Riva E, Andreoni G, Bianchi R, Latini R, Luvarà G, Jeremic G, Traquandi C, Tuccinardi L
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Pharmacol Res. 1998 Mar;37(3):233-40. doi: 10.1006/phrs.1998.0290.
We investigated the relationship between left ventricular diastolic function and interstitial collagen content in the endocardium, mesocardium and epicardium of transverse sections of the heart, using an image analysis system in normotensive and hypertensive long-term streptozotocin (STZ) diabetic rats. STZ-induced diabetes was characterised by elevated blood glucose, polyuria, polydypsia and loss of body weight. In vivo systolic blood pressure was 165 +/- 4, 136 +/- 3 and 129 +/- 7 mmHg in hypertensive and normotensive diabetic rats and age-matched controls, respectively. Heart rate was significantly lower (P < 0.01) in diabetic rats (283 +/- 8 and 280 +/- 10 beats min-1 in normotensive and hypertensive rats, respectively) than controls (393 +/- 18 beats min-1). Pressure-volume (P-V) curves were studied in isolated Langendorff perfused hearts at rest and after 20 min global ischaemia and 30 min reperfusion 6 months after induction of diabetes. Left ventricular volumes were significantly smaller in diabetic rats than age-matched controls, but volumes normalised for heart weight were higher in normotensive (by 28%) and hypertensive (by 10%) diabetic rats. Slopes of end-diastolic P-V curves were similar between groups in basal conditions, but left ventricular systolic P-V curves were steeper in normotensive and flatter in hypertensive diabetic hearts. Post-ischaemic left ventricular end-diastolic pressure was significantly higher than the pre-ischaemic value at comparable increments of volume in each group. Collagen content significantly increased in the heart of rats with STZ-diabetes both in the free left ventricular wall and septum, and suggested this may play a role in the cardiac defects in contractility and relaxation in our experimental conditions. These results indicate that diabetes, irrespective of associated hypertension, can cause major changes in cardiac performance and susceptibility to ischaemia and reperfusion.
我们使用图像分析系统，研究了正常血压和高血压长期链脲佐菌素（STZ）糖尿病大鼠心脏横切面的心内膜、心肌中层和心外膜中左心室舒张功能与间质胶原含量之间的关系。STZ诱导的糖尿病表现为血糖升高、多尿、多饮和体重减轻。高血压和正常血压糖尿病大鼠及年龄匹配的对照组的体内收缩压分别为165±4、136±3和129±7 mmHg。糖尿病大鼠的心率显著低于对照组（正常血压和高血压大鼠分别为283±8和280±10次/分钟）（P<0.01），而对照组为393±18次/分钟。在糖尿病诱导6个月后，对离体Langendorff灌注心脏在静息状态下、20分钟全心缺血后和30分钟再灌注后进行压力-容积（P-V）曲线研究。糖尿病大鼠的左心室容积显著小于年龄匹配的对照组，但以心脏重量标准化后的容积在正常血压（高28%）和高血压（高10%）糖尿病大鼠中更高。基础状态下各组之间舒张末期P-V曲线的斜率相似，但正常血压糖尿病心脏的左心室收缩期P-V曲线更陡，高血压糖尿病心脏的更平坦。在每组中，缺血后左心室舒张末期压力在可比的容积增加时显著高于缺血前值。STZ糖尿病大鼠心脏的左心室游离壁和室间隔中的胶原含量显著增加，提示这可能在我们的实验条件下的心脏收缩和舒张缺陷中起作用。这些结果表明，糖尿病，无论是否伴有高血压，均可导致心脏功能以及对缺血和再灌注易感性的重大变化。
