Relation of Nonperfused Myocardial Volume and Surface Area to Left Ventricular Performance in Coronary Microembolization

Abstract

Background-After occlusion of an epicardial artery, left ventricular (LV) dysfunction is closely related to the volume of nonperfused myocardium (NPM). The impact of coronary microembolization (ME) on LV function, however, is larger relative to the total volume of NPM. We hypothesized that the total surface area (SA), rather than the total volume, of NPM is the major determinant of ME-induced LV dysfunction. Methods and Results-We injected microspheres of 10-, 30-, or 100-m diameter at each of 3 doses selectively into the left anterior descending coronary artery of 48 anesthetized pigs. Electron beam computed tomography (CT) was used to measure regional myocardial perfusion and changes in LV wall thickening (⌬WT) and stroke volume (⌬SV) after ME. At postmortem, a transmural "biopsy" of 1 to 2 cm 3 of embolized myocardium was imaged by micro-CT, resulting in 3D images that provided volumes and SAs of the individual nonperfused foci. Additionally, in 9 pigs, creatine phosphokinase (CK) activity in embolized myocardium was measured as an index of washout of substances from the NPM. After ME, ⌬WT, ⌬SV, and CK washout were correlated more closely with the total SA (rϭ0.95, PϽ0.001; rϭ0.68, PϽ0.01; and rϭ0.88, Pϭ0.01, respectively) than with the total NPM volume (rϭ0. 59, PϾ0.05; 0.46, PϾ0.05; and rϭ0.69, Pϭ0.04, respectively). Conclusion-After coronary ME, LV dysfunction is more closely related to the total SA than to the total volume of nonperfused microregions in the myocardium.

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

“…Using this method and a similar model of coronary microembolization, we have previously shown that microembolization resulted in a contiguous spectrum of perfusion defects that were related to the number of injected microspheres (22). We further demonstrated that the total surface area in a given volume of embolized myocardium was related to the total number of perfusion defects and to the consequent regional myocardial contractile dysfunction (23). Nevertheless, the relationship between the surface area of myocardial perfusion defects and the increase in microvascular permeability following experimental microembolization remained unknown.…”

“…To ensure that the measurements of the wall thickness were performed in the same location within the myocardium before and after embolization, markers such as the diagonal branches of the LAD were used as fiducial markers as described previously (22,23). Hemodynamic parameters, such as heart rate and arterial blood pressure, ECG, and body temperature, were continuously monitored.…”

“…Transmural myocardial samples of ϳ1 cm 3 were matched using internal landmarks to the embolized and previously EBCTscanned regions and were then cut out and scanned with the micro-CT scanner, resulting in three-dimensional images (20 m, on-a-side cubic voxel). Image analysis for obtaining the surface area of the embolized myocardial volume was performed as previously described (22,23). Briefly, the outline of each nonopacified intramyocardial island was traced, and its surface area and volume calculated.…”

“…We have previously demonstrated that experimental coronary microembolization leads to a decrease in regional myocardial contractility that is proportional to the surface area of the embolization-induced nonperfused islands (microperfusion defects) in the myocardium (23). However, the effect of this maneuver on microvascular integrity or the factors that determine the magnitude of the extravascular accumulation of contrast agent remained unknown.…”

“…After completion of the EBCT-based studies, an X-ray microcomputed tomography scanner (micro-CT) was used to obtain directly, ex vivo, the volume and the total surface area of the individual nonperfused, ischemic, myocardial territories within the same region of myocardium that was previously scanned by the EBCT. Micro-CT provides a unique tool for quantification of 3D vascular structures and the number, volume, and surface area of the individual myocardial perfusion defects in a relatively large volume (Ͼ1 cm 3 ) of embolized myocardium (22,23). For testing our hypotheses in an in situ heart in an animal model, we used anesthetized pigs because their coronary circulation closely resembles human heart anatomy, blood flow distribution, and function (37).…”