Vasodilation In Patients Research Articles

Nasal continuous positive airway pressure improves myocardial perfusion reserve and endothelial-dependent vasodilation in patients with obstructive sleep apnea.

BackgroundObstructive sleep apnea (OSA) has been associated with cardiovascular disease (CVD), but whether OSA is an independent risk factor for CVD is controversial. The purpose of this study is to determine if patients with OSA have subclinical cardiovascular disease that is detectable by multi-modality cardiovascular imaging and whether these abnormalities improve after nasal continuous positive airway pressure (nCPAP).ResultsOf the 35 consecutive subjects with newly diagnosed moderate to severe OSA recruited from the Stanford Sleep Disorders Clinic, 20 patients were randomized to active vs. sham nCPAP. Active nCPAP was titrated to pressures that would prevent sleep disordered breathing based on inpatient polysomnography. OSA patients had baseline vascular function abnormalities including decreased myocardial perfusion reserve (MPR), brachial flow mediated dilation (FMD) and nitroglycerin-induced coronary vasodilation. Patients randomized to active nCPAP had improvement of MPR (1.5 ± 0.5 vs. 3.0 ± 1.3, p = 0.02) and brachial FMD (2.5% ± 5.7% vs. 9.0% ± 6.5%, p = 0.03) after treatment, but those randomized to sham nCPAP showed no significant improvement. There were no significant changes seen in chamber sizes, systolic and diastolic function, valvular function and coronary vasodilation to nitroglycerin.ConclusionsPatients with moderate to severe OSA had decreased MPR and brachial FMD that improved after 3 months of nCPAP. These findings suggest that relief of apnea in OSA may improve microvascular disease and endothelial dysfunction, which may prevent the development of overt cardiovascular disease. Further study in a larger patient population may be warranted.

Randomized Placebo-Controlled Crossover Trial of Tadalafil in Raynaud's Phenomenon Secondary to Systemic Sclerosis

Conclusion: Tadalafil is well tolerated and safe in patients with systemic sclerosis but lacks efficacy in comparison with placebo. Summary: The endothelial injury of systemic sclerosis is associated with decreased nitric oxide production (Kahaleh et al, Rheum Diseases Clin N Am 2008;34:57-71). Type V cyclic GMP phosphodiesterase (PDE-5) affects the tone of smooth muscle. An intracellular regulator of smooth muscle tone is cyclic nucleotide monophosphate, cGMP. Nitric oxide synthase produces nitric oxide. Through a complex pathway, nitric oxide facilitates conversion of GTP into cGMP. PDE-5 breaks down intracellular cGMP. Therefore, inhibition of PDE-5 results in increased availability of intracellular cGMP and results in vasodilatation. Tadalafil is a PDE-5 inhibitor effective in the use of male erectile dysfunction. However, PDE-5 inhibitors have also been suggested as beneficial in patients with severe Raynaud's syndrome (Fries R et al, Circulation 2005;119:2980-5). Tadalafil is an intriguing PDE-5 inhibitor in that it has a half-life of 17.5 hours and efficacy up to 36 hours. The pharmacokinetics of tadalafil are not affected by food or alcohol, age, diabetes, or moderate hepatic insufficiency. It therefore would seem an ideal drug for facilitating vasodilatation in patients with Raynaud's syndrome. This was a randomized, prospective, double-blind, placebo-controlled, crossover study comparing oral tadalafil with a fixed daily dose of 20 mg for 4 weeks vs placebo. The study was conducted in patients with Raynaud's syndrome secondary to systemic sclerosis. Thirty-nine completed the study. All patients fulfilled American College of Rheumatology classification criteria for systemic sclerosis. All were at least 18 years of age and had evidence of at least six Raynaud's attacks during the 2-week pretreatment period. Patients with unstable angina, congestive heart failure, or use of nitrites for angina pectoris or any other condition as well as those with significant central nervous system disease were excluded. Before enrollment, all patients discontinued any other type of vasodilator. Patients were evaluated for duration and frequency of Raynaud's attacks and Raynaud condition scores (RCS). At the end of the evaluation period, there were no significant statistical differences in RCS scores, frequency of Raynaud's attacks, or duration of Raynaud's attacks between the treatment and placebo groups. Comment: The results of the study are disappointing but not conclusive. The participants in this trial had a longer duration of Raynaud's syndrome than those in other trials. Severity of Raynaud's syndrome secondary to systemic sclerosis often increases over time. Patients here may have had greater endothelial cumulative damage than those in other studies. Other studies have primarily evaluated the effect of PDE-5 inhibitors on ulcer healing. Only two patients in this study had active digital ulcers. However, overall, the current results do not support the use of tadalafil as treatment for Raynaud's syndrome secondary to systemic sclerosis at the dosage of 20 mg/d. The study was also burdened by a large placebo effect.

Prostacyclin and milrinone by aerosolization improve pulmonary hemodynamics in newborn lambs with experimental pulmonary hypertension

Aerosolized prostacyclin (PGI2) produces selective pulmonary vasodilation in patients with pulmonary hypertension (PH). The response to PGI2 may be increased by phosphodiesterase type 3 inhibitors such as milrinone. We studied the dose response effects of aerosolized PGI2 and aerosolized milrinone both alone and in combination on pulmonary and systemic hemodynamics in newborn lambs with Nomega-nitro-L-arginine methyl ester (L-NAME)-induced PH. We hypothesized that coaerosolization of PGI2 with milrinone would additively decrease pulmonary vascular resistance (PVR), prolong the duration of action of PGI2, and selectively dilate the pulmonary vasculature. Near-term lambs were delivered by C-section and instrumented and PH was induced by L-NAME (bolus 25 mg/kg; infusion 10 mg.kg(-1).h(-1)) and indomethacin. In the first set of experiments, PGI2 was aerosolized at random doses of 2, 20, 100, 200, 500, and 1,000 ng.kg(-1).min(-1) followed by milrinone at doses of 0.1, 1, and 10 microg.kg(-1).min(-1) over 10 min. In the second set of experiments, milrinone at 1 microg.kg(-1).min(-1) was aerosolized in combination with PGI2 at doses of 20, 100, and 200 ng.kg(-1).min(-1) over 10 min. Pulmonary arterial pressures (PAP) and PVR decreased significantly with increasing doses of aerosolized PGI2 and milrinone. The combination of PGI2 and milrinone significantly reduced PAP and PVR more than either of the drugs aerosolized alone. Addition of milrinone significantly increased the duration of action of PGI2. When aerosolized independently, PGI2 and milrinone selectively dilated the pulmonary vasculature but the combination did not. Milrinone enhances the vasodilatory effects of PGI2 on the pulmonary vasculature but caution must be exercised regarding systemic hypotension.

Acute Cardiovascular Effects of Apelin in Humans

Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure. Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr(1))apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all P<0.0001). Vasodilatation to acetylcholine (P=0.01) but not apelin (P=0.3) or sodium nitroprusside (P=0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all P<0.05). Systemic infusions of (Pyr(1))apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all P<0.01) but increased heart rate only in control subjects (P<0.01). Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure.

Endothelial function in patients with polycystic ovary syndrome: a long-term follow-up study

To investigate pulse wave reflection and endothelial-dependent vasodilation in patients with polycystic ovary syndrome (PCOS) and age-matched healthy controls. Long-term follow-up study. Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden. Sixty-seven patients with PCOS and with a mean age of 43.3 years at the follow-up investigation and 66 age-matched controls. Aplanation tonometry before and after β-2 receptor agonist (terbutaline) challenge. Baseline augmentation index (AI) aorta, baseline AI-radial, and change in AI-radial after terbutaline administration as a measure of endothelial-dependent vasodilation. There was no difference in baseline AI-aorta between patients with PCOS and control subjects. Change in AI-radial after terbutaline administration was less pronounced in patients with PCOS compared with control subjects. This difference remained when adjusted for use of combined oral contraceptives (OC)/hormone replacement therapy (HT) and postmenopausal status but not after adjustment for body mass index (BMI). Middle-aged patients with PCOS display signs of endothelial dysfunction in comparison to age-matched controls, but this is largely due to the increased prevalence of independent risk factors for cardiovascular disease found in this group.

Microalbuminuria is associated with impaired arterial and venous endothelium-dependent vasodilation in patients with Type 2 diabetes

Microalbuminuria in Type 2 diabetes is associated with arterial endothelial dysfunction, but the venous bed was never evaluated. To study the endothelial function in the venous and arterial bed in patients with Type 2 diabetes with normoalbuminuria or microalbuminuria. We evaluated 28 patients with Type 2 diabetes, glycated hemoglobin (HbA(₁c)) <7.5%, who were classified as normo- (albuminuria <30 mg/24 h; no.=16) or microalbuminuric (albuminuria 30-300 mg/24 h; no.=12). Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation by acetylcholine) and brachial artery flow-mediated vasodilation, respectively. Patients were normotensive (systolic arterial pressure: 131.1±10.6 mmHg) and on good metabolic control (HbA(₁c): 6.6±0.6%). Microalbuminuric patients presented impaired venous (32.9±17.4 vs 59.3±26.5%; p=0.004) and arterial vasodilation (1.8±0.9 vs 5.1±2.4; p<0.001), as compared to normoalbuminuric patients. There was a negative correlation between acetylcholine-induced venodilation and albuminuria (r=-0.62; p<0.001) and HbA(₁c) (r=-0.41; p=0.032). The same was observed between flow mediated arterial vasodilation and albuminuria (r=-0.49; p=0.007) and HbA(₁c) (r=-0.44; p=0.019). Venous and arterial vasodilation was positively correlated (r=0.50; p=0.007). Both venous and arterial endothelial function are impaired in Type 2 microalbuminuric diabetics, in spite of good metabolic control, suggesting that other factors are involved in its pathogenesis.

Vasodilators in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

Vasodilators in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

Alpha‐lipoic acid improves vascular endothelial function in patients with type 2 diabetes: a placebo‐controlled randomized trial

The aim of this study was to investigate the effect of alpha-lipoic acid (ALA) treatment on endothelium-dependent and -independent vasodilatation, assessed by forearm blood flow (FBF), in patients with type 2 diabetes mellitus. A total of 30 subjects with type 2 diabetes were included in this randomized, controlled, double-blinded, parallel group study. FBF responses to intra-arterial acetylcholine (ACh) and glycerol trinitrate (GTN) were measured before and after 21 days of intravenous treatment with 600 mg alpha-lipoic acid or placebo. FBF responses were comparable at baseline. After treatment, FBF reactivity to ACh and GTN was unchanged in subjects receiving placebo. By contrast, ALA treatment increased endothelium-dependent vasodilatation to ACh (P < 0.05) but not to GTN compared with baseline. Intravenous ALA treatment improves endothelium-dependent vasodilatation in patients with type 2 diabetes, in the absence of effects on forearm vasomotor function. If this salutary action translates into vascular risk reduction remains to be established.

Sarpogrelate Hydrochloride, a Selective 5-hydroxytryptamine2A Antagonist, Augments Autologous Bone Marrow Mononuclear Cell Implantation–induced Improvement in Endothelium-dependent Vasodilation in Patients With Critical Limb Ischemia

The purpose of this study was to determine the effect of a combination of bone marrow mononuclear cell (BM-MNC) implantation and sarpogrelate, a selective 5-HT(2A) antagonist, on endothelial function in patients with critical limb ischemia (CLI). We evaluated the leg blood flow (LBF) responses to acetylcholine (ACh) and sodium nitroprusside before and after BM-MNC implantation in 16 patients with CLI. We divided patients with CLI into 2 groups: those cotreated with sarpogrelate orally for 12 weeks (sarpogrelate group, n = 8) and those who remained on conventional therapy (control group, n = 8). LBF was measured by strain gauge plethysmography. BM-MNC implantation improved ankle brachial pressure index, transcutaneous oxygen pressure, and pain-free walking time. There was no significant difference in these parameters between the 2 groups. Before BM-MNC implantation, LBF responses to ACh were similar in the sarpogrelate group and control group. Twelve weeks of BM-MNC implantation enhanced LBF responses to ACh in the sarpogrelate and control groups. After 12 weeks of BM-MNC implantation, LBF response to ACh was significantly greater in the sarpogrelate group than in the control group. BM-MNC implantation did not alter the LBF responses to sodium nitroprusside in either group. These findings suggest that BM-MNC implantation improved not only limb ischemic symptoms but also endothelium-dependent vasodilation in patients with CLI. A combination of BM-MNC implantation and sarpogrelate had a more beneficial effect on vascular function in these patients.

Chakalaka-induced vasodilatation in patients with chronic myeloid leukaemia on tyrosine kinase inhibitors.

The tyrosine kinase inhibitors (TKIs) are a new group of drugs providing targeted therapy for chronic myeloid leukaemia (CML). They vastly increase survival, but compliance is an issue because they cause vasodilatation as a side-effect. In our experience spices, especially the African sauce or relish chakalaka (that contains garlic and chilli), may aggravate the vasodilatation induced by TKIs. These spices produce serious oedema and headaches. We have found that stopping the intake of spice allows some patients to maintain therapeutic doses of TKIs. This has been confirmed and put into practice by a growing number of South African haematologists. As spice that contains chilli and garlic is used by a large proportion of our South African (and the world) population, this observation is significant in that it can help to prevent the ‘compliance decay’ associated with TKI therapy, which adversely affects patient survival. CML represents up to 20% of all leukaemias, with a worldwide incidence of about 1 - 2/100 000 per year. There may be up to 450 new cases annually in South Africa. Imatinib is a tyrosine kinase receptor antagonist that inhibits the mutated tyrosine kinases such as Bcr-Abl, c-kit, and plateletderived growth factor receptor (PDGFR) in some malignancies. It has revolutionised the treatment of Philadelphia chromosome-positive CML. Imatinib causes fluid retention in 7 - 81% of patients. 1 Facial, peri-orbital and peripheral oedema occur most frequently. It causes headache in 27 - 39% of cases, 1 and even cerebral oedema. 2 Pietras et al. 3 have proposed that a second, still elusive, trigger is needed for these rare effects to occur. Dasatinib, another TKI, is a potent PDGFR inhibitor that causes fluid retention in up to 50% of patients. 4

Abstract 5147: GLP-1 Improves Insulin-Stimulated Nitric Oxide-Dependent Vasodilator Responsiveness in Patients With Metabolic Syndrome

Our previous work has shown that patients with metabolic syndrome (MetS) have impaired insulin-stimulated vasodilation, which may be involved in the development of hypertension and contribute to insulin resistance by affecting the glucose uptake. Glucagon-like peptide-1 (GLP-1), an amino acid gut hormone that stimulates both insulin secretion and sensitivity, is also provided of cardioprotective and vasoactive properties. We therefore examined the effects of exogenous GLP-1 on insulin-stimulated, nitric oxide (NO)-dependent vasodilation in patients with obesity-related MetS by use of the forearm perfusion technique. Forearm blood flow (FBF) responses to intra-arterial infusion of graded doses of acetylcholine (ACh; stimulus for endothelial release of NO) and sodium nitroprusside (SNP; exogenous NO donor) were assessed in 10 patients with MetS during coinfusion of either saline or regular insulin (0.2 mU/Kg/min). Thereafter, patients underwent to intra-arterial infusion of GLP-1 (30 ng/min for 45 minutes) and responses to ACh and SNP were then reassessed. In the absence of hyperinsulinemia, GLP-1 did not impact unstimulated FBF (from 3.5±0.2 [mean±SEM] to 3.6±0.3 ml/min/dl; P=0.59); similarly, exogenous GLP-1 did not affect vascular responses to both ACh (from 8.8±1.1 to 8.7±1.2 ml/min/dl at the highest dose; P=0.97) and SNP (from 10.7±0.6 to 9.6±0.7 ml/min/dl; P=0.68). In the presence of hyperinsulinemia, GLP-1 infusion was associated with mild increase in basal FBF (from 4.7±0.4 to 5.7±0.6 ml/min/dl; P=0.25); under those conditions, however, exogenous GLP-1 resulted in a significant improvement in vascular reactivity to both ACh (from 13.7±0.7 to 17.4±1.5 ml/min/dl; P=0.03) and SNP (from 12.7±1.0 to 15.9±1.2; P=0.02). In conclusion, exogenous GLP-1 improves both endothelium-dependent and -independent vasodilator responsiveness during hyperinsulinemia in patients with MetS. This suggests that GLP-1 may exert a facilitatory effect on insulin signaling to enhance NO-dependent reactivity in vascular smooth muscle. As a consequence, strategies targeting the GLP-1 system for treatment of type 2 diabetes might beneficially affect both metabolic and hemodynamic abnormalities associated with insulin resistance.

Alcohol Acutely Increases Vascular Reactivity together with Insulin Sensitivity in Type 2 Diabetic Men

Moderate alcohol consumption is associated with increased insulin sensitivity and reduced cardiovascular risk. We hypothesized that this relates to a direct effect of alcohol and therefore investigated whether acute alcohol intake altered insulin sensitivity or endothelial function in patients with type 2 diabetes. In an open-label two period design, the effect of a single oral dose of 40 g of alcohol (168 ml 40% vodka) on an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT) and on endothelium-dependent (flow mediated, FMD) or endothelium-independent (glyceroltrinitrate (GTN)-induced) vasodilation of the brachial artery measured by ultrasound was studied. Experiments were carried out in twelve male patients with type 2 diabetes mellitus (64+/-6 years, body mass index 28.4+/-5.7 kg/m (2)). Baseline insulin sensitivity index (S (I)) was 1.10+/-0.34 min (-1).microU (-1).ml, baseline FMD was +4.1+/-3.0%, and GTN-induced vasodilation +7.4+/-2.3% from resting brachial artery diameter. Acute alcohol intake increased alcohol plasma levels to 0.33+/-0.04 per thousand, S (I) to 1.86+/-0.45 min (-1).microU (-1).ml (p<0.05), and FMD to +8.2+/-2.8% (p<0.05), while GTN-induced dilation remained unchanged. No relationship was detectable between the observed changes. We conclude that alcohol intake acutely increases endothelium-dependent brachial artery vasodilation in patients with type 2 diabetes together with insulin sensitivity. This acute effect might explain some beneficial effects of low alcohol consumption in epidemiological observations.

Effect of Nebivolol and Atenolol on Brachial Artery Flow-Mediated Vasodilation in Patients with Coronary Artery Disease

Effect of Nebivolol and Atenolol on Brachial Artery Flow-Mediated Vasodilation in Patients with Coronary Artery Disease

Endothelium-dependent contractions and endothelial dysfunction in human hypertension.

The endothelium is a crucial regulator of vascular physiology, producing in healthy conditions several substances with a potent antiatherosclerotic properties. Accordingly, the presence of endothelial dysfunction is associated with subclinical atherosclerosis and with an increased future risk of cardiovascular events. A large body of evidence supports the fundamental role of nitric oxide (NO) as the main endothelium-derived relaxing factor. However, in the presence of pathological conditions, such as hypertension, endothelial cells, in response to a number of agents and physical stimuli, become also a source of endothelium-derived contracting factors (EDCFs), including endothelins and angiotensin II and particularly cyclooxygenase-derived prostanoids and superoxide anions. These latter were at first identified as responsible for impaired endothelium-dependent vasodilation in patients with essential hypertension. However, cyclooxygenase-dependent EDCFs production is characteristic of the aging process, and essential hypertension seems to only anticipate the phenomenon. It is worth noting that both in aging and hypertension EDCF production is associated with a parallel decrease in NO availability, suggesting that this substance could be oxygen free radicals themselves. Accordingly, in hypertension both indomethacin, a cyclooxygenase inhibitor, and vitamin C, an antioxidant, increase the vasodilation to acetylcholine by restoring NO availability. In conclusion, hypertension is characterized by a decline in endothelial function, associated with a progressive decrease in NO bioavailability and increase in the production of EDCF. The mechanisms that regulate the balance between NO and EDCF, and the processes transforming the endothelium from a protective organ to a source of vasoconstrictor, proaggregatory and promitogenic mediators remain to be determined.

Correlation of Flicker-Induced and Flow-Mediated Vasodilatation in Patients With Endothelial Dysfunction and Healthy Volunteers

OBJECTIVEFlicker-induced vasodilatation is reduced in patients with vascular-related diseases, which has at least partially been attributed to endothelial dysfunction of retinal vessels. Currently, the standard method to assess endothelial function in vivo is flow-mediated vasodilatation (FMD). Thus, the present study was performed to investigate whether a correlation exists between flicker-induced vasodilatation and FMD in patients with known endothelial dysfunction and healthy subjects.RESEARCH DESIGN AND METHODSIn the present study, 20 patients with type 1 diabetes, 40 patients with systemic hypertension (systolic blood pressure 140–159 mmHg; diastolic blood pressure 90–99 mmHg) and/or serum cholesterol levels ≥0.65 mmol/l, and 20 healthy control subjects were included. The flicker response was measured using the Dynamic Retinal Vessel Analyzer. FMD was determined using a high-resolution ultrasound system, measuring brachial artery diameter reactivity during reperfusion after arterial occlusion.RESULTSThe flicker response of both retinal arteries and veins was significantly reduced in the two patients groups. Likewise, FMD was significantly reduced in patients compared with healthy control subjects. However, only a weak correlation between flicker-induced vasodilatation and FMD was observed.CONCLUSIONSThe study confirms that flicker responses and FMD are reduced in the selected patient groups. Whether the weak correlation between FMD and flicker is due to the different stimulation type, the different vascular beds measured, or other mechanisms has yet to be investigated.

Impaired endothelial- and nonendothelial-mediated vasodilation in patients with acute or chronic hypothyroidism

Vascular dysfunction and accelerated atherosclerosis are prominent features of hypothyroidism. The relative roles of thyroid hormone (TH) deficiency and the associated vascular risk conditions are still unclear. We studied the impact of acute and chronic hypothyroidism on vascular reactivity. We studied 12 patients with chronic primary hypothyroidism (cHY; TSH: 52 +/- 14 mU/l), seven patients with acute hypothyroidism secondary to total thyroidectomy (aHY; TSH: 97 +/- 24) and 13 healthy subjects (TSH: 1.2 +/- 0.5). We measured forearm blood flow (FBF) using plethysmography during intra-brachial infusion of: acetylcholine (ACh), sodium nitroprusside (NP) and norepinephrine (NE). We also measured serum C-reactive protein (CRP), TNF-alpha, asymmetric dimethylarginine (ADMA) and the forearm balance of nitric oxide (NO) during ACh infusion. As compared with the controls, the vasodilatory response to ACh was reduced in cHY (P = 0.001) and aHY (P = 0.04), as was the forearm release of NO (P < 0.05). During NP infusion, FBF rose to 24 +/- 2 ml/dl/min in the controls and to significantly lower values in cHY (12 +/- 1; P = 0.001) and aHY (15 +/- 2; P = 0.004). NE-induced vasoconstriction was similar in the controls and aHY, but blunted in cHY. Serum CRP, TNF-alpha and ADMA were not different in the three groups. (i) Hypothyroidism associates with endothelial and nonendothelial mediated vascular dysfunction; (ii) these defects are evident even after short-term hypothyroidism, indicating that TH deficiency per se is sufficient to alter vascular homeostasis; and (iii) chronic, but not acute, hypothyroidism impairs the vasoconstrictory effect of NE in the resistance vessels.

Comparison of inhaled and intravenous milrinone in patients with pulmonary hypertension undergoing mitral valve surgery

Increased pulmonary vascular resistance (PVR) is detrimental to cardiac output in postoperative cardiac-surgery patients. The aim of this study was to investigate the postoperative hemodynamic effects of milrinone inhalation, and determine whether it has a selective effect of pulmonary vasodilation in patients with pulmonary hypertension undergoing mitral valve replacement surgery. In this study, 48 patients with pulmonary hypertension who underwent mitral valve replacement surgery were included. Patients were randomly divided into two groups with 24 patients in each: the inhaled group and the control group (intravenous [i.v.] milrinone). In the inhaled group, milrinone was administered with a jet nebulizer, and nebulized for 4 hours. In the control group, patients received a bolus of 50 microg/kg i.v. milrinone, then received a continuous milrinone infusion, 0.5 microg/kg/min, for 4 hours. A number of hemodynamic changes in all patients were evaluated. With milrinone administration, mean pulmonary artery pressure (MPAP) and PVR showed a comparable decrease in both groups. However, after initiation of milrinone, both mean arterial pressure and systemic vascular resistance in the inhaled group were significantly higher than in the control group. MPAP and PVR returned to baseline values 60 minutes after termination of milrinone inhalation. In addition, in the inhaled group, there was a reduction in intrapulmonary shunt fraction (Qs/Qt), with an improvement in PaO(2)/FiO(2) (arterial oxygen tension/fraction of inspired oxygen). The major advantage of inhaled milrinone is its pulmonary selectivity, thereby avoiding systemic side effects and ventilation-perfusion mismatch. Inhaled milrinone is an effective pulmonary vasodilator and appears to be an alternative promising approach in addressing the problem of right-ventricular decompensation following cardiopulmonary bypass.

Acquisition and reconstruction of undersampled radial data for myocardial perfusion magnetic resonance imaging

To improve myocardial perfusion magnetic resonance imaging (MRI) by reconstructing undersampled radial data with a spatiotemporal constrained reconstruction method (STCR). The STCR method jointly reconstructs all of the time-frames for each slice. In 7 subjects at rest, on a 3-T scanner, the method was compared with a conventional (GRAPPA) Cartesian approach. Increased slice coverage was obtained, as compared with Cartesian acquisitions. On average, 10 slices were obtained per heartbeat for radial acquisitions (8 of which are suitable for visual analysis with the remaining 2 slices, in theory, usable for quantitative purposes), whereas 4 slices were obtained for the conventional Cartesian acquisitions. The new method was robust to interframe motion, unlike using Cartesian undersampling and STCR. STCR produced images with an image quality rating (1 for best and 5 for worst) of 1.7 +/- 0.5; the Cartesian images were rated 2.6 +/- 0.4 (P = 0.0006). A mean improvement of 44 (+/-17) in signal-to-noise (SNR) ratio and 46 (+22) in contrast-to-noise ratio (CNR) was observed for STCR. The new radial data acquisition and reconstruction scheme for dynamic myocardial perfusion imaging is a promising approach for obtaining significantly higher coverage and improved SNR ratios. Further testing of this approach is warranted during vasodilation in patients with coronary artery disease.

Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: Results of the CEZAR study

BackgroundEffects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease. We aimed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease (CAD) in a setting of comparable cholesterol reduction. Methods and resultsFifty-eight patients with CAD were randomly assigned to double-blind treatment for 8 weeks with atorvastatin 80mg per day (A80) or atorvastatin 10mg+ezetimibe 10mg per day (A10E10), respectively. Flow-mediated vasodilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent vasodilation (NMD), lipid, C-reactive protein (CRP) plasma concentrations and urinary 8-iso-prostaglandin F2alpha excretion were measured before and after treatment. Total cholesterol, triglycerides and LDL-cholesterol levels were significantly reduced with no difference between A80 and A10E10. A80 caused significantly stronger improvement of FMD compared to A10E10 (absolute change FMD: A80+2.7±3.0% (post vs. pre p<0.001), A10E10+0.6±2.9% (post vs. pre p=0.25), A80 vs. A10E10 p=0.018). NMD was improved by A80 but not by A10E10 (absolute change NMD: A80+2.7±4.6%, A10E10+0.7±3.5%, p=0.12). Both treatment groups caused a comparable reduction of CRP and did not effect urinary 8-iso-prostaglandin F2alpha excretion. There was no correlation between FMD or NMD change and LDL-cholesterol change in either treatment group. ConclusionsThe present findings clearly suggest that in the presence of comparable LDL-lowering effects of both treatment forms, LDL-cholesterol independent effects of high dose atorvastatin therapy account for the improvement of endothelium-dependent vasodilation in patients with stable CAD.

Association between flicker‐induced vasodilatation and flow mediated vasodilatation in patients with diabetes, systemic hypertension and hypercholesterolemia

Abstract Purpose Flicker induced vasodilatation is reduced in patients with vascular related diseases. However, the reason for this diminished response is unclear, but may be related to endothelial dysfunction. Currently, the standard method to assess endothelial function in vivo is flow mediated vasodilatation (FMD). Thus, the present study was performed to investigate whether a correlation exists between flicker induced vasodilatation and FMD in patients with diabetes and patients with mild systemic hypertension and/or hypercholesteremia. Methods In the present study 20 patients with insulin dependent diabetes, 40 patients with systemic hypertension (systolic blood pressure:140‐159 mmHg; diastolic blood pressure 90‐99 mmHg) and/or serum cholesterol plasma levels &gt; 250 mg/dl and 20 healthy control subjects were included. The flicker response was measured using the Dynamic Retinal Vessel Analyzer. FMD was determined using a high resolution ultrasound system, measuring brachial artery diameter reactivity during reperfusion after arterial occlusion. Results The flicker response of both retinal arteries and veins was significantly reduced in the two patients groups. Likewise, FMD was significantly reduced in patients as compared to healthy controls. However, only a weak correlation between flicker induced vasodilatation and FMD was observed. Conclusion The study confirms evidence that flicker responses and FMD is reduced in the selected patients groups. Whether the weak correlation between FMD and flicker is due to the different stimulation type, the different vascular beds measured or other mechanisms has yet to be investigated.