To study arterial dilatation in response to increased flow, we observed the bilateral common carotid arteries (CCAs) of 10 16-week-old rats that were maintained for 8 weeks after construction of an arteriovenous (AV) fistula between the left CCA and the jugular vein at a level 20 mm distal from the aortic orifice. The flow in the left CCA increased 11-fold and that of the right CCA increased twofold compared with values before surgery. The left CCA showed complete desquamation of endothelial cells in the distal one third of the segment proximal to the AV fistula. In the left CCA the endothelium-preserved area dilated significantly (the luminal radius was 134 times larger than control; p<0.001, n=4) with a significant increase of the cross-sectional area of the media (p<0.01, n=4) and showed high wall shear stress (70±ll dynes/cm 1 near the aortic orifice). In contrast, the endothelial cell-desquamated area did not dilate but did show very high wall shear stress (231 ±23 dynes/cm 2 ) without any intimal smooth muscle cell proliferation. The right CCA dilated significantly (luminal radius was 1.07 times larger than control; p<0.001, n=4) with a wall shear stress of 30 dynes/cm 2 near the brachiocephalic orifice. All CCAs retained their fundamental arterial structure. We conclude that in the rat CCA, arterial dilatation in response to increased flow is a gradual remodeling process related to the presence of endothelial cells that have been influenced by the level of flow increase. ( 1 As a long-term response to flow, Kamiya and Togawa, 2 using the arteriovenous (AV) fistula model in the canine carotid artery, suggested that the increased wall shear stress (WSS) induced the adaptive enlargement of the vessel radius, which acted as a negative feedback to reduce the stress itself. Recently Zarins et al, 3 using the AV fistula model, showed a reduction of WSS to baseline level in the flow-loaded iliac artery of cynomolgus monkeys. As a short-term response to flow, Hull et al 4 showed that acute dilatation due to increased flow velocity was endothelium dependent after the endothelial surface of the canine femoral artery was rubbed with a cotton ball. On the other hand, Guyton and Hartley 5 and Langille et al 6 -7 demonstrated that the in vivo reductions in arterial diameter could be induced by a decrease in flow and were endothelium dependent.Our experiments were designed to induce a blood flow increase in the common carotid artery (CCA) by formation of an AV fistula between the left CCA and From the Second Department of Pathology, Akita University School of Medicine, Akita, Japan.Address for reprints: Hirotake Masuda, MD, Second Department of Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010, Japan.Received Jury 8, 1991; revision accepted January 3, 1992.the left external jugular vein in rats; we then observed the morphological changes in the bilateral CCAs after 8 weeks. In this model, because the shunted left CCA showed a marked increase of flow (over 10-fold) and the right contralateral CCA show...

To Investigate the morphologic basis of blood flow-dependent adaptive vascular enlargement, we quantltated endothelial cell density, dimensions, and structure in canine carotid arteries that were flow-loaded for 4 weeks, i.e., Just before the development of significant adaptive enlargement Increased flow was produced In the right common carotid artery of seven adult beagle dogs by an arterlovenous shunt to the right external Jugular vein. The left common carotid artery was used to produce sham-operated controls. Five additional animals were used to produce sham-shunted controls, and two dogs were used as nonoperated controls. The blood flow rate (BFR) and wall shear rate (WSR) were markedly Increased immediately after anastomosis In the proximal segment of the shunted artery (BFR=719±142 ml/min, WSR>4127±1002/sec) and after 4 weeks (BFR=628±157 ml/mln, WSR>2919±388/ sec) compared to the same artery before anastomosis (BFR=154±50 ml/mln, WSR=904±314/sec, p<0.01x10~3 for both comparisons) and to the contralateral control artery after 4 weeks (BFR=365±110 ml/mln, WSR=2136±876/sec, p<0.01 and p<0.05, respectively, compared to the shunted side). In the shunted artery, endothelial cell density was markedly Increased (6.15±0.68x10 3 cells/mm 2 compared to 3.33±0.70x10 3 cells/mm 2 for the controls, p<0.001). Endothelial cells on the high flow side were markedly narrowed In both axial and circumferential directions, but were radially thickened; nuclei became prolate-spheroid in shape. On the control side, cells were relatively flat and thin. We conclude that elevated wall shear stress Induces an early Increase in endothellal cell number and that this Increase precedes the development of significant blood flow-dependent vascular enlargement (Arteriosclerosis 9:812-823, November/December 1989)

To investigate the effects of volume loading of the heart, the endocardium was studied histologically and ultrastructurally. Thirteen adult female beagle dogs were used. An arterio-venous shunt was constructed between the right common carotid artery and the right external jugular vein in nine animals to induce a volume load. Four animals were used as controls. All were kept for 6-12 months. Heart weight, relative heart weight (heart weight/body weight), cardiac output index, stroke volume index and volumes of both ventricles in the experimental animals were significantly larger than in the controls. Shunted blood volume was significantly correlated with heart weight. The endocardium of the left ventricle in the experimental animals showed elastofibrosis and was significantly thicker than in the controls. In 5 hearts, it was more than 2 0 p m thick and its endothelial cells showed many long microvilli with a very thick basement membrane (1.5-2.0pm).The thickness of the endocardium was significantly correlated with the heart weight, relative heart weight and cardiac output index, within 1% 5% and 5% risk, respectively. These endocardial changes were thought to be induced by hemodynamic changes in the left ventricle of the volume-loaded heart, probably being correlated with changes in cardiac function and morphology. Acta Pathol Jpn 39: 111-120, 1989.

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