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Biomedical subjects

R Rubio

Publications and source records attributed to R Rubio.

At least 127 records · Page 7Linked to original sources
PubMed1989

Adenosine stimulates glycolytic flux in isolated perfused rat hearts by A1-adenosine receptors.

This study was designed to assess the role of adenosine in the regulation of exogenous glucose utilization by myocardium. Perfusion of isolated rat hearts with buffer containing D-[3-3H]glucose and analysis of the coronary effluent for 3H2O production was used as an indicator of glycolytic flux. Initially, glycolytic flux was determined during five different conditions: 1) normoxia; 2) normoxia plus 100 microM adenosine; 3) normoxia plus 100 microM adenosine and 10 microM 8-(sulfophenyl)-theophylline (SPT), an adenosine receptor antagonist; 4) hypoxia; and 5) hypoxia plus 10 microM SPT. Both adenosine and hypoxia produced an approximate threefold increase in glycolytic flux that was attenuated by adenosine receptor blockade with SPT. Next, hearts were perfused during normoxic conditions with various concentrations of either R-phenylisopropyladenosine (PIA), an A1-adenosine receptor agonist, or 5'-N-ethylcarboxamidoadenosine (NECA), an A2-adenosine receptor agonist. Significant increases in glycolytic flux occurred with PIA, whereas NECA treatment resulted in only a marginal stimulation of glycolytic flux. These data provide evidence that: 1) exogenous adenosine stimulated glycolytic flux in the normoxic myocardium; 2) endogenous adenosine stimulated glycolytic flux during hypoxia; and 3) the effect of adenosine on glycolytic flux was mediated by interaction with A1-adenosine receptors.

Adenine Nucleotides↗
PubMed1989

[Syncope: general characteristics and its relation to age].

We retrospectively analyzed the clinical data of 146 patients admitted to a general hospital with the diagnosis of syncope. A definite or highly likely cause was identified in 91 patients (62%). These were of cardiovascular origin in 78%: conduction defects (31), sinus node disease (9), obstructive causes (8), ventricular arrhythmia (8), ischemia (5) and miscellaneous (14). A non cardiovascular origin was present in 22% of patients: intoxication (7), hysteria (5), hypoxemia (3), vasovagal (2), gastrointestinal bleeding (2) and 2 others. The final diagnosis in patients with a known cause was established by the history and physical examination in 16, the ECG in 42, Holter 9, ECG monitoring in ICU 8 and echocardiogram 6. No difference in the distribution of causes was present between patients below or above 65 years of age. In hospital mortality was 2%.

Adult↗
PubMed1988

Intracellular adenosine formation and its carrier-mediated release in cultured embryonic chick heart cells.

Adenosine formation and release was examined in 48 hr old primary cultures of chick ventricular myocytes. Dilazep greater than hexobendine greater than dipyridamole inhibit incorporation of adenosine into chick embryonic heart cellular nucleotides in a concentration dependent manner. A combination of 30 mM 2-deoxyglucose and 2 micrograms of oligomycin/ml reduces the ATP content of the cells by 71% in 10 min. This change is accompanied by an increase in total adenosine concentration of 3.4 nmoles/10(7) cells in 10 min. Although the ATP concentration is not altered during hypoxia (95%N2/5%CO2), adenosine concentration increases by 0.52 nmoles/10(7) cells in 30 min. When nucleoside incorporation is inhibited by 85-90% by dipyridamole, dilazep or hexobendine, efflux of adenosine decreases by 70-90%, and 60-90% of the newly formed adenosine is trapped inside the cells compared to 10% in the absence of the transport inhibitors. alpha, beta -Methylene ADP inhibits the ecto 5'-nucleotidase activity by 91 +/- 6% but does not inhibit adenosine formation or alter its distribution between cells and medium, thus ruling out the involvement of this enzyme in adenosine formation. We conclude that adenosine is formed intracellularly during 2-deoxyglucose and oligomycin-induced ATP degradation and during hypoxia and that the nucleoside is released via the symmetric nucleoside transporter.

5'-Nucleotidase↗
PubMed1988

Brain interstitial adenosine and sagittal sinus blood flow during systemic hypotension in piglet.

We sampled, using the brain dialysis technique, interstitial fluid adenosine from the frontal cortex of newborn piglets subjected to hemorrhagic hypotension while measuring sagittal sinus blood flow, cerebrovascular resistance (CVR), and cerebral O2 delivery. In group 1 (n = 8), MABP was reduced in successive steps from 76 to 30 mm Hg with decrements of approximately 10 mm Hg. At 60 mm Hg, CVR decreased by 19% (p less than 0.001), but sagittal sinus blood flow and interstitial fluid adenosine remained unchanged. At 50 mm Hg, both sagittal sinus blood flow and CVR decreased by 19% (p less than 0.001) and interstitial fluid adenosine rose 4.7-fold (p less than 0.05). At 40 and 30 mm Hg, sagittal sinus blood flow decreased further but CVR remained steady, whereas interstitial fluid adenosine rose 10- and 16-fold, respectively. In group 2 (n = 7), an abrupt reduction of MABP from 80 to 47 mm Hg produced no change in sagittal sinus blood flow and a 29% decrease in CVR (p less than 0.01). Interstitial fluid adenosine increased twofold (p less than 0.01). In group 3 (n = 7), an abrupt reduction of MABP from 79 to 40 mm Hg decreased sagittal sinus blood flow and CVR by 24 and 30%, respectively (p less than 0.01). Interstitial fluid adenosine rose threefold (p less than 0.01). In groups 1, 2, and 3, the increases in interstitial fluid adenosine accompanied decreases in cerebral O2 delivery. In group 4 (n = 7), artificial CSF with a PO2 of 152 mm Hg was perfused through the brain dialysis cannula during graded hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1988

Release of purines from postsynaptic structures of amphibian ganglia.

Isolated sympathetic paravertebral ganglia of the frog were incubated for 1 h with [3H]adenosine. Then, after washout of excess label, the contribution of pre- and post-synaptic activation on the release of 3H-labeled purines was studied. The ganglion was superfused with Ringer's solution at room temperature, and extracellular electrodes were used for stimulation and recording. Preganglionic stimulation enhanced overall release of 3H-labeled purines. At rest, the release of 3H-labeled purines per minute represented 0.62 +/- 0.02% of the total 3H-label in the ganglion, and this fraction increased depending on the frequency of orthodromic stimulation. Analyses of the effluent from resting and stimulated ganglia showed that in both cases the nonnucleotide fractions constituted greater than 97% of the total counts in the medium: adenosine (58.4 +/- 10.1%); inosine (31.7 +/- 12.9%); hypoxanthine (7.1 +/- 2.4%); and AMP, ADP, and ATP together (1.6 +/- 0.9%) (n = 11). Nucleotides were released, but their levels were not increased significantly during stimulation. Inclusion of ectophosphatase inhibitors slightly enhanced nucleotide release (from 1.1 +/- 0.5 to 1.8 +/- 0.7%; n = 5) but did not alter the amount of nucleosides. Hence, nucleosides are the main products released by the ganglion and do not arise from hydrolysis of extracellular ATP. Preganglionic stimulation enhanced release of labeled purines, which was frequency dependent from 1 to 20 Hz. Atropine (2 microM) and tubocurarine (150 microM) totally blocked the release of 3H-labeled purines associated with preganglionic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

Estimates of left ventricular interstitial fluid adenosine during catecholamine stimulation.

The hypothesis that changes in myocardial interstitial fluid (ISF) adenosine (Ado) concentrations couple coronary blood flow (CBF) with myocardial oxygen need is still controversial. Measurements of Ado in cardiac tissue, coronary sinus plasma, and pericardial infusates have commonly been used as indexes of ISF Ado, but recent studies have highlighted the potential invalidity of many of the assumptions underlying these sampling methods. With the use of an epicardial chamber (EC) to contain a small volume of buffer on the undisturbed left ventricular epicardium of anesthetized open-chest dogs, estimates of ISF Ado can be obtained without invoking these assumptions. In experiments designed to validate our method and investigate the role of Ado in the regulation of CBF during myocardial catecholamine stimulation, we found that endogenous Ado accumulated in the EC exponentially and attained constant steady-state concentrations, ranging from 75 to 125 nM, within 4 min. Intravenous infusions of two catecholamines increased steady-state EC Ado concentrations twofold, but did not affect Ado influx kinetics. We conclude that the EC technique yields more direct estimates of steady-state ISF Ado concentrations than previously available and that ISF Ado is involved in the mediation of the hyperemia accompanying myocardial catecholamine stimulation.

Adenosine↗
PubMed1988

Release of adenosine from pig aortic endothelial cells during hypoxia and metabolic inhibition.

The purpose of this study was to determine the effects of acute hypoxia on the ATP content of, and release of adenosine from, cultured endothelial cells. Pig aortic endothelial cells grown on plastic dishes or on microcarrier beads were incubated in physiological saline and gassed to achieve normoxia (media PO2 = 80-85 mmHg) or hypoxia (media PO2 = 2-12 mmHg) in the presence and absence of glucose and dipyridamole. Acute hypoxia did not significantly augment adenosine release from cells but did appear to decrease the reuptake of adenosine by cells. Hypoxia of a longer duration (3 h) led to ATP degradation and increased adenosine release when glucose was absent from the incubating medium, but not otherwise. Similarly, incubation of cells with NaCN in a glucose-free medium led to an increase in extracellular adenosine accumulation, whereas NaCN in the presence of glucose did not increase the accumulation of adenosine above the control level. The results suggest that the adenine nucleotide metabolism of cultured endothelial cells is not acutely sensitive to hypoxia or to inhibition of oxidative metabolism and can be maintained by glycolysis.

Adenosine↗
PubMed1988

Cerebral blood flow and interstitial fluid adenosine during hemorrhagic hypotension.

This study was designed to assess the role of adenosine in autoregulation of cerebral blood flow (CBF) with the use of the brain dialysis technique to sample cerebral interstitial fluid (ISF) and hydrogen clearance to measure local CBF in ketamine-anesthetized rats. In group 1 (n = 11), animals were hemorrhaged to reduce mean arterial blood pressure (MABP) from control levels (MABP = 101.1 +/- 2.6) to 80, 70, 60, 50, 40, and 30 mmHg. Cerebral autoregulation was evidenced by no significant decrease in CBF until MABP decreased to 60 mmHg. However, dialysate adenosine concentration did not increase until MABP decreased to 50 mmHg. In group 2 (bilateral dialysis; n = 11), in which the left carotid artery was ligated before reductions in MABP, left-side dialysate adenosine concentration increased at a MABP of 70 mmHg. In group 3 (bilateral dialysis; n = 6), one dialysis probe was perfused with artificial cerebrospinal fluid containing 10(-3) M 8(p-sulfophenyl)theophylline (8-SPT), an adenosine receptor antagonist, during reduction of MABP to 50 mmHg. Although there were similar reductions in CBF with or without adenosine receptor blockade, dialysate adenosine concentration was greater on the side of locally infused 8-SPT at a MABP of 50 mmHg. These data suggest that adenosine is not responsible for cerebral autoregulation at blood pressures greater than 50 mmHg but may contribute to the decrease in cerebral vascular resistance observed at arterial pressures below the autoregulatory range.

Adenosine↗
PubMed1988

Adenosine stimulates glucose uptake in the isolated rat heart.

Adenosine (Ado) is a potent coronary vasodilator. Recent studies suggest that Ado may also have an important effect on myocardial carbohydrate metabolism. To determine whether Ado has a direct effect on myocardial glucose uptake, a recirculating, constant-flow, isolated rat-heart preparation was used. The hearts were perfused with Krebs-Henseleit buffer solution with an initial glucose concentration of 11 mmol/L. A control group was compared with hearts treated with Ado infusions (50 and 100 micrograms/min) or insulin (100, 200, and 300 microU/ml). In a separate series of experiments, nitroprusside was used to evaluate the effect of a nonspecific coronary vasodilator. The rate of glucose uptake was calculated as the amount of glucose removed from the perfusate normalized for heart weight and time. Developed pressure (DP) was assessed with an intraventricular balloon, and the coronary perfusion pressure (CPP) was monitored. At the end of 1 hour, the hearts were freeze-clamped and adenine nucleotide content was measured with HPLC. Ado treatment increased glucose uptake by 80% and 140%, respectively, at the two infusion rates (p less than 0.001). Myocardial adenosine triphosphate content was 18% and 26% higher in the Ado-treated hearts than in the controls (p less than 0.001). Ado also decreased the mean DP by 30% and 36% (p less than 0.001) and decreased CPP by 10% and 22%, respectively (p less than 0.001). Insulin increased glucose uptake in a similar dose response fashion but had no effect on myocardial nucleotide content, DP, or CPP. Nitroprusside decreased CPP but had no effect on glucose uptake, adenine nucleotide content, or DP. These results suggest that Ado may have a direct effect on glucose uptake independent of its properties as a coronary vasodilator.

Adenosine↗
PubMed1987

Interstitial fluid adenosine and sagittal sinus blood flow during bicuculline-seizures in newborn piglets.

Changes of interstitial fluid adenosine concentrations and effects of O2 supply on interstitial fluid adenosine were studied by the brain dialysis technique in the frontal cortex of newborn piglets subjected to bicuculline-induced seizures. The O2 supply was changed globally by changing MABP and locally by varying PO2 in the artificial CSF perfusing the dialysis cannula. Sagittal sinus blood flow (SSBF), cerebrovascular resistance (CVR), and CMRO2 were also examined in the same animals. Seizures increased interstitial fluid adenosine 7.9-fold (p less than 0.05) when ictal MABP was maintained at preictal level and perfusate PO2 was 24 mm Hg (group 1, n = 6). Interstitial fluid adenosine increased 11.8-fold (p less than 0.05) during seizures associated with moderate systemic hypotension and the low perfusate PO2 (group 2, n = 6). By contrast, seizures increased interstitial fluid adenosine three-fold (p less than 0.05) when perfusate PO2 was increased to 182 mm Hg and ictal MABP was maintained at preictal level (group 3, n = 8). When ictal MABP was elevated from the preictal level and the perfusate was rich in oxygen, seizures failed to increase interstitial fluid adenosine (group 4, n = 7). In groups 1 and 3, the increase in interstitial fluid adenosine during seizures was associated with significant increases in SSBF and CMRO2, as well as significant decreases in CVR. These data suggest that the increase in O2 supply during seizures in piglets did not match completely the increase in O2 demand and resulted in enhanced release of adenosine into the interstitial space.

Adenosine↗
PubMed1987

Increased brain interstitial fluid adenosine concentration during hypoxia in newborn piglet.

The effects of arterial hypoxia on interstitial fluid adenosine concentrations were studied in the frontal cortex and thalamus by the brain dialysis technique and in CSF from the cisterna magna of the newborn piglet. Acute hypoxia (PaO2 = 20 +/- 1 mm Hg) increased the interstitial fluid adenosine concentrations significantly from 0.68 +/- 0.29 (SEM) to 1.60 +/- 0.35 microM in the frontal cortex and from 1.03 +/- 0.32 to 2.60 +/- 0.86 microM in the thalamus (n = 8). Interstitial fluid inosine and hypoxanthine also increased significantly during hypoxia. In separate groups of piglets, the adenosine concentration in the cisterna magna CSF under normoxic conditions was 0.04 +/- 0.01 microM (n = 5), which increased significantly to 0.17 +/- 0.04 microM (n = 6) with hypoxia (PaO2 = 4.7 +/- 1.2 mm Hg). Cisterna magna CSF inosine levels did not change significantly during the severe hypoxia. Adenosine concentrations found in the interstitial space and CSF of newborn piglets under normoxic and hypoxic conditions are within the vasodilator range. These results thus suggest that in the neonatal brain adenosine may play a role in regulating blood flow during hypoxia.

Adenosine↗
PubMed1987

[Biological significance of the endogenous secretion of insulin in response to breakfast in diabetic children].

In 20 insulin dependent diabetics and in eight age-matched healthy children, we have measured basally HbA1 and the plasma lipid profile; and both basally and after a standard breakfast of 400 cal, blood glucose, C-peptide (CPR), immunoreactive glucagon (IRG), growth hormone and nonesterified fatty acids (NEFA). No difference was found in the lipid profile of diabetic and non diabetic children. In diabetics basal blood glucose was significantly correlated to both basal C-peptide (r = 0.5332, p less than 0.05) and to the ratio C-peptide/glucagon (r = 0.8563, p less than 0.01). The C-peptide response to the breakfast was accompanied of a significant increase in IRG and NEFA in diabetics, while in non-diabetics there was no change in IRG and a significant decrease in NEFA levels. Diabetic children with basal C-peptide levels higher than 0.6 ng/ml had lower blood glucose levels (187 +/- 43 vs 315 +/- 20 mg/dl, p less than 0.02), but no difference in blood glucose or any other parameter was observed as a function of the increase in CPR after breakfast. From these results we conclude that the evaluation of residual B-cell function in diabetic children by measuring the C-peptide response to a provocative stimulus is not more informative than the single basal measurement of C-peptide and does not have an additional biological significance, at least in hyperglycaemic insulin dependent diabetic children.

Blood Glucose↗
PubMed1986

Extraction of adenine nucleotides from cultured endothelial cells.

The goal of this work was to find a method suitable for the extraction of adenine nucleotides from cultured vascular endothelial cells. Extraction of cell monolayers with 80% methanol in water yielded extracts with a higher content of ATP than did extraction of cells with perchloric acid, trichloroacetic acid, or boiling water. The optimal extraction solution was 80% methanol with 0.5 mM ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA) or EDTA, heated to 70 degrees C immediately before use. Extraction of nucleotides by this solution was rapid and the recovery of exogenous ATP added during the extraction process was generally greater than 90%. An aqueous methanol or ethanol solution may be applicable for the extraction of nucleotides and other metabolites from cultured animal cells, dispersed cells, and frozen, powdered tissues.

Adenine Nucleotides↗