Topical hepatic hypothermia plus ischemic preconditioning: analysis of bile flow and ischemic injuries after initial reperfusion in rats

Abstract

Purpose:To evaluate the effects of the topical liver hypothermia and IPC combination against I/R injury after initial reperfusion. Methods: In 32 Wistar rats, partial liver ischemia was induced for 90 minutes in normothermia (IN), ischemic preconditioning (IPC), 26ºC topical hypothermia (H) and 26ºC topical hypothermia plus IPC (H+IPC). MAP, body temperature and bile flow were recorded each 15 minutes. Plasmatic injury markers and tissue antioxidant defenses were assessed after 120 minutes of reperfusion. Results: MAP and body temperature remained constant during all experiment. Bile flow returned to levels similar to controls after 45 minutes of reperfusion in the H and H+IPC groups and increased significantly in comparison to the NI and IPC groups after 105 and 120 minutes. AST and ALT increased significantly in the normothermic groups in comparison to controls. TBARS levels decreased significantly in the H+IPC group in comparison to the other groups whereas Catalase levels increased significantly in the IPC group. SOD levels were significantly higher in the H group in comparison to all groups. Conclusion: The induction of 26ºC topical hypothermia associated or not to IPC protected the ischemic liver against ischemia/reperfusion injuries and allowed an early recovery of the hepatic function. Key words: Ischemia. Reperfusion. Ischemic Preconditioning. Hypothermia. Liver. Rats. RESUMOObjetivo: Avaliar os efeitos da hipotermia hepática tópica combinada ao pré-condicionamento isquêmico na proteção dos danos iniciais de isquemia e reperfusão. Métodos: Trinta e dois ratos Wistar foram submetidos à isquemia hepática parcial durante 90 minutos em Normotermia (IN), Pré-condicionamento Isquêmico (IPC), Hipotermia a 26ºC (H) e Hipotermia a 26ºC mais PCI (H+PCI). A PAM, a temperatura corporal e o fluxo biliar foram aferidos em intervalos de 15 minutos. Marcadores plasmáticos de danos hepáticos e as defesas antioxidantes foram avaliados após 120 minutos de reperfusão. Resultados: A PAM e a temperatura corporal permaneceram constantes durante o experimento. O fluxo biliar retornou a valores semelhantes ao grupo C nos grupos H e H+PCI após 45 minutos de reperfusão e aumentou significativamente nos grupos H e H+PCI em comparação aos grupos IN e PCI após 105 e 120 minutos. Os níveis plasmáticos da AST e ALT demonstraram aumento significativo no grupo IN em comparação ao grupo C. Os níveis de TBARS diminuíram significativamente no grupo H+PCI em comparação aos grupos IN, PCI e H. Os níveis de Catalase aumentaram significativamente no grupo PCI em comparação aos grupos C, IN e H+PCI. Os níveis de SOD foram significativamente maiores no grupo H em comparação aos grupos C, IN, PCI e H+PCI. Conclusão: A hipotermia tópica protegeu o fígado isquêmico contra os danos de isquemia e reperfusão e permitiu uma recuperação precoce da função hepática.

Effects of hypothermia on skeletal ischemia reperfusion injury in rats

“…However, they found no difference in levels of SOD, NO3 (nitrite), or NO2 (nitrate) between hypothermic or normothermic reperfusion in IR kidney injury. Grezzana Filho [22] indicated that hypothermia during reperfusion decreased TBARS levels and increased SOD and CAT in IR liver injury. In our study, the decrease in MDA levels in the hypothermia group compared with that in the IR group was consistent with the above studies that showed hypothermia reduced reperfusion injury.…”

Assessment of effects of IR and IPC on activities of cytochrome P450 isozymes in rats by a five-drug cocktail approach

“…IPC has been shown to protect organs against subsequent sustained ischemia. In the liver, IPC is a promising strategy in assisting preservation of the liver in clinical situations of anticipated hepatic ischemia such as transplantation and improving outcome after surgical procedures 18 . Drug metabolism and elimination is frequently altered in patients with liver disease and one major reason is believed to be the impaired activity of hepatic microsomal drug metabolizing enzymes 19 .…”

Rodent models of hepatic ischemia–reperfusion injury: time and percentage-related pathophysiological mechanisms

“…The rise may be noted even after 30 min of reperfusion, it peaks at 6 h (5393 IU/L) or 12 h (2985 IU/L) [49] and later declines, but still remains high after 24 h of reperfusion [49,50]. At 120 min of reperfusion, ALT has been found to be 4660 IU/L [51]. Serum AST levels also rise at 2 h (3910 IU/L) [52], 5 h and 24 h of reperfusion [49].…”

“…On the other hand, NO levels are high after 90 min of ischemia and they remain increased 4-fold (42 mM) even after 24 h [50]. Moreover, after 90 min of ischemia the peroxide levels augment and maximize after 10 min of reperfusion [51]. Furthermore, high mobility group box 1, an early mediator in inflammation and organ injury, augments as early as 30 min, up to 24 h after reperfusion; messenger RNA (mRNA) expression of high mobility group box 1's receptors RAGE (receptor for advanced glycation endproducts) and TLR-4 is high even 24 h after reperfusion.…”

“…Histologically, hemorrhage [50], substantial hepatocellular necrosis [52,53], swelling of hepatocytes [53], slight sinusoidal dilation [53,54] sinusoidal congestion in the centrilobular regions [50], severe cytoplasmic vacuolization [53,54], neutrophilic infiltrates [52] and polymorphonuclear leukocyte infiltration throughout the necrotic areas and sinusoidal spaces [50] are observed. In addition, mean arterial pressure rises and remains high [51]. Mitochondrial enlargement rate is high.…”