The safety and efficacy of novel dual function coronary stent in porcine model of myocardial infarction

Objectives: We aimed in this study to evaluate the effectiveness of a dual function coronary stent in both inhibiting In Stent Restenosis (ISR) and salvaging the injured myocardium following acute myocardial infarction in pigs. Background: For more than a decade, drug eluting stents have written a successful chapter in coronary revascularisation following myocardial infarction. However, none so far has further exploited these stents beyond their primary function as a scaffolding structure to maintain the patency of the vessel. We aim in this study to use these stents as a delivery platform of cardioprotective drug (IGF-1) downstream the coronary artery to the injured myocardium while maintaining the patency of the vessel via anti-proliferative drug (AZ1193). Methods: The stent coating was designed to deliver IGF-1 from the outer (external) layer while delivering AZ1193 to the vessel wall. AZ1193 was sandwiched between a basal layer of Ti02 and an outer layer of AL203 using Atomic Layer Deposition (ALD) technique while IGF-1 was coated over AL203 layer. In vitro studies evaluated the release profile of IGF-1 and AZ1193 from the stent. Four groups of stents were used in 36 pigs following induced myocardial infarction: TAZA stent (Ti02-AZ1193-AL203), TAZA IGF-1 stent (TAZA stent coated with IGF-1), TA stent (Ti02-AL203) and TA IGF-1 (TA stent coated with IGF-1). ISR, Infarct size and LV ejection fraction (LVEF) were evaluated after 6 weeks of stent implantation. Results: Mortality was higher in IGF-1 stent groups (TAZA IGF-1 and TA IGF-1) comparable to other groups. Mortality rate was 14.2% (N7), 30% (NlO), 0% (N6), and 25% (NB) in TAZA, TAZA IGF-1, TA, and TA IGF-1 stent groups respectively (P=0.82). There was a significant restenosis in all groups (78.45 ± 10.01 %, 74.76 ± 14.64 %, 63.72 ± 14.41, and 70.10 ± 4.86 in TAZA, TAZA IGF-1, TA, and TA IGF-1 stent groups) (P<0.01). There was no significant difference in ISR among the groups (P=0.26). IA/AAR was 28.3 ± 2.3, 29.9 ±2.8, 27.1 ±1.4 and 28.0 ±1.8 in TAZA, TAZA IGF-1, TA, and TA IGF-1 groups respectively. There was no significant difference in infarct size among the groups (P=0.39). Baseline LVEF was 40.1% ± 3.9%, 40.5% ± 1.8%, 42.9% ± 4.8%, and 42.3% ± 3.4% for TAZA, TAZA IGF-1, TA and TA IGF-1 stent groups respectively (P=0.56). AT 6 weeks, LVEF was 27.5% ± 2.2%, 28.6% ± 6%, 25.9% ± 4%, and 24.9% ± 5.8% for TAZA, TAZA IGF-1, TA and TA IGF-1 stent groups respectively (P=0.62). There was a significant decline in EF secondary to LV remodelling at 6 weeks (P<0.05). Conclusions: This study demonstrated the feasibility to develop dual function coronary stent carrying anti-restenotic and cardioprotective drugs. Despite favourable in vitro results, the stent failed to reduce ISR and infarct size or to improve LVEF.

Grantor dc:publisher

University College Cork

Year dc:date.issued

2018

Author dc:creator

• Khider, Wisam

Advisor dc:contributor.advisor

• Caplice, Noel M.

• Dual function coronary stent
• Myocardial infarction
• Anti-restenotic and cardioprotective drugs

Statement dc:rights

• © 2018, Wisam Khider.

Licence dc:rights.uri

• https://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10468/18157

OAI identifier oai:identifier

oai:cora.ucc.ie:10468/18157