HEPATIC AND RENAL DISPOSITION OF PANCURONIUM AND GALLAMINE IN PATIENTS WITH EXTRAHEPATIC CHOLESTASIS

The plasma clearance of pancuronium in patients with extrahepaticcholestasis was 16% lower than in a control group (1.47±0.11ml min^–1 kg^–1 v. 1.76±0.21 ml min^–1kg^–1), but the difference was not significant. A significantincrease in the elimination half-life T^ß of pancuronium(from 141 to 224 min) and a significant increase in the volumeof the peripheral compartment (V₂ was found in patients withextrahepatic cholestasis when compared with control patients.There was a significantly lower cumulative biliary excretionof pancuronium (0.3±0.3% v. 10.9±3.2% in the controls)during the 48-h period of observation. The biotransformationand cumulative urinary excretion patterns of pancuronium revealedno significant differences between the two groups of patients.The increase of T^ß pancuronium in patients with extrahepaticcholestasis was mainly a consequence of the increase in thevolume of distribution. No significant differences in the plasmaclearance, T^ß or in the volume of distribution wereobserved with gallamine in the patients with extrahepatic cholestasiswhen compared with the control patients. The cumulative urinaryexcretion of gallamine during 48 h in both groups of patientswas approximately 100%. We concluded that in patients with cholestasisand normal glomerular filtration, gallamine is probably morereliable than pancuronium for neuromuscular blockade.     

PHARMACOKINETICS OF ATRACURIUM IN ANAESTHETIZED INFANTS AND CHILDREN

The pharmacokinetics of atracurium were studied in infants andchildren anaesthetized with isoflurane and nitrous oxide inoxygen. There were no significant differences in volume of distribution(area) (139 v. 152 ml kg^–1), clearance (5.1 v. 5.3 mlkg^–1 min^–1), T (2.1 v. 2.0 mim), or T^ß(19.1 v. 20.3 min) between children with normal hepatic andrenal function and those with moderately impaired hepatic functionpresenting for hepatic transplantation. There were significantdifferences in volume of distribution (area) (176 v. 139 mlkg^–1) and in clearance of atracurium (9.1 v.5.1 ml kg^–1min^–1) between infants and children with normal excretoryfunction. In infants the clearance of atracurium in ml m^–1min^–1 (153 v. 133) tended to be greater and the T andT^ß tended to be shorter (1.0 v. 2.0 and 13.6 v. 19.1)than in children with normal excretory function; however, thesetrends did not reach statistical significance. Plasma laudanosineconcentration was around 100 ng ml^–1 greater in patientswith liver disease than in normal children from 15–45min following a bolus of atracurium 0.5 mg kg^–1.     

FENTANYL PHARMACOKINETICS IN ANAESTHETIZED PATIENTS WITH CIRRHOSIS

Fentanyl kinetics were studied in patients with cirrhosis andin patients with normal hepatic and renal function undergoingsurgery under general anaesthesia, the latter group served asthe controls. Plasma fentanyl concentrations declined bi-exponentiallyin the controls with an average elimination half-life (T^ß)of 263 mm; total plasma clearance (C7) was 10.8mlmin^–1kg^–1,and total apparent volume of distribution (V^ß) 3 81litre kg^–1. No significant change was observed in patientswith cirrhosis: T( T^ß) was 304mm, Cl 11.3 ml min^–1kg^–1 and V^ß 4.41 litre kg^–1. These datasuggest that the elimination half-life of fentanyl is not primarilyinfluenced by the rate at which it is metabolized in the liver.     

PHARMACOKINETICS OF SINGLE-DOSE I.V.MORPHINE IN NORMAL VOLUNTEERS AND PATIENTS WITH END-STAGE RENAL FAILURE

Morphine 0.125 mgkg^–1 was administered i.v. to 11 normalsubjects and nine patients with chronic renal failure requiringregular haemodialysis. Plasma morphine concentrations were measuredusing high pressure liquid chromatography (HPLC). Although therewas considerable individual variation in both groups, mean plasmaconcentrations of morphine were significantly higher in thepatients with renal failure for 15 min after administration.The decay of plasma concentration fitted a three-compartmentmamillary pharmacokinetic model in all subjects. Derived values(mean $ SEM) of T^x, volume of distribution of the second compartment(V₂), total volume of distribution at steady state ( V^ss1) andtransfer rate constant from the first to the second compartment(k₁₂) were significantly different between groups. Mean valuesof terminal elimination half-life (T⁷) and total body clearancewere similar in the two groups. It was concluded that eliminationof unchanged morphine is not impaired significantly in patientswith chronic renal failure, although accumulation of morphine-3-glucuronideprobably occurs. Although the pharmacological effect of morphineis not related temporally to plasma morphine concentrations,the higher values in patients with renal failure may be implicatedin their increased sensitivity to the drug     

PHARMACOKINETICS OF ATRACURIUM AND LAUDANOSINE IN THE ELDERLY

The pharmacokinetics of a bolus dose of atracurium 0.6 mg kg^–1and its metabolite laudanosine were studied in 11 elderly (meanage 80.9 yr) and 10 young patients (mean age 23.8 yr) undergoingelective surgery. The elimination half-'life (T^ß)of atracurium was significantly longer in the elderly group(23.1 v. 20.1 min), but there was no significant differencebetween the two groups in clearance (Cl), the volume of distribution(Vß) or the mean residence time (MRT) of atracurium.Laudanosine T^ß was also significantly longer (229.1v. 173.1 min) and the clearance significantly slower (4.85 v.7.29 ml min^–1 kg^–1) in the elderly. There was, however,no significant difference in V^ß for laudanosine betweenthe two groups. These data suggest that atracurium depends toa small extent on the liver or the kidney for its metabolismand excretion, and that, as these routes of excretion are lessefficient in the elderly, T^ß is prolonged in thisage group. The deteriorating function of these organs with increasingage may also explain the altered pharmacokinetics of laudanosine. ^*Present address: Broadgreen Hospital, Thomas Drive, LiverpoolL14 3LB.     

DECAY OF NITROPRUSSIDE. II: IN VIVO

Clinical experience suggests that nitroprusside (SNP) concentrationsdecay more rapidly in vivo than in vitro. Plasma concentrationsof SNP were measured therefore in 20 patients at the end ofan infusion, with mean arterial pressure (MAP) and cyanide (HCN)concentrations. Plasma SNP concentrations (20–243 µglitre^–1; mean = 123.5 µg litre^–1), were relatedto infusion rate (r = 0.66, P < 0.001), and declined rapidlyto a mean (SD) of 7.7 (4.5) µg litre^–1 in 15 min.The decay of SNP correlated closely with the increase in arterialpressure (mean MAP vs log mean plasma SNP concentrations: r= –0.993, P < 0.001), and was probably biphasic: mean(SD) = 0.89 (0.62) min, T^ß= 14.3 (12) min. Mean plasmaHCN and mean plasma SNP concentrations decreased together (r= 0.955, P < 0.001), thus confirming that in vivo decompositionof the drug is the source of HCN.     

SUFENTANIL DISPOSITION IN PATIENTS UNDERGOING RENAL TRANSPLANTATION: INFLUENCE OF CHOICE OF KINETIC MODEL

We studied the disposition of sufentanil in 10 patients undergoingrenal transplantation, and compared the data with those fromeight healthy anaesthetized patients undergoing lower abdominalsurgery. Patients received sufentanil 2.5 µg kg^–1as part of a balanced anaesthetic technique. Central venousblood samples were collected at intervals up to 600 min, andplasma sufentanil concentrations assayed by radioimmunoassay.Pharmacokinetic parameters were calculated from drug concentration—timeprofiles by extended least squares non-linear regression analysis(ELSFIT) and by a model independent (Ml) approach using AUCand its first moment, AUMC. There were no differences (basedon Ml results) between the two groups for elimination half-life(T^ß) (renal failure: 188 min; anaesthetized controls:195 min), clearance (Cl) (1030 and 1093 ml min^–1) andapparent volume of distribution at steady state (V^ss) (223.0and 215.3 litre). Sufentanil binding to plasma proteins was91.4% in the renal patients and 92.2% in the healthy group (ns).Comparison of kinetic methods showed significant correlationof the individual estimates for T^ß, Cl and V^ss (P< 0.01). The mean absolute differences between methods were:T^ß2.7 min (95%limits: –26.2 to 31.5), Cl 36.5ml min^–1 (–5.5 to 78.4), V^ss –18.4 litre (–47.7to 10.9). When the mean estimate for the two methods ((ELSFIT+ Ml)/2) was compared with the difference, there was no correlationfor the estimates of Cl and V^ss. Ml tended to overestimate clearanceand underestimate volume of distribution. There was a significantrelationship between estimates for elimination half-life, witha slope greater than zero. Presented in part at the Anaesthetic Research Society, BristolMeeting, June 1988.     

PHARMACOKINETICS OF GALANTHAMINE (A LONG-ACTING ANTICHOLINESTERASE DRUG) IN ANAESTHETIZED PATIENTS

The pharmacokinetics of the long-acting anti-cholinesterasedrug, galanthamine, were investi-gated in eight patients. Afteri.v. injection of 0.3 mg kg^–1, the decrease in the serumconcen-tration of galanthamine followed a biexponential curve.The serum concentration decreased rapidly from 543±47ng ml^–1 to 128±14 ng ml^–1 be-tween 2 and30 min with a T of 6.42 ± 2.15 min, and then declinedmore slowly with a T^ß of 264±28min. Total serumclearance of galanthamine amounted to 5.37±0.87ml min^–1kg^–1, and the renal clearance was 1.36±0.10 mlmin^–1 kg^–1. The cumulative urinary excretion ofgalanthamine between 0 and 48 h after injection amounted to28.0±5.4% of the administered dose. The biliary excretionof galanthamine during 24 h amounted to 0.2 ±0.1% ofthe dose. There was no evidence of glucuronide or sulphate conjugationof galanthampine.     

Applying a physiological model to quantify the delay between changes in end-expired concentrations of sevoflurane and bispectral index

Background: The delay between changes in end-expired sevoflurane concentrationsand bispectral index (BIS) may be characterized by a ‘rateconstant’ (k_e0). A smaller k_e0 reflects a longer delay.Values for k_e0 vary substantially among studies. The questionarises how k_e0 depends on experimental conditions, includingventilation and apparatus. Methods: Increasing and decreasing sevoflurane concentrations were cyclicallydelivered to our validated model. First, we quantified theoreticalk_e0 values for distinct alveolar ventilations, estimating k_e0from sevoflurane tensions in alveolar space and grey matter.Secondly, we investigated the impact of experimental conditions.To predict BIS, the model was extended with a pharmacodynamicsection, including k_e0. Known values, matching theoretical values,were assigned to this k_e0. These were recovered from end-expiredconcentrations and BIS. Possible determinants of error (differencebetween assigned and recovered k_e0) were varied, that is fractionof dead space gas in end-expired gas (d), and time delays inmeasuring BIS (t_BIS) and end-expired concentrations (t_EE). Results: Theoretical k_e0s were 0.7, 0.53, 0.35, and 0.2 min^–1 foran arterial PCO₂ of 8, 6.67, 5.33 (normocapnia), and 4 kPa,respectively. For spontaneous ventilation, k_e0 = 0.53 min^–1.Recovered k_e0s depended on d and t (= t_BIS – t_EE) andwere smaller than assigned values (if t > 0). Errors increasedwith increasing d and t. For normocapnia, k_e0 was between 0.32and 0.23 min^–1 (d = 0.1; any t = 0–60 s). For spontaneousventilation, k_e0 was between 0.51 and 0.40 min^–1 (d =0–0.1; t = 5–20 s). Conclusions: Published k_e0s (0.22–0.53 min^–1), including ourown for sevoflurane-depressed spontaneous ventilation (0.48min^–1), are in the ranges dictated by investigation-specificconditions.     

ACUTE I.V. METHADONE KINETICS IN MAN: RELATIONSHIP TO CHRONIC STUDIES

Twenty-six patients were given methadone 10mg i v to obtainacute human kinetics. Plasma methadone concentrations from separate3- and 6-h studies were measured by radioimmunoassay Kineticparameters derived from triexponential NONLIN analysis showedthat T and T^ß were 2 and 30 min respectively, no reliableestimate for T could be obtained. The clearance was estimatedas 149 ±62 and 163 ± 49 ml min^–1 in the3- and 6-h studies respectively. These values were comparedwith those published for chronic administration, The difficultiesin determining accurate terminal half-life and clearance valuesfrom short duration studies are discussed; these difficultiesare accentuated by the long terminal half-life of methadone.Appropriate estimates of clearance may be derived from an acuteshort duration study provided that the average of triexponentialfits to individual patient data is used, even when data extendfor only 3 h. As might be anticipatedj no analysis producedappropriate terminal half-life values for this drug.     

LIGNOCAINE KINETICS DURING CARDIOPULMONARY BYPASS: Optimum Dosage and the Effects of Haemodilution

Lignocaine was administered to patients undergoing cardiopulmonarybypass at 28–29°C in bolus doses of 1.5, 2.5 and 3.5mg kg^–1. Plasma concentrations greater than 1.5 µgml^–1 were found briefly and inconsistently in patientsreceiving the usually recommended dose (1.5 mg kg^–1),but reliably for 14min in those receiving 2.5 mg kg^–1.The 3.5 mg kg^–1 dose produced statistically and clinicallysignificant decreases in mean arterial pressure. Examinationof calculated kinetic parameters showed a two-fold decreasein T, two-fold increases in Tß and V^es and unalteredCl_p and V_p when compared with those of unanaesthetized, normothermicpatients. The alteration in pharmacokinetics may be attributedlargely to decreased binding to albumin following haemodilution.     

Do fluid administration and reduction in norepinephrine dose improve global and splanchnic haemodynamics?

We studied global and splanchnic haemodynamics in patients withseptic shock, while reducing norepinephrine doses by progressivefluid loading administration. Ten patients (six female, fourmale, aged 39–86 yr, mean 61 yr) were assessed using atranspulmonary thermo-dye dilution technique to measure cardiacoutput, intrathoracic blood volume and total blood volume. Splanchnicblood flow was measured by the steady state indocyanine greentechnique using a hepatic venous catheter. Gastric mucosal bloodflow was estimated by regional carbon dioxide tension (P_CO2). Hydroxyethylstarch was infused in two stageswhile maintaining mean arterial pressure, allowing a reductionin norepinephrine dose from 0.54 to 0.33 to 0.21 µg kg^–1min^–1. Mean () heart rate significantly decreased, from 104 (13) to 94 (15) beats min^–1. Totalblood volume index (mean ()) increased from 2650 (638) to 3655 (885) ml m^–2, intrathoracic blood volumeindex from 888 (204) to 1050 (248) ml m^–2 and cardiacindex from 3.6 (1.0) to 4.0 (0.9) litres min^–1 m^–2.Splanchnic blood flow did not change significantly–eitherabsolute (from 0.81 to 0.98 litres min^–1 m^–2) orfractional (from 22.3% to 23.9%). Gastric mucosal (P_CO2) increased from 7.5 (2.5) to 9.0 (2.8) kPa. TheP₂ gap, i.e. the difference between regionaland end-tidal P₂, increased from 3.1 (2.5)to 4.0 (2.9) kPa. Marked individual variation in responses suggeststhat norepinephrine dose reduction by fluid loading in patientswith stabilized septic shock does not necessarily increase globalor splanchnic blood flow.     

FAZADINIUM PHARMACOKINETICS IN PATIENTS WITH LIVER DISEASE

Serum concentrations of fazadinium were measured in eight patientswith cirrhosis and eight patients with total binary obstructionwho underwent abdominal surgery. A biexponential decay of theconcentration was observed after a single i.v. injection offazadinium. A two-compartment open model was used in the pharmacokineticanalysis of the data. The pharmacokinetic parameters were comparedwith those obtained in 11 normal patients. A 90% increase inboth the distribution half-life (T), from 10 min to 19 min,and in the elimination half-life (T^ß)3 from 82 minto 153 min, was observed in patients with cirrhosis. These changesare the consequence of an increase (60%) in the total apparentvolume of distribution {V). In contrast, the plasma clearance(CI) was not modified. Total biliary obstruction was associatedwith very little change in the pharmacokinetics of fazadinium,T^ß being slightly prolonged to 103 min. No significantdecrease in plasma clearance was observed in patients with cholestasis.These results suggest that biliary excretion of fazadinuim doesnot represent an important supplementary pathway to renal excretion.The relatively rapid decrease of the blood concentration offazadinium compared with other non-depolarizing relaxants isprobably related to another extrarenal pathway of eliminationwhich has not yet been identified.     

An investigation to show the effect of lung fluid on impedance cardiac output in the anaesthetized dog

Background. Accumulation of lung fluid in the critically illpatient is believed to attenuate impedance cardiac output (CO_IC)measurements. However, this phenomenon has never been shownexperimentally. Methods. In eight anaesthetized and ventilated dogs (weight15–22 kg) a high-precision flow probe was placed on theascending aorta via a left thoracotomy incision and the directcardiac output (CO_FP) was measured. Simultaneous CO_IC measurementswere made using a RheoCardioMonitor (ACMA, Singapore). Lungoedema was induced by intravenous oleic acid 0.1 mg kg^–1.Lung fluid was assessed by the decrease in basal thoracic impedance(Z_b). Percentage errors between the two methods (CO_IC–CO_FP)were calculated and compared as Z_b decreased at 1 intervals. Results. During the experiment mean Z_b decreased from 35.9 (SD5.2) to 27.8 (6.5) (P=0.0037). This occurred over a periodof 225 (range 112–338) min and Z_b decreased by 1 every51 (22–68) min. The presence of excessive lung fluid wasconfirmed at post-mortem. Before lung oedema was induced, CO_ICwas 1.5 (0.6) litre min^–1 and the corresponding valueof CO_FP was1.5 (0.7) litre min^–1 (data from eight dogs).As Z_b decreased, and lung fluid accumulated, the error betweenCO_IC and CO_FP widened (P<0.0001, ANOVA for repeated measures).Eventually, CO_IC decreased to 0.7 (0.3) litre min^–1 andthe corresponding value of CO_FP was1.2 (0.3) litre min^–1(Z_b=5 , data from six dogs). Mean arterial pressure, centralvenous pressure and systemic vascular resistance were kept constant. Conclusion. The presence of lung fluid attenuates CO_IC measurementswith respect to CO_FP.     

PHARMACOKINETICS AND ANALGESIC EFFECT OF KETAMINE IN MAN

The pharmacokinetics and analgesic effect of i.v. ketamine indoses of 125 µg kg^–1 and 250 µg kg^–1were determined in five healthy volunteers. Analgesia was measuredwith the submaximal effort tourniquet test. Both doses of ketamineprolonged the period of pain-free ischaemic exercise while theplasma ketamine concentration was greater than 100 ng ml^–1.Ketamine was distributed rapidly (T^z=17 min). The eliminationhalf-life was 186 min.     

Actions of morphine on noradrenaline efflux in the rat locus coeruleus are mediated via both opioid and {alpha}2 adrenoceptor mechanisms

A recent report showed that morphine inhibited [³H]clonidinebinding to human platelet ₂ receptors. As the analgesic effectsof morphine and clonidine are clinically additive, we investigatedthe possibility that morphine might stimulate ₂ receptors or₂ mechanisms in rat locus coeruleus (LC) slices. StimulatedLC noradrenaline efflux was measured by fast cyclic voltammetry.Cumulatively applied morphine 10^–8–10^–4mollitre^–1 had no effect on noradrenaline efflux evoked bypseudo-single-pulse stimulations (20 pulses at 100 Hz) whilethe ₂ agonist dexmedetomidine 2 x 10^–10–10^–7mol litre^–1 decreased efflux of noradrenaline in a concentration-dependentmanner. Administration of single concentrations of morphine10^–6–10^–4 mol litre^–1 significantlydecreased efflux of noradrenaline (by 22% and 17%, respectively)and attenuated the effect of dexmedetomidine in a concentration-dependentfashion. Morphine 10^–6–10^–4mol litre^–1also decreased efflux of noradrenaline on long stimulus trains(50 pulses at 50 Hz). These data suggest that the analgesicpotentiation of ₂ and opioid agonists is not mediated via LC₂ receptors.     

VENTILATORY RESPONSES TO CARBON DIOXIDE IN CHILDREN DURING NITROUS OXIDE-HALOTHANE ANAESTHESIA

The ventilatory response to carbon dioxide was studied in 12unpremedicated children, aged 20–68 months, weighing between10 and 20 kg, under nitrous oxide-halothane anaesthesia. Tidalvolume (VT) and end-tidal carbon dioxide tension (PE'_CO2) werecontinuously measured by pneumotachograph and capnograph. Minuteventilation (), respiratory rate (f), mean in-spiratory flow (VT) and effective inspiratorycycle (T1/T^tot) were calculated during anaesthesia at threedifferent inspired halothane concentrations (0.5, 7 and 1.5%).The ventilatory response to carbon dioxide was determined byrelating the increase in ventilation during exposure to 2% carbondioxide to the change in end-tidal carbon dioxide concentration.When the inspired concentration of halothane increased, therewere significant decreases in , VT, , and a significant increase in PE'_CO2 The slope of the carbon dioxide response under lightnitrous oxide-halothane anaesthesia (0.5% halothane) was relativelyflat (18.64 ml min^–1 kg^– mm Hg^-1) when comparedwith the mean values published for anaesthetized adults, childrenor neonates. When the inspired concentration of halothane wasincreased, the slope decreased significantly (39% of initialvalue at 1 % inspired halothane, 26% at 1.5%). The additionof carbon dioxide produced significant increases in , VT and but no change in respiratory rate. No statistical differencewas observed in the slope of carbon dioxide response betweenthe initial and "control" periods which were measured at thesame inspired halothane concentration (0.5%).     

VENTILATORY EFFECTS AND PLASMA CONCENTRATION OF MORPHINE IN MAN

The relationship between the plasma concentration of morphineand morphine-induced changes in ventilation and the ventilatoryresponse to carbon dioxide was studied in 17 healthy adultsundergoing elective surgery under general anaesthesia. Eachsubject was given morphine sulphate 0.15 mg kg^–1 i.m.;ventilation (E), end-tidal Pco₂(PE'_CO2), mixed venous PV_CO2(P_CO2)and ventilatory response to carbon dioxide (E/P_CO2) were measured before and within 90 min afterinjection. Mixed venous P_CO2 and E/P_CO2were measured by standard rebreathing methods; plasma morphineconcentration was measured by radioimmunoassay. Maximum plasmamorphine ranged from 30 to 120 ng ml^–1, between 4 and60 min after injection. There was a significant increase inmixed venous PE'_CO2 (P<0.001), and PE'_CO2 (P<0.01) aftermorphine while E decreased insignificantly. Morphine displaced the carbon dioxide responsecurve to the right (P<0.01) and E/P_CO2decreased from 12.3 to 10.0 litre min^–1 kPa^–1 (P<0.05).The magnitude of changes in E and E/P_CO2 were not relatedto the peak plasma concentration of morphine or to the meanconcentration immediately before and after the carbon dioxideresponse measurement. Plasma concentrations of morphine, underthe conditions of the present study, are not an objective indicatorof pharmacological activity between one patient and another. Presented in part at the VI World Congress of Anaesthesiology,MexicoCity, Mexico, April 1976     

Inhibition of active sodium absorption leads to a net liquid secretion into in vivo rabbit lung at two levels of alveolar hypoxia

Active sodium transport across alveolar epithelium is knownto contribute to the resolution of pulmonary oedema. We haveattempted to assess whether sodium transport is essential toprevent liquid accumulation in healthy pulmonary alveoli exposedto mild hypoxia, and whether its contribution to liquid absorptiondiffers between mild and moderate levels of hypoxia. In twenty-fouranaesthetized adult rabbits we used direct bronchial cannulationto measure liquid movement from the liquid-filled left lungover 3.5 h. Half of the rabbits were studied at a level of mixedvenous (and alveolar) oxygen partial pressure, P_O2, of 6.5 kPaand half at 4.5 kPa. P_O2 was altered by changing the inspiredoxygen fraction in the ventilated right lung. Alveolar hydrostaticpressure was 0.3 kPa. In each group of 12, six animals withinhibitors of sodium transport in the isosmotic instillate werecompared with six controls. We have shown an alveolar liquidsecretion (approximately 0.6 µl min^–1 (kg bodyweight)^–1) in the presence of inhibitors of active transportand an absorption (approximately 4 µl min^–1 (kgbody weight)^–1) in controls. Changing P_O2 had no influenceon these movements. We conclude that, in this model of pulmonaryoedema, active sodium transport appears to be essential forprevention of alveolar liquid accumulation via secretion. Furthermore,the contribution of active sodium transport to liquid absorptionremains constant at oxygen tensions between 4.5 and 6.5 kPa. Br J Anaesth 2001; 87: 897–904     

HALF-LIFE OF ANGIOTENSIN II IN THE CONSCIOUS AND BARBITURATE-ANAESTHETIZED RAT

The half-life (T) of angiotuuin II was measured in rats withchronic indwelling catheters. In conscious animals T was 14.8±2.5s; during anaesthesia T increased by 60%. Anaesthesia deacasedthe control arterial pressure, but did not alter the sensitivityto injected angiotensin II. The causes and consequences of thischange in angiotcmin catabolism are discussed.