cardiovascular-agents and Hyperemia

Chest pain in patients without obstructive coronary artery disease has been realized as a frequent problem encountered in clinical practice. Invasive flow investigations have suggested that up to two-thirds of patients with nonobstructive coronary atherosclerosis may have microvascular dysfunction (MVD). Positron emission tomography myocardial perfusion imaging in conjunction with tracer-kinetic modeling enables the concurrent quantification of myocardial blood flow (MBF) in milliliters per minute per gram of tissue. This allows the assessment of hyperemic MBFs and myocardial flow reserve for the noninvasive identification and characterization of MVD as an important functional substrate for angina symptoms amenable to intensified and individualized medical intervention with nitrates, calcium-channel blockers, statins, angiotensin-converting enzyme inhibitors, and/or angiotensin II type 1 receptor blockers. Recent investigations suggest that cardiac magnetic resonance and computed tomography may also be suitable for the noninvasive detection of MVD. Whether intensified and individualized treatment related improvement or even normalization of hyperemic MBF and/or myocardial flow reserve may lead to a persistent reduction in angina symptoms and/or improved cardiovascular outcome as compared to standard care, deserves further testing in large-scale randomized clinical trials.

Topics: Adult; Aged; Angina Pectoris; Blood Flow Velocity; Cardiovascular Agents; Coronary Artery Disease; Coronary Circulation; Female; Humans; Hyperemia; Magnetic Resonance Imaging; Male; Microcirculation; Middle Aged; Myocardial Perfusion Imaging; Positron Emission Tomography Computed Tomography; Predictive Value of Tests; Progression-Free Survival; Risk Factors; Risk Reduction Behavior

The pathophysiologic interactions that link the heart and kidney are multiple and complex, and have been grouped under the umbrella term "cardiorenal syndrome." In the setting of acute decompensated heart failure, worsening renal function has been directly associated with poor clinical prognosis and complicates treatment. However, the pathophysiology underlying acute cardiorenal syndrome remains incompletely understood and treatment options remain limited. Traditionally, the development of worsening renal function in acute decompensated heart failure has been attributed to renal arterial underfilling due to reduced cardiac output or intravascular volume depletion. However, increasing data have expanded our understanding of the roles that venous congestion and intra-abdominal pressure play in driving renal injury, with important implications for therapeutic management and the development of novel renal-sparing therapies.

Topics: Acute Kidney Injury; Cardiac Output; Cardiovascular Agents; Critical Pathways; Fluid Shifts; Heart Failure; Humans; Hyperemia; Kidney; Kidney Function Tests; Plasma Volume; Treatment Outcome

We investigated the effect of ranolazine on endothelial-dependent vasodilatation (EDV), serum markers of endothelial dysfunction, and inflammation.. Endothelial dysfunction has been shown to be independently associated with the occurrence of cardiovascular events. We sought to investigate whether ranolazine, a novel antianginal medication with no effect on heart rate or blood pressure, improves endothelial function in patients with stable coronary artery disease (CAD).. Twenty-seven patients with stable CAD were randomly assigned to either 1000 mg twice daily of ranolazine or to matching placebo for 6 weeks and then crossed over for an additional 6 weeks in a double-blind design. EDV was assessed using reactive hyperemia peripheral arterial tonometry (RH-PAT) at baseline, 6, and 12 weeks. Markers of endothelial dysfunction and inflammation were also evaluated.. After 6 weeks, treatment with ranolazine significantly increased the EDV RH-PAT index as compared with baseline (1.85+/-0.42 vs. 2.08+/-0.57, P = 0.037). EDV RH-PAT did not change while on placebo (1.69+/-0.35 vs. 1.78+/-0.41, P = 0.29). In addition, there was a significant drop in asymmetric dimethylarginine levels with ranolazine treatment (0.66+/-0.12 vs. 0.60+/-0.11 micromol/l, P = 0.02) and a near significant decrease in C-reactive protein levels (0.40+/-0.80 vs. 0.30+/-0.61 mg/dl, P = 0.05).. Ranolazine improves endothelial function, asymmetric dimethylarginine, and C-reactive protein levels in a group of patients with stable CAD. Our results suggest a novel mechanism of action of ranolazine.

Topics: Acetanilides; Aged; Arginine; Biomarkers; C-Reactive Protein; Cardiovascular Agents; Coronary Artery Disease; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hyperemia; Inflammation Mediators; Male; Manometry; Middle Aged; Piperazines; Ranolazine; Time Factors; Treatment Outcome; Vasodilation

Endothelial function (EF) impairment is one of the first events in the process of atherosclerosis, which is known to be associated with psoriasis. Nevertheless, the effect of antipsoriatic treatments, some of them with atherogenic risks, on cardiovascular morbidity and EF is still unclear.. To investigate the effect of short-term antipsoriatic treatments on EF values as a potential marker of their effect on cardiovascular morbidity.. EF was evaluated in 26 patients with moderate-to-severe psoriasis by measuring microvascular blood flow, expressed as the reactive hyperaemia index (RHI), before and after phototherapy (8 weeks) or systemic antipsoriatic treatment (12 weeks).. Antipsoriatic intervention was effective (46% achieving ≥ 75% improvement in Psoriasis Area and Severity Index), while the average RHI did not improve during the study (1·73 ± 0·48. vs. 1·66 ± 0·35, average difference -0·12 ± 0·43, not significant). Patients with baseline preserved EF exhibited a decline in RHI (difference -0·2 ± 0·4, P = 0·053), while patients with abnormal baseline RHI presented nonsignificant RHI improvement (RHI difference 0·1 ± 0·2).. There was no positive effect on EF of short-term antipsoriatic treatment. It is possible that a longer period of treatment and EF evaluation would uncover a positive endothelial effect, especially in patients with baseline abnormal EF.

Topics: Adult; Cardiovascular Agents; Chronic Disease; Dermatologic Agents; Endothelium, Vascular; Female; Humans; Hyperemia; Male; Prospective Studies; Psoriasis; Ultraviolet Therapy

To determine if age-associated vascular dysfunction in older adults with heart failure (HF) is due to insufficient synthesis of nitric oxide (NO), we performed two separate studies: 1) a kinetic study with a stable isotope tracer method to determine in vivo kinetics of NO metabolism, and 2) a vascular function study using a plethysmography method to determine reactive hyperemic forearm blood flow (RH-FBF) in older and young adults in the fasted state and in response to citrulline ingestion. In the fasted state, NO synthesis (per kg body wt) was ∼ 50% lower in older vs. young adults and was related to a decreased rate of appearance of the NO precursor arginine. Citrulline ingestion (3 g) stimulated de novo arginine synthesis in both older [6.88 ± 0.83 to 35.40 ± 4.90 μmol · kg body wt(-1) · h(-1)] and to a greater extent in young adults (12.02 ± 1.01 to 66.26 ± 4.79 μmol · kg body wt(-1) · h(-1)). NO synthesis rate increased correspondingly in older (0.17 ± 0.01 to 2.12 ± 0.36 μmol · kg body wt(-1) · h(-1)) and to a greater extent in young adults (0.36 ± 0.04 to 3.57 ± 0.47 μmol · kg body wt(-1) · h(-1)). Consistent with the kinetic data, RH-FBF in the fasted state was ∼ 40% reduced in older vs. young adults. However, citrulline ingestion (10 g) failed to increase RH-FBF in either older or young adults. In conclusion, citrulline ingestion improved impaired NO synthesis in older HF adults but not RH-FBF, suggesting that factors other than NO synthesis play a role in the impaired RH-FBF in older HF adults, and/or it may require a longer duration of supplementation to be effective in improving RH-FBF.

Topics: Adult; Aged; Arginine; Cardiovascular Agents; Citrulline; Dietary Supplements; Elder Nutritional Physiological Phenomena; Endothelium, Vascular; Female; Forearm; Heart Failure; Humans; Hyperemia; Kinetics; Male; Middle Aged; Nitric Oxide; Regional Blood Flow; Severity of Illness Index; Up-Regulation; Young Adult

Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) may create an ischemic substrate conducive to sudden death, but it remains unknown whether the extent of hypertrophy is associated with proportionally poorer perfusion reserve. Comparisons between magnitude of hypertrophy, impairment of perfusion reserve, and extent of fibrosis may offer new insights for future clinical risk stratification in HCM but require multiparametric imaging with high spatial and temporal resolution.. Degree of hypertrophy, myocardial blood flow at rest and during hyperemia (hMBF), and myocardial fibrosis were assessed with magnetic resonance imaging in 35 HCM patients (9 [26%] male/26 female) and 14 healthy controls (4 [29%] male/10 female), aged 18 to 78 years (mean+/-SD, 42+/-14 years) with the use of the American Heart Association left ventricular 16-segment model. Resting MBF was similar in HCM patients and controls. hMBF was lower in HCM patients (1.84+/-0.89 mL/min per gram) than in healthy controls (3.42+/-1.76 mL/min per gram, with a difference of -0.95+/-0.30 [SE] mL/min per gram; P<0.001) after adjustment for multiple variables, including end-diastolic segmental wall thickness (P<0.001). In HCM patients, hMBF decreased with increasing end-diastolic wall thickness (P<0.005) and preferentially in the endocardial layer. The frequency of endocardial hMBF falling below epicardial hMBF rose with wall thickness (P=0.045), as did the incidence of fibrosis (P<0.001).. In HCM the vasodilator response is reduced, particularly in the endocardium, and in proportion to the magnitude of hypertrophy. Microvascular dysfunction and subsequent ischemia may be important components of the risk attributable to HCM.

Topics: Adolescent; Adult; Aged; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Contrast Media; Coronary Circulation; Endocardium; Female; Fibrosis; Gadolinium DTPA; Humans; Hyperemia; Image Processing, Computer-Assisted; Magnetic Resonance Angiography; Male; Microcirculation; Middle Aged; Myocardial Ischemia; Myocardium; Rest; Risk; Vasodilation

We have characterized the coronary vascular reserve, left ventricular function and inotropic response in dogs with chronic heart failure consequent to intracoronary embolization (EMB) with 50 microns spheres. We conducted studies 12-39 months after embolization and contrasted the findings with normal (CON) dogs. Acute embolization produced sustained LV volume enlargement and increased wall thickness, reduction of LV ejection fraction and elevated end-diastolic pressures; resting catecholamine levels were also increased. Responses to phenylephrine, nitroprusside, and dobutamine were identical in CON and EMB and coronary vasodilator reserve was reduced despite larger coronary vascular volume. Analysis by light microscopy showed a diffuse focal and interstitial fibrosis distributed uniformly from endocardium to epicardium associated with 14% loss of myocytes. This created a functional separation of myocardial muscle bundles and a disruption of the syncytial nature of the heart. Electron microscopy of the areas of fibrosis revealed myocytes in states ranging from normal appearing, to ghosts with evidence of cytolysis and loss of the sarcolemma. This model of chronic congestive heart failure with LV systolic dysfunction and elevated LV diastolic pressures shares a number of features with the syndrome in humans.

Topics: Animals; Blood Flow Velocity; Cardiovascular Agents; Chronic Disease; Coronary Circulation; Coronary Vessels; Disease Models, Animal; Dogs; Echocardiography; Embolism; Heart Failure; Hemodynamics; Hyperemia; Microscopy, Electron; Myocardial Ischemia; Myocardium; Ventricular Dysfunction, Left