Donald, David E.

Large changes in stroke volume and peripheral vascular resistance were induced by varying the heart rate and by intra-aortically infusing acetylcholine or angiotensin II in six dogs with heart block and electromagnetic flowmeters chronically implanted around their ascending aortas. Changes in stroke volume, aortic and atrial pressures, and systemic resistance were monitored continuously for 3-6 hours under morphine-pentobarbital anesthesia. The characteristics of diastolic pressure decay at heart rates ranging from 60 beats/min to 200 beats/min and during transient periods of asystole were studied, especially with reference to the distortions caused by reflected pressure waves. The diastolic phase of pressure pulses recorded over a segment of the thoracic aorta several centimeters long centered about 4 cm cephalad to the dorsal insertion of the diaphragm could be closely approximated by a straight line on a semilogarithmic scale. Under the conditions of these experiments, changes in the slope of that line and of its reciprocal, the time constant, correlated well with concomitant variations in peripheral vascular resistance. This relationship appears to be of practical value for continuous monitoring of systemic resistance directly from the diastolic segments of pressure pulses recorded from the lower thoracic aorta.

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.

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%.

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.

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.

The possibility of sympathetic vasoconstrictor control of blood flow to active muscles was studied in dogs during graded exercise by comparing the blood flow in the normal with that in the Sympathectomized hind limb. Blood flow was measured by electromagnetic flow transducers around each external iliac artery, or inferred from the oxygen saturation of blood samples from the common iliac veins. The dogs either ran for successive periods of 3 minutes at 5.5 km/hr and grades of 0, 7, 14, 21, and 28% or ran each level of exercise separately. Unilateral lumbar sympathectomy (L-2 through L-7) was performed when the flow transducers were implanted or later by a snare technique. The latter allowed observations during exercise as early as 4 hours after sympathectomy. The magnitude of limb blood flow during exercise and the decline of exercise hyperemia were similar in the normal and the sympathectomized limb, as were the changes in the oxygen saturation of limb venous blood. However, electric stimulation of the lumbar sympathetic chain at the L-5 level in the conscious dog by a chronically implanted electrode reduced limb blood flow at all levels of exercise, the maximal flow of 1,000 ml/min was almost halved.

In anesthetized dogs, the vasoconstrictor nerves to the vessels of the hind limb left the spinal cord in the anterior spinal nerve roots from T-10 through L-4 levels. Maximal vasoconstrictor responses occurred on stimulation of the T-12, T-13, and L-l roots; none occurred on stimulation of roots caudal to L-4. The nerves first entered the lumbar paravertebral chain at or above L-1; the last point of entry was at the L-4, L-5 level. No fibers left the lumbar chain at L-1, L-2, and L-3 levels. The first point of exit was at L-4, and nerves continued to leave as far distal as S-1, The most caudal point examined. The maximal response to stimulation of the lumbar chain was at the L-4, L-5 level. With a single exception, the responses to electric stimulation of the anterior spinal nerve roots, lumbar chain, or sympathetic ganglia were confined to the vessels of the ipsilateral limb. In 22 dogs with unilateral sympathectomy (L-2 through L-7), changes in hind-limb vascular resistance were induced reflexly or by electric stimulation of the anterior spinal roots. The results indicated that sympathetic control of the resistance vessels of the hind limb was still absent 77 days after sympathectomy.

The ability of a left ventricular balloon pump to provide support of the circulation when myocardial function had been severely impaired was examined in six dogs. When the unassisted damaged left ventricle could not maintain systemic blood flows adequate for survival, left ventricular balloon pumping resulted in peripheral blood flows which ranged from 37 to 77 ml/min/kg. These balloon-generated blood flows have been maintained for periods up to three hours. Assist of the circulation by balloon pumping was accompanied by an increase in systemic arterial blood pressure and a decrease in left atrial end-diastolic pressure. The effectiveness of left ventricular balloon pumping was reduced in hypovolemia and in the presence of ventricular extrasystolic beats. Left ventricular balloon pumping was not effective in generating a sustained peripheral flow of blood when the heart was fibrillating.

Administration of a moderately large or large dose of cortisone to dogs having acute myocardial infarctions inhibited slightly the rate of removal of necrotic muscle fibers in these animals as compared with untreated animals. Delay was appreciable at four and six days after production of the infarct in animals receiving 2.5 mg. of cortisone per kilogram of body weight and at 4, 6, 12 and 21 days in animals receiving 10 mg. per kilogram. At all other periods up to essentially complete healing of the infarcts as defined at 60 days, no appreciable differences existed between treated and untreated animals.