Pressure-heart rate relationship in intact and after stepwise elimination of three major baroreflex loops in dogs.

Systemic arterial blood pressure (BP)-heart rate (HR) relationship (the pressor test) is often used as an index of baroreflex. We evaluated this index by simultaneously comparing BP-HR, right carotid sinus pressure (CSP)-nerve action potentials (NAP), and NAP-HR relationship in dogs anesthetized with pentobarbital. BP was increased or decreased stepwise by intravenous (IV) infusions of phenylephrine or sodium nitroprusside, respectively. In nine dogs BP-HR and CSP-NAP relationships were measured and NAP-HR relationship was constructed before and after sequential and stepwise sectioning of the left aortic depressor nerve (LADN), the right aortic depressor nerve (RADN), and blockade of the left carotid sinus nerve (BLK) with 1% lidocaine. We found that HR was a negative sigmoidal function of BP in intact dogs. Linear slope of this relationship was significantly reduced after sectioning of LADN and RADN, but returned toward baseline after BLK. NAP was a positive sigmoidal function of CSP in intact dogs. Linear slope of this relationship was significantly depressed after sectioning of LADN and RADN. However, after BLK, the slope surpassed control, suggesting the existence of a central communication between the two carotid sinuses. HR was a negative function of NAP in intact dogs. However, as the other baroreflex feedback loops were eliminated, the slope of the NAP-HR relationship approached zero indicating that a closed integrated parallel feedback system is required for reflex regulation of HR. Our findings suggest that under normal conditions the pressor test is a valid index for baroreceptor function, but its use may not be warranted in chronic pathological states, such as atherosclerosis and hypertension. However, in contrast to the present acute experimental model, chronic pathological processes may not develop in sequence, and baroreceptor function on the affected site may not be completely eliminated from the baroreceptor loop such as performed in this study.

Carotid endarterectomy. Lessons from intraoperative monitoring--a decade of experience.

OBJECTIVE: The authors analyzed a single institution's 10-year experience with intraoperative monitoring during 709 primary carotid endarterectomies and investigated the impact of contralateral internal carotid artery stenosis on carotid artery stump pressure (SP). SUMMARY BACKGROUND DATA: Stump pressure reflects the combination of contralateral carotid artery anatomy, collateral intracranial vasculature, and systemic blood pressure. By controlling for blood pressure with a stump index (SI) (SI = [SP/mean arterial pressure] x 100), a correlation between pressure and contralateral carotid artery anatomy can be demonstrated. Although the use of SP has long been advocated as an indicator of adequate cerebral perfusion, its correlation with perioperative complications while using an intraluminal shunt has not been evaluated completely. METHODS: From a series of 886 primary carotid endarterectomy cases, SP and mean arterial pressure were measured prospectively in 709 procedures. Temporary intraluminal shunts were used in cases with demonstrated contralateral carotid occlusion, prior cerebrovascular accident (CVA), or SPs less than 35 mmHg. Ipsilateral and contralateral angiographic degree of carotid stenosis was recorded at the time of the operation. Neurologic status was recorded prospectively for all 709 procedures. Operative electroencephalogram (EEG) changes and SP then were compared with the neurologic status of the patient in the perioperative period. RESULTS: The mean SP for the group (n = 709) was 46.7 +/- 15.3 mmHg (mean +/- standard deviation [SD]) with a mean SI of 54.9 +/- 22.6. The distribution for the SI is a more gaussian curve than that for SP. There were 19 ipsilateral CVAs (2.7%). The mean SP in the nonstroke group was 47.1 +/- 15.2 mmHg (mean SI = 54.7 +/- 16.5) compared with 31.9 +/- 13.2 mmHg (mean SI = 38.8 +/- 18.2) in the stroke group (P < 0.0001). Stroke rate for SP < or = 35 mmHg was 7% (13/185) versus 1.1% (6/524) for SP > 35 (p < 0.0001). Stump index and SP are related to contralateral carotid artery stenosis. The pattern of SI or SP versus contralateral stenosis is biphasic, with an increase at 75%. If SI is < or = 40, the mean contralateral stenosis is 55.1%; if SI is > 40, the mean contralateral stenosis is 35.1% (p < 0.05). Continuous EEG monitoring was completed for the 549 most recent operations. Patients who had a perioperative stroke had EEG changes observed during the procedure in only 6 of 12 cases (50% sensitivity), with 76% specificity. Using SP < or = 35 mmHg, sensitivity was 68% and specificity was 75%.

Effects of hyperosmotic mannitol infusion on hemodynamics of dog kidney.

This study evaluated the effect of systemic infusion of hypertonic mannitol on renal hemodynamics (aortic pressure [P]-renal blood flow [RBF] relationship, glomerular filtration rate [GFR], and effective renal plasma flow [ERPF]) during 50% reduction of left kidney blood flow. Conditioned mongrel dogs anesthetized with halothane were hydrated by continuous infusion of lactated Ringer's solution containing creatinine to measure GFR and p-aminohippurate (PAH), to measure ERPF. The left kidney was exposed and two hydraulic occluders were placed, one around the aorta just above the renal arteries and the other around the left renal artery. Experimental design consisted of measuring P near the left renal artery, RBF by electromagnetic flowmeter, and ERPF and GFR by clearance methods in both kidneys in response to stepwise reduction in the aortic pressure by aortic occlusion before and after 50% reduction in the left kidney blood flow. The P-RBF relationship, GFR, and ERPF thus obtained were compared with those obtained during systemic intravenous infusion of 20% mannitol for a period of 1 h. We found that 1) a transient increase occurred in RBF with step reduction of P from 80 to 60 mm Hg under control conditions; 2) reducing the RBF by 50% changed the shape of the P-RBF relationship from a convex to the P axis to a linear form with a marked shift toward the P axis; 3) infusion of mannitol, during reduced RBF, caused a significant shift of the P-RBF curve toward the RBF axis and returned the linear P-RBF relationship toward normal, but had no effect on altered yield pressure; and 4) infusion of hypertonic mannitol had slightly increased GFR and ERPF in the right (unconstricted) kidney. However, hypertonic mannitol significantly increased GFR and ERPF values in the left (constricted) kidney suggesting a beneficial effect of mannitol on ischemic kidney. The results are consistent with the hypothesis that infusion of hypertonic mannitol to ischemic kidney increases RBF, presumably by decreasing the intrarenal vascular resistance. We speculate that this compensatory response may be mediated either 1) by stimulating the release of a vasodilator substance (e.g., prostaglandins), or 2) by washing out interstitial sodium, thereby reducing the sensitivity of the renal vasculature to ischemia-induced stimulation of renin-angiotensin system.

Partition of carotid baroreceptor response in two-kidney renal hypertensive dogs.

This study evaluated the mechanism of carotid sinus baroreceptor resetting in two-kidney one-clip Goldblatt hypertension in dogs by partitioning the resetting between carotid sinus wall compliance and receptor neural elements. With dogs under halothane anesthesia, the left renal artery was constricted 70-80% with a Goldblatt clamp without disturbing the contralateral kidney. Ten weeks later, when mean blood pressure had risen to 151 +/- 6 mmHg (means +/- SE) compared with 105 +/- 5 mmHg in controls, we measured simultaneously whole nerve action potentials (N) and carotid sinus volume (V) during step changes in intrasinus pressure (P). Hypertensive N vs. P relationship was sigmoid shaped and shifted toward the P-axis compared with controls. Hypertensive V vs. P relationship was not significantly different from controls. The hypertensive N vs. V relationship derived from the composite plots of N vs. P and V vs. P was sigmoid shaped and shifted toward the V-axis compared with controls. These results suggest that the resetting of baroreceptors is due to changes in receptor properties rather than carotid sinus wall compliance.

Blockade of contralateral carotid sinus nerve enhances ipsilateral nerve action potentials under halothane anaesthesia.

In 10 dogs, one carotid sinus was isolated from the systemic circulation without disturbing its sympathetic innervation. The isolated sinus was connected to a servo-controlled pressure generator which kept mean intrasinus pressure, pulse pressure, and frequency of pulsation constant. The carotid sinus baroreceptor nerve action potentials (NAP) were measured, together with the intransinus and systemic pressures. Following control measurements, the end-tidal concentrations of halothane in oxygen were varied between 0.0 and 2%, in random increments of 0.5%, each with 30 min of stabilization. The carotid sinus NAP response to halothane was biphasic in a dose-dependent manner. The series was repeated after neural blockade of the contralateral sinus with 1% lignocaine 2-3 ml. This blockade enhanced all NAP responses (P less than 0.001), suggesting that a central inhibitory effect, initiated by the contralateral sinus, had been removed.

Renal tissue oxygenation following induced hypotension in dogs.

Renal oxygenation was studied during induced hypotension in mongrel dogs, anaesthetized with 1-1.5% halothane in oxygen. Hypotension was induced with an infusion i.v. of sodium nitroprusside (SNP) 70 +/- 17 micrograms kg-1 min-1 (mean +/- SEM) or trimetaphan (TMP) 36 +/- 16 micrograms kg-1 min-1, or by controlled arterial haemorrhage (45 +/- 6 ml/kg of body weight). Mean arterial pressure (MAP), cortical (Pcto2) and medullary (Pmto2) tissue oxygen tensions, arterial (Pao2), renal venous (Prvo2), and urine (Puo2) oxygen tensions were measured during the 40-min control, hypotension, and recovery periods. MAP was decreased to approximately 60% of the control value. Pcto2 decreased significantly (P less than 0.05) in all three groups while Pmto2 decreased significantly only in the haemorrhage group. Upon restoration of MAP to normal values, renal tissue oxygen tensions recovered in all groups, somewhat more rapidly in the SNP group. There were no significant differences in Pao2, Prvo2, and Puo2 during control, hypotension and recovery periods in the three groups. Tissue oxygen tension values followed the changes in MAP, but were not hypoxic, leading us to believe that both SNP and TMP are hypotensive agents safe for the kidney.

Local versus central effect of halothane on carotid sinus baroreceptor function.

Depressive effect of halothane on carotid sinus baroreceptor function may be due to direct local action, in the CNS, or both. Paris of dogs were anesthetized with pentobarbital and ventilated with oxygen. The carotid sinus of the recipient dog was isolated and perfused with blood from the common carotid artery of the donor dog. Blood from the recipient sinus was returned through its external carotid to the donor common carotid. Thus, both carotid sinuses of the donor and the contralateral carotid sinus of the recipient dog received uninterrupted circulation. Carotid sinus nerve action potentials and lingual artery pressure of the isolated recipient sinus were recorded before and during steady state end-tidal halothane concentrations of 0, 0.5, 1.0, 1.5, 2.0, and 2.5% in oxygen, given randomly first to the donor dog (to evaluate direct local effect) and then to the recipient dog (to determine central effect). The dog not given halothane received pentobarbital. Plots of normalized nerve activity versus halothane concentrations showed approximately zero slope when the donor was given halothane but showed significant decrease in nerve activity when the recipient was given halothane. Halothane appears to have no direct local effect but causes depression of baroreceptor nerve activity, possibly via CNS inhibition of sympathetic efferents to the carotid sinus.

Trimethaphan-induced hypotension: effect on renal function.

This study was designed to evaluate the effects of trimethaphan-induced hypotension on renal function in healthy young patients undergoing maxillofacial surgery. Anaesthesia was induced with thiopentone and was maintained with halothane 1.5-2.0 per cent in oxygen. Each patient served as his own control, and data were analyzed using the paired t-test. Trimethaphan was infused at a rate of 45-52 microgram.kg-1.min-1 for an average hypotensive period of 53 +/- 4 (mean +/- SEM) minutes to reduce the mean arterial pressure (MAP) to 49 +/- 2 torr. Endogenous creatinine clearance, urinary Po2, sodium reabsorption rate (Tna), and serum and urine osmolalities were determined before, during and after arterial hypotension with trimethaphan. Urine flow averaged 2.9 +/- 1 ml/min during the period of hypotension. Endogenous creatinine clearance and Tna were significantly decreased (p less than 0.05) in the hypotensive period. These values returned to normal levels within one hour upon discontinuation of trimethaphan and restoration of blood pressure. We found no statistical difference in urine Po2, and serum and urine osmolalities during control, hypotensive and recovery periods. These results suggest that medullary renal tissue oxygenation, an index of tissue viability, may have remained adequate despite a significant reduction in endogenous creatinine clearance during the hypotensive period. Furthermore, it appears that the effect of trimethaphan-induced hypotension on renal function is similar to the sodium nitroprusside-induced hypotension in man which we have reported previously.

A planimetric technique for measuring deformation of the carotid sinus region.

This paper describes a planimetric technique for measuring the volume of the carotid sinus region from still photographs taken during pressure and volume forcings. The method consists of first digitizing the curves defining the boundary of the carotid sinus and then calculating its volume by assuming that the carotid sinus region is made up of a finite number of circular "pancake" slices. Plots of the calculated volume (Vc) vs. applied pressure forcings (P) were compared with plots of injected volume (Vi) vs. recorded pressure to assess the sensitivity of the method used to calculate volume changes from still photographs. The plots of Vc vs. P were remarkably similar to the plots of Vi vs. recorded pressure, and a plot of Vc vs. Vi was linear, suggesting that this method provides a good estimate of volume changes. Application of this method can yield useful data on mechanisms of the baroreceptor process.

Partition of carotid sinus baroreceptor response in dogs with chronic renal hypertension.

This study was designed to determine whether resetting of the carotid sinus baroreceptors in chronic renal hypertension is due to altered distensibility of the wall, or changes in the properties of the receptor elements, or both. Dogs were made hypertensive by 50% constriction of the left renal artery with a Goldblatt clamp and by right nephrectomy one week later. Five to nine weeks after nephrectomy, when mean blood pressure had risen by 35-46 mm Hg, the isolated carotid sinus wall deformation, measured from still photographs, and gross baroreceptor nerve action potentials (N) were recorded in response to step intrasinus pressure forcings (P), ranging from zero to 300 mm Hg, in increments of 25 mm Hg. Measured wall deformation was converted to strain-energy density (SED), a scalar value, as the best indicator of the mechanical state of the sinus wall. Plots of N vs. P data followed an S-shaped pattern, but were shifted toward the P-axis, as compared to controls. Plots of SED vs. P, though linear over most of the pressure range, were shifted toward the SED-axis, as compared to controls. A plot of N vs. SED, derived from the composite plots of N vs. P and SED vs. P, followed an S-shaped pattern and also was shifted toward the SED-axis. We conclude that the nonlinearity in the N vs. P curve is due largely to the inability of the receptor elements to respond to increasing wall strain and to resetting of the baroreceptors due to changes in the receptor properties rather than in the wall elements.