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Biomedical subjects

J L Alvarez

Publications and source records attributed to J L Alvarez.

At least 37 records · Page 2Linked to original sources
PubMed1992

Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current.

The properties of the low threshold Ca current (ICaT) in bullfrog (Rana catesbeiana) isolated atrial cardiomyocytes were studied using the whole-cell recording patch-clamp technique and compared with those of the high threshold Ca current (ICaL). In 91% of atrial cells we observed both ICaT and ICaL when collagenase and trypsin were used to dissociate the cells. But when pronase was used, only 30% of the cells exhibited ICaT. ICaT was never found in ventricular cells. ICaT could be investigated more easily when ICaL was inhibited by Cd ions (50 microM). Its kinetics were unchanged by substituting Ba for Ca, or in the presence of high concentrations of Ba. Both ICaT and ICaL exhibited reduced inactivation after high depolarizing prepulses. ICaT was found to be sensitive to dihydropyridines: 1 microM nifedipine decreased this current while 1 microM BAY K 8644 increased it; this occurred without significant variations in the steady-state inactivation curve. ICaT was more sensitive than ICaL to alpha 1-adrenergic and P2-purinergic stimulations, while ICaL was more sensitive to beta-adrenergic stimulation. Isoproterenol was still able to increase ICaT in the presence of high intracellular cAMP. Both currents were increased by 1 microM ouabain (although ICaL only transiently) and decreased by 10 microM ouabain. It is concluded that the two types of Ca channels can be observed in bullfrog atrial cells and that they are specifically altered by pharmacological agents and neuromediators. This may have implications for cardiac behavior.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Prajmalium, an antiarrhythmic with positive inotropic effect: mechanism of action in rabbit single cardiomyocytes.

The propyl derivative of ajmaline, N-n-propylajamaline (prajmalium), is an antiarrhythmic compound that lacks the commonly reported negative inotropic effects of all others under clinical use. The present study was undertaken to establish and understand its effects at the cellular level in mammalian preparations. Electrical and mechanical activities were recorded from right ventricular strips and Na and L-type Ca currents (INa and ICaL, respectively) were recorded with the whole-cell patch-clamp technique in right ventricular myocytes freshly dissociated from rabbit hearts. Prajmalium decreased the maximal rate of depolarization of the action potential in a dose-dependent manner with an EC50 of 3 microM. This effect was use and frequency dependent. Action potential duration was increased by 1 microM prajamalium but decreased on applying higher concentrations. The force of contraction was slightly (15%) increased at 0.1 microM, not affected at all at 1 microM and depressed by 30% at 20 microM. In single cardiomyocytes maintained at negative holding potentials, INa was slightly depressed by prajmalium at 10 nM and reduced by 75% at 10 microM. ICaL was increased by 30 and 20% on applying prajmalium at 1 and 10 microM, respectively; on the other hand, ICaL was reduced by these two concentrations of prajmalium at less negative holding potentials. A higher prajmalium concentration (100 microM) decreased ICaL at all holding potentials studies and this effect was enhanced with depolarization. The increase in ICaL induced by prajmalium (1 microM) was also observed after ICaL had been fully beta-adrenergic and P2-purinergic stimulated by isoproterenol (1 microM) in the presence of IBMX (100 microM) and ATP (10 microM). It is concluded that prajmalium is able to increase ICaL in rabbit ventricular cells in a voltage-dependent manner, an effect that could account in part for the observed lack of negative inotropism of this antiarrhythmic in clinics.

Action Potentials↗
PubMed1991

Dual action of prajmalium on the Ca currents in frog isolated cardiomyocytes.

The effects of N-n-propylajmaline (prajmalium) on the Na and Ca currents of single frog atrial and ventricular cells were studied by means of the whole-cell patch-clamp technique. Prajmalium (10(-9) to 10(-6) M) depressed the Na current (INa) in a dose- and use-dependent manner. In the same range of concentrations, prajmalium induced a dual effect on the high (ICaL) and low (ICaT) threshold Ca currents (the latter being only present in atrial cells). At a low concentration (10(-9) M), prajmalium increased both Ca currents while at high concentrations (10(-6) M) it depressed them. Prajmalium appeared very potent on ICaT although this current is generally reported to be barely sensitive to agonists and drugs. The action of the drug was also accompanied by a shortening in the half-time of inactivation of the Ca currents and a slight hyperpolarizing shift of their availability curves. The increase in ICaL by prajmalium was not prevented by prazosin (10(-7) M) nor by propranolol (10(-6) M), and it was also observed after ICaL had been fully stimulated by isoproterenol (10(-7)M). Nifedipine (10(-6) M), however, was able to prevent or block the prajmalium-induced increase in ICaL. Some similarities between the actions of prajmalium and dihydropyridine agonists on Ca currents are discussed.

Animals↗
PubMed1990

[Vasculitis associated with proliferation of large granular lymphocytes].

We report a patient with the syndrome of large granular lymphocytes in whom the initial clinical features were polyarthritis, hepatosplenomegaly and neutropenia. Relative lymphocytosis was also demonstrated at the expense of a subpopulation with morphology and surface markers characteristic of large granular lymphocytes (CD2+, CD8+, CD16+ and HNK-1+). After 6 months of asymptomatic course, without changes in clinical or laboratory data, the patient died from an acute abdomen with mesenteric ischemia of different likely causes as suggested by necropsy data (multivisceral diffuse infiltrate by large granular lymphocytes, systemic vasculitis and Clostridium sepsis). The association between this syndrome and systemic vasculitis is discussed.

Cell Movement↗
PubMed1990

Effects of purinergic stimulation on the Ca current in single frog cardiac cells.

Ca current (ICa) was measured by whole-cell voltage clamp in single cells isolated from frog ventricle, in which the Na current was inhibited by tetrodotoxin (0.3 microM) and K currents were blocked by substituting K with 120 mM intracellular and 20 mM extracellular Cs. The influence of stimulation by ATP (0.1-100 microM) was assessed in the presence of propranolol (1 microM) or pindolol (0.1 microM), prazozin (0.1 microM) and atropine (10 microM). ATP, in the micromolar range, had two types of effect. Like other P1-purinoagonists, it antagonized the increase in ICa elicited by beta-adrenostimulation. When added alone, 1 microM ATP could increase ICa up to twofold. An increase in ICa was also observed even after it had been maximally enhanced by intracellularly applied cAMP (50 microM). Voltage dependence and kinetics of ICa were not affected. These effects were considered to be related to P2-purinoceptor activation. At higher ATP concentrations the increase in ICa was less; at 100 microM, ATP reduced ICa. The ATP-induced increase in ICa was prevented by internal perfusion of the cells with GDP [beta-S] or neomycin, respectively, to block signal transduction to phospholipase C or its phosphodiesterase activity on the polyphosphoinositides. We conclude that P2-purinoceptor stimulation increases the Ca current in frog ventricular cells by a pathway that might involve phosphoinositide turnover.

Adenosine Triphosphate↗
PubMed1990

[Acute hepatic lesion caused by Giardia lamblia].

A study was made of 20 rats infested by Giardia muris in which a histologic study was made of the liver, as well as of 25 patients with giardiasis and elevated alanine-aminotransferase levels. Patients with positive A or B hepatitis markers, cholelithiasis or history of drug or alcohol use were excluded. Tests of liver function and liver biopsy were performed and antiparasite therapy was given during three months of follow-up, after which the liver biopsy was repeated. Humoral alterations were compared to those of 30 patients with acute viral hepatitis (15 type A and 15 type B) over the same periods of time. In 20% of the rats, nonspecific liver lesions were found. In the patients liver enzymes and the thymol test normalized a month after treatment and serum bile acids became normal in the third month. The liver biopsy demonstrated hepatic damage in 94% of the patients (in 20 cases cell lesions and in 12 cases inflammatory lesions) which regressed in the third month, the follow-up biopsy being normal after eradication of the parasite was confirmed. The comparative study with viral hepatitis showed highly significant differences in all the variables studied during the follow-up stage. Emphasis is placed on the importance of this lesion and its differential diagnosis to prevent its progression to chronic liver disease.

Acute Disease↗
PubMed1987

Angular dependence of shallow dose from energetic electrons.

A definite angular dependence of shallow dose from energetic electrons was observed when measuring the angular response of several detectors. This angular dependence of dose appeared to be fundamental, not a detector artifact. The theoretical response of a detector is discussed and compared to measurements of shallow dose with tissue and phantom response detectors. The energy-dependent angular response of the dose observed could not be explained by simple trigonometric arguments. The response, which is backscatter-dependent, must be considered in detector design and dose measurements. It is not possible for standard detectors to follow this response.

Beta Particles↗
PubMed1985

Effects of manganese chloride on the outward currents in frog atrial trabeculae.

The effects of MnCl2 on outward currents in frog atrial muscle were investigated under voltage-clamp conditions. MnCl2 (3 mmol/L), which completely abolished the slow inward current, produced a decrease in the outward background current (Ib) at potentials positive to -50 mV. The delayed outward current (Ix, time dependent) was not altered by Mn. "Isochronic activation curves" for Ix and decay of current tails at -40 mV remained unaffected after Mn. Effects on Ib probably reflect a decrease in IK1 related to the decrease in Ca influx as well as a reduction in the Na-Ca exchange current.

Action Potentials↗
PubMed1984

Evolution of the alimentary toxic oil syndrome due to ingestion of denatured rapeseed oil.

Three hundred seventeen patients with toxic oil syndrome caused by ingestion of denatured rapeseed oil were followed up after one year. Total mortality for the 317 patients was 4.4%. After 12 months, 3.2% of the surviving patients have a severe motor neuropathy, 52.9% are asymptomatic, and the remaining 39.4% have mild residual myalgia. The cause of death in seven patients during the acute phase of toxic oil syndrome was respiratory failure due to interstitial pneumonitis with cerebral edema. The death of five patients in the second phase was due to motor neuropathy that involved respiratory muscles and was complicated by aspiration pneumonia.

Adolescent↗
PubMed1981

Effects of low pH on the action potential and contraction of normal and hypoxic papillary muscles.

The effects of low pH (6.5) on action potentials and contractions of rabbit papillary muscles were examined under aerobic and hypoxic conditions (pO2 = 65- 75 mmHg, 8.6-10.0 kPa). An acid medium reduced overshoot, Vmax of phase O and action potential duration, without changing the resting potential, under aerobic aerobic conditions. Maximum twitch tension was reduced and resting tension was increased by 40% and 6% respectively of control values. Upon returning to normal Tyrode, all parameters returned to control values. The effects of acidosis under hypoxic conditions were essentially the same as those described above; acidosis potentiated the effects of hypoxia. It is concluded that in the given experimental conditions, low pH potentiates the effects of hypoxia on electrical and contractile activity, although probably by different mechanisms. The effects of acid medium on the action potential could be well accounted for the a reduction in slow inward current and by an increase in outward background potassium current, probably in relation to an increase in internal free calcium concentration.

Action Potentials↗
PubMed1980

Enhancement of ouabain arrhythmias by fatty acids.

Possible enhancement by free fatty acids (FFA) of the arrhythmogenic actions of ouabain was studied in rabbits. The mean dose of ouabain required for inducing ventricular tachycardia or fibrillation in conscious animals was significantly lowered by intravenous injection of 5 ml of a 20% fat emulsion (Lipofundin), which significantly elevated circulating FFA. Lipofundin alone did not initiate arrhythmias in another group of animals. The transmembrane action potential duration (APD) and the maximum rate of depolarization (Vmax)recorded from rabbit papillary muscles were markedly reduced under the influence of 2 mM octanoate, a short-chain FFA. Ouabain, 10(-7M), reduced significantly only the APD measured at zero level of repolarization. In papillary muscles exposed to both octanoate and ouabain, resting potential, overshoot, APD, and Vmax were all significantly decreased below control values. The synergistic arrhythmogenic actions of FFA and ouabain might be explained by the inhibiting effect of both agents on membrane (Na+ + K+)ATPase.

Animals↗
PubMed1980

Action potential characteristics of rabbit papillary muscle.

The ionic components of the action potential (AP) in rabbit right papillary muscle (RRPM) were determined by simple methods such as changes in external concentrations of sodium and calcium ions and addition of MnCl2 ot the perfusion fluid. Two components (fast and slow) were clearly visible in the upstroke of AP in normal Tyrode solution. MnCl2 (5 mmol/l) eliminated the slow component which forms the overshoot (OS) leaving the fast one unaffected, indicating that the former was related to a slow inward current. Mn also drastically reduced AP duration without changing the slope of phase 3 of repolarization. Reduction of Na concentration to 90 mmol/l did not affect the peak voltage of the OS but shortened AP. This low-Na solution reduced both (Vmax)f and the amplitude of the fast component. Ca-free solution reduced OS and increased AP duration. In high-Ca Tyrode (7.2 mmol/l) OS was increased and AP shortened. The effects of MN were reversed in this solution. The results suggest that the upstroke of the RRPM action potential is determined by two different ionic currents: a fast Na current responsible for the fast component and a slow inward current carried mainly by Ca, this latter being responsible for the slow component in the upstroke and for the plateau phase. The existence of propagated, Ca-dependent slow responses was demonstrated. Emphasis is placed on the fact that the major determination of the repolarization process in this type of AP is probably the inactivation of the slow inward Ca current.

Action Potentials↗
PubMed1980

Effects of moderate hypoxia on action potential and contraction of rabbit ventricular muscle.

Experiments were performed on rabbit right ventricular strips in order to investigate the effects of moderate hypoxia on electrical and mechanical activities of this preparation. The results indicate that a slow inward current (Isi) is responsible for overshoot (OS) and the plateau phase of the action potential (AP). Hypoxia (pO2 = 65-70 mmHg; 8.66-10.0 kPa) induced a rapid shortening of AP and an increase in the phase-3 slope. It also markedly reduced twitch tension and time to peak tension, and increased resting tension. The resting potential (RP), OS and maximum rate of depolarization of phase O were not affected during 60 min of hypoxic perfusion. Isoproterenol under this condition had a positive inotropic effect and also increased AP duration (APD) measured at -60 mV, having a less pronounced effect on the plateau phase. MnCl2 in hypoxic conditions drastically reduced OS indicating that even in this condition, Isi was present. These results suggest that an increase in gK is responsible for the hypoxia-induced reduction in APD. This also partially explains the maintenance of RP during hypoxic incubation.

Action Potentials↗