Assessment of inotropic and vasodilating effects of milrinone lactate in patients with dilated cardiomyopathy and severe heart failure

OBJECTIVE: To assess the hemodynamic and vasodilating effects of milrinone lactate (ML) in patients with dilated cardiomyopathy (DCM) and New York Heart Association (NYHA) class III and IV heart failure. METHODS: Twenty patients with DCM and NYHA class III and IV heart failure were studied. The hemodynamic and vasodilating effects of ML, administered intravenously, were evaluated. The following variables were compared before and during drug infusion: cardiac output (CO) and cardiac index (CI); pulmonary capillary wedge pressure (PCWP); mean aortic pressure (MAP); mean pulmonary artery pressure (MPAP); mean right atrial pressure (MRAP); left ventricular systolic and end-diastolic pressures (LVSP and LVEDP, respectively); peak rate of left ventricular pressure rise (dP/dt); systemic vascular resistance (SVR); pulmonary vascular resistance (PVR); and heart rate (HR). RESULTS: All patients showed a significant improvement of the analysed parameters of cardiac performance with an increase of CO and CI; a significant improvement in myocardial contractility (dP/dt) and reduction of the LVEDP; PCWP; PAP; MAP; MRAP; SVR; PVR. Were observed no significant increase in HR occurred. CONCLUSION: Milrinone lactate is an inotropic dilating drug that, when administered intravenously, has beneficial effects on cardiac performance and myocardial contractility. It also promotes reduction of SVR and PVR in patients with DCM and NYHA class III and IV of heart failure.

Growth hormone for optimization of refractory heart failure treatment

It has been reported that growth hormone may benefit selected patients with congestive heart failure. A 63-year-old man with refractory congestive heart failure waiting for heart transplantation, depending on intravenous drugs (dobutamine) and presenting with progressive worsening of the clinical status and cachexia, despite standard treatment, received growth hormone replacement (8 units per day) for optimization of congestive heart failure management. Increase in both serum growth hormone levels (from 0.3 to 0.8 mg/l) and serum IGF-1 levels (from 130 to 300ng/ml) was noted, in association with clinical status improvement, better optimization of heart failure treatment and discontinuation of dobutamine infusion. Left ventricular ejection fraction (by MUGA) increased from 13 % to 18 % and to 28 % later, in association with reduction of pulmonary pressures and increase in exercise capacity (rise in peak VO2 to 13.4 and to 16.2ml/kg/min later). The patient was "de-listed" for heart transplantation. Growth hormone may benefit selected patients with refractory heart failure.

Quantitative study of myocardial microcirculation in arterial hypertension due to progressive inhibition of NO synthesis

OBJECTIVE: To study the quantitative changes in intramyocardial blood vessels in rats in whom nitric oxide synthesis was inhibited. METHODS: Four groups of 10 rats were studied: control (C25 and C40) and L-NAME (L25 and L40). The animals L25 and L40 received L-NAME in the dosage of 50mg/kg/day for 25 and 40 days, respectively. On days 26 and 41 the animals in groups 25 and 40 were sacrificed. Analysis of the myocardium was performed using light microscopy and stereology. RESULTS: Arterial blood pressure and heart weight increased 74.5 and 57.8% after 25 days and 90.2 and 34.6% after 40 days, respectively. Comparing the L-NAME rats with the respective controls revealed that vessel volume density decreased 31.3% after 40 days, and the vessel length-density decreased 53.5% after 25 days and 25.7% after 40 days. The mean cross-sectional area of the vessels showed an important reduction of 154.6% after 25 days. The intramyocardial vessels decreased significantly in length- density in the L-NAME animals. The mean cross-sectional area of the vessels, which normally increases during heart growth between 25 and 40 days, showed a precocious increase by the 25th day in the L-NAME rats. This suggests an increase of the size of the heart, including blood vessels. CONCLUSION: The inhibition of the NO synthesis provokes rarefaction in the intramyocardial vessels that progresses with the time of administration of L-NAME.

The effect of siesta in parameters of cardiac structure and in interpretation of ambulatory arterial blood pressure monitoring

OBJECTIVE: To evaluate the influence of the siesta in ambulatory blood pressure (BP) monitoring and in cardiac structure parameters. METHODS: 1940 ambulatory arterial blood pressure monitoring tests were analyzed (Spacelabs 90207, 15/15 minutes from 7:00 to 22:00 hours and 20/20 minutes from 22:01 to 6.59hours) and 21% of the records indicated that the person had taken a siesta (263 woman, 52±14 years). The average duration of the siesta was 118±58 minutes. RESULTS: (average ± standard deviation) The average of systolic/diastolic pressures during wakefulness, including the napping period, was less than the average for the period not including the siesta (138±16/85±11 vs 139±16/86±11 mmHg, p<0.05); 2) pressure loads during wakefulness including the siesta, were less than those observed without the siesta); 3) the averages of nocturnal sleep blood pressures were similar to those of the siesta, 4) nocturnal sleep pressure drops were similar to those in the siesta including wakefulness with and without the siesta; 5) the averages of BP in men were higher (p<0.05) during wakefulness with and without the siesta, during the siesta and nocturnal sleep in relation to the average obtained in women; 6) patients with a reduction of 0- 5% during the siesta had thickening of the interventricular septum and a larger posterior wall than those with a reduction during the siesta >5%. CONCLUSION: The siesta influenced the heart structure parameters and from a statistical point of view the average of systolic and diastolic pressures and the respective pressure loads of the wakeful period.

Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease

OBJETIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6±4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5±3.8) and diltiazem (3.2±4.2) when compared with placebo (7.9±8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2±31.9min; diltiazem: 19.3±29.6min; placebo: 46.1±55.3min; p<0.05). CONCLUSION: In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.

Application of receptive music therapy in internal medicine and cardiology

OBJECTIVE: To investigate the effects of receptive music therapy in clinical practice. METHODS: Receptive music therapy was individually applied via musical auditions, including five stages: musical stimulation, sensation, situation, reflection, and behavioral alteration. Following anamnesis and obtainment of consent, patients answered a first questionnaire on health risk evaluation (Q1), and after participating in 16 weekly music therapy sessions, answered a second one (Q2). RESULTS: Two men and 8 women, aged above 18 years, referred to us due to symptoms of stress, emotional suffering, and the need to change lifestyles (health risk behavior) were studied between August 1998 and December 1999. Comparison between answers to Q1 and Q2, showed a trend (P=0.059) for reduction of ingestion of cholesterol-rich foods and for increased prospects in life with a tendency towards improvement, and also of increased intake of fiber-rich food (55.6%), increased levels of personal satisfaction (44.5%), and decreased levels of stress (66.7%). CONCLUSION: The study demonstrated decreased stress levels and increased personal satisfaction, higher consumption of fiber-rich food, lower cholesterol intake, and a better perspective on life, suggesting that receptive music therapy may be applied in clinical practice as an auxiliary therapeutic intervention for the treatment of behavioral health risks.

Evaluation of the Medical Care of Patients with Hypertension in an Emergency Department and in Ambulatory Hypertension Unit

OBJECTIVE: To evaluate the characteristics of the patients receiving medical care in the Ambulatory of Hypertension of the Emergency Department, Division of Cardiology, and in the Emergency Unit of the Clinical Hospital of the Ribeirão Preto Medical School. METHODS: Using a protocol, we compared the care of the same hypertensive patients in on different occasions in the 2 different places. The characteristics of 62 patients, 29 men with a mean age of 57 years, were analyzed between January 1996 and December 1997. RESULTS: The care of these patients resulted in different medical treatment regardless of their clinical features and blood pressure levels. Thus, in the Emergency Unit, 97% presented with symptoms, and 64.5% received medication to rapidly reduce blood pressure. In 50% of the cases, nifedipine SL was the elected medication. Patients who applied to the Ambulatory of Hypertension presenting with similar features, or, in some cases, presenting with similar clinically higher levels of blood pressure, were not prescribed medication for a rapid reduction of blood pressure at any of the appointments. CONCLUSION: The therapeutic approach to patients with high blood pressure levels, symptomatic or asymptomatic, was dependent on the place of treatment. In the Emergency Unit, the conduct was, in the majority of cases, to decrease blood pressure immediately, whereas in the Ambulatory of Hypertension, the same levels of blood pressure, in the same individuals, resulted in therapeutic adjustment with nonpharmacological management. These results show the need to reconsider the concept of hypertensive crises and their therapeutical implications.

Implications of the Hemodynamic Optimization Approach Guided by Right Heart Catheterization in Patients with Severe Heart Failure

OBJECTIVE: To report the hemodynamic and functional responses obtained with clinical optimization guided by hemodynamic parameters in patients with severe and refractory heart failure. METHODS: Invasive hemodynamic monitoring using right heart catheterization aimed to reach low filling pressures and peripheral resistance. Frequent adjustments of intravenous diuretics and vasodilators were performed according to the hemodynamic measurements. RESULTS: We assessed 19 patients (age = 48±12 years and ejection fraction = 21±5%) with severe heart failure. The intravenous use of diuretics and vasodilators reduced by 12 mm Hg (relative reduction of 43%) pulmonary artery occlusion pressure (P<0.001), with a concomitant increment of 6 mL per beat in stroke volume (relative increment of 24%, P<0.001). We observed significant associations between pulmonary artery occlusion pressure and mean pulmonary artery pressure (r=0.76; P<0.001) and central venous pressure (r=0.63; P<0.001). After clinical optimization, improvement in functional class occurred (P< 0.001), with a tendency towards improvement in ejection fraction and no impairment to renal function. CONCLUSION: Optimization guided by hemodynamic parameters in patients with refractory heart failure provides a significant improvement in the hemodynamic profile with concomitant improvement in functional class. This study emphasizes that adjustments in blood volume result in imme-diate benefits for patients with severe heart failure.

Metabolic and hemodynamic effects of saline infusion to maintain volemia on temporary abdominal aortic occlusion

OBJECTIVE: To analyze hemodynamic and metabolic effects of saline solution infusion in the maintenance of blood volume in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. METHODS: We studied 20 dogs divided into 2 groups: the ischemia-reperfusion group (IRG, n=10) and the ischemia-reperfusion group with saline solution infusion aiming at maintaining mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, n=10). All animals were anesthetized with sodium thiopental and maintained on spontaneous ventilation. Occlusion of the supraceliac aorta was obtained with inflation of a Fogarty catheter inserted through the femoral artery. After 60 minutes of ischemia, the balloon was deflated, and the animals were observed for another 60 minutes of reperfusion. RESULTS: IRG-SS dogs did not have hemodynamic instability after aortic unclamping, and the mean systemic blood pressure and heart rate were maintained. However, acidosis worsened, which was documented by a greater reduction of arterial pH that occurred especially due to the absence of a respiratory response to metabolic acidosis that was greater with the adoption of this procedure. CONCLUSION: Saline solution infusion to maintain blood volume avoided hemodynamic instability after aortic unclamping. This procedure, however, caused worsening in metabolic acidosis in this experimental model.

Cost-Effectiveness of High, Moderate and Low-Dose Statins in the Prevention of Vascular Events in the Brazilian Public Health System

Background:Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial.Objective:To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective.Methods:We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40mg), intermediate dose; and above 40% (atorvastatin 20-80mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied.Results:Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios.Conclusions:Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil.

Vascular Response of Ruthenium Tetraamines in Aortic Ring from Normotensive Rats

Background: Ruthenium (Ru) tetraamines are being increasingly used as nitric oxide (NO) carriers. In this context, pharmacological studies have become highly relevant to better understand the mechanism of action involved. Objective: To evaluate the vascular response of the tetraamines trans-[RuII(NH3)4(Py)(NO)]3+, trans-[RuII(Cl)(NO) (cyclan)](PF6)2, and trans-[RuII(NH3)4(4-acPy)(NO)]3+. Methods: Aortic rings were contracted with noradrenaline (10−6 M). After voltage stabilization, a single concentration (10−6 M) of the compounds was added to the assay medium. The responses were recorded during 120 min. Vascular integrity was assessed functionally using acetylcholine at 10−6 M and sodium nitroprusside at 10−6 M as well as by histological examination. Results: Histological analysis confirmed the presence or absence of endothelial cells in those tissues. All tetraamine complexes altered the contractile response induced by norepinephrine, resulting in increased tone followed by relaxation. In rings with endothelium, the inhibition of endothelial NO caused a reduction of the contractile effect caused by pyridine NO. No significant responses were observed in rings with endothelium after treatment with cyclan NO. In contrast, in rings without endothelium, the inhibition of guanylate cyclase significantly reduced the contractile response caused by the pyridine NO and cyclan NO complexes, and both complexes caused a relaxing effect. Conclusion: The results indicate that the vascular effect of the evaluated complexes involved a decrease in the vascular tone induced by norepinephrine (10−6 M) at the end of the incubation period in aortic rings with and without endothelium, indicating the slow release of NO from these complexes and suggesting that the ligands promoted chemical stability to the molecule. Moreover, we demonstrated that the association of Ru with NO is more stable when the ligands pyridine and cyclan are used in the formulation of the compound.

Role of microRNAs 221/222 on Statin Induced Nitric Oxide Release in Human Endothelial Cells

Background: Nitric oxide (NO) has been largely associated with cardiovascular protection through improvement of endothelial function. Recently, new evidence about modulation of NO release by microRNAs (miRs) has been reported, which could be involved with statin-dependent pleiotropic effects, including anti-inflammatory properties related to vascular endothelium function. Objective: To evaluate the effects of cholesterol-lowering drugs including the inhibitors of cholesterol synthesis, atorvastatin and simvastatin, and the inhibitor of cholesterol absorption ezetimibe on NO release, NOS3 mRNA expression and miRs potentially involved in NO bioavailability. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to atorvastatin, simvastatin or ezetimibe (0 to 5.0 μM). Cells were submitted to total RNA extraction and relative quantification of NOS3 mRNA and miRs -221, -222 and -1303 by qPCR. NO release was measured in supernatants by ozone-chemiluminescence. Results: Both statins increased NO levels and NOS3 mRNA expression but no influence was observed for ezetimibe treatment. Atorvastatin, simvastatin and ezetimibe down-regulated the expression of miR-221, whereas miR-222 was reduced only after the atorvastatin treatment. The magnitude of the reduction of miR-221 and miR-222 after treatment with statins correlated with the increment in NOS3 mRNA levels. No influence was observed on the miR-1303 expression after treatments. Conclusion: NO release in endothelial cells is increased by statins but not by the inhibitor of cholesterol absorption, ezetimibe. Our results provide new evidence about the participation of regulatory miRs 221/222 on NO release induction mediated by statins. Although ezetimibe did not modulate NO levels, the down-regulation of miR-221 could involve potential effects on endothelial function.

Impact of Physical Activity Interventions on Blood Pressure in Brazilian Populations

Background:High blood pressure is associated with cardiovascular disease, which is the leading cause of mortality in the Brazilian population. Lifestyle changes, including physical activity, are important for lowering blood pressure levels and decreasing the costs associated with outcomes.Objective:Assess the impact of physical activity interventions on blood pressure in Brazilian individuals.Methods:Meta-analysis and systematic review of studies published until May 2014, retrieved from several health sciences databases. Seven studies with 493 participants were included. The analysis included parallel studies of physical activity interventions in adult populations in Brazil with a description of blood pressure (mmHg) before and after the intervention in the control and intervention groups.Results:Of 390 retrieved studies, eight matched the proposed inclusion criteria for the systematic review and seven randomized clinical trials were included in the meta-analysis. Physical activity interventions included aerobic and resistance exercises. There was a reduction of -10.09 (95% CI: -18.76 to -1.43 mmHg) in the systolic and -7.47 (95% CI: -11.30 to -3.63 mmHg) in the diastolic blood pressure.Conclusions:Available evidence on the effects of physical activity on blood pressure in the Brazilian population shows a homogeneous and significant effect at both systolic and diastolic blood pressures. However, the strength of the included studies was low and the methodological quality was also low and/or regular. Larger studies with more rigorous methodology are necessary to build robust evidence.

The Benefits of Prone SPECT Myocardial Perfusion Imaging in Reducing Both Artifact Defects and Patient Radiation Exposure

AbstractBackground:Prone imaging has been demonstrated to minimize diaphragmatic and breast tissue attenuation.Objectives:To determine the role of prone imaging on the reduction of unnecessary rest perfusion studies and coronary angiographies performed, thus decreasing investigation time and radiation exposure.Methods:We examined 139 patients, 120 with an inferior wall and 19 with an anterior wall perfusion defect that might represented attenuation artifact. Post-stress images were acquired in both the supine and prone position. Coronary angiography was used as the “gold standard” for evaluating coronary artery patency. The study was terminated and rest imaging was obviated in the presence of complete improvement of the defect in the prone position. Quantitative interpretation was performed. Results were compared with clinical data and coronary angiographic findings.Results:Prone acquisition correctly revealed defect improvement in 89 patients (89/120) with inferior wall and 12 patients (12/19) with anterior wall attenuation artifact. Quantitative analysis demonstrated statistically significant difference in the mean summed stress scores (SSS) of supine and mean SSS of prone studies in patients with disappearing inferior wall defect in the prone position and patent right coronary artery (true negative results). The mean difference between SSS in supine and in prone position was higher with disappearing than with remaining defects.Conclusion:Technetium-99m (Tc-99m) tetrofosmin myocardial perfusion imaging with the patient in the prone position overcomes soft tissue attenuation; moreover it provides an inexpensive, accurate approach to limit the number of unnecessary rest perfusion studies and coronary angiographies performed.