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J R López

Publications and source records attributed to J R López.

At least 19 recordsLinked to original sources
PubMed1997

Adenosine prevents hyperkalemia-induced calcium loading in cardiac cells: relevance for cardioplegia.

BACKGROUND: Hyperkalemic cardioplegic solutions effectively arrest the heart but also induce membrane depolarization, which could lead to intracellular Ca2+ loading and contribute to ventricular dysfunction associated with cardiac operations. Adenosine, which possesses cardioprotective properties, has been proposed as an adjunct to conventional cardioplegic solutions. However, it is not known whether adenosine supplementation enables cardiac cells to withstand hyperkalemia-induced Ca2+ loading. METHODS: Single ventricular cardiomyocytes were isolated from guinea pig hearts, loaded with a Ca(2+)-sensitive fluorescent probe, and imaged by digital epifluorescent microscopy. The emitted fluorescence of the probe, a measure of the intracellular Ca2+ concentration, was recorded from single myocytes during hyperkalemic challenges in the absence and the presence of adenosine to assess the protective effectiveness of this agent. RESULTS: Hyperkalemic solutions induced intracellular Ca2+ loading (estimated intracellular Ca2+ concentration, 88 +/- 5 nmol/L before and 1,825 +/- 112 nmol/L after addition of 16 mmol/L KCl). Adenosine (1 mmol/L) prevented K(+)-induced Ca2+ loading (intracellular Ca2+ concentration, 86 +/- 6 nmol/L before and 85 +/- 8 nmol/L after exposure to K+). Whereas glyburide (3 mumol/L), an antagonist of adenosine triphosphate-sensitive K+ channels, had no effect, staurosporine (200 nmol/L) and chelerythrine (5 mumol/L), two inhibitors of protein kinase C, did abolish the action of adenosine. CONCLUSIONS: Adenosine prevents hyperkalemia-induced Ca2+ loading in cardiomyocytes. This effect is due to a direct action on ventricular cells, as the preparation employed was free from atrial, neuronal, and vascular elements, and appears to be mediated through a protein kinase C-dependent mechanism. The property of adenosine to prevent hyperkalemia-induced Ca2+ loading may contribute to the cytoprotective efficacy of this agent as an adjunct to conventional hyperkalemic cardioplegic solutions.

Adenosine↗
PubMed1996

Dual effect of glyburide, an antagonist of KATP channels, on metabolic inhibition-induced Ca2+ loading in cardiomyocytes.

Whether sulfonylurea therapy, which blocks ATP-sensitive K+ (KATP) channels, impedes endogenous cardioprotective mechanisms during cellular metabolic impairment remains controversial. Therefore, the effect of glyburide, a prototype sulphonylurea drug, on cytosolic Ca2+ concentration and KATP channel activity, was measured in 2-4-dinitrophenol-treated guinea-pig cardiomyocytes, using epifluorescent digital-imaging and cell-attached patch-clamp electrophysiology. Dinitrophenol (200 microM), which uncouples oxidative phosphorylation, induced opening of KATP channels and Ca2+ loading. Glyburide (6 microM) which reduced the opening of KATP channels, aggravated Ca2+ loading only when applied to dinitrophenol-pretreated myocytes but not when applied with dinitrophenol treatment. We conclude that a blocker of KATP channels has differential effects upon dinitrophenol-induced intracellular Ca2+ loading, which appear to depend upon the stage of metabolic insult.

2,4-Dinitrophenol↗
PubMed1996

Adenosine slows the rate of K(+)-induced membrane depolarization in ventricular cardiomyocytes: possible implication in hyperkalemic cardioplegia.

Hyperkalemic cardioplegic solutions produce cardiac arrest during open heart surgery by depolarizing the sarcolemma. A recognized adverse effect of hyperkalemic cardioplegia is the possible development of ventricular dysfunction believed to be related to intracellular Ca2+ loading, a consequence of K(+)-induced membrane depolarization. Adenosine has been proposed as an adjunct to hyperkalemic cardioplegic solutions. However, it is not known whether adenosine can affect K(+)-induced membrane depolarization, and associated intracellular Ca2+ loading. Perforated patch-clamp method, applied to isolated single guinea-pig ventricular myocytes, revealed that adenosine (1 mM) did not significantly reduce the magnitude of K(+)-induced membrane depolarization (35.7 +/- 1.7 v 31.0 +/- 1.1 mV in the absence v presence of adenosine). Yet, adenosine significantly slowed the rate of K(+)-induced membrane depolarization (167 +/- 32.8 v 67.9 +/- 12.9 mV/min in the absence v presence of adenosine) without directly affecting Ca2+, Na+, and K+ currents. Imposed ramp-pulses, with different rates (ranging from 0.33 to 0.05 V/s), but same magnitude of depolarization (100 mV), demonstrated that reduction in the rate of membrane depolarization decreases net inward Ca2+ current. Indeed, in Fluo-3 loaded ventricular myocytes, imaged by laser confocal microscopy, adenosine (1 mM) prevented K(+)-induced intracellular Ca2+ loading. The present findings indicate that adenosine slows the rate of K(+)-induced membrane depolarization, and reduces K(+)-induced intracellular Ca2+ loading in ventricular myocytes. Such findings support the notion that adenosine may play a cardioprotective role in hyperkalemic cardioplegia.

Adenosine↗
PubMed1996

Inositol 1,4,5-trisphosphate-induced Ca2+ release is regulated by cytosolic Ca2+ in intact skeletal muscle.

Microinjection of inositol 1,4,5-trisphosphate (InsP3) into intact skeletal muscle fibers isolated from frogs (Rana temporaria) increased resting cytosolic Ca2+ concentration ([Ca2+]i) as measured by double-barreled Ca2+-selective microelectrodes. In contrast, microinjection of inositol 1-phosphate, inositol 1,4-biphosphate, and inositol 1,4,5,6-tetrakisphosphate did not induce changes in [Ca2+]i. Incubation in low-Ca2+ solution, or in the presence of L-type Ca2+ channel blockers did not affect InsP3-induced release of cytosolic Ca2+. Neither ruthenium red, a blocker of ryanodine receptor Ca2+-release channels, nor cytosolic Mg2+, a known inhibitor of the Ca2+-induced Ca2+-release process, modified the InsP3-induced release of cytosolic Ca2+. However, heparin, a blocker of InsP3 receptors, inhibited InsP3-induced release of cytosolic Ca2+. Also, pretreatment with dantrolene or azumulene, two inhibitors of cytosolic Ca2+ release, reduced [Ca2+]i, and prevented InsP3 from inducing release of cytosolic Ca2+. Incubation in caffeine or lengthening of the muscle increased [Ca2+]i and enhanced the ability of InsP3 to induce release of cytosolic Ca2+. These results indicate that InsP3, at physiological concentrations, induces Ca2+ release in intact muscle fibers, and suggest that the InsP3-induced Ca2+ release is regulated by [Ca2+]i. A Ca2+-dependent effect of InsP3 on cytosolic Ca2+ release could be of importance under physiological or pathophysiological conditions associated with alterations in cytosolic Ca2+ homeostasis.

Animals↗
PubMed1996

Potassium channel openers prevent potassium-induced calcium loading of cardiac cells: possible implications in cardioplegia.

Hyperkalemic solutions that are used as cardioplegic agents, while effective in inducing electromechanical arrest, are only partially cardioprotective, and ventricular dysfunction has been observed. The underlying pathophysiology of cardioplegia-associated ventricular dysfunction is complex and not fully understood, but it could be related, in part, to intracellular Ca2+ loading induced by high K+ concentrations present in cardioplegic solutions. Yet no effective cytoprotective means against possible intracellular Ca2+ loading, under these conditions, has been described. Recently, potassium channel openers, which open adenosine triphosphate-sensitive K+ channels, have been reported to possess cardioprotective properties under global ischemic conditions. However, it is not known whether these novel agents could prevent intracellular Ca2+ loading that could occur during cardioplegia. Intracellular Ca2+ was monitored in ventricular myocytes, loaded with the Ca(2+)-sensitive fluorescent probe Fluo-3AM, using epifluorescent digital imaging and laser confocal microscopy. Exposure of a myocyte to a 16 mmol/L concentration of K+, a concentration of K+ commonly used in cardioplegic solutions, induced a nonhomogeneous increase in intracellular Ca2+. Potassium channel opening drugs, such as aprikalim or nicorandil, effectively prevented these solutions from increasing intracellular Ca2+. The preventive effect of potassium channel opening drugs was antagonized by glyburide, a selective blocker of adenosine triphosphate-sensitive K+ channels. This study demonstrates, at the single cardiac cell level, that solutions containing a 16 mmol/L concentration of K+ promote intracellular Ca2+ loading, which can be prevented by potassium channel opening drugs. Therefore, potassium channel opening drugs should be considered to prevent intracellular Ca2+ loading associated with the use of cardioplegic solutions.

Adenosine Triphosphate↗
PubMed1996

A KATP channel opener protects cardiomyocytes from Ca2+ waves: a laser confocal microscopy study.

Laser confocal microscopy was used to visualize intracellular spatiotemporal Ca2+ patterns in single guinea pig ventricular myocytes loaded with the Ca2+ indicator, fluo 3-acetoxymethyl ester (fluo 3-AM), and exposed to moderately elevated extracellular K+ to induce partial membrane depolarization. Analysis of K(+)-induced intracellular Ca2+ elevation revealed three distinct paradigms: 1) diffuse, nonoscillatory Ca2+ elevation across the myocyte; 2) localized Ca2+ elevation in anatomically restricted areas (Ca2+ sparks); and 3) regenerative frontal propagations of Ca2+ that traversed the length of the cell (Ca2+ waves). The first two patterns were more frequently observed when the extracellular K+ concentration was raised to 8 mM. Ca2+ waves became more common when extracellular K+ concentration was increased to 16 mM, suggesting that a minimum threshold of increase in intracellular Ca2+ is necessary for the organization of Ca2+ waves. The velocity of propagation was typically approximately 60 microns/s with an average frequency of one wave per second crossing at a given point in the cell. Wave propagation resulted in spatial and temporal oscillations in cytosolic and nuclear Ca2+ concentration. Treating cardiac cells with aprikalim, a potassium channel-opening drug, prevented 16 mM K+ (but not 32 mM K+) from inducing an increase in Ca2+ concentration and from generating Ca2+ waves. In cardiomyocytes treated with glyburide, a selective antagonist of ATP-sensitive K+ channels, aprikalim failed to prevent 16 mM K+ from inducing Ca2+ waves. In summary, moderate hyperkalemia induces distinct nonuniform form patterns of intracellular Ca2+ elevation in ventricular cells, which can be prevented by a potassium channel-opening drug through a glyburide-sensitive mechanism.

Adenosine Triphosphate↗
PubMed1995

Spontaneous calcium waves without contraction in cardiac myocytes.

Spontaneous Ca2+ waves were visualized in quiescent cardiomyocytes loaded with the Ca(2+)-sensitive fluorescent probe, Fluo-3, and imaged by laser confocal microscopy. No sarcomere shortening was detected during wave propagation. This type of Ca2+ waves began at the periphery or in a central region of a myocyte and propagated the length of the cell in one or two directions. The average velocity of wave propagation was 32 microns/sec and the estimated concentration of Ca2+ oscillated from 124, at the bottom, to 311 nM, at the pick of the wave. Ca2+ waves were not confined to a single cell but could spread from cell to cell. These results describe a type of spontaneous Ca2+ waves which does not induce a contractile response in cardiomyocytes.

Aniline Compounds↗
PubMed1995

Myoplasmic Ca2+ concentration during exertional rhabdomyolysis.

Exertional rhabdomyolysis can destroy muscle but the pathophysiology is unknown. Using intracellular selective microelectrodes, we found that intracellular Ca2+ concentration ([Ca2+]i) was 1.27 (0.17) mumol/L (median and interquartile range) in skeletal-muscle biopsy specimens from patients with exertional rhabdomyolysis compared with 0.12 (0.01) mumol/L in controls. 3 days treatment with dantrolene, a drug that inhibits Ca2+ release from the sarcoplasmic reticulum, decreased [Ca2+]i to 0.22 (0.05) mumol/L and accelerated patients' recovery. This study demonstrated that exertional rhabdomyolysis is associated with elevated [Ca2+]i, and that dantrolene has a beneficial effect in this syndrome.

Adult↗
PubMed1995

Hypersensitive response of malignant hyperthermia-susceptible skeletal muscle to inositol 1,4,5-triphosphate induced release of calcium.

Malignant hyperthermia (MH) is associated with abnormal regulation of intracellular calcium in skeletal muscle fibers. Besides a mutation in the ryanodine receptor gene, an increase in inositol, 1,4,5-triphosphate (InsP3) levels could be a possible candidate for the abnormal regulation of intracellular calcium. However, the effect of InsP3 on [Ca2+]i in MH is not known. Microinjection of InsP3 increased intracellular Ca2+ in intact skeletal muscle from malignant hyperthermia susceptible swines (MHS) with a higher potency and efficacy than in muscles from nonsusceptible (MHN) swines. Omission of extracellular Ca2+ or incubation of muscle fibers with Ca2+ channel blockers did not modify the response to InsP3. However, dantrolene (50 microM) a known blocker of intracellular Ca2+ release, decreased resting intracellular Ca2+ concentration and prevented the InsP3-induced increase in intracellular Ca2+. This suggests (i) that MHS skeletal muscles exhibit a higher responsiveness to InsP3-induced release of Ca2+, which could implicate InsP3 in the pathophysiology of MH, and (ii) that the beneficial effect of dantrolene in MHS could be related to its ability to prevent the InsP3-induced release of Ca2+.

Calcium↗
PubMed1995

Elevated myoplasmic calcium in exercise-induced equine rhabdomyolysis.

Exertional rhabdomyolysis is a myopathy of unknown pathophysiology. We measured intracellular resting calcium concentration ([Ca2+]i) by means of Ca(2+)-selective microelectrodes in intercostal muscle fibers from horses suffering from rhabdomyolysis, and from horses with no evidence of neuromuscular disorder. [Ca2+]i was several-fold higher in muscle fibers from horses suffering from rhabdomyolysis when compared to controls. Treatment of rhabdomyolytic horses with dantrolene, an agent that prevents Ca2+ release from the sarcoplasmic reticulum, reduced [Ca2+]i toward control values, and accelerated the recovery from this myopathy. These results indicate that an acute episode of rhabdomyolysis is associated with elevation in [Ca2+]i in skeletal muscles, and that dantrolene might be of benefit in treating this disease.

Animals↗
PubMed1992

EU 4093 decreases intracellular [Ca2+] in skeletal muscle fibers from control and malignant hyperthermia-susceptible swine.

The mechanisms causing the malignant hyperthermia (MH) syndrome are related to a malfunction of intracellular Ca2+ homeostasis and can be prevented or reversed by dantrolene. EU 4093 (Azumolene, 1-[[[5-(4-bromophenyl)-2-oxyzolyl] methylene]amino]-2-4- imidazolidinedione) is a 30-fold more water-soluble analogue of dantrolene that is believed to have the same effects as dantrolene on the intracellular free Ca2+ concentration [( Ca2+]i) in skeletal muscle and that should have similar efficacy in treating and preventing the clinical manifestations of MH in response to a halothane/succinylcholine challenge. To test this hypothesis, experiments were carried out in four controls (Yorkshire) and eight MH-susceptible crossbreed swine (Poland China X Pietrain). The resting [Ca2+]i in normal muscle fibers measured by Ca(2+)-selective microelectrodes was 111 +/- 12 nM (mean +/- standard deviation, n = 30), whereas in the MH muscles the resting [Ca2+]i was 395 +/- 36 nM, (n = 28) (P = 0.0001). EU 4093 decreased [Ca2+]i in MH-susceptible skeletal muscle in a dose-related fashion from 207 to 38 nM after 0.5 to 2.0 mg/kg, respectively, and had a similar effect in control skeletal muscle (58 to 30 nM) after the same doses. In MH-susceptible swine, a dose of 2.0 mg/kg was successful in preventing any clinical signs of the MH syndrome during a subsequent halothane/succinylcholine challenge. A dose of 0.5 mg/kg was able to attenuate but not reverse the clinical signs of the MH syndrome after a halothane challenge, whereas a dose of 1.0 mg/kg was completely successful in reversing this effect in all subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Percutaneous surgery in renal lithiasis. Current indications].

The indiscriminate use of extracorporeal shock waves in the treatment of urinary calculi has changed the place of percutaneous surgery in the treatment of renal lithiasis. The authors analyse current indications of PCN highlighting stone size. In their view, calculi greater than 2 cm warrant treatment by PCN since only 15-20% of patients are completely stone-free following a single session of ESWL. Attention is focussed on the staghorn calculus and the percutaneous approach. They describe the difficulty encountered in the fragmentation of the cystine calculus owing to its hardness and discuss the difficulties that may arise when using the percutaneous approach in patients with coexisting renoureteral conditions, in the treatment of lithiasis in children and in the obese patients.

Adult↗
PubMed1989

[Persistent alpha-vegetative state].

After briefly reviewing the concepts of "coma" and "alpha-coma", we report the case of a patient with presumable Pick's disease who spent several weeks in a vegetative state with a normal and reactive EEG in the alpha range in the later stages of her illness. We (a) emphasize some implications of the appearance of the eyes in such patients, b) stress the importance of distinguishing alpha activity from true alpha rhythm and (c) suggest the category "alpha-coma" should include only those individuals bearing evidence of disorders of the junctional tegmentum of the pons and midbrain. In a complementary way, we propose that patients in a persistent vegetative state displaying normal EEG should be separately classified as persistent "alpha-vegetative state".

Alpha Rhythm↗
PubMed1989

[Levels of L-carnitine in the Venezuelan infant population].

The L-carnitine blood serum and amniotic fluid levels were measured in 133 samples obtained from clinically healthy patients: 39 pregnant women with a fetal gestational age ranging from 14 to 40 weeks, 13 newborn children less than a day old, 19 newborn children between the ages of 1 and 30 days, 8 breast-feed babies and 19 children over two years of age. No significant statistical differences were seen in the maternal blood serum and amniotic fluid samples for the different gestational ages considered in the study. The average values were found to be 22.6 +/- 5.1 nmol/mL for maternal blood serum and 25.3 +/- 9.4 nmol/mL for amniotic fluid. The blood serum levels were found to be greater in the group between the ages of 1 to 30 days, reaching levels of 43.1 +/- 7.4 nmol/mL. In the group aged 1 month-18 years, the serum levels were on the average 34.3 +/- 6.7 nmol/mL. The variations found among these groups reflect characteristics specific of our population. These values should be further researched since they differ from those values reported by the Anglo-Saxons. L-carnitine concentration; blood serum level; amniotic fluid level.

Amniotic Fluid↗
PubMed1989

Intracellular free [Ca2+] in human skeletal muscle with myopathic carnitine deficiency.

Carnitine is required for the transport of activated long chain fatty acids through the mitochondrial inner membrane. We measured the intracellular free calcium concentration [( Ca2+]i) by means of a calcium selective microelectrode in skeletal muscle biopsies obtained from nine patients in which myopathic carnitine deficiency (MCD) was diagnosed, and from six subjects with no evidence of neuromuscular disease. Intact intercostal muscle bundles were dissected and then split for electron microscopic studies and electrophysiological measurements. The [Ca2+]i in muscle fibers from MCD patients was 0.46 +/- 0.02 mumol.l-1 (mean +/- SEM) and 0.10 +/- 0.01 mumol.l-1 in control subjects. At the electron microscopic level, the predominant abnormality was the presence of lipid vacuoles between the myofibrils. These results show that in patients with myopathic carnitine deficiency there is a significant increase in the resting myoplasmic calcium concentration which might be related to a malfunction of some mechanisms responsible for the homeostasis of intracellular calcium.

Adolescent↗
PubMed1988

Myoplasmic free [Ca2+] during a malignant hyperthermia episode in swine.

Malignant hyperthermia (MH) is a genetic syndrome usually initiated by exposure to volatile anesthetic agents or depolarizing neuromuscular blocking agents. We have used Ca2+-selective microelectrodes to measure in vivo the intracellular ionized calcium ([Ca2+]i) in skeletal muscle fibers of MH-susceptible swines before and during hyperthermic episodes and also after dantrolene administration. The animals were anesthetized with thiopental and fentanyl and maintained with a mixture of nitrous oxide (66%) and oxygen (34%). The malignant hyperthermic episode was triggered by exposure to halothane. Determinations of [Ca2+]i during the episode show an increase from 0.44 +/- 0.01 microM +/- SEM, n = 20) to 8.44 +/- 0.68 microM (mean +/- SEM, n = 10). Administration of dantrolene (2 mg/kg) during the hyperthermic episode reduces [Ca2+]i to 0.17 + 0.01 microM (mean +/- SEM, n = 10) and reverses the clinical symptoms. These results show that the MH episode is associated with an increase in the myoplasmic free Ca2+ concentration and that the therapeutic effect of dantrolene is related to a decrease in [Ca2+]i.

Animals↗