Fluoroscopy Guided Minimally Invasive Swine Model of Myocardial Infarction by Left Coronary Artery Occlusion for Regenerative Cardiology

Abstract

Background: Despite the recent advancements in the cardiac regenerative technologies, the lack of an ideal translationally relevant experimental model simulating the clinical setting of acute myocardial infarction (MI) hurdles the success of cardiac regenerative strategies.

Methods: We developed a modified minimally invasive acute MI model in Yucatan miniswine by catheter-driven controlled occlusion of LCX branches for regenerative cardiology. Using a balloon catheter in three pigs, the angiography guided occlusion of LCX for 10-15 minutes resulted in MI induction which was confirmed by the pathological ECG changes compared to the baseline control.

Results: Ejection fraction was considerably decreased post-procedure compared to the baseline. Importantly, the highly sensitive MI biomarker Troponin I was significantly increased in post-MI and follow-up groups along with LDH and CCK than the baseline control. The postmortem infarct zone tissue displayed the classical features of MI including ECM disorganization, hypertrophy, inflammation, and angiogenesis confirming the MI at the tissue level.

Conclusions: The present model possesses the advantage of minimal mortality, simulating the pathological features of clinical MI and the suitability for injectable regenerative therapies suggesting the translational significance in regenerative cardiology.

Keywords: Infarct Zone; Ischemic Injury; LCX occlusion; Myocardial Infarction; Regenerative Cardiology.

Figure 1:

Coronary angiography: (A) Blood flow through the coronary showing the LAD and LCX branches and (B) inflated balloon showing the occlusion of blood flow in the LCX.

Figure 2:

Representative cardiac EKG displaying the alterations in the patterns in (A) control, (B) post-MI and (C) follow-up MI. (D) Scatter plot showing the distribution of the amplitudes of P, QRS and T waves based on individual pigs (P1, P2 and P3) and (E) representing the amplitudes of P, QRS and T in pre-MI, post-MI, and follow-up EKGs. The statistical significance based on one-way ANOVA test is represented in the figure (* P<0.05, and unlabeled are non-significant).

Figure 3:

Representative echocardiography displaying the alterations in the ejection fraction (A) control, (B) post-MI and (C) follow-up MI. (D) Scatter plot showing the distribution of the ejection fractions based on individual pigs with respect to the mean in pre-MI, post-MI, and follow-up ultrasound. *The pig which successfully underwent occlusion.

Figure 4:

The level of blood biomarkers confirming the MI as evident from the increased concentrations of (A) high sensitive Trop I, (B) LDH and (C) CCK. The statistical significance based on one-way ANOVA test is represented in the figure (* P<0.05, *** P<0.001, and unlabeled are non-significant).

Figure 5:

(A) The postmortem heart displaying the infarct zone. Representative images of the histology examination of formalin fixed sections of MI tissue showing the control (B) and MI group (C): yellow star represent normal ECM, blue star points ECM disorganization, red star shows blood vessels, and the green star displays inflammation. The images were acquired at 20x magnification.