Provisional stenting in small vessels

Based on the currently available data, the strategy of routine stent placement in unselected lesions located in small coronary arteries provides good immediate results but is still associated with a high incidence of in-stent restenosis. Randomized trials comparing elective stenting with balloon angioplasty have not provided the demonstration that routine stenting is the best strategy for percutaneous intervention in coronary arteries with a reference diameter smaller than 2.75-3.0 mm. This paper describes the rationale for provisional stenting in this clinical setting and reviews the role of quantitative coronary angiography, intracoronary ultrasound and intracoronary Doppler measurements in the identification of lesions that would benefit from adjunctive stent placement after balloon angioplasty and in guiding stent implantation.     

Thrombosis of microvascular anastomoses in traumatized vessels: fibrin versus platelets

Thrombosis is the end result of two closely interrelated processes: the coagulation cascade and the platelet aggregation process. To determine their relative contribution, we used pharmacologic agents that selectively block each process. The specific effect of each pharmacologic agent on either fibrin deposition or platelet activity was confirmed morphologically by scanning electron microscopy and was substantiated with ADP-induced platelet aggregation and blood clotting time determinations. Forty-two rats had both femoral arteries subjected to a standardized crush-avulsion injury. A total of 84 femoral microvascular anastomoses were subsequently performed. None of the 24 control anastomoses treated with saline remained patent, whereas 6 of 24 of the anastomoses treated with dazmagrel (a selective thromboxane synthetase and platelet aggregation inhibitor), 2.5 mg/kg IV, remained patent and 18 of 24 of those treated with a single dose of heparin, 200 U/kg IV, remained patent. All 12 anastomoses treated with both drugs remained patent but developed a 33 percent hematoma rate. We conclude that in this microvascular model, fibrin mesh deposition is a more significant factor than platelet aggregation in the pathogenesis of occlusional thrombosis within traumatized arteries. Its temporary inhibition with a single dose of heparin yielded a 75 percent improvement in patency rate.     

Mesoscale simulation of blood flow in small vessels

Computational modeling of blood flow in microvessels with internal diameter 20-500 microm is a major challenge. It is because blood in such vessels behaves as a multiphase suspension of deformable particles. A continuum model of blood is not adequate if the motion of individual red blood cells in the suspension is of interest. At the same time, multiple cells, often a few thousands in number, must also be considered to account for cell-cell hydrodynamic interaction. Moreover, the red blood cells (RBCs) are highly deformable. Deformation of the cells must also be considered in the model, as it is a major determinant of many physiologically significant phenomena, such as formation of a cell-free layer, and the Fahraeus-Lindqvist effect. In this article, we present two-dimensional computational simulation of blood flow in vessels of size 20-300 microm at discharge hematocrit of 10-60%, taking into consideration the particulate nature of blood and cell deformation. The numerical model is based on the immersed boundary method, and the red blood cells are modeled as liquid capsules. A large RBC population comprising of as many as 2500 cells are simulated. Migration of the cells normal to the wall of the vessel and the formation of the cell-free layer are studied. Results on the trajectory and velocity traces of the RBCs, and their fluctuations are presented. Also presented are the results on the plug-flow velocity profile of blood, the apparent viscosity, and the Fahraeus-Lindqvist effect. The numerical results also allow us to investigate the variation of apparent blood viscosity along the cross-section of a vessel. The computational results are compared with the experimental results. To the best of our knowledge, this article presents the first simulation to simultaneously consider a large ensemble of red blood cells and the cell deformation.     

X-ray TV system for measuring microcirculation in small pulmonary vessels

We developed a new system that consists of 1) a specially designed X-ray apparatus, 2) an X-ray-sensitive 1-in. Vidicon camera, and 3) a digital image-processing device. The picture element is approximately 20 micron in size, and the time required for one frame is 1/30 s. Using this system, we measured the internal diameter (ID), the cross-sectional area, flow velocity, volume flow, and transit time of small pulmonary vessels of approximately 100-500 micron at control and with serotonin in anesthetized cats. Flow velocity and volume flow from large [458 +/- 22 (SE) micron] to small (340 +/- 32 micron) arteries were 5.4 +/- 0.4 cm/s and 0.53 +/- 0.06 ml/min, respectively. Transit times of the contrast medium from large to small arteries (Ta) and to large veins (Tv) were 0.68 +/- 0.04 and 3.71 +/- 0.25 s, respectively. Serotonin injection (20-30 micrograms/kg iv) decreased ID, flow velocity, and volume flow of arteries by 8-48, 32, and 76%, respectively, whereas Ta and Tv increased by 91 and 69%, respectively. The system can provide useful information regarding the local circulation in the lung.     

Neuropeptide Y-induced constriction in small resistance vessels of skeletal muscle

The in vivo responsiveness of small arterioles and venules in the rat cremaster muscle to topical administration of neuropeptide Y was assessed using closed-circuit television microscopy. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital (50 mg/kg) and the cremaster muscle was exposed to increasing bath concentrations of neuropeptide Y (10(-10)-10(-7) M). Neuropeptide Y produced dose-dependent constrictions in first (90 +/- 8 microns), second (50 +/- 6 microns) and third (21 +/- 4 microns) order arterioles. Arteriolar reactivity to the peptide was inversely related to vessel diameters. Venules were relatively unresponsive to neuropeptide Y. Exposure to the alpha-adrenergic receptor antagonist, phentolamine (10(-6) M), failed to modify the arteriolar constrictor responses to neuropeptide Y, while pretreatment with the sympathetic neuronal blocking agent, guanethidine (10(-5) M), produced a small, but significant, reduction in sensitivity. These data suggest that neuropeptide Y causes constriction of arterioles of skeletal muscle, primarily by acting directly on vascular smooth muscle to induce contraction, and not via release of endogenous norepinephrine.     

Accuracy of colour Doppler ultrasound velocity measurements in small vessels

Colour Doppler ultrasound offers the possibility of imaging small vessels not visible by B-mode alone. The colour Doppler image of velocities allows the course of small vessels to be imaged in the X-Y plane of the scan provided the Doppler frequency shift is of sufficient magnitude. This permits alignments of the Doppler cursor, allowing angle correction to provide true velocity measurements from the Doppler shift obtained. Before attempting to make velocity measurements, however, it is essential to be aware of the possible error in the Z plane caused by the thickness of the Doppler sample volume. To quantify this source of error, hydrophone and flow-rig measurements were performed on an Acuson 128 colour Doppler scanner with both 5 MHz linear-array and 3.5 MHz phased-array transducers. Measurements of the transmitted pulses using a point hydrophone showed that both probes employ approximately 3.5 MHz Doppler pulses (in both colour and pulsed Doppler modes). The two transducers have the same axial resolution. In colour Doppler mode the axial length of the sample volume increases automatically with depth by up to 0.5 mm. Measurements of colour and pulsed Doppler signal strength were obtained in a controlled flow rig. Both transducers produced accurate colour flow images of the phantom at their optimum depths; flow velocity errors due to Z-plane thickness are < 5%. There was, however, substantial error outside these optimum conditions (up to 20%).     

A morphological quantitative study of small vessels in diabetic cardiomyopathy

In 25 adult diabetic patients, tissue fragments from myocardium were removed at necropsy and processed routinely. The morphometrical analysis was made using eye-piece ocular micrometer on a definite microscopic area. The arteriolar wall thickness increased from 5.10 mu +/- 1.71 in control group to 7.37 mu +/- 1.98 in the diabetic heart. The arterioles number decreased from 5.82/mm2 +/- 0.54 in the nondiabetics to 2.51/mm2 +/- 0.65 in the diabetic heart. The mean arteriolar diameter increased from 24.61 mu +/- 7.7 in the control group to 29.45 mu +/- 8.25 in the diabetic myocardium. The mean capillary diameter increased from 4.09 mu +/- 0.63 to 5.69 mu +/- 1.34 in diabetics. The capillaries number/mm2 decreased from 6.98 +/- 1.55 in the nondiabetics to 4.39 +/- 1.54 in diabetic patients. All differences, less the mean arteriolar diameter, are statistically significant. The following microscopical aspects were found in the small intramural coronary arteries: proliferation of endothelial cells with focal protuberances leading to partial narrowing of the lumen; increased thickness of the arteriolar wall due to fibrosis and accumulation of neutral mucopolysaccharides; alterations of elastic fibers. Frequently small areas of perivascular fibrosis and isolated foci of myocytolysis were found as well. These results suggest that the arteriolar impairment, especially the thickening of the arteriolar wall, could play a role in the pathogenesis of diabetic cardiomyopathy.     

Nonuniform effects of histamine on small pulmonary vessels in cats

In in vivo cat lung, using an X-ray TV system, we analyzed responses in internal diameter (ID), flow velocity, and volume flow of arteries and veins (100-500 microns ID) to histamine (8-15 micrograms/kg iv) under three conditions. With histamine alone, three types of ID response (constriction, dilatation, and no change) occurred in parallel-arranged arteries. Relative frequency and magnitude of constriction were maximum in arteries of 300-400 micron ID, whereas those of dilatation were maximum in arteries of 100-200 micron ID. In veins, relatively uniform constriction occurred. Under H2-blockade, histamine caused greater constriction than that with histamine alone in arteries and veins of 300-500 micron ID. Under beta-blockade, with histamine, ID of all vessels decreased significantly below the ID sizes under the above two conditions, and no dilatation occurred. In two parallel arteries that showed opposite ID changes to histamine, flow velocity increased, but volume flow decreased in a constricted artery while it increased in a dilated one. Those data indicated that, with histamine, qualitatively and quantitatively nonuniform ID response was induced in both parallel- and series-arranged small pulmonary arteries and, in turn, produced heterogeneous flow distribution. Factors to cause the nonuniformity may be partly explained by difference in density of H2- and beta-receptors in vascular walls.     

Vagally and acetylcholine-mediated constriction in small pulmonary vessels of rabbits

Using a new X-ray TV system, we analyzed effects of vagal nerve stimulation (VNS; 1-30 Hz) and intravenous injection of acetylcholine (Ach; 0.3-0.9 microgram) on the internal diameter (ID; 100-1,500 microns) of small pulmonary arteries and veins in anesthetized rabbits. In selective segments of the arteries, ID decreased abruptly and maximally by 50-70% in a specific stimulus frequency to the vagal nerve and a dose of ACh. The vasoconstrictor sites were distributed near the branching points of the arteries, particularly those downstream, and their numbers increased with an increase in the stimulus frequencies and ACh doses. The relative frequencies of occurrences were 15.3% with VNS (30 Hz) and 5.3% with ACh (0.9 microgram). In nonselective segments with VNS, ID decreased frequency dependently by 0, 4, 12, and 26% at 1, 4, 15, and 30 Hz, respectively, and with ACh, decreased dose dependently by 21 and 35% with 0.3 and 0.9 microgram, respectively. The vasoconstriction in response to VNS and ACh was attenuated by atropine, enhanced by eserine, and not affected by phentolamine. That vasoconstriction to VNS was abolished by hexamethonium. No selective constriction was found in veins and the ID was decreased uniformly by 1-2% with VNS and ACh.