Human adult cardiac autonomic innervation: Controversies in anatomical knowledge and relevance for cardiac neuromodulation.

BACKGROUND: Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These treatments require detailed knowledge of the spatial location and distribution of cardiac autonomic nerves, however, there are controversies on this subject in humans. OBJECTIVE: To provide a systematic overview of current knowledge on human anatomy of the cardiac autonomic nervous system. RESULTS: In contrast to the often claimed assumption that human preganglionic sympathetic cardiac neurons originate mainly from thoracic spinal segments T1-T4 or T5, there is ample evidence indicating involvement of cervical spinal segment C8 and thoracic spinal segments below T5. Whether cervical ganglia besides the stellate ganglion play a role in transmission of cardiac sympathetic signals is unclear. Similarly, there is debate on the origin of cardiac nerves from different thoracic ganglia. Most human studies report thoracic cardiac nerves emerging from the first to fourth thoracic paravertebral ganglia; others report contributions from the fifth, sixth and even the seventh thoracic ganglia. There is no agreement on the precise composition of nerve plexuses at the cardiac level. After years of debate, it is generally accepted that the vagal nerve contributes to ventricular innervation. Vagal distribution appears higher in atria, whereas adrenergic fibers exceed the number of vagal fibers in the ventricles. CONCLUSION: Anatomy of the human cardiac autonomic nervous system is highly variable and likely extends beyond generally assumed boundaries. This information is relevant for thoracic epidural anesthesia and procedures targeting neuronal modulation of cardiac sympathetic innervation.

Association of preoperative anaemia with postoperative morbidity and mortality: an observational cohort study in low-, middle-, and high-income countries.

BACKGROUND: Anaemia is associated with poor postoperative outcomes, but few studies have described the impact of preoperative anaemia in low- and middle- (LMICs), and high-income countries (HICs). METHODS: This was a planned analysis of data collected during an international 7 day cohort study of adults undergoing elective inpatient surgery. The primary outcome was in-hospital death, and the secondary outcomes were in-hospital complications. Anaemia was defined as haemoglobin <12 g dl-1 for females and <13 g dl-1 for males. Hierarchical three-level mixed-effect logistic regression models were constructed to examine the associations between preoperative anaemia and outcomes. RESULTS: We included 38 770 patients from 474 hospitals in 27 countries of whom 11 675 (30.1%) were anaemic. Of these, 6886 (17.8%) patients suffered a complication and 198 (0.5%) died. Patients from LMICs were younger with lower ASA physical status scores, but a similar prevalence of anaemia [LMIC: 5072 (32.5%) of 15 585 vs HIC: 6603 (28.5%) of 23 185]. Patients with moderate [odds ratio (OR): 2.70; 95% confidence interval (CI): 1.88-3.87] and severe anaemia (OR: 4.09; 95% CI: 1.90-8.81) were at an increased risk of death in both HIC and LMICs. Complication rates increased with the severity of anaemia. Compared with patients in LMICs, those in HICs experienced fewer complications after an interaction term analysis [LMIC (OR: 0.92; 95% CI: 0.87-0.97) vs HIC (OR: 0.86; 95% CI: 0.84-0.87); P<0.01]. CONCLUSIONS: One-third of patients undergoing elective surgery are anaemic. These patients have an increased risk of complications and death. The prevalence of anaemia is similar amongst patients in LMICs despite their younger age and lower risk profile. CLINICAL TRIAL REGISTRATION: ISRCTN51817007.

Determination of the median effective dose (ED50 ) of spinal chloroprocaine in labour analgesia.

The primary goal of this study was to determine the median effective dose (ED50 ) of spinal chloroprocaine for labour analgesia. Thirty-eight parturients requesting neuraxial analgesia were enrolled. Doses of 1% chloroprocaine were determined by the technique of up-down sequential allocation, with an initial dose of 20 mg and steps of 2 mg. The chloroprocaine spinal dose was given as the spinal component of a combined spinal-epidural, which was then supplemented with an epidural dose of 7.5 µg sufentanil in 7 ml saline. Effective analgesia was defined as a score ≤ 10 mm within 15 min on a 100-mm visual analogue pain scale. Using the isotonic regression estimator method, the ED50 of chloroprocaine for the spinal component of a combined spinal-epidural for labour was calculated to be median (95%CI) 12.0 (9.3-17.0) mg.

In-vivo validation of a new clinical tool to quantify three-dimensional myocardial strain using ultrasound.

Three-dimensional (3D) strain analysis based on real-time 3-D echocardiography (RT3DE) has emerged as a novel technique to quantify regional myocardial function. The goal of this study was to evaluate accuracy of a novel model-based 3D tracking tool (eSie Volume Mechanics, Siemens Ultrasound, Mountain View, CA, USA) using sonomicrometry as an independent measure of cardiac deformation. Thirteen sheep were instrumented with microcrystals sutured to the epi- and endocardium of the inferolateral left ventricular wall to trace myocardial deformation along its three directional axes of motion. Paired acquisitions of RT3DE and sonomicrometry were made at baseline, during inotropic modulation and during myocardial ischemia. Accuracy of 3D strain measurements was quantified and expressed as level of agreement with sonomicrometry using linear regression and Bland-Altman analysis. Correlations between 3D strain analysis and sonomicrometry were good for longitudinal and circumferential strain components (r = 0.78 and r = 0.71) but poor for radial strain (r = 0.30). Accordingly, agreement (bias ± 2SD) was -5 ± 6 % for longitudinal, -5 ± 7 % for circumferential, and 15 ± 19 % for radial strain. Intra-observer variability was low for all components (intra-class correlation coefficients (ICC) of respectively 0.89, 0.88 and 0.95) while inter-observer variability was higher, in particular for radial strain (ICC = 0.41). The present study shows that 3D strain analysis provided good estimates of circumferential and longitudinal strain, while estimates of radial strain were less accurate between observers.

Influence of variations in systemic blood flow and pressure on cerebral and systemic oxygen saturation in cardiopulmonary bypass patients.

BACKGROUND: Although both pressure and flow are considered important determinants of regional organ perfusion, the relative importance of each is less established. The aim of the present study was to evaluate the impact of variations in flow, pressure, or both on cerebral and whole-body oxygen saturation. METHODS: Thirty-four consenting patients undergoing elective cardiac surgery on cardiopulmonary bypass were included. Using a randomized cross-over design, four different haemodynamic states were simulated: (i) 20% flow decrease, (ii) 20% flow decrease with phenylephrine to restore baseline pressure, (iii) 20% pressure decrease with sodium nitroprusside (SNP) under baseline flow, and (iv) increased flow with baseline pressure. The effect of these changes was evaluated on cerebral (Sc(O2)) and systemic (Sv(O2)) oxygen saturation, and on systemic oxygen extraction ratio (OER). Data were assessed by within- and between-group comparisons. RESULTS: Decrease in flow was associated with a decrease in [from 63.5 (7.4) to 62.0 (8.5) %, P<0.001]. When arterial pressure was restored with phenylephrine during low flow, Sc(O2) further decreased from 61.0 (9.7) to 59.2 (10.2) %, P<0.001. Increase in flow was associated with an increase in Sc(O2) from 62.6 (7.7) to 63.6 (8.9) %, P=0.03, while decreases in pressure with the use of SNP did not affect Sc(O2). Sv(O2) was significantly lower (P<0.001) and OER was significantly higher (P<0.001) in the low flow arms. CONCLUSIONS: In the present elective cardiac surgery population, Sc(O2) and Sv(O2) were significantly lower with lower flow, regardless of systemic arterial pressure. Moreover, phenylephrine administration was associated with a reduced cerebral and systemic oxygen saturation.

Relation between mixed venous oxygen saturation and cerebral oxygen saturation measured by absolute and relative near-infrared spectroscopy during off-pump coronary artery bypass grafting.

BACKGROUND: We hypothesized that previously reported contradictory results regarding the equivalence of mixed venous (Smv(O(2))) and cerebral (rS(c)O(2)) oxygen saturation might be related to time delay issues and to measurement technology. In order to explore these two factors, we designed a prospective clinical study comparing with relative (INVOS(®)) and absolute (Foresight(®)) rS(c)O(2) measurements. METHODS: Forty-two consenting patients undergoing elective off-pump coronary artery bypass grafting were included. Two INVOS and two Foresight sensors continuously registered rS(c)O(2). Smv(O(2)) was measured continuously via a pulmonary artery catheter. Data were assessed by within- and between-group comparisons and correlation analysis. RESULTS: A similar time delay of 19 (4) and 18 (4) s was found for compared with rS(c)O(2) measurements by Foresight and INVOS, respectively, during haemodynamic changes. After adjusting for this time delay, the correlation between Smv(O(2)) and rS(c)O(2) increased from r=0.25 to 0.75 (P<0.001) for Foresight, and from r=0.28 to 0.73 (P<0.001) for INVOS. Comparison of Foresight and INVOS revealed significant differences in absolute rS(c)O(2) values (range 58-89% for Foresight and 28-95% for INVOS). Changes in rS(c)O(2) in response to acute haemodynamic alterations were significantly more pronounced with INVOS compared with Foresight (P<0.001). CONCLUSIONS: Considering the important time delay with Smv(O(2)), rS(c)O(2) seems to reflect more appropriately acute haemodynamic alterations. This might suggest its use as a valid alternative to invasive monitoring of tissue oxygen saturation. Relative and absolute rS(c)O(2) measurements demonstrated significant differences in measured rS(c)O(2) values and in the magnitude of rS(c)O(2) changes during haemodynamic alterations.

Anaphylactic shock and hyperfibrinolysis measured with thromboelastography.

This case report presents anaphylactic shock in which hyperfibrinolysis was diagnosed with Thromboelastography (TEG). A 45 year old female patient was scheduled for vacuum-assisted wound closure. At induction, she developed an anaphylactic shock that stabilized after standard treatment. TEG analysis revealed hyperfibrinolysis. Surgery was delayed and there were no signs of spontaneous bleeding. A repeat TEG analysis performed 30 minutes later showed a completely normalized coagulation pattern. Few reports have documented the association between anaphylactic shock and hyperfibrinolysis. This case illustrates the transient and short-lived nature of the phenomenon. The mechanisms and potential consequences are discussed.

The value of pulse pressure and stroke volume variation as predictors of fluid responsiveness during open chest surgery.

SUMMARY: We investigated the ability of pulse pressure variation and stroke volume variation to predict fluid responsiveness during mechanical ventilation in patients undergoing open chest surgery by comparing their respective correlations with cardiac output changes induced by leg elevation. Serial leg elevation manoeuvres were performed before and after sternotomy in 15 patients scheduled for elective off-pump coronary bypass surgery. Under closed chest conditions, both pulse pressure variation and stroke volume variation correlated well with the induced cardiac output changes (r = 0.856, p = 0.002 and r = 0.897, p = 0.0012, respectively). These correlations were lost for both parameters following sternotomy. Our data show that pulse pressure variation and stroke volume variation are valid predictors of fluid responsiveness under closed chest conditions but that this property no longer holds when the chest is open.

Gravity is an important determinant of oxygenation during one-lung ventilation.

BACKGROUND: The role of gravity in the redistribution of pulmonary blood flow during one-lung ventilation (OLV) has been questioned recently. To address this controversial but clinically important issue, we used an experimental approach that allowed us to differentiate the effects of gravity from the effects of hypoxic pulmonary vasoconstriction (HPV) on arterial oxygenation during OLV in patients scheduled for thoracic surgery. METHODS: Forty patients with chronic obstructive pulmonary disease scheduled for right lung tumour resection were randomized to undergo dependent (left) one-lung ventilation (D-OLV; n=20) or non-dependent (right) one-lung ventilation (ND-OLV; n=20) in the supine and left lateral positions. Partial pressure of arterial oxygen (PaO2) was measured as a surrogate for ventilation/perfusion matching. Patients were studied before surgery under closed chest conditions. RESULTS: When compared with bilateral lung ventilation, both D-OLV and ND-OLV caused a significant and equal decrease in PaO(2) in the supine position. However, D-OLV in the lateral position was associated with a higher PaO2 as compared with the supine position [274.2 (77.6) vs. 181.9 (68.3) mmHg, P<0.01, analysis of variance (ANOVA)]. In contrast, in patients undergoing ND-OLV, PaO2 was always lower in the lateral as compared with the supine position [105.3 (63.2) vs. 187 (63.1) mmHg, P<0.01, ANOVA]. CONCLUSION: The relative position of the ventilated vs. the non-ventilated lung markedly affects arterial oxygenation during OLV. These data suggest that gravity affects ventilation-perfusion matching independent of HPV.

Differential effects of lumbar and thoracic epidural anaesthesia on the haemodynamic response to acute right ventricular pressure overload.

BACKGROUND: The safety of epidural anaesthesia in patients at risk for right ventricular pressure overload remains controversial. We compared the haemodynamic effects of vascular and cardiac autonomic nerve block, induced by selective lumbar (LEA) and high thoracic epidural anaesthesia (TEA), respectively, in an animal model subjected to controlled acute right ventricular pressure overload. METHODS: Eighteen pigs were instrumented with epidural catheters at the thoracic (T) and lumbar (L) level and received separate injections at T2 (1 ml) and L3 (4 ml) with saline (s) or bupivacaine 0.5% (b). Three groups of six animals were studied: (i) a control group (Ls+Ts), (ii) LEA group (Lb+Ts), and (iii) TEA group (Ls+Tb). Haemodynamic measurements including biventricular pressure-volumetry were performed. Right ventricular afterload was then increased by inflating a pulmonary artery (PA) balloon. Measurements were repeated after 30 min of sustained right ventricular afterload increase. RESULTS: LEA decreased systemic vascular resistance (SVR) and did not affect ventricular function. TEA had minor effects on SVR but decreased left ventricular contractility while baseline right ventricular function was not affected. Control and LEA-treated animals responded similarly to a PA balloon occlusion with an increase in right ventricular contractility and heart rate. Animals pretreated with a TEA did not show this positive inotropic response and developed low cardiac output in the presence of right ventricular pressure overload. CONCLUSIONS: In contrast to LEA, TEA reduced the haemodynamic tolerance to PA balloon occlusion by inhibiting the right ventricular positive inotropic response to acute pressure overload.

Load-sensitivity of regional tissue deformation in the right ventricle: isovolumic versus ejection-phase indices of contractility.

OBJECTIVE: Doppler myocardial imaging is increasingly being used to evaluate regional and global cardiac function. Quantitative measurements of tissue deformation obtained during ejection as well as isovolumic contraction have been proposed as new indices of contractility; however, their load-sensitivity remains a matter of controversy. Maximum strain rate (SR(max)) and isovolumic strain acceleration (ISA(max)) were compared with regard to sensitivity for inotropic state, heart rate and loading conditions in the right ventricle (RV), using pressure-volume analysis as the reference method. DESIGN: Prospective animal study. SETTING: University hospital laboratory. INTERVENTIONS: RV contractility was measured at baseline, after inotropic modulation with esmolol and dobutamine, at different atrial pacing rates and during controlled alterations of RV preload and afterload. MAIN OUTCOME MEASURES: RV contractility was assessed with the slope (Mw) of preload recruitable stroke work and longitudinal SR(max) and ISA(max). RESULTS: SR(max) and ISA(max) reflected the drug-induced changes in contractility, while only ISA(max) increased with higher pacing rates. Acute lowering of RV preload did not affect either of the indices studied. In contrast, an increase in RV afterload consistently decreased SR(max) (from 1.05 (SD 0.41) to 0.73 (SD 0.26) s(-1),p = 0.03) but had variable effects on ISA(max) and Mw. However, a significant correlation was found between proportional changes in ISA(max) and Mw during high-afterload conditions (r2 = 0.89, p = 0.005). CONCLUSIONS: Both SR(max) and ISA(max) reflected changes in RV contractility. ISA(max) was less sensitive to changes in RV afterload than SR(max) and may therefore be a more robust index of global RV contractility.

Accuracy of cardiac output measurements with pulse contour analysis (PulseCO) and Doppler echocardiography during off-pump coronary artery bypass grafting.

BACKGROUND AND OBJECTIVE: During off-pump coronary bypass grafting, surgical manipulation and dislocation of the heart may cause cardiovascular instability. Monitoring of cardiac output facilitates intraoperative haemodynamic management but pulmonary artery catheters are often considered too invasive. Pulse contour analysis and transoesophageal echocardiography could serve as alternatives, but there is controversy about their accuracies. We validated pulse contour analysis using a standard radial arterial catheter (PulseCO) and aortic Doppler flowmetry with transoesophageal echocardiography in patients undergoing off-pump coronary bypass surgery. Pulmonary arterial thermodilution served as the reference technique. METHODS: In 20 patients undergoing off-pump coronary bypass, cardiac output was measured with bolus thermodilution (COTD), pulse contour analysis (COPC), and transoesophageal echocardiography (COecho) at fixed time intervals during the procedure. Data were compared using linear regression and Bland-Altman analysis. At the end of the procedure, dobutamine was infused at a rate of 2.5 microg kg(-1) min(-1) in six patients to study the agreement between methods in quantifying changes in cardiac output. RESULTS: Comparison between COPC and COTD showed a bias +/- limits of agreement of -0.03 +/- 1.30 L min(-1) (mean error 29%). Doppler echocardiography was not always feasible when the heart was displaced from the oesophagus and had lower accuracy: bias +/- limits of agreement vs. COTD was 0.45 +/- 1.93 (mean error 43%). Increases in cardiac output induced by dobutamine were well quantified both by pulse contour analysis (COPC = 0.76 x COTD + 0.58; r(2) = 0.65) and Doppler, although the latter tended to overestimate these changes (COecho = 1.58 x COTD - 0.13; r(2) = 0.53). CONCLUSIONS: Calibrated pulse contour analysis using the PulseCO system is an acceptable technique to measure cardiac output non-invasively in off-pump coronary bypass patients. Doppler echocardiography performs less well and is not always feasible with transoesophageal echocardiography when the heart is displaced.

Acute pulmonary hypertension causes depression of left ventricular contractility and relaxation.

BACKGROUND AND OBJECTIVE: The haemodynamic effects of acute pulmonary hypertension can be largely attributed to ventricular interdependence during diastole. However, there is evidence that the two ventricles also interact during systole. The aim of the present study was to examine the effects of acute pulmonary hypertension on both components of left ventricular systole, i.e. contraction and relaxation, using load-independent indices. METHODS: Ten pigs were instrumented with biventricular conductance catheters, a pulmonary artery flow probe and a high-fidelity pulmonary pressure catheter. Haemodynamic measurements were performed in baseline conditions and during stable pulmonary vasoconstriction induced by the thromboxane analogue U46619. Contractility was quantified using the end-systolic pressure-volume and preload recruitable stroke work relationships. The tau-end-systolic pressure relationship was used to assess load-dependency of relaxation. RESULTS: Acute pulmonary hypertension caused a decrease in the slope of the left ventricular preload recruitable stroke work relationship (from 6.64 +/- 1.7 to 5.19 +/- 1.9, mean +/- SD; P < 0.05), a rightward shift of the end-systolic pressure-volume relationship (P < 0.05), and an increase in the slope of the tau-end-systolic pressure relationship (from -0.15 +/- 0.5 to 0.35 +/- 0.17; P < 0.05). The diastolic chamber stiffness constant of both ventricles increased during pulmonary hypertension (P < 0.05). CONCLUSIONS: In the present model, acute pulmonary hypertension impairs left ventricular contractile function and relaxing properties. The present study provides additional evidence that, besides the well-known diastolic ventricular cross talk, systolic ventricular interaction may play a significant role in the haemodynamic consequences of acute pulmonary hypertension.

Evaluation of a new continuous cardiac output monitor in off-pump coronary artery surgery.

We evaluated a new, ultra-fast response continuous cardiac output monitor in 34 adult patients undergoing off-pump coronary artery bypass graft surgery. Cardiac output was measured with the TruCCOMS continuous cardiac output monitor (Aortech International plc, Lanarkshire, UK), using triplicate cold bolus thermodilution as the criterion standard, at fixed time points during surgery and during dobutamine infusion. The two techniques were compared using linear regression and Bland-Altman analysis. Overall, the study device displayed a bias of 0.4 l.min(-1) with limits of agreement of +2.5 l.min(-1) and -1.7 l.min(-1). The study device failed to detect the change in cardiac output caused by dobutamine accurately (y = 0.18x + 0.45; r(2) = 0.13), with an error linearly related to the magnitude of the change measured. We conclude that the device's failure to detect changes in cardiac output could be a major limitation in its clinical use in its current form.

Effects of propofol on the systolic and diastolic performance of the postischaemic, reperfused myocardium in rabbits.

BACKGROUND AND OBJECTIVE: The effect of propofol on myocardial dysfunction during ischaemia and reperfusion is controversial yet important because of its frequent use in cardiac anaesthesia. Although animal studies suggest a free radical-scavenging potential, the cardioprotective properties of propofol have not been demonstrated consistently in vivo. Previous studies focused on systolic function while diastolic function may be a more sensitive marker of ischaemic injury. The main aim was to document the effect of propofol on diastolic function in isolated, blood perfused rabbit hearts subjected to moderate global ischaemia and reperfusion. METHODS: Propofol 168 micromol L(-1), or the equivalent of its vehicle, Intralipid, was administered to 34 paced parabiotic Langendorff blood-perfused isolated rabbit hearts before and after 30 min of global normothermic ischaemia. Recovery of systolic function was quantified with the maximum rate of rise of left ventricular pressure. Diastolic performance was assessed using the time constant of the decline in left ventricular pressure (tau) and chamber stiffness (VdP/dV at 12 mmHg). RESULTS: Recovery of systolic function during reperfusion was comparable in the two groups. There was no difference in left ventricular pressure between the two groups at any time during the experiments. Chamber stiffness increased significantly during ischaemia and reperfusion in the control group (from 34 +/- 9 to 54 +/- 8 mmHg during ischaemia, and 43 +/- 5 mmHg after 30 min reperfusion; mean +/-95% confidence interval) but not in the propofol-treated group (29 +/- 5, 36 +/- 8 and 30 +/- 8 at baseline, ischaemia and 30 min reperfusion, respectively). CONCLUSIONS: Propofol has no protective effect on active relaxation or on systolic function in the present model, but it reduces ischaemic and postischaemic chamber stiffness.

Oesophageal Doppler monitoring overestimates cardiac output during lumbar epidural anaesthesia.

Oesophageal Doppler monitoring (ODM) has been advocated as a non-invasive means of measuring cardiac output (CO). However, its reliance upon blood flow measurement in the descending aorta to estimate CO is susceptible to error if blood flow is redistributed between the upper and lower body. We hypothesize that lumbar epidural anesthesia (LEA), which causes blood flow redistribution, causes errors in CO estimates. We compared ODM with thermodilution (TD) measurements in fourteen patients under general anaesthesia for radical prostatectomy, who had received an epidural catheter at the intervertebral level L2-L3. Coupled measurements of CO by means of the TD and ODM techniques were performed at baseline (general anaesthetic only) and after epidural administration of 10 ml of 0.25% bupivacaine. The two methods were compared using Bland-Altman analysis: before LEA there was a bias of -0.89 litre min(-1) with limits of agreement ranging between -2.67 and +0.88 litre min(-1). Following lumbar sympathetic block, bias became positive (+0.55 litre min(-1)) and limits of agreement increased to -3.21 and +4.30 litre min(-1). ODM measured a greater increase in CO after LEA (delta=+1.71 (1.19) litre min(-1) (mean (SD)) compared with TD (delta=+0.51 (0.70) litre min(-1)). We conclude that following LEA, measurements with the Oesophageal Doppler Monitor II overestimate CO and show unacceptably high variability. Blood flow redistribution may limit the value of ODM.

Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts.

OBJECTIVES: High concentrations of free fatty acids may increase myocardial ischaemic damage. However, the administration of lipid emulsions during reperfusion improves the functional recovery of stunned myocardium. From this apparent controversy we hypothesise that the effect of lipids is related to the time of its administration: we compared the effects of pre- and post-ischaemic administration of Intralipid((R)) on stunned myocardium. We also examined the role of fatty acids and phospholipids, respectively, in the effect of lipid emulsions on stunned myocardium. METHODS: Myocardial stunning was produced by 15 min of ischaemia and 90 min of reperfusion in isolated blood perfused rabbit hearts. Intralipid((R)) was administered either prior to ischaemia or during reperfusion. Left ventricular pressure (LVP) and its first derivative (LVdP/dt) were measured to assess functional recovery. High energy phosphates were measured with HPLC. The effects of linoleic acid, phosphatidylcholine and their combination were also studied. RESULTS: Only when Intralipid((R)) was administered during reperfusion, it improved recovery from contractile function and increased high energy phosphate content in globally stunned myocardium. Both linoleic acid and phosphatidylcholine significantly improved myocardial function in stunned myocardium. CONCLUSIONS: The effect of lipids on the contractile performance and metabolic state of stunned myocardium depends mainly on the timing of its administration with regard to the ischaemia/reperfusion event. Both free fatty acids and phospholipids contribute to the beneficial effect of lipid emulsions on functional recovery of stunned myocardium.

Effect of clevidipine, an ultra-short acting 1,4-dihydropyridine calcium channel blocking drug, on the potency of isoflurane in rats and dogs.

Clevidipine is a new lipophilic, ultra-short acting 1, 4-dihydropyridine calcium channel antagonist for intraoperative use. Because sarcolemnal calcium currents are involved in the mechanism of action of anaesthetics we questioned whether clevidipine alters the potency of volatile anaesthetics. We studied the effects of clevidipine on minimal alveolar concentration and the time to awaken from isoflurane anaesthesia. Sprague-Dawley rats were anaesthetized with isoflurane, and were allocated to one of four treatments prior to minimal alveolar concentration determination: (a) saline control; (b) clevidipine 20 nmol kg-1 min-1; (c) clevidipine 40 nmol kg-1 min-1; (d) clonidine 1 microg kg-1 - positive control. Ten mongrel dogs were anaesthetized with isoflurane and received a continuous infusion of clevidipine 6 nmol kg-1 min-1 or the solvent (Intralipid 20% - control). After 2 h of steady-state anaesthesia, minimal alveolar concentration awake and the time to awakening were recorded. Clevidipine reduced minimal alveolar concentration to a small but statistically significant extent (from 1.40 +/- 0.16 control to 1.23 +/- 0.13 vol % with 20 nmol kg-1 min-1 and to 1.27 +/- 0.12 vol % with 40 nmol kg-1 min-1; mean +/- SD; P < 0.05) in rats. Clonidine reduced minimal alveolar concentration to 0.90 +/- 0.17 vol % (mean +/- SD; P < 0.05). Minimal alveolar concentration awake and the duration of sleep were not affected by clevidipine in dogs. Clevidipine mildly reduces minimal alveolar concentration of isoflurane but does not prolong the duration of sleep and does not affect minimal alveolar concentration awake after a 2-h steady-state isoflurane anaesthesia.