Effect of young age on coronary adaptations to left ventricular pressure overload hypertrophy in sheep

Flanagan, Michael F.; Aoyagi, Takaaki; Currier, Joseph J.; Colan, Steven P.; Fujii, Alan M.

doi:10.1016/0735-1097(94)90188-0

Cited by 37 publications

(40 citation statements)

References 31 publications

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“…Notably, our study is limited by the use of relatively young animals that may have been more sensitive to the effect of hypertension (55) and statins on vascular development. Furthermore, changes in small resistance arterioles under 80 m in size were not fully addressed by our method and could account for some of the discrepancies with other studies.…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Prevents Coronary Microvascular Remodeling in Renovascular Hypertensive Pigs

Zhu

Daghini

Chade

et al. 2007

Journal of the American Society of Nephrology

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Patients with hypertension and chronic kidney disease are at risk for cardiovascular diseases, possibly related to inflammation. Statins have beneficial anti-inflammatory effects on vascular structure regardless of cholesterol reduction. It was hypothesized that alterations in myocardial microvascular structure in swine renovascular hypertension (RVH) would be improved by simvastatin treatment. Three groups of pigs were studied after 12 wk: Normal (n ‫؍‬ 7), RVH (n ‫؍‬ 7), or RVH؉simvastatin (RVH؉S; 80 mg/d; n ‫؍‬ 6). Left ventricular muscle mass and myocardial perfusion were determined in vivo using electron beam computed tomography, and myocardial samples then were scanned ex vivo using micro-computed tomography for measurement of the spatial density of myocardial microvessels (80 to 500 m) in situ. Capillary density and myocardial expression of inflammatory and growth factors were determined in myocardial tissue. The effects of simvastatin on inflammation-induced tube formation were evaluated in vitro in human umbilical vein endothelial cells that were exposed to TNF-␣. RVH and RVH؉S had similarly increased arterial pressure and serum creatinine. However, left ventricular hypertrophy was prevented by simvastatin, and myocardial perfusion was increased. Compared with normal, RVH showed increased spatial density of microvessels (169.6 ؎ 21 versus 107.7 ؎ 15.2 vessels/cm 2 ; P < 0.05), which was decreased in RVH؉S (72.5 ؎ 14.9 vessels/cm 2 ), whereas capillary density remained similar to normal. RVH also increased myocardial expression of inflammatory and growth factors, which were reversed by simvastatin. Furthermore, simvastatin attenuated TNF-␣-induced angiogenesis in vitro. Simvastatin prevents myocardial microvascular remodeling and hypertrophy in experimental RVH independent of lipid lowering. This protective effect is partly mediated by blunted expression as well as angiogenic activity of inflammatory cytokines. 18: 120918: -121718: , 200718: . doi: 10.1681 P atients with chronic kidney disease (CKD) and hypertension are at particularly high risk for cardiovascular diseases, characterized by cardiomyopathy and high prevalence of heart failure. The underlying mechanisms are not clear (1-3) but may be partly mediated by increased systemic and local inflammation in target organs (4). Microvascular remodeling and dysfunction often precede overt large-vessel injury in cardiovascular diseases and represents a strong, independent predictor of prognosis in hypertrophic cardiomyopathy (5). Microvascular remodeling, which may include remodeling of the wall; three-dimensional (3D) architecture; and spatial density of the arteries, arterioles, and capillaries, contributes critically to elevated peripheral resistance and complications of hypertension by interfering with blood supply and leading to ischemia. We previously demonstrated in pigs that renovascular hypertension (RVH) impairs coronary microvascular function (6). Indeed, CKD is often accompanied by hypertension, which may be partly responsible for its ass...

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Section: Discussionmentioning

confidence: 99%

Simvastatin Prevents Coronary Microvascular Remodeling in Renovascular Hypertensive Pigs

Zhu

Daghini

Chade

et al. 2007

Journal of the American Society of Nephrology

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“…Studies in fetal and newborn animals suggest that increased cardiac mass resulting from a variety of factors, including pulmonary artery and/or ascending aorta banding or chronic isovolemic anemia, is accompanied by increased myocardial vascularization (13,14,24). In young pigs, pulmonary artery banding results in rapid induction (2 h) of genes important for vascular growth, including VEGF and VEGFR-2 mRNA (3).…”

Section: Vascular Adaptationsmentioning

confidence: 99%

Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep

Mascio

Olison

Ralphe

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…As the adult heart progresses to hypertrophy, there is a relative decrease in microvascular density and an increase in intercapillary diffusion distance and coronary vascular resistance (43). In contrast, young animals with pressure overload display angiogenesis proportionate to hypertrophy such that capillary density and coronary conductance remain normal (12).…”

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confidence: 99%

Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts

Dalshaug¹,

Scholz

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts. Am J Physiol Heart Circ Physiol 282: H1359-H1369, 2002. First published December 6, 2001 10.1152/ajpheart.00686.2001.-To test the hypothesis that coronary flow and coronary flow reserve are developmentally regulated, we used fluorescent microspheres to investigate the effects of acute (6 h) pulmonary artery banding (PAB) on baseline and adenosine-enhanced right (RV) and left ventricular (LV) blood flow in two groups of twin ovine fetuses (100 and 128 days of gestation, term 145 days, n ϭ 6 fetuses/ group). Within each group, one fetus underwent PAB to constrict the main pulmonary artery diameter by 50%, and the other twin served as a nonbanded control. Physiological measurements were made 6 h after the surgery was completed; tissues were then harvested for analysis of selected genes that may be involved in the early phase of coronary vascular remodeling. Within each age group, arterial blood gas values, heart rate, and mean arterial blood pressure were similar between control and PAB fetuses. Baseline endocardial blood flow in both ventricles was greater in 100 than 128-day fetuses (RV: 341 Ϯ 20 vs. 230 Ϯ 17 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 ; LV: 258 Ϯ 18 vs. 172 Ϯ 23 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , both P Ͻ 0.05). In both age groups, RV and LV endocardial blood flows increased significantly in control animals during adenosine infusion and were greater in PAB compared with control fetuses. After PAB, adenosine further increased RV blood flow in 128-day fetuses (from 416 Ϯ 30 to 598 Ϯ 33 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , P Ͻ 0.05) but did not enhance blood flow in 100-day animals (490 Ϯ 59 to 545 Ϯ 42 ml ⅐ min Ϫ1 ⅐ 100 g Ϫ1 , P Ͼ 0.2). RV vascular endothelial growth factor and Flk-1 mRNA levels were increased relative to controls (P Ͻ 0.05) in 128 but not 100-day PAB fetuses. We conclude that in the ovine fetus, developmentally related differences exist in 1) baseline myocardial blood flows, 2) the adaptive response of myocardial blood flow to acute systolic pressure load, and 3) the responses of selected genes involved in vasculogenesis to increased load in the fetal myocardium.hypertrophy; vascular endothelial growth factor; angiogenesis IN THE ADULT, adaptive growth of the heart in response to hypertrophic stimuli involves functional and morphological changes that are predictable depending on the stimuli (32, 33). Concomitant with the development of cardiac hypertrophy in the adult are qualitative and quantitative changes in gene expression, including upregulation of the so-called fetal cardiac genes, including ␤-myosin heavy chain, ␣-actin, and atrial natriuretic factor, and a reversion to fetal metabolic pathways for energy production (1,32,33,43). In the fetal heart, however, the molecular triggers for increasing ventricular mass in response to increased load are poorly understood and may be quite different from those in the adult, particularly given the ability of the fetal heart to increase mass by both hypertrop...

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Effect of young age on coronary adaptations to left ventricular pressure overload hypertrophy in sheep

Cited by 37 publications

References 31 publications

Simvastatin Prevents Coronary Microvascular Remodeling in Renovascular Hypertensive Pigs

Simvastatin Prevents Coronary Microvascular Remodeling in Renovascular Hypertensive Pigs

Myocardial vascular and metabolic adaptations in chronically anemic fetal sheep

Effects of gestational age on myocardial blood flow and coronary flow reserve in pressure-loaded ovine fetal hearts

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