John G. Wade

Effect of Carotid Endarterectomy on Carotid Chemoreceptor and Baroreceptor Function in Man

Abstract The ventilatory response to inhaled carbon dioxide was measured during hyperoxia (Pao2 over 200 torr) and hypoxia (Pao2 of 40 torr) in 14 patients before and one to nine weeks after caroti...

Impairment of Cerebral Blood Flow Autoregulation in the Newborn Lamb by Hypoxia

ABSTRACT. Autoregulation of cerebral blood flow has been demonstrated in both fetal and newborn animal models under normoxic conditions. In the present experiments we have attempted to define the minimal hypoxic insult which impairs autoregulation in the newborn Iamb and to assess the time to recovery. We measured cerebral blood flow by the intracarotid 133Xe method in fifteen 4- to 9-day-old lambs and tested autoregulation of cerebral blood flow by increasing blood pressure 20-30% with phenylephrine. Autoregulation was tested in the control state and at successive time intervals after an hypoxic stress (Pao2 of 30 mm Hg) of 10 or 20 min. We found that cerebral autoregulation was abolished after 20 min of hypoxia and recovered within 7 h. Since this model identifies the minimal hypoxic insult to abolish autoregulation it might be used to study means to protect autoregulation or to hasten its recovery after hypoxia.

The effect of subarachnoid epinephrine and phenylephrine on spinal cord blood flow

Eighteen mongrel dogs were divided into three equal groups. Spinal cord and spinal durat blood flow in the cervical, thoracic and lumbosacral regions were measured using the radioactive microsphere technique. Measurements were taken before and 10 and 40 minutes after lumbar subarachnoid injection of one of the following: (I) physiologic saline; (2) epinephrine200 μg or (3) phenylephrine 5 mg. No significant change in spinal cord blood flow occurred in any of the groups, nor was there any difference between the groups. Dogs receiving subarachnoid phenylephrine did demonstrate a significant reduction of thoracic dura! blood flow at ten minutes. Dogs receiving intraihecal epinephrine or phenylephrine demonstrated a significant reduction in lumbosacral dural blood flow at ten minutes after injection. The reduction in dural blood flow was still evident at 40 minutes in dogs receiving phenylephrine. Subarachnoid epinephrine (200 μ.g) and phenylephrine (5 mg) do not effect spinal cord blood flow but do produce regional dural vasocomtriction.RésuméChez 18 chiens bâtards répartis en trois groupes égaux, le flux sanguin de la moelle épiniere et de la duremère a été mesuré dans les régions cervkales, thoraciques et lombosacrées par microsphères radioactives. Les mesures ont été effectiées avant el 10 minutes et 40 minutes après l’ injection de l’ un des produits suivants: 1) soluté salin, 2) épinéphrine 200 μg, 3) phényléephrine 5 mg. On n’a pas observé de changement notable de la perfusion médullaire dans aucun groupe et aucune difference n’a été observée d’un groupe à 1’autre.Seule la perfusion duremérienne a été modifiée par les injections comme suit: la phényléphrine sous-arach-noi ïdienne a réduit de façon significative le flux dure-mérien thoracique dix minutes après I’injection. De même on a observé une réduction significative du flux dure-mérien lombo-sacré dix minutes après I’ injection a“ epinéphrine et de phényléphrine; cette diminution du flux duremérien était encore présents 40 minutes après I’injection de phényléphrine. On en concittt que dans ce modèle expérimental, I’ épinéphrine sous-arachnoi-dienne (200 μg) et la phényléphrine (5 mg) ne modifient pas le flux médullaire mais provoquent une vasoconstriction dans la circulation duremérienne régionale.

Halothane Depresses Baroreflex Control of Heart Rate in Man

Baroreflex control of heart rate was determined during three awake control situations and during two depths of halothane anesthesia in man. Baroreflex function was quantiated by calculating the pressor test slope from the R-R interval change on the ECG produced by a pharmacologically induced pressor response. During the three awake control situations the subjects breathed room air or 100 per cent O2 spontaneously or 100 per cent O2 with ventilation controlled. Mean (+/- SD) slopes obtained were 15.1 +/- 4.5, 15.6 +/- 6.8 and 18.4 +/- 9.9, respectively. No significant difference in baroreflex function slope was observed. During light halothane anesthesia (0.7 per cent endtidal) baroreflex function was significantly depressed (mean slope = 2.5 +/- 1.5), and it was abolished at 1.1 per cent end-tidal halothane (mean slope = 0.03 +/- 0.04). It is concluded that halothane anesthesia produces depression of baroreflex control of heart rate in man.

The effects of age on baroreceptor reflex function in man

SummaryThe relationship of age to baroreceptor reflex activity was determined in 35 healthy volunteers ranging in age from 19 to 65 years. Intra-arterial catheters were placed and blood pressure and pulse rate responses of each subject were observed during a Valsalva maneuver (31 subjects) and during the Pressor Test (33 subjects). The Valsalva maneuver consisted of a forced expiration sufficient to raise a column of mercury 40 torr for 10 seconds. This resulted in a reduction in pulse pressure (Baroreceptor stimulus) during the maneuver followed by a transient overshoot in diastolic pressure (response) following its termination. In comparison to younger subjects, older subjects had a greater reduction in pulse pressure but similar overshoot in diastolic pressure. The pressor test consisted of observing the effect of increasing systolic blood pressure (stimulus) on pulse duration (response) following the intravenous administration of phenylephrine. By relating each systolic pressure to the immediately succeeding R-R interval, a linear relationship was found. Its slope expressed in milliseconds of R-R interval change per torr increase in systolic pressure is an index of baroreflex function. Older subjects have less cardiac slowing compared to younger subjects and a hyperbolic relationship exists between age and slope ( r = 0.84, p < 0.05 ). These tests indicate that baroreceptor reflex function decreases with aging.RésuméNotre étude sur l’activité réflexe baroréceptrice en fonction de l’âge a porté sur 35 volontaires en bonne santé et âgés de 19 à 65 ans.Après mise en place de canules artérielles, l’on a enregistré la pression et la fréquence cardiaque au cours d’une manœ uvre de Valsalva, chez 31 sujets et durant un test d’hypertension chez 33 sujets.La manœ uvre de Valsalva consistait pour fins de cette étude en une expiration forcée suffisante pour élever une colonne de mercure de 40 torr durant 10 secondes. L’on observait dans ces circonstances une chute de la pression différentielle (stimulus) suivie d’une élévation passagère de la pression diastolique survenant à la fin de la manœ uvre (réponse). Par comparaison aux plus jeunes, les plus vieux sujets montraient une plus grande diminution de la pression différentielle, mais leur élévation de la diastolique ( réponse ) était comparable.Le test d’hypertension consistait à élever les effets de l’élévation de la pression systolique (stimulus) consécutive à l’administration intraveineuse de Phenylephrine, sur la fréquence cardiaque. Les modifications de l’espace RR (en millisecondes) inscrites en fonction de l’élévation de la pression (torr) permettaient d’établir une relation linéaire témoin de la fonction baroréflexe. Les sujets plus âgés ont montré moins de ralentissement de la fréquence en fonction de l’élévation de la pression. Ces tests indiquent que l’activité baroréflexe diminue avec l’âge.

Subarachnoid bupivacaine decreases spinal cord blood flow in dogs

Eigtheen mongrel dogs were randomized into two equal groups. Cervical, thoracic and lumbosacral spinal cord and spinal dural blood flows were measured using the radioactive microsphere technique. Blood flow determinations were made prior to, and 20 and 40 minutes following lumbar subarachnoid injection of: (1) 0.4 per cent bupivacaine (20 mg), or (2)0.4 per cent bupivacaine (20 mg) with 1/25,000 epinephrine (200 μg).In dogs given subarachnoid bupivacaine or bupivacaine with epinephrine, the maximum decrease in mean arterial blood pressure (33 per cent) occurred at 40 minutes post-injection. Cardiac index decreased in dogs given subarachnoid bupivacaine (197 ± 11 ml·kg-1·min-1 controlvs. 141 ± 19 ml·kg-1 min-1 at 40 minutes), while it increased in dogs given bupivacaine with epinephrine (201 ± 11ml·kg-1·min-1 - control vs. 252 ± 15 ml · kg-1 · min-1 at 40 minutes). Dogs receiving subarachnoid bupivacaine demonstrated a significant decrease in spinal cord blood flow to all regions. Dogs receiving subarachnoid bupivacaine with epinephrine demonstrated a significant decrease in thoracic and lumbosacral spinal cord blood flow; however, cervical cord blood flow remained unchanged. Thoracic and lumbosacral dural blood flows were significantly decreased in both groups following subarachnoid injection.Subarachnoid bupivacaine 0.4 per cent (20 mg) and 0.4 per cent with epinephrine 1/25,000 (200 μg) decrease spinal cord and spinal dural blood flow in dogs.RésuméDix-huit chiens bâtards ont été randomisés en deux groupes égaux. Les débits sanguins de la moelle épinière et de la duremère dans les régions cervicale, thoracique et lombo-sacrée ont été mesurés en utilisant la technique des microspherès radioactives. Les déterminations des flots snaguins ont été faites avant, 20 et 40 minutes après l’injection sous-arachnoïdienne lombaire de: 1) 0.4 pour cent bupivacaïne (20 mg) ou, 2) 0.4 pour cent bupivacaine (20 mg) avec 1/25,000 épinéphrine (200 μg @#@). Les chiens ayant requ l’injection de bupivacaïne sous-arachnoïdienne ont démontré une diminution significative dans le flot sanguin de la moelle épinière dans toutes les régions. Les chiens ayant reçu la bupivacaïne intrathecale avec épinéphrine ont démontré une diminution significative du flot sanguin dans les régions thoracique et lombo-sacrée; cependant, le flot sanguin de la moelle épinière dans la région cervicale est demeure inchangé. Les flots sanguins de la duremère dans les régions thoracique et lombo-sacrée ont été diminués significativement dans les deux groupes après injection sous-arachnoïdienne.L’injection sous-arachnoïdienne de bupivacaïne 0.4 pour cent (20 mg) et 0.4 pour cent avec épinéphrine 1/25,000 (200 μg @#@) diminue le flot sanguin dans la moelle epiniere ainsi que dans la duremére chez les chiens.

Fetal Anesthetic Requirement (MAC) for Halothane

We asked whether the anesthetic requirement (MAC) of fetal lambs is lower than that of pregnant ewes. In five pregnant ewes anesthetized with a subarachnoid block, a fetal foot was withdrawn through a hysterotomy. The ewe then breathed 1.5% halothane and a clamp was applied to the fetal foot at 2-min intervals. We concomitantly obtained arterial blood from previously implanted catheters. When fetal movement in response to clamping the foot ceased, halothane was discontinued and the stimulus and sampling continued until the fetus began to move. Anesthesia was again resumed and continued until movement stopped. Anesthesia was then deepened and MAC was determined in the mother (stimulus—ear clamp). The fetal blood concentrations of halothane at MAC were 48 ± 28 mg/L; they were 133 ± 5 mg/L in the mother. This difference was highly significant (P < 0.001). Calculated end-tidal concentrations were 0.33% and 0.69%, respectively. In two animals delivered by cesarean section, MAC increased progressively over the first 12 h of life. Progesterone levels concomitantly decreased.

Effect of halothane on cardiac output and regional flow in the fetal lamb in utero.

: We studied the effect of halothane on the fetal cardiovascular system of six lambs in utero by measuring fetal heart rate and femoral arterial blood pressure and by injecting labeled microspheres during a control period and again after 60 and 90 min of halothane anesthesia administered to six pregnant ewes at an inspired concentration of 1.5%. There were no significant effects on maternal cardiovascular function or acid-base balance, but fetal blood pressure decreased significantly by 27% after 8 min of halothane anesthesia and remained at this level for the duration of the experiment. However, there were no significant changes either in fetal regional blood flow to the vital organs or in fetal cardiac output. Fetal oxygenation and acid-base status remained stable. We conclude that in normal fetal lamb in utero the decrease in mean fetal arterial blood pressure associated with maternal halothane anesthesia is due to a decrease in peripheral vascular resistance because regional blood flow and acid-base status are well maintained.

Dose-response relationship of clonidine in tetracaine spinal anesthesia.

The study was undertaken to define a dose-response relationship for clonidine in prolonging canine tetracaine spinal anesthesia. Using a randomized blind cross-over design, six mongrel dogs were given subarachnoid injections (1 ml) of the following solutions over an 8-week period: tetracaine 4 mg (control), or tetracaine 4 mg with clonidine in doses of 10, 25, 50, 100, 150, 200, and 300 μg. With clonidine doses equal to or exceeding 50 μg/ml, motor and sensory blockade were significantly (P < 0.01) prolonged, when compared to the control times. Analysis of data by second order polynomial regression analysis produced a relationship defined by Y = 23.241 + 1.104(x) - 0.0023 (x2) with r2 = 0.92 and P < 0.001 for sensory blockade and Y = 38.7072 + 1.64425(x) - 0.004125(x2) with r2 = 0.90 and P < 0.005 for motor blockade. From these curves, a plateau in clonidine dose-response for both sensory blockade and motor blockade occurred at 150 μg. The increase in duration of spinal anesthesia with clonidine may be related to a direct post-synaptic alpha2 adrenoceptor arteriolar effect, a spinal cord pre- or post-synaptic alpha2 antinociceptive action or supraspinal alpha2 modulation of nociception. No animals showed evidence of neurologic dysfunction during the study. The authors conclude that a well-defined dose-response relationship exists for clonidine in canine tetracaine spinal anesthesia.

Preservation of fetal brain blood flow relative to other organs during hypovolemic hypotension.

Summary: The asphyxiated newborn is particularly vulnerable to hypotension, which contributes to hypoxic brain damage by reducing cerebral perfusion. During asphyxia, cerebral blood flow (CBF) is pressure passive, that is, CBF autoregulation is abolished. It is important to know if the nonasphyxiated fetus and newborn are similarly vulnerable to hypotension. In the present study, we have measured acute responses of organ blood flow to a hypovolemic/hypotensive stress in the normoxic near term sheep fetus. Changes in brain flow were compared to changes in other organs.Eight chronically prepared fetal lambs were studied. Organ blood flows were measured by the microsphere technique during a control period, after a 20% blood volume reduction, and again after reinfusion of that volume.Hypovolemia was accompanied by a 21% decrease in blood pressure and a 4 torr increase in Pco2; after reinfusion blood pressure increased 16% above control. Control measurements of organ perfusion were similar to those reported by other investigators. Cardiac output and flow to all organs, with the exception of the brain, were reduced 30–56% during hypovolemia. Brain blood flow was insignificantly reduced by 9%. If a correction is applied for the increase in Pco2, CBF corrected to control Pco2 would have been significantly reduced by 18%. After reinfusion, flow to all organs increased to near control levels.We conclude that the normoxic fetal lamb shows evidence of CBF autoregulation, and is able to preserve relative constancy of CBF within a blood pressure range of ± 20% of normal. However, the evidence presented in this study suggests that autoregulation may be less effective in response to a hypotensive stress, even though CBF is better preserved than flow to most other organs.Speculation: The brain of the lamb is more mature than that of the human at to changing blood pressure was of particular interest. birth. Although the normoxic fetal lamb shows evidence of cerebral blood flow autoregulation, these studies suggest that even unde normal physiologic conditions in utero, the fetal brain may not be fully protected against acute hypotension. This may be because the normal fetal blood pressure is close to the lower limit of autoregulation. Previous work by ourselves and others has also demonstrated the vulnerability of autoregulation to hypercapnea, hypoxia, and acidosis. Since these are common manifestations of fetal and newborn asphyxia, and even to some extent of the normal birth process, it is reasonable to speculate that autoregulation is generally impaired when there is fetal or newborn distress. There- fore, cerebral blood flow of even the nonasphyxiated neonate may be vulnerable to marked deviations of blood pressure.