Di Petta Antonio, Simas Rafael, Ferreira Clebson L, Capelozzi Vera L, Salemi Vera M C, Moreira Luiz F P, Sannomiya Paulina
Heart Institute (InCor), LIM-11, University of São Paulo Medical School, São Paulo, SP, Brazil.
Department of Pathology, University of São Paulo Medical School, São Paulo, SP, Brazil.
Int J Exp Pathol. 2015 Oct;96(5):350-7. doi: 10.1111/iep.12146. Epub 2015 Oct 29.
Chronic obstructive pulmonary disease is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate the effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats. Wistar rats were divided into control non-diabetic instilled with saline (CS) or elastase (CE), diabetic instilled with saline (DS) or elastase (DE), DE treated with insulin (DEI) groups and echocardiographic measurements, morphometric analyses of the heart and lungs, and survival analysis conducted 50 days after instillation. Diabetes mellitus was induced [alloxan, 42 mg/kg, intravenously (iv)] 10 days before the induction of emphysema (elastase, 0.25 IU/100 g). Rats were treated with NPH insulin (4 IU before elastase plus 2 IU/day, 50 days). Both CE and DE exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in right ventricular (RV) wall thickness (P = 0.0022), cavity area (P = 0.0001) and cardiomyocyte thickness (P = 0.0001). Diabetic saline group demonstrated a reduction in left ventricular (LV) wall, interventricular (IV) septum, cardiomyocyte thickness and an increase in cavity area, associated with a reduction in LV fractional shortening (P < 0.05), and an increase in LViv relaxation time (P < 0.05). Survival rate decreased from 80% in DS group to 40% in DE group. In conclusion, alloxan diabetes did not affect RV hypertrophy secondary to chronic emphysema, even in the presence of insulin. Diabetes per se induced left ventricular dysfunction, which was less evident in the presence of RV hypertrophy. Survival rate was substantially reduced as a consequence, at least in part, of the coexistence of RV hypertrophy and diabetic cardiomyopathy.
慢性阻塞性肺疾病常与心血管疾病、糖尿病和高血压等慢性合并症相关。本研究旨在探讨糖尿病与肺气肿的关联对大鼠心脏结构和功能的影响。将Wistar大鼠分为对照组(非糖尿病,滴注生理盐水,即CS组或滴注弹性蛋白酶,即CE组)、糖尿病组(滴注生理盐水,即DS组或滴注弹性蛋白酶,即DE组)、胰岛素治疗的DE组(即DEI组),并在滴注后50天进行超声心动图测量、心脏和肺的形态学分析以及生存分析。在诱导肺气肿(弹性蛋白酶,0.25 IU/100 g)前10天诱导糖尿病(四氧嘧啶,42 mg/kg,静脉注射)。大鼠用中性鱼精蛋白锌胰岛素治疗(弹性蛋白酶前4 IU加每天2 IU,共50天)。CE组和DE组的平均肺泡直径均有相似增加,且与右心室(RV)壁厚度增加(P = 0.0022)、腔面积增加(P = 0.0001)和心肌细胞厚度增加(P = 0.0001)呈正相关。糖尿病生理盐水组显示左心室(LV)壁、室间隔、心肌细胞厚度减小,腔面积增加,同时LV缩短分数降低(P < 0.05),LViv舒张时间增加(P < 0.05)。DS组的生存率从80%降至DE组的40%。总之,即使存在胰岛素,四氧嘧啶糖尿病也不影响继发于慢性肺气肿的RV肥大。糖尿病本身可诱导左心室功能障碍,在存在RV肥大时这种情况不太明显。生存率大幅降低,至少部分是由于RV肥大和糖尿病性心肌病并存的结果。