[Experimental study on influence of ischemia-reperfusion on expression of hyperpolarization activated cyclic nucleotide gated cation channel 4 of sinoatrial node cells in rabbits in vivo].

Abstract

OBJECTIVE:

To study the influence of ischemia-reperfusion on the expression of the hyperpolarization activated cyclic nucleotide gated cation channel 4 (HCN4) and to discuss the mechanism of functional disturbance of sinoatrial node tissue (SANT) after ischemia reperfusion injury (IRI).

METHODS:

Eighty five healthy adult rabbits, weighing 2-3 kg, were randomly divided into 3 groups: control group [a suture passed under the root section of right coronary artery (RCA) without ligation, n=5], experimental group A (occluding the root section of RCA for 30 minutes, then loosening the root 2, 4, 8 and 16 hours, n=10), experimental group B (occluding the root section of RCA for 1 hour, then loosening the root 2, 4, 8 and 16 hours, n=10). At the end of the reperfusion, the SANT was cut off to do histopathological, transmission electron microscopical and immunohistochemical examinations and semi-quantitative analysis.

RESULTS:

The result of HE staining showed that patho-injure of sinoatrial node cell (SANC) happened in experimental groups A and B after 2 hours of reperfusion, the longer the reperfusion time was, the more serious patho-injure of SANC was after 4 and 8 hours of reperfusion, SANC reached peak of damage after 8 to 16 hours of reperfusion; patho-injure of SANC was more serious in experimental group B than in experimental group A at the same reperfusion time. Immunohistochemical staining showed that the expression of HCN4 located in cellular membrane and cytoplasm in the central area of SANC and gradually decreased from the center to borderline. The integral absorbance values of HCN4 expression in the control group (397.40 +/- 34.11) was significantly higher than those in the experimental group A (306.20 +/- 35.77, 216.60 +/- 18.59, 155.40 +/- 19.11 and 135.00 +/- 12.30) and in the experimental group B (253.70 +/- 35.66, 138.70 +/- 13.28, 79.10 +/- 9.60 and 69.20 +/- 8.42) after 2, 4, 8 and 16 hours of reperfusion (P < 0.05). With reperfusion time, the expression of HCN4 of SANC decreased, which was lowest after 8 hours of reperfusion; showing significant difference among 2, 4 and 8 hours after reperfusion (P < 0.05) and no significant difference between 8 and 16 hours after reperfusion (P > 0.05). At the same reperfusion time, the expression of HCN4 was higher in the experimental group A than in the experimental group B. The result of transmission electron microscope showed that ultramicrostructure of SANC was damaged after reperfusion in experimental groups A and B. The longer the reperfusion time was, the more serious ultramicrostructure damage of SANC was, and reached the peak of damage after 8 hours of reperfusion. Ultramicrostructure of SANC was not different between 8 and 16 hours of reperfusion. At the same reperfusion time, the ultramicrostructure damage of SANC was more serious in experimental group B than in experimental group A.

CONCLUSION:

IRI is harmful to the morphous and structure of SANC, and effects the expression of HCN4 of SANC, which is concerned with functional disturbance and arrhythmia.

• Authors: Yong Fu, Bin Liao, Fengxu Yu, Mingbin Deng, Zhiqiang Feng, Fusheng Zhan, Xin Li, Juyi Wan
• Journal: Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery (Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi) Vol. 23 Issue 7 Pg. 856-60 (Jul 2009) ISSN: 1002-1892 [Print] China
• PMID: 19662993 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic Nucleotide-Gated Cation Channels

Topics

• Animals
• Cyclic Nucleotide-Gated Cation Channels (metabolism)
• Female
• Male
• Rabbits
• Reperfusion Injury (metabolism, pathology)
• Sinoatrial Node (cytology, metabolism, ultrastructure)