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R Sciacca

Publications and source records attributed to R Sciacca.

29 records · Page 2Linked to original sources
PubMed1993

Restoration of the cAMP second messenger pathway enhances cardiac preservation for transplantation in a heterotopic rat model.

Current organ preservation strategies subject graft vasculature to severe hypoxia (PO2 approximately 20 Torr), potentially compromising vascular function and limiting successful transplantation. Previous work has shown that cAMP modulates endothelial cell (EC) antithrombogenicity, barrier function, and leukocyte/EC interactions, and that hypoxia suppresses EC cAMP levels. To explore the possible benefits of cAMP analogs/agonists in organ preservation, we used a rat heterotopic cardiac transplant model; dibutyryl cAMP added to preservation solutions was associated with a time- and dose-dependent increase in the duration of cold storage associated with successful graft function. Preservation was also enhanced by 8-bromo-cAMP, the Sp isomer of adenosine 3',5'monophosphorothioate, and types III (indolidan) and IV (rolipram) phosphodiesterase inhibitors. Neither butyrate alone nor 8-bromoadenosine were effective, and the cAMP-dependent protein kinase antagonist Rp isomer of adenosine 3',5'monophosphorothioate prevented preservation enhancement induced by 8-bromo-cAMP. Grafts stored with dibutyryl cAMP demonstrated a 5.5-fold increase in blood flow and a 3.2-fold decreased neutrophil infiltration after transplantation. To explore the role of cAMP in another cell type critical for vascular homeostasis, vascular smooth muscle cells were subjected to hypoxia, causing a time-dependent decline in cAMP levels. Although adenylate cyclase activity was unchanged, diminished oxygen tensions were associated with enhanced phosphodiesterase activity (59 and 30% increase in soluble types III and IV activity, respectively). These data suggest that hypoxia or graft ischemia disrupt vascular homeostasis, at least in part, by perturbing the cAMP second messenger pathway. Supplementation of this pathway provides a new approach for enhancing cardiac preservation, promoting myocardial function, and maintaining vascular homeostatic properties.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Quantitative effects of myocardial edema on the left ventricular pressure-volume relation. Influence of cardioplegia osmolarity over two hours of ischemic arrest.

We previously studied edema and left ventricular pressure-volume relations in a porcine heart model in which edema occurred even with hyperosmolar crystalloid cardioplegia. This susceptibility to edema was attributed to venous occlusion and an initial 20-minute period of ischemia. Results did not demonstrate reversal of edema by hyperosmolar perfusates. Accordingly, in the present study, heart weight, myocardial water content, and left ventricular pressure-volume curves were measured before and after perfusion-induced edema in eight isolated, arrested, hypothermic porcine hearts. Cardioplegic solution was infused 2.1 +/- 0.8 minutes after the onset of ischemia, and the atrioventricular ring was not clamped during the administration of cardioplegic solution. Cardioplegic solution (1 L) was infused at intervals of 33 +/- 6 minutes at 4 degrees C. Solution osmolarity was 380 (Stanford solution) or 294 mOsm/L (Plegisol solution). The perfusion sequence was 380-1, 380-2, 294-1, 380-3. Pressure-volume relations were assessed with the use of left ventricular volume at a pressure of 10 mm Hg and the ventricular chamber stiffness constant, beta, derived from P = alpha e beta V. Perfusions 380-1 and 380-2 did not affect the pressure-volume curve. Perfusion 294-1 increased heart weight and water content (p < 0.05) and decreased left ventricular volume at 10 mm Hg compared with perfusions 380-1, 380-2, and 380-3. In addition, beta increased (0.023 +/- 0.005 versus 0.029 +/- 0.006, p < 0.05) after perfusion 294-1, compared with 380-1. Correlation coefficients for linear regressions between left ventricular volume at 10 mm Hg and heart weight and water content were r = 0.84 and r = 0.70, respectively. We conclude that under conditions similar to those used clinically, the left ventricle of the pig does not develop edema with Stanford solution (380 mOsm/L). Edema does follow Plegisol solution (294 mOsm/L) cardioplegia. Edema and reduced compliance are incompletely reversed by hypertonic cardioplegia. The porcine left ventricle can usefully replicate the clinical model.

Animals↗
PubMed1992

Importance of adequate staging and of hormone receptors in women older than age 70 with breast cancer.

This report includes 479 women older than 70 years of age who were operated on between January 1980 and January 1988 and who were followed for 2.5 to 10.5 years (mean, 4.6 years). There were no operative deaths. Staging was available on 90.8%. Eighty-one per cent of patients were estrogen receptor positive (ER+), and 64% had negative lymph nodes (LN-). There were 50 deaths from breast cancer (10.4%), and 56 (11.6%) from other causes (mostly cardiovascular). Estrogen receptor negativity was significant by both univariate and multivariate analysis for increased risk of death from breast cancer (by factors of 3 and 1.4). Only four of 152 (2.6%) women who were node negative and estrogen receptor positive died during the follow-up of 4.9 years. The results of this study suggest that elderly women should be fully staged with axillary node dissections, and the hormone receptor assay should be performed because these are important indicators of prognosis. Because only 2.6% of the LN- and ER+ women in this study died of breast cancer, and only 3% in this group were treated with adjuvant systemic therapy (tamoxifen), the authors conclude that this therapy is unnecessary, although a prospective randomized study of elderly women would be required to state this definitively.

Age Factors↗
PubMed1989

Relation between survival and development of coronary artery disease and anti-HLA antibodies after cardiac transplantation.

The importance of chronic humoral rejection in cardiac transplant patients has not been studied extensively. In an attempt to determine whether lymphocytotoxic antibodies are related to heart allograft survival, we evaluated 123 patients whose sera were monitored for cytotoxic antibodies against HLA antigens after transplantation. Patients underwent serial sampling of peripheral blood at the time of right-heart catheterization and endomyocardial biopsy. Patients with three or more sera containing lymphocytotoxic antibodies were considered alloantibody producers (81 of 123 patients). With similar follow-up, mortality was greater for antibody producers (27 of 81 patients) than for nonproducers (three of 42 patients, p less than 0.01). Among antibody producers, the mortality rate was higher when multiple samples obtained during the first 6 months after transplantation contained anti-HLA class I or class II antibodies. Coronary artery disease was documented in 12 of 81 antibody producers and only one of 42 nonproducers (p = 0.05). The presence of anti-HLA antibodies in the serum showed no association with the presence of lymphocytic infiltrates in myocardial biopsies or with hemodynamic abnormalities. However, histologic rejection was present in 14 of 19 antibody producers who died. Thus, the presence of anti-HLA antibodies was associated with increased mortality and the development of coronary artery disease and was a major correlate of the clinical course after cardiac transplantation. High- and low-risk groups can be differentiated within the first 6 months after transplantation.

Coronary Disease↗
PubMed1988

Hemodynamic effects of labetalol in patients with combined hypertension and left ventricular failure.

To investigate the safety of labetalol in the treatment of hypertension in patients with heart failure, sixteen hypertensive patients with a history of congestive heart failure and an ejection fraction at rest less than 45%, had measurements of ejection fraction and cardiac output by first pass radionuclide angiography at baseline, at the end of 2 weeks maintenance with labetalol (titrated to the effective antihypertensive dose of 200-1600 mg daily), and in the post-treatment placebo period. On labetalol, heart rate and blood pressure were significantly lower than placebo at rest and the ejection fraction was higher (30 vs 25%) (p less than 0.05). At maximal exercise on labetalol the heart rate and blood pressure were lower than at placebo maximal exercise (p less than 0.05) and the ejection fraction was higher (32 vs 27%) (p less than 0.01). Exercise tolerance was not changed by labetalol. No patient was discontinued from the study because of worsening heart failure. Dizziness was reported in 5 of 16 patients usually at one visit. Dyspnea that was reported in 4 of 16 patients improved with minor adjustments in digitalis or diuretic dose. In conclusion, labetalol reduces blood pressure in hypertensive patients with left ventricular dysfunction without reducing cardiac performance.

Angiography↗
PubMed1981

Continuous measurement of minute ventilation and gaseous metabolism of newborn infants.

A system of instrumentation for continuous measurement of gaseous metabolism and minute volume (VI) in the human newborn is described. O2 uptake and CO2 production are measured by open-circuit techniques utilizing a Servomex OA184 differential paramagnetic O2 analyzer and a BEckman LB-2 infrared CO2 analyzer. VI is measured with bias-flow pneumotachometry. Bench performance is described, methodological errors are defined, and clinical data are presented. The instrumentation is capable of safe, accurate, and continuous measurement of respiratory and metabolic variables in low-birth-weight infants.

Calorimetry↗
PubMed1981

Spontaneous variability in minute ventilation oxygen consumption and heart rate of low birth weight infants.

Continuous measurements of minute ventilation (VI), oxygen consumption (VO2), heart rate (HR), activity, and temperature were made in eleven low birth weight infants during the interval between feedings. Significant increases in VI, VO2, and HR were noted between quiet and active sleep. (VI Active - VI Quiet/VI Quiet) X 100 = 18.4% VO2 Active - VO2 Quiet/VO2 Quiet) X 100 = 10.1% and HR Active - HR Quiet/HR Quiet) X 100 = 6.4%. Significant differences were also noted within epochs of the same state of sleep: mean slope VI versus time in epoch (t) = -156 ml/kg . min/hr, VO2 versus t. = 1.49 ml/kg . min/hr and HR versus t = -15.0 beats/min/hr. Differences between successive epochs of the same state of sleep were also observed: VI, +5.9 to 46.6%; VO2, 4.7 to 24.6%; HR, 1.0 to 9.7%. These differences were related to the length of time after feeding. These data indicate that steady state conditions do not occur in growing low birth weight infants and that the design of studies of respiration and metabolism in these infants should include continuous assessment of the state of sleep or activity and time after feeding to ensure that experimental and control periods are truly comparable.

Heart Rate↗
PubMed1980

Air bubbles and temperature effect on blood gas analysis.

The effect of temperature, time of storage, and presence of air bubbles in specimens for blood gas analysis was studied. The results show that air bubbles in a 10% proportion are undesirable because of significant elevation in the PO2, and the storage of anaerobic blood samples at room temperature (25 degrees C) is acceptable when measurements are done within the first 20 minutes.

Air↗
PubMed1980

Radioimmunoassay studies of human apolipoprotein E.

This report describes the development and first applications of a sensitive and specific double antibody radioimmunoassay for human apoplipoprotein E (apoE). ApoE was purified from the very low density lipoproteins of hypertriglyceridemic patients by heparin-agarose affinity chromatography, DEAE-cellulose chromatography, and preparative polyacrylamide gel electrophoresis. The purified apoprotein had an amino acid composition characteristic of apoE and resulted in the production of monospecific antisera when injected into rabbits. The radioimmunoassay, which was carried out in the presence of 5 mM sodium decyl sulfate, had a working range of 0.8-12 ng. The withinassay coefficient of variation was 9% and the coefficient of variation for systematic between-assay variability was 3%. Prior delipidation of samples with organic solvents did not alter their immunoreactivity. In 26 normal volunteers, the mean plasma apoE concentration was 36 +/- 13 microgram/ml. Hyperlipidemic patients (n = 68) had higher mean apoE levels. A single patient with type III hyperlipoproteinemia had a plasma apoE level of 664 microgram/ml. The plasma apoE level was independently related to plasma cholesterol and triglyceride levels in a population of 108 normal and nonchylomicronemic hyperlipidemic patients. The multiple correlation coefficient for this relationship was 0.73. Thus, variation in plasma cholesterol and triglyceride concentrations described 53% of the variation in apoE concentrations in this population. The lipoprotein distribution of apoE was investigated by agarose column chromatography and ultracentrifugation of plasma. Agarose column chromatography demonstrated that all or nearly all plasma apoE is associated with lipoproteins. In plasma from normal volunteers and hypercholesterolemic patients, apoE was found in two discrete lipoprotein classes: very low density lipoproteins and a set of lipoprotein particles with size and density characteristics similar to HDL2. In hypertriglyceridemic patients, nearly all apoE was associated with the triglyceride-rich lipoproteins.

Adult↗