EFFECTS OF ALFENTANIL ON CEREBRAL VASCULAR REACTIVITY IN DOGS

The effects of high dose alfentanil on the cerebral vascularresponses to alterations in mean arterial pressure (MAP), arterialoxygen tension (Pa^O2) and arterial carbon dioxide tension (Pa^CO2)were studied in 17 dogs, using the cerebral venous outflow technique.In six animals anaesthetized with sodium pentobarbitone 30 mgkg^–1 i.v., bolus injection of alfentanil 0.32 mg kg^–li.v. decreased MAP without a change in cerebral blood flow (CBF).In another group of animals(n = 5) anaesthetized with pentobarbitone30mg kg^–1 i.v. the CBF responses to changes in MAP. Pa^O2,and Pa^CO2 were studied. In a third group of animals (n = 6)anaesthetized with alfentanil 0.32 mg kg^–1 i.v. plus pentobarbitone1–2 mg kg^–1 i.v. and an infusion of alfentanil 0.32mg kg^–1h^–1 the CBF responses to alterations inMAP, Pa^O2, and Pa^CO2 were studied and compared with the barbiturate-anaesthetizedanimals. The CBF responses to hypercapnia and hypoxia in thealfentanil-anaesthetized animals were not different from thoseobserved in animals anaesthetized with barbiturate only. Thelower and upper limits of cerebral autoregulation in alfentanil-anaesthetizedanimals were not different from those observed in animals anaesthetizedwith barbiturate only. The data suggest that alfentanil, indoses sufficient to cause profound analgesia and anaesthesia,does not alter cerebral reactivity to changes in Pa^O2, Pa^CO2and MAP.     

Ultrasound guidance as a gold standard in regional anaesthesia

It is now just over 2 yr since Marhofer and colleagues,¹ inthis journal, reviewed the use of ultrasound in regional anaesthesia.They concluded with the hope that the availability of portableultrasound systems with high-frequency probes would promotethe routine use of ultrasound guidance in regional anaesthesia.This review, however, was accompanied by an editorial that queriedthe evidence base for preferring ultrasound guidance to othertechniques of nerve localization.² With the widespread availabilityto anaesthetists of high-resolution portable ultrasound machines,³it is timely to consider if sufficient evidence has accumulatedto quell the doubts expressed by Denny and Harrop-Griffiths.² Denny and Harrop-Griffiths² pointed out the difficulties inproving increased success rates in comparison with those ofexperienced regional anaesthetists and emphasized the paucityof data concerning improvements     

Thoracic epidural anaesthesia for cardiac surgery: are we missing the point?

Anaesthetic techniques have always had to adapt to changingsurgical interventions. Several developments over the last 15yr have changed practice in cardiac surgery. First, standardaccess to the heart via median sternotomy can often be replacedby less invasive approaches, as used in minimally invasive directcoronary artery bypass surgery, robotic surgery, or endovascularvalve surgery.¹ Secondly, perioperative management strategieshave adopted more ‘physiological’ techniques, suchas normothermic extracorporeal circulation^{2 3} or blood cardioplegia.⁴Thirdly, off-pump aorto-coronary bypass grafting (OPCAB) avoidingextracorporeal circulation has been shown to have the potentialto decrease postoperative morbidity.^{5 6} The absence of extracorporealcirculation     

CLEARANCE OF ATRACURIUM AND LAUDANOSINE IN THE URINE AND BY CONTINUOUS VENOVENOUS HAEMOFILTRATION

We have measured the steady state urinary clearances of atracurium,given by constant infusion, and laudanosine in eight patientsundergoing artificial ventilation; all had normal renal function(mean creatinine clearance 81 ml min^–1). Mean (so) urinaryclearance of atracurium was 0.55 (0.5) ml kg^–1 min^–1;that of laudanosine was 0.33 (0.2) ml kg^–1 min^–1.Simultaneous plasma clearances were 7.1 (1.4)ml kg^–1 min^–1and3.8 (1.5) ml kg^–1 min^–1, re-spectively. Notionalhaemofiltration clearances of the two substances were measuredalso in seven critically ill patients with renal and respiratoryfailure undergoing continuous venovenous haemofiltration. Mean(SD) clearances of atracurium and laudanosine in the haemofiltratefluid were 0.11 (0.06) ml kg^–1 min^–1 and 0.09 (0.02)ml kg^–1 min^–1, respectively whilst plasma clearanceswere atracurium 6.7 (1.8) mlkg^–1min^–1 and laudanosine4.5 (1.8) ml kg^–1 min^–1. There were no significantdifferences between the plasma clearances of the drugs in thetwo groups, despite the difference in severity of sickness.Urinary clearance rates of atracurium and laudanosine were approximately8 and 9% of that in the plasma, but the haemofiltration clearanceof both substances was only 2 %. Part of this work was presented at meetings of the AnaestheticResearch Society in April and July, 1990.     

Mg2+ dependence of Ca2+ release from the sarcoplasmic reticulum induced by sevoflurane or halothane in skeletal muscle from humans susceptible to malignant hyperthermia

Background. In normal resting muscle, cytosolic Mg²⁺ exertsa potent inhibitory influence on the sarcoplasmic reticulum(SR) Ca²⁺ release channel (ryanodine receptor, RyR1). ImpairedMg²⁺-regulation of RyR1 has been proposed as a causal factorin malignant hyperthermia (MH). The aim of this study was tocompare the effects of cytosolic Mg²⁺ on SR Ca²⁺ release inducedby halothane or sevoflurane in normal (MHN) and MH susceptible(MHS) human skeletal muscle fibres. Methods. Samples of vastus medialis muscle were obtained frompatients under investigation for MH susceptibility. Single fibreswere mechanically skinned and perfused with solutions mimickingthe intracellular milieu. Changes in [Ca²⁺]_i were detected usingfura-2 fluorescence after application of equimolar halothaneor sevoflurane. Results. In MHN fibres, concentrations of sevoflurane or halothaneas high as 10 mM typically failed to induce SR Ca²⁺ releaseat physiological free [Mg²⁺] (1 mM). However, when [Mg²⁺] wasdecreased to 0.4 mM, SR Ca²⁺ release occurred in 51% (16/33)and 6% (2/33) of MHN fibres after the addition of 1 mM halothaneor 1 mM sevoflurane, respectively. Further decreases in [Mg²⁺]increased the proportion of responsive fibres. In the presenceof 0.1 mM [Mg²⁺], Ca²⁺ release occurred in all fibres (33/33)after the introduction of 1 mM halothane or 1 mM sevoflurane.In MHS fibres, 1 mM halothane or 1 mM sevoflurane-induced Ca²⁺release in 54% (7/13) or 15% (2/13) of fibres, respectively,at 1 mM Mg²⁺. A decrease in [Mg²⁺] to 0.2 mM Mg²⁺ was sufficientto render 100% of MHS fibres (13/13) responsive to 1 mM halothaneor 1 mM sevoflurane. Conclusions. In both MHS and MHN fibres (i) halothane is a morepotent activator of SR Ca²⁺ release than sevoflurane and (ii)as with halothane, the efficacy of sevoflurane-induced SR Ca²⁺release exhibits a marked dependence on cytosolic [Mg²⁺]. Themarked potentiation of SR Ca²⁺ release after a moderate reductionin cytosolic [Mg²⁺] suggests that conditions which cause hypomagnesaemiawill increase the probability and possibly severity of an MHevent. Conversely, maintenance of a normal or slightly increasedcytosolic [Mg²⁺] may reduce the probability of MH.     

Protective effects of cromolyn sodium on intestinal ischaemia-reperfusion-triggered lung injury in rats

Editor—Intestinal ischaemia-reperfusion (IR) injury isrecognized clinically.¹ The mechanism of lung injury inducedby intestinal IR is complex. Both Giakoustidis and colleagues²and Ito and colleagues³ found that malondialdehyde (MDA) contentin lung increased significantly and superoxide dismutase (SOD)activity in lung decreased     

ProSeal laryngeal mask airway for laparoscopic gastric banding in a myasthenic, morbidly obese patient

Editor—Although the actual incidence of difficult trachealintubation in obese patients is questioned,¹ a subset of morbidlyobese patients with obstructive sleep apnoea, a large neck circumference,or a Mallampati score of 3 or higher,² and restricted cranio-cervicalmovement³ is at greater risk of difficult tracheal intubationand hypoxia than normal-weight patients.⁴ Laryngeal masks havebeen recommended in the guidelines on difficult intubation andhave been used in obese subjects, mostly as intubating     

EFFECTS OF THIOPENTONE OR CHLORMETHAZOLE ON HUMAN PLACENTAL STEM VILLOUS ARTERIES

Small placenta/ stem villous arteries were micro dissected fromspecimens obtained at normal term vaginal delivery (n= 25).Ring preparations of the vessels were mounted in organ bathsand isometric tension was measured. Prostaglandin F_2a(PGF_2a)10^{– 7} mol litre^–1 produced concentration-dependentcontractile responses that were inhibited by thiopentone 10^–410^–3/>‘mollitre^–1 and by ch/ormethiazole 3x10^–4-3x 10* mollitre^–1. Thiopentone 10^–410^–3mol litre^–1and chlormethiazole 3x x 10^–4/>-3x x 10^–3 mollitre^–1 decreased the tension in vessels previously treatedwith PGF_2a10^{– 5} mol litre^–1. Chlormethiazole 3x10^–3 mol litre’^–1 inhibited, and thiopenone10^–4-10‘^–3 mol litre abolished contractileresponses to 5-hydroxytryptamine. Contractions induced by angiotensinII were inhibited by thiopentone 1O^–3 mol litre^–1and chlormethiazole 3x 10^{– 3} mol litre^–1. The concentrationsof the two drugs needed to affect contractile activation ofisolated human stem villous arteries exceeded the free plasmaconcentrations reached during anaesthesia induced by the agentsduring Caesarean section, and the present results do not suggestany major effects of thiopentone or chlormethiazole on fetalplacenta/ vascular resistance during the clinical use of thesedrugs.     

PROPOFOL AND ALFENTANIL IN CHILDREN: INFUSION TECHNIQUE AND DOSE REQUIREMENT FOR TOTAL I.V. ANAESTHESIA

We estimated the dose of propofol (initial dose followed bya stepped infusion) when given with two different infusion ratesof alfentanil for total i. v. anaesthesia in 59 children aged3–12 yr. Patients in series 1 (four groups) received analfentanil loading dose of 85g kg^–1 and an infusion of65 g kg^–1 h^–1. Patients in series 2 (groups 5 and6) received an alfentanil loading dose of 65 g kg^–1 andinfusion of 50 g kg^–1 h^–1. Parents gave their informedconsent. Premedication comprised temazepam 0.3 mg kg^–1.Glycopyrronium 5 g kg^–1 was administered and anaesthesiainduced and maintained with alfentanil (loading dose and infusion)followed by propofol (loading dose and three-stage manual infusionscheme). Suxa-methonium 1 mg kg^–1 was used to facilitatetracheal intubation and the lungs were ventilated artificiallyto normocapnia with 30% oxygen in air. Probit analysis was usedto determine the dose requirement of propofol. In series 1.the ED₅₀ was 6.0 mg kg^–1 h^–1 (95% confidence limits5.5-6.2 mg kg^–1 h^–1) and ED₉₅ 8.6 (6.8-7.8) mg kg^–1h^–1. Corresponding values for series 2 were ED₅₀ 7.5 (8.0-9.8)mg kg^–1 h^–1 and ED₉₅ 10.5 (9.6^–13.1) mg kg^–1h^–1. ^*Department of Anaesthesia, University of Newcastle upon Tyne,Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP.      

FLUMAZENIL DOES NOT ANTAGONIZE HALOTHANE, THIAMYLAL OR PROPOFOL ANAESTHESIA IN RATS{dagger}

We have studied the effects of flumazenil on sleep time andEEG in rats anaesthetized with 1.5% halothane, propofoi 20 mgkg^–1, thiamylal 30 mg kg^–1, or combinations of diazepam5 mg kg^–1 and anaesthetic agents. We also studied theeffects of flumazenil 0.3, 3 and 30 mg kg^–1 on behaviourand EEG. Flumazenil 0.3 and 3 mg kg^–1 alone had no effecton behaviour or EEG, but flumazenil 30 mg kg^–1 had depressiveeffects similar to those of diazepam on behaviour and EEG. Flumazenil0.3, 3 and 30 mg kg^–1 i.v., antagonized the effects ofdiazepam 10 mg kg^–1 i.v. on behaviour and EEG. Flumazenilhad no antagonistic effect on sleep time induced by anaestheticagents, but flumazenil 30 mg kg^–1 potentiated propofol-inducedanaesthesia. Flumazenil did not affect anaesthesia-induced EEGchanges. Diazepam 5 mg kg^–1 potentiated anaesthesia. Flumazenilantagonism of diazepam potentiation varied with anaestheticagent: flumazenil 0.3 mg kg^–1 antagonized diazepam actionin halothane anaesthesia, but 30 mg kg^–1 was requiredin propofoi anaesthesia; this large dose was insufficient inthiamylal anaesthesia. ^*Present address: Department of Anesthesia, Omiya Medical Center,Omiya 330, Japan.      

Ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs

Editor—Absolute ethyl alcohol (ETOH) is used with increasedfrequency in the treatment of conditions such as percutaneousablation of unresectable hepatic tumours, sclerotherapy of oesophagealvarices, ventricular septal ablation, and i.v. embolizationof arteriovenous malformations.^1–3 Although the incidenceof complications with the use of ETOH is relatively low, episodesof cardiopulmonary collapse have been described.⁴ The postulatedmechanism is severe pulmonary vasoconstriction from the suddenpassage of ETOH into the pulmonary circulation,⁵ causing pulmonaryhypertension (PHTN) and right ventricular (RV) strain.⁶ However,there is limited information on the effects of i.v. ETOH onheart function, pulmonary and systemic haemodynamics,⁷ and inclinical conditions similar to those encountered during therapeuticprocedures. We have studied the causal relationship between     

Differential effects of propofol and ketamine on cytosolic calcium concentrations of astrocytes in primary culture

Propofol has been shown recently to alter cellular communicationmediated by gap junctions between astrocytes (a glial cell subpopulationinvolved in major brain functions). As marked increases in concentrationsof cytosolic calcium ([Ca²⁺]_i) produce closure of the gap junction,we have investigated the effects of both propofol and ketamineon resting [Ca²⁺]_i concentrations in mouse cultured astrocytesusing microfluorimetry with the indo-1 fluorescent probe. Propofol10^–5and 10^–4mol litre^–1 induced a monophasictransitory Ca²⁺ peak in a large subpopulation of the cells tested.This response exhibited characteristics close to those of thepeak elicited by [L-Pro⁹] substance P (10^{– 7} mol litre^–1),an activator of phospholipase C in astrocytes. In both cases,it possibly corresponded to mobilization of Ca²⁺ from endogenousstores. In a few cases, however, administration of propofolinduced a moderate, but sustained increase in [Ca²⁺+]_j, correspondingto the entry of external Ca²+ into the cells. In contrast ketamine10^–5 and 10^–4mol litre^–1 failed to affect[Ca²⁺+]_i resting concentrations. These findings indicate thatclinically relevant concentrations of propofol, but not ketamine,increased [Ca²⁺_j concentration in astrocytes. (Br. J. Anaesth.1994: 72: 351–353) ^*Present address for correspondence: Department of Anaesthesiology,Hospital Bichat, 46 rue Henri Huchard, 75018 Paris, France.     

Crystalloid infusion rate during fluid resuscitation from acute haemorrhage

Background: Information is lacking concerning optimal infusion rates ofcrystalloid during resuscitation from acute haemorrhage. Inthis study, a mathematical model was used to predict infusionvolume of crystalloid needed to restore and maintain blood volumeafter acute haemorrhage. Methods: The scenario was a haemorrhage of 15 ml kg^–1 over 30 minin a 70 kg man. A bolus of crystalloid was administered at arate of 40, 60, 80, 100, or 120 ml kg^–1 h^–1 untilblood volume was restored. Fluid infusion rate needed to maintainblood volume for a further 1 h was computed. Results: Blood volume was restored earlier at high bolus infusion ratescompared with low bolus infusion rates (6 min at 120 ml kg^–1h^–1 vs 63 min at 40 ml kg^–1 h^–1). Fluid infusionrates for blood volume maintenance approached 33 ml kg^–1h^–1 irrespective of bolus infusion rates. The restorationfluid volume at 40 ml kg^–1 h^–1 was 2.9 litre, threetimes that at 80–120 ml kg^–1 h^–1. The maintenancefluid volume at 80–120 ml kg^–1 h^–1 was 2.9litre, 0.6 litre more than that at 40 ml kg^–1 h^–1.During the blood volume maintenance, the interstitial volumeincreased to 3.8 litre above normal at 40 ml kg^–1 h^–1and to 2.5 litre at 80–120 ml kg^–1 h^–1. Conclusions: Bolus crystalloid infusion exceeding 80 ml kg^–1 h^–1may not increase effectiveness of fluid resuscitation. Crystalloidresuscitation for more than 2 h may be detrimental in view ofan excessive net fluid retention.     

Etomidate and injection pain in children

Editor—We read with interest the study by Nyman and colleagues¹concerning etomidate and injection pain in children. It is wellaccepted that a single bolus dose of etomidate can result inadrenal suppression in adult patients, not only the criticallyill² but also in healthy young adults.³ Single     

EFFECT OF PROPOFOL, THIOPENTONE AND ETOMIDATE ON ADRENAL STEROIDOGENESIS IN VITRO

The i.v. anaesthetic agents propofol, thiopentone and etomidateinhibited ACTH-stimulated production of cortisol by guineapigdispersed adrenal cells in a dose-related manner. For two ofthe drugs, propofol and thiopentone, inhibition occurred overa similar concentration range: 2 x 10^–5 – 5 x 10^–4mol litre^–1. With etomidate, inhibition occurred overa much lower concentration range (5 x 10^–8 – 5 x10^–6 mol litre^–1). The concentrations of anaestheticwhich induced 50% inhibition of cortisol secretion were propofol1.7 x 10^–4, thiopentone 1.6 x 10^–4, and etomidate1.0 x 10^–7 mol litre^–1.     

In vitro Neuronal Production and Differentiation by Precursor Cells Derived from the Adult Human Forebrain

It has traditionally been held that the adult brain is incapableof significant self-repair, due in part to its inability togenerate new neurons. Nevertheless, rodents and birds have beenfound to harbor neural precursor cells in adulthood. We askedwhether the adult human brain might retain such precursors,by culturing samples of temporal lobe under conditions permissivefor neuronal differentiation, while exposed to ³H-thy-midine.Adult human temporal lobe cultures, derived from cortex, subcortex,and periventricular subependymal zone (SZ), were incubated for7–28 d, stained for neuronal and glial antigens, and autoradiographed.Neuron-like cells were found in explant outgrowths and monolayerdissociates of SZ and periventricular white matter, but notcortex; they expressed neuronal antigens including MAP-2, MAP-5,NF, and N-CAM, and were GFAP-. Neurons responded to K⁺ depolarizationwith rapid and reversible increases in intracellular Ca²⁺, withmuch greater increments than those noted in glia. Although mostneurons were not ³H-thymidine labeled, a small number of MAP-2⁺and MAP-5⁺/GFAP^– cells did incorporate ³H-thymidine, suggestingneuronal production from precursor mitosis. Rare ³H-thymidine⁺neurons were also found in cultures of subventricular whitematter; in these, GFAP⁺ astrocytic mitogenesis was common, whileO4⁺ oligodendrocytes, although the predominant cell type, werelargely postmitotic. Thus, the adult human forebrain harborsprecursor cells that retain the potential for neuronal productionand differentiation in vitro.     

Cardiovascular responses to graded doses of three catecholamines during lactic and hydrochloric acidosis in dogs

We have studied the cardiovascular effects of incremental dosesof three catecholamines in dogs subjected to lactic (LAC) andhydrochloric (HCl) acidosis. Fifty-four dogs were allocatedrandomly to one of three groups: control, LAC and HCl acidosis(n = 18 each group). In the acidotic models, 2 mol litre^–1of lactic acid (4 ml kg^–1 h^–1 or 2 mol litre^–1of HCl (1 ml kg^–1 h^–1) was infused i.v. until arterialpH was reduced to 7.00±0.1. Within each group, six dogsreceived one of three different drugs in logarithmically incrementaldoses: adrenaline 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 µg kg^–1min^–1, noradrenaline 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 µgkg^–1 min^–1 and dobutamine 5, 10, 20, 40, 80, 160µg kg^–1 min^–1 Cardiovascular variables weremonitored, with periodic measurements of plasma electrolyteand lactate concentrations. The pH reduction induced by HClor lactic acid was associated with a statistically significantincrease in mean pulmonary arterial pressure (MPAP), prominentespecially in the LAC group where MPAP increased from mean 18(SD 5) to 27 (6) mm Hg. In the acidotic models, the reductionin myocardial responsiveness to adrenaline or noradrenalinewas more prominent than that for the control for correspondingdoses of drugs. In the LAC group mean cardiac index decreasedsignificantly from 5.2 (1.8) to 2.2 (0.7) litre min^–1m^–2 after infusion of adrenaline 3.2 µg kg^–1min^–1 and decreased from 5.1 (1.1 to 2.4 (0.9) litre min^–1m^–1 after infusion of noradrenaline 3.2 µg kg^–1min^–1. In contrast, dobut amine showed dose-dependentincreases in cardiac index and heart rate in control, as wellas acidotic groups. The acute HCl acidosis induced greater hyperkalaemiathan the lactic acidosis. (Br. J. Anaesth. 1995; 74: 583–590)      

EFFECTS OF ETOMIDATE ON THE ADRENOCORTICAL AND METABOLIC ADAPTATION OF THE NEONATE

The effects of etomidate on corticosteroid synthesis were comparedwith those of methohexitone. We studied 40 neonates, 22 deliveredby elective and 18 by emergency Caesarean section. Apgar scores,blood sugar and plasma concentrations of cortisol and etomidatewere evaluated at birth and 2 and 6 h postpartum. There wasno difference in Apgar scores attributable to the inductionagent. The median cortisol concentrations in cord blood weresmall (136 nmol litre^–1; range 47–478 nmol litre¹,and 259 nmol litre^–1; range 58–1504 nmol litre^–1after elective and emergency sections, respectively). Duringthe study, cortisol concentrations increased in the infantsin the methohexitone groups and decreased in those in the etomidategroups; this effect was most evident 2 h after delivery (methohexitonegroups 245 nmol litre^–1, range 70–959 nmol litre^–1;etomidate groups 121 nmol litre^–1, range 56–320nmol litre^–1). There was no difference at 6h postpartum(methohexitone groups 183 nmol litre^–1, range 25–756nmol litre^–1; etomidate groups 190 nmol litre^–1,range 33–628 nmol litre^–1). The concentration changesduring the study period differed significantly (P < 0.005)with respect to the induction agent. Blood glucose concentrationswere small (mean (SD) in all 40 neonates 2h postpartum was 2.64(0.77) mmol litre^–1), and did not differ between the groups.There were 17 cases of moderate to severehypoglycaemia (bloodglucose concentrations less than 2.5 mmol litre^–1): ninein the etomidate group and eight in the methohexitone group.Mean (SD)fetal: maternal etomidate concentration ratio was 0.48(0.27) with an umbilical arterial etomidate concentration of83 (39) ng ml^–1 (340 (160) nmol litre^–1). The concentrationwas 9.3 (42) ng ml^–1 (38.0 (22) nmol litre^–1) at2 h and 6 (2.9) ng ml¹ (24.6–15 nmol litre^–1) at6 h. (Br. J. Anaesth. 1993; 70: 47–53)     

Dose-response relation of ornipressin with regard to vasoconstriction in human skin

We have studied the vasoconstrictor potency of ornipressin inthe skin of 30 volunteers. Subjects received intradermal injections(50µl) of five different concentrations of ornipressin(10^–4–10° u. ml^–1 in 0.9% saline) andplain 0.9– saline as a control. Immediately before injection,basal cutaneous blood flow in the test field was enhanced with1 % histamine. Capillary flux was measured by laser Dopplerflowmetry and the size of pallor was determined. Ornipressinwas effective at 10^–4 u. ml^–1 and had its largestconstrictor effect at concentrations of 10^–2 and 10^–1u. ml^–1 Larger concentrations were less effective in reducingcapillary flux. Interindividually, the most effective concentrationvaried between 10^–3 and 10^–1 u. ml^–1. Thesize of pallor grew in a dose-dependent manner but 10° u.ml^–1 always caused reddening in its centre. Capacitancevessels (skin colour) were more sensitive to ornipressin thanresistance vessels (capillary flux). The shortest latency ofvasoconstriction was obtained with concentrations of 10^–2and 10^–1 u. ml^–1. The results of this study suggestthat for haemostasis of the skin a concentration of ornipressin10^–2 u. ml^–1 is useful; this low concentration wouldreduce total dosage and unwanted side effects.     

EFFECT OF DOBUTAMINE ON OXYGEN SUPPLY AND UPTAKE IN HEALTHY VOLUNTEERS

We have measured the changes in Vo₂ and the Vo₂; D_o2 relationshipduringinfusion of dobutamine in healthy volunteers. Nine healthy,adult, non-obese, male physicians were infused with an incrementalinfusion of dobutamine starting at 2.5 µg kg^–1 min^–1increasing to 5.0 and then 7.5 y.g kg^–1 min^–1 for15 min each. Vo ₂ and cardiac index were measured every fiveminutes. Vo₂/(VO₂ m^–2) increased from a baseline of 128(SEM 6.1) ml min^–1 m^–2 to 159 (8.0)ml min¹ m^–2(P< 0.05) at 7.5 fig kg^–1 min^–1. The correspondingchanges for Do₂l (Do₂m^–2) were from 643 (35) ml min^–1m^–2 to 1240 (142) ml min^–1 m^–2 (P<0.05).The coefficient of correlation for pairs of Vo₂ and DO₂ values,at baseline and each dobutamine infusion in individual subjects,range from 0.89 to 0.99 (mean 0.95, SD 0.03). Dobutamine haspotent calorigenic effects; demonstration of a positive correlationbetween Vo₂ and Do₂ after infusion of dobutamine does not necessarilyimply an underlying tissue oxygen debt.