Acute hemodynamic effects of captopril in children with a congestive or restrictive cardiomyopathy

The acute hemodynamic effects of captopril were evaluated at cardiac catheterization in 16 children (age, 0.3-18 years) with cardiomyopathy. Twelve children had congestive cardiomyopathy, whereas four had restrictive cardiomyopathy. Hemodynamic measurements were obtained 30 and 60 minutes after the oral administration of captopril (0.5 mg/kg). Blood pressures were measured in the aorta, pulmonary artery, right atrium, and pulmonary capillary wedge position; cardiac outputs were measured by the thermodilution technique. Hemodynamic data could not be obtained after the administration of captopril in one child with congestive cardiomyopathy because of an immediate, severe hypotensive response. In 11 of 12 children with congestive cardiomyopathy, cardiac index increased by 22%, from 2.3 to 2.8 l/min/m2 (p less than 0.05), and stroke volume increased by 22%, from 23 to 28 ml/m2 (p less than 0.05). Systemic vascular resistance decreased from 32 to 21 units.m2 (p less than 0.01), but the mean aortic pressure did not change significantly. In contrast, four children with restrictive cardiomyopathy had no change in cardiac output after captopril, but there was a trend toward significant arterial hypotension (mean aortic pressure decreased from 78 to 59 mm Hg). Thus, captopril acutely reduced systemic vascular resistance and increased both cardiac output and stroke volume in children with congestive cardiomyopathy. In children with restrictive cardiomyopathy, however, captopril did not affect cardiac output, but it did decrease aortic pressure. These data indicate that captopril may benefit children with a congestive cardiomyopathy but that captopril probably should not be used in children with restrictive disease.     

Arterial plasma norepinephrine correlates to blood pressure in middle-aged men with sustained essential hypertension

Increased plasma catecholamine levels assessed from the venous blood have been found in a number of studies of younger patients with essential hypertension, but hypertensive-normotensive differences could not easily be demonstrated in subjects above 40 years of age. For several reasons, measurement of arterial plasma catecholamines may be a more sensitive tool for the detection of hypertensive-normotensive differences. The present study therefore aimed at examining both venous and arterial plasma catecholamines in a group of white men, all 50 years of age, with never-treated, established essential hypertension (n = 61, blood pressure 165 +/- 2/112 +/- 1 mm Hg, means +/- SE) and comparing them with a similar group of normotensive men (n = 51, blood pressure 128 +/- 1/85 +/- 1 mm Hg). Arterial and venous plasma epinephrine, heart rate, and body weight were significantly elevated in the hypertensive group. Plasma norepinephrine was similar between the groups in the venous blood, whereas in the arterial blood the values in hypertensive subjects were moderately, but significantly increased (p less than 0.03). However, stepwise multiple regression analysis suggested arterial plasma norepinephrine was the only significant independent explanatory variable of raised blood pressure in the hypertensive group (r = 0.51, t = 4.05, p = 0.0002). Such a relationship was not found in the normotensive group. Thus based on measurements in arterial blood, we conclude that plasma norepinephrine, representing sympathetic tone, may be an important pathogenetic factor for high blood pressure in middle-aged men with established hypertension.     

An unusual case of vaccine-associated paralytic poliomyelitis

The present article reports a case involving an immunocompetent, previously well child who, despite two previous doses of inactivated poliovirus vaccine, developed severe flaccid paralysis consistent with polio after receiving oral polio vaccine.     

Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research.     

"White coat" versus "sustained" borderline hypertension in Tecumseh, Michigan

During a survey of young subjects not receiving treatment for hypertension in Tecumseh, Michigan, clinic and self-monitored blood pressures taken at home (14 readings in 7 days) were obtained in 737 subjects (387 men, 350 women, average age 31.5 years). Hypertension in the clinic was diagnosed if the clinic blood pressure exceeded 140 mm Hg systolic or 90 mm Hg diastolic. In the absence of firm criteria for what constitutes hypertension at home, subjects whose average home blood pressure was in the upper decile of the whole population were considered to have hypertension at home. By these criteria, 7.1% of the whole population had "white coat" hypertension (i.e., high clinic but not elevated home readings). The prevalence of "sustained" hypertension (i.e., high readings in the clinic and at home) was 5.1%. Subjects with white coat and sustained borderline hypertension in Tecumseh were very similar. Both groups showed, at previous examinations (at ages 5, 8, 21, and 23 years), significantly higher blood pressure readings than the normotensive subjects. As young adults (average age 33.3 years), the parents of both hypertensive groups had significantly higher blood pressure readings than the parents of normotensive subjects. Both hypertensive groups had faster heart rates, higher systemic vascular resistance, and higher minimal forearm vascular resistance. Both hypertensive groups were more overweight, had higher plasma triglycerides, insulin, and insulin/glucose ratios than normotensive subjects. The white coat hypertensive group also had lower values of high density lipoprotein than the normotensive group. White coat hypertension is a frequent condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostacyclin protects ischemic reperfused myocardium in the dog by inhibition of neutrophil activation

Prostacyclin (PGI2) and the stable PGI2 analogue SC39902 (6,9 alpha-epoxy,5S-fluoro-11 alpha, 15S-dehydroxyprosta-6,13E-dien-1-oic acid, sodium salt) were studied in anesthetized open-chest dogs subjected to 90 minutes of left circumflex coronary artery (LCCA) occlusion and 6 hours of reperfusion. PGI2 (50 ng/kg/min, infused into the left atrium) reduced infarct mass by 59% compared to control, but SC39902 (1.5 micrograms/kg/min) failed to produce a significant reduction in infarct size. Both PGI2 and SC39902 reduced mean arterial blood pressure, heart rate, and rate-pressure product to the same extent. Regional myocardial blood flow measured with radiolabelled tracer microspheres did not demonstrate an increase in regional blood flow to the ischemic myocardium during the 90 minutes of LCCA occlusion in the PGI2 and control treatment groups. Canine neutrophils were isolated from whole blood and activated with opsonized zymosan. PGI2 produced a concentration-dependent inhibition of neutrophil activation as measured by superoxide production in vitro, whereas SC39902 failed to effectively inhibit neutrophil activation. Neutrophil migration into inflammatory skin lesions was effectively attenuated when dogs were pretreated with PGI2 (50 ng/kg/min, intravenously). Therefore, it is suggested that the cytoprotective effect of PGI2 during myocardial ischemia and reperfusion is related to an inhibition of neutrophil migration and the production of cytotoxic activated oxygen species.     

The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques

The detection and quantitation of apoptotic cells is becoming increasingly important in the investigation of the role of apoptosis in cellular proliferation and differentiation. The pathogenesis of hematologic disorders such as aplastic anemia and the development of neoplasia are believed to involve dysregulation of apoptosis. To quantitate accurately the proportion of apoptosis cells within different cell types of a heterogeneous cell population such as blood or bone marrow, a method is required that combines the analysis of large numbers of cells with concurrent immunophenotyping of cell surface antigens. In this study, we have evaluated such a method using the fluorescent DNA binding agent, 7-amino actinomycin D (7AAD), to stain three diverse human cell lines, induced to undergo apoptosis by three different stimuli. Flow cytometric analysis defines three populations on the basis of 7AAD fluorescence and forward light scatter. We have shown by cell sorting and subsequent morphological assessment and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling that the populations defined by 7AAD represent live, apoptotic, and late-apoptotic/dead cells. This method is quick, simple, reproducible, and cheap and will be a valuable tool in the investigation of the role of apoptosis in normal physiology and in disease states.