Citations

Pressure-dependent changes in afferent activity in the aortic and the sinus nerves were studied in 17 anesthetized dogs that were artificially ventilated with oxygen. Systemic arterial blood pressure was varied either continuously or in steps over the range of mean aortic blood pressure from 220 to 50 mm Hg with a pressurized reservoir connected to the abdominal aorta. Multifiber preparations from 20 aortic and 8 sinus nerves were used, and stimulusresponse curves were defined by measuring the mean impulse frequency at the various levels of pressure. Heart rate and pulse pressure were similar during recordings from both nerves. The two curves were S-shaped, with that for the aortic nerve being to the right of that for the sinus nerve. The change in activity was approximately linear from 200 to 120 mm Hg (mean aortic blood pressure) in the aortic nerve and from 180 to 80 mm Hg in the sinus nerve; there was no significant change in impulse frequency below mean blood pressures of 100 and 70 mm Hg, respectively. The threshold systolic blood pressure was 95 ± 3 (SE) mm Hg for the aortic receptors and 62 ± 4 mm Hg for the carotid sinus receptors. Thus, in the dog, the aortic baroreceptors are involved mainly in the control of high blood pressure, whereas at lower pressures the major control occurs through the carotid sinus baroreflex.

The vascular effects of graded stimulation of the carotid chemoreceptors were studied in 13 anesthetized and artificially ventilated dogs, and stimulus-response curves were defined. The carotid bifurcations were isolated and perfused at constant pressure, and the vagi were cut. Autologous blood collected in a reservoir was equilibrated at Po 2 varying from 104 to 34 mm Hg, Pco 2 from 39 to 81 mm Hg, and pH from 7.46 to 6.87 and was used to stimulate the carotid chemoreceptors. Systemic arterial Po 2 , Pco 2 , and pH were kept normal. Reflex increases in aortic blood pressure and in hind-limb perfusion pressure (constant-flow perfusion) were first seen with Po 2 of 70 mm Hg or Pco 2 > 39 mm Hg. The vascular responses increased linearly with lower Po 2 or higher Pco 2 , until tensions of 34 and 71 mm Hg, respectively, were reached. These stimuli caused a reflex dilatation of the perfused saphenous vein that was also proportional to the degree of stimulation. Increasing the pH of the blood perfusing the chemoreceptors decreased these changes by more than 50%; decreases in pH, with normal Po 2 and Pco 2 , caused marked vascular responses, indicating an important role of pH in the activation of the chemoreflex mechanism.

In dogs anesthetized with α-chloralose, passive alterations in splanchnic blood flow over a range of flows between 10 ml/kg min -1 and 50 ml/kg min -1 produced by a blood flow pump or by a change in perfusion pressure were associated with changes in splanchnic blood volume of 0.19 ± 0.1 (SD) ml/kg and 0.43 ± 0.15 ml/kg, respectively, for a change in flow of 1 ml/kg min -1 . Mechanical increase in splanchnic outflow resistance raised portal venous pressure from a control mean of 6.9 ± 4.1 mm Hg to 15.4 ± 3.5 mm Hg and increased splanchnic blood volume by 8.1 ± 2.2 ml/kg. Of the total change in splanchnic blood volume during an 18-second supramaximal stimulation of the thoracic splanchnic nerves, an estimated 65% was released "passively." The magnitude of this passive release was related linearly to splanchnic blood flow. During increased resistance to splanchnic outflow, the passive release was absolutely and relatively reduced, but the volume of blood actively released by constriction of capacitance elements was absolutely and relatively increased. During hemorrhage (7.2 ml/kg body weight), an average of 4.7 ± 0.6 ml/kg of blood (21% of the calculated splanchnic blood volume) was mobilized, and arterial blood pressure decreased an average of 5%. Repetition of the bleeding after bilateral splanchnicectomy passively mobilized 3.25 ± 0.9 ml/kg of blood (68% of the innervated value), but arterial blood pressure declined by an average of 20%.

Cerebral adenosine triphosphate and lactate concentrations were measured in the squirrel monkey ( Saimiri sciureus ) before, during, and at selected times after various periods of middle cerebral artery occlusion. The gradual decrease in ATP to 55, 35, and 20%, of normal and the increase in lactate to 7, 8, and 10 times normal after 2, 3, and 4 hours of occlusion, respectively, were reversible with restoration of flow. Electrocorticograms recorded in acute preparations indicated potential for recovery. The correlation of lactate levels with previous determinations of blood flow in this preparation supports the theory that loss of autoregulation and "luxury perfusion" in cerebral ischemia results from localized metabolic acidosis due to accumulation of lactic acid. In a separate group of monkeys, the ischemic lesions were found to be largely reversible after 2 or 3 hours and irreversible after 4 hours of middle cerebral artery occlusion; the cause of death in the monkeys subjected to 4 hours of occlusion was edema, which progressed even after restoration of flow.

Experiments were conducted in 35 anesthetized dogs to study the circulatory adjustments, after hemorrhage, mediated by vagal afferents from the cardiopulmonary area. With the aortic baroreceptors and chemoreceptors denervated and carotid baroreceptor and chemoreceptor activity held constant, hemorrhage of 10% of blood volume caused an increase in heart rate and constriction of the resistance vessels of the hindlimb, renal, and mesenteric beds and of the splanchnic venous bed. Vagotomy abolished these responses to hemorrhage, resulting in a greater decrease in blood pressure. With the carotid baroreflex operative, the constriction of the renal and mesenteric resistance vessels and of the splanchnic venous bed were similar to that obtained with only the vagi operative, but the constriction of the hindlimb resistance vessels was much greater and aortic pressure was better maintained. It is concluded that receptors in the cardiopulmonary area, subserved by vagal afferents, exert their main influence on the splanchnic resistance and capacitance vessels and on the renal circulation, whereas the carotid baroreceptors predominantly affect the muscle vessels.

Arterial inflow to and venous outflow from the vascularly isolated splanchnic region were measured simultaneously by using cannulating electromagnetic square-wave flow transducers in 25 anesthetized dogs with intact abdomens. Change in splanchnic blood volume (SBV) was calculated as the instantaneous difference between inflow and outflow. Addition of the respective increases and decreases in SBV induced by changing carotid sinus pressure from the control value (mean, 136 mm Hg) to 200 or to 40 mm Hg gave an average total volume of 93 ml of blood ( SD , ±21.7) that could be mobilized reflexly from the splanchnic circulation, Electrical stimulation (15 v, 2 cps, 3 msec duration) of the left thoracic splanchnic nerve for 2 to 10 minutes decreased SBV by 159 ml of blood ( SD , ±84). These mean values represent 32 and 48%, respectively, of the calculated total SBV. In both situations the translocation of blood was rapid, 50% of the total change in splanchnic blood flow and SBV occurring within 30 seconds. During a 2-minute hemorrhage (7.2 ml/kg), a mean volume of 56 ml of blood ( SD , ±16) was mobilized from the splanchnic region. This represented 54% of the total volume bled. Under these circumstances, blood moved out of the splanchnic circulation at a fairly constant rate.

Correlative studies of cortical blood flow measured by the 85 Kr washout technique and observations of the cortical blood vessels of 10 squirrel monkeys subjected to temporary occlusion of the middle cerebral artery are described. During occlusion, cortical blood flow in core areas of ischemia decreased to 0.12 to 0.90 ml/g/min (20 to 50% of preocclusion values) and became pressure dependent with failure of autoregulation. After release of the occluding clip, cortical blood flow was restored. Correlation between degree of vascular reaction judged by observation of the cortex and degree of hyperemia as determined by cortical blood flow was poor. There was incomplete correlation between the degree of hyperemia and the degree of preceding ischemia. Hyperemia, or "luxury perfusion," manifested by red venous blood, appears to be related to failure of cerebral tissue to utilize available oxygen as well as to "reactive" hyperemia, or supernormal blood flow, in regions previously ischemic. There was no demonstrable gradual failure of collateral circulation during occlusion. Cerebral edema was progressive and even progressed after restoration of cortical blood flow; it was incompletely correlated with the degree of ischemia and degree of hyperemia.

In isolated canine papillary muscle-false tendon preparations it was possible by selecting the pattern of stimulation to obtain conduction block within the peripheral distribution of the Purkinje network. Action potentials recorded just proximal to the site of block were always extremely brief in duration; refractory periods were abbreviated accordingly. When propagation from specialized fibers to muscle fibers was made very critical, conduction block occurred at some Purkinje-muscle junctions while propagation continued through others. Under these conditions very early reentrant activity could be obtained in terminal Purkinje fibers. With proper timing, the impulse propagated back to the false tendon and emerged as a closely coupled extrasystole. Occasionally, the activity returned again to muscle and resulted in a double reentry. Electrotonic shortening of action potentials of Purkinje fibers at relatively long distances upstream from a site of block facilitated the reentry of proximal elements. Partial reentry of the Purkinje system created conditions favoring fractionation of the reentrant wave front.

The reflex cardiovascular response to stretch of left pulmonary vein-atrial junctions was studied in anesthetized dogs in which both aortic nerves were cut and the carotid sinuses were isolated vascularly. After thoracotomy, the root of the left lung was tied and a small Silastic balloon (1.5-cm long), attached to a nylon catheter, was inserted into each of the three left pulmonary veins and tied so that its tip lay at the junction of the vein with the left atrium. In six dogs, heart rate response to balloon distension of 2.0 ml was studied over a range of initial heart rates (75 to 240 beats/min) achieved by varying the carotid sinus pressure. On distension of the balloons, slowing occurred if the initial heart rate was > 140 to 150 beats/min and acceleration if it were less. In eight dogs, aortic blood pressure and cardiac output measured before, during, and after balloon distension (0.25 to 2.0 ml) demonstrated a hyperbolic relationship between balloon volume and decrease in calculated systemic vascular resistance. All responses were abolished by vagotomy. The reflex vasodilatation was sustained and caused by decreased adrenergic activity; the reflex bradycardia or tachycardia was due to interplay of vagal and sympathetic cardiac efferents.