Mechanism of the Protective Effects of N-acetylcysteine on the Heart of Brain-Dead Ba-Ma Miniature Pigs

Zhai, Wenlong; Feng, Ruo; Huo, Liang; Li, Jie; Zhang, Shuijun

doi:10.1016/j.healun.2009.05.006

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…More frequent sampling around the induction of BD in future studies will better characterise the time course of ET-1. Small numbers of animals in each group raise the possibility of type 2 error, although pre-clinical animal models have used similar numbers [ 18 , 19 ]. Myoglobin and CK-MB were chosen to assess for cardiac injury in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…Interventions utilised in human BD donors, such as fluid or vasoactive agent administration, may have significant effects on genomic expression of inflammatory mediators [ 16 , 17 ], further limiting the ability of small animal models to replicate comprehensive, modern, intensive care monitoring and management. To begin to address these issues, porcine models have been extended to 24 h [ 18 , 19 ]. Zhai et al .…”

Section: Introductionmentioning

confidence: 99%

“…Zhai et al . investigated hepatic injury after BD in BaMa miniature pigs [ 18 ]. Although this is a valid extended model, the animals were small compared to humans (average of 25 kg), and the use of other clinically relevant interventions, such as vasopressors, inotropes and hormone resuscitation, were not reported.…”

Section: Introductionmentioning

confidence: 99%

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Novel 24-h ovine model of brain death to study the profile of the endothelin axis during cardiopulmonary injury

Watts

Bilska

Diab

et al. 2015

ICMx

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BackgroundUpregulation of the endothelin axis has been observed in pulmonary tissue after brain death, contributing to primary graft dysfunction and ischaemia reperfusion injury. The current study aimed to develop a novel, 24-h, clinically relevant, ovine model of brain death to investigate the profile of the endothelin axis during brain death-associated cardiopulmonary injury. We hypothesised that brain death in sheep would also result in demonstrable injury to other transplantable organs.MethodsTwelve merino cross ewes were randomised into two groups. Following induction of general anaesthesia and placement of invasive monitoring, brain death was induced in six animals by inflation of an extradural catheter. All animals were supported in an intensive care unit environment for 24 h. Animal management reflected current human donor management, including administration of vasopressors, inotropes and hormone resuscitation therapy. Activation of the endothelin axis and transplantable organ injury were assessed using ELISA, immunohistochemistry and standard biochemical markers.ResultsAll animals were successfully supported for 24 h. ELISA suggested early endothelin-1 and big endothelin-1 release, peaking 1 and 6 h after BD, respectively, but there was no difference at 24 h. Immunohistochemistry confirmed the presence of the endothelin axis in pulmonary tissue. Brain dead animals demonstrated tachycardia and hypertension, followed by haemodynamic collapse, typified by a reduction in systemic vascular resistance to 46 ± 1 % of baseline. Mean pulmonary artery pressure rose to 186 ± 20 % of baseline at induction and remained elevated throughout the protocol, reaching 25 ± 2.2 mmHg at 24 h. Right ventricular stroke work increased 25.9 % above baseline by 24 h. Systemic markers of cardiac and hepatocellular injury were significantly elevated, with no evidence of renal dysfunction.ConclusionsThis novel, clinically relevant, ovine model of brain death demonstrated that increased pulmonary artery pressures are observed after brain death. This may contribute to right ventricular dysfunction and pulmonary injury. The development of this model will allow for further investigation of therapeutic strategies to minimise the deleterious effects of brain death on potentially transplantable organs.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-015-0067-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel 24-h ovine model of brain death to study the profile of the endothelin axis during cardiopulmonary injury

Watts

Bilska

Diab

et al. 2015

ICMx

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“…[239] Limitations of the Study numbers. [332,333] Myoglobin and CK-MB were chosen to assess for cardiac injury in the current study. Although troponin may reflect cardiac function in the donor, the correlation between troponin levels and recipient outcome remains controversial.…”

Section: Discussionmentioning

confidence: 99%

The implications of brain death in donor lung injury: investigation and blockade of the endothelin axis

Watts¹

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N-acetylcysteine attenuates neuroinflammation associated depressive behavior induced by chronic unpredictable mild stress in rat

Fernandes

Gupta

2019

Behavioural Brain Research

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Mechanism of the Protective Effects of N-acetylcysteine on the Heart of Brain-Dead Ba-Ma Miniature Pigs

Cited by 6 publications

References 21 publications

Novel 24-h ovine model of brain death to study the profile of the endothelin axis during cardiopulmonary injury

Novel 24-h ovine model of brain death to study the profile of the endothelin axis during cardiopulmonary injury

The implications of brain death in donor lung injury: investigation and blockade of the endothelin axis

N-acetylcysteine attenuates neuroinflammation associated depressive behavior induced by chronic unpredictable mild stress in rat

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