Biomedical subjects
J Ludbrook
Publications and source records attributed to J Ludbrook.
Circulatory changes during spontaneous motor activity: role of arterial baroreflexes.
Systemic arterial pressure (SAP) and heart rate (HR) were continuously measured in rabbits during spontaneous motor activity such as postural change, exploration, grooming, and eating, and during interposed periods of inactivity within which SAP and HR were defined as basal. Six rabbits were observed for 2 h under each of 3 conditions of arterial baroreceptor afferents: all intact (B4); one carotid sinus intact (B1); all interrupted (B0). In B4, SAP and HR were above basal levels 82% of the time; in B1, 64% and 76% of the time, respectively; in B0, only 21% and 28% of the time, respectively. Supplementary experiments in another six rabbits established that the activity-associated falls of SAP in condition B0 were independent of HR, were not due to engagement of cardiac receptor reflexes, and were not abolished by autonomic ganglion blockade. We conclude that the transient rises of SAP and HR that occur during everyday activity are associated with partial or complete suppression of the reflex effects of arterial baroreceptor input, and we suggest that this is due to transient upward resetting of the arterial baroreflex.
Acute deletion of arterial baroreceptor input in the conscious rabbit.
We describe the use of a snare to denervate the carotid sinus in conscious rabbits whose other arterial baroreceptors had been denervated 8-14 days previously by surgical operation. Within 2 min of tightening the snare arterial blood pressure had risen from 81 +/- 2 to 119 +/- 5 mmHg, and heart rate had risen from 214 +/- 9 to 280 +/- 9 beats min-1. They remained at these high levels for 15 min but then fell, so that after 30 min blood pressure and heart rate were 103 +/- 9 mmHg and 265 +/- 8 beats min-1 respectively. They declined somewhat further, but irregularly, over the succeeding 7 days. The previously brisk baroreceptor-heart rate and carotid sinus reflexes were abolished by ensnaring the carotid sinus nerve, and remained absent over the succeeding 7 days. This method of deleting input from the arterial baroreceptors is not confounded by general anaesthesia or surgical injury, and allows observations to be made within minutes. The rapid decline in blood pressure and heart rate after 15 min, and the subsequent slow downward trend, are unexplained. They are of potential importance in experiments designed to quantitate the effects of baroreceptor input on the circulation. We also noted that, whereas spontaneous activities of the baroreceptor-intact rabbit were usually associated with transient rises of blood pressure and heart rate, after deletion of baroreceptor input the same activities were usually associated with transient falls.
Circulatory responses to onset of exercise: role of arterial and cardiac baroreflexes.
Six rabbits were exercised on a moving belt at 13 m/min for 60's. Heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), and systemic vascular resistance index (SVRI) were measured. Exercise was done under the following four permutations of input from baroreceptors (B) and cardiac receptors (C): BC, both inputs present; B, only baroreceptor input (intrapericardial procaine); C, only cardiac receptor input (surgical barodenervation); 0, both inputs deleted. The reflex effects on SVRI of the two inputs were calculated as (B - 0) and (C - 0) and their interaction as (BC - 0) - [(B - 0) + (C - 0)]. The effects of baroreceptor input plus interaction on all cardiovascular variables were also calculated, as (BC - C). At rest, (B - 0) and (C - 0) each tonically depressed SVRI without interacting, and (BC - C) tonically depressed SVRI, MAP, and HR. Within 10 s of the start of exercise these tonic effects were abolished, although a small, SVRI-lowering interaction appeared. Suppression of the tonic reflex effects of arterial baroreceptor and cardiac receptor input supported systemic vascular resistance at the onset of exercise and contributed to the rise of arterial pressure.
Central suppression of the arterial baroreflexes during spontaneous behaviour.
When input to the central nervous system from arterial baroreceptors was intact, or reduced to one carotid sinus, spontaneous behavioural activities in rabbits caused transient rises of systemic arterial pressure (SAP) and heart rate (HR) from low, basal levels. Complete elimination of baroreceptor input caused an immediate reversal of this pattern, so that the same activities caused abrupt falls of SAP and HR from high basal levels. This same reversal of the SAP response occurred if basal SAP was kept low by sodium nitroprusside, if cardiac nerves were blocked, or if HR was rendered invariable by propranolol and methscopolamine. It is concluded that activity-associated rises of SAP and HR can be accounted for by central suppression of baroreflex mechanisms.
The role of cardiac receptor and arterial baroreceptor reflexes in control of the circulation during acute change of blood volume in the conscious rabbit.
We have studied overall reflex control of the circulation by the arterial baroreceptors and cardiac receptors during acute change of blood volume in seven conscious rabbits. A factorial experimental design allowed analysis of the direction, magnitude, and significance of the reflex effects of independent input from each set of receptors, and the reflex interactions when the inputs were combined. Right atrial pressure, arterial pressure, systemic vascular resistance, cardiac output, and heart rate were measured during acute, graded, isohemic change of blood volume over the range +/- 27%. This was done with both reflexes present, only the arterial baroreceptor reflex present (intrapericardial 2% procaine), only the cardiac receptor reflex present (surgical baroreceptor denervation), and with both reflexes absent. As blood volume was depleted, the arterial baroreceptor reflex independently increased systemic vascular resistance and sustained arterial pressure, but the cardiac receptor reflex had no significant independent or interactive effects. As blood volume was expanded, each reflex had an independent effect in decreasing systemic vascular resistance and preventing arterial pressure from rising, the cardiac receptor reflex being the more powerful. Their effect in combination on systemic vascular resistance and arterial pressure was only two-fifths of the sum of their independent effects, so that they interacted negatively. In combination, the reflexes supported right atrial pressure during blood loss, despite their negative interaction, but did not significantly affect the relation of cardiac output to blood volume change in either direction. Thus both reflexes have important actions in moderating the overall effects of acute blood volume changes in conscious rabbits, but these are markedly diminished by their interactions.
Blockade of cardiac nerves by intrapericardial local anaesthetics in the conscious rabbit.
Local anaesthetic drugs were instilled into the pericardial sac of conscious rabbits through a chronically implanted catheter. Twenty mg of procaine HCl always caused complete blockade of cardiac vagal and sympathetic efferent nerves, tested by eliciting the baroreceptor-heart rate reflex, and abolished the reflex depression of renal sympathetic nerve activity elicited by impeding left ventricular outflow. It also slowed heart rate by a direct effect on the sinoatrial pacemaker. When the same dose of procaine was given intravenously there were only transient changes in blood pressure, heart rate and the baroreceptor-heart rate reflex. Lignocaine HCl and bupivacaine HCl were relatively less effective in blocking cardiac sympathetic efferent nerves. Intrapericardial procaine can be used in conscious animals to elucidate the part played by the cardiac receptor reflexes in control of the circulation.
Mechanical effects of right atrial pressure on heart rate in the conscious rabbit.
We attempted to detect and quantify the mechanical effects of change in right atrial pressure on the chronotropic properties of the cardiac pacemaker, when blood volume was altered in an isohaemic fashion by +/- 27% in 8 conscious rabbits. Under control conditions there was a strong negative association between heart rate and right atrial pressure, attributable to the baroreceptor-heart rate reflex. After deletion of the main afferent sources of reflex effects on heart rate, by denervating the arterial baroreceptors and chemoreceptors, there was an insignificant association between heart rate and right atrial pressure or arterial pressure. Then, in addition, the main neurohumoral effects on the cardiac pacemaker were eliminated by three different pharmacologic treatments: (1) the cardiac nerves were blocked by instilling 2% procaine into the pericardial sac, (2) cardiac beta-adrenoceptors and cholinergic receptors were blocked with intravenous propranolol and hyoscine methyl bromide, (3) the above treatments were combined with autonomic ganglion-blockade by intravenous pentolinium. The combination of cardiac afferent and efferent blockade (1 and 3) revealed a small but consistent positive association between heart rate and right atrial pressure of 1.3 and 0.7 beats/min/mmHg, respectively. With efferent blockade alone (2), there was a steeper positive association of 2.3 beats/min/mmHg. We conclude that in the conscious rabbit there may be a mechanical effect of right atrial pressure on the cardiac pacemaker, but that it is so small as to be of little importance under physiological conditions.
Effects of acute changes in blood volume on the carotid sinus baroreceptor reflex in conscious rabbits.
The control of blood pressure, heart rate, cardiac output and systemic vascular resistance by the carotid sinus baroreceptor reflex was studied in six conscious rabbits during states of acute hypervolaemia and acute hypovolaemia. These states were produced by infusing blood equal to 20% and 40%, and withdrawing blood equal to 20% and 35%, of the initial blood volume. The properties of the reflex were characterized by creating sinusoidal pressure changes across the wall of the carotid sinus at a frequency of 0.01 Hz and amplitudes of 54 and 83 mmHg. From the effects of the lower-amplitude stimulus the dynamic gain of the reflex was calculated for blood pressure, heart rate, cardiac output and systemic vascular resistance. The higher-amplitude stimulus was used to determine the near maximal responses of the circulatory variables to changes in carotid sinus transmural pressure. The gain for systemic vascular resistance was reduced by hypervolaemia, and increased by 20% hypovolaemia. The gains for heart rate and blood pressure were not affected by hypervolaemia or by 20% hypovolaemia. 35% hypovolaemia reduced the gain for heart rate, but the resting value was close to the upper limit of the reflex response. It also reduced the gain for cardiac output and blood pressure, and the increase in gain for systemic vascular resistance that had been caused by 20% hypovolaemia was not sustained.
Reflex control of blood pressure during exercise.
The exercise stimuli exert a powerful drive to elevate blood pressure. This may be facilitated by spinal sympatho-sympathetic reflexes arising from the heart and aorta. The role of the Bainbridge reflex as a feed-forward mechanism in exercise remains unclear. Other, homeostatic, reflexes may modulate the pressor effects of the exercise stimuli. The balance of evidence strongly suggests that the arterial baroreceptors are still able to restrain disturbances of blood pressure during exercise, even though their control of heart rate is modified. Vagally innervated cardiopulmonary, and especially left ventricular, receptors may also subserve buffer reflexes in exercise, but whether their thresholds are reached has not been determined.
Effect of exercise on gain of the carotid-sinus reflex in rabbits.
1. Blood pressure, heart rate and cardiac output were measured in six rabbits before, during and immediately after treadmill exercise. During the same periods the dynamic gain of the carotid-sinus baroreceptor reflex was estimated by creating a sinusoidal oscillation of carotid-distending pressure. 2. The average blood pressure did not change significantly during or after exercise, but heart rate and cardiac output rose markedly and there was a concomitant fall in systemic vascular resistance. 3. The reflex gain for blood pressure decreased by one-fifth during exercise, and the gains for heart rate and vascular resistance by two-fifths. Immediately after exercise the gains for all three variables decreased further, to between one-half and one-third of the resting values. 4. Our results indicate that during and after dynamic exercise the correction of a potential disturbance of blood pressure by the carotid-sinus baroreceptor reflex is decreased in magnitude or in speed.
The effects of varying current levels of electrical stimulation.
An effort has been made to find an experimental delayed union of a long bone that could be used to evaluate the osteogenic effect of different current strengths. It is important that the optimum current strength be determined. Any such model should be able to produce a difference in new bone formation with an active and an inactive stimulator, particularly one using a 20 microA direct current. Attempts to produce a nonunion model in dogs were unsatisfactory, possibly because the defect was too small and surrounded by normal bone, and excessive movement occurred at the cathode plate. The optimum range of electrical stimulation using a titanium cathode has not been established by this work. The changes in serum alkaline phosphatase, serum calcium and serum phosphorus concentrations in response to trauma have been shown to be the same in the bone formation induced by electrical current.
The carotid sinus-blood pressure reflex in conscious rabbits: the relative importance of changes in cardiac output and peripheral resistance.
This paper reports experiments to determine the relative roles of changes in cardiac output and systemic vascular resistance in determining the blood pressure response to intermittent step-changes and continuous sinusoidal changes in carotid sinus transmural pressure. Conscious rabbits with a variable-pressure capsule implanted around an innervated carotid sinus were used. After step-change in capsule pressure the approximate proportions of the changes in blood pressure attributable to changes in cardiac output were, during the pressor response, 7% after 2.5 s, 22% after 10 s and 27% at plateau, and during the depressor response 100%, 8% and 17%, respectively. During sinusoidal change in capsule pressure a mean 7% of the change in blood pressure over the full cycle was attributable to change in cardiac output.
Blood volume and the carotid baroreceptor reflex in conscious rabbits.
1. The effects of acute blood volume change in conscious rabbits on a.c. gain of the carotid baroreceptor reflex with respect to heart rate, blood pressure, cardiac output and systemic vascular resistance were studied. 2. With acute, isohaemic increase in blood volume by 20% and 40% the only consistent trend was a decrease in gain for systemic vascular resistance. 3. With acute reduction in blood volume there was a consistent tendency for gain for heart rate to fall. With 20% reduction in blood volume, gain for cardiac output fell but gain for systemic vascular resistance rose and its phage-lag became shorter, so that gain for blood pressure was unaltered. The enhanced gain for systemic vascular resistance was not sustained with 35% reduction in blood volume, so that gain for blood pressure fell. 4. Thus control of blood pressure by the carotid sinus reflex is remarkably unaffected by acute change in blood volume, and is impaired only when there is depression of gain for cardiac output without a concomitant rise in gain for systemic vascular resistance.
The circulatory effects of acute hypervolemia and hemodilution in conscious rabbits.
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The carotid sinus baroreceptor reflex in conscious rabbits.
1. A method is described for altering the pressure across the wall of the carotid sinus in conscious rabbits by enclosing the carotid bifurcation in a rigid, fluid-filled capsule. The extracapsular arterial baroreceptors were denervated. 2. The baroreceptor--heart rate reflex, elicited by injecting vasoactive drugs or inflating aortic and vena caval cuffs, was used to test the new method. The function of the carotid sinus was shown to be unaffected by enclosure in the capsule. Denervation of the extracapsular baroreceptors reduced the gain of the baroreceptor--heart rate reflex two- to threefold. 3. The characteristics of the carotid baroreceptor reflex were studied in sixteen animals by the capsule method. Median estimates of maximum gain, and the range over which blood pressure changed, were 1.1 mmHg/mmHg and 57 mmHg respectively. There was good agreement between duplicate estimates made 1--20 days apart. 4. There was only a weak association between the effects on blood pressure and heart rate of altering carotid sinus transmural pressure. Autonomic blockade of the heart, so that its rate was fixed, did not reduce the gain or range of blood pressure change.
A selective approach to bleeding esophageal varices.
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