The effects of nerve stimulation on pacemaking activities of biological tissues.

Abstract

The effects on the cardiac cycle length of stimulating the vagus nerves with single supramaximal electrical shocks depended upon when they were stimulated during the cycle. A maximum prolongation of the cardiac cycle was obtained when the vagi were stimulated 167 msec (SD±64) after the peak of an electrocardiogram P wave. The interval between a P wave and the subsequent vagal stimulation was called Pl-St interval. Pl-St(max) was the Pl-St interval at which maximum prolongation of the cardiac cycle occurred. Pl-St(max) increased significantly (p (0.001) with longer cardiac cycles. When the Pl-St intervals were shorter or longer than 167 msec (SD±64) the effects of vagal stimulation were less. The latent period for the effects of vagal stimulation was 195 msec (SD±32) The latent period also increased significantly (p(O.Ol) with longer cardiac cycles. The rise time of the vagal effect, obtained by subtracting (Pl-St(max)+ latent period) from the control cardiac cycle length, was 124 msec (SD+31) and occurred between Pl-St intervals of 167 msec (SD±64) and 291 msec (SD±70). The rise time did not vary with cardiac cycle length (p) 0.1), but the magnitude of the maximum response to vagal stimulation was inversely proportional to rise time (p <. 0.02). The peak response to vagal stimulation must have occurred when the vagal effects pegan somewhere in the middle of diastolic depolarization of the pacemaker cells in the S-A node. The reasons for this were discussed. The half-decay time for the effects of vagal stimulation was 210 msec (SD±102). The slope of the curve relating the prolongation of the cardiac cycle length to Pl-St is positive at Pl-St intervals less than 167 msec (SD±64) and negative at Pl-St intervals between 167 msec (SD±64) and 291 msec (SD±90). The positive slope ranged from 0.13 to 0.48 with a mean of 0.23. The paradoxical responses of the S-A node to vagal inhibitory input obtained by Reid (1969), Levy et al (1969)and Dong and Reitz (1970) would be explained by the dependence of the cardiac cycle length upon the time of arrival of vagal stimulus in relation to the previous P wave and upon the slope of the curve relating the prolongation of the cardiac cycle length to Pl-St interval being positive and between zero and two at Pl-St intervals less than 167 msec (SD±64. The effects of single shock stimulation of the vagus nerves persisted for 3.890 sec (SD+l.255)7 the number of cardiac cycles involved varied between 5 and 11. The duration of the effects of vagal stimulation did not depend upon when during the cardiac cycle the vagi were stimulated. A "dip" in the response to vagal stimulation was present in all the experiments. The possibility of the "dip" phenomenon being due to simultaneous stimulation of the sympathetic fibres in the vago-sympathetic trunk was ruled out. It is suggested that the "dip" phenomenon may be due to transient accumulation of K+ in the interstitial fluid surrounding the pacemaker cells in the S-A node.There was no paradoxical response of the smooth muscle in the distal colon of the adult rabbit when the frequency of sympathetic inhibitory input was continuously increased. A paradoxical response in the frequency but not in the size of the contraction of the smooth muscle was obtained when the sympathetic nerves were stimulated with bursts of stimuli, each burst consisting of 5-40 impulses, 10 msec apart. One may conclude from this that the delay of the next spontaneous contraction but not the inhibition of the size of smooth muscle contraction is dependent upon the arrival time of a burst of stimuli during a contraction cycle. This was confirmed in an experiment when the sympathetic nerves were stimulated with single bursts of stimuli applied at different times during the contraction cycle. It is unlikely that such a paradoxical response would occur under physiological conditions as this would require the natural sympathetic efferent discharges to the smooth muscle to occur in regular bursts, each burst consisting of impulses at a high frequency. Stimulation of the sympathetic nerves at 3, 5, 10 and 25 PPS caused an inhibition of the size and frequency of smooth muscle contraction in the distal colon of the newborn rabbit. Assuming that the cholinergic fibres are excitatory there is therefore no evidence for the sympathetic fibres to the distal colon being cholinergic in the newborn rabbit. This is contrary to Burn's (1968) report of the sympathetic fibres being motor and cholinergic to the small intestinal smooth muscle in the newborn rabbit.The heart rate increased rapidly at the onset of exercise and then more gradually over the rest of the exercise period. The initial increase in the heart rate during exercise was not affected by adrenergic blockade but the subsequent increase in heart rate was significantly reduced by adrenergic blockade. Hence the increase in heart rate at the onset of exercise is due primarily to a decrease in the cardiac vagal efferent discharge, whereas the subsequent increase in heart rate is due to both a further decrease ln vagal discharge and an increase in sympathetic discharge to the S-A node. In almost all the sub jects there was initially a rapid decline in the heart rate in the post-exercise period, but subsequently the heart rate returned to resting levels in a variety of ways. These were classified into 5 types. Of particular interest to the present study was the Type V pattern of heart rate change. This was characterised by an increase in heart rate of 6 beats or more per minute during the post-exercise period, with or without superimposed arrhythmia. The Type V pattern may be the equivalent of the paradoxical responses to inhibitory input demonstrated in animal experiments i.e. an increase in the heart rate with increasing vagal stimulation frequency. Type V pattern occurred more frequently at mild exercise levels (4 out of 14) than at moderate exercise level (lout of 14) and also more frequently in adrenergic blocked individuals (11 out of 28) than in control subjects (5 out of 28) It is suggested that the sympathetic effects on the P-R interval and arterial baroreceptor modulation of vagal efferent discharge protect again st the occurrence of paradoxical responses to vagal inhibitory input. They may do so by confining the vagal discharge to the rise time of vagal effect during the cardiac cycle. On the other hand the Type V pattern in p-adrenergic blocked individuals may be due to a decrease in the vagal discharge, in which case Type V pattern would not be a paradoxical response. The changes in minute ventilation in the post-exercise period were also variable. Besides a gradual decline in minute ventilation there were also gradual increases and sudden increases and decreases in minute ventilation. These may represent a form of paradoxical response to increasing inhibitory input and decreasing excitatory input to the respiratory neurones in man. However, all the changes in minute ventilation could also be explained by fluctuating excitatory and inhibitory neural input to the respiratory neurones.