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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of prostacyclin (PGI2) with and without heparin were studied in 28 dogs that underwent 2 hours of cardiopulmonary bypass. Five groups were created: group I (six dogs) received heparin, 1.25 mg/kg; group II (six dogs) received low-dose heparin, 0.5 mg/kg, and PGI2, 500 ng/kg/min; group III (six dogs) received low-dose heparin alone; group IV (four dogs) received PGI2, 500--1000 ng/kg/min; and group V (six dogs) received ibuprofen, 12.5 mg/kg, dipyridamole, 1 mg/kg, PGI2, 20 ng/kg/min, and low-dose heparin. Significant clot deposition occurred in the oxygenators in groups III, IV and V. Platelet counts decreased to a mean of 36.8 +/- 5.7% (+/- SEM) of control in group I, which had normal clinical heparin dose for dogs, but to only 74 +/- 7% of control in group II. This improvement was significant (p less than 0.005). Platelet aggregation induced by adenosine diphosphate 60 minutes after CPB showed poor aggregation in group I but almost normal aggregation in group II. Protamine was unnecessary in groups that received PGI2. PGI2 in combination with low-dose heparin provides adequate anticoagulation during cardiopulmonary bypass in dogs, preserves platelet number and function and is associated with minimal postoperative bleeding.
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PMID:Preservation of platelets and their function in prolonged cardiopulmonary bypass using prostacyclin. 701 36

The effects of sequential prostacyclin infusions at 2, 4, and 8 ng/kg/min for 1 hr were determined in six patients with chronic renal failure. Diastolic blood pressure decreased in a dose-dependent fashion from 74 +/- 4 mm Hg (mean +/- SEM) to 70 +/- 4, 66 +/- 5, and 55 +/- 5 during the 2, 4, and 8 ng/kg/min infusions, respectively; systolic blood pressure was not affected by prostacyclin. The fall in diastolic blood pressure was associated with a progressive rise in heart rate from 77 +/- 3 to 91 +/- 4 bpm and lowering of body temperature from 36.7 +/- 0.1 to 36 +/- 0.2 degrees. The threshold concentration of adenosine diphosphate that evoked reversible and irreversible platelet aggregation increased progressively from 1.2 to 2.8 and from 2.8 to 6 microM, respectively, during the prostacyclin infusions. Prostacyclin infusions had no effect on prothrombin time, activated partial thromboplastin time, or platelet count, but template bleeding time increased (not statistically significantly) from 5.8 to 12.3 min. In three of six patients, the 8 ng/kg/min infusion was terminated prematurely due to nausea, vomiting, and/or hypotension. We conclude that platelet aggregability can be inhibited in patients with chronic uremia by infusing 4 ng/kg/min prostacyclin without causing untoward side effects. When infused at hemodynamically tolerable doses, prostacyclin might serve as an in vivo inhibitor of platelet aggregation during hemodialysis or cardiopulmonary bypass.
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PMID:Effects of prostacyclin infusion in uremic patients: hematologic and hemodynamic responses. 701 91

In 14 patients with coronary heart disease the effect of long-term treatment (mean 16 months, range 12-33) with alprenolol on platelet function and fibrinolytic activity was studied. While on the beta-blocker and two weeks after gradual withdrawal of it, the patients performed a bicycle-ergometer test and blood samples were obtained before and following exercise. Pre-exercise fibrinolytic activity, assessed by the euglobulin clot lysis time, was 183 +/- 27 min (mean +/- SEM) while on alprenolol as compared to 111 +/- 18 min (p less than 0.01) after its withdrawal. Activation of fibrinolysis following exercise was not significantly influenced by alprenolol. In patients treated with alprenolol, the pre-exercise threshold level of ADP, producing platelet aggregation was 3.3 muM (geometric mean) and 5.1 muM after stopping treatment (p less than or equal to 0.05). In patients receiving the beta-blocker, the ADP- threshold value dropped from 3.3 muM before exercise to 2.3 muM immediately after exercise (not significant). The corresponding values after withdrawal of alprenolol were 5.1 muM and 2.7 muM (p less than or equal to 0.02). Adrenaline - stimulated aggregation was not significantly influenced by alprenolol. Serotonin release from platelets following maximal ADP- and adrenaline stimuli was not significantly changed by exercise in patients on beta-blockade. After stopping treatment, ADP-induced serotonin release was 22 +/- 4.1% before and 15 +/- 4.7% after exercise (p less than 0.02). the corresponding values using the adrenaline stimulus were 29 +/- 5.7% and 17 +/- 4.7% (p less than 0.05). It is suggested that during physical stress alprenolol may protect platelets against aggregatory stimuli.
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PMID:Effect of long-term beta-blockade with alprenolol on platelet function and fibrinolytic activity in patients with coronary heart disease. 703 Jul 49

A cell-free system prepared from rat liver containing cytosol and mitochondria as well as a number of cofactors at near physiological concentrations was shown to form glucose 6-phosphate from malate + 3-phosphoglycerate at a rate of 1.11 +/- 0.09 mumol . min-1 . g liver-1 (mean +/- SEM, n = 9, 30 degrees C). At least 70% of glucose 6-phosphate formed was derived from malate as calculated from experiments with [U-14C]malate. The indicated rates were measured between 10 min and 30 min incubation time when the system was near steady state with respect to the lactate/pyruvate ratio and to most of the gluconeogenic intermediates. In the absence of mitochondria, the rate of formation of glucose 6-phosphate from malate was about seven times lower than in their presence. A comparison between incubations carried out in presence or absence of mitochondria revealed that mitochondria decreased the lactate/pyruvate ratio and increased the ratio of (ATP + ITP)/(ADP + IDP). It could be shown that under the present incubation conditions, formation of glucose 6-phosphate was closely linked to the ratio of (ATP + ITP)/(ADP + IDP) whereas changing redox ratios had little influence on the gluconeogenic rate.
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PMID:Gluconeogenesis in vitro. Formation of glucose 6-phosphate from malate by a cell-free rat-liver system consisting of cytosol and mitochondria. 710 24

Soluble fibrinogen binding to agonist-stimulated blood platelets is the essential physiologic function of the glycoprotein IIb-IIIa (GPIIb-IIIa) receptor. We describe a method of quantifying this receptor-ligand interaction by using flow cytometry to detect the binding of fluorescein-labeled fibrinogen to activated platelets. Fibrinogen conjugated with fluorescein isothiocyanate (FITC-FGN) was structurally and functionally indistinguishable from native fibrinogen when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, thrombin clottability, and receptor affinity studies. Platelet samples, at a concentration of 2 x 10(7) ml, were incubated with FITC-FGN and activated with adenosine diphosphate (ADP) before cytometric acquisition of fluorescence and scatter data. ADP-induced binding of soluble FITC-FGN to platelet GPIIb-IIIa was specific, time dependent, and saturable. Cytometric analysis of FITC calibration beads allowed generation of standard curves relating bead fluorescence intensity to the number of fluorescein equivalents per bead. With this information, platelet fluorescence intensity was converted into the number of FITC-FGN molecules bound per platelet. Such quantitative analysis of fibrinogen binding yielded a dissociation constant of 2.48 +/- 0.5 x 10(-7) mol/L and a maximum fibrinogen binding capacity of 42, 124 +/- 5, 628 molecules per platelet (mean +/- SEM), which are comparable to published results with radioligand assays. The simplicity, sensitivity, and quantifiability of this method may make it a useful technique for basic and clinical research involving GPIIb-IIIa function.
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PMID:Quantitation of soluble fibrinogen binding to platelets by fluorescence-activated flow cytometry. 751 93

Previously, our laboratory has demonstrated inhibition of mitochondrial state 3 (ADP-dependent) respiration 5 min after resuscitation from an asphyxial insult in lambs less than 3 days of age. Older lambs were resistant to this transient mitochondrial dysfunction. This study was designed to examine if age-related differences in baseline state 3 mitochondrial respiration, electron transport chain activity, or susceptibility to oxygen free radical-mediated lipid peroxidation were related to the previously observed differences in postasphyxial mitochondrial respiration. Mitochondrial respiration was measured in 24 nonasphyxiated control lambs aged 1-10 days using four different substrates. Electron transport chain activity was assessed in 15 of these lambs, and lipid peroxidation measured as conjugated diene production was measured in 11 of these lambs. These lambs were all ventilated to maintain normal blood gases for a time period equal to the length of the hypoxic insult in asphyxiated lambs (see below), after which samples of brain were removed for isolation of mitochondria. A second group of 11 lambs (seven < or = 3 days of age and four > 3 days of age) were asphyxiated. The insult was a 75-to-90-min episode of hypoxia and hypercarbia that resulted in bradycardia and systemic hypotension over the final 15 min of the insult. At the end of asphyxia, the lambs were resuscitated and returned to control ventilator settings. Samples of brain were removed 5 min after resuscitation. Postasphyxia electron transport chain activity and lipid peroxidation were measured. All measurements described above were done in both nonsynaptic (primarily glial in origin) and synaptic mitochondria. State 3 mitochondrial respiration varied significantly with age, decreasing by an average of 41.2% +/- 11.1% (mean +/- SEM) from Day 2 to Day 5-6 and then increasing back to levels similar to Day 2 by Day 8-10 in nonsynaptic mitochondria. State 3 respiration in synaptic mitochondria decreased 60.6% +/- 5.2% from Day 2 to Day 5-6 before returning to levels similar to Day 2 by Day 8-10. Resting (nonADP-dependent) state 4 respiration demonstrated similar developmental patterns. Electron transport chain activities did not vary with age in the nonasphyxiated control animals. In addition, an asphyxial insult did not diminish electron transport chain activities in either lambs < or = 3 days old or those > 3 days of age.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Developmental changes in newborn lamb brain mitochondrial activity and postasphyxial lipid peroxidation. 777 Apr 68

The injury and recovery processes of complex reactions of liver mitochondrial ATP synthesis during warm ischemia and after reflow were studied separately in terms of the changes in oxidation (electron transfer system) and phosphorylation (H(+)-ATPase). Oxidative activity decreased significantly from the control value of 40 +/- 0.9 (mean +/- SEM, n = 5) to 31.5 +/- 1.13 (nanoatoms oxygen consumed/min/mg protein) after 40 min of warm ischemia, while phosphorylative activity decreased significantly from the control value of 1.06 +/- 0.12 to 0.42 +/- 0.03 (mumole ATP hydrolyzed/min/mg protein) after 20 min of warm ischemia. During 120 min of reflow after 20 min of warm ischemia, the decreased phosphorylation activity recovered to 0.52 +/- 0.01 concomitant with a recovery of intramitochondrial total adenine nucleotide and an increase in the ATP/ADP ratio, while oxidative activity decreased further to 23.9 +/- 0.81. These results indicate that H(+)-ATPase is more vulnerable to warm ischemia than the electron transfer system, but that it is restored concomitant with the recovery of intramitochondrial adenine nucleotide content.
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PMID:Primary and reversible injury of H(+)-ATPase in warm ischemia and reperfusion of rat liver in relation to intramitochondrial adenine nucleotide. 786 69

cAMP is commonly measured using either immunoassay or high-performance liquid chromatography. The current methods are sensitive but may lack versatility and be expensive; also, radioactivity is potentially harmful to the operator and environment. Given these concerns, we developed a highly sensitive enzymatic fluorometric assay for cAMP. The method consists of five steps: (1) destruction of interfering compounds with apyrase, 5' nucleotidase, adenosine deaminase, and alkaline phosphatase; (2) conversion of cAMP to AMP; (3) conversion of AMP to ATP; (4) amplification of ATP by ATP-ADP cycling; and (5) fluorometric measurement of resultant NADPH. cAMP was measured in male Sprague Dawley rats anesthetized with pentobarbital. Stimulated rats (n = 4) received isoproterenol (16 micrograms/kg, s.q.) and aminophylline (20 mg/kg, s.q.), whereas controls (n = 4) received no additional drug. With the enzymatic fluorometric assay, cAMP content in heart, liver, and kidney (pmol/mg wet wt, mean +/- SEM) was 0.34 +/- 0.03, 0.33 +/- 0.03, and 0.92 +/- 0.11 in the control group and 0.77 +/- 0.10, 0.66 +/- 0.04, and 1.53 +/- 0.12 in the stimulated group, respectively. The total assay duration including sample reading procedure varied at 4.5-9.5 hr, depending on its sensitivity. cAMP from the same samples was measured using a commercially available enzyme immunoassay kit and was found to be very similar to the enzymatic fluorometric assay. We conclude that this new assay is sensitive, safe, versatile, and inexpensive and can be used to measure cAMP in multiple types of tissue, including biopsy samples weighing < 200 micrograms.
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PMID:Enzymatic fluorometric assay for tissue cAMP. 786 85

Several studies of phosphorus 31 (31P) magnetic resonance spectroscopy (MRS) have demonstrated the presence of skeletal muscle metabolic abnormalities during exercise in patients with chronic heart failure (CHF). We studied the contribution of these abnormalities to the limitation of exercise capacity in CHF. In 25 patients (age 57 +/- 2 years, left ventricular ejection fraction [LVEF] 28% +/- 1.6%, peak oxygen consumption (VO2) 16 +/- 1.2 ml/kg/mm) (mean +/- SEM), we studied the calf muscle at rest and during plantar flexion with 31P MRS. The phosphocreatine (PCr) depletion rate was significantly negatively correlated to peak VO2 (r = -0.62, p = 0.001) but not to LVEF. Muscle pH was correlated with the inorganic phosphorus (Pi)/PCr ratio (r = -0.69, p = 0.0001) and with the PCr/adenosine triphosphate beta (ATP beta) ratio (which negatively relates to adenosine diphosphate [ADP] concentration) (r = 0.65, p = 0.00001). Although muscle ATP (ATP/sum of phosphorus [sigma P] remained stable, in 8 patients ATP/sigma P decreased significantly (-15% +/- 4%, p = 0.0002). In this ATP-depleted group, peak VO2 was significantly lower than that of the nondepleted group and PCr depletion more rapid, whereas LVEF did not differ. Skeletal muscle metabolic abnormalities in CHF contribute markedly to the alteration of exercise capacity. Rapid PCr depletion and muscle acidosis are the most relevant abnormalities. ATP depletion and excessive increase in ADP during exercise may contribute further to exercise limitation specifically in patients with more marked CHF.
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PMID:Contribution of specific skeletal muscle metabolic abnormalities to limitation of exercise capacity in patients with chronic heart failure: a phosphorus 31 nuclear magnetic resonance study. 794 49

In the present study we measured membrane fluidity as the lateral mobility of the lipid probe 1,1'-ditetradecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate by fluorescence recovery after photobleaching in the plasma membrane of a single megakaryocyte, the progenitor cell of platelets. Megakaryocytes after 13 days in culture (maturation stage III) had a lateral diffusion coefficient (D) of (4.56 +/- 0.10) x 10(-9) cm2/s and a mobile fraction of 65 +/- 2% (means +/- SEM, n = 140). Megakaryocytes isolated from rib had a similar D and mobile fraction. Stimulation with alpha-thrombin (1-10 U/ml) induced a dose-dependent decrease in D to (3.40 +/- 0.22) x 10(-9) cm2/s between 1-5 min after stimulation (P < 0.001). The mobile fraction did not change. A similar decrease in D was found following stimulation with ADP (20 microM) and ionomycin (100 nM). Modulation of calpain I activity with calpain I inhibitor or tetracain had no effect. Pretreatment with cytochalasin B or colchicine decreased D to (3.64 +/- 0.29) x 10(-9) cm2/s (P < 0.003) and (3.96 +/- 0.18) x 10(-9) cm2/s (P < 0.013) respectively. After stimulation D decreased further in cytochalasin-treated cells (3.37 +/- 0.16) x 10(-9) cm2/s (P < 0.020) but remained at the same level in colchicine-treated cells. Both treatments increased the mobile fraction to 73-75% in stimulated megakaryocytes (P < 0.03). These data indicate that the diffusion velocity of lipids in megakaryocytes is low and decreases further after stimulation. These changes are independent of calpain I. Treatments that decrease the cytoskeletal mass and thereby increase the mobility of proteins in the plasma membrane increase the number of lipids that participate in this process.
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PMID:Rapid alterations in lateral mobility of lipids in the plasma membrane of activated human megakaryocytes. 816 23


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