Citations

Measurements of stroke volume were made in dogs during graded exercise on a horizontal treadmill up to the maximal exercise which they could maintain for 2 to 3 minutes. Eleven series of experiments were performed on 7 dogs. The cardiac output was measured by the indicator-dilution technic and the heart rate was measured from the aortic pressure tracing. At all grades of exercise, there was little or no change in stroke volume. Even with severe exercise, when the cardiac output had increased from 1.5 to 3.5 (average, 2.4) times the values obtained with the dog standing at rest, the stroke volume showed less than 5 per cent change over resting values in 5 experiments on 4 dogs, while in the remainder the increases were 8, 11, 11, 14, 15, and 19 per cent. Thus, the increase in cardiac output in the untrained exercising dog is almost directly proportional to the increase in heart rate. This is in contrast to other situations, such as the combination of exercise with infusion of catecholamines, where an increase in stroke volume may make an important contribution to the increase in cardiac output.

The indicator-dilution method was used in the dog in an attempt to define the proportion of the "central" blood volume contained in the lung vessels. When injections were made into the pulmonary artery with sampling from the femoral artery only half or even less of the calculated blood volume could be accounted for by the lungs. When a venous injection site was used, the proportion in the lungs was reduced to a third or less. Thus when peripheral sites are used for the inscription of indicator-dilution curves few deductions can be made about either the actual volume or even relative changes in the volume of blood in the lungs.

The lateral saphenous vein of the dog was perfused with homologous blood at constant flow. Changes in driving pressure were used to measure active changes in venous tone. Administration of tranylcypromine greatly reduced the activity of monoamine oxidase in the vein and increased its response to electric stimulation of the lumbar sympathetic chain and to norepinephrine infusions. Administration of pyrogallol (a catechol-O-methyl transferase inhibitor) also increased the response of the vein to adrenergic stimulation. These chemicals did not alter the increase in the sensitivity of the venous smooth muscle to sympathetic nerve impulses and infused norepinephrine produced by cooling the perfusate. Thus, the potentiating effect of local cooling on the response of the cutaneous veins to adrenergic stimulation cannot be explained by interference with the local enzymatic inactivation of catecholamines.

Acetylstrophanthidin, 0.3 to 10 µg/ml, caused contraction of helical strips of the dog cutaneous vein in an organ bath at 37°C. A latent period of 12 to 60 minutes preceded the contraction. During this time, the vein exhibited a progressive increase in response to transmural electric stimulation and added norepinephrine. As the dose of acetylstrophanthidin was increased, the latent period shortened and the increased response during the latent period was potentiated. When the contraction caused by 10 µg/ml was maximal, no additional contraction occurred with electric stimulation; the response to electric stimulation was only partially restored by the repeated washing out of the drug, despite relaxation of the strip to almost base-line tension. Since transmural electric stimulation causes contraction by release of tissue catecholamines, these experiments demonstrate that digitalis glycosides sensitize the cutaneous veins of the dog to adrenergic stimulation. This was confirmed in dogs anesthetized with pentobarbital. Intravenous injections of acetylstrophanthidin and digoxin, in doses too small (12.5 to 15.5 µ/kg) to cause direct constriction of the lateral saphenous vein, potentiated the constriction of this vein caused by electric stimulation of the lumbar sympathetic chain.

The cutaneous veins of the dog constrict and dilate with local cooling and warming, respectively. This response, which is dependent on the integrity of the adrenergic nerves, might be explained by an altered response of the smooth muscle to a given frequency of sympathetic nerve impulses or by local temperature receptors that initiate alterations in sympathetic nerve activity. In the lateral saphenous vein perfused at 42°, 27°, and 17°C, the constriction caused by stimulation of lumbar sympathetic nerves was 40%, 160%, and 200%, respectively, of that at 37°C; the constriction caused by norepinephrine at the same temperatures was 70%, 187%, and 318% of that at 37°C. Division of the dorsal spinal roots from L-1 to S-1 made no difference to the veno-constrictor response to local cooling. It is concluded that an alteration in the sensitivity of the smooth muscle to arriving sympathetic nerve impulses accounts for the venous responses to local temperature changes seen in the intact dog.

To study the separate actions of peripheral and central temperature-sensitive systems on the cutaneous veins of the dog, a cross-circulation preparation was made in which hindleg and central temperatures could be varied independently. The lateral saphenous vein of a vascularly isolated hindleg was cross-perfused at constant flow; the difference between perfusion and femoral vein pressures was a measure of venomotor activity. With central temperature constant, local cooling of one leg from 47° to 17°C caused the lateral saphenous vein to constrict; sensitivity to cooling was maximal between 42° and 27°C. With leg temperature constant, central cooling caused the lateral saphenous vein to constrict; over the range of 40° to 33°C, the constriction was linearly related to the decrease in temperature. Central heating reduced the response to local cooling, whereas central cooling had the opposite effect. Thus a decrease in central temperature from 38° to 34°C increased the venoconstrictor response to local cooling from 42° to 22°C by a factor of ten or more.

The lateral saphenous vein of the dog was perfused with homologous blood at constant, flow. Changes in perfusion pressure were used to measure active changes in venous tone. Cooling of the perfusate caused the vein to constrict and warming to relax. Most of the change occurred over the temperature range of 27° to 42°C. The powerful venoconstrictor response to cooling depended on intact sympathetic nerves, since it was reduced by lumbar sympathectomy and largely abolished by alpha-receptor or ganglionic blockade. The response was confined to the vein being cooled. By comparison, cooling the body core when the temperature of the blood in the vein was 37°C caused a generalized constriction of the superficial limb veins. These responses were impaired by anesthetic agents (for example, pentobarbital), by generalized hypoxia, and by arterial hypotension. The data indicate a role for the cutaneous veins in temperature regulation. In the cold, the venous return is directed preferentially to the venae comitantes for heat preservation through countercurrent exchange with the arteries, and in warmth to the superficial veins for heat dissipation.

Isolated cat lungs perfused at constant flow (75 ml/min per kg total body weight) were ventilated with gases of varying CO 2 content (0 to 10%), 20% O 2 , and the balance N 2 . Tidal volume was constant, and airway pressure did not change. Left atrial pressure was held constant, and changes in pulmonary artery pressure (PPA) were taken to reflect changes in pulmonary vascular resistance. Progressive hypercapnia (Pco 2 = 0 to 60 mm Hg) resulted in an increase in PPA as pH decreased. Equivalent degrees of acidosis, produced by the infusion of 0.3 N lactic acid, resulted in a higher PPA. Changes in PPA produced by lactic acid were reversible with 0.89 M sodium bicarbonate. With Pco 2 constant, and pH changed by lactic acid or sodium bicarbonate infusion, PPA was higher in lungs ventilated with room air (Pco 2 = 0) than in those ventilated with 5 or 10% CO 2 (Pco 2 = 30 or 60 mm Hg) at the same hydrogen ion concentration of the perfusate. These findings can be explained by two opposing actions of CO 2 on pulmonary vessels: a dilator action due to the direct effect of CO 2 and a constrictor action caused by the increase in hydrogen ion concentration.

In 13 anesthetized dogs with their vagi cut and their carotid sinuses kept at constant pressure, the gracilis artery, cranial tibial artery, and lateral saphenous vein of the left hind limb were isolated and perfused at constant flow. In the right hind limb, muscle afferents were stimulated by electrodes in the thigh muscles. At 5 Hz, aortic blood pressure decreased 45 ± 8 mm Hg; perfusion pressure decreased in the gracilis muscle and the paw (26 ± 6 mm Hg and 26 ± 5 mm Hg, respectively) and increased in the saphenous vein (13 ± 3 mm Hg). These effects were not prevented by paralysis of the stimulated muscles, beta-receptor blockade, or administration of atropine or antihistaminic drugs. At 40 Hz, aortic blood pressure increased 29 ± 8 mm Hg; perfusion pressure increased in the gracilis muscle and the paw (33 ± 5 mm Hg and 33 ± 3 mm Hg, respectively) and decreased in the saphenous vein (20 ± 2 mm Hg). These effects were prevented or reversed by paralysis of the stimulated muscles. Similar effects were obtained by central stimulation of the femoral nerve. Left sympathectomy or alpha-receptor blockade abolished the responses in the isolated vascular beds. Thus, muscle contraction is necessary only to activate the muscle afferents which cause constriction of resistance vessels in muscle and paw and dilation of cutaneous veins.

In closed-chest atropinized dogs anesthetized with chloralose and ventilated artificially, the aortic nerves were cut beneath the nodose ganglion, and the carotid sinuses were either denervated or vascularly isolated and maintained at a pressure of 40 mm Hg. Denervation was established by the failure of the pressoreceptor systems to respond to mechanical stimulation. Cold block or section of the cervical vagi resulted in statistically significant increases in arterial blood pressure (18%), heart rate (3%), central venous pressure (13%), hind-limb perfusion pressure (12%), pressure within the occluded spleen (18%), and efferent renal sympathetic nerve activity (28%). There was no change in saphenous vein perfusion pressure. The vascular responses were abolished by a-receptor blockade and were not affected by section of the vagi at the diaphragm. When the pressure in the vascularly isolated innervated carotid sinuses was varied from 40 to 220 mm Hg, the vascular responses to vagal block decreased steeply between 100 and 160 mm Hg and were absent at 200 mm Hg. Thus, receptors in the cardiopulmonary region with afferent vagal fibers exert a continuous restraint on the sympathetic adrenergic outflow to resistance and capacitance vessels, especially when the input from the carotid baroreceptors is decreased.