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Biomedical subjects

J G Webb

Publications and source records attributed to J G Webb.

At least 109 records · Page 6Linked to original sources
PubMed1980

Adaptation of left ventricle to chronic pressure overload: response to inotropic drugs.

Left ventricular (LV) force-generating capacity was determined in eight anesthetized dogs with pressure-overload hypertrophy. Length-contractile force (CF) curves recorded from the LV with a modified Walton-Brodie arch were displaced upward from control. However, when CF was normalized for LV wall thickness changes accompanying hypertrophy and expressed as g/cm2, the length-CF curve was depressed compared to normal. The CF response to isoproterenol and calcium was depressed in dogs with hypertrophy; however, the CF response to ouabain was not different from control. Taken collectively these findings suggest that pressure-overload hypertrophy is associated with a depressed force-generating capacity per unit cross section of myocardium at any given muscle length, i.e., a depressed inotropic state, but that the hypertrophied LV has a greater than normal force-generating capacity due to an increased number of weaker cross-sectional units. Further, the depressed inotropic state is not associated with augmented plasma norepinephrine levels. Therefore, adaptation of the LV to pressure overload is by cardiac hypertrophy alone.

Animals↗
PubMed1979

Collateral circulation in the rabbit tongue after common carotid ligation.

A study was undertaken to ascertain the microvascular pattern of the collateral circulation of the tongue after unilateral ligation of the common carotid artery. The right common carotid artery was ligated in 25 New Zealand White male rabbits. These animals were killed in groups of five at intervals of an hour, six hours, 24 hours, one week, and two weeks. The vasculature in the head and neck of these animals was flushed with heparinized saline solution and perfused with latex. The results show that circulation was present but signifincatly reduced in the one-hour group, slightly reduced in the six-hour and 24-hour groups, and normal in the one- and two-week groups. This study indicates that the collateral circulation of the tongue is extensive and that a normal vascular pattern returns within a week after unilateral ligation of the common carotid artery.

Animals↗
PubMed1979

The effects of perhexiline on the sympathetic nervous system.

The effects of perhexiline on sympathetic nervous system function were studied in vitro and in vivo. Perhexiline decreased the field stimulation-induced contractile response of the isolated vas deferens and significantly decreased the quantity of norepinephrine released during stimulation of this preparation. In vivo studies in dogs showed that perhexiline reduced the heart rate response to cardiac accelerator nerve stimulation, an effect not associated with an increase in cholinergic tone or beta adrenergic blockade. Measurements of norepinephrine released from the heart during cardiac nerve stimulation showed that perhexiline (3 mg/kg) decreased norepinephrine release by approximately 35%. These results suggest that a presynatpic effect of perhexiline, which results in a decrease in norepinephrine release, contributes significantly to the attenuated heart rate response which occurs after administration of this drug. A decrease in transmitter release during sympathetic stimulation could play an important role in the mechanism for the protective effects of perhexiline in myocardial ischemic damage.

Animals↗
PubMed1978

Studies of the interrelationship between plasma norepinephrine, plasma renin activity and acute myocardial infarction in dogs.

Serial determinations of plasma norepinephrine and renin activity were made in dogs following acute ligation of the left anterior descending coronary artery. Increases in both substances closely paralleled increases in creatine phosphokinase activity, heart rate and the incidence of ventricular premature contractions. Following acute myocardial infarction, significant correlations were found to exist between plasma norepinephrine and plasma renin activity and between the levels of these vasoactive substances and the measured indices of ischemic damage. These data suggest that changes in vasoactive systems associated with myocardial infarction may contribute to the extent of ischemic injury.

Animals↗
PubMed1976

A positive inotropic effect of propranolol on the canine myocardium: a presynaptic effect.

Administration of propranolol directly into the anterior descending branch of the left coronary artery (LAD) resulted in a localized increase in myocardial contractile force in the area of the left ventricle perfused by the LAD. The onset of the positive inotropic response occurred within 30 seconds after drug administration with a duration of action of approximately 8 minutes and was associated with a significant increase in the coronary sinus/arterial ratio of norepinephrine. Contractile force in an area of the left ventricle perfused by the circumflex artery decreased concomitantly with the characteristic negative chronotropic action of propranolol. Pretreatment with reserpine abolished the positive inotropic effect of propranolol while ganglionic blockade with hexamethonium failed to alter the character of the response. Imipramine pretreatment not only blocked the positive inotropic effect of propranolol but resulted in an exaggerated negative inotropic effect in both areas of the left ventricle along with a significant fall in systemic arterial blood pressure. The data demonstrate that propranolol can evoke the release of norepinephrine from cardiac adrenergic nerve endings and raise the possibility that propranolol may be taken up by the amine uptake system.

Animals↗
PubMed1975

Biochemical and histofluorescence studies of catecholamines in superior cervical ganglia in organ culture.

The metabolism of catecholamines in rat superior cervical ganglia in organ culture was examined by biochemical and histofluorescence methods. Pronounced increases in both norepinephrine and dopamine content were observed in the cultured ganglia. Norepinephrine levels were more than doubled after 12 hours in culture and reached a maximum after 24 hours. The greatest increase in norepinephrine concentration occurred in the region of the postganglionic nerve trunks and was correlated with an accumulation of intense catecholamine fluorescence in the stumps of the severed postganglionic nerves. Since the rate of norepinephrine synthesis was unaltered, the increase in norepinephrine levels in cultured ganglia appears to be a result of blocked axoplasmic transport of this amine out of the ganglia. The dopamine content of the cultured preparations was not altered after 24 hours but increased rapidly thereafter and attained a maximum at 48 hours. The changes in dopamine did not parallel the changes in norepinephrine either in time course or distribution. The elevated levels of dopamine were accompanied by an increased rate of dopamine synthesis. It is suggested that the increased dopamine content in cultured ganglia is the result of an enhanced synthesis of this amine by specific dopaminergic cells.

Animals↗
PubMed1969

The effects of reserpine, alpha-methyltyrosine, and L-3,4-dihydroxyphenylalanine on brain tyrosine transaminase.

The effects of a variety of pharmacological and physiological manipulations on the activity of hepatic tyrosine transminase have been extensively investigated. Brain tyrosine transaminase, however, has received only limited attention. Since tyrosine transaminase may be important in the regulation of catecholamine biosynthesis in the brain, the effects of agents affecting catecholamine storage and synthesis on brain tyrosine transamination were investigated. Transamination in the 12,000 x g fraction was measured by a radioactive procedure. alpha-Methyltyrosine and reserpine, agents which deplete brain catecholamines, decreased tyrosine transaminase activity. Administration of the catecholamine precursor, L-3,4-dihydroxyphenylalanine to the reserpine-and alpha-methyltyrosine-treated rats elevated the tyrosine transaminase activity to normal. The possible implications of these findings in the regulation of the biosynthesis of the catecholamines are discussed.

Animals↗
PubMedDate not supplied

Adenosine receptors in an enriched fraction of plasma membranes from canine ventricular myocardium.

[3H]Phenylisopropyladenosine ([3H]PIA) was used to characterize adenosine receptor sites in a sarcolemma-enriched membrane fraction from canine ventricle. Specific [3H]PIA binding to the cardiac membrane preparation was rapid, readily reversible, and saturable with increasing free ligand concentrations. Scatchard analysis indicated a single class of binding sites having a Bmax of 601 fmol/mg protein. The Kd of [3H]PIA for its binding site was 52-85 nM as determined independently from kinetic and equilibrium studies, respectively. Binding was stereospecific in that (-)PIA was ninefold more potent than (+)PIA in competing for [3H]PIA binding sites. Adenosine receptor agonists such as N6-cyclohexyladenosine, (-)PIA, 2-chloroadenosine, N6-methyladenosine, and adenosine-5'-ethylcarboxamide were the most potent agents found to compete for [3H]PIA binding sites and displayed IC50 values of 14-224 nM, while 2',5'-dideoxyadenosine, a potent P-site agonist, inhibited binding only weakly. Alkylxanthines also inhibited [3H]PIA binding with relative potency relationships that paralleled their known pharmacological activity as adenosine receptor antagonists. (-)PIA inhibited activation of membrane adenylate cyclase by isoproterenol in a concentration-dependent manner with a maximum of 22% inhibition occurring at 1 microM PIA. It is concluded that the specific binding of [3H]PIA to the sarcolemma-enriched fraction of canine ventricle represents an Ri adenosine receptor on the surface of the myocardial cell. Such a receptor has been postulated to mediate the adenosine-induced attenuation of the effects of catecholamines on intact ventricular myocardium.

Adenylyl Cyclases↗