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Biomedical subjects

D McCall

Publications and source records attributed to D McCall.

At least 37 records · Page 2Linked to original sources
PubMed1987

The effect of ethanol and acetaldehyde on Na pump function in cultured rat heart cells.

To further define the sarcolemmal effects of ethanol and acetaldehyde, their effects on Na pump function were studied in synchronously contracting monolayers of neonatal rat myocardial cells. The effects of ethanol (10 mg/dl to 1000 mg/dl: 2 X 10(-3) M-0.2 M) and acetaldehyde (10(-6) M to 10(-4) M) on total 42K influx, ouabain-sensitive 42K influx, Na pump density (from specific 3H-ouabain binding) and pump turnover rates were measured. Applied acutely ethanol had no effect on 42K influx but after 30 min of treatment 42K influx was decreased by 13%, 23% and 48% in 100 mg/dl, 300 mg/dl and 1000 mg/dl ethanol respectively. This primarily reflected a decrease in mean ouabain-sensitive K+ influx from a control of 12.54 to 9.90, 8.95 and 6.68 (p-mol/cm2/s) in 100, 300 and 1000 mg/dl (2 X 10(-2) M, 6 X 10(-2) M) ethanol. Acetaldehyde in the concentrations tested had no effect on K+ influx. Ethanol treatment produced a decrease in Na pump density, maximum within 30 min and dose-dependent, at concentrations of 100 mg/dl (22%), 300 mg/dl (37%) and 1000 mg/dl (55%). Acetaldehyde had no effect on Na pump density. In the presence of ethanol (300 mg/dl and 1000 mg/dl) intracellular Na+ increased significantly and the Na+ efflux declined in parallel with the K+ influx. From the ouabain-sensitive K+ and Na+ fluxes and the Na pump density individual pump turnover rates were calculated at 62.5/s in control cells and 66/s and 84/s in cells treated with 300 mg/dl (6 X 10(-2) M) and 1000 mg/dl (0.2 M) respectively. We conclude that ethanol, but not acetaldehyde has a depressant effect on sarcolemmal Na pump function. The results suggest this is due primarily to a decrease in the number of sarcolemmal Na pump sites.

Acetaldehyde↗
PubMed1987

Excitation-contraction coupling in cardiac and vascular smooth muscle: modification by calcium-entry blockade.

In recent years therapy with the calcium entry-blocking drugs nifedipine, verapamil, and diltiazem has made a major impact on the treatment of cardiovascular disease. Although all three of these drugs are approved for the treatment of angina pectoris, some are effective in treating supraventricular tachyarrhythmias and all appear to be effective in the treatment of mild-to-moderate hypertension. Reports of their therapeutic potential, however, are not confined to the cardiovascular system, which reflects the ubiquity of calcium ions as stimulus-effect couplers in a wide variety of organ systems. Although chemically heterogeneous, all three drugs produce similar negative inotropic effects in the myocardium and similar relaxant effects in vascular smooth muscle. From a review of the excitation-contraction coupling process in cardiac and smooth muscle it is apparent that "calcium blockade" could occur at any one of several loci. Our present understanding is that the effect of nifedipine, verapamil, and diltiazem is confined to an inhibitory one on channel-mediated membrane calcium influx. There is, in fact, a close parallel between their ability to decrease slow-channel calcium influx in the myocardium and the negative inotropic action of the drugs. Similarly, in vascular smooth muscle their ability to inhibit voltage- or receptor-mediated calcium influx parallels their vasorelaxant properties. With the use of radiolabeled ligands, particularly of the dihydropyridines (nifedipine, nitrendipine, nicardipine, nisoldipine) it has been shown that the drugs show high-affinity stereospecific binding to vascular smooth muscle channels in the same concentration range as their relaxant properties. In contrast, it was originally thought that myocardial binding was of a lower affinity and correlated poorly with the negative inotropic effect. More recent data, however, have cast some doubt on the validity of these observations. Attempts to define specific drug receptors are incomplete at this time. It appears that the dihydropyridine receptor is a 30-60 K D peptide subunit of the calcium channel. Distinct receptors for verapamil and diltiazem are poorly defined, but appear to be allosterically related to the dihydropyridine receptor. By their interactions with the calcium channel, the calcium entry-blocking drugs modulate excitation-contraction coupling, which produces their negative inotropic and vasorelaxant effects. They also interact with other slow channel-dependent functions in the specialized conducting tissues of the heart to slow the spontaneous sinus rate and decrease atrioventricular conduction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Identification of a genetic locus, Rsm-1, controlling protective immunity against Schistosoma mansoni.

Mice of most inbred strains develop moderate to high levels of resistance to challenge infection on vaccination with radiation-attenuated cercariae of Schistosoma mansoni. P strain mice, however, fail to display significant protective immunity after exposure to the same vaccine. To examine the genetic basis of this polymorphism in host immunity, vaccine-induced resistance was examined in (C57/BL6J X P/N)F1, F2, and reciprocal backcross generations. The defective immunity which characterizes the P strain parent was found to be inherited in a fully recessive manner and to be controlled by a single genetic locus, which we have designated Rsm-1. Linkage analyses revealed that Rsm-1 is not genetically associated with the major histocompatibility complex (chromosome 17), the immunoglobulin heavy chain locus (chromosome 12), or a single locus influencing defective anti-schistosomulum IgM antibody responses in the P parental stock. These data provide the first example of single gene control of vaccine-induced immunity against a helminth infection. Because P mice are also defective in their capacity to develop tumoricidal macrophages and in their immunity to Leishmania major, genes encoded by the Rsm-1 locus may play a general role in resistance to infection and malignancy.

Animals↗
PubMed1986

Duplex pulsed Doppler echocardiography in mitral regurgitation.

The accuracy of duplex pulsed Doppler echocardiography (d-PDE) for detecting mitral regurgitation was evaluated in 35 patients undergoing d-PDE, cardiac auscultation, and left ventriculography. With three transducer positions, the overall d-PDE sensitivity was 95%, specificity was 100%, positive predictive value was 100%, negative predictive value was 94%, and diagnostic accuracy was 97% compared with ventriculography. This technique was superior to auscultation (sensitivity 74%, specificity 94%, positive predictive value 93%, negative predictive value 75%, diagnostic accuracy 83%). No false-positive d-PDE results occurred, but discordant false-negative results occurred frequently among the three transducer positions. If discordant negative results are considered to be false negative, then d-PDE is both sensitive and specific when mitral regurgitation is defined as systolic spectral broadening in any one transducer position.

Echocardiography↗
PubMed1986

Preventive dentistry in a health centre: effectiveness and cost.

The clinical and economic effects of a programme of preventive dentistry for children in an inner-city health centre are compared with those for traditional restorative care. Reductions in the rate of dental caries are estimated to be 70% for children aged 4-6 after 4 years in the programme (dmft) and 85% for children aged between 7 and 10 years after 4 years (DMFT). The cost-effectiveness analysis on which the economic appraisal is based identifies the issue of differences in the quality of output as critical to choices between the two treatment regimes. The preventive programme was primarily intended for pre-school children; for this younger group, assumptions about the quality of the preventive outcome would have to value it at between 0.8 and 1.2 times the quality of the restorative outcome in order to make up the difference in cost between the two regimes. For 7-10 year olds, the 4-year analysis showed the preventive programme to be more costly than restorative care largely because of low rates of incremental change at these ages. These rates were partly influenced by the design of the study and partly by the eruption status of the permanent dentition across this age-group. There is a need for further study of measures of dental outcome which combine aspects of both the quality and length of life of teeth.

Child↗
PubMed1986

The effects of histamine on contraction frequency, sodium influx, and cyclic AMP in cultured rat heart cells.

Histamine has been shown to have both positive inotropic and chronotropic effects. To evaluate the chronotropic effects, spontaneously contracting monolayers of cultured rat myocardial cells were treated with histamine, 10(-7) M-10(-4) M. This resulted in a dose-dependent increase in contraction frequency reaching a maximum in 10(-5) M histamine. Contraction frequency (mean +/- SEM) increased from a control of 121 +/- 5 contractions per minute to 153 +/- 4.5, 181 +/- 9, 212 +/- 4, and 216 +/- 1 in 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M histamine, respectively (for each n = 10, p less than 0.001). The effect was time-dependent, taking 30 minutes to develop fully. Changes in contraction frequency were accompanied by parallel dose- and time-dependent increases in the verapamil-sensitive sodium influx. Verapamil-sensitive sodium influx (pmol/cm2/sec) increased from a control of 10.45 +/- 1.44 (mean +/- SEM) to 24.34 +/- 2.41 and 32.57 +/- 2.35 at 10- and 30-minute treatment with 10(-6) M histamine (n = 5, p less than 0.001). These data fit the previously described relation between verapamil-sensitive sodium influx and contraction frequency in these cells. Cimetidine (10(-4) M) but not diphenhydramine (10(-4) M) abolished both the contraction frequency and sodium influx response to histamine. Subsequent studies showed a dose- and time-dependent elevation of cyclic adenosine monophosphate (cAMP) with histamine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗
PubMed1985

Kinetics of thallium exchange in cultured rat myocardial cells.

The kinetics of thallium exchange in cultured rat myocardial cells were studied and compared to those of potassium in the same tissue. Studies were carried out using low concentrations (10 nM to 5 microM) of thallium-204, approximating those likely to be encountered during clinical myocardial scintigraphy. Both thallium uptake and release could be described by a single exponential with a half-time of exchange which was approximately half that of potassium and which was largely independent of extracellular thallium concentration. Some 60% of thallium uptake occurred via an "active" or ouabain-inhibitable mechanism which, in the absence of extracellular potassium, could be activated by low concentrations (10 nM to 5 microM) of thallium. The apparent Km for thallium on this active transport mechanism was 2-7 microM. Increasing extracellular potassium from 0-10 mM caused significant, concentration-dependent decreases in both the total and the active component of the thallium influx. Similarly nonradioactive thallium (0.10 microM to 0.10 mM) caused a concentration-dependent decrease in active potassium influx. Analysis of these results by both Lineweaver-Burk plots and Dixon plots confirmed competitive inhibition, potassium on thallium influx and vice versa, for the active component of the fluxes, and noncompetitive in the remainder. These findings indicate that active transport accounts for the greater portion of the influx of thallium and potassium, and that this active transport occurs via a common mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Single coronary artery with the right coronary artery arising from the first septal perforator.

A 50-year-old woman with chest pain and an exercise thallium-201 scintigram positive for focal ischemia was found on coronary arteriography to have a heretofore unreported variant of single left coronary artery with the right coronary artery originating as a branch from the first septal perforator. Proximally, the aberrant vessel coursed through the ventricular septum at the level of the right ventricular outflow tract. A conus artery was absent and this is a possible basis for the focal basal ventricular ischemia and the patient's symptoms.

Coronary Vessel Anomalies↗
PubMed1979

Cation exchange and glycoside binding in cultured rat heart cells.

The Na/K-exchange characteristics, ouabain-binding kinetics, and Na pump turnover rates of synchronously contracting monolayers of neonatal rat myocardial cells were studied. The cells exchange Na rapidly (T1/2 = 35 s) with a mean Na flux of approximately 25 (pmol/cm2)/s. The half time (T1/2) of K exchange is much longer (12 min); the mean K flux is 13 (pmol/cm2)/s. Active Na/K transport, as measured by K influx, is relatively ouabain sensitive, and 10(-6) M ouabain produces half-maximal inhibition. Ouabain (10(-2)M) inhibits 60% of the Na efflux and 75% of the K influx. The cells bind [3H]ouabain rapidly (T1/2 = 8 min), but release it very slowly (T1/2 = 11 h), and both the amount bound and the rate of binding were inversely proportional to extracellular K. Specific [3H]ouabain binding demonstrates saturation reaching a maximum of 1.6 x 10(6) molecules per cell at 2 x 10(-7) M [3H]ouabain. From cell surface area and ouabain-sensitive flux measurements, the Na pump density was calculated at 720/micrometer2 with an individual pump turnover rate of 50/s. Thus the studies indicate that despite their neonatal origin, the behavior of the Na pump in these cells is very similar to that in other mammalian tissues.

Animals↗
PubMed1978

Responses of cultured heart cells to procainamide and lignocaine.

The effects of procainamide and lignocaine, in concentrations from 10(-6) to 10(-2) mol.litre(-1), on the Na influx and contraction frequency of cultured heart cells were studied. Both drugs produced a prompt, dose-dependent reduction in Na influx which was significant (P less than 0.01) for all concentrations tested. Lignocaine affected only that portion of the Na influx which was also verapamil-sensitive, whereas procainamide suppressed in addition, the verapamil-insensitive influx. In addition both drugs produced a concomitant decrease in the spontaneous contraction frequency of the cells. A close linear correlation (r = 0.99) between verapamil-sensitive Na influx and contraction frequency, in the presence of both procainamide and lignocaine was found. From this, and previous studies indicating a dependency of contraction frequency on the inward verapamil-sensitive Na influx, it is suggested that the drugs modify the automaticity of this preparation by a primary influence on membrane Na exchange.

Animals↗
PubMed1976

Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.

Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs.

Adrenergic Agonists↗
PubMed1976

Effect of verapamil and of extracellular Ca and Na on contraction frequency of cultured heart cells.

Monolayer cultures of myocardial cells were prepared by trypsin dispersion of neonatal rat ventricles. The cells were cultured for 4-5 days by which time a synchronously contracting monolayer of some 1.0 x 10(6) cells per 6-cm diam petri dish had formed. The contraction frequency and Na influx of the cells were unaffected by tetrodotoxin (2 x 10(-5) mg/ml) but both were markedly reduced by the addition of verapamil (10(-9) M to 10(-5) M). The effect of verapamil on both parameters occurred very rapidly. Although unresponsive to change in [Ca]0 between 0.3 mM and 3.0 mM, the contraction frequency of the cells declined rapidly as the [Ca]0 was reduced below 0.3 mM. On the other hand the beating rate of the cells was linearly related to [Na]0 below 40 mM the cells ceased to contract. It is therefore apparent that both [Ca]0 and [Na]0 contribute to the maintenance of the contraction frequency of cultured myocardial cells, but the latter is by far the more important. There also appeared to be, under all conditions, a close relationship between verapamilsensitive Na influx and contraction frequency. For the greater part this relationship was linear although at higher Na influx values it appeared to show evidence of saturation.

Animals↗