Preclinical Evaluation of an Everolimus-Eluting Bioresorbable Vascular Scaffold Via a Long-Term Rabbit Iliac Artery Model

BACKGROUND@#Biodegradable poly (l-lactic acid) (PLLA), a bio safe polymer with a large elastic modulus, is widely used in biodegradable medical devices. However, because of its poor mechanical properties, a PLLA strut must be made twice as thick as a metal strut for adequate blood vessel support. Therefore, the mechanical properties of a drug-eluting metal-based stents (MBS) and a bioresorbable vascular scaffolds (BVS) were evaluated and their safety and efficacy were examined via a long-term rabbit iliac artery model. @*METHODS@#The surface morphologies of the MBSs and BVSs were investigated via optical and scanning electron microscopy. An everolimus-eluting (EE) BVS or an EE-MBS was implanted into rabbit iliac arteries at a 1.1:1 stent-toartery ratio. Twelve months afterward, stented iliac arteries from each group were analyzed via X-ray angiography, optical coherence tomography (OCT), and histopathologic evaluation. @*RESULTS@#Surface morphology analysis of the EE coating on the MBS confirmed that it was uniform and very thin (4.7 lm). Comparison of the mechanical properties of the EE-MBS and EE-BVS showed that the latter outperformed the former in all aspects (radial force (2.75 vs. 0.162 N/mm), foreshortening (0.24% vs. 1.9%), flexibility (0.52 vs. 0.19 N), and recoil (3.2% vs. 6.3%). At all time points, the percent area restenosis was increased in the EE-BVS group compared to the EE-MBS group. The OCT and histopathological analyses indicate no significant changes in strut thickness. @*CONCLUSION@#BVSs with thinner struts and shorter resorption times should be developed. A comparable long-term safety/efficacy evaluation after complete absorption of BVSs should be conducted.

XperCT-guided Intra-cisterna Magna Injection of Streptozotocin for Establishing an Alzheimer’s Disease Model Using the Cynomolgus Monkey (Macaca fascicularis)

Till date, researchers have been developing animal models of Alzheimer’s disease (AD) in various species to understand the pathological characterization and molecular mechanistic pathways associated with this condition in humans to identify potential therapeutic treatments. A widely recognized AD model that mimics the pathology of human AD involves the intracerebroventricular (ICV) injection with streptozotocin (STZ).However, ICV injection as an invasive approach has several limitations related to complicated surgical procedures. Therefore, in the present study, we created a customized stereotaxic frame using the XperCT-guided system for injecting STZ in cynomolgus monkeys, aiming to establish an AD model. The anatomical structures surrounding the cisterna magna (CM) were confirmed using CT/MRI fusion images of monkey brain with XperCT, the c-arm cone beam computed tomography. XperCT was used to determine the appropriate direction in which the needle tip should be inserted within the CM region. Cerebrospinal fluid (CSF) was collected to confirm the accurate target site when STZ was injected into the CM.Cynomolgus monkeys were administered STZ dissolved in artificial CSF once every week for 4 weeks via intracisterna magna (ICM) injection using XperCT-guided stereotactic system. The molecular mechanisms underlying the progression of STZ-induced AD pathology were analyzed two weeks after the final injection. The monkeys subjected to XperCT-based STZ injection via the ICM route showed features of AD pathology, including markedly enhanced neuronal loss, synaptic impairment, and tau phosphorylation in the hippocampus. These findings suggest a new approach for the construction of neurodegenerative disease models and development of therapeutic strategies.

Impact of Bisoprolol on Ventricular Arrhythmias in Experimental Myocardial Infarction / 전남의대학술지

Following acute myocardial infarction (AMI), early use of beta-blockers (BBs) reduced the incidences of ventricular arrhythmia (VA) and death in the pre reperfusion era.However, some studies have reported a worsening of clinical outcomes and therefore, this study used a porcine model of AMI to evaluate the efficacy of bisoprolol on VAs and mortality. Twenty pigs were divided into two groups with one group using oral bisoprolol which was given for 3 hours before the experiment and then maintained for 7 days. A loop recorder was implanted, AMI was induced by balloon occlusion for 60 min, and then, reperfusion. One week later, the echocardiography and loop recorder data were analyzed in the surviving animals. Bisoprolol did not increase the heart rate (62.9±14.5 vs 79.0±20.3; p=0.048), lower the rate of premature ventricular contractions (PVC) (0.8±0.8 vs 11.0±12.8; p=0.021) or tend to lower recurrent VA (0.6±0.5 vs 1.1±1.1;p=0.131) during coronary artery occlusion. After reperfusion, bisoprolol did reduce VA in the early AMI period (0.1±0.3 vs 4.2±4.6; p=0.001) and it was not associated with the extent of myocardial recovery. In this porcine model, early oral bisoprolol might help reduce the incidences of PVC and recurrent VA and determine whether effects are more pronounced during the early AMI period. Our results suggest that bisoprolol might help reduce lethal VA and cardiac death following AMI in this reperfusion era.

Impact of Bisoprolol on Ventricular Arrhythmias in Experimental Myocardial Infarction / 전남의대학술지

Following acute myocardial infarction (AMI), early use of beta-blockers (BBs) reduced the incidences of ventricular arrhythmia (VA) and death in the pre reperfusion era.However, some studies have reported a worsening of clinical outcomes and therefore, this study used a porcine model of AMI to evaluate the efficacy of bisoprolol on VAs and mortality. Twenty pigs were divided into two groups with one group using oral bisoprolol which was given for 3 hours before the experiment and then maintained for 7 days. A loop recorder was implanted, AMI was induced by balloon occlusion for 60 min, and then, reperfusion. One week later, the echocardiography and loop recorder data were analyzed in the surviving animals. Bisoprolol did not increase the heart rate (62.9±14.5 vs 79.0±20.3; p=0.048), lower the rate of premature ventricular contractions (PVC) (0.8±0.8 vs 11.0±12.8; p=0.021) or tend to lower recurrent VA (0.6±0.5 vs 1.1±1.1;p=0.131) during coronary artery occlusion. After reperfusion, bisoprolol did reduce VA in the early AMI period (0.1±0.3 vs 4.2±4.6; p=0.001) and it was not associated with the extent of myocardial recovery. In this porcine model, early oral bisoprolol might help reduce the incidences of PVC and recurrent VA and determine whether effects are more pronounced during the early AMI period. Our results suggest that bisoprolol might help reduce lethal VA and cardiac death following AMI in this reperfusion era.

Effect of Renal Denervation on Suppression of PVC and QT Prolongation in a Porcine Model of Acute Myocardial Infarction

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.

Impaired Hand Dexterity Function in a Non-human Primate Model with Chronic Parkinson’s Disease

ymptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

Assessment of Hand Motor Function in a Non-human Primate Model of Ischemic Stroke

Ischemic stroke results from arterial occlusion and can cause irreversible brain injury. A non-human primate (NHP) model of ischemic stroke was previously developed to investigate its pathophysiology and for efficacy testing of therapeutic candidates; however, fine motor impairment remains to be well-characterized. We evaluated hand motor function in a cynomolgus monkey model of ischemic stroke. Endovascular transient middle cerebral artery occlusion (MCAO) with an angiographic microcatheter induced cerebral infarction. In vivo magnetic resonance imaging mapped and measured the ischemia-induced infarct lesion. In vivo diffusion tensor imaging (DTI) of the stroke lesion to assess the neuroplastic changes and fiber tractography demonstrated three-dimensional patterns in the corticospinal tract 12 weeks after MCAO. The hand dexterity task (HDT) was used to evaluate fine motor movement of upper extremity digits. The HDT was modified for a home cage-based training system, instead of conventional chair restraint training. The lesion was localized in the middle cerebral artery territory, including the sensorimotor cortex. Maximum infarct volume was exhibited over the first week after MCAO, which progressively inhibited ischemic core expansion, manifested by enhanced functional recovery of the affected hand over 12 weeks after MCAO. The total performance time decreased with increasing success rate for both hands on the HDT. Compensatory strategies and retrieval failure improved in the chronic phase after stroke. Our findings demonstrate the recovery of fine motor skill after stroke, and outline the behavioral characteristics and features of functional disorder of NHP stroke model, providing a basis for assessing hand motor function after stroke.

Effect of Renal Denervation on Suppression of PVC and QT Prolongation in a Porcine Model of Acute Myocardial Infarction

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.

Influence of Local Myocardial Infarction on Endothelial Function, Neointimal Progression, and Inflammation in Target and Non-Target Vascular Territories in a Porcine Model of Acute Myocardial Infarction

BACKGROUND: Patients with acute myocardial infarction (AMI) have worse clinical outcomes than those with stable coronary artery disease despite revascularization. Non-culprit lesions of AMI also involve more adverse cardiovascular events. This study aimed to investigate the influence of AMI on endothelial function, neointimal progression, and inflammation in target and non-target vessels. METHODS: In castrated male pigs, AMI was induced by balloon occlusion and reperfusion into the left anterior descending artery (LAD). Everolimus-eluting stents (EES) were implanted in the LAD and left circumflex (LCX) artery 2 days after AMI induction. In the control group, EES were implanted in the LAD and LCX in a similar fashion without AMI induction. Endothelial function was assessed using acetylcholine infusion before enrollment, after the AMI or sham operation, and at 1 month follow-up. A histological examination was conducted 1 month after stenting. RESULTS: A total of 10 pigs implanted with 20 EES in the LAD and LCX were included. Significant paradoxical vasoconstriction was assessed after acetylcholine challenge in the AMI group compared with the control group. In the histologic analysis, the AMI group showed a larger neointimal area and larger area of stenosis than the control group after EES implantation. Peri-strut inflammation and fibrin formation were significant in the AMI group without differences in injury score. The non-target vessel of the AMI also showed similar findings to the target vessel compared with the control group. CONCLUSION: In the pig model, AMI events induced endothelial dysfunction, inflammation, and neointimal progression in the target and non-target vessels.

Increased CD68/TGFβ Co-expressing Microglia/Macrophages after Transient Middle Cerebral Artery Occlusion in Rhesus Monkeys

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.

Abnormal Mitochondria in a Non-human Primate Model of MPTP-induced Parkinson's Disease: Drp1 and CDK5/p25 Signaling

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD.

Evaluation of fecal microbiomes associated with obesity in captive cynomolgus monkeys (Macaca fascicularis)

Microorganisms play important roles in obesity; however, the role of the gut microbiomes in obesity is controversial because of the inconsistent findings. This study investigated the gut microbiome communities in obese and lean groups of captive healthy cynomolgus monkeys reared under strict identical environmental conditions, including their diet. No significant differences in the relative abundance of Firmicutes, Bacteroidetes and Prevotella were observed between the obese and lean groups, but a significant difference in Spirochetes (p < 0.05) was noted. Microbial diversity and richness were similar, but highly variable results in microbial composition, diversity, and richness were observed in individuals, irrespective of their state of obesity. Distinct clustering between the groups was not observed by principal coordinate analysis using an unweighted pair group method. Higher sharedness values (95.81% ± 2.28% at the genus level, and 79.54% ± 5.88% at the species level) were identified among individual monkeys. This paper reports the association between the gut microbiome and obesity in captive non-human primate models reared under controlled environments. The relative proportion of Firmicutes and Bacteroidetes as well as the microbial diversity known to affect obesity were similar in the obese and lean groups of monkeys reared under identical conditions. Therefore, obesity-associated microbial changes reported previously appear to be associated directly with environmental factors, particularly diet, rather than obesity.

Intramyocardial Injection of Stem Cells in Pig Myocardial Infarction Model: The First Trial in Korea

Although cell therapy is emerged for cardiac repair, its efficacy is modest by intracoronary infusion. Therefore, we established the intramyocardial delivery technique using a left ventricular (LV) mapping system (NOGA® XP) using 18 pigs. After adipose tissue-derived mesenchymal stem cells (ATSCs) were delivered intramyocardially to porcine infarcted heart, LV ejection fraction (EF) was increased, and LV chamber size was decreased. We proved the therapeutic effect of intramyocardial injection of ATSC through a LV mapping system in the porcine model for the first time in Korea. The adoption of this technique may accelerate the translation into a clinical application in the near future.

Effect of Stents Coated with Artemisinin or Dihydroartemisinin in a Porcine Coronary Restenosis Model

BACKGROUND AND OBJECTIVES: Artemisinin and dihydroartemisinin are drugs used to treat malaria. These drugs suppress inflammatory reactions. The aim of this study was to examine the anti-intima hyperplasia effect of a novel drug-eluting stent with artemisinin or dihydroartemisinin in a porcine coronary restenosis model. MATERIALS AND METHODS: Pigs were randomized into four groups; in the first, the coronary arteries (20 pigs, a total of 40 coronary arteries, with 10 coronary arteries in each group) was implanted with bare metal stents (BMS, n=10); the second group was given polymer-coated stents (PCS, n=10); the third group was treated with artemisinin-eluting stents (AES, n=10); and the fourth group was given dihydroartemisinin-eluting stents (DAES, n=10). Histopathologic analysis was performed 28 days after stenting. RESULTS: The injury and fibrin scores among the four groups were not significantly different. However, the internal elastic lamina, lumen area, and neointima area were significantly different. Moreover, the percent area of stenosis (46.2±18.66% in BMS vs. 89.4±10.92% in PCS vs. 83.3±17.07% in AES vs. 36.7±11.20% in DAES, p<0.0001) and inflammation score (1.0 [range: 1.0-1.0] vs. 3.0 [range: 2.25-3.0] vs. 3.0 [range: 1.0-3.0] vs. 2.0 [range: 1.75-3.0] in BMS, PCS, AES, and DAES, respectively; p<0.001) were markedly decreased in the DAES group compared to the PCS group. CONCLUSION: DES, which uses a natural substance, dihydroartemisinin, showed a neointima and inflammatory suppressive effect in a porcine coronary restenosis model.

The Control of Drug Release and Vascular Endothelialization after Hyaluronic Acid-Coated Paclitaxel Multi-Layer Coating Stent Implantation in Porcine Coronary Restenosis Model

BACKGROUND AND OBJECTIVES: Hyaluronic acid (HA) is highly biocompatible with cells and the extracellular matrix. In contrast to degradation products of a synthetic polymer, degradation products of HA do not acidify the local environment. The aim of this study was to fabricate an HA-coated paclitaxel (PTX)-eluting stent via simple ionic interactions and to evaluate its effects in vitro and in vivo. MATERIALS AND METHODS: HA and catechol were conjugated by means of an activation agent, and then the stent was immersed in this solution (resulting in a HA-coated stent). After that, PTX was immobilized on the HA-coated stent (resulting in a hyaluronic acid-coated paclitaxel-eluting stent [H-PTX stent]). Study groups were divided into 4 groups: bare metal stent (BMS), HA, H-PTX, and poly (L-lactide)-coated paclitaxel-eluting stent (P-PTX). Stents were randomly implanted in a porcine coronary artery. After 4 weeks, vessels surrounding the stents were isolated and subjected to various analyses. RESULTS: Smoothness of the surface was maintained after expansion of the stent. In contrast to a previous study on a PTX-eluting stent, in this study, the PTX was effectively released up to 14 days (a half amount of PTX in 4 days). The proliferation of smooth muscle cells was successfully inhibited (by 80.5±12.11% at 7 days of culture as compared to the control) by PTX released from the stent. Animal experiments showed that the H-PTX stent does not induce an obvious inflammatory response. Nevertheless, restenosis was clearly decreased in the H-PTX stent group (9.8±3.25%) compared to the bare-metal stent group (29.7±8.11%). CONCLUSION: A stent was stably coated with PTX via simple ionic interactions with HA. Restenosis was decreased in the H-PTX group. These results suggest that HA, a natural polymer, is suitable for fabrication of drug-eluting stents (without inflammation) as an alternative to a synthetic polymer.

Novel Fabrication of MicroRNA Nanoparticle-Coated Coronary Stent for Prevention of Post-Angioplasty Restenosis

BACKGROUND AND OBJECTIVES: MicroRNA 145 is known to be responsible for cellular proliferation, and its enhanced expression reportedly inhibits the retardation of vascular smooth muscle cell growth specifically. In this study, we developed a microRNA 145 nanoparticle immobilized, hyaluronic acid (HA)-coated stent. MATERIALS AND METHODS: For the gene therapy, we used disulfide cross-linked low molecular polyethylenimine as the carrier. The microRNA 145 was labeled with YOYO-1 and the fluorescent microscopy images were obtained. The release of microRNA 145 from the stent was measured with an ultra violet spectrophotometer. The downstream targeting of the c-Myc protein and green fluorescent protein was determined by Western blotting. Finally, we deployed microRNA 145/ssPEI nanoparticles immobilized on HA-coated stents in the balloon-injured external iliac artery in a rabbit restenosis model. RESULTS: Cellular viability of the nanoparticle-immobilized surface tested using A10 vascular smooth muscle cells showed that MSN exhibited negligible cytotoxicity. In addition, microRNA 145 and downstream signaling proteins were identified by western blots with smooth muscle cell (SMC) lysates from the transfected A10 cell, as the molecular mechanism for decreased SMC proliferation that results in the inhibition of in-stent restenosis. MicroRNA 145 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis at the post-implantation. We investigated the qualitative analyses of in-stent restenosis in the rabbit model using micro-computed tomography imaging and histological staining. CONCLUSION: MicroRNA 145-eluting stent mitigated in-stent restenosis efficiently with no side effects and can be considered a successful substitute to the current drug-eluting stent.

Cardioprotective Effect of Fimasartan, a New Angiotensin Receptor Blocker, in a Porcine Model of Acute Myocardial Infarction

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.

Effect of Pretreatment of Ezetimibe/Simvastatin on Arterial Healing and Endothelialization after Drug-Eluting Stent Implantation in a Porcine Coronary Restenosis Model

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.

Effect of Atorvastatin-Eluting Stents in a Rabbit Iliac Artery Restenosis Model / 전남의대학술지

Statins have pleiotropic effects, which include the inhibition of neointima hyperplasia, the inhibition of vascular inflammation, and platelet inhibition. The aim of this study was to examine the effect of an atorvastatin-eluting stent (AES) in a rabbit iliac artery overstretch restenosis model. Ten rabbits were used in this study (10 rabbits, 10 iliac arteries for each stent). An AES and paclitaxel-eluting stent (PES) were implanted in the left and right iliac arteries in a rabbit (2 stents in each rabbit). The stents were deployed with oversizing (stent/artery ratio 1.3:1), and histopathologic analysis was assessed at 28 days after stenting. There were no significant differences in the injury score, lumen area, or inflammation score. There were significant differences in the neointimal area (0.7+/-0.18 mm2 in the AES group vs. 0.4+/-0.25 mm2 in the PES group, p<0.01), in the percentage stenosis area (14.8+/-5.06% in the AES group vs. 10.5+/-6.80% in the PES group, p<0.05), and in the fibrin score (0.4+/-0.51 in the AES group vs. 2.7+/-0.48 in the PES group, p<0.001). Although the AES did not suppress neointimal hyperplasia compared with the PES, it showed a superior arterial healing effect in a rabbit iliac artery overstretch restenosis model.

Mechanical and Histopathological Comparison between Commercialized and Newly Designed Coronary Bare Metal Stents in a Porcine Coronary Restenosis Model / 전남의대학술지

The aim of this study was to compare the stent designed by Chonnam National University Hospital (designated as CNUH) with commercial cobalt-chromium coronary stent in a porcine coronary overstretch restenosis model. CNUH stent was subjected to mechanical performance tests. Pigs were randomized into two groups in which the coronary arteries (10 pigs, 10 coronaries in each group) had either CNUH stent or control commercial bare metal stent. Histopathologic analysis was assessed at 28 days after stenting. In mechanical performance tests, CNUH stent showed 2.65N, 35.1N, 0.52N, 1.94%, 4.29% in the flat plate radial compression, radial force, 3 point bending, Foreshortening and recoil test, respectively. There was no significant difference in the injury score, internal elastic lamina (IEL), lumen area, neointima area, percent area stenosis, inflammation score and fibrin score between the two groups (1.2+/-0.35, 4.1+/-0.41 mm2, 2.7+/-0.56 mm2, 1.6+/-0.47 mm2, 36.7+/-11.2%, 1.2+/-0.62, 0.2+/-0.34 in CNUH stent group vs. 1.2+/-0.38, 3.7+/-0.64 mm2, 2.5+/-0.49 mm2, 1.5+/-0.61 mm2, 36.3+/-12.17%, 1.1+/-0.12, 0.4+/-0.46 in commercial stent group, respectively). In the mechanical performance test, CNUH stent showed the moderated performance under the guideline of FDA. CNUH stent demonstrated similar histological reactions compared with commercial cobalt-chromium stent in a porcine coronary overstretch restenosis model.