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围手术期胰岛素治疗对轻度肥胖小鼠心脏抑制的影响。

The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice.

作者信息

Boly Chantal A, Eringa Etto C, Bouwman R Arthur, van den Akker Rob F P, de Man Frances S, Schalij Ingrid, Loer Stephan A, Boer Christa, van den Brom Charissa E

机构信息

Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.

出版信息

Cardiovasc Diabetol. 2016 Sep 20;15(1):135. doi: 10.1186/s12933-016-0453-y.

Abstract

BACKGROUND

While most studies focus on cardiovascular morbidity following anesthesia and surgery in excessive obesity, it is unknown whether these intraoperative cardiovascular alterations also occur in milder forms of adiposity without type 2 diabetes and if insulin is a possible treatment to improve intraoperative myocardial performance. In this experimental study we investigated whether mild adiposity without metabolic alterations is already associated with cardiometabolic dysfunction during anesthesia, mechanical ventilation and surgery and whether these myocardial alterations can be neutralized by intraoperative insulin treatment.

METHODS

Mice were fed a western (WD) or control diet (CD) for 4 weeks. After metabolic profiling, mice underwent general anesthesia, mechanical ventilation and surgery. Cardiac function was determined with echocardiography and left-ventricular pressure-volume analysis. Myocardial perfusion was determined with contrast-enhanced echocardiography. WD-fed mice were subsequently treated with insulin by hyperinsulinemic euglycemic clamping followed by the same measurements of cardiac function and perfusion.

RESULTS

Western-type diet feeding led to a 13 % increase in bodyweight, (p < 0.0001) and increased adipose tissue mass, without metabolic alterations. Despite this mild phenotype, WD-fed mice had decreased systolic and diastolic function (end-systolic elastance was 2.0 ± 0.5 versus 4.1 ± 2.4 mmHg/μL, p = 0.01 and diastolic beta was 0.07 ± 0.03 versus 0.04 ± 0.01 mmHg/μL, p = 0.02) compared to CD-fed mice. Ventriculo-arterial coupling and myocardial perfusion were decreased by 48 % (p = 0.003) and 43 % (p = 0.03) respectively. Insulin treatment in WD-fed mice improved echo-derived systolic function (fractional shortening 42 ± 5 % to 46 ± 3, p = 0.05), likely due to decreased afterload, but there was no effect on load-independent measures of systolic function or myocardial perfusion. However, there was a trend towards improved diastolic function after insulin treatment (43 % improvement, p = 0.05) in WD-fed mice.

CONCLUSIONS

Mild adiposity without metabolic alterations already affected cardiac function and perfusion during anesthesia, mechanical ventilation and surgery in mice. Intraoperative insulin may be beneficial to reduce afterload and enhance intraoperative ventricular relaxation, but not to improve ventricular contractility or myocardial perfusion.

摘要

背景

虽然大多数研究聚焦于过度肥胖患者麻醉和手术后的心血管疾病发生率,但尚不清楚这些术中的心血管改变是否也会出现在无2型糖尿病的轻度肥胖患者中,以及胰岛素是否可能是改善术中心肌功能的一种治疗方法。在本实验研究中,我们调查了无代谢改变的轻度肥胖是否在麻醉、机械通气和手术期间就已与心脏代谢功能障碍相关,以及这些心肌改变是否可通过术中胰岛素治疗得到缓解。

方法

将小鼠分为两组,分别给予西式饮食(WD)或对照饮食(CD),持续4周。在进行代谢分析后,对小鼠进行全身麻醉、机械通气和手术。通过超声心动图和左心室压力-容积分析来测定心脏功能。通过造影增强超声心动图来测定心肌灌注。随后,对喂食WD的小鼠进行高胰岛素-正常血糖钳夹胰岛素治疗,之后再次测量心脏功能和灌注。

结果

西式饮食喂养使小鼠体重增加了13%(p < 0.0001),脂肪组织量增加,且无代谢改变。尽管表现为轻度肥胖,但与喂食CD的小鼠相比,喂食WD的小鼠收缩和舒张功能下降(收缩末期弹性为2.0±0.5 vs 4.1±2.4 mmHg/μL,p = 0.01;舒张期β为0.07±0.03 vs 0.04±0.01 mmHg/μL,p = 0.02)。心室动脉耦联和心肌灌注分别下降了48%(p = 0.003)和43%(p = 0.03)。对喂食WD的小鼠进行胰岛素治疗后,超声心动图测得的收缩功能得到改善(缩短分数从42±5%提高到46±3%,p = 0.05),这可能归因于后负荷降低,但对与负荷无关的收缩功能测量指标或心肌灌注无影响。然而,喂食WD的小鼠在胰岛素治疗后舒张功能有改善趋势(改善43%,p = 0.05)。

结论

无代谢改变的轻度肥胖在小鼠麻醉、机械通气和手术期间已影响心脏功能和灌注。术中使用胰岛素可能有助于降低后负荷并增强术中心室舒张,但无助于改善心室收缩力或心肌灌注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0534/5029087/a4ddbb5e9050/12933_2016_453_Fig1_HTML.jpg

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