Molecular and particulate depositions for regional myocardial flows in sheep.

Abstract

The deposition of microspheres in small tissue regions is not strictly flow dependent. In comparison with the soluble flow marker 2-iododesmethylimipramine (IDMI), deposition of 16.5-,um microspheres was mildly but systematically biased into high flow regions of rabbit hearts (Bassingthwaighte JB, Malone MA, Moffett T-C, King RB, Little SE, Link JM, Krohn KA. Am J Physiol 1987;253(Heart Circ Physiol 22):H184-H193). To examine the possibility of bias in larger hearts, a similar study was undertaken in sheep. 141Ce-and '03Ru-labeled 16.5 -,um microspheres in one syringe and 1251-and '311-DMI in another syringe were injected simultaneously into the left atrium of five open-chest sheep while obtaining reference blood samples from the femoral artery. In six other sheep, one microsphere type and one IDMI were used. Hearts were removed 1 minute after injection, cut into approximately 254 pieces averaging 217 mg, and regional deposition densities calculated for each tracer from the isotopic counts. Correlations in the five animals between the two differently labeled IDMIs and between the two microspheres were both .0.98. In all 11 sheep, scatter plots of microsphere deposition densities versus IDMI densities showed that differences between microspheres and IDMI had substantially more scatter (0.84<r<0.98) but were not random. Microsphere depositions tended to be lower than IDMI depositions in low flow regions and higher in high flow regions, in accord with the expected bias that at a bifurcation a microsphere is most likely to enter the branch with higher flow. There was less bias ascribable to endomyocardial/epicardial maldistribution. Thus, while microsphere depositions appear to err systematically with respect to flow when the regions of interest are small enough that the diameters of their arterioles are only a few times those of the microspheres, microspheres are, in sheep as in rabbits, adequate for estimating regional flows. (Circulation Research 1990;66:1328-1344 In rabbit hearts we observed that 16-,um microsphere distributions were mildly biased compared with a soluble flow marker (the so-called "molecular microsphere," 2-iododesmethylimip- The results show that, while the noniodinated compound 3H-DMI is 99% extracted, IDMI is only 95% extracted in blood perfused sheep hearts. However, the excess microsphere deposition in high flow by guest on May 7, 2018

High-resolution imaging reveals a limit in spatial resolution of blood flow measurements by microspheres

“…This has profound consequences for the spatial scale where microsphere can be a valid means to test the local perfusion. Previous studies supported the validity of microsphere flow determinations down to 200 mg in larger animals (3,16) and 50 mg in smaller animals (4). The present data indicate that at a spatial scale Ͻ2 mg ( l) local flow may not be the dominant force governing microsphere deposition.…”

“…This is supported by the fact that multiple injections of FMS resulted in stacking of spheres in the same vessel implying that although the MS was "trapped", the flow, or delivery of spheres, was not reduced to zero in the vessel. These streaming artifacts were previously recognized in rather large areas of high flow, ranging from 1 to 0.25% of left ventricular mass (3,4), and are consistent with in vitro experiments demonstrating a bias of spherical particles at branch points toward the higher flow branch (7). Consequently, for small individual sample sizes, supplied by small arteriolar vessels, microspheres will not represent a valid means for flow determinations.…”

“…In contrast, when perfusion of organs and large tissue regions is studied, all available evidence indicates the validity of the microsphere approach (22). The close correlation between plasma flow measured by molecular flow markers and the blood flow determined by microspheres in individual samples as small as 50 mg in rabbits and 250 mg in sheep and dogs (3,4,16), clearly supports the validity of local perfusion measurements by microspheres for samples as small as 0.25-1% of the left ventricular (LV) myocardial mass. Dividing the LV myocardium into 4, 8, 16, .…”

“…Whereas microsphere extraction in a given arteriolar or capillary vessel may result in blockage of the vessel (8), both enhanced collateral circulation and incomplete obstruction (described as a "poorly fitting ball valve with individual blood cells squeezing past") (12) will reduce its impact. In addition, in two studies, Bassingthwaighte et al (3,4) demonstrated reassuringly a close correlation between the deposition density of radioactive microspheres and a nearly ideal molecular marker (2-iododesmethylimipramine) in sheep and rabbit hearts. In these studies, microsphere deposition density exceeded the deposition density of the molecular marker only at high local flow rates, suggesting some streaming artifacts only in these high-flow regions.…”

Coronary Reserve of High- and Low-Flow Regions in the Dog Heart Left Ventricle

“…However, when analysis of the local deposition density of microspheres [2][3][4][5] and diffusible plasma flow markers [6][7][8] in volume elements of a few millimeters diameter showed that the local flow distribution within individual hearts is markedly heterogeneous, covering a range from 20% to 200% of the mean value. This flow heterogeneity is remarkably stable over periods of several hours, 4 even if the heart is intermittently stimulated.…”