Endothelium-derived hyperpolarization factor (EDHF) is up-regulated in a pig model of acute liver failure

Ekse, Sveinung; Revhaug, Arthur; Ytrebø, Lars Marius

doi:10.1080/00365520600930636

Cited by 2 publications

(1 citation statement)

References 39 publications

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“…These include (1) metabolites of the cytochrome P450 pathway, such as an epoxyeicosatrienoic acid (EET); (2) the monovalent cation K + ; (3) hydrogen peroxide; and (4) C-natriuretic peptide [3]. In addition, the effect of many other well-characterized vasodilatory mechanisms, such as NO, PGI 2 , and carbon monoxide, has been shown to be at least partly mediated via opening of potassium channels on VSMC and thereby induce hyperpolarization [20].…”

Section: Discussionmentioning

confidence: 99%

Adenosine instead of supranormal potassium in cardioplegic solution preserves endothelium-derived hyperpolarization factor-dependent vasodilation☆

Jakobsen

Stenberg

Losvik

et al. 2008

European Journal of Cardio-Thoracic Surgery

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Objective: We have recently shown that adenosine instead of supranormal potassium in cold crystalloid cardioplegia improves cardioprotection. Studies indicate that hyperkalemia has unfavorable effects on vascular endothelial function. Three pathways have been identified as major vasodilatory pathways: the nitric oxide (NO) pathway, the cyclooxygenase (COX) pathway, and the endothelium-derived hyperpolarization (EDHF) pathway, where the EDHF pathway, in particular, seems susceptible to hyperkalemia. We hypothesized that adenosine cardioplegia improves postcardioplegic endothelial function. Methods: Sixteen pigs were randomized to receive either cold (6 8C) hyperkalemic cardioplegia (n = 8) or cardioplegia where hyperkalemia was substituted with 1.2 mM adenosine (n = 8). After 1 h of cold ischemic arrest, coronary blood flow was monitored for the following 2 h. The LAD artery was then explanted, and cylindrical rings were mounted for isometric tension recordings in organ chambers. Vessels were preconstricted with U46610 (Thromboxane A 2 analog) and then bradykinin-mediated relaxation was investigated. To differentiate between the vasodilatory pathways the relaxation was assessed in the absence and presence of inhibitors of the COX (indomethacin), NO (L-NAME + carboxy-PTIO), and EDHF (apamin + charybdotoxin) pathways. Results: In vivo: The adenosine group had, as distinct from the hyperkalemic group, a significantly increased coronary blood flow index 1 h after cross-clamp release (from (ml/min/100 g, mean AE SD) 50.9 AE 13.9 to 72.8 AE 21.9, p = 0.010). The difference was, however, not statistically significant between groups. In vitro: Maximal relaxation without blockers was 27.4 AE 10.1% of maximal tension in the adenosine group and 22.2 AE 7.5% in the hyperkalemic group. To investigate EDHFdependent vasodilation the vessel rings were simultaneously treated with indomethacin, L-NAME, and carboxy-PTIO. Maximal relaxation in the hyperkalemic group was then reduced to 47.4 AE 17.4% of maximal tension, which was a significant reduction compared to the adenosine group with a maximal relaxation of 20.6 AE 8.7% ( p = 0.028). Conclusion: Adenosine instead of supranormal potassium in cold crystalloid cardioplegia increases postcardioplegic myocardial blood flow and preserves EDHF-dependent vasodilation. #

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Section: Discussionmentioning

confidence: 99%

Adenosine instead of supranormal potassium in cardioplegic solution preserves endothelium-derived hyperpolarization factor-dependent vasodilation☆

Jakobsen

Stenberg

Losvik

et al. 2008

European Journal of Cardio-Thoracic Surgery

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An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

Tuñón¹,

Álvarez²,

Culebras³

et al. 2009

WJG

175

101

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Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.

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Endothelium-derived hyperpolarization factor (EDHF) is up-regulated in a pig model of acute liver failure

Abstract: Endothelium dependent hyperpolarization of vascular smooth muscle contributes to the development of hyperdynamic circulation in ALF.

Cited by 2 publications

References 39 publications

Adenosine instead of supranormal potassium in cardioplegic solution preserves endothelium-derived hyperpolarization factor-dependent vasodilation☆

Adenosine instead of supranormal potassium in cardioplegic solution preserves endothelium-derived hyperpolarization factor-dependent vasodilation☆

An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

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