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Biomedical subjects

S E Freeman

Publications and source records attributed to S E Freeman.

At least 55 records · Page 3Linked to original sources
PubMed1975

The effects of l-propranolol and practolol on atrial and nodal transmembrane potentials.

Effects of l-propranolol, racemic propranolol and practolol have been determined on transmembrane potentials recorded in guinea-pig left atrium and in sinoatrial and atrioventricular nodes of the rabbit heart. In addition to the voltage -time recording of the action potential, its first time derivative was displayed as a function of membrane voltage, forming a phase-plane trajectory. A number of parameters of the action potential were determined from this trajectory. At the concentrations used the beta adrenoceptor blocking agents reduced the maximum rate of rise of the atrial action potential and slowed repolarization. The velocity of the propagated spike was reduced, and the maximum ionic conductance was also reduced. The excitation potential of the propagated spike was unaffected. The membrane effects were markedly dependent on the frequency of stimulation. The beta adrenoceptor blocking agents were without effect on either the sinoatrial or atrioventricular nodes. Since the spontaneously active right atrium beats more slowly than the heart of the intact rabbit, the atrioventricular node was electrically stimulated at 5 to 6 Hz. Neither drug affected the ability of the node to follow these stimulation frequencies. The importance of these effects in the control of cardiac arrhythmias is discussed.

Action Potentials↗
PubMed1972

A myotoxin secreted by some piscivorous Conus species.

1. Toxins isolated from the venom apparatus of Conus magus and Conus achatinus have the same pharmacological properties, but differ from the toxins of several other piscivorous species of cone shells.2. C. magus and C. achatinus toxins are heat labile at pH 8.5. A single lethal component with an approximate molecular weight of 10,000 was isolated from C. achatinus toxin by exclusion chromatography.3. Animals died from a characteristic spastic paralysis after intravenous injection of the toxin.4. Nerve transmission was unaffected by the toxin; skeletal muscle appeared to be the primary site of action. The toxin caused a persistent contracture of rat diaphragm muscle, and a dose-dependent decline in twitch tension. The contracture was potentiated by caffeine.5. The decline in twitch tension was associated with depolarization of the cell membrane. Action potential height and the maximum rate of rise declined, and spike propagation failed when the resting potential had declined to approximately 60 mV. The muscle recovered very slowly on washout of the toxin. The depolarization could be reversed by exposure of the preparation to 5 mM Na(+) solution or tetrodotoxin or saxitoxin.6. Miniature end-plate potential frequency in the rat diaphragm decreased, as did the quantal content of the end-plate potential. The acetylcholine-induced contraction and depolarization of the chronically denervated rat diaphragm were increased by low doses of toxin and reduced by higher, depolarizing toxin doses. The K(+)-induced contraction and depolarization of innervated diaphragm were similarly affected by the toxin.7. Cardiac and smooth muscle were relatively resistant to the toxin. The isotonic contraction of the isolated perfused guinea-pig heart was increased by the toxins from both Conidae. The heart rate decreased. Guinea-pig atrial cells showed a small decrease in action potential height and maximum rate of rise. Rabbit sino-atrial cells showed increases in action potential height, maximum diastolic potential and maximum rate of rise of the spike at low toxin levels, and no change in any of these parameters at high levels. There was a decrease in the rate of the spontaneously beating atrium. Atrioventricular nodal potentials showed no change other than a slight increase in the maximum rate of rise of the action potential.8. It is postulated that the action of the toxin may be related to a change in the Ca(++) permeability of the excitable membrane, which makes it unstable, leading to a secondary, depolarizing entry of Na(+). The effects of the toxin are compared with those of batrachotoxin, which it somewhat resembles.

Animals↗
PubMed1971

Cardiovascular effects of toxins isolated from the cnidarian Chironex fleckeri Southcott.

1. Two unstable high molecular weight toxins have been isolated from tentacles of Chironex fleckeri by exclusion chromatography. Both are cardiotoxic; the lower molecular weight fraction is also a potent haemolysin.2. Both toxins reduce the rate, amplitude of contraction and coronary flow in the isolated, perfused guinea-pig heart. Relative to the mouse lethal dose the haemolytic fraction is less potent in this preparation than the purely cardiotoxic fraction.3. Both toxins cause a rise in arterial pressure in anaesthetized rats and rabbits by a direct action on the vascular musculature. This is followed by hypotension, bradycardia and cardiac irregularity. An increase in respiratory rate is followed by apnoea of variable duration, which is associated with a rise in arterial pressure. Animals frequently show arterial pressure oscillations with periods of apnoea interspersed with hyperpnoea.4. The carotid occlusion reflex is depressed during hypotensive periods after both toxins, although (-)-noradrenaline can still elicit a marked pressor response. Bilateral cervical vagotomy has but little effect on the response to either toxin, save to prevent hyperpnoea, but radical denervation of sinoaortic afferents reduces the arterial pressure fall after the initial hypertensive response, suggesting that this fall is due to a combination of baroreceptor stimulation and a fall in cardiac output. Blood pressure oscillations are still seen, possibly due to central stimulation by hypercapnia.5. Interference with the efferent arm of the vasomotor reflex arc with hexamethonium, bretylium or phenoxybenzamine either abolishes or markedly reduces the blood pressure oscillations without affecting the initial hypertensive response.6. The cardiovascular effects of the two toxins are thought to be due to direct vasoconstriction, cardiotoxicity, baroreceptor stimulation and possibly depression of the vasomotor centre. The resultant disordering of the feed-back system regulating vasomotor tone leads to the characteristic arterial pressure oscillations.

Animals↗