Myocardial Involvement During Ischemia-Induced Acute Liver Failure in the Pig

Τsaroucha, Athanasia; Chondrogiannis, Constantinos; Mani, A.; Staikou, Chryssoula

doi:10.3109/08941939.2012.705953

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…The clinical evidence is supplemented by results from experimental animal models: porcine ALF models investigating ALF induction by either surgical devascularization of the liver or hepatic ischemia/reperfusion injury showed significantly increased cTnI values compared to baseline, which were not observed in sham-operated controls [ 12 , 13 ]. These results were paralleled by histological findings showing myocardial cell necrosis and edema.…”

Section: Introductionmentioning

confidence: 99%

Acute myocardial injury secondary to severe acute liver failure: A retrospective analysis supported by animal data

et al. 2021

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To investigate whether acute liver failure (ALF) leads to secondary acute myocardial injury, 100 ALF patients that were retrospectively identified in a single center based on ICD 10 codes and 8 rats from an experimental study that died early after bile duct ligation (BDL) were examined. Creatine kinase (CK), creatine kinase-MB isoenzyme (CKMB) and cardiac troponin-I (cTnI) were analyzed as markers of myocardial injury. For histological analysis, hematoxylin-eosin (HE), elastic Van Gieson (EVG), CD41 and myeloperoxidase were used to stain rat hearts. Major adverse cardiac events (MACEs) were a critical factor for mortality (p = 0.037) in human ALF. Deceased patients exhibited higher levels of CKMB than survivors (p = 0.023). CKMB was a predictor of mortality in ALF (p = 0.013). Animals that died early after BDL exhibited increased cTnI, CKMB, tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) levels compared to controls (cTnI: p = 0.011, CKMB: p = 0.008, TNFα: p = 0.003, IL-6: p = 0.006). These animals showed perivascular lesions and wavy fibers, microthrombi and neutrophilic infiltration in the heart. MACEs are decisive for mortality in human ALF, and elevated CKMB values indicate that this might be due to structural myocardial damage. Accordingly, CKMB was found to have predictive value for mortality in ALF. The results are substantiated by data from a rat BDL model demonstrating diffuse myocardial injury.

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Section: Introductionmentioning

confidence: 99%

Acute myocardial injury secondary to severe acute liver failure: A retrospective analysis supported by animal data

et al. 2021

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“…The partial hepatectomy model, usually also involving devascularization, is seldom used because currently there is no unified standard for the volume of removed liver [9]. Ischemic models (complete/transient devascularization) are the most commonly used surgical models at present [10, 11], usually involving a portacaval shunt followed by hepatic artery occlusion and, in many situations, also requiring devascularization of accessory hepatic vessels and occlusion of the common bile duct [9, 11]. In order to control hepatic ischemic time and prolong survival time of the experimental animals, surgical procedures to create this model normally are performed in two or three steps [12].…”

Section: Introductionmentioning

confidence: 99%

Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

Cai

Weng

Feng

et al. 2016

BioMed Research International

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Models using large animals that are suitable for studying artificial liver support system (ALSS) are urgently needed. Presently available acute liver failure (ALF) models mainly involve pigs or dogs. Establishment of current surgical ALF models (hepatectomy/devascularization) requires either very good surgical skills or multistep processes—even multiple stages of surgery. Therefore, it is necessary to develop a simplified surgical method. Here we report a novel simplified surgical ALF model using cynomolgus monkeys. Six monkeys underwent portal-right renal venous shunt combined with common bile duct ligation and transection (PRRS + CBDLT). Postoperatively, the monkeys had progressively increased listlessness, loss of appetite, and obvious jaundice. Blood biochemistry levels (Amm, ALT, AST, TBiL, DBiL, ALP, LDH, CK, and Cr) and prothrombin time (PT) were significantly increased (all P < 0.01) and albumin (ALB) was markedly reduced (P < 0.01) compared with baseline values. Histological examination of liver specimens on postoperative day 10 revealed cholestasis and inflammation. PRRS + CBDLT produced ALF that closely correlated with clinical situations. Compared with other surgical or drug ALF models, ours was simplified and animals were hemodynamically stable. This model could provide a good platform for further research on ALSS, especially regarding their detoxification functions.

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Cardioprotective effects and underlying mechanism of Radix Salvia�miltiorrhiza and Lignum Dalbergia�odorifera in a pig chronic myocardial ischemia model

Lin

Duan

et al. 2018

Int J Mol Med

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Traditional Chinese medicines, including Radix Salvia miltiorrhiza (SM) and Lignum Dalbergia odorifera (DO) extracts, have historically been used to treat myocardial ischemia and other cardiovascular diseases. The volatile oil of DO (DOO) is one of the main components of DO. The aim of the present study was to assess the cardioprotective effects and possible underlying mechanisms of SM-DOO in pigs with ameroid constriction-induced chronic myocardial ischemia. An ameroid constrictor was placed around the left anterior descending coronary artery of pigs to induce chronic myocardial ischemia. At weeks 2, 6 and 8, myocardial injury markers and blood gas levels were detected. At week 8, coronary angiography, echocardiography and hemodynamics analysis were performed to evaluate myocardial function. Following sacrifice, myocardial tissue was collected and subjected to morphological, histopathological and apoptosis assays. Western blotting was used to detect the protein expression of Bcl-2 associated X (Bax), Bcl-2, Akt, phosphorylated (p)-Akt, glycogen synthase kinase (GSK)-3β and p-GSK-3β. It was revealed that SM-DOO treatment following chronic myocardial ischemia significantly downregulated the expression of myocardial injury markers, ameliorated myocardial oxygen consumption, increased collateralization, reduced regional cardiac dysfunction and limited the extent of myocardial damage. Furthermore, the results of an apoptosis assay revealed that the apoptosis rate was decreased, the expression of Bax decreased and Bcl-2 increased, and the ratio of Bcl-2/Bax was increased. Further experiments indicated that treatment with SM-DOO increased the phosphorylation of Akt and GSK-3β. These findings suggest that SM-DOO treatment ameliorates myocardial injury in a chronic myocardial ischemia model, and that the underlying mechanisms responsible may be associated with the activation of the Akt/GSK-3β signal pathway. Thus, experimental evidence that SM-DOO may be an effective drug for the prevention and treatment of chronic myocardial ischemia in clinical applications has been provided.

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Myocardial Involvement During Ischemia-Induced Acute Liver Failure in the Pig

Abstract: In a porcine model of acute liver failure, a significant increase of cTnI serum levels was found, indicating that a subclinical myocardial damage may occur as a result of heart involvement in the multiple organ dysfunction.

Cited by 3 publications

References 29 publications

Acute myocardial injury secondary to severe acute liver failure: A retrospective analysis supported by animal data

Acute myocardial injury secondary to severe acute liver failure: A retrospective analysis supported by animal data

Establishment of a Novel Simplified Surgical Model of Acute Liver Failure in the Cynomolgus Monkey

Cardioprotective effects and underlying mechanism of Radix Salvia�miltiorrhiza and Lignum Dalbergia�odorifera in a pig chronic myocardial ischemia model

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