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.

Study of Coronary Sinus Flow Reserve Through Transesophageal Doppler Echocardiography in Normal Subjects

OBJECTIVE - To evaluate the Coronary Flow Reserve in the Coronary Sinus through transesophageal Doppler echocardiography in normal subjects. METHODS - We obtained technically adequate flow samples for analysis in 10 healthy volunteers (37±8 years, 5 men) with no history of heart or systemic disease and with mean left ventricular mass index by transthoracic echocardiography of 87±18 g/m². Coronary sinus flow velocity was recorded within the coronary sinus with the patient in a resting condition and during intravenous adenosine infusion at a dose of 140 µg/kg/min for 4 minutes. Recording of coronary sinus blood flow was possible in all cases with measurement of peak systolic, diastolic, and retrograde velocities (PSV, PDV, and PRV, cm/sec), mean systolic and diastolic velocities (MSV and MDV, cm/sec), and systolic and diastolic velocity time integral (VTI S and VTI D, cm/sec). RESULTS - The coronary flow reserve was calculated as the ratio between the blood flow in the basal state and the maximum measured hyperemic blood flow with adenosine infusion. Results are shown as mean and standard deviations. (CFR = PSV + PDV -- PRV/basal PSV): 1st min = 2.2±0.21; 2nd min = 3±0.3; 3rd min = 3.4±0.37; 4th min = 3.6 ± 0.33. CONCLUSION - Although coronary sinus flow had significantly increased in the first minute, higher velocities were seen at third and fourth minutes, indicating that these should be the best times to study coronary sinus flow with intravenous adenosine in continuous infusion.

Characterization of the in vivo cardiac electrophysiologic effects of high-dose cocaine in closed-chest, anesthetized dogs with normal hearts

OBJECTIVE: To characterize the cardiac electrophysiologic effects of cocaine. METHODS: In 8 dogs (9-13 kg), electrophysiologic parameters and programmed stimulation were undertaken using transvenous catheters at baseline, and after cocaine intravenous infusion (12 mg/kg bolus followed by 0.22 mg/kg/min for 25 minutes). RESULTS: Cocaine plasma levels (n=5) rose to 6.73± 0.56 mg/mL. Cocaine did not affect sinus cycle length and arterial pressure. Cocaine prolonged P wave duration (54±6 vs 73±4 ms, P<0.001), PR interval (115±17 vs 164±15 ms, P<0.001), QRS duration (62±10 vs 88±14 ms, P<0.001), and QTc interval (344±28 vs 403±62 ms, P=0.03) but not JT interval (193±35 vs 226±53 ms, NS). Cocaine prolonged PA (9±6 vs 23±8 ms, P<0.001), AH (73±16 vs 92±15 ms; P=0.03), and HV (35±5 vs 45±3ms; P<0.001) intervals and Wenckebach point (247±26 vs 280±28 ms, P=0.04). An increase occurred in atrial (138±8 vs 184± 20 ms; P<0.001) and ventricular (160±15 vs 187±25 ms; P=0.03) refractoriness at a cycle length of 300 ms. Atrial arrhythmias were not induced in any dog. Ventricular fibrillation (VF) was induced in 2/8 dogs at baseline and 4/8 dogs after cocaine. CONCLUSION: High doses of cocaine exert significant class I effects and seem to enhance inducibility of VF but not of atrial arrhythmias.

Effects of high glucose concentrations on the endothelial function of the renal microcirculation of rabbits

OBJECTIVE: To assess the acute effects of high glucose concentrations on vascular reactivity in the isolated non diabetic rabbit kidney. METHODS: Rabbits were anaesthetized for isolation of the kidneys. Renal arteries and veins were cannulated for perfusion with Krebs-Henselleit solution and measurement of perfusion pressure. After 3 hours of perfusion with glucose 5,5 mM (control ) and 15 mM, the circulation was submitted to sub maximal precontraction (80% of maximal response) trough continuous infusion of noradrenaline 10 mM. Vascular reactivity was then assessed trough dose-responses curves with endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators. The influence of hyperosmolarity was analyzed with perfusion with mannitol 15mM. RESULTS: A significant reduction in the endothelium-dependent vasodilation in glucose 15mM group was observed compared to that in control, but there was no difference in endothelium-independent vasodilation. After perfusion with mannitol 15 mM, a less expressive reduction in endothelium-dependent vasodilation was observed, only reaching significance in regard to the greatest dose of acetylcholine. CONCLUSION: High levels of glucose similar to those found in diabetic patients in the postprandial period can cause significant acute changes in renal vascular reactivity rabbits. In diabetic patients these effects may also occur and contribute to diabetes vascular disease.

Fibrinolytic therapy for thrombosis in cardiac valvular prosthesis short and long term results

OBJECTIVE: To assess the short- and long-term results of the use of streptokinase (SK) for the treatment of thromboses in cardiac valvular prostheses. METHODS: Seventeen patients with cardiac prosthetic thrombosis diagnosed by clinical, echocardiographic, and radioscopic findings underwent fibrinolytic treatment with a streptokinase bolus of 250,000 U followed by 100.000 U/hour. Short- and long-term results were assessed by radioscopy and echocardiography. RESULTS: Of the 17 patients, 12 had mechanical double-disk prostheses (4 aortic, 6 mitral, 2 tricuspid), 4 had single-disk prostheses (2 aortic, 1 mitral, and 1 tricuspid), and 1 had a tricuspid bioprosthesis. The success rate was 64.8%, the partial success rate was 17.6%, and the nonsuccess rate was 17.6%. All patients with a double-disk prosthesis responded, completely or partially, to the treatment. None of the patients with a single-disk prosthesis had complete resolution of the thrombosis. The time of streptokinase infusion ranged from 6 to 80 hours (mean of 56 h). The mortality rate due to the use of streptokinase was 5.8% and was secondary to cerebral bleeding. During streptokinase infusion, 3 (17.6%) embolic episodes occurred as follows: 1 cerebral, 1 peripheral, and 1 coronary. The rethrombosis index was 33% in a mean follow-up of 42 months. CONCLUSION: The use of fibrinolytic agents was effective and relatively safe in patients with primary thrombosis of a double-disk prosthesis. A fatal hemorrhagic complication occurred in 1 (5.8%) patient, and embolic complications occurred in 3 (17.6%) patients. In a mean 42-month follow-up, 67% of the patients were free from rethrombosis.

Levosimendana em pacientes com insuficiência cardíaca descompensada: eficácia em uma coorte brasileira. Resultados do estudo BELIEF

FUNDAMENTO: A levosimendana é um novo agente inodilatador que aumenta a contratilidade cardíaca pela sensibilização ao Ca(2+) e induz vasodilatação por meio da ativação dos canais KATP/BKCa. OBJETIVO: Estudar a eficácia e segurança da levosimendana em uma coorte brasileira portadora de insuficiência cardíaca descompensada e em pacientes resistentes a agonistas b-adrenérgicos. MÉTODOS: O BELIEF (Brazilian Evaluation of Levosimendan Infusion Efficacy) foi um estudo aberto, prospectivo, multicêntrico e observacional realizado com 182 portadores de ICD de alto risco, todos tratados com levosimendana. O desfecho primário do estudo era alta hospitalar sem terapia inotrópica adicional (pacientes que responderam ao tratamento). Os desfechos secundários eram alterações nos parâmetros clínicos e hemodinâmicos e nos níveis de peptídeo natriurético cerebral (BNP). RESULTADOS: A taxa de mortalidade foi de 14,8%, e 139 dos 182 pacientes responderam ao tratamento. Entre os que não responderam, a taxa de mortalidade foi de 62,8%. A pressão arterial sistólica foi um preditor de resposta ao tratamento. No grupo resistente aos agonistas b-adrenérgicos, 55,8% responderam ao tratamento. Ao todo, 54 pacientes tiveram pelo menos um evento adverso, a maioria dos quais desapareceu espontaneamente ou após redução da dose da levosimendana. Houve uma melhora significativa na qualidade de vida entre 2 e 6 meses do acompanhamento (p < 0,0001). CONCLUSÃO: Nossos resultados indicam que a infusão de levosimendana é uma terapia alternativa de curto prazo para tratamento de pacientes com ICD. A gravidade da insuficiência cardíaca pode influenciar a resposta ao tratamento com levosimendana. São necessários estudos prospectivos com uma coorte brasileira que inclua também pacientes com doença de Chagas.

Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

Background:Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients.Objective:Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III.Methods:We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year.Results:During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years.Conclusion:Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation.

Validation of a Brazilian Portuguese Version of the Walking Estimated-Limitation Calculated by History (WELCH)

Abstract Background: The Walking Estimated-Limitation Calculated by History (WELCH) questionnaire has been proposed to evaluate walking impairment in patients with intermittent claudication (IC), presenting satisfactory psychometric properties. However, a Brazilian Portuguese version of the questionnaire is unavailable, limiting its application in Brazilian patients. Objective: To analyze the psychometric properties of a translated Brazilian Portuguese version of the WELCH in Brazilian patients with IC. Methods: Eighty-four patients with IC participated in the study. After translation and back-translation, carried out by two independent translators, the concurrent validity of the WELCH was analyzed by correlating the questionnaire scores with the walking capacity assessed with the Gardner treadmill test. To determine the reliability of the WELCH, internal consistency and test–retest reliability with a seven-day interval between the two questionnaire applications were calculated. Results: There were significant correlations between the WELCH score and the claudication onset distance (r = 0.64, p = 0.01) and total walking distance (r = 0.61, p = 0.01). The internal consistency was 0.84 and the intraclass correlation coefficient between questionnaire evaluations was 0.84. There were no differences in WELCH scores between the two questionnaire applications. Conclusion: The Brazilian Portuguese version of the WELCH presents adequate validity and reliability indicators, which support its application to Brazilian patients with IC.

Diversity and stability of fishes (Teleostei) in a temporary river of the Brazilian semiarid region

The effects of hydrological disturbances by flooding and drought on the diversity and stability in a temporary river fish community in the Brazilian semiarid region were analyzed over the 1996 hydrological cycle. Twelve collections of fishes were made during the wet and dry phases, and 789 individuals of 16 species were collected. Diversity was measured using Simpson's Index (S) and community stability was analyzed by the variation in abundance using Kendall's W concordance test. Fish diversity in the Taperoá river was subjected to hydrological disturbances by flooding and drought. During the wet phase the diversity was higher (S = 0.855) than during the dry phase (S = 0.771). The community was considered stable during the whole annual hydrological cycle (W = 0.418 p < 0.001), but a higher stability in the community was found during the dry phase. During the dry phase the number of dominant species was smaller than during the wet phase.

Quantitative fidelity of recent freshwater mollusk assemblages from the Touro Passo River, Rio Grande do Sul, Brazil

This study represents one of the first contributions to the knowledge on the quantitative fidelity of the recent freshwater molluscan assemblages in subtropical rivers. Thanatocoenoses and biocoenoses were studied in straight and meandering to braided sectors, in the middle course of the Touro Passo River, a fourth-order tributary of the Uruguay River, located in the westernmost part of the State of Rio Grande do Sul. Samplings were carried out through quadrats of 5 m², five in each sector. A total area of 50 m² was sampled. Samplings were also made in a lentic environment (abandoned meander), with intermittent communication with the Touro Passo River, aiming to record out-of-habitat shell transportation from the lentic communities to the main river channel. The results show that, despite the frequent oscillation of the water level, the biocoenosis of the Touro Passo River shows high ecological fidelity and undergoes little influence from the lentic vicinal environments. The taxonomic composition and some features of the structure of communities, especially the dominant species, also reflect some ecological differences between the two main sectors sampled, such as the complexity of habitats in the meandering-sector. Regarding the quantitative fidelity, 60% of the species found alive were also found dead and 47.3% of the species found dead were also found alive, at river-scale. However, 72% of the dead individuals belong to species also found alive. This value might be related with the good rank order correlation obtained for live/dead assemblages. Consequently, the dominant species of the thanatocoenoses could be used to infer the ecological attributes of the biocoenoses. The values of all the indexes analyzed were very variable in small-scale samplings (quadrat), but were more similar to others registered in previous studies, when they were analyzed in a station and river scale.

Estudos sobrea determinação da vitamina B¹ (aneurina, tiamina) na herva mate

The infusion used as a beverage and known as tea of Paraguay or male (Ilex paraguarensis, St. Hil.) contains vitamin B (aneurin). 2) Aneurin determinations were made on the infusion commonly used (water extract) and on the complete water and alcohol extracts. The presence of aneurin was detected in both extracts. For quantitative study aneurin was adsorbed from the extracts (pH 3.8-4.0) by means of fuller's earth and kaolin. 3) Animal tests with pigeons and mice (curative, preventive and maintenance of body weight) give positive but inconstant results. No exact quantitative values could be obtained with the animal test. 4) Schopfer-Jung test based on the development of the mould « Phycomyces blakesleeanus, Bgf » showed constant results. Regular growth curves were obtained with the adsorbate of kaolin and fuller's earth. 5) The thiochrome fluorescence test introduced by Jansen was applied to the detection of aneurin in the adsorbate and good results were found which check closely with those encountered by the Schopfer-Jung test. 6) The determinations of aneurin by means of the Phycomyces and thiochrome tests gave values varying from 60 to 280 y per 100 gr. 7) Green leaves are more rich in aneurin than dry ones.

Prevention of bone marrow graft failure by an anti LFA-1 monoclonal antibody

Graft rejection is the major cause of failure of HLA mismatched bone marrow transplantation because of residual host immunity. we have proposed to use a monoclonal murine antibody specific for the LFA-1 molecule (25-3) to prevent graft failure in HLA mismatched bone marrow transplantation (BMT). The rationale for this approach is three fold: LFA-1 deficient patients (3/3) do not reject HLA mismatched BMT; anti LFA-1 blocka in vitro the induction of T cell responses and T/ non T cytotoxic functions; LFA-1 is not expressed by other cells than leucocytes. We have accordingly treated twenty two patients with inherited diseases and 8 with leikemia. The bone marrow was T cells depled by E rosetting of Campath antibody. The antibody was given at days -3, -1, +1, +3, +5 at dose of .1 mg/kg/d for the first 9 and then .2mg/kg/d from day -3 to +6. Engraftment occured in 23/30 patients as shown by at least HLA typing. Hematological recovery was rapid, GVH was limited. Side effects of antibody infusion included fever and possibly an increased incidence of early bacteral infection (sepsis, 1 death). Immunological reconstitution occured slowly leading in six cases to EBV-induced B cell poliferation (1 death and in two others to transient auto immune hemolytic anemia. There has been only one secondary graft rejection. Sisteen patients are alive 3 to 26 months post transplant with functional grafts. Although the number of patients treated is still low the absence of late rejection so far, gives hope for long term maintenance of the graft using anti LFA-1. Since the antibody is an IgG 1 unable to bind human complement, and since it is known to inhibit phagocytosis, there is a good suggestion that 25-3 act through functional blocking of host T and non T luymphocytes at both induction and effector levels.

Evaluation of Chagas' disease transmission through breast-feeding

On hundred milk or colostrum samples from 78 mothers with chronic Chagas' disease were parasitologically studied for Trypanosoma cruzi infection by means of direct examination and inoculation of mice. The mice were submitted to direct bllod examination three times a week. At the end of 45 days, xenodiagnosis and indirect immunofluorescent test (IFAT) for T. cruzi antibodies were carried out in the animals. No parasitized sample was observed even though five mothers had parasitemia at milk collection. In addition, 97 breast-fed children of chronic chagasic mothers, born free of infection, were tested for IgG antibodies to T. cruzi using IFAT. No case of T. cruzi infection was detected. The authors conclude that breast-feeding should not be avoided for children for chronic chagasic women. However, as these mothers had intermittent parasitemia, they should avoid nursing when there is nipple bleeding.

Evaluation of antinociceptive effect of Petiveria alliacea (guiné) in animals

Petiveria alliacea (Phytolaccaceae) is a bush widely distributed in South America including Brazil, where it is popularly known as "guiné", pipi", "tipi" or "erva-de-tipi". Brazilian folk medicine attributes to the hot water infusion of its roots or leaves the following pharmacologicalproperties: antipyretic, antispasmodic, abortifacient, antirrheumatic, diuretic, analgesic and sedative. The present study has evaluated the alleged effects of P. alliacea on central nervous system (CNS), particularly, the sedative and analgesic properties of root crude aqueous extract of this plant in mice and rats. This extract showed an antinociceptive effect in acetic acid - acetylcholine - and hypertonic saline - induced abdominal constrictions, but not in hot-plate and tail flick tests P. alliacea did not produce any CNS depressor effect. Thus its antinociceptive action in animals can be responsible by its poplar use as an analgesic.