Beighley, Patricia E.

Patients with congenital heart disease who have a morphological right ventricle (RV) serving as a systemic ventricle have an increased incidence of RV dysfunction. A different structural response of micro‐vessels to increased stress in the RV wall is a possible mechanism for this dysfunction. We examined this possibility by measuring the volume of myocardium perfused by arteries less than 200μm in lumen diameter (V) 7 weeks after a 5mg/kg IV injection of monocrotaline in three 2‐week old and three 18‐week old pigs. This information was obtained by use of 3D micro‐CT of transmural segments (~ 2cm 3 ) of the RV wall. The table provides the average values of V (mm 3 /mm 2 ± SD). Pulmonary artery pressures in the mature, treated pigs were 35±6 mmHg and in the juvenile were 25±2 mmHg. V did not differ from control in the treated 2.5‐month old pigs but trended down in the 6‐month old pigs. We conclude that the volume of myocardium perfused by an arteriole in the RV wall may be an indicator of the perfusion reserve available to the microcirculation in response to increased wall stress. A more definitive answer would require delayed study of the early onset treatment group at the age of 6 months. (Supported in part by NIH grant EB000305)

We tested the hypothesis that changes in the arteriolar branching architecture contributed to increased running capacity of rats subjected to two-way artificial selection for intrinsic aerobic endurance treadmill running capacity resulting in strains of low-capacity and high-capacity endurance rats. Hearts and gastrocnemius muscles were harvested from each strain, and the microvasculature's branching geometry measured from micro-CT images. The vascular branching geometry of the hearts and skeletal muscle from the high capacity was indistinguishable from low-capacity rats. Our hypothesis was not supported. Neither remodeling nor an increase in arteriolar microvasculature branching appears to play a role in the enhanced performance of the high capacity rats. We are led to speculate that endothelial tolerance for shear stress and/or increased coupling of myocardial muscle fiber metabolic-to-contractile function is increased in the high-capacity runner strain to the effect of allowing either higher flow rate per unit volume of muscle or more efficient use of oxygen and nutrients in the high-capacity endurance rats.

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.

Objective— We hypothesized that apolipoprotein E (apoE) −/− /low-density lipoprotein (LDL) −/− double knockout mice might develop vasa vasorum (VV) in association with advanced lesion formation. Methods and Results— Aortas from apoE −/− /LDL −/− mice aged 16, 18, 20, or 80 weeks were infused in situ with Microfil, harvested, and scanned with micro-computed tomography (CT). We characterized plaque volume and CT “density” as well as VV luminal volume along the aorta using Analyze 6.0 software. Results were complemented by a detailed histological plaque classification according to American Heart Association guidelines. From 16 to 80 weeks, plaque volume and VV opacified lumen volume increased with age ( P <0.001). The 3-dimensional micro-CT images of arterial and venous VV trees allowed perfusion territories to be delineated. The spatial location and magnitude of VV density and adventitial inflammation were strongly correlated in advanced atherosclerotic lesions ( r =0.91) and identified as an independent correlate to advanced lesions. At age 80 weeks, VV luminal volume was increased 20-fold compared with animals at age 16 weeks ( P <0.001). Micro-CT showed that adventitial VV communicate with intraplaque microvessels. Conclusion— Our results show that apoE −/− /LDL −/− double knockout mice develop VV and advanced atheromas along the aorta. Lesion volume was closely associated with amount of neovascularization in advanced atheromas.

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-μm 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 (ΔWT) and stroke volume (ΔSV) 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, ΔWT, ΔSV, and CK washout were correlated more closely with the total SA ( r =0.95, P <0.001; r =0.68, P <0.01; and r =0.88, P =0.01, respectively) than with the total NPM volume ( r =0.59, P >0.05; 0.46, P >0.05; and r =0.69, P =0.04, 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.