Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization

Abstract

Myocardial microvascular permeability and coronary sinus concentration of muscle metabolites have been shown to increase after myocardial ischemia due to epicardial coronary artery occlusion and reperfusion. However, their association with coronary microembolization is not well defined. This study tested the hypothesis that acute coronary microembolization increases microvascular permeability in the porcine heart. The left anterior descending perfusion territories of 34 anesthetized pigs (32 ± 3 kg) were embolized with equal volumes of microspheres of one of three diameters (10, 30, or 100 μm) and at three different doses for each size. Electron beam computed tomography (EBCT) was used to assess in vivo, microvascular extraction of a nonionic contrast agent (an index of microvascular permeability) before and after microembolization with microspheres at baseline and during adenosine infusion. A high-resolution three-dimensional microcomputed tomography (micro-CT) scanner was subsequently used to obtain ex vivo, the volume and corresponding surface area of the embolized myocardial islands within the perfusion territories of the microembolized coronary artery. EBCT-derived microvascular extraction of contrast agent increased within minutes after coronary microembolization (P < 0.001 vs. baseline and vs. control values). The increase in coronary microvascular permeability was highly correlated to the micro-CT-derived total surface area of the nonperfused myocardium (r = 0.83, P < 0.001). In conclusion, myocardial extravascular accumulation of contrast agent is markedly increased after coronary microembolization and its magnitude is in proportion to the surface area of the interface between the nonperfused and perfused territories.

Fig. 1.

Left and middle: electron beam computed tomography (EBCT) images of the porcine left ventricle showing selective opacification of left anterior descending coronary artery (LAD) perfusion territory (A), which was manually outlined and used as the region of interest for the subsequent flow scans (B). LCX, left circumflex coronary artery; LV, left ventricle; RV, right ventricle. Right: representative time-density curve obtained from EBCT images of the LAD perfusion territory. HU, Hounsfield Unit. Our algorithm allows differentiation of the time density curve (Dens) into an intravascular curve (Art), which provides information about the transit time through the myocardial vasculature, and an extravascular curve (Extr), which represents the diffusion of contrast into the myocardial interstitium. From these data, myocardial perfusion (F, flow), intramyocardial blood volume (Bv), and an index of myocardial microvascular permeability were calculated.

Fig. 2.

Four consecutive flow-scan sequences were performed with a 20-min recovery period in between computed tomography (CT) scans to allow washout of the extravascular contrast agent.

Fig. 3.

Change in permeability index (arbitrary units) in % compared with baseline values in control and embolized animals after intracoronary injection of 10, 30, or 100 μm microspheres (μsph) at equivalent dose (1/2 of the fatal dose). IC, intracoronary; Post-CME, after coronary microembolization. *P < 0.01 vs. baseline and IC adenosine values; †P < 0.01 vs. 30 μm and 100 μm microspheres.

Fig. 4.

A: LV muscle volume of the LAD perfusion territory determined by EBCT at baseline and at 20 min postembolization. Numbers in the legend (10, 30, or 100 μm) indicate the diameter, and a, b, or c corresponds to the number of the injected microspheres of each size (see Table 1). Bars indicate means ± SD of all animals. B: illustration of the correlation between the total surface area of nonperfused myocardium, as determined by micro-CT, with the embolization-induced increase (%) in diastolic anterior wall (AW) thickness (as the surrogate of myocardial edema) as determined by EBCT. *P < 0.01, embolized vs. baseline (excluding the control animal).

Fig. 5.

Linear regression analysis illustrating the relationship of increase in myocardial microvascular permeability (MMP, %) to the total surface area (SA) per gram myocardium (A) and to the volume of nonperfused myocardium per gram myocardium (B). Squares = 10 μm, triangles = 30-μm, and circles = 100 μm microspheres, each size at the 3 different doses (white = low dose; grey = medium dose; black = high dose). For the exact number of the injected microspheres see Table 1.