Borges Giulianna R, de Oliveira Mauro, Salgado Helio C, Fazan Rubens
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.
Cardiovasc Diabetol. 2006 Dec 4;5:26. doi: 10.1186/1475-2840-5-26.
In spite of a large amount of studies in anesthetized animals, isolated hearts, and in vitro cardiomyocytes, to our knowledge, myocardial function was never studied in conscious diabetic rats. Myocardial performance and the response to stress caused by dobutamine were examined in conscious rats, fifteen days after the onset of diabetes caused by streptozotocin (STZ). The protective effect of insulin was also investigated in STZ-diabetic rats.
Cardiac contractility and relaxation were evaluated by means of maximum positive (+dP/dtmax) and negative (-dP/dtmax) values of first derivative of left ventricular pressure over time. In addition, it was examined the myocardial response to stress caused by two dosages (1 and 15 mug/kg) of dobutamine. One-way analysis of variance (ANOVA) was used to compare differences among groups, and two-way ANOVA for repeated measure, followed by Tukey post hoc test, to compare the responses to dobutamine. Differences were considered significant if P < 0.05.
Basal mean arterial pressure, heart rate, +dP/dtmax and -dP/dtmax were found decreased in STZ-diabetic rats, but unaltered in control rats treated with vehicle and STZ-diabetic rats treated with insulin. Therefore, insulin prevented the hemodynamic and myocardial function alterations observed in STZ-diabetic rats. Lower dosage of dobutamine increased heart rate, +dP/dtmax and -dP/dtmax only in STZ-diabetic rats, while the higher dosage promoted greater, but similar, responses in the three groups. In conclusion, the results indicate that myocardial function was remarkably attenuated in conscious STZ-diabetic rats. In addition, the lower dosage of dobutamine uncovered a greater responsiveness of the myocardium of STZ-diabetic rats. Insulin preserved myocardial function and the integrity of the response to dobutamine of STZ-diabetic rats.
The present study provides new data from conscious rats showing that the cardiomyopathy of this pathophysiological condition was expressed by low indices of contractility and relaxation. In addition, it was also demonstrated that these pathophysiological features were prevented by the treatment with insulin.
尽管在麻醉动物、离体心脏和体外培养的心肌细胞方面已有大量研究，但据我们所知，尚未对清醒的糖尿病大鼠的心肌功能进行过研究。在链脲佐菌素（STZ）诱导糖尿病发病15天后，对清醒大鼠的心肌性能以及对多巴酚丁胺引起的应激反应进行了检查。还研究了胰岛素对STZ诱导的糖尿病大鼠的保护作用。
通过左心室压力随时间的一阶导数的最大正值（+dP/dtmax）和最大负值（-dP/dtmax）来评估心脏的收缩性和舒张性。此外，还检测了两种剂量（1和15μg/kg）多巴酚丁胺引起的心肌应激反应。采用单因素方差分析（ANOVA）比较组间差异，采用重复测量的双因素方差分析，随后进行Tukey事后检验，以比较对多巴酚丁胺的反应。如果P<0.05，则认为差异具有统计学意义。
发现STZ诱导的糖尿病大鼠的基础平均动脉压、心率、+dP/dtmax和 -dP/dtmax降低，但在用赋形剂处理的对照大鼠和用胰岛素处理的STZ诱导的糖尿病大鼠中未发生改变。因此，胰岛素可预防STZ诱导的糖尿病大鼠中观察到的血流动力学和心肌功能改变。较低剂量的多巴酚丁胺仅使STZ诱导的糖尿病大鼠的心率、+dP/dtmax和 -dP/dtmax增加，而较高剂量在三组中引起更大但相似的反应。总之，结果表明清醒的STZ诱导的糖尿病大鼠的心肌功能明显减弱。此外，较低剂量的多巴酚丁胺揭示了STZ诱导的糖尿病大鼠心肌的更大反应性。胰岛素保留了STZ诱导的糖尿病大鼠的心肌功能以及对多巴酚丁胺反应的完整性。
本研究提供了来自清醒大鼠的新数据，表明这种病理生理状态下的心肌病表现为收缩性和舒张性指标较低。此外，还证明了胰岛素治疗可预防这些病理生理特征。
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