Abstract 1125: Percutaneous Optofluidic Catheter-guided Photo-triggered Nanogoldsomes Reduce Infarct Size And Mitigate Myocardial Dysfunction In A Swine Model Of Acute Myocardial Infarction

Abstract

Introduction: S-nitrosoglutathione (GSNO) is an endogenous S-nitrosothiol that plays important roles in nitric oxide (NO) generation and signaling. We previously designed an Au-polymersomes/GSNO nanoparticle (nanogoldsome) that can be triggered by laser or ultrasound to accelerate the release of NO, which effectively dilates the arteries of the target organ and induces anti-apoptotic protection against ischemia-reperfusion injury. In this study we integrated an optofluidic coronary catheter with the photo-triggered nanogoldsomes, and investigate their roles in mitigating the infarct size in a swine model of acute myocardial infarction (AMI). Methods: In a swine AMI model of 90 min coronary artery (CA) occlusion, nanogoldsomes (0.145 mg Au and 3.66 μg GSNO/kg) were administered 5 min after balloon-off using a percutaneous coronary optofluidic catheter with 532 nm laser stimulation at the tip. The CA diameter was measured at baseline and at 0 and 15 min of reperfusion. Left ventricular (LV) function (max dp/dt) were measured at baseline, and 1 h and 7 days after reperfusion. The infarct area was determined at day 7 using triphenyltetrazolium chloride stain with the infarct fraction calculated in reference to the area at risk stained by Evan’s blue coronary infusion with balloon occlusion at the same site. Results: Compared to AMI group, the CA diameter showed significant dilatation 10 min after nanogoldsome/laser treatment (1.22 vs. 0.98 folds, P < 0.05), while systemic blood pressure showed no significant drop. The infarct fraction was significantly reduced (49% vs. 73%, P < 0.05) and LV function markedly better 7 days after AMI. By contrast, no significant differences were noted in the control groups of GSNO (3.66 μg/kg) and nanogoldsomes without laser stimulation. Conclusion: Percutaneous optofluidic catheter-guided infusion of nanogoldsomes at coronary orifice with simultaneous tip laser stimulation in the first minutes of AMI reperfusion magnified NO release in the most critical reperfusion period. This instantly dilated coronary arteries, and reduced infarct area and mitigated LV dysfunction 7 days after AMI. With large animal experiments showing pathophysiological benefits, further translation to pre-clinical studies is encouraged.