Increase In Rate Of Rise Research Articles

Effects of 3,4-diaminopyridine on mechanical and electrical responses of frog single muscle fibres.

The effects of 3,4-diaminopyridine (3,4-DAP) were studied on isolated muscle fibres of the frog in concentrations ranging between 0.025 and 5.0 mM. Isometric twitch and tetanus responses were recorded at temperatures between 2.5 and 3.9 degrees. 3,4-DAP caused a concentration-dependent increase in twitch amplitude, maximum effects being obtained at a concentration of 3 mM with a mean increase in tension of 70 +/- 12% of control (n = 7). 3,4-DAP in 3 mM concentration had only a slight increase in initial rate of rise of twitch tension (mean increase 8 +/- 4%) but increased the time to half peak tension by 59 +/- 9% and the time from peak tension to half relaxation by 78 +/- 10%. No significant effect of 3,4-DAP was observed on the initial rate of rise and total amplitude of the isometric tetanus. The twitch potentiating effect of 3,4-DAP developed gradually with the number of times the fibre was stimulated and reached a maximum level after 40-50 stimulations. A gradual increase in the duration of the action potential was also observed. It is suggested that 3,4-DAP, like 4-aminopyridine, potentiates the twitch by means of prolonging the duration of the action potential.

Magnesium restores high K-induced inactivation of the fast Na channel in guinea pig ventricular muscle.

The effect of extracellular magnesium concentration (Mgo) on the upstroke of the action potential was studied in guinea pig ventricular muscle under various K+ concentrations (2.7–19mM). Increased Mgo shifted the steady state inactivation curve of the fast Na channel in the depolarizing direction and this effect was concentration-dependent (0–20mM). Such an effect could explain the Mg-induced increase in maximum rate of rise of the action potential which Spah and Fleckenstein (1979) proposed to be due to a “Mg channel”.

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.

Action potentials in chick atria. Increased susceptibility to blockade by tetrodotoxin during embryonic development.

Tetrodotoxin (TTX) at a concentration of 1.6 x 10 -7 M blocked intracellularly recorded action potentials in 12- and 18-day-old embryonic chick atria. However, TTX, 1 x 10 -5 M, did not abolish action potentials recorded from cells in 6-day-old atria. TTX-sensitive receptor sites were present in 6-day-old atrial membranes because the toxin depressed the early Na + conductance that generated the rapid depolarization phase and the maximum rate of rise of the action potential. TTX at 0.9 x 10 -8 M reduced the maximum rate of rise by 50% in 6-day-old atria, and TTX at 2 x 10 -8 M had the same effect in 12- and 18-day-old preparations. Action potential overshoot changed about 10-20 mv/tenfold variation in external Na + concentration in 6-day-old atria in contrast to the change of about 60 mv/decade observed in 18-day-old atria. Moreover, the TTX-resistant action potentials in 6-day-old atria depended primarily on an inward Ca 2+ current because overshoot changed 24 mv/decade variation in external Ca 2+ concentration. The improvement in sodium-electrode properties that occurred during maturation was accompanied by an increase in the maximum rate of rise of the action potential, which averaged 64 v/sec in 6-day-old atria and 94 v/sec in 18-day-old atria. These findings suggested that the early Na + conductance mechanism became more critical in generating the action potential in older embryonic atria. These data were consistent with the hypothesis that the membrane density of early conductance sites increased with embryonic age. The TTX resistance of 6-day-old atria depended on an inward Ca 2+ current that generated action potentials after the early Na + conductance sites had been blocked by the toxin.

Collision of excitation waves in the dog Purkinje system. Extracellular identification.

The ventricular conduction system of the dog was explored with a 50µ extracellular electrode in an in vitro preparation with an intact right and left ventricular bundle branch system connected at the bundle of His. Two pacing electrodes at opposite ends of a functionally single strand produced collision of excitation waves with a distinctive extracellular wave form (uniphasic and positive instead of biphasic). The only changes in the intracellular potential associated with collision were a decrease in the time constant of the foot and an increase in the maximum rate of rise of the action potential, changes not uniquely produced hy collisions. During pacing at one point, collisions were detected at many places throughout the conduction system. The peripheral Purkinje system consisted of fine strands forming a network of interconnecting swirls, each covering 2-25 mm 2 Collisions were found in all swirls and their sites often shifted with a shift in the pacemaker site. Collisions also shifted in location between basic and premature beats which originated from a single point on the bundle of His.

Effect of isoproterenol, glucagon and calcium on myocardial oxygen consumption in intact dogs. A comparative study.

Twelve dogs were subjected to a similar increase in maximal rate of rise of left ventricular pressure (dP/dt) by isoproterenol, glucagon, or calcium. Augmentation of myocardial oxygen consumption (MVO2) was less with glucagon (p<0.025) or calcium (p<0.01) than with isoproterenol. In contrast to isoproterenol, glucagon or calcium induced no increase in myocardial uptake of free fatty acids (FFA). The additional rise in MVO2 with isoproterenol was probably caused by a metabolic stimulation of high FFA.

The inotropic action of paired pulse stimulation in the normal and failing heart: an experimental study.

Fixed rate single and paired pulse stimulation has been compared in the normal dog left ventricle and in the left ventricle failing after myocardial damage. In the normal heart a persistent positive inotropic effect occurred, seen mainly as an increase in rate of rise of left ventricular pressure, rather than total work. In the failing heart there was a transient positive inotropic effect, followed by increasing ventricular failure. The increasing failure was reversed by a return to single pulse stimulation.

Autonomic influences on cardiac function in the newborn lamb.

The influences of reflexly induced changes of sympathetic outflow to the heart on left ventricle contractility, heart rate, and systemic vascular resistance were studied in 26 technically successful experiments with newborn lambs ranging in age from 1 to 11 days. Reduction of brachiocephalic artery perfusion pressure was associated with a large increase of heart rate and of systemic vascular resistance. Under conditions of constant aortic pressure, heart rate and cardiac output, cephalic hypotension in most preparations induced a rapid onset of a fall of left ventricular end-diastolic pressure and an increase in the maximal rate of rise of left ventricular pressure (dp/dt max). Ventricular function curves obtained under conditions of constant aortic pressure and heart rate were shifted to the left. The average increase of stroke volume at left ventricular end-diastolic pressure of 10 cm H 2 O (SV 10 ) was 23.3%, and of dp/dt max was 30.7% in the reactive preparations. The average of the largest responses for each preparation was an increase of SV 10 of 42%, and for left ventricular dp/dt max, 48.8%. Three preparations previously subjected to carotid sinus nerve sectioning showed similar responses. No evidence for diminution of the response following parasympathetic blockade with atropine was found. In all preparations, ganglionic blockade virtually or completely eliminated the response.

Comparison of single and paired electrical heart stimulation on cardiac hemodynamics at rest and during exercise in dogs with atrioventricular heart block.

1. On transition from a single electrical heart stimulation to a paired stimulation at a same fixed heart rate, no major differences arc noted in cardiac output, left ventricular systolic pressure, mean systemic blood pressure and calculated peripheral resistance in dogs with a chronic total atrioventricular heart block both at rest and during muscular exercise.2. However, paired stimulation was characterised by a significant increase in the peak rate of rise dP/dT of the ventricular pressure curve, which in the presence of an unchanged peak systolic pressure, suggests an augmentation of the contraction velocity.3. The administration of a beta adrenergic blocking agent propranolol does not abolish this « electroaugmentation » induced by paired stimulation in such dogs.

Influence of the sympathetic nervous system on the response of the normal heart to digitalis

In experiments designed to clarify the effects of glycoside on the normal heart, acetyl strophanthidin was found to increase myocardial contractility, as reflected by the relation of stroke work to left ventricular end-diastolic pressure in dogs deprived of autonomie control of cardiac performance by ganglionic blockade and chronic cardiac denervation. Reflexly intact animals showed no consistent change in left ventricular end-diastolic pressure at constant arterial pressure, cardiac output and heart rate. All animals receiving the glycoside demonstrated a significant increase in maximal rate of rise of left ventricular pressure. Peripheral vascular resistance following the glycoside increased only in animals whose peripheral autonomie reflexes were abolished by ganglionic blockade. These data indicate that the direct inotropic effect of the glycoside on the normal heart may be obscured in the intact animal by a reflex withdrawal of cardiac sympathetic tone. The data support the position that there is no fundamental difference in glycoside action on the normal versus the failing heart.