BACKGROUND AND OBJECTIVES: Antiarrhythmic effect of renal denervation (RDN) after acute myocardial infarction (AMI) remains unclear. The goal of this study was to evaluate the effect of RDN on ventricular arrhythmia (VA) after AMI in a porcine model.METHODS: Twenty pigs were randomly divided into 2 groups based on RDN (RDN, n=10; Sham, n=10). After implanting a loop recorder, AMI was induced by occlusion of the middle left anterior descending coronary artery. Catheter-based RDN was performed for each renal artery immediately after creating AMI. Sham procedure used the same method, but a radiofrequency current was not delivered. Electrocardiography was monitored for 1 hour to observe VA. One week later, the animals were euthanized and the loop recorder data were analyzed.RESULTS: Ventricular fibrillation event rate and the interval from AMI creation to first VA in acute phase were not different between the 2 groups. However, the incidence of premature ventricular complex (PVC) was lower in the RDN than in the Sham. Additionally, RDN inhibited prolongation of the corrected QT (QTc) interval after AMI. The frequency of non-sustained or sustained ventricular tachycardia, arrhythmic death was lower in the RDN group in the early period.CONCLUSIONS: RDN reduced the incidence of PVC, inhibited prolongation of the QTc interval, and reduced VA in the early period following an AMI. These results suggest that RDN might be a therapeutic option in patients with electrical instability after AMI.
Animals ; Arrhythmias, Cardiac ; Autonomic Denervation ; Coronary Vessels ; Denervation ; Electrocardiography ; Humans ; Incidence ; Methods ; Myocardial Infarction ; Renal Artery ; Swine ; Tachycardia, Ventricular ; Ventricular Fibrillation ; Ventricular Premature Complexes

BACKGROUND AND OBJECTIVES: Antiarrhythmic effect of renal denervation (RDN) after acute myocardial infarction (AMI) remains unclear. The goal of this study was to evaluate the effect of RDN on ventricular arrhythmia (VA) after AMI in a porcine model. METHODS: Twenty pigs were randomly divided into 2 groups based on RDN (RDN, n=10; Sham, n=10). After implanting a loop recorder, AMI was induced by occlusion of the middle left anterior descending coronary artery. Catheter-based RDN was performed for each renal artery immediately after creating AMI. Sham procedure used the same method, but a radiofrequency current was not delivered. Electrocardiography was monitored for 1 hour to observe VA. One week later, the animals were euthanized and the loop recorder data were analyzed. RESULTS: Ventricular fibrillation event rate and the interval from AMI creation to first VA in acute phase were not different between the 2 groups. However, the incidence of premature ventricular complex (PVC) was lower in the RDN than in the Sham. Additionally, RDN inhibited prolongation of the corrected QT (QTc) interval after AMI. The frequency of non-sustained or sustained ventricular tachycardia, arrhythmic death was lower in the RDN group in the early period. CONCLUSIONS RDN reduced the incidence of PVC, inhibited prolongation of the QTc interval, and reduced VA in the early period following an AMI. These results suggest that RDN might be a therapeutic option in patients with electrical instability after AMI.

BACKGROUND AND OBJECTIVES: We sought to evaluate the effect of the early use of ezetimibe/simvastatin (Vytorin(R)) on arterial healing and endothelialization after the implantation of a drug-eluting stent (DES) in a porcine model of coronary restenosis. MATERIALS AND METHODS: A total of 20 pigs (40 coronary arteries) were randomly allocated to a pretreatment or no treatment group. The pretreatment group (n=20) received oral ezetimibe/simvastatin (10/20 mg) daily for 7 days before stenting and the no pretreatment group (n=20) did not. All pigs were treated with ezetimibe/simvastatin (10/20 mg) daily after stenting for 4 weeks. Stenting was performed using a bare-metal stent (BMS, n=10) and three types of DES: biolimus A9-eluting stent (BES, n=10), zotarolimus-eluting stent (ZES, n=10), and everolimus-eluting stents (EES, n=10). Four weeks later, pigs underwent a follow-up coronary angiography and were sacrificed for histopathologic analysis. RESULTS: There were no significant differences between the pretreatment and no pretreatment groups in the internal elastic lamina area, lumen area, neointima area, stenotic area, injury score, fibrin score, and inflammation score. In both groups, the fibrin score was higher in pigs with DES than in BMS, particularly in ZES and EES. The inflammatory score was not different between DES and BMS. CONCLUSION: In a porcine model of coronary restenosis, pretreatment with ezetimibe/simvastatin before DES implantation failed to improve arterial healing and endothelialization compared to treatment after stenting.
Coronary Angiography ; Coronary Restenosis* ; Drug-Eluting Stents* ; Fibrin ; Follow-Up Studies ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Inflammation ; Neointima ; Stents ; Swine ; Ezetimibe

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.
3-Iodobenzylguanidine ; Angiotensin II Type 1 Receptor Blockers/therapeutic use ; Angiotensin Receptor Antagonists/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Animals ; Anterior Wall Myocardial Infarction/*drug therapy/physiopathology ; Biphenyl Compounds/*therapeutic use ; Cardiotonic Agents/*therapeutic use ; Disease Models, Animal ; Echocardiography ; Fluorodeoxyglucose F18 ; Perindopril/therapeutic use ; Positron-Emission Tomography ; Pyrimidines/*therapeutic use ; Random Allocation ; Swine ; Tetrazoles/*therapeutic use ; Tomography, Emission-Computed, Single-Photon ; Valsartan/therapeutic use ; Ventricular Function, Left/*physiology

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of a stent coated with abciximab and alpha-lipoic acid (ALA) in a porcine coronary overstretch restenosis model. MATERIALS AND METHODS: A total of 10 pigs were randomized into two groups (10 pigs, 10 coronaries in each group) in which the coronary arteries were stented with a dual-coated stent and a bare metal stent (control) by randomization. Stents were deployed with oversizing (stent/artery ratio 1.3 : 1) in the porcine coronary arteries, and histopathology was assessed 28 days after stenting. RESULTS: There was no significant difference in the injury score between the two groups. In the neointima, the lymphohistiocyte count was significantly lower in dual-coat stent group compared with the control stent group (120+/-85 cells vs. 159+/-80 cells, p=0.048). There was no significant difference in the fibrin score between the two groups (0.16+/-0.34 in the dual-coated stent group vs. 0.25+/-0.48 in the control stent group, p=0.446). The neointima area was not significantly different between both groups (1.55+/-0.8 mm2 in dual-coated stent group vs. 1.40+/-0.86 mm2 in the control stent group, p=0.447). CONCLUSION: Although the dual-coated stent with abciximab and ALA showed no significant difference in inhibition of neointimal hyperplasia when compared with the bare metal stent, it was associated with a reduced inflammatory reaction when compared with the control stent in a porcine coronary restenosis model.
Antibodies, Monoclonal ; Antioxidants ; Coronary Restenosis ; Coronary Vessels ; Drug-Eluting Stents ; Fibrin ; Hyperplasia ; Immunoglobulin Fab Fragments ; Neointima ; Platelet Aggregation Inhibitors ; Random Allocation ; Stents ; Swine ; Thioctic Acid

BACKGROUND AND OBJECTIVES: The renin-angiotensin-aldosterone system has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenotic lesions has been proposed. The aim of this study was to determine the anti-proliferative and anti-inflammatory effects of ramiprilat-coated stents in a porcine coronary overstretch restenosis model. SUBJECTS AND METHODS: Pigs were randomized into two groups in which the coronary arteries {16 pigs (16 coronaries in each group)} had a 3.0x17 mm ramiprilat-coated MAC stent or a 3.0x17 mm control MAC stent (AMG, Munich, Germany) implanted with oversizing (stent-to-artery ratio, 1.3 : 1) in porcine coronary arteries, and histopathologic analysis was assessed 28 days after stenting. RESULTS: There were no significant differences in the injury and inflammation scores between the two groups (1.20+/-0.43 vs. 1.23+/-0.57, p=0.8; and 1.21+/-0.39 vs. 1.25+/-0.49, p=0.6, respectively). Within the neointima, most inflammatory cells were lymphohistiocytes. Significant positive correlations existed between inflammatory cell counts and the neointima areas (r=0.567, p<0.001), and between inflammatory cell counts and the percent area stenosis (r=0.478, p<0.001). There was no significant difference in the inflammatory cell counts normalized to the injury (110+/-89 vs. 123+/-83, p=0.4) and fibrin scores (0.15+/-0.06 vs. 0.17+/-0.07, p=0.8) between the 2 groups. There were trends toward a smaller neointima area (1.06+/-0.51 mm2 vs. 1.28+/-0.35 mm2, p=0.083) and a smaller percent area stenosis (18.9+/-8.7% vs. 21.8+/-7.2%, p=0.088) in the ramiprilat-coated stent group. CONCLUSION: Although the ramiprilat-coated stent did not show significant inhibitory effects on neointimal hyperplasia, the ramiprilat-coated stent showed good effects on the inflammatory reaction and arterial healing similar to the control stent in a porcine coronary restenosis model.
Angiotensin II ; Angiotensin-Converting Enzyme Inhibitors ; Cell Count ; Constriction, Pathologic ; Coronary Restenosis ; Coronary Vessels ; Fibrin ; Hyperplasia ; Inflammation ; Muscle, Smooth, Vascular ; Neointima ; Renin-Angiotensin System ; Stents ; Swine

The aim of this study was to examine the anti-proliferative and anti-inflammatory effects of ezetimibe/simvastatin (E/S) after drug-eluting stent (DES) implantation in a porcine coronary restenosis model. Pigs were randomized into two groups in which the coronary arteries (23 pigs) had DES. Stents were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries. Fifteen pigs were taken 10/20 mg of E/S and eight pigs were not taken E/S. Histopathologic analysis was assessed at 28 days after stenting. In neointima, most inflammatory cells were lymphohistiocytes. Lymphohistiocyte count was not different between two groups (337+/-227 vs. 443+/-366 cells, P=0.292), but neointima area was significantly smaller (1.00+/-0.49 mm2 vs. 1.69+/-0.98 mm2, P=0.021) and percent area stenosis was significantly lower (23.3+/-10% vs. 39+/-19%, P=0.007) in E/S group compared with control group. There were no significant differences in fibrin score (1.99+/-0.79 vs. 1.81+/-0.88, P=0.49), endothelial score (1.75+/-0.66 vs. 1.80+/-0.59, P=0.79), and the percent of endothelium covered lumen (43+/-21% vs. 45+/-21%, P=0.84) between E/S group and control group. Combined therapy with ezetimibe and simvastatin inhibits neointimal hyperplasia, but does not inhibit inflammatory infiltration and arterial healing after DES implantation in a porcine coronary restenosis model.
Animals ; Anticholesteremic Agents/administration & dosage ; Azetidines/*administration & dosage ; Coronary Restenosis/diagnosis/drug therapy/*etiology ; *Disease Models, Animal ; Drug Combinations ; Drug Implants/administration & dosage ; Drug-Eluting Stents/*adverse effects ; Female ; Graft Occlusion, Vascular/diagnosis/*drug therapy/*etiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage ; Simvastatin/*administration & dosage ; Swine ; Treatment Outcome

BACKGROUND AND OBJECTIVES: Angiotensin II receptor blocker (ARB) has emerged as an alternative to angiotensin converting enzyme inhibitor (ACEI) for the treatment of heart failure. This study aimed at comparing the effectiveness and safety of valsartan with ramipril in patients with heart failure, and these patients were hospitalized at Chonnam National University Hospital, Wonkwang University Hospital, Gunsan Medical Center, Presbyterian Medical Center, Seonam University Hospital and Gwangju Christian Hospital. SUBJECTS AND METHODS: Between March 2005 and March 2007, 82 patients (60.5+/-12.4 years, 59 males) who complained of class II to IV dyspnea, according to the New York Heart Association (NYHA) classification, and who had low left ventricular ejection fraction (LVEF) less than 50% were randomly allocated to valsartan or ramipril. After 6 months, the clinical symptoms, vital signs, biochemical tests and echocardiography were compared between the two groups. RESULTS: The NYHA class was improved in both groups (the valsartan group: 2.31+/-0.51 vs. 1.46+/-0.58, p<0.001; the ramipril group: 2.21+/-0.55 vs. 1.61+/-0.50, p<0.001). The incidence of cough, as measured by the cough index, was significantly lower in the valsartan group than in the ramipril group (p=0.045). The LVEF was improved in both groups (the valsartan group: 36.4+/-8.5% vs. 46.9+/-12.9%, p<0.001; the ramipril group: 35.1+/-8.5% vs. 45.3+/-11.2%, p<0.001). The improvements of the left ventricular end-systolic dimension (p=0.754) and end-diastolic dimension (p=0.998) were not different between the two groups. N-terminal Pro-B-type natriuretic peptide level was improved in both groups (the valsartan group: 2619.6+/-4213.5 vs. 995.4+/-2186.0 pg/mL, p=0.012; the ramipril group: 3267.9+/-4320.0 vs. 828.1+/-1232.8 pg/mL, p=0.009), and there was no difference between the groups (p=0.877). CONCLUSION: Both valsartan and ramipril were effective treatments, with relatively low adverse events, in patients with heart failure.
Angiotensins ; Cough ; Dyspnea ; Echocardiography ; Heart ; Heart Failure ; Humans ; Incidence ; New York ; Peptidyl-Dipeptidase A ; Protestantism ; Ramipril ; Receptors, Angiotensin ; Stroke Volume ; Tetrazoles ; Valine ; Ventricular Remodeling ; Vital Signs ; Valsartan

BACKGROUND AND OBJECTIVES: This study was conducted to evaluate the inflammatory reaction at sites of overlapping stents in a porcine in-stent restenosis (ISR) model. MATERIALS AND METHODS: Twenty bare metal stents (BMS, Group I; n=10), 20 sirolimus-eluting stents (SES, Group II; n=10), 20 paclitaxel-eluting stents (PES, Group III; n=10), 10 PESs and 10 SESs (Group IV; n=10) were deployed and overlapped in the left anterior descending coronary arteries of 40 pigs. Follow-up coronary angiograms and histopathologic analysis were performed at 4 weeks after stenting. RESULTS: The minimal luminal diameter of the overlapped segment at 4 weeks was smaller in group I than that in the other groups (1.78+/-0.13 mm vs. 2.79+/-0.09 mm vs. 2.90+/-0.04 mm vs. 2.80+/-0.07 mm, respectively, p<0.001). The neointimal area (5.51+/-0.58 mm2 vs. 2.38+/-0.53 mm2 vs. 2.07+/-0.37 mm2 vs. 2.39+/-0.58 mm2, respectively, p<0.001) and the area stenosis (68.74+/-4.02% vs. 27.79+/-4.73% vs. 23.66+/-3.24% vs. 27.63+/-4.07%, respectively, p<0.001) of the overlapped segment were significantly higher in Group I than that in the other groups. The inflammatory score of the overlapped segment was significantly higher in Group III than that in the other groups (1.80+/-0.42 vs. 2.10+/-0.32 vs. 2.90+/-0.31 vs. 2.50+/-0.52, respectively, p<0.001). The endothelization score of the overlapped segment was significantly lower in Group III than that in the other groups (2.80+/-0.42 vs. 2.30+/-0.67 vs. 1.30+/-0.48 vs. 2.10+/-0.74, respectively, p<0.001). CONCLUSION: Compared with the BMS, the DES inhibits neointimal hyperplasia, but inflammation and poor endothelization are observed at the sites of overlapped stents.
Constriction, Pathologic ; Coronary Disease ; Coronary Vessels ; Drug-Eluting Stents* ; Follow-Up Studies ; Hyperplasia ; Inflammation ; Phenobarbital ; Stents ; Swine

BACKGROUND AND OBJECTIVES: Carvedilol is a beta- and alpha-receptor blocker, a direct inhibitor of smooth muscle cell proliferation and migration, and it produced a significant suppression of neointimal hyperplasia in our porcine experiment. The purpose of the study was to investigate the safety and efficacy of carvedilol-eluting BiodiVysio stent implantation for de novo lesions. SUBJECTS AND METHODS: We performed a prospective randomized trial to compare two types of stents for revascularization in 39 patients [Group I (carvedilol-eluting stent): n=20, 58.3+/-11.1 years, and Group II (control stent): n=19, 59.9+/-8.5 years]. The primary effective end points were major adverse cardiac events (MACE): cardiac death, acute myocardial infarction, target lesion revascularization (TLR), in-stent restenosis and late lumen loss at the one-year clinical and angiographic follow-up. RESULTS: All the stents were successfully deployed and the patients were discharged without experiencing any clinical events. The baseline clinical characteristics, baseline diameter stenosis and minimal luminal diameter were not different between the two groups. The follow-up diameter stenosis and late loss were significantly lower in the group I compared with group II (23.1+/-12.7% vs. 47.3+/-23.6%, p=0.012; and 0.52+/-0.26 mm vs. 1.12+/-0.67 mm; p=0.020, respectively). There were no TLR and MACE in group I; however the differences were not significant [0% (0/20) vs. 10.5% (2/19); p=0.231 and 0% (0/20) vs. 15.8% (3/19), p=0.106, respectively]. CONCLUSION: Carvediloleluting stents appear feasible to use and they may be effective in the prevention of coronary restenosis. These results warrant further confirmation with a large, randomized multi-center trial.
Antioxidants ; Constriction, Pathologic ; Coronary Artery Disease* ; Coronary Disease ; Coronary Restenosis ; Coronary Vessels* ; Death ; Follow-Up Studies ; Humans ; Hyperplasia ; Myocardial Infarction ; Myocytes, Smooth Muscle ; Phenobarbital ; Prospective Studies ; Stents*