부산대학교 도서관

Background/Aims:New therapies to positively impact scar formation after myocardial infarction (MI) could prevent ensuing heart failure or death from ventricular arrhythmias. We have previously shown that recombinant human Platelet Derived Growth Factor-AB (rhPDGF-AB) improves cardiac function in a rodent model of MI. To progress clinical translation, we evaluated the effect of rhPDGF-AB treatment in a clinically relevant porcine model of ischemia-reperfusion.Methods:36 pigs underwent balloon occlusion of the left anterior descending coronary artery or sham procedure. Infarcted pigs were randomized to receive a 7-day intravenous infusion of rhPDGF-AB or vehicle alone.Results:At 1-month after MI, rhPDGF-AB (compared to vehicle) improved survival by 40% and cardiac magnetic resonance imaging showed improved left ventricular (LV) ejection fraction by 11.5%. Pressure volume loop analyses revealed improved myocardial contractility and energetics after rhPDGF-AB treatment with minimal effect on ventricular compliance. Interestingly, rhPDGF-AB enhanced vasculogenesis (Fig. a,b) and increased scar anisotropy (high fiber alignment) (Fig. c,d) without affecting overall scar size or stiffness. rhPDGF-AB decreased inducible ventricular tachycardia by attenuating heterogeneity of the ventricular scar, a substrate for re-entrant circuits (Fig. e,f).Conclusion:Here, we demonstrate that rhPDGF-AB promotes post-MI cardiac wound repair by altering infarct scar mechanics, resulting in robust cardiac functional improvement, decreased ventricular arrhythmias and improved survival. Our findings suggest a strong translational potential for rhPDGF-AB as an adjunct to current MI treatment.