Pre-clinical studies aimed at treating ischemic heart disease (i.e. stem cell- and growth factor therapy) often consider restoration of the impaired microvascular circulation as an important treatment goal. However, serial in vivo measurement hereof is often lacking. The purpose of this study was to evaluate the applicability of intracoronary pressure and flow velocity as a measure of microvascular resistance in a large animal model of chronic myocardial infarction (MI). Myocardial infarction was induced in Dalland Landrace pigs (n = 13; 68.9 ± 4.1 kg) by a 75-min. balloon occlusion of the left circumflex artery (LCX). Intracoronary pressure and flow velocity parameters were measured simultaneously at rest and during adenosine-induced hyperemia, using the Combowire (Volcano) before and 4 weeks after MI. Various pressure- and/or flow-derived indices were evaluated. Hyperemic microvascular resistance (HMR) was significantly increased by 28% in the infarct-related artery, based on a significantly decreased peak average peak flow velocity (pAPV) by 20% at 4 weeks post-MI (P = 0.03). Capillary density in the infarct zone was decreased compared to the remote area (658 ± 207/mm2 versus 1650 ± 304/mm2, P = 0.017). In addition, arterioles in the infarct zone showed excessive thickening of the alpha smooth muscle actin (αSMA) positive cell layer compared to the remote area (33.55 ± 4.25 μm versus 14.64 ± 1.39 μm, P = 0.002). Intracoronary measurement of HMR successfully detected increased microvascular resistance that might be caused by the loss of capillaries and arteriolar remodelling in the chronic infarcted pig heart. Thus, HMR may serve as a novel outcome measure in pre-clinical studies for serial assessment of microvascular circulation.

Introduction: For optimal success of cardiac regenerative therapy intramyocardial catheter guided stem cell transplantations are performed in infarct border zone areas i.e. the closest region of viable myocardium in the vicinity of the infarct area. To optimize the therapeutic effect this area should be accurately identified. The gold standard technique to determine the infarct size and location is late gadolinium enhanced (LGE) MRI. Nevertheless, the NOGA®XP electromechanical mapping (EMM) system is used to guide injections to the infarct border zone. Since EMM is expensive, time consuming and has a low spatial resolution, we have developed a practical and accurate technique to fuse the NOGA®XP electromechanical maps with LGE-MRI to guide injections based on high resolution MRI data. Methods: LGE-MRI and EMM were obtained in 17 pigs with chronic myocardial infarction. MRI and EMM datasets were registered using our in-house developed 3D CartBox image registration software toolbox. Comparisons between MRI and EMM were performed to assess: 1) feasibility of the 3D CartBox fusion technique, 2) the EMM values measured in the areas with a distinct infarct transmurality (IT). Results: Registration was successful in all datasets, and resulted in a mean error of 3.01±1.94mm between the MRI mesh and EMM points (Fig 1A). The highest sensitivity and specificity to identify infarct border zone of 50% IT was found for bipolar voltage between 1.2 and 1.7mV (Fig 1B). Conclusions: Our new 3D CartBox image registration toolbox enables real time registration of the EMM on MRI during the injection procedure. The optimal spatial resolution and the instant visualization of the MRI images enables users to easily guide injections to the most optimal injection location for cardiac regenerative therapy based on the gold standard infarct imaging technique. This technique allows physicians to harness the full therapeutic effect of the therapy.