Roger J. Bagshaw

EVOLUTION OF CARDIOVASCULAR BARORECEPTOR CONTROL

During animal evolution the circulatory system has shown a progressive modification in structure, function and short‐term control.

Baroreceptor reflex control of arterial hemodynamics in the dog.

The regional differentiation of carotid sinus control of arterial pressure-flow relationships was studied in chloralose-anesthetized dogs. Simultaneous pressure-flow measurements were made in the ascending aorta, the celiac artery, the cranial mesenteric artery, the renal artery, and the femoral artery. The carotid sinuses were bilaterally isolated and perfused with pulsatile pressure. The open-loop reflex gain was not symmetrical about and was maximum at pressures below the closed-loop operating point pressure. Changes in both peripheral resistance and cardiac output contributed significantly to the open-loop gain, with the former predominating. Aortic impedance for frequencies above 3 Hz was at a minimum at the closed-loop operating point and increased for both higher and lower values of carotid sinus pressure. For the frequency range from 3 to 9 Hz, regional impedance in all of the beds varied inversely with carotid sinus pressure. The sensitivity of the various beds to changes in carotid sinus pressure around the operating point increased in the order celiac < mesenteric < renal < femoral. Following vagotomy, operating point values of regional resistance and sensitivity were significantly increased. This fact suggests that the aortic arch receptors exert a significant influence on regional vascular impedances at operating point pressures. The fraction of cardiac output in the celiac, mesenteric, and renal beds was nearly independent of carotid sinus pressure before and after vagotomy, but that in the femoral bed increased with carotid sinus pressure. These results demonstrate the nonuniform nature of carotid sinus and aortic arch baroreceptor control of regional blood flow.

Effects of angioplasty upon carotid sinus mechanical properties and blood pressure control in the dog.

The effects of vein patch angioplasty of the carotid sinus upon carotid sinus control of blood pressure and carotid sinus mechanical properties were studied in nine vagotomized dogs. Pressures in the isolated carotid sinuses were increased from 60 to 180 mm Hg in steps of 30 mm Hg, and the resulting reflex changes in mean aortic pressure were measured both before and after unilateral angioplasty. Angioplasty significantly decreased aortic pressure for carotid sinus pressures above 60 mm Hg, decreased the calculated carotid sinus reflex set point pressure, and increased the range of control of arterial blood pressure together with the maximal capacity of the arterial baroreceptors to effect vasoconstriction. In five dogs, concomitant changes in carotid sinus diameter were measured. From the latter, together with accompanying changes in sinus wall geometry, were calculated the tension-strain modulus of elasticity of the carotid sinus wall, together with the radial displacement of the media-adventitial junction. Calculated increases in the latter were consistent with the observed increased effectiveness of the carotid sinus baroreceptors after angioplasty. It was concluded that the modification of blood pressure and its control was predominantly due to the surgical exaggeration of normal carotid sinus geometry accompanied by modest changes in carotid sinus wall mechanical properties.

Nitrous Oxide and the Baroreceptor Reflexes in the Dog

The effects were studied of 67 % nitrous oxide on the baroreceptor control of systemic haemodynamics in the dog. Nitrous oxide was added to end‐tidal halothane concentrations of about 0.9% (H2) together with halothane levels approximately 25 % above (H3) and below (H1) the H2 concentration. Baroreceptor function was assessed by brachiocephalic artery occlusion (BCO) or perfusion of the isolated carotid sinuses. In the intact animal, nitrous oxide significantly increased mean arterial pressure only at the H2 level (P<0.001). At the closed loop operating point of the carotid sinus reflex (CSR), for all halothane levels, nitrous oxide decreased cardiar output and stroke volume, increased systemic vascuIar resistance and central venous pressure with no effect upon mran arterial pressure. The operating point gain of the CSR was significantly depressed by nitrous oxide at the H1 and H3 levels (P<0.05). The Csr operating characteristics were significantly modified by N2O in a manner which depended upon the underlying concentration of halothane.

Baroreceptor reflexes and pulmonary hemodynamics during halothane and halothane-nitrous oxide anesthesia in the dog.

The effects of reflexly induced changes in sympathetic nerve activity on pulmonary hemodynamics during halothane and halothane-nitrous oxide anesthesia were investigated. Perfusion pressure was changed in the isolated carotid sinuses (60 to 180 mm Hg) of vagotomized, open chested dogs, anesthetized at three end-tidal halothane concentrations of 0.66% ± 0.02% (H1), 0.88% ± 0.02% (H2), and 1.16% ± 0.03% (H3) with and without 67% nitrous oxide. At no levels of carotid sinus pressure were pulmonary vascular resistance or pulmonary input resistance affected by halothane or nitrous oxide. With increasing carotid sinus stimulation, pulmonary vascular resistance increased at high levels of carotid sinus pressure at the H3 halothane level and with nitrous oxide at the H1 level. Changes in pulmonary input resistance were opposite in direction to baroreceptor stimulation and were greatest at the H3 level with nitrous oxide. Thus for a wide range of baroreceptor stimulation, pulmonary vascular resistance and pulmonary input resistance remained constant at end-tidal halothane concentrations of approximately 0.9%, with or without nitrous oxide. Only when halothane concentrations were significantly above or below 0.9% did reflex changes become significant, particularly with respect to the pulmonary component of the resistive load upon the right venticle.

Sudden hypotension with a test dose of chymopapain

Chymopapain (Chymodiactin) injection for the treatment of herniated intervertebral discs has been associated with allergic reactions of varying severity including cardiovascular collapse and death (1). This reaction to chymopapain, a proteolytic component of carica papaya latex, has been well described (2). However, the current commercially available preparation of the drug contains no preservatives and less extraneous protein and thus may be less of a problem with respect to allergic reactions (3) . The allergic reaction after chymopapain appears to be more common in women, in patients with multiple allergies, and in patients with allergies to papaya or papaya derivatives (l), but at present there appears to be no reliable way to predict which patients will develop a reaction to injection of chymopapain. Premedication with high doses of steroids, H1-, and H2-receptor blockers are thought to decrease the incidence and severity of the allergic reactions. The injection of a small volume of chymopapain into the disc as a test dose is thought to help identify patients at risk by producing a definite but attenuated hypotensive response. This case report describes a patient who had a significant hypotensive episode after a test dose of chymopapain. This report is significant for five reasons. The patient had a history of papaya ingestion, although he had never had an allergic reaction to papaya. Severe hypotension occurred despite large doses of steroids as well as HIand H,-blocking agents administered for 48 hr before and shortly before the

Effects of Incremental Halothane Levels on the Reflex Responses to Carotid Hypotension in the Dog

Arterial baroreceptor function was assessed in trained, chronically instrumented dogs by measuring the systemic haemodynamic responses to brachiocephalic artery occlusion (BCO). BCO was carried out in awake dogs and repeated at end‐tidal halothane levels of 0.75 ± 0.01 % (H1), 0.94 ± 0.02% (H2) and 1.13±0.02% (H3). Before BCO, at H1 only the increased heart rate and decreased stroke volume were significantly different from awake controls (P<0.01). Mean arterial pressure and cardiac output at H2 and H3 were significantly lower than in the awake controls (P<0.05). The pressor response to BCO fell progressively with increasing halothane levels, the decrease being significant at the H2 and H3 levels (P<0.001). There was a good linear correlation between the pressor response to BCO as a percentage of the response in awake animals, and the end‐tidal halothane levels (r= ‐0.816, P<0.001). This indicated a sensitive dose‐dependent modification of the haemodynamic response to BCO by halothane. However, halothane levels existed between about 0.7‐0.8%, at which levels the average pressor response to BCO was not significantly different from awake values.

Connective tissue analysis of the canine circle of Willis in hypertension

The collagen and elastin contents of the major arterial components of the canine circle of Willis (basilar artery, posterior cerebral artery, internal carotid artery, middle cerebral artery, and anterior cerebral artery) were determined as measures of the passive mechanical properties of these vessels. Studies were carried out in seven normotensive dogs and seven dogs in which experimental renal hypertension of 3 months duration had been induced. In the normotensive animals, the collagen content of the middle cerebral artery exceeded that of the other vessels considered. The elastin content and the total connective tissue were not significantly affected by arterial site. The middle cerebral artery collagen to elastin ratio was greater than corresponding values for the basilar, posterior cerebral, and internal carotid arteries. Connective tissue differences were less pronounced in the hypertensive animals. No component of the canine circle of Willis in the hypertensive dogs showed a significantly different collagen content, elastin content, total connective tissue content, or collagen to elastin ratio. In comparing cerebral vessels from normotensive and hypertensive dogs, total connective tissue values were greater in hypertension for all arterial sites considered. These acute physiological changes in connective tissue content over small distances in intracranial blood vessels from normotensive animals, together with unique connective tissue responses of these vessels to short term hypertension, may suggest additional possible factors important in the natural history of cerebrovascular pathological conditions.

Baroreceptor control of central and regional hemodynamics with isoflurane in the dog

Central and regional hemodynamics were studied at five levels of carotid sinus baroreceptor stimulation and three isoflurane levels. Apart from iliac blood flow, all regional blood flows, together with mean aortic–pressure, power and flow decreased in response to an increasing anesthetic level and/or carotid sinus baroreceptor stimulation. These effects were additive with no significant interaction between the two experimental factors. At the carotid sinus reflex set point pressure, isoflurane attenuated the ability of carotid sinus baroreceptors to change mean aortic pressure and power together with the maximum capacity of the carotid sinus baroreceptors to produce vasoconstriction. The maximum capacity of the carotid sinus baroreceptors to produce vasodilation was unaffected by isoflurane. Vagotomy only modified hemodynamic set point values at low isoflurane levels, increasing regional resistances at the expense of flow except for the iliac bed. Following vagotomy, reflex gain was increased as was the maximum capacity of the cardiovascular system to vasoconstrict and vasodilate in response to carotid sinus pressure stimulation, together with the range of arterial pressure control.

Baroreceptor Control of Systemic Haemodynamics at Incremental Halothane Levels in the Dog

The open‐loop carotid sinus reflex control of systemic haemodynamics was studied in an acute dog preparation with isolated perfused carotid sinuses at three end‐tidal halothane levels of 0.66±0.02% (HI); 0.88±0.02% (H2); and 1.17 ±0.02% (H3), in order to investigate the dose dependency of the carotid sinus reflex operating characteristics for halothane. Corresponcling to the above halothane levels were reflex operating point pressures (set point pressures) of 104.9±2.9, 103.3±4.1 and 76.0±3.8 mmHg, respectively. Carotid sinus reflex gain decreased significantly with progressively increasing halothane levels (1.41 ±0.18; 0.84±0.12; 0.48±0.09), as did the range of reflex changes in systemic arterial pressure for equal overall changes in carotid sinus pressure (87.1 ±7.9; 64.1 ±7.4; 33.6±5.1 mmHg; P<0.01). For halothane levels below approximately 0.9%, this depression was not dependent upon changes in mean systemic arterial pressure. The relationship between reflex gain and halothane concentration could be described by a first‐order exponential which suggested virtual ablation of the carotid sinus reflex control of mean arterial pressure at an end‐tidal halothane concentration exceecling about 1.6%.