayed graft function, acute rejection, and outcome after cadaver renal transplantation. The multivariate analysis. Transplantation (1995) 59:962–968 Cerca con Google

Shoskes DA, Halloran PF Delayed graft function in renal transplantation: etiology, management and long-term significance. J Urol (1996) 155:1831–1840 Cerca con Google

Awad AS, Ye H, Huang L, Li L, Foss FW Jr, Macdonald TL, Lynch KR, Okusa MD Selective sphingosine 1-phosphate 1 receptor activation reduces ischemia-reperfusion injury in mouse kidney. Am J Physiol Renal Physiol (2006) 290:F1516–F1524 Cerca con Google

Hassoun H, Grigoryev DN, Lie M, Liu M, Cheadle C, Tuder RM, Rabb H Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy. Am J Physiol Renal Physiol (2007) 204:921-925 Cerca con Google

Nath KA, Norby SM Reactive oxygen species and acute renal failure. Am J Med (2000) Cerca con Google

109:655–678 Cerca con Google

Nose K Role of reactive oxygen species in the regulation of physiological functions. Biol Pharm Bull (2000) 23:897–903 Cerca con Google

Chatterjee PK, Cuzzocrea S, Brown PAJ, Zacharowski K, Stewart KN, Mota-Filipe H, Thiemermann C Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated renal dysfunction and injury in the rat. Kidney Int (2000) 58:658–673 Cerca con Google

Greene EL, Paller MS Oxygen free radicals in acute renal failure. Miner Electrolyte Metab (1991) 17:124–132 Cerca con Google

Venkatachalam MA, Bernard DB, Donohue JF, Levinsky NG Ischemic damage and repair in the rat proximal tubule. Differences among the S1, S2 and S3 segments. Kidney Int (1978) 14:31– 49 Cerca con Google

Kloner RA, Przyklenk K, Whittaker P Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation (1989) 80:1115–1127 Cerca con Google

Bowie A, O’Neill LA Oxidative stress and NF-B activation: a reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol (2000) 59:13–23 Cerca con Google

Pincemail J, Defraigne JO, Detry O, Franssen C, Meurisse M, Limet R Ischemiareperfusion injury of rabbit kidney: comparative effects of desferrioxamine and N-acetylcysteine as antioxidants. Transplant Proc (2000) 32:475–476 Cerca con Google

Baker GL, Corry RJ, Autor AP Oxygen free radical induced damage in kidneys subjected to warm ischemia and reperfusion. Protective effect of superoxide dismutase. Ann Surg (1985) 202:628–641 Cerca con Google

Kulah E, Tascilar O, Acikgoz S, Karadeniz G, Tekin IO, Can M, Gun B, Barut F, Comert M Oxidized LDL accumulation in experimental renal ischemia reperfusion injury model. Ren Fail (2007) 29:409–415 Cerca con Google

Solmazgul E, Uzun G, Cermik H, Atasoyu EM, Aydinoz S, Yildiz S Hyperbaric oxygen therapy attenuates renal ischemia/reperfusion injury in rats. Urol Int (2007) 78:82–85 Cerca con Google

McCord JM, Edeas MA SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed Pharmacother (2005) 59:139–142 Cerca con Google

Kone BC, Baylis C Biosynthesis and homeostatic roles of nitric oxide in the normal kidney. Am J Physiol (1997) 272:F561–F578 Cerca con Google

Chatterjee PK, Kvale EO, Patel NS, Thiemermann C GW274150 inhibits nitric oxide production by rat proximal tubular cells. Med Sci Monit (2003) 9:BR357–BR362 Cerca con Google

Weight SC, Nicholson ML (1998) Nitric oxide and renal reperfusion injury: a review. Eur J Vasc Endovasc Surg (1998) 16:98–103 Cerca con Google

Goligorsky MS, Brodsky SV, Noiri E - NO bioavailability, endothelial dysfunction, and acute renal failure: new insights into pathophysiology. Semin Nephrol (2004) 24:316–323 Cerca con Google

Pryor W, Squadrito G - The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol (1995) 268:L699–L772 Cerca con Google

Radi R, Beckman JS, Bush KM, Freeman BA - Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys (1991) Cerca con Google

288:481–487 Cerca con Google

Beckman JS, Beckman TW, Chen J, Marshalland PA, Freeman BA - Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA (1990) 87:1620–1624 Cerca con Google

Chatterjee PK, Patel NSA, Kvale EO, Cuzzocrea S, Brown PAJ, Stewart KN, Mota-Filipe H, Thiemermann C - Inhibition of inducible nitric oxide synthase reduces renal ischemia reperfusion Cerca con Google

injury. Kidney Int (2002) 61:862–871 Cerca con Google

Yamakura F, Taka H, Fujimura T, Murayama K - Inactivation of human manganesesuperoxide Cerca con Google

dismutase by peroxynitrite is caused by exclusive nitration of tyrosine 34 to 3- nitrotyrosine. J Biol Chem (1998) 273:14085–14089 Cerca con Google

Noiri E, Nakao A, Uchida K, Tsukahara H, Ohno M, Fujita T, Brodsky S, Goligorsky MS - Oxidative and nitrosative stress in acute renal ischemia. Am J Physiol (2001) 281:F948–F957 Cerca con Google

Kelly KJ - Acute renal failure: much more than a kidney disease. Semin Nephrol (2006) 26:105–113 Cerca con Google

76 Kaysen GA - Inflammation and oxidative stress in end-stage renal disease. Adv Nephrol Necker Hosp (2000) 30:201–214 Cerca con Google

Thurman JM - Triggers of inflammation after renal ischemia/reperfusion. Clin Immunol (2007) 123:7–13 Cerca con Google

Dong X, Swaminathan S, Bachman LA, Croatt AJ, Nath KA, Griffin MD – Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury. Kidney Int (2007) 71:619–628 Cerca con Google

Montoliu J - Clearance of inflammatory mediators through continuous renal replacement therapy. Blood Purif (1997) 15:305–308 Cerca con Google

Burne-Taney MJ, Rabb H - The role of adhesion molecules and T cells in ischemic renal injury. Curr Opin Nephrol Hypertens (2003) 12:85–90 Cerca con Google

Viedt C, Dechend R, Fei J, Hansch GM, Kreuzer J, Orth SR - MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-kappaB and activating protein-1. J Am Soc Nephrol (2002) 13:1534–1547 Cerca con Google

Salvemini D, Doyle TM, Cuzzocrea S - Superoxide, peroxinitrite and oxidative/nitrosative stress in inflammation. Biochem Soc Trans (2006) 34:965–970 Cerca con Google

Bonventre JV, Zuk A - Ischemic acute renal failure: an inflammatory disease? Kidney Int (2004) 66:480–485 Cerca con Google

Schindler R - Causes and therapy of microinflammation in renal failure. Nephrol Dial Transplant (2004) 19:V34–V40 Cerca con Google

Bonventre JV - Pathophysiology of acute kidney injury: roles of potential inhibitors of inflammation. Contrib Nephrol (2007) 156:39–46 Cerca con Google

Duffield JS, Hong S, Vaidya VS, Lu Y, Fredman G, Serhan CN, Bonventre JV – Resolvin D series and protectin D1 mitigate acute kidney injury. J Immunol (2006) 177:5902–5911 Cerca con Google

Xie J, Guo Q - Par-4 is a novel mediator of renal tubule cell death in models of ischemiareperfusion injury. Am J Physiol Renal Physiol (2007) 292:F107–F115 Cerca con Google

P. Chowdhury, S.H. Sacks, N.S. Sheerin, Minireview - functions of the renal tract epithelium in coordinating the innate immune response to infection, Kidney Int. (2004) 66 1334– 1344. Cerca con Google

Hye Ryoun Jang, Hamid Rabb - The innate immune response in ischemic acute kidney injury Clinical Immunology (2009) 130: 41–50 Cerca con Google

F. Gueler, J.K. Park, S. Rong, T. Kirsch, C. Lindschau, W. Zheng, M. Elger, A. Fiebeler, D. Fliser, F.C. Luft, H. Haller, Statins attenuate ischemia–reperfusion injury by inducing heme oxygenase-1 in infiltrating macrophages, Am. J. Pathol. (2007) 170:1192–1199. Cerca con Google

J.J. Friedewald, H. Rabb, Inflammatory cells in ischemic acute renal failure, Kidney Int (2004) 66: 486–491. Cerca con Google

X. Dong, S. Swaminathan, L.A. Bachman, A.J. Croatt, K.A. Nath, M.D. Griffin, Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia–reperfusion injury, Kidney Int. (2007) 71: 619–628. Cerca con Google

L. Li, L. Huang, S.S. Sung, P.I. Lobo, M.G. Brown, R.K. Gregg, V.H. Engelhard, M.D. Okusa, NKT cell activation mediates neutrophil IFN-gamma production and renal ischemia– Cerca con Google

reperfusion injury, J. Immunol. (2007) 178:5899–5911. Cerca con Google

N. Yokota, M. Burne-Taney, L. Racusen, H. Rabb, Contrasting roles for STAT4 and STAT6 signal transduction pathways in murine renal ischemia–reperfusion injury, Am. J. Physiol. Renal. Physiol. (2003) 285:F319–F325. Cerca con Google

S. Wang, H. Diao, Q. Guan, W.W. Cruikshank, T.L. Delovitch, A.M. Jevnikar, C. Du, Decreased renal ischemia–reperfusion injury by IL-16 inactivation, Kidney Int. (2008) 73: 318–326. Cerca con Google

J.M. Thurman, D. Ljubanovic, P.A. Royer, D.M. Kraus, H. Molina, N.P. Barry, G. Proctor, M. Levi, V.M. Holers, Altered renal tubular expression of the complement inhibitor Crry permits complement activation after ischemia/reperfusion, J. Clin. Invest. (2006) 116:357–368. Cerca con Google

S. David, L. Biancone, C. Caserta, B. Bussolati, V. Cambi, G. Camussi, Alternative pathway complement activation induces proinflammatory activity in human proximal tubular epithelial cells, Nephrol. Dial. Transplant. (1997) 12:51–56. Cerca con Google

J.C. Leemans, G. Stokman, N. Claessen, K.M. Rouschop, G.J. Teske, C.J. Kirschning, S. Akira, T. van der Poll, J.J. Weening, S. Florquin, Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney, J. Clin. Invest. (2005) 115:2894–2903. Cerca con Google

K. Furuichi, T.Wada, Y. Iwata, S. Kokubo, A. Hara, J. Yamahana, T. Sugaya, Y. Iwakura, K. Matsushima, M. Asano, H. Yokoyama, S. Kaneko, Interleukin-1-dependent sequential chemokine expression and inflammatory cell infiltration in ischemia– reperfusion injury, Crit. Care Med. (2006) 34:2447–2455. Cerca con Google

B. Chandrasekar, J.B. Smith, G.L. Freeman, Ischemia–reperfusion of rat myocardium activates nuclear factor-KappaB and induces neutrophil infiltration via lipopolysaccharide-induced CXC chemokine, Circulation (2001) 103: 2296–2302. Cerca con Google

Antonia Loverre, Pasquale Ditonno, Antonio Crovace, Loreto Gesualdo, Elena Ranieri, Paola Pontrelli, Giovanni Stallone, Barbara Infante, Antonio Schena, Salvatore Di Paolo, Carmen Capobianco, Michele Ursi, Silvano Palazzo, Michele Battaglia, Francesco Paolo Selvaggi, Francesco Paolo Schena and Giuseppe Grandaliano Ischemia-Reperfusion Induces Glomerular and Tubular Activation of Proinflammatory and Antiapoptotic Pathways: Differential Modulation by Rapamycin J Am Soc Nephrol (2004)15: 2675-2686, American Society of Nephrology Cerca con Google

Judith Lechner, Nadia Malloth, Thomas Seppi, Bea Beer, Paul Jennings, and Walter Pfaller IFN- induces barrier destabilization and apoptosis in renal proximal tubular epithelium Am J Physiol Cell Physiol (2007)294: C153-C160, 2008. November, 21 Cerca con Google

Young C.; Tenkova T.; Dikranian K.; Olney J.W. Excitotoxic Versus Apoptotic Mechanisms of Neuronal Cell Death in Perinatal Hypoxia / Ischemia Volume 4, Number 2, March (2004) , pp. 77-85(9) Cerca con Google

S.A. Tisherman, A. Rodriguez and P. Afar, Therapeutic hypothermia in traumatology. Surg Clin North Am (1999), 79:pp. 1269–1289 Cerca con Google

H.T. Hassoun, R.A. Kozar, B.C. Kone, H.J. Safi and F.A. Moore, Intraischemic hypothermia differentially modulates oxidative stress proteins during mesenteric ischemia/reperfusion. Surgery (2002) 132: pp. 369–376. Cerca con Google

M.D. Carattino, F. Cueva, A. Zuccollo, J.L. Monti, M. Navarro and O.L. Catanzaro, Renal ischemia-induced increase in vascular permeability is limited by hypothermia. Immunopharmacology (1999) 43:pp. 241–248. Cerca con Google

R.A. Zager, D.J. Gmur, C.R. Bredl and M.J. Eng, Degree and time sequence of hypothermic protection against experimental ischemic acute renal failure. Circ Res (1989) 65:pp. 1263–1269 Cerca con Google

L.G. Svensson, J.S. Coselli, H.J. Safi, K.R. Hess and E.S. Crawford, Appraisal of adjuncts to prevent acute renal failure after surgery on the thoracic or thoracoabdominal aorta. J Vasc Surg (1989) 10:pp. 230–239 Cerca con Google

Vikram S. Kashyap MD, Richard P. Cambria MD, J.Kenneth Davison MD and Gilbert J. L'Italien PhDRenal failure after thoracoabdominal aortic surgery Eastern Vascular Society, (1997)May 2–4,. Cerca con Google

Basso, D., Pesarin, F., Salmaso, L., Solari, A. Permutation Tests for Stochastic Ordering and ANOVA: Theory and Applications with R. Springer, Heidelberg. (2009). Cerca con Google

111 Pesarin, F. Multivariate Permutation Tests: With Applications in Biostatistics. Wiley, Chichester. (2001). Cerca con Google

Edgington, E.S., Onghena, P. Randomization tests (4th edn). Chapman and Hall, London. (2007). Cerca con Google

Corain, L., Salmaso, L.,. Multivariate and Multistrata Nonparametric Tests: the NPC method. Journal of Modern Applied Statistical Method, (2004)3 :(2), 443–461. Cerca con Google

Blair, R.C., Higgins, J.J., Karnisky, W., Kromrey, J.D.,. A study of multivariate permutation tests which may replace Hotelling’s T2 test in prescribed circumstances. Multivariate Behavior Research, (1994) 29: 141–163. Cerca con Google

Vinuesa E, Hotter G, Jung M, Herrero-Fresneda I, Torras J, Sola A – Acute Heart Inflammation: ultrastructural and functional aspects - J Pathol. 2008 Jan;214(1):104-13. Cerca con Google

E. Hulse, P. E. Kunkler, J. P. Fedynyshyn and R. P. Kraig -Optimization of multiplexed bead-based cytokine immunoassays for rat serum and brain tissue- Journal of Neuroscience Methods Volume 136, Issue 1, 15 June 2004, Pages 87-98 Cerca con Google

Gary Toedter,* Karen Hayden, Carrie Wagner, and Carrie Brodmerkel -Simultaneous Detection of Eight Analytes in Human Serum by Two Commercially Available Platforms for Multiplex Cytokine Analysis Clin Vaccine Immunol. 2008 January; 15(1): 42–48. Cerca con Google

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