The effects of changes in left ventricular pressure on respiratory activity in anaesthetized dogs.

This study was undertaken to determine whether moderate increases in left ventricular systolic pressure in anaesthetized dogs result in changes in respiratory activity. Left ventricular systolic pressure was changed using a preparation in which the applied pressure did not distend the aortic arch and in which left atrial and carotid sinus pressures were held constant. The systemic circulation was perfused at constant flow and respiratory activity was assessed from the phrenic electroneurogram. Increases in aortic root and left ventricular systolic pressures resulted in a decrease in arterial perfusion pressure, no significant change in heart rate and a decrease in phrenic nerve activity. These responses differed from those to changes in carotid sinus pressure, which were decreases in perfusion pressure and heart rate but no significant steady-state change in phrenic activity. Responses to changes in ventricular pressure were obtained to each small step between 16 and 28 kPa (120 and 210 mmHg). Following cervical vagotomy, changes in ventricular pressure resulted in neither respiratory nor vascular responses. These results indicate that left ventricular receptors may play a role in the control of respiration.

Reflex vascular responses to changes in left ventricular pressure in anaesthetized dogs.

In dogs anaesthetized with chloralose, changes in left ventricular systolic pressure were induced using a preparation in which the pressure changes did not distend the aortic arch and in which left atrial and carotid sinus pressures were held constant. The systemic circulation was perfused at constant flow and drained from the venae cavae at constant pressure. An increase in left ventricular systolic pressure caused reflex dilatation of systemic resistance and capacitance vessels as indicated by decreases in arterial perfusion pressure and venous outflow. Responses were obtained when ventricular systolic pressure changed between 16 and 28 kPa (120-210 mHg). Responses to changes in ventricular pressure were reduced when the carotid sinuses were perfused at high pressures. These results indicate that changes in pressure in the left ventricle result in reflex changes in vascular resistance and capacitance and that responses are obtained to changes in ventricular pressure over a physiological range.

Peripheral vascular responses to changes in left ventricular pressure in anaesthetized dogs.

In dogs anaesthetized with chloralose, cardiac receptors were stimulated by increases in left ventricular systolic pressure effected by changes in aortic root pressure. Left atrial and carotid sinus pressures were controlled. A large step increase in ventricular pressure resulted in transient decreases in heart rate, systemic arterial perfusion pressure and perfusion pressure to a vascularly isolated hind limb. The magnitudes of these responses were about three-quarters of those to either a large change in carotid sinus pressure or aortic root injection of 20 micrograms veratridine. Steady-state responses were smaller. There was no significant change in perfusion pressure to a perfused cutaneous vein. Graded changes in ventricular systolic pressure showed that the most sensitive pressure range was between 20 and 24 kPa. These results indicate that changes in left ventricular pressure result in significant vasodilation in the hind limb and in other regions and that responses are obtained when the pressure is moderately elevated.

Hind-limb vascular responses in anaesthetized dogs to aortic root injections of veratridine.

In dogs anaesthetized with chloralose we determined the reflex responses of the blood vessels in the vascularly isolated hind limb to injection of veratridine into the aortic root. The presence of a cannula tied in the ascending aorta ensured that responses were due to stimulation of nerves only in the region perfused by the coronary arteries. Injections of veratridine resulted in transient decreases in vascular resistance and in venous resistance in a perfused cutaneous vein. The responses were reduced when carotid perfusion pressure was elevated. The afferent pathway for the reflex lay in the vagus nerves and the efferent pathway to the limb was in the sciatic and femoral nerves, but the vasodilatation was shown to be predominantly non-cholinergic.

Effect of veratridine injected into the aortic root on resistance and capacitance in the abdominal circulation in anaesthetized dogs.

In dogs anaesthetized with chloralose, cardiac receptors were stimulated by injections of veratridine into the aortic root and the effects studied on resistance and capacitance in the vascularly isolated and perfused abdominal circulation. Unless carotid sinus pressure was high, veratridine injections consistently resulted in dilatation of resistance and capacitance vessels. However, at high carotid pressures, the resistance response to veratridine was inhibited and the capacitance response was usually reversed. These results indicate that stimulation of cardiac receptors can affect resistance and capacitance in the abdominal circulation. Further experiments are required to evaluate the physiological role of these responses.

Adrenergic mechanisms in oxygen chemoreception in the cat aortic body.

Sixteen cats were studied to test the hypothesis that oxygen chemoreception in the cat aortic body is dependent on the beta-adrenergic mechanism. The chemoreceptor activity was measured from a few aortic chemoreceptor afferents in each cat, anesthetized with alpha-chloralose (60 mg X kg-1). Three types of experiments were conducted. Aortic chemoreceptor responses to steady-state hypoxia (PaO2 range, 100-30 Torr) were measured (a) before and during intravenous infusion of the beta-receptor agonist, isoproterenol (0.5 micrograms X kg-1) in nine spontaneously breathing cats, and (b) before and after intravenous injection of the beta-receptor antagonist, propranolol (1 mg X kg-1) in seven cats which were paralyzed and artificially ventilated. In the third category (c) the stimulatory effect of hypotension on aortic chemoreceptor activity was measured in six of the seven cats in group (b) before and after propranolol injection. Isoproterenol infusion only moderately stimulated aortic chemoreceptor activity. This stimulation was blocked by propranolol. However, propranolol did not attenuate aortic chemoreceptor responses to hypoxia or to hypotension. We conclude that the beta-receptor adrenergic mechanism does not mediate oxygen chemoreception in the cat aortic body.

Effects of lung inflation on abdominal vascular resistance in anaesthetized dogs.

In chloralose-anaesthetized dogs, the airways to each lung were separated by cuffed endobronchial cannulae and one vagus nerve was cut. We determined the effects of inflation of the innervated lung on abdominal vascular resistance, assessed in the unopened abdomen from changes in perfusion pressure at constant flow. Both static and phasic lung inflation resulted in variable responses of heart rate and abdominal vascular resistance. However, there was a significant correlation between the responses and when heart rate increased there was a significant vasoconstriction. When vasodilatation occurred this was unaffected by vascular isolation of the abdomen indicating that it could not have resulted directly from a blood-borne agent. The bradycardia and vasodilatation were prevented by administration of antagonists to histamine and prostaglandin synthesis. These experiments indicate that, when lung inflation results in tachycardia, abdominal vascular resistance increases. The responses of bradycardia and vasodilatation appear to involve the action of histamine and/or prostaglandins.

Cardiac inotropic responses from changes in carbon dioxide tension in the cephalic circulation of anaesthetized dogs.

Experiments were performed on anaesthetized dogs to determine the effects of moderate changes in PCO2 in the cephalic circulation on the inotropic state of the heart and on the reflex inotropic responses from changes in carotid sinus pressure. The cephalic circulation was perfused, through the brachiocephalic and left subclavian arteries, with blood taken from the superior vena cava and equilibrated with various gas mixtures in a gas exchange unit. The carotid sinus regions were vascularly isolated and perfused with arterial blood at controlled pressures. Cardiac inotropic responses were assessed from the maximum rate of change of left ventricular pressure (dP/dtmax) with heart rate and mean aortic pressure held constant. An increase in cephalic blood PCO2 resulted in an increase in dP/dtmax and an increase in the unpaced heart rate. Small, graded changes in cephalic PCO2 resulted in graded responses of dP/dtmax. A change in carotid sinus pressure resulted in a significantly greater response of dP/dtmax when cephalic PCO2 was high. After interruption of the left cardiac sympathetic nerves, the responses of dP/dtmax to changes in cephalic PCO2 and carotid sinus pressure were nearly abolished. These results indicate that the tension of carbon dioxide in the cephalic circulation is likely to be of importance in the control of the inotropic state of the heart. They also imply that, in studies of cardiovascular reflex responses, it is important to control the carbon dioxide tension in the arterial blood.

A morphometric study of the carotid body in chronically hypoxic rats.

We performed morphometric studies of carotid body in acutely and chronically hypoxic rats (inspired PO2 = 70 Torr, at sea level). Acute exposure was for the duration of about 10 min, and chronic exposure lasted for 28 days. We confirmed that the total volume of the organ increased by severalfold. At the light-microscopy level we found an enlargement of the volume density of the blood sinuses from 14 to 31% due to chronic hypoxia. The morphometric hematocrit increased from 39 to 70% paralleling changes in the conventionally measured venous hematocrit. These data do not show any specific plasma skimming in the carotid body blood vessels. With the electron microscope we found that the mean average volume of type I cells increased from 320 micron3 in controls to 1,120 micron3 in the chronically hypoxic rats without hyperplasia, whereas type II cells had increased in number without alteration in size. Qualitative observations revealed that the normal appearance of clusters of ovoid type I cells interspersed by capillaries had been transformed into a pattern of individual cells forming plates between expanded blood vessels with a large increase of contact area between the cells and vessels. Type II cells appeared to have proliferated without changes in individual size to cover the enlarged periphery of type I cells. The observed structural changes in the carotid body parenchyma and vasculature appear to be physiologically adaptive and provide further support for the idea that various elements in the organ are particularly sensitive to hypoxia.

Dopaminergic efferent inhibition of carotid body chemoreceptors in chronically hypoxic cats.

The observations that the dopamine concentration of the carotid body and efferent inhibition of carotid chemoreceptors are increased during chronic hypoxia led to the hypothesis that the inhibition was due to the effect of an increased dopamine release by the activity of carotid sinus nerve (CSN) efferents. The hypothesis was tested by measuring the effect of dopamine receptor blockade on efferent inhibition of carotid chemosensory responses to graded levels of arterial O2 partial pressure in chronically hypoxic and normoxic cats. Chronically hypoxic cats were prepared by exposing the cats to 10% O2 at sea level for 30-34 days. Carotid chemosensory activity was first measured from a slip of an otherwise intact CSN. The measurements were then repeated after sectioning the remaining nerve trunk. The effect of sectioning the CSN provided the measure of efferent inhibition. In each group of cats the effects of sectioning the CSN with and without dopamine receptor blockade by haloperidol were also studied. CSN section augmented the chemosensory responses in the chronically hypoxic cats. Haloperidol, a dopamine antagonist, augmented the responses further, indicating that a part of the endogenous dopamine effect was independent of the CSN efferents. After haloperidol treatment CSN section did not influence the chemosensory responses. This study confirmed that the efferent inhibition significantly increased in the chronically hypoxic cats and demonstrated that haloperidol blocked the efferent inhibition, suggesting that the mechanism of the augmented inhibition is dopaminergic.

Hind-limb vascular-capacitance responses in anaesthetized dogs.

In anaesthetized dogs a hind limb was vascularly isolated, perfused through the femoral artery at either constant flow or constant pressure and drained from the femoral vein at constant pressure. Inflow and outflow were recorded. Vascular-resistance changes were calculated from changes in pressure or flow and volume changes from the differences between inflow and outflow. During constant-flow perfusion, both changes in carotid sinus pressure and direct stimulation of efferent sympathetic nerves resulted in large resistance responses. However, changes in carotid sinus pressure did not result in changes in limb blood volume and only small decreases were obtained in response to direct stimulation. During constant-pressure perfusion, both reflex and direct stimulation resulted not only in significant changes in resistance but also in significant volume changes which were much larger than those obtained during constant-flow perfusion. Similar responses were obtained when the flow rate was changed by altering the pump speed. These results indicate that changes in pressure to carotid baroreceptors do not result in active capacitance responses in the limb circulation and that only very small responses are obtained even to electrical stimulation of sympathetic nerves. The larger responses occurring during constant-pressure perfusion are thought to be secondary to changes in blood flow.

Responses of abdominal vascular resistance and capacitance to stimulation of carotid chemoreceptors in anaesthetized dogs.

1. In anaesthetized dogs the regions of the carotid bifurcations were isolated vascularly and perfused at constant non-pulsatile pressures. The abdominal circulation was isolated vascularly, perfused at constant flow and drained through the inferior vena cava at constant pressure. Vascular resistance and capacitance responses were determined from the changes in perfusion pressure and changes in venous outflow. 2. Stimulation of carotid chemoreceptors with venous blood resulted in an increase in arterial perfusion pressure of 38% (S.E. +/- 4.6) and a decrease in vascular capacitance of 24.4 +/- 2.5 ml. (1.05 +/- 0.24 ml. kg-1). 3. When carotid perfusion pressure was higher than 17 kPa, stimulation of chemoreceptors resulted in significantly (P less than 0.05) smaller resistance responses but significantly (P less than 0.05) greater capacitance responses than those obtained at lower carotid pressures. 4. These results show that abdominal resistance and capacitance vessels constrict in response to stimulation of carotid chemoreceptors. We suggest that the larger responses of capacitance and the smaller responses of resistance obtained at higher carotid sinus pressures may be due to different sensitivities of resistance and capacitance vessels to efferent sympathetic nerve activity.

Effects of stimulation of aortic chemoreceptors on abdominal vascular resistance and capacitance in anaesthetized dogs.

1. Dogs were anaesthetized with chloralose, ventilated artificially, and the regions of the aortic arch and carotid sinuses were isolated vascularly and perfused with blood. The abdominal circulation was isolated vascularly, perfused at constant flow and drained from the inferior vena cava at constant venous pressure. Changes in vascular resistance were determined by calculating changes in abdominal aortic perfusion pressure, and changes in capacitance by integrating the changes in venous outflow. 2. Stimulation of aortic body chemoreceptors, either by changing the aortic arch perfusate from arterial to venous blood at constant perfusion pressure or by injection of sodium cyanide into the aortic arch, resulted in an increase in abdominal vascular resistance and a decrease in abdominal vascular capacitance. 3. After both cervical vagosympathetic trunks had been cut, stimulation of aortic chemoreceptors no longer resulted in resistance or capacitance responses. 4. These results indicate that stimulation of aortic chemoreceptors, like carotid chemoreceptors, results in reflex constriction of both resistance and capacitance vessels in the abdominal circulation.