Donald, David E.

Abstract The sections in this article are: General Considerations Passive Changes in Splanchnic Blood Volume Active Constriction of Resistance and Capacitance Elements Active and Passive Components of Sympathetically Induced Change in Splanchnic Blood Volume Spleen Innervation Arterial Inflow Reflexly Mediated Changes in Splenic Blood Volume Conscious Dogs Humans Intestine Blood Flow and Blood Volume Sympathetic Adrenergic Nerve Activity Stress (Exercise, Excitement, and Body Heating) Effect of Food Intake Liver Hepatic Microcirculation Studies in Conscious Animals Hepatic Blood Flow Uptake and Release of Blood by the Liver Conclusion

Ten consecutive time trials were run at 2-day intervals by six racing greyhounds over a 5/16-mile track. Cardiac denervation was then performed on four dogs, and a sham operation that included removal of the pericardium was performed on two dogs. After cardiac denervation, one dog died and another was rejected from the study because of a massive intrathoracic hemorrhage. The time trials were repeated with the addition of telemetry of the heart rate in the four survivors. There was no significant difference between mean preoperative and postoperative race times in the control group. The mean postoperative running speeds of 33.6 and 33.3 mph in the denervated group, although representing a significant slowing of 1.1 and of 2.1 mph, respectively, from preoperative values, indicate the adequate manner in which the denervated heart meets the circulatory demands of maximal running effort. cardiac output; heart rate and exercise Submitted on March 11, 1964

Following attempted denervation of the heart by the technic of regional neural ablation, dogs with incomplete cardiac denervation were shown to have the same supersensitivity to l-norepinephrine as dogs in which the denervation of the heart was complete. Dogs with chronic bilateral stellate ganglionectomy or those pretreated with reserpine had cardiac acceleration in response to the administration of tyramine or to stimulation of the stellate cardiac nerves, but did not demonstrate supersensitivity to l-norepinephrine. No supersensitivity was seen in dogs with chronic bilateral cervical vagotomy. Excision of the right stellate and caudal cervical ganglia and the immediately adjacent right vagus nerve resulted in supersensitivity to l-norepinephrine. In these animals cardiac acceleration resulted from stimulation of the left stellate cardiac nerves or from the administration of tyramine. The supersensitivity was lost after excision of the sinoatrial node. It is concluded that one can uniquely denervate the sinus node and that dogs so treated will develop supersensitivity to l-norepinephrine despite the presence of functional sympathetic nerves to the rest of the heart.

In three normal dogs and in six dogs with cardiac denervation, there was a rapid increase in cardiac output (electromagnetic flowmeter) from the start of exercise. The denervated group showed an average delay of 25 sec in reaching plateau values of cardiac output and a deficit of 18% in the accumulated flow over the first minute of running; augmentation of output was due principally to a rapid increase in stroke volume since acceleration of heart rate was slow. In normal dogs, the augmentation of output came from a rapid increase in heart rate. The steady-state values for cardiac output and oxygen consumption were similar in the two groups as was the pattern of oxygen consumption in the first minutes of exercise and the manner in which the oxygen debt was repaid. This suggested that the denervated dogs extracted more oxygen from the circulating blood in the first moments of running. The changes with exercise in aortic blood pressure were similar in the two groups.

Dogs with chronic cardiac denervation by the technic of regional neural ablation showed an unchanged capacity for work as measured by oxygen consumption. The relation of cardiac output to oxygen consumption during exercise remained unchanged from preoperational values. When the dogs started to run, the heart rate rose slowly over 1.5 min to reach a steady value proportional to the work performed. When exercise was stopped, the heart rate declined slowly. With mild exercise, the increase in cardiac output was mainly through stroke volume; with more severe exercise, increase in stroke volume and heart rate contributed equally, in contrast to the normal dog where the increase in rate predominates. Neither the pattern of the change in heart rate nor the plateau values were altered by adrenalectomy. The change in rate was not attributable to change in intravascular temperature. In an equivalent dose of base, norepinephrine caused tachycardia but little or no change in cardiac output, whereas epinephrine resulted in an increase in cardiac output with but a modest increase in heart rate.

5-Hydroxytryptamine (serotonin) was infused into anesthetized dogs at a rate of 20 µg/kg/min. In nine sets of observations on three dogs the increase in the difference of pressure between the pulmonary artery and the left atrium, which averaged 55%, consistently exceeded the increase in pulmonary blood flow, which averaged 16%. 5-HT therefore is a potent constrictor of pulmonary vessels, even in small concentrations. No changes in the pulmonary-artery wedge and pulmonary-vein pressures were detected during the infusions of 5-HT, nor was there any change in the volume of blood between the pulmonary artery and the root of the aorta. With this dose of 5-HT the principal site of the increased resistance to flow through the lungs appeared to be in the precapillary vessels. In the isolated perfused lung, moderate constriction of pulmonary veins also was produced by large doses of 5-HT.