| Diabetes mellitus has spread all over the world. Many factors, such as the improvement of living standard and large proportion of aging people, contribute to increased morbidity of diabetes. The amount of diabetes patients will be 2 billions in 2010 and 3 billions in 2015. Diabetes is a risk factor for the high morbidity and mortality in cardiovascular disease. It is important to study the mechanism of diabetic cardiovascular complications. Myocardial ischemic preconditioning (IPC) is a powerful endogenous cardioprotective mechanism against ischemia-reperfusion(I/R)injury. It remains a topic of intensive ongoing investigation. The purpose of this study is to establish IPC modles in Wistar rats and to study the effect of ischemic preconditioning in diabetic hearts.56 healthy male Wistar rats were divided randomly into six groups. ALL rats were subject to open-chest surgery. A ligature was passed below the left anterior descending coronary artery (LAD) to form a snare. In I/R group, the injury was induced by ligation for 30 minutes followed by reperfusion for 1 hour. In IPC group, the LAD of rats were occluded three times each for 5 minutes, followed by reperfusion for 5 minutes (IPC). Arrhythmia corresponding to ischemic injury, heart rate and ST-segment in ECG were recorded continuously throughout the whole test. The activity of plasma creatine kinase (CK) and the concentration of plasma NO, NOS, iNOS were measured after anesthesia , 30 minutes after ischemia and 1 hour after reperfusion. HE and TTC stainings were performed to determine myocardial necrosis at the end of the test. Results1. The effects of ischemic preconditioning in normal rat hearts Compared with that of NDMIR group, In NDMIP group the elevation ofST-segment was decreased (0. 308 + 0. 115 vs 0. 456+0. 122, P<0. 01). The onset of VPC and VT were delayed (551. 88 + 107. 15vs295. 38 + 127. 73sec , P<0. 01;784. 50+159. 71vs394. 86+132. 55sec , P<0. 01, respectively). The durations of VT was decreased (5. 00 + 2. 16vslO. 142 + 2. 911 sec P<0. 01 ) and the incidence of VF was decreased (0vs25% P<0.01) . The ele vation of plasma CK, NO, NOS corresponding to reperfusion injury were reduced significantly (41. 52 + 8. 13 U/L vs61. 64 + 12. 21U/L, P<0. 05, 41. 86±9.89nmol/Lvs24. 27+10. 49 u mol/L , P<0. 01, 49. 48±15. 93 u mol/L v s28. 94 + 11. 42 u mol/L P<0. 05, respectively) .And the myocardial infar ct size were reduced significantly (23. 33 + 8. 98% vs37.16 + 5. 44%, P<0. 01). HE staining showed that the extent of interstitial hyperemia inmyocardial tissue and cloudy swelling of myocardium were attenuated.No fragmentation was found. However, the incidence of VPC during is chemia was not lowerd.2. The effects of ischemic preconditioning in different phases of diabetic hearts1) Compared with DMIR(4w)group, In DMIP(4w)group the onset of VPC was delayed (214. 5±26. 59secvsl42. 7 + 67. 57 sec, P<0. 01 ) and the incidence of VT, VF were decreased (50% vs 70%, P<0.05, 40% vs 50%, P<0. 05 respectively ) The elevation of plasma CK, corresponding to ischemic injury were reduced significantly (58. 71±5. 03 U/L vs73. 36 + 7. 49 U/L, P<0. 05). The concentration of NOS increases significantly (24. 84 + 3. 09 u mol/L vsl8. 70 + 6. 09 P mol/L , P<0. 05) . And the myocardial infarct size were reduced significantly ( 45.55 + 4.39% vs 58.48 ± 8.52% , P<0. 01) . Morphological observation on HE staining slides showed that the interstitial hyperemia was severe. No fragmentation was found. But the incidence of VPC, the onset and duration of VT during ischemia were not lowered. The activity of plasma CK , NOS ,NO during reperfusion were not reduced.2) Compared with DMIR(8w)group, In DMIP(8w)group the ST-segment corresponding to ischemic injury was elevated significantly (0.629+ 0. 061mv vsO. 583 + 0. 059mv , P<0. 05), the onset of VPC and VT were delayed(.214. 5 + 26. 59sec vsl42. 7+67. 57, P<0. 01 , 313.10+80. 99sec vs200. 70 + 97.49 sec, P<0. 05) , but the duration of them were increased significantly. The incidence of VF was increased (80% vs 70%, P<0. 05) . The activity of plasma CK during ischemia injury and reperfusion were increased significantly (145.47 + 46.35 U/L vslll. 36 + 20. 57 U/L , P<0. 05,160. 75±49. 28 U/L vsl23. 71 +23. 10 U/L,P<0. 05, respectivly) . And the myocardial infarct size were increased significantly (70.36 + 8.61% vs63. 10 + 7. 84%, P<0. 05) . The incidence of VPC, the onset and duration of VT, the concentration of NO and NOS had not significant discrimination.3) Compared with DMIR(4w)group, In DMIR(8w)group the ST-segment corresponding to ischemic injury was elevated significantly (0.683 ±0. 059mv vsO. 591+0. 916 mv ,P<0. 05) , the onset of VPC and VT were delayed (36. 90+12. 08sec vsl42. 7 + 67. 57 sec,P<0.01, 200. 70 + 97. 49sec vs305. 14+117.98 sec P<0. 01) , but the duration of them were increased significantly. The concentration of plasma CK during ischemia injury and reperfusion were increased significantly (111. 36±20. 57 vs73. 36 + 7. 49 U/L, P<0. 01, 123.71+23.10 U/L vs 96.38 + 18.56 U/L,P<0. 01, respectivly) . And the myocardial infarct size were increased significantly (63.10±7. 84% vs58. 48+8. 52% , P<0. 05). The myocardial apoptosis rate increased significantly(38. 17±6. 24% vs29. 92 + 6. 08% P<0. 01). The incidence of VPC, the onset and duration of VT, the concentration of NO (12. 62 + 4. 05u mol/L vsl7. 49 + 3. 94 u mol/L P<0. 05) and the activity of plasma NOS during reperfusion decreased significantly. The duration of VT had not significant discrimination. 4) Compared with DMIP(4w)group, In DMIP(8w)group the ST-segment corresponding to ischemic injury was elevated significantly (0.699 ±0. 061mv vs 0. 627±0. 186 mv ,P<0. 05) , the onset of VPC and VT were delayed (78. 90+16. 95sec vs214. 5 + 26. 59 sec, P<0. 01, 313. 10 + 80. 99sec vs348. 89 + 96. 79 sec P<0. 05) , and the duration of them (33. 80±7. 30sec vs324. 18+10. 79 sec P<0. 05) were increased significantly. The concentration of plasma CK during ischemia injury and reperfusion were increased significantly (145.47 + 46.35 U/L vs58. 71+5. 03 U/L, P<0. 01, 160. 75 + 49. 28 U/L vs 84. 49 + 8. 92 U/L, P<0. 01, respectivly) .The concentration of NO (12. 14 + 4. 18u mol/L vs21. 40 + 6. 99 u mol/L P<0. 05) and the activity of plasma NOS during reperfusion(17. 08±l. 71 u mol/L vs28. 13±5. 91 p mol/L P<0. 05) decreased significantly. The duration of VT had not significant discrimination. And the myocardial infarct size were increased significantly (70.36 + 8.61% vs45. 55 + 4. 39% , P<0. 05) ; The myocardial apoptosis rate increased significantly(44.12 + 4.46% vs22. 75 + 12. 45% P<0.01). Conclusions:1. IPC could reduce the severity of ischemia / reperfusion induced arrhythmias and myocardial infarct size , improve cardiac function... |
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