The Effect of Local Delivery of IBMX on the Neointimal Proliferation in Rat Carotid Balloon Injury Model.
10.4070/kcj.1999.29.10.1097
- Author:
Bong Ki LEE
;
Junghan YOON
;
Han Hyo LEE
;
Jang Young KIM
;
Ji Yean KO
;
Seung Hwan LEE
;
Byung Soo YOO
;
Sung Oh HWANG
;
Kyung Hoon CHOE
- Publication Type:Original Article
- Keywords:
IBMX;
Phosphodiesterase inhibitor;
Neointima;
Compensatory remodeling
- MeSH:
1-Methyl-3-isobutylxanthine*;
Angina Pectoris;
Angioplasty, Balloon;
Animals;
Arteries;
Body Weight;
Carotid Arteries;
Carotid Artery, Common;
Catheters;
Dimethyl Sulfoxide;
Formaldehyde;
Humans;
Hyperplasia;
Ketamine;
Male;
Muscle, Smooth, Vascular;
Neointima;
Phenobarbital;
Phosphoric Diester Hydrolases;
Polymers;
Rats*;
Rats, Sprague-Dawley
- From:Korean Circulation Journal
1999;29(10):1097-1104
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Hyperplastic neointima is one of the major mechanisms of restenosis following balloon angioplasty in selected patients with symptomatic angina pectoris. Elevation of cellular cyclic nucleotide levels such as cAMP and cGMP are known to inhibit the proliferation of vascular smooth muscle cells. 3-isobutyl-1-methylxanthine (IBMX) increases intracellular cAMP and cGMP by nonselective inhibition of phosphodiesterases (PDEs). We conducted this study under the hypothesis that local delivery of IBMX could inhibit neointimal hyperplasia after balloon injury of the rat carotid artery. METHODS: Left common carotid artery of 10 week old male Sprague-Dawley rats were subjected to arterial injury by 2F Fogarty balloon catheter. After injury, animals were allocated to the control groups (control 1: injury control and control 2: pluronic gel plus DMSO control) and IBMX group, which received pluronic polymer gel, DMSO and IBMX mixture periadventitially. After 3 weeks, the rats were killed by overdose of ketamine, and the injured left arteries were pressure-fixed with 10% formalin and subjected to histomorphological analysis. RESULTS: Mean body weight of rats was not statistically different among study groups. The mean area of neointima (control group 1:0.28+/-0.05 mm2,Control group 2:0.27+/-0.08 mm2 , IBMX group:0.18+/-0.08 mm2 : p<0.05) and the mean ratio of neointima to medial area[versus (control group 1:1.89+/-0.37, control group 2:1.95+/-0.41, IBMX group: 1.41+/-0.47: p<0.05)] were significantly less in IBMX group. The mean area of external elastic lamina was significantly larger in control group 1 than IBMX group (0.57+/-0.07 mm2 versus 0.47+/-0.10 mm2 ) and mean luminal area showed no significant difference among groups (control group1:0.14+/-0.07 mm2 , control group 2: 0.10+/-0.05 mm2 , control group 3: 0.16+/-0.06 mm2). CONCLUSION: Peri-adventitial single administration of IBMX showed its effectiveness in reducing the neointimal proliferation in rat carotid balloon injury model. Furthermore we observed the positive correlation between intimal area and EELA suggesting vascular remodeling depending on the intima volume.
