Details

Autor(en) / Beteiligte

• Harrell, Kayla P
• Nair, Arjun
• Boakye Tanoh, Desmond
• Singh, Sunit
• Andrews, Emily
• Dean, Tameka
• CHEN, Qian
• Barsotti, Robert
• Young, Lindon

Titel

Abstract 14364: Protein Kinase C Beta II Inhibitor Provides Cardiovascular Protection When Combined With Conjugated Myristic Acid and Trans-Activator of Transcription in Porcine Ischemia-Reperfusion Injury

Ist Teil von

• Circulation (New York, N.Y.), 2022-11, Vol.146 (Suppl_1)

Erscheinungsjahr

2022

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Abstract only Prompt reperfusion is vital to resuscitating ischemic myocardium. However, cardiomyocyte death still occurs due to ischemia-reperfusion (I/R) injury, which is mediated in part by oxidative stress. Major sources of reactive oxygen species (ROS) during I/R are NADPH oxidase (NOX-2) and mitochondria, which are principally activated by protein kinase C βII (PKCβII). Previously, myristic acid (Myr) and trans-activator of transcription (Tat) conjugated PKCβII inhibitor (Myr-Tat-PKCβII-; N-Myr-Tat-CC-SLNPEWNET) exhibited cardioprotective effects in ex vivo rat hearts. In this study, we hypothesize that Myr-Tat-PKCβII- will mitigate cardiac injury in an in vivo porcine myocardial I/R model compared to scrambled peptide controls. Male Yorkshire pigs (38-50kg) underwent regional I(1hr)/R(3hrs) through balloon-assisted occlusion of the second diagonal branch of the left anterior descending coronary artery (LAD) supplying ~40% of the anterior portion of the myocardium. During reperfusion (balloon deflation), a bolus of Myr-Tat-PKCβII- or scrambled control was infused into the LAD. Cardiac function was evaluated as the relative change in ejection fraction (EF) at the end of 3hr reperfusion compared to baseline. Serial measurements of serum creatine phosphokinase (CPK), troponin I, and myoglobin were evaluated to assess cardiac injury. Post-reperfused hearts were stained with Evans Blue dye to identify the area at risk (AR) and 1% triphenyltetrazolium chloride to demarcate the area of necrosis (AN). Infarct size (AN/AR), EF, and cardiac injury markers were analyzed via Student’s t-test. Myr-Tat-PKCβII- preserved EF with a relative change of 1.2±2.8% compared to 8.9±2.2% in control hearts (p<0.05) from mean baseline EF (61.4±0.5%). Myr-Tat-PKCβII- significantly decreased myoglobin levels at 1hr reperfusion (135±132ng/mL, n=4) compared to scrambled control (1022±346ng/mL, n=3 p<0.05). Myr-Tat-PKCβII- reduced infarct size to 13.5±3.9% (n=4) compared to scrambled control hearts (27.5±7.9%, n=6). CPK and troponin I levels were comparable in both groups. These results suggest Myr-Tat-PKCβII- mitigates cardiac injury when given at reperfusion onset. Future studies will examine Myr-Tat-PKCβII- in an 8 week in-vivo, porcine MI survival study.