Blood oxygen level-dependent magnetic resonance imaging identifies cortical hypoxia in severe renovascular disease.

Atherosclerotic renal artery stenosis has a range of manifestations depending on the severity of vascular occlusion. The aim of this study was to examine whether exceeding the limits of adaptation to reduced blood flow ultimately leads to tissue hypoxia, as determined by blood oxygen level dependent MRI. We compared 3 groups of hypertensive patients, 24 with essential hypertension, 13 with "moderate" (Doppler velocities 200-384 cm/s), and 17 with "severe" atherosclerotic renal artery stenosis (ARAS; velocities >384 cm/s and loss of functional renal tissue).

Enhanced endothelial progenitor cell angiogenic potency, present in early experimental renovascular hypertension, deteriorates with disease duration.

Background: Endothelial progenitor cells (EPCs) augment neovascularization and repair of damaged tissues, but may undergo functional changes during exposure to cardiovascular risk factors. This study tested the hypothesis that early renovascular hypertension (RVH) modulates the temporal pattern of EPC function that deteriorates with disease duration.

Methods: RVH was induced in domestic pigs by unilateral renal artery stenosis.

Blood oxygen level-dependent (BOLD) MRI in renovascular hypertension.

Establishing whether large vessel occlusive disease threatens tissue oxygenation and viability in the post-stenotic kidney is difficult for clinicians. Development of blood oxygen level-dependent (BOLD) MRI methods can allow functional evaluation of regional differences in deoxyhemoglobin levels within the kidney without requiring contrast. The complex renal circulation normally provides a gradient of oxygenation from a highly vascular cortex to much reduced levels in the deep sections of medulla, dependent upon adjustments in renal afferent arterioles, oxygen consumption related to solute transport, and arteriovenous shunting related to the juxtaposition of descending and ascending vasa recta.

Role of oxidative stress in hypoxia preconditioning of cells transplanted to the myocardium: a molecular imaging study.

Aim: Cell-based therapies are a potential therapeutic alternative for the treatment of coronary artery disease (CAD). However, transplanted cells undergo significant death in the living subject. Hypoxic preconditioning (HPC) is a potential intervention to increase transplanted cell survival.

Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation.

Metabolic syndrome (MetS) is associated with glomerular hyperfiltration and is a risk factor for chronic kidney disease, but the underlying mechanisms are poorly defined. This study tested the hypothesis that increased glomerular filtration rate (GFR) in early MetS is associated with renal adiposity and microvascular proliferation. Twelve MetS-prone Ossabaw pigs were randomized to 10 wk of a standard (lean, n = 6) or atherogenic (MetS, n = 6) diet.

Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice.

Objective: Humanin (HN) is a cytoprotective peptide derived from endogenous mitochondria, expressed in the endothelial layer of human vessels, but its role in atherogenesis in vivo is not known. In vitro study, however, HN reduced oxidized low-density lipoprotein induced formation of reactive oxygen species and apoptosis. The present study tested the hypothesis that long term treatment with HN will have a protective role against endothelial dysfunction and progression of atherosclerosis in vivo.

Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization.

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.

Noninvasive In vivo assessment of renal tissue elasticity during graded renal ischemia using MR elastography.

Objectives: : Magnetic resonance elastography (MRE) allows noninvasive assessment of tissue stiffness in vivo. Renal arterial stenosis (RAS), a narrowing of the renal artery, promotes irreversible tissue fibrosis that threatens kidney viability and may elevate tissue stiffness. However, kidney stiffness may also be affected by hemodynamic factors.

Association of kidney function and metabolic risk factors with density of glomeruli on renal biopsy samples from living donors.

Objective: To test the hypothesis that kidney function and metabolic risk factors are associated with glomerular density on renal biopsy samples from healthy adults.

Patients And Methods: This study compared glomerular density with predonation kidney function, blood pressure, and metabolic risk factors in living kidney donors at Mayo Clinic in Rochester, MN, from May 10, 1999, to February 4, 2009. During implantation of the kidney allograft, an 18-gauge core needle biopsy sample of the renal cortex was obtained, sectioned, and examined by pathologists.

Effects of statins on coronary and peripheral endothelial function in humans: a systematic review and meta-analysis of randomized controlled trials.

Objective: The purpose of this study was to quantify the effect of statins on peripheral and coronary endothelial function in patients with and without established cardiovascular disease.

Background: Early atherosclerosis is characterized by endothelial dysfunction, a known prognostic factor for cardiovascular disease.

Methods And Results: The search included MEDLINE, Cochrane Library, Scopus, and EMBASE to identify studies up to 1 December 2009.

Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect.

Objective: Isolated diastolic dysfunction is present in 40% of heart failure patients. It has been attributed to myocardial fibrosis and related to cardiovascular risk factor exposure. We hypothesized that simvastatin will improve these dynamics in experimental hypercholesterolemia (HC).

Persistent kidney dysfunction in swine renal artery stenosis correlates with outer cortical microvascular remodeling.

Percutaneous transluminal renal stenting (PTRS) does not consistently improve renal function in patients with atherosclerotic renovascular disease, but the mechanisms underlying irreversible kidney injury have not been fully elucidated. We hypothesized that renal dysfunction after PTRS is linked to ongoing renal microvascular (MV) remodeling. Pigs were studied after 10 wk of atherosclerosis and renal artery stenosis (ARAS), ARAS treated with PTRS 4 wk earlier, and normal controls (n = 10 each).

Renovascular hypertension: screening and modern management.

The diagnosis and management of patients with renovascular disease and hypertension continue to elude healthcare providers. The advent of novel imaging and interventional techniques, and increased understanding of the pathways leading to irreversible renal injury and renovascular hypertension, have ushered in commendable attempts to optimize and fine-tune strategies to preserve or restore renal function and control blood pressure. Large randomized clinical trials that compare different forms of therapy, and smaller trials that test novel experimental treatments, will hopefully help formulate innovative concepts and tools to manage the patient population with atherosclerotic renovascular disease.

Reversal of experimental renovascular hypertension restores coronary microvascular function and architecture.

Background: Hypertension (HTN) may lead to left ventricular hypertrophy and vascular dysfunction, which are independent factors for adverse cardiovascular outcomes. We hypothesized that decreased blood pressure by percutaneous transluminal renal angioplasty (PTRA) would improve the function and architecture of coronary microvessels, in association with decreased inflammation and fibrosis.

Methods: Three groups of pigs were studied: normal, HTN, and HTN+PTRA.

Early experimental hypertension preserves the myocardial microvasculature but aggravates cardiac injury distal to chronic coronary artery obstruction.

Coronary artery disease is a leading cause of death. Hypertension (HT) increases the incidence of cardiac events, but its effect on cardiac adaptation to coexisting coronary artery stenosis (CAS) is unclear. We hypothesized that concurrent HT modulates microvascular function in chronic CAS and aggravates microvascular remodeling and myocardial injury.

Endothelial function and vascular response to mental stress are impaired in patients with apical ballooning syndrome.

Objectives: The aim of the current study was to test the hypothesis that vascular and endothelial functional responses to acute mental stress are abnormal in patients with apical ballooning syndrome (ABS).

Background: Apical ballooning syndrome is a transient cardiomyopathy that occurs predominantly in post-menopausal women and may be triggered by acute mental stress. The mechanism for ABS is unknown.

Improved survival of mesenchymal stromal cell after hypoxia preconditioning: role of oxidative stress.

Aims: To investigate the mechanisms underlying the beneficial effect of hypoxia preconditioning (HPC) on mesenchymal stromal cells (MSCs) and optimize novel non-invasive methods to assess the effect of biological interventions aimed to increased cell survival.

Main Methods: MSCs from rat femur, with or without HPC, were exposed to hypoxic conditions in cell culture (1% O(2) for 24h) and cell survival (by the LDH release assay and Annexin-V staining) was measured. Oxidant status (conversion of dichloro-fluorescein-DCF- and dihydro-ethidium-DHE-, protein expression of oxidant enzymes) was characterized, together with the mobility pattern of cells under stress.

Coronary endothelial dysfunction in humans is associated with coronary retention of osteogenic endothelial progenitor cells.

Aims: Endothelial progenitor cells (EPC) may participate in the repair of injured coronary endothelium. We have recently identified EPC co-expressing the osteoblastic marker osteocalcin [OCN (+) EPC] and found that their numbers are increased in patients with early and late coronary atherosclerosis. The current study was designed to test the hypothesis that early coronary atherosclerosis is associated with the retention of osteogenic EPC within the coronary circulation.

Renovascular hypertension and ischemic nephropathy.

Renovascular disease remains among the most prevalent and important causes of secondary hypertension and renal dysfunction. Many lesions reduce perfusion pressure including fibromuscular diseases and renal infarction, but most are caused by atherosclerotic disease. Epidemiologic studies establish a strong association between atherosclerotic renal-artery stenosis (ARAS) and cardiovascular risk.

Determinations of renal cortical and medullary oxygenation using blood oxygen level-dependent magnetic resonance imaging and selective diuretics.

Objective: This study was undertaken to test the hypothesis that blood O2 level-dependent magnetic resonance imaging (BOLD MRI) can detect changes in cortical proximal tubule (PT) and medullary thick ascending limb of Henle (TAL) oxygenation consequent to successive administration of furosemide and acetazolamide (Az). Assessment of PT and TAL function could be useful to monitor renal disease states in vivo. Therefore, the adjunct use of diuretics that inhibit Na reabsorption selectively in PT and TAL, Az and furosemide, respectively, may help discern tubular function by using BOLD MRI to detect changes in tissue oxygenation.

Determination of aqueous stability and degradation products of series of coumarin dimers.

The stability in aqueous solution of five classes of coumarin dimers (I-V, compounds 1-29) was studied by HPLC-MS/MS at various pH values. The relationship between chemical structure and stability is discussed. It was found that dimeric compounds with strong electron withdrawing groups (EWGs) on the α-carbon to the bridging C-atom are stable at all pH values, whereas other derivatives undergo retro-Michael addition at rates which are also affected by the substituents on the aromatic rings.

Long-term administration of endothelin receptor antagonist improves coronary endothelial function in patients with early atherosclerosis.

Background: Endothelin (ET-1) is one of the most potent vasoconstrictors and plays a seminal role in the pathogenesis of atherosclerosis. The present study was designed to test the hypothesis that long-term treatment with an endothelin-A (ET(A)) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis.

Methods And Results: Forty-seven patients with multiple cardiovascular risk factors, nonobstructive coronary artery disease, and coronary endothelial dysfunction were randomized in a double-blind manner to either the ET(A) receptor antagonist atrasentan (10 mg) or placebo for 6 months.