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Jugular vein temperature reflects brain temperature during hypothermia.

PURPOSE: The neuroprotective properties of mild to moderate hypothermia are well recognized but may not be employed correctly because brain temperature cannot usually be measured directly. This study investigated the jugular vein as a more accessible site that accurately reflects the actual brain temperature during mild, induced hypothermia. METHODS: We selected ten mongrel dogs (mean weight 12 +/- 2 kg) and measured temperatures of the brain, jugular vein, cisterna magna, pulmonary artery and rectum during hypothermia, including cooling and rewarming. The brain temperature needle probe was inserted 2.0 cm into the parenchyma. A temperature probe was placed in the cisterna magna with an epidural needle. Swan-Ganz thermistor probes measured the jugular venous and pulmonary artery blood temperatures. RESULT: The brain temperature decreased from 37.5 +/- 0.3 to 33.0 +/- 0.3 degrees C over an average 150 +/- 45 min cooling period. Stable cool was maintained for 245 +/- 32 min, followed by 165 +/- 50 min for rewarming from 33.5 +/- 0.3 to 37.5 +/- 0.3 degrees C. Jugular, cisterna magna and pulmonary arterial blood (PAB), but not rectal temperature, were close to brain temperature during stable cool. The mean jugular and cisterna magna temperatures were near the brain temperature at 0.1 degrees C higher and 0.1 degrees C lower, respectively. No significant effects of hypothermia were noted on hemodynamics in any phase. CONCLUSION: Jugular vein temperature, along with cisterna magna and pulmonary artery blood and rectal temperature, reflected brain temperature during hypothermia. The jugular vein and cisterna magna sites more sensitively reflected brain temperature than other sites.

Animals↗

Rapid temperature changes induce adenosine-mediated depression of synaptic transmission in hippocampal slices from rats (non-hibernators) but not in slices from golden hamsters (hibernators).

Disturbances in neuronal communication induced by rapid temperature changes are a risk in the context of accidental hypothermia and would be fatal for hibernators during arousal from hibernation. Therefore, we investigated the effects of rapid temperature changes on synaptically induced CA1 population spikes in hippocampal slices from golden hamsters (hibernators) and rats (non-hibernators). Temperature was changed ramp-like by 0.3 degrees C/min, which corresponds to the rise of body temperature in golden hamsters during arousal from hibernation. During cooling from 35 to 10-15 degrees C, the population spike amplitude increased, reached maximal values at 25-30 degrees C and 20-25 degrees C in hamster and rat slices, respectively, and then decreased with further cooling. During rewarming, hamster slices displayed the same temperature dependence as during cooling. In contrast, in rat slices dynamic effects of the temperature change occurred. These were most obvious in a strong depression of the spike amplitude during rewarming as compared to cooling. Above 26-29 degrees C, the depression was superimposed by an excitatory effect. The depression was largely attenuated by theophylline (100-200 microM) and thus seems to be based on an increase of the concentration of endogenous adenosine, which in turn may result from an imbalance in energy metabolism during warming. The lack of warming-related depression in hamster slices can be explained by a lower sensitivity for adenosine as compared to rat slices. In addition, a better resistance of metabolic balance against rapid temperature changes may prevent large elevations of endogenous adenosine in the hamster hippocampus. For hibernators, the avoidance of temperature change-induced disturbances of neuronal communication may be a prerequisite for safe arousal from hibernation.

Acclimatization↗

Physiological blocking of the mechanisms of cold death: theoretical and experimental considerations.

The cold inhibited functions of skin thermoreceptors, of the thermoregulation centre, and the respiration centre during deep hypothermia can be restored without rewarming the body. The methods used were developed to test the hypothesis that during deep hypothermia calcium ion concentration [Ca(2+)](i) in the cytoplasm increases. This causes a perturbation of cell metabolism, the impairment of cell membrane function that cause the inhibition of cell functioning, resulting in cell death. Such an increase in [Ca(2+)](i) most likely would result from an energy deficit in a deeply cooled cell, which would compromise the processes that maintain the [Ca(2+)](i) at about 10(-7) M. These processes require large amounts of energy since they occur against a large concentration gradient. With the use of EDTA the extracellular concentration of Ca(2+) has been lowered by 15-27%, so reducing the concentration gradient for Ca(2+) between the cell and the medium and in consequence facilitated the process the extrusion of cell Ca(2+).During a period of cooling, sufficient to impair normal functioning, the experimental lowering of blood Ca(2+) allowed the restoration of normal function without the need to rewarm. In such cases the animals survived after cooling the body to temperatures at which they would normally have succumbed. The data presented support the stated hypothesis that the impairment of cellular function in mammals by low temperatures is the result of an uncorrected rise in [Ca(2+)](i).

Journal Article↗

Preparation of equine isolated hepatocytes.

In this study a detailed description of the equine hepatocyte isolation procedure is presented. Livers were obtained from horses slaughtered at the local slaughterhouse. For blood removal and liver preservation the following steps are suggested: perfusion with the oxygenated HBSS (0-2 degrees C, with continuous flow of 500-800 ml/min for 3-6 min), protection from ischemia injury by flushing with ice-cold University of Wisconsin Solution (UW, flow rate of 500-800 ml/min), and finally immersion of the liver lobe in UW solution (2 degrees C) during its transport to the laboratory. For equine isolated hepatocyte preparation a "three-step" perfusion procedure was elaborated: rewarming, chelating and collagenase perfusion. We found optimal cell yield and viability under the following conditions: rewarming with UW (38 degrees C) for 8-14 min, chelating with calcium free Hanks' Balanced Salt Solution (HBSS, 38 degrees C) supplemented with 1 mM ethylene glycol-bis[beta-aminoethyl esther]-N,N,N'N'-tetracetic acid at the flow rate of 450 ml/min for 6 min and enzymatic digestion with HBSS supplemented with 0.1% collagenase at 38 degrees C and 450 ml/min flow rate for 8-27 min. These conditions consistently generated cell harvests of 21 x 10(6)+/-4.86 cells/g of perfused liver tissue with viability of 82.7%+/-10.2.

Animals↗

The efficacy of thymoxamine in primary Raynaud's phenomenon.

A randomised double-blind, three-way cross-over trial comparing oral thymoxamine 40 mg, oral thymoxamine 80 mg with a matched placebo was performed in 24 patients with primary Raynaud's phenomenon. The response to treatment was objectively assessed by monitoring digital skin temperature response for 7 min after exposure to a mild cold stimulus (20 C for 1 min). Thymoxamine treatment "normalised" rewarming responses in a statistically significant number of patients (P less than 0.01). Absolute digital temperatures and maximum rewarming rates were increased and the length of the latent period reduced (P less than 0.001). These effects were more pronounced with thymoxamine 80 mg than with thymoxamine 40 mg.

Adolescent↗

Impact of hypothermic selective cerebral perfusion compared with hypothermic cardiopulmonary bypass on cerebral hemodynamics and metabolism.

OBJECTIVE: Hypothermic selective cerebral perfusion (SCP) is widely used for cerebral protection during aortic arch surgery, but the effect of the absence of systemic perfusion on cerebrovascular dynamics it has never been established. This study explored the physiology of prolonged SCP compared to hypothermic cardiopulmonary bypass (HCPB) in pigs. METHODS: In this blinded protocol, 29 juvenile pigs (20-23 kg) were randomized after cooling on cardiopulmonary bypass (CPB) to 20 degrees C. Group I pigs (n=14) underwent 90 min of SCP, while group II (HCPB, n=15) underwent total body perfusion. Fluorescent microspheres were injected during perfusion and recovery, enabling calculation of total and regional cerebral blood flow (CBF). Cerebrovascular resistance (CVR), oxygen consumption and intracranial pressure (ICP) were also monitored. RESULTS: CBF decreased significantly (P=0.0001) during cooling, but remained at significantly higher levels with SCP than with HCPB throughout perfusion and recovery (P<0.0001). CVR was significantly lower with SCP than with HCPB throughout perfusion (P=0.04). Oxygen consumption fell significantly with cooling (P=0.0001), remained low during perfusion, and rebounded promptly with rewarming; with SCP it was significantly higher than with HCPB throughout the perfusion interval (P=0.03), and remained higher thereafter. ICP rose significantly less with SCP than with HCPB (P=0.02). CONCLUSION: We conclude that, compared with HCPB, SCP results in beneficial cerebral vasodilatation, as evidenced by significantly higher CBF and oxygen consumption during SCP, by prompt recovery of oxygen consumption after rewarming, and by significantly lower ICP during perfusion and in the post-bypass period.

Animals↗

Thromboxane A2-receptor blockade improves cerebral protection for deep hypothermic circulatory arrest.

OBJECTIVE: Following the use of deep hypothermic circulatory arrest in cardiac surgery, cerebral blood flow and cerebral oxygen metabolism are impaired. These may result from abnormal cerebral vasospasm. Powerful vasoconstrictors including endothelins and thromboxane A2 could mediate these processes. We investigated possible involvement of these two factors by assessing the effects of (a) phosphoramidon-an inhibitor of endothelin converting enzyme, and (b) vapiprost (GR32191B)-a specific thromboxane A2-receptor antagonist, on the recovery of cerebral blood flow and cerebral oxygen metabolism following deep hypothermic circulatory arrest. METHODS: A total of 18 1-week-old piglets were randomised into three groups (n = 6 per group). At induction, the control group received saline; group PHOS received phosphoramidon 30 mg kg-1 intravenously. Group VAP received vapiprost 2 mg kg-1 at induction and at 30 min intervals thereafter. All groups underwent cardiopulmonary bypass cooling to 18 degrees C, exposed to 60 min of deep hypothermic circulatory arrest, rewarmed and reperfused for 1 h. Cerebral blood flow was measured with radio-labeled microspheres: cerebral oxygen metabolism was calculated at baseline before deep hypothermic circulatory arrest and at 1 h of reperfusion and rewarming. RESULTS: In the control group, cerebral blood flow decreased to 40.2 +/- 2.0% of baseline after deep hypothermic circulatory arrest and cerebral oxygen metabolism decreased to 50.0 +/- 5.5% (P < 0.0005). The responses in group PHOS were similar. In group VAP, cerebral blood flow and cerebral oxygen metabolism were 64.3 +/- 10.6 and 80.1 +/- 9.8% of baseline, respectively, after deep hypothermic circulatory arrest. Thus, treatment with vapiprost significantly improved recovery of cerebral blood flow (P = 0.046) and cerebral oxygen metabolism (P = 0.020) following deep hypothermic circulatory arrest. No such improvement was seen after treatment with phosphoramidon. CONCLUSIONS: Thromboxane A2 mediates impairments in cerebral perfusion and metabolism following deep hypothermic circulatory arrest. These changes were attenuated by blockade of thromboxane A2-receptors using vapiprost. Endothelins are not shown to be involved. Better knowledge of injury mechanisms will enable development of more effective cerebral protection strategies and allow safer application of deep hypothermic circulatory arrest.

Animals↗

Determinants of cerebral perfusion during cardiopulmonary bypass.

The risk of postoperative neurologic dysfunction in patients undergoing cardiac surgery remains high despite continued improvements in myocardial protective strategies. Part of this neurologic morbidity can be attributed to patients' increased age and underlying pathology, but other factors adversely affecting cerebral blood flow and cerebral metabolism during cardiopulmonary bypass may also contribute. Particulate microembolization during cardiopulmonary bypass appears to be a major cause of postoperative neurologic dysfunction and the pH-stat method of carbon dioxide management during hypothermia may potentiate neurologic damage by allowing a greater embolic load to be delivered to the brain. Echocardiography and transcranial Doppler methods may contribute to reducing the incidence of cerebral embolization by recognizing the timing and number of microemboli. Although hypothermia confers cerebral protection, rewarming may unmask and perhaps potentiate any ischemic damage that occurred with embolization during hypothermia. Both the degree and speed of rewarming may be important factors contributing to the extent of ischemic damage and ultimately neurologic function. In addition, many other factors related to cardiopulmonary bypass can alter cerebral perfusion and metabolism, such as nonpulsatile flow, hemodilution, pressure autoregulation, anesthetic and cerebroprotective drugs, and the neuroimmune response to bypass. In this review, the major factors affecting cerebral blood flow during cardiopulmonary bypass are discussed and their relative importance evaluated with regard to postoperative neurologic function.

Brain↗

Arousal from torpor in the Chilean mouse-opposum (Thylamys elegans): does non-shivering thermogenesis play a role?

We examined the effect of norepinephrine injections on non-shivering thermogenesis (NST), rewarming rate, and metabolic cost during torpor arousal in warm- and cool-acclimated Chilean mouse-opposums, Thylamys elegans. Warm- and cool-acclimated animals did not display NST in response to NE injections. Values of VO2 (resting, after saline and NE injections) were not significantly different within treatments. Rewarming rates of warm-acclimated animals did not differ significantly from those in cool-acclimated animals. In contrast, the metabolic cost of torpor arousal was significantly affected by acclimation temperature. Warm-acclimated animals required more energy for arousal than cool-acclimated animals. Our study suggests that the main thermoregulatory mechanism during torpor arousal in this Chilean marsupial is shivering thermogenesis, and that its amount can be changed by thermal acclimation.

Animals↗

Identification of two chilling-regulated 1-aminocyclopropane-1-carboxylate synthase genes from citrus (Citrus sinensis Osbeck) fruit.

Diurnal change in the temperature below or above 12.5 degrees C hastens the degreening of citrus peel and elicits the phytohormone ethylene production in citrus fruit. Ethylene triggers the degradation of chlorophyll and synthesis of carotenoids in citrus peel. To investigate if ethylene is required for the degreening of citrus peel elicited by low temperatures, we studied the chilling-regulated gene expression of ACC synthase, one of the key enzymes catalyzing ethylene biosynthesis. We isolated and characterized a chilling-inducible 1-aminocyclopropane-1-carboxylate synthase (ACC synthase) gene, CS-ACS1, and a chilling-repressible gene, CS-ACS2, from citrus peel. The CS-ACS1 transcript 1.7 kb in length encodes a polypeptide of 483 amino acids (Mr 54,115, pI 6.63), whereas the CS-ACS2 transcript of 1.8 kb encodes a polypeptide of 477 amino acids (Mr 53,291, pI 6.72). Both genes showed a rapid but transient induction (within 2.4 h) of transcripts upon rewarming after the chilling (4 degrees C) treatment. After 24 h of incubation at room temperature, CS-ACS1 mRNA diminished to an undetectable level, whereas the CS-ACS2 mRNA regained its basal level of expression attained prior to the chilling treatment. Chilling-induced ethylene production and ACC accumulation were also observed upon rewarming. Both genes were also induced by the wound stress (excision). The protein synthesis inhibitor cycloheximide super-enhances the accumulation of both ACS transcripts at room temperature. Molecular analysis of the 3.3 kb genomic DNA of CS-ACS1 revealed that this gene consists of three introns and four exons. The intron 3 is exceptionally large ( 1.2 kb) and shares significant homology with mitochondrial DNA, supporting the intron-late theory.

Amino Acid Sequence↗

Localised cerebral phosphorus-31 MR spectroscopy in man before and immediately after coronary bypass surgery with hypothermic cardiopulmonary bypass.

Coronary artery bypass surgery classically is undertaken with hypothermic cardiopulmonary bypass (CPB). There is a high incidence of neuropsychological defects after cardiac surgery, which may be related to cerebral ischaemia during the rewarming period. In this study, phosphorus-31 magnetic resonance spectroscopy (31P MRS) was used to identify changes in cerebral 31P MR spectra in patients before and immediately after hypothermic CPB. Four neurologically normal patients undergoing coronary artery bypass surgery were studied. Localised cerebral 31P MRS (TR 5000 ms) was performed at 1.5 Tesla on each patient the day before and within an hour of completion of surgery. Peak areas for phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and beta ATP (betaATP) were measured. Metabolite peak area ratios and relative percentages of each 31P MR resonance with respect to the total 31P MR signal were calculated. In the post-operative MR spectra, each patient displayed a marked reduction in Pi/betaATP and increase in PCr/Pi ratios. Spectral changes in percentage metabolite signals following surgery varied both in magnitude and pattern between patients. In two patients there was an increased postoperative percentage PME and percentage PCr with a decrease in percentage betaATP. The converse was found in the other two patients, but all four subjects displayed a markedly decreased percentage Pi after CPB. These metabolite changes probably reflect rebound phosphorylation in the immediate postoperative period and suggest increased metabolic activity in the hyperaemic brain on rewarming from hypothermic CPB.

Aged↗

Sequential anastomosis of accessory renal artery to inferior epigastric artery in the management of multiple arteries in live related renal transplantation: a critical appraisal.

In live related renal transplant program, management of multiple renal arteries (MRA) is technically demanding and used to be considered a relative contraindication because of increased risk of vascular and urologic complications. We present a retrospective analysis of the outcome of grafts with MRA and suggest certain guidelines. Of the 680 live related kidney transplantations done, 53 allografts had MRA. Cases were grouped according to the reconstruction technique: group A, MRA reconstructed ex vivo into a single renal artery (n=27); group B, MRA with multiple anastomoses in vivo (n =13); group C, MRA with sequential revascularization using inferior epigastric artery (n=11). We compared serum creatinine, acute tubular necrosis, rejection rates and the rewarm ischemia time between the three groups. Overall patient survival and graft survival were excellent (100 and 96%). Mean serum creatinine at 1 yr did not differ significantly between the three groups. Rewarm ischemia time was significantly less in group C (p<0.01). Incidence of acute tubular necrosis and rejection episodes was also less in group C although the difference was statistically significant only between group C and group B. We conclude that allografts with MRA can be used successfully in a live related renal transplantation program. Bench reconstruction should be done whenever possible. For reconstruction of an accessory vessel, inferior epigastric artery with sequential revascularization is recommended.

Adolescent↗

Postischemic hypothermia fails to reduce ischemic injury in gerbil hippocampus.

The objective of this study was to determine whether postischemic hypothermia diminishes ischemic injury in gerbil hippocampus. Cerebral ischemia was produced by occluding both carotid arteries for 5 min, while maintaining the temperature of the cranium and rectum at 38 degrees C. Upon recirculation, the animals were divided into three groups: normothermic (38 degrees C), moderately hypothermic (33 degrees C), and deeply hypothermic (23 degrees C). In the normothermic group, cranial and rectal temperatures were maintained at 38 degrees C for 30 min and 2 h, respectively, prior to the removal of the temperature probes. In the moderately hypothermic group, cranial and rectal temperatures were reduced within 10 min to 33 degrees C for 1 h, and then rewarmed to 38 degrees C. In the deeply hypothermic group, rectal temperature was lowered within 10 min to 23 degrees C for 2 h prior to rewarming to 38 degrees C. After recovery for 1 week, the extent of histologic injury in the hippocampus was assessed in stained sections. Maximal injury was present in the CA1 subfield in all three groups. These results indicate that hippocampal injury was not diminished by postischemic hypothermia during the first 2 h of reperfusion. Thus, pharmacologic studies of postischemic protection in the gerbil model may not be strongly influenced by transient postischemic hypothermia.

Animals↗

Evaluation of digital blood pressure measured with the Omron F3 device as an index of brachial arterial pressure, under different thermal and hormonal conditions.

BACKGROUND: Devices that record from the finger have potential practical advantages for home monitoring of blood pressure. However, digital arterial pressure may vary substantially from that in the brachial artery, due to the influence of peripheral wave reflection. AIMS: (1) To compare digital arterial pressure, as measured with the Omron F3 device, with brachial arterial pressure and (2) to determine the effect on digital pressure of changing local vascular resistance. METHOD: The subjects were normotensive young adult non-smokers (12 males, 14 females). Pressures were recorded simultaneously from arm (using an Omron HEM-705CP) and finger with subjects seated and both recording sites at the level of the xiphisternum. Measurements were made at ambient temperatures of 19 degrees C and 30 degrees C; at rest, during brief contralateral hand cooling and after hand rewarming. RESULTS: In many cases, resting finger values differed substantially from arm values; sometimes by 20 mm Hg or more. The extent of individual variations was not correlated with gender or temperature. However, group pressure differences between the sites were greater in females at ovulation than at menstruation and greater at 30 degrees C than at 19 degrees C. For all groups, pressure differences between sites were attenuated during hand cooling and restored by rewarming. CONCLUSIONS: Finger blood pressure, as measured with the Omron F3, misestimates brachial blood pressure in a high proportion of normal subjects. This error is increased under circumstances associated with cutaneous vasodilation. The Omron F3 does not appear to be suitable for unsupervised home monitoring of blood pressure.

Adult↗

Autofluorescence properties of isolated rat hepatocytes under different metabolic conditions.

The contribution of endogenous fluorophores - such as proteins, bound and free NAD(P)H, flavins, vitamin A, arachidonic acid - to the liver autofluorescence was studied on tissue homogenate extracts and on isolated hepatocytes by means of spectrofluorometric analysis. Autofluorescence spectral analysis was then applied to investigate the response of single living hepatocytes to experimental conditions resembling the various phases of the organ transplantation. The following conditions were considered: 1 h after cells isolation (reference condition); cold hypoxia; rewarming-reoxygenation after cold preservation. The main alterations occurred for NAD(P)H and flavins, the coenzymes strictly involved in energetic metabolism. During cold hypoxia NAD(P)H, mainly the bound form, showed an increase followed by a slow decrease, in agreement with the inability of the respiratory chain to reoxidize the coenzyme, and a subsequent NADH reoxidation through alternative anaerobic metabolic pathways. Both bound/free NAD(P)H and total NAD(P)H/flavin ratio values were altered during cold hypoxia, but approached the reference condition values after rewarming-reoxygenation, indicating the cells capability to restore the basal redox equilibrium. A decrease of arachidonic acid and vitamin A contributions occurred after cold hypoxia: in the former case it may depend on the balance between deacylation and reacylation of fatty acids, in the latter it might be related to the vitamin A antioxidant role. An influence of physico-chemical status and microenvironment on the fluorescence efficiency of these fluorophores cannot be excluded. In general, all the changes observed for cell autofluorescence properties were consistent with the complex metabolic pathways providing for energy supply.

Animals↗

Autofluorescence spectroscopy of rat liver during experimental transplantation procedure. An approach for hepatic metabolism assessment.

Ischemia-reperfusion injury, a major cause of organ metabolic alterations and consequent dysfunction in liver transplantation, could be overcome by optimizing organ preservation procedures. The potential of autofluorescence analysis was investigated with the aim to define parameters suitable for in vivo monitoring tissue functionality. Spectrofluorometric analysis was performed on explanted rat livers during cold storage, under standard (4 degrees C University of Wisconsin medium for 20 h) and purposely damaging (4 degrees C Eurocollins medium for 20, 43 and 72 h) preservation conditions, and reperfusion (rewarming-reoxygenation). For both preservation conditions, cold hypoxia caused a signal amplitude increase, mainly attributable to NAD(P)H, and a spectral shape modification, ascribable to changes in the relative contributions of NAD(P)H and flavins, as a result of the tissue reduced state enhancement. Upon rewarming-reoxygenation the autofluorescence signal decreased with a rate depending on the preservation conditions. The time constant changed according to the extent of the liver functionality impairment, as assessed by conventional biochemical and histochemical analyses, thus providing a parameter exploitable for an in situ, real time monitoring of the efficacy of experimental preservation procedures.

Animals↗

Parathyroid hormone transport effects and hormonal processing in primary cultured rat proximal tubular cells.

The development of satisfactory cell culture models for the study of parathyroid hormone (PTH)-induced inhibition of Pi transport has proven difficult. Using subcellular fractionation techniques we investigated the response of primary cultures of rat proximal tubular cells to PTH-(1-34). Specific binding of 125I-bPTH-(1-34) occurred at 2 degrees C. After 5 min of rewarming, trypsin-releasable radioactivity decreased from 90 to 50%, indicating internalization of the ligand. Cell disruption, followed by density centrifugation with 17% Percoll either directly after binding at 2 degrees C or post-rewarming for 20 min, showed a shift of 125I label from the plasma membrane (5'-nucleotidase) to lysosomal fractions (beta-D-glucosaminidase), confirming the sequential occurrence of cell surface binding, internalization and transport to lysosomes of 125I-bPTH-(1-34). Reculture at 37 degrees C revealed steady accumulation of trichloroacetic acid-soluble radioactivity in the medium, indicating degradation of 125I-bPTH-(1-34). Phosphate transport in the absence of sodium was minimal. Incubation of the cells with bPTH-(1-34) resulted in up to 50% inhibition of sodium-dependent phosphate transport. Prior phosphate depletion abrogated the response to PTH.

Animals↗

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium.

This study was conducted to examine the effect of cardiopulmonary bypass surgery on the total and unbound plasma concentrations of fentanyl and the total plasma concentrations of alcuronium. Total fentanyl concentrations were measured by gas chromatography, the plasma protein binding of fentanyl by ultrafiltration, and alcuronium concentrations by high-performance liquid chromatography. Sixteen patients were studied. On initiation of cardiopulmonary bypass (CPB), there were mean decreases of 58.8 +/- 7.1% and 47 +/- 3.2% for total concentrations of fentanyl in plasma and haemoglobin in blood, respectively. The magnitude of these reductions in individual patients was significantly related (Spearman p = 0.65, P < 0.05). The unbound fraction of fentanyl rose from 0.23 to 0.34 after the start of CPB. The total fentanyl concentration remained relatively stable during bypass until near the end of CPB when the mean total concentration increased, coinciding with rewarming. The size of the increase was related to the body mass index (BMI) of the patient (Spearman p = 0.85, P < 0.01). The estimated elimination half-life of fentanyl using the grouped data was 4.7 h. The total alcuronium concentration in plasma fell by 29% on initiation of CPB and there was no increase on rewarming. The estimated elimination half-life of alcuronium using the grouped data was 234 min. Despite marked declines in the plasma concentrations of both drugs on initiation of CPB, suitable levels of anaesthesia were maintained throughout the procedure.

Adjuvants, Anesthesia↗