Kop Willem J, Galvao Tatiana F, Synowski Stephen J, Xu Wenhong, Can Adem, O'Shea Karen M, Gould Todd D, Stanley William C
Department of Medicine, Division of Cardiology, University of Maryland, Baltimore, MD, USA; Department of Medical and Clinical Psychology, Center of Research on Psychology in Somatic diseases (CoRPS), Tilburg University, Tilburg, The Netherlands.
Department of Medicine, Division of Cardiology, University of Maryland, Baltimore, MD, USA; Intensive Care Unit, Hospital Israelita Albert Einstein, Sao Paulo, Brazil;
Physiol Behav. 2015 Dec 1;152(Pt A):168-74. doi: 10.1016/j.physbeh.2015.09.024. Epub 2015 Sep 28.
Heart failure (HF) prognosis is negatively influenced by adverse environmental conditions associated with psychological distress and depression. The underlying mechanisms are not well understood because of insufficient experimental control in prior clinical and epidemiological studies. Using a validated animal model we examined whether distress-producing environmental manipulations (social isolation and crowding) increase HF progression following myocardial infarction (MI).
MI was induced using coronary artery ligation in 8-week old male Wistar rats (N=52) and results were compared to sham surgery (N=24). Housing conditions were randomly assigned at 5 days post MI or sham surgery (1/cage=isolation, 2/cage=standard reference condition, or 4/cage=crowding) and continued for 17 weeks until the end of observation. The open field test was used to test behavioral responses. Echocardiograms were obtained at weeks 8 and 16, and left ventricular (LV) weight at week 17.
Housing conditions increased behavioral markers of distress (p=0.046) with the strongest effects for the isolated (1/cage) (p=0.022). MI did not increase distress-related behaviors compared to sham. MI-surgery resulted in characteristic HF indices (left ventricular ejection fraction (LVEF) at week 16=46 ± 12% vs. 80 ± 7% in sham, p<0.001). Housing condition was not related to LVEF or LV weight (p>0.10).
Adverse environmental conditions, particularly isolated housing, produce increases in some of the behavioral indicators of distress. No effects of housing were found on post-MI progression of HF. The distress-HF associations observed in humans may therefore reflect common underlying factors rather than an independent causal pathway. Stronger environmental challenges may be needed in future animal research examining distress as related HF progression.
心力衰竭(HF)的预后受到与心理困扰和抑郁相关的不良环境条件的负面影响。由于先前临床和流行病学研究中的实验控制不足,其潜在机制尚未得到充分理解。我们使用经过验证的动物模型,研究了产生困扰的环境操纵(社会隔离和拥挤)是否会加速心肌梗死(MI)后的HF进展。
在8周龄雄性Wistar大鼠(N = 52)中使用冠状动脉结扎诱导MI,并将结果与假手术(N = 24)进行比较。在MI或假手术后5天随机分配饲养条件(1只/笼 = 隔离,2只/笼 = 标准参考条件,或4只/笼 = 拥挤),并持续17周直至观察结束。使用旷场试验测试行为反应。在第8周和第16周获得超声心动图,在第17周获得左心室(LV)重量。
饲养条件增加了困扰的行为指标(p = 0.046),其中隔离组(1只/笼)的影响最强(p = 0.022)。与假手术相比,MI并未增加与困扰相关的行为。MI手术导致了典型的HF指标(第16周时左心室射血分数(LVEF)= 46 ± 12%,而假手术组为80 ± 7%,p < 0.001)。饲养条件与LVEF或LV重量无关(p > 0.10)。
不良环境条件,特别是隔离饲养,会导致一些困扰行为指标增加。未发现饲养条件对MI后HF进展有影响。因此,在人类中观察到的困扰与HF的关联可能反映了共同的潜在因素,而非独立的因果途径。在未来研究困扰与HF进展关系的动物研究中,可能需要更强的环境挑战。