Dataset Information

Moderate Hypothermia Provides Better Protection of the Intestinal Barrier than Deep Hypothermia during Circulatory Arrest in a Piglet Model: A Microdialysis Study.

ABSTRACT:

Introduction

This study aimed to assess the effects of different temperature settings of hypothermic circulatory arrest (HCA) on intestinal barrier function in a piglet model.

Methods

Twenty Wuzhishan piglets were randomly assigned to 40 min of HCA at 18°C (DHCA group, n = 5), 40 min of HCA at 24°C (MHCA group, n = 5), normothermic cardiopulmonary bypass (CPB group, n = 5) or sham operation (SO group, n = 5). Serum D-lactate (SDL) and lipopolysaccharide (LPS) levels were determined. Microdialysis parameters (glucose, lactate, pyruvate and glycerol) in the intestinal dialysate were measured. After 180 min of reperfusion, intestinal samples were harvested for real-time polymerase chain reaction and western blotting measurements for E-cadherin and Claudin-1.

Results

Higher levels of SDL and LPS were detected in the DHCA group than in the MHCA group (P < 0.001). Both MHCA and DHCA groups exhibited lower glucose levels, higher lactate and glycerol levels and a higher lactate to pyruvate (L/P) ratio compared with the CPB group (p<0.05); the DHCA group had higher lactate and glycerol levels and a higher L/P ratio (p<0.05) but similar glucose levels compared to the MHCA group. No significant differences in E-cadherin mRNA or protein levels were noted. Upregulation of claudin-1 mRNA levels was detected in both the DHCA and MHCA animals' intestines (P < 0.01), but only the DHCA group exhibited a decrease in claudin-1 protein expression (P < 0.01).

Conclusion

HCA altered the energy metabolism and expression of epithelial junctions in the intestine. Moderate hypothermia (24°C) was less detrimental to the markers of normal functioning of the intestinal barrier than deep hypothermia (18°C).

SUBMITTER: Liang M

PROVIDER: S-EPMC5042434 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Moderate Hypothermia Provides Better Protection of the Intestinal Barrier than Deep Hypothermia during Circulatory Arrest in a Piglet Model: A Microdialysis Study.

Liang Mengya M Feng Kangni K Yang Xiao X Chen Guangxian G Tang Zhixian Z Lin Weibin W Rong Jian J Wu Zhongkai Z

PloS one 20160929 9

<h4>Introduction</h4>This study aimed to assess the effects of different temperature settings of hypothermic circulatory arrest (HCA) on intestinal barrier function in a piglet model.<h4>Methods</h4>Twenty Wuzhishan piglets were randomly assigned to 40 min of HCA at 18°C (DHCA group, n = 5), 40 min of HCA at 24°C (MHCA group, n = 5), normothermic cardiopulmonary bypass (CPB group, n = 5) or sham operation (SO group, n = 5). Serum D-lactate (SDL) and lipopolysaccharide (LPS) levels were determine ...[more]

PMID: 27685257

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Project description:BACKGROUND:Various studies evaluated the relationship between hypothermic circulatory arrest and neurological outcome in patients undergoing replacement of ascending aorta. The current analysis focuses on the effect of moderate hypothermic circulatory arrest (MHCA) on elderly patients. The aim of our study was to evaluate the impact of MHCA on neurological outcomes in elderly patients undergoing replacement of the ascending aorta. RESULTS:We retrospectively analyzed 905 consecutive patients, who underwent elective replacement of ascending aorta in MHCA (24?±?2?°C, nasopharyngeal) between 2001 and 2015. Patients with acute aortic dissection were excluded from this study. Patients were divided into two groups: those aged 75?years and older (elderly group 22.4%, n?=?203) and those younger than 75?years (younger group 77.6%, n?=?702). The average age was 63.2?±?10.2 in the young group vs. 78.7?±?3.0?years in elderly group (p?<?0.001). The elderly group had a significantly higher EuroSCORE II [26.7% (18.1, 36.3) vs. 11.6% (7.4, 19.9); p?<?0.001)]. The incidence of coronary heart disease (49.8% vs. 35.6%, p?<?0.001) and chronic renal failure (17.2% vs. 9.1%, p?=?0.001) was significantly higher in the elderly group. Intraoperatively, the time of MHCA [14?min (12, 17) vs. 15?min (12, 18); p?=?0.42], cardiopulmonary bypass [139?min (110, 183) vs. 144?min (113, 189); p?=?0.225], and cross-clamping [91?min (63, 116) vs. 92?min (65, 127); p?=?0.348] was similar in both groups. Postoperatively, a higher incidence of delirium was significantly reported in the elderly group (24.1% vs. 9.0%, p?<?0.001). However, there was no significant difference regarding neurological complications between both groups. A 30-day mortality was acceptable for the elderly group, but significantly higher compared with the younger group (7.1% vs. 3.5%, p?=?0.031). CONCLUSIONS:Our study suggests that surgical replacement of the ascending aorta in MHCA can also be applied safely in elderly patients without increasing the risk of severe neurological complications.

Project description:As therapeutic hypothermia is only partially protective for neonatal encephalopathy, safe and effective adjunct therapies are urgently needed. Melatonin and erythropoietin show promise as safe and effective neuroprotective therapies. We hypothesized that melatonin and erythropoietin individually augment 12-h hypothermia (double therapies) and hypothermia + melatonin + erythropoietin (triple therapy) leads to optimal brain protection. Following carotid artery occlusion and hypoxia, 49 male piglets (<48 h old) were randomized to: (i) hypothermia + vehicle (n = 12), (ii) hypothermia + melatonin (20 mg/kg over 2 h) (n = 12), (iii) hypothermia + erythropoietin (3000 U/kg bolus) (n = 13) or (iv) triple therapy (n = 12). Melatonin, erythropoietin or vehicle were given at 1, 24 and 48 h after hypoxia-ischaemia. Hypoxia-ischaemia severity was similar across groups. Therapeutic levels were achieved 3 hours after hypoxia-ischaemia for melatonin (15-30 mg/l) and within 30 min of erythropoietin administration (maximum concentration 10 000 mU/ml). Compared to hypothermia + vehicle, we observed faster amplitude-integrated EEG recovery from 25 to 30 h with hypothermia + melatonin (P = 0.02) and hypothermia + erythropoietin (P = 0.033) and from 55 to 60 h with triple therapy (P = 0.042). Magnetic resonance spectroscopy lactate/N-acetyl aspartate peak ratio was lower at 66 h in hypothermia + melatonin (P = 0.012) and triple therapy (P = 0.032). With hypothermia + melatonin, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells were reduced in sensorimotor cortex (P = 0.017) and oligodendrocyte transcription factor 2 labelled-positive counts increased in hippocampus (P = 0.014) and periventricular white matter (P = 0.039). There was no reduction in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells with hypothermia + erythropoietin, but increased oligodendrocyte transcription factor 2 labelled-positive cells in 5 of 8 brain regions (P < 0.05). Overall, melatonin and erythropoietin were safe and effective adjunct therapies to hypothermia. Hypothermia + melatonin double therapy led to faster amplitude-integrated EEG recovery, amelioration of lactate/N-acetyl aspartate rise and reduction in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells in the sensorimotor cortex. Hypothermia + erythropoietin double therapy was in association with EEG recovery and was most effective in promoting oligodendrocyte survival. Triple therapy provided no added benefit over the double therapies in this 72-h study. Melatonin and erythropoietin influenced cell death and oligodendrocyte survival differently, reflecting distinct neuroprotective mechanisms which may become more visible with longer-term studies. Staggering the administration of therapies with early melatonin and later erythropoietin (after hypothermia) may provide better protection; each therapy has complementary actions which may be time critical during the neurotoxic cascade after hypoxia-ischaemia.

Dataset Information

Moderate Hypothermia Provides Better Protection of the Intestinal Barrier than Deep Hypothermia during Circulatory Arrest in a Piglet Model: A Microdialysis Study.

Introduction

Methods

Results

Conclusion

Publications

Moderate Hypothermia Provides Better Protection of the Intestinal Barrier than Deep Hypothermia during Circulatory Arrest in a Piglet Model: A Microdialysis Study.

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