Acute myocardial infarction (MI) affects more than 3 million Americans per year. With an estimated door-to-balloon time of 90 minutes, clinicians can reperfuse the blocked coronary artery to restore blood flow through a stent or angioplasty. However, the reperfusion process after a period of ischemia causes injury in the form of cardiomyocyte death. Intrapericardial (IPC) delivery offers an alternative means to introduce a drug that can improve cardiac function post-MI and aid in preventing future coronary events. In this work, we test this approach in a porcine model that offers a translationally relevant model due to similarities in the size, location, and vasculature of the heart when compared to humans. After ischemic-reperfusion injury, we administered drug or saline into the pericardium using slow administration with a syringe pump. By using IPC delivery, we leverage the low turnover rate of pericardial fluid to distribute treatment across the entire heart. Analytes from blood plasma, pericardial fluid and cardiac tissue samples taken during and after the acute procedure were extracted with acetonitrile containing internal standard Diclofenac prior to performing liquid chromatography with tandem mass spectroscopy (LC-MS/MS). Angiograms and ventriculograms were also taken during the acute procedure. Confirmation of MI was determined by the presence of troponin and creatine kinase, soluble markers of cardiac damage, in the blood. LC-MS/MS of cardiac tissue samples and samples of plasma from the coronary sinus and pericardial fluid all showed the presence of the molecule in treated pigs. Using the ventriculograms, the stroke volume (SV) and ejection fraction (EF) were calculated to evaluate improvements in left ventricle performance following treatment compared to ischemic-reperfusion injury. Treatment resulted in improved ejection fraction compared to the saline-treated pigs, which showed a decrease in ejection fraction. Our data demonstrates intrapericardial delivery of a molecule following ischemic-reperfusion injury in a porcine model shows improved ejection fraction as compared to saline-treated pigs. This treatment strategy has implications for improved MI treatment, recovery and future prevention.

Intrapericardial treatment in a porcine model of reperfused myocardial infarction

ACS Fall 2021

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