McDonagh P F, Hokama J Y, Copeland J G, Reynolds J M
Section of Cardiovascular and Thoracic Surgery, College of Medicine, University of Arizona, Tucson 85724, USA.
Diabetes. 1997 Nov;46(11):1859-67. doi: 10.2337/diab.46.11.1859.
Cardiovascular disease is excessive in diabetes, and blood cell function is altered. It is not clear, however, if alterations in the blood contribute to the excessive cardiovascular complications of this disease. In this study, we compared the contribution of nondiabetic and diabetic blood to myocardial reperfusion injury. The recovery of cardiac contractile function following no-flow ischemia was studied in isolated diabetic and nondiabetic rat hearts perfused with diabetic or nondiabetic diluted whole blood. Hearts were isolated from 10- to 12-week-old diabetic (streptozotocin, 65 mg/kg, i.v.) and nondiabetic rats and perfused with a Krebs-albumin-red cell solution (K2RBC, Hct 20%). After a 30-min pre-ischemic control period, during which cardiac pump function was evaluated, diabetic and nondiabetic hearts were perfused for 5 min with diluted whole blood (DWB; Hct 20%) collected from either diabetic or nondiabetic donor animals. Coronary flow was then stopped and the hearts subjected to 30 min of no-flow ischemia. Following ischemia, the hearts were reperfused with the K2RBC perfusate. Cardiac contractile function was evaluated throughout the 60-min reperfusion period. Six groups were studied: diabetic and nondiabetic hearts perfused before ischemia with either K2RBC, nondiabetic DWB (NDDWB), or diabetic DWB (DDWB). Perfusion with DWB prior to ischemia impaired the recovery of contractile function in all cases. The impairment to recovery was greater with DDWB than with NDDWB. Although diabetic hearts perfused with K2RBC throughout recovered quite well, the effect of DDWB perfusion in the diabetic hearts was dramatic. In an effort to determine why diabetic blood impaired functional recovery, measures of blood filterability and the generation of reactive oxygen species (ROS) were made. We found that diabetic blood was less filterable than nondiabetic blood; that is, the diabetic blood cells tended to plug the 5-microm filter pores more readily than the nondiabetic blood cells. Also, we found that the diabetic blood was capable of generating significantly greater ROS (oxygen free radicals) than nondiabetic blood (P < 0.05). These findings suggest that the blood contribution to myocardial reperfusion injury is amplified in diabetes. A tendency for diabetic blood cells to plug capillary-sized pores and show enhanced oxygen free radical production may account for the excessive contribution of diabetic blood to reperfusion injury in the heart.
心血管疾病在糖尿病患者中较为常见，且血细胞功能会发生改变。然而，血液的变化是否会导致该疾病过多的心血管并发症尚不清楚。在本研究中，我们比较了非糖尿病血液和糖尿病血液对心肌再灌注损伤的影响。在分离的糖尿病和非糖尿病大鼠心脏中，用糖尿病或非糖尿病稀释全血灌注，研究无血流缺血后心脏收缩功能的恢复情况。从10至12周龄的糖尿病（链脲佐菌素，65mg/kg，静脉注射）和非糖尿病大鼠中分离心脏，并用Krebs-白蛋白-红细胞溶液（K2RBC，血细胞比容20%）灌注。在30分钟的缺血前对照期（在此期间评估心脏泵功能）后，糖尿病和非糖尿病心脏用从糖尿病或非糖尿病供体动物收集的稀释全血（DWB；血细胞比容20%）灌注5分钟。然后停止冠状动脉血流，使心脏经历30分钟的无血流缺血。缺血后，心脏用K2RBC灌注液再灌注。在整个60分钟的再灌注期评估心脏收缩功能。研究了六组：缺血前用K2RBC、非糖尿病DWB（NDDWB）或糖尿病DWB（DDWB）灌注的糖尿病和非糖尿病心脏。缺血前用DWB灌注在所有情况下都会损害收缩功能的恢复。DDWB对恢复的损害比NDDWB更大。尽管全程用K2RBC灌注的糖尿病心脏恢复得相当好，但DDWB灌注对糖尿病心脏的影响却很显著。为了确定糖尿病血液为何会损害功能恢复，我们检测了血液滤过性和活性氧（ROS）的生成情况。我们发现糖尿病血液的滤过性低于非糖尿病血液；也就是说，糖尿病血细胞比非糖尿病血细胞更容易堵塞5微米的滤孔。此外，我们发现糖尿病血液比非糖尿病血液能产生显著更多的ROS（氧自由基）（P<0.05）。这些发现表明，在糖尿病中血液对心肌再灌注损伤的影响会放大。糖尿病血细胞堵塞毛细血管大小孔的倾向以及氧自由基生成增加，可能解释了糖尿病血液对心脏再灌注损伤的过度影响。
