Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

Stimulus-coupled secretion of gamma-aminobutyric acid from rat brain synaptosomes.

Synaptosomes treated with radioactive gamma-aminobutyric acid can be stimulated to release this substance. The release is maximal within 40 seconds after stimulation and is dependent on calcium. Magnesium and manganese ions, known to block stimulus-secretion coupling processes, depress calcium-dependent release. This release is specific to synaptosomes because microsomal or myelin fractions do not release accumulated gamma-aminobutyric acid. The data illustrate a simple in vitro system suitable for analysis of secretion of gamma-aminobutyric acid in brain and in addition describe several new aspects of uptake and secretion of this compound at brain nerve endings.

Inducible macrophage cytotoxins. I. Biokinetics of activation and release in vitro.

Peritoneal exudate macrophage monolayers (PEMM) from C57BL/6 and DBA/2 mice inoculated ip with tumor allografts were induced to release in vitro labile cell toxin(s), herein called "macrophage cytotoxin(s)" (MCT). Macrophages released MCT spontaneously for a short interval when initially established as monolayers, and they were reinduced to secrete MCT by exposure to allogeneic and syngeneic tumor cells (but not to normal cells) and by exposure to polyinosinic-polycytidylic acid (poly I . poly C) and lipopolysaccharide (LPS). PEMM from normal mice treated ip 3 days previously with thioglycollate were also induced to release toxins in vitro. These cells did not release MCT spontaneously before or after treatment with neoplastic cells but were induced to release MCT by exposure to poly I . poly C or LPS. Resident peritoneal macrophages did not release MCT either spontaneously or after treatment with tumor cells, poly I . poly C, or LPS. MCT released from alloimmune mice stimulated with syngeneic or allogeneic tumor cells were resolved by molecular sieving into a major peak at 140,000--160,000 daltons, called "alpha-MCT," and into a minor peak at 60,000 daltons, called "beta-MCT." However, supernatants from thioglycollate-induced PEMM, stimulated with poly I . poly C or LPS, appeared to be composed entirely of the alpha-class. alpha-MCT from poly I . poly C-stimulated PEMM caused 31--56% lysis of syngeneic EL-4 and allogeneic L-929, NS-1, and YAC-1 tumor cells in vitro but was not cytotoxic for normal cells. Secretion of the MCT by PEMM derived from thioglycollate-treated animals stimulated with poly I . poly C was inhibited by colchicine, emetine, iodoacetic acid, trypan blue, and cytochalasin B.

Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

Carnosine (ß-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders.

Ovarian function following marrow transplantation for aplastic anemia or leukemia.

One hundred eighty-seven women between 13 and 49 years of age had ovarian function evaluated from 1 to 15 years (median, 4) after marrow transplant for aplastic anemia or leukemia. Among 43 women transplanted for aplastic anemia following 200 mg/kg cyclophosphamide (CY), all 27 less than 26 years of age, but only five of 16 greater than 26 years of age recovered normal ovarian function. Nine of the 43 have had 12 pregnancies, resulting in eight live births, and two elective and two spontaneous abortions. All eight children are normal. Nine of 144 women transplanted for leukemia following 120 mg/kg CY and 9.20 to 15.75 Gy total body irradiation (TBI) recovered ovarian function. Two of these nine have had three pregnancies, resulting in two spontaneous and one elective abortion. The probability of having ovarian failure was 0.35 by 7 years for patients receiving CY alone and was 1.00 at 1 year for patients receiving CY plus TBI (P less than .0001). By 7 years after transplant the probabilities of having normal ovarian function were 0.92 after CY alone and 0.24 after CY plus TBI (P less than .0001). Multivariate analysis showed that TBI was the only factor significantly influencing ovarian failure and that both TBI and greater patient age at transplant were significantly associated with a decreased probability of recovering normal ovarian function. These data demonstrate that after high-dose CY, recovery of ovarian function occurs in younger women and in a minority of older women, but after CY and TBI, recovery occurs in only a few younger women and none of the older women.

Methionine restores the venodilative response to nitroglycerin after the development of tolerance.

Depletion of sulfhydryl groups may contribute to nitroglycerin tolerance after long-term exposure. This study was performed to assess whether methionine, an amino acid capable of augmenting sulfhydryl availability, would restore the venodilative response to sublingual nitroglycerin once tolerance had developed. The venodilative response to organic nitrates was assessed with use of the equilibration technique of forearm plethysmography. Venous volume was measured before and after sublingual administration of 0.4 mg of nitroglycerin at baseline study and after 5 g of intravenous methionine. Retesting was performed 2 h after application of a 10 mg nitroglycerin patch and compared with the response after 74 h of nitroglycerin patch exposure before and after intravenous methionine. Methionine alone had no intrinsic venodilative action. Although the venous volume at rest was unchanged after methionine administration, the response to sublingual nitroglycerin was potentiated compared with baseline values (37 +/- 15% versus 32 +/- 13%, p less than 0.02). During nitroglycerin patch exposure, the response to sublingual nitroglycerin was significantly attenuated at 74 h compared with the response at 2 h of exposure (16 +/- 10% versus 31 +/- 13%, p less than 0.001). The venodilative response to sublingual nitroglycerin was restored at 74 h after methionine administration (35 +/- 14% versus 16 +/- 10%, p less than 0.001). Thus, methionine potentiates the venodilative effect of sublingual nitroglycerin both immediately and in the setting of nitrate tolerance.

Fibrinolytic response during exercise and epinephrine infusion in the same subjects.

To determine whether exercise-induced increases in tissue plasminogen activator (t-PA) were related to plasma epinephrine concentration during exercise, 14 healthy men (aged 24 to 62 years) were studied during epinephrine infusions (10, 25 and 50 ng/kg per min) and graded supine bicycle exercise, beginning at 33 W and increasing in 33-W increments until exhaustion. Plasma epinephrine, active and total t-PA, active plasminogen activator inhibitor type 1 (PAI-1) and t-PA/PAI-1 complex concentrations were measured at each exercise and infusion level. During epinephrine infusion, active and total t-PA levels increased linearly with the plasma epinephrine concentration (respective slopes [+/- SEM] of 0.062 +/- 0.003 and 0.076 +/- 0.003 pmol/ng epinephrine). During exercise, t-PA levels did not increase until plasma epinephrine levels increased, after which both active and total t-PA levels again increased linearly with the plasma epinephrine concentration, but at twice the rate observed with epinephrine infusion (0.131 +/- 0.005 and 0.147 +/- 0.005 pmol/ng, respectively). The t-PA level in blood was directly proportional to the plasma epinephrine concentration during both exercise and epinephrine infusion, suggesting that epinephrine release during exercise stimulates t-PA secretion. In these healthy subjects, active plasminogen activator inhibitor type 1 and t-PA/PAI-1 complex levels were low (41 +/- 11 and 21 +/- 5 pmol/liter, respectively) and did not change significantly during exercise or epinephrine infusion. It is concluded that approximately 50% of the increase in t-PA during exercise is due to stimulated release of t-PA by epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothalamic dysfunction in overtrained athletes.

Some athletes who undertake strenuous training programs for a prolonged period of time develop the overtraining syndrome. The pathophysiology of the condition is unknown. Hypothalamic-pituitary function was studied by determining the hormonal responses to insulin-induced hypoglycemia in five asymptomatic male marathon runners during a 4-month period in which they ran 42-, 56-, and 92-km races and in four overtrained male athletes. The response of the asymptomatic runners was not different when tested 1 month before and within 48 h after the 42- and 92-km races. All four overtrained athletes presented with impaired training and racing times, apathy, and a heavy-legged feeling and were tested when overtrained and again after 4 weeks of rest. The plasma cortisol, ACTH, GH, and PRL responses to insulin-induced hypoglycemia in the four overtrained athletes were lower than their responses after the rest and lower than the responses of the asymptomatic runners. In both groups, the LH, TSH, and PRL responses to LHRH and TRH were normal. The impaired hormonal responses to insulin-induced hypoglycemia, with recovery after 4 weeks of rest, indicate hypothalamic dysfunction and may be a diagnostic marker of the overtraining syndrome.

Dendritic caliber and the 3/2 power relationship of dentate granule cells.

A quantitative examination of granule cell dendritic caliber and knowledge of dendritic lengths allows assessment of the distribution of dendritic membrane and the 3/2 power relationship at branch points. This paper presents caliber data of Golgi-impregnated rat dentate gyrus. We used camera lucida drawings of the dendritic trees of 15 dorsal leaf and 15 ventral leaf granule cells to quantify mean dendritic caliber, dendritic taper, the 3/2 power relationship of parent and sibling dendritic diameters at branch points, and surface area. First-order dendrites vary substantially in diameter. However, the mean caliber of all other dendrites is uniform across the proximal two-thirds of the molecular layer for the dorsal and ventral leaves. The average diameter here is 1 micron. More distally, only mean ventral leaf dendritic caliber declines. Granule cell dendritic taper is due primarily to caliber decreases at branch points and not to a gradual decline in diameter across the length of a dendritic segment. Comparing the parent segment diameter raised to the 3/2 power with the sum of the 3/2 powers of the two sibling segment diameters reveals, for the dendritic tree located within the distal two-thirds of the molecular layer, the desired 3/2 power relationship for the dorsal and ventral leaves. More proximally, where first-, second-, and third-order dendrites branch sequentially across a 60-100-micron extent, a 3/2 power relationship is not obtained. For the average dorsal leaf granule cell, dendritic surface area (without spines) is 11,984 micron2. The ratio of dendritic to somatic surface area is 28:1. Discussion of these data includes their implications for electrotonic modeling of the dentate granule cell.

A quantitative anatomical study of the granule cell dendritic fields of the rat dentate gyrus using a novel probabilistic method.

The granule cell dendritic fields of the adult rat dentate gyrus were analyzed quantitatively using a probabilistic method developed to correct dendritic length and segment number for dendrites cut during sectioning. Golgi-impregnated, linearized hippocampi were sectioned serially in one of the three hippocampal planes. Three dendritic field parameters were quantified from camera lucida drawings of these dendritic fields: dendritic field spread, dendritic length, and the branching and termination patterns of dendritic segments. Granule cell dendritic fields resembled cones, their maximal extent occurring in the distal third of the molecular layer. The ratio of transverse to longitudinal dendritic field spread was greater than 1:1 for the dorsal leaf and crest regions, but close to or less than 1:1 for the ventral leaf. The probabilities of segment branching and termination were highly similar for transversely and longitudinally sectioned tissue. The probability of branching varied among dendritic orders and across the molecular layer for the same order. The probability of termination did not vary greatly across orders. Most nonbranching segments terminated adjacent to the hippocampal fissure. On the average, a granule cell had 2.23 first-order dendrites that branched into a dendritic field containing seventh-order dendrites. Total dendritic length, corrected for cut dendrites and projection errors, averaged 3,662 +/- 88 microns. The somatic layer and proximal third of the molecular layer contained approximately 35% of this total length. The remainder, ca. 60%, was restricted to the distal two-thirds of the molecular layer, the predominant termination zone of perforant path axons. These data provide a quantitative characterization of the rat granule cell dendritic fields. Implementation of the probabilistic correction method overcomes methodological problems common to quantitative Golgi studies. These data permit a more precise relationship to be drawn between dendritic architecture and granule cell physiology.

Changes in the numerical density of synaptic contacts with long-term potentiation in the hippocampal dentate gyrus.

Long-term potentiation (LTP) in the rat dentate gyrus is a multifaceted phenomenon, including synaptic potentiation; simultaneous synaptic depression at neighboring, unconditioned synapses; and a change in the amount of cell firing produced by a specified amount of synaptic current (see Levy and Desmond: In G. Buzsaki and C. Vanderwolf (eds): Electrical Activity of The Archicortex. Budapest: Akademiai Kiado, pp. 359-373, '85b). This study presents long-term anatomical modifications that seem related to excitatory synaptic modification. These anatomical alterations appear early and persist for at least 60 minutes following conditioning stimulation. Each animal received test pulse stimulation delivered alternately to the angular bundles before and after brief, unilateral high-frequency conditioning stimulation that is typical of many LTP paradigms. Anatomical preparation followed standard procedures. Double-blind scoring procedures quantified the number of asymmetric synapses in the dentate molecular layer. These counts were converted to the number of synapses per unit volume using stereological corrections that combined geometrically derived theory and modest serial sectioning. Multivariate analysis of variance evaluated the statistical significance of changes in synapse density. Across all three groups of animals, conditioning stimulation does not significantly change the density of synaptic contacts across the entire molecular layer. There is a trend for a decreased density of synaptic contacts in the middle molecular layer, the region activated by the conditioning stimulation. Here the density of concave spine profiles increases significantly in all three groups of animals with conditioning stimulation. This increase accompanies significant decreases in the density of nonconcave, simple and ellipsoid, spine profiles. No significant changes in the density of shaft synapses occur with LTP-inducing conditioning stimulation. These data suggest that the concave spine profiles are a correlate of LTP-inducing stimulation and may be the potentiated synapses. We hypothesize that with synaptic potentiation there occurs an interconversion of spine synapses such that some nonconcave spine profiles become concave spine profiles. Such an interconversion apparently begins shortly after the conditioning stimulation and persists for at least 60 minutes.

Changes in the postsynaptic density with long-term potentiation in the dentate gyrus.

The present study documents alterations in the size of the postsynaptic density (PSD) of synapses formed by entorhinal afferents with granule cell dendritic spines with long-term potentiation (LTP). These changes appear early and persist for at least 60 minutes after LTP-inducing conditioning stimulation. Each animal received test and conditioning stimulation typical of LTP paradigms. Electron microscopic preparation of the dentate gyri from each animal followed conventional procedures. PSD trace lengths of identified asymmetric synaptic profiles were measured. The total PSD length for four categories of synaptic profiles was determined for each third of the molecular layer. PSD surface area per unit volume of tissue (SV) was then computed from these data. Statistical analysis of the SV data used multivariate analysis of variance. PSD surface area per synapse was also estimated. Total PSD surface area per unit volume does not change significantly throughout the entire molecular layer with LTP-inducing conditioning stimulation. However, in the activated portion of the molecular layer, total PSD surface area per unit volume tends to increase with conditioning stimulation. In the middle third of the molecular layer, total PSD surface area per unit volume associated with the concave spine profiles increases significantly while there is a statistically significant decrease in total PSD SV associated with the nonconcave spine profiles. The PSD surface area per synapse also increases markedly. Since it seems that there is an interconversion of spine synapses from nonconcave to concave with LTP (Desmond and Levy: J. Comp. Neurol. In press, '86a), these data suggest that potentiated synapses have larger responses because, in part, they have larger neurotransmitter receptive regions.

The short- and long-term prognosis of patients with transmural and nontransmural myocardial infarction.

To compare the long-term prognosis in patients surviving transmural with patients surviving nontransmural myocardial infarctions, the records of 188 consecutive patients with clinical histories and enzyme elevations consistent with acute infarction were reviewed. According to standard electrocardiographic criteria the patients were divided into two groups: 148 with transmural myocardial infarction (group 1) and 40 with nontransmural myocardial infarction (group 2). Of the patients who survived hospitalization, follow-up data were obtained on 119 of 124 patients in group 1 and 36 of 37 patients in group 2 at a mean follow-up period of 36 months. In group 2, the patients had a high incidence of sudden death after discharge (33 per cent in group 2 versus 15 per cent in group 1, p less than 0.02) as well as a significantly higher incidence of death from all cardiac causes (41.6 per cent in group 2 versus 24.3 per cent in group 1, p less than 0.05). Furthermore, the patients in group 2 still alive at the end of the follow-up period had an increased incidence of angina pectoris and of recurrent infarction. The data suggest that patients with nontransmural myocardial infarction carry a particularly guarded prognosis.

Estradiol increases delayed, N-methyl-D-aspartate receptor-mediated excitation in the hippocampal CA1 region.

Hippocampal functions, e.g. synaptic plasticity and hippocampal-dependent behavior, are influenced by the circulating levels of ovarian steroids in adult, female rats. The mechanisms underlying this estradiol-dependent modulation, however, are poorly understood. One possibility is that estradiol alters N-methyl-D-aspartate (NMDA)-receptor functioning in the hippocampus. Here, using the in vitro hippocampal slice preparation, we evaluate estradiol-dependent changes in the NMDA receptor- and the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated components of excitatory postsynaptic potentials (EPSPs) evoked in CA1 by Schaffer collateral test stimulation. Using established experimental conditions [J Neurosci 17 (1997) 1848], we replicate the observation that estradiol pretreatment of ovariectomized rats increases a pharmacologically isolated NMDA receptor-mediated EPSP evoked by Schaffer collateral stimulation. However, using different conditions that optimize study of this evoked response, the estradiol-dependent increase in the monosynaptic NMDA receptor-mediated EPSP is eliminated. Low-intensity test stimulation of the Schaffer collaterals in this optimized medium reveals a novel, late NMDA receptor-mediated EPSP in CA1 from estradiol-pretreated rats. The mechanism(s) underlying this estradiol-dependent increase in a late, NMDA receptor-mediated EPSP is not known, but enhanced CA1-CA1 excitatory circuitry and glutamate spillover could contribute to this response. We conclude that estradiol pretreatment enhances NMDA receptor function in the female hippocampus by increasing not the monosynaptic, but rather a late NMDA receptor-mediated response. Variations in the magnitude of this late response may well contribute to ovarian steroid-dependent modulation of hippocampal synaptic plasticity.

Factors influencing serial measurements of cardiac volumes by count-based methods: effects of elevated catecholamines, position, and exercise on technetium-99m-blood radioactivity concentration.

Most radionuclide methods for measuring cardiac volume require a determination of the blood radioactivity concentration. Thus, changes in blood radioactivity over time or during interventions might lead to spurious volume estimates unless blood radioactivity is serially measured. The effects of elevated epinephrine, posture and exercise on 99mTc-labeled blood radioactivity concentration were studied in 15 young (mean age = 28 yr) and 14 older (mean age = 68 yr) healthy males. An epinephrine infusion of 50 ng/kg/min resulted in a 4.1% +/- 1.0% increase in 99mTc-blood radioactivity (p less than or equal to 0.001) compared to baseline. Sitting increased blood radioactivity concentration by 12.3% +/- 3.0% (p less than 0.0002) compared to the supine position and peak supine bicycle exercise caused an 11.0% +/- 1.7% increase (p less than or equal to 0.0001) compared to supine rest. There was a significantly greater increase during peak supine exercise in the young compared to the older subjects (15.0% +/- 2.3% versus 6.3% +/- 2.0%, p less than or equal to 0.01). The mechanism of the increase in blood radioactivity concentration is uncertain, but presumably reflects the addition of hemoconcentrated red blood cells from the spleen and/or the loss of plasma volume. Failure to correct for the increased blood radioactivity concentration during exercise or pharmacological interventions will result in a significant error in serial measurements of cardiac volumes by methods requiring RBC radioactivity measurements.

Four radionuclide methods for left ventricular volume determination: comparison of a manual and an automated technique.

This study compared the accuracy and reproducibility of three previously described and one new radionuclide method of measuring left ventricular volumes in 19 subjects using contrast ventriculographic volumes (n = 38, mean volume = 126.6 ml) as the gold standard. The four methods were compared using both manual and automated ROIs. For manual ROIs, the Links (189.7 ml, r = 0.85), Starling (183.2 ml, r = 0.77) and the new count ratio method (141.4 ml, r = 0.90) overestimated contrast volumes, while the Massardo method (122.5 ml, r = 0.91) provided accurate volumes. For the automated ROIs, we performed an interpolative background subtraction and used a 50% threshold of the highest count pixel to define the ventricular regions. The automated Massardo method severely underestimated the contrast volume (59.5 ml, r = 0.90), while the other automated methods yielded accurate volumes: Links (122.4 ml, r = 0.89), Starling (118.1 ml, r = 0.81) and the new count ratio method (125.0 ml, r = 0.90). The interobserver reproducibility of the automated methods was excellent (mean difference = 1%-4%) compared to the manual methods (2%-8%). Because no additional images, blood counting, attenuation, or decay correction were necessary, the manual Massardo method and the automated count ratio method are the simplest to perform. We conclude that automated determination of left ventricular volumes using the new count ratio method is rapid, accurate, reproducible and could readily be incorporated into routine clinical use.

Radionuclide cardiac volumes: effects of region of interest selection and correction for Compton scatter using a buildup factor.

The effects of region of interest (ROI) selection and correction for Compton-scattered photons using a buildup factor on radionuclide left ventricular volumes calculated by the Links method were compared in 19 humans with contrast ventriculography and in phantoms. Three different methods of ROI selection were compared: a manual ROI, a second derivative ROI and a 50% count-threshold ROI. In phantoms without Compton scatter correction, volumes were overestimated by 30% (manual ROI), 20% (derivative ROI) and 1% (count threshold ROI). In subjects, results without Compton scatter correction were similar with overestimates of 50% (manual ROI) and 20% (derivative ROI) and an underestimate by 3% (count threshold method). Correction for Compton-scattered photons with the use of a phantom-derived buildup factor resulted in improved accuracy for the manual ROI (+15%) and the derivative ROI (0%). A 50% count threshold ROI following interpolative background subtraction allows the accurate calculation of cardiac volumes without the need for scatter correction, while a second derivative ROI method requires a correction for Compton scatter with the use of a buildup factor.

Prevalence of cardiac abnormalities in human immunodeficiency virus infection.

The prevalence of cardiac abnormalities in the spectrum of human immunodeficiency virus (HIV) infection is unknown. Sixty consecutive HIV-infected patients were studied using echocardiograms, electrocardiograms (50 patients) and ambulatory electrocardiographic monitoring (43 patients). Group A (25 patients) were seropositive but pre-AIDS, whereas group B (35 patients) had AIDS and included 24 with an active opportunistic infection (group B1) and 11 without it (group B2). Abnormalities were identified in 32 of 60 patients (53%) and were more frequent in group B (23 of 35, 66%) than in group A (9 of 25, 36%, p less than 0.05) but independent of active opportunistic infection (15 of 24, 62%, in group B1 vs 8 of 11, 73%, in group B2). Echocardiographic abnormalities were identified in 21 of 60 patients (35%), including 7 of 25 (28%) in group A vs 14 of 35 (40%) in group B (difference not significant), and 7 of 24 (29%) in group B1 vs 7 of 11 (64%) in group B2 (difference not significant). Those patients with an absolute CD4 lymphocyte count less than or equal to 100/mm3 had a higher prevalence of echocardiographic abnormalities (12 of 22) than those with CD4 counts greater than 100/mm3 (1 of 14, p less than 0.01). Left ventricular dilation or hypokinesis was identified in 14 of 60 patients (23%), including 4 of 25 (16%) in group A and 10 of 35 (29%) in group B. Electrocardiographic abnormalities were seen in 22 of 50 patients (44%) including 5 of 18 (28%) in group A and 17 of 32 (53%) in group B (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Early patency of the infarct-related artery after myocardial infarction preserves diastolic filling.

A patent infarct-related artery (IRA) following myocardial infarction has been associated with lower mortality, increased systolic function, decreased left ventricular remodeling, and electrical stability. The purpose of this study was to determine whether coronary artery patency early after myocardial infarction is associated with greater early diastolic filling than a closed artery. Radionuclide ventriculograms were performed at a central laboratory on 167 patients who received alteplase for an acute myocardial infarction and had infarct artery patency determined by cardiac catheterization. The peak early filling rate (PEFR) was assessed by 4 different methods: (1) PEFR (EDV/s)--normalized to the end-diastolic volume; (2) PEFR (SV/s)--normalized to the stroke volume; (3) PEFR (ml/s/m(2))--an absolute diastolic filling rate; and (4) PEFR (PER)--normalized to the peak ejection rate. Patients with a closed IRA (n = 16, Thrombolysis In Myocardial Infarction [TIMI] 0 or 1 flow) and patients with an open IRA (n = 151, TIMI 2 or 3 flow) had similar ages, ejection fractions, and cardiac volumes. However, among patients with an occluded IRA, the PEFR was decreased by 12% to 18% by the 4 measures of diastolic filling (3 of 4 methods, p <0.05). PEFR (EDV/s) was 1.69 +/- 0.9 in the occluded group versus 2.06 +/- 0.4 EDV/s in the open artery group (p = 0.005). By multivariate analysis, IRA patency was an independent predictor of the PEFR by all 4 methods. Early coronary artery patency after an acute myocardial infarction preserves diastolic filling. Improved diastolic function may in part explain part of the long-term benefits of a patent IRA after thrombolytic therapy when there is no documented improvement in the ejection fraction.