Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

BACKGROUND: Central neuraxial blocks (CNBs) for surgery and analgesia are an important part of anaesthesia practice in the Nordic countries. More active thromboprophylaxis with potent antihaemostatic drugs has increased the risk of bleeding into the spinal canal. National guidelines for minimizing this risk in patients who benefit from such blocks vary in their recommendations for safe practice. METHODS: The Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) appointed a task force of experts to establish a Nordic consensus on recommendations for best clinical practice in providing effective and safe CNBs in patients with an increased risk of bleeding. We performed a literature search and expert evaluation of evidence for (1) the possible benefits of CNBs on the outcome of anaesthesia and surgery, for (2) risks of spinal bleeding from hereditary and acquired bleeding disorders and antihaemostatic drugs used in surgical patients for thromboprophylaxis, for (3) risk evaluation in published case reports, and for (4) recommendations in published national guidelines. Proposals from the taskforce were available for feedback on the SSAI web-page during the summer of 2008. RESULTS: Neuraxial blocks can improve comfort and reduce morbidity (strong evidence) and mortality (moderate evidence) after surgical procedures. Haemostatic disorders, antihaemostatic drugs, anatomical abnormalities of the spine and spinal blood vessels, elderly patients, and renal and hepatic impairment are risk factors for spinal bleeding (strong evidence). Published national guidelines are mainly based on experts' opinions (weak evidence). The task force reached a consensus on Nordic guidelines, mainly based on our experts' opinions, but we acknowledge different practices in heparinization during vascular surgery and peri-operative administration of non-steroidal anti-inflammatory drugs during neuraxial blocks. CONCLUSIONS: Experts from the five Nordic countries offer consensus recommendations for safe clinical practice of neuraxial blocks and how to minimize the risks of serious complications from spinal bleeding. A brief version of the recommendations is available on http://www.ssai.info.

Perioperative use of alpha2-adrenoceptor agonists and the cardiac patient.

The centrally acting alpha2-adrenoceptor agonists clonidine and dexmedetomidine have been used with success to provide haemodynamic stability for patients undergoing surgery. Particularly in the case of patients with overt or underlying cardiac disease the actions of alpha2-adrenoceptor agonists, which include maintenance of stable systemic blood pressure and low heart rate and a reduction in overall oxygen consumption, can be expected to reduce the risk of procedure-related cardiac events. This expectation has been corroborated in clinical trials with clonidine, dexmedetomidine and mivazerol and meta-analyses; additional large controlled trials would be instructive in establishing a robust estimate of the scale of the benefit. In addition, alpha2-adrenoceptor agonists used as premedication have been shown to substantially reduce anaesthetic requirements among surgical patients, and the use of these agents has been associated with a reduced risk of postoperative delirium, which may be expected to improve considerably the postoperative course for at-risk patients. Dexmedetomidine is the only alpha2-adrenoceptor agonist currently approved for use in the intensive care unit. A distinctive feature of dexmedetomidine in that setting is that in addition to haemodynamic stability it confers a distinctive and advantageous quality of sedation: patients are tranquil but responsive to requests from attending staff. This review examines the pharmacological principles underlying the use of alpha2-adrenoceptor agonists as adjuncts to surgery and clinical experience in that indication.

Isobaric bupivacaine via spinal catheter for hip replacement surgery: ED50 and ED95 dose determination.

BACKGROUND: Continuous spinal anaesthesia with spinal catheters allows incremental dosing of the local anaesthetic and, consequently, less haemodynamic change. However, little is known about the required doses. Therefore, we designed a study to assess the local anaesthetic doses of isobaric bupivacaine which were effective in 50% (ED50) and 95% (ED95) of patients undergoing hip replacement surgery. METHODS: Forty-eight patients undergoing hip replacement surgery were randomly allocated to one of six possible groups of eight patients to receive 6, 7, 8, 9, 10 or 12 mg of isobaric bupivacaine in a double-blind manner. The ED50 and ED95 values were calculated by a logistic regression model. The position of the spinal catheter tip was confirmed by X-rays. RESULTS: The ED50 and ED95 values were 7.1 mg (95% confidence interval, 6.0-8.4) and 12.3 mg (95% confidence interval, 8.9-15.7), respectively. The location of the tip of the intrathecal catheter had no effect on local anaesthetic requirements. Eight patients required ephedrine after anaesthesia induction and a further 11 patients required ephedrine for correction of hypotension during surgery. CONCLUSION: The observed ED50 and ED95 values may guide us to use small doses of isobaric bupivacaine for hip replacement surgery. Hypotension is still possible even if low doses of isobaric bupivacaine are used.

Effect of age and repeated hyperbaric oxygen treatments on vagal tone.

OBJECTIVES: To evaluate the influence of repeated hyperbaric oxygen (HBO2) exposures and age on vagal response to hyperbaric oxygenation, and to evaluate the timing of changes in vagal activity during the treatments. STUDY DESIGN: Open, controlled, non-randomized study. METHODS: Heart rate variability of 23 patients with chronic osteomyelitis or radionecrosis of the jaw or reconstructive surgery of the facial region was studied during repeated treatments. During each treatment, the patients were exposed to HBO2 at 2.5 ATA and heart rate variability was measured using power spectral analysis before compression, three times at 2.5 ATA and during and after decompression. The patients were grouped according to age (Cut-off point 50 years). Statistical analysis was carried out using analysis of variance for repeated measurements. RESULTS: Repeated exposures did not change vagal response to hyperbaric oxygenation. Vagal activity measured by HF power increased significantly in both age groups during the HBO2 exposures but there were no significant difference between the groups in the response. However, the level of HF power was significantly higher in the subjects under 50 years old. Significant differences between consecutive measurements were related to pressure changes. CONCLUSIONS: Repeated therapeutic HBO2exposures are not causing permanent changes in vagal control of the heart. Vagal responsiveness to hyperbaric hyperoxia is preserved in advanced age.

Minimum effective local anaesthetic dose of isobaric levobupivacaine and ropivacaine administered via a spinal catheter for hip replacement surgery.

BACKGROUND: Continuous spinal anaesthesia with spinal catheters allows incremental dosing of local anaesthetic and, consequently, less haemodynamic changes. However, little is known about the required doses. Therefore, we designed a study to assess the minimum effective local anaesthetic dose (MLAD) of levobupivacaine and ropivacaine in this context. METHODS: Forty-one patients undergoing hip replacement surgery were randomly allocated to one of the two local anaesthetic groups in a double-blind manner. The initial dose of local anaesthetic was determined by the response of the previous patient: the effective dose resulted in a 1 mg decrease in the dose of levobupivacaine or ropivacaine, and an ineffective dose resulted in a 1 mg increase. The MLAD was calculated by the Dixon up-and-down method. RESULTS: The MLAD of levobupivacaine was 11.7 mg (95% CI, 11.1-12.4) and that of ropivacaine 12.8 mg (95% CI, 12.2-13.4). CONCLUSIONS: These doses are significantly smaller than doses reported before for single-shot spinal anaesthesia. Continuous spinal anaesthesia allows the use of relatively small doses of local anaesthetic.

Instantaneous beat-to-beat variability reflects vagal tone during hyperbaric hyperoxia.

Hyperbaric hyperoxia affects heart rate variability (HRV) by increasing parasympathetic activity. The purpose of this study was to evaluate the applicability of instantaneous beat-to-beat variability (SD1 of Poincaré plot analysis) in detecting changes in vagal tone and to evaluate possible changes in the fractality of heart rate dynamics (alpha1 of detrended fluctuation analysis) during hyperbaric hyperoxia. Continuous three-lead ECG recordings were taken in ten divers who were treated at 2.5 ATA with air (PO2 47 kPa) and oxygen (PO2 235 kPa) for 60 min. Power spectral analysis, Poincaré plot analysis and alpha1 were analyzed before compression, after 30 min and after 55 min at 2.5 ATA. Correlations between the variables were calculated after 55 min exposure. SD1 and high frequency (HF) power increased significantly but alpha1 decreased during hyperbaric hyperoxia (PO2 235 kPa). HF power and SD1 also correlated significantly. However, HF power and SD1 correlated inversely with alpha1. During hyperbaric hyperoxia, SD1 reflects vagal activity and can be used instead of HF power, if stationary conditions cannot be achieved. The decreasing alpha1 indicates more random heart rate dynamics during hyperbaric hyperoxia.

Comparison of the effects of antenatal magnesium sulphate and ritodrine exposure on circulatory adaptation in preterm infants.

We examined the effects of maternal magnesium sulphate (MgSO4) and ritodrine treatments on the autonomic cardiovascular control in preterm neonates with respiratory distress syndrome during the first 2 days of life. Serial measurements of heart rate (HR), blood pressure (BP) and respirogram were performed during the first 2 days of life in 28 preterm infants below 33 weeks of gestation with antenatal exposure to MgSO4 (n = 13) or ritodrine (n = 15), and in 12 nonexposed preterm controls. Spectral analysis was used for the quantification of HR and BP variability. Although antenatal MgSO4 exposure had no effect on HR or the systolic, diastolic or mean BP, it was associated with significant decreased beat-to-beat changes in BP. In contrast, ritodrine exposure had no consistent effects on the autonomic cardiovascular control during the first 2 days of life. Our data suggest that maternal MgSO4 treatment decreases the neonatal high frequency changes in BP. This early vascular stabilizing effect of antenatal MgSO4 exposure may contribute to a lowered risk of cerebral vascular catastrophes, in the vulnerable areas of the brain, among the preterm infants with respiratory distress syndrome.

Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution.

beta-Oxidation of amino acyl coenzyme A (acyl-CoA) species in mammalian peroxisomes can occur via either multifunctional enzyme type 1 (MFE-1) or type 2 (MFE-2), both of which catalyze the hydration of trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral specificity. MFE-2 has a modular organization of three domains. The function of the C-terminal domain of the mammalian MFE-2, which shows similarity with sterol carrier protein type 2 (SCP-2), is unclear. Here, the structure of the SCP-2-like domain comprising amino acid residues 618-736 of human MFE-2 (d Delta h Delta SCP-2L) was solved at 1.75 A resolution in complex with Triton X-100, an analog of a lipid molecule. This is the first reported structure of an MFE-2 domain. The d Delta h Delta SCP-2L has an alpha/beta-fold consisting of five beta-strands and five alpha-helices; the overall architecture resembles the rabbit and human SCP-2 structures. However, the structure of d Delta h Delta SCP-2L shows a hydrophobic tunnel that traverses the protein, which is occupied by an ordered Triton X-100 molecule. The tunnel is large enough to accommodate molecules such as straight-chain and branched-chain fatty acyl-CoAs and bile acid intermediates. Large empty apolar cavities are observed near the exit of the tunnel and between the helices C and D. In addition, the C-terminal peroxisomal targeting signal is ordered in the structure and solvent-exposed, which is not the case with unliganded rabbit SCP-2, supporting the hypothesis of a ligand-assisted targeting mechanism.

Cone voltage and collision cell collision-induced dissociation study of triphenylethylenes of pharmaceutical interest.

Fragmentations of three triphenylethylene compounds (toremifene and its two metabolites) with different functional side-chain groups (alcohol, acid and amine) were studied. The compounds were dissociated by collision-induced dissociation (CID) in the interface region of an electrospray ionization source (ESI(+)) and in the collision cell of a triple quadrupole mass spectrometer. Fragmentation pathways for these molecules are proposed, based on accurate mass measurements of in-source fragment ions and MS/MS experiments using product and precursor ion scanning. The side-chain functional groups were found to strongly affect the fragmentations of the molecular ions. The fragmentation pathways of the protonated molecule and sodium ion adduct were quite similar, but the subsequent stabilities of certain common fragments were surprisingly different.

Antenatal magnesium sulphate exposure is associated with prolonged parathyroid hormone suppression in preterm neonates.

UNLABELLED: The effects of maternal magnesium sulphate treatment on neonatal mineral status and parathyroid hormone secretory response were studied in 8 exposed and 27 control preterm infants during the first 2 wk of life. Antenatal magnesium sulphate resulted in hypermagnesaemia during the first 3-7 d of life without affecting other serum mineral concentrations. CONCLUSION: Early hypermagnesaemia was associated with hypercalciuria during the first 3 d and parathyroid hormone suppression up to the age of 2 wk in the exposed infants.

Radioiodinated tyrosyl-ouabain and measurement of a circulating ouabain-like compound.

BACKGROUND: Assays for endogenous ouabain, a cardiac glycoside believed to be involved in blood pressure and volume regulation, are characterized by laboratory-specific plasma values that are measured by different assays. Because of this variability, our study focused on the development of a new (125)I-labeled ouabain derivative for RIA of high sensitivity. METHODS: We generated rabbit antisera against a ouabain-thyroglobulin conjugate. A tyrosylated ouabain derivative for radioiodination was synthesized using periodate and sodium cyanoborohydride reagents. RESULTS: Mass spectrometric analyses showed that the main product of the tyrosylating reaction was tyrosyl-ouabain (molecular mass, 702 Da). This was radioiodinated with Chloramine-T and used as a tracer in a RIA, which gave an assay detection limit of 5 pmol/L (4 ng/L), 2-100 times lower than that in the corresponding (3)H-RIAs and 2-20 times lower than ouabain ELISAs, making it possible to measure low plasma concentrations of immunoreactive ouabain. Different amounts of SepPak C(18)-extracted plasma samples displaced the (125)I-labeled tyrosyl-ouabain tracer at the same rate at which authentic ouabain was displaced. Plasma immunoreactive ouabain coeluted with authentic ouabain in two different HPLC conditions. Using the new RIA, we found plasma ouabain concentrations, assayed as immunoreactive equivalents, of 10.0 +/- 1.3 pmol/L in healthy women and 12.0 +/- 0. 9 pmol/L in healthy men (mean +/- SE; n = 10), as well as 41.2 +/- 9. 6 pmol/L in rats. The concentrations were 2-90 times lower than those previously reported using different assay methods. CONCLUSIONS: Our ouabain (125)I-RIA enables reliable measurements of low endogenous concentrations of a ouabain-like compound for both physiological and clinical purposes.

Epidural infusion of bupivacaine and fentanyl reduces perioperative myocardial ischaemia in elderly patients with hip fracture--a randomized controlled trial.

BACKGROUND: Perioperative myocardial ischaemia is an important risk factor for cardiac morbidity and mortality after noncardiac surgery. The impact of analgesic management on the incidence and severity of cardiac ischemia was studied in 77 elderly patients undergoing surgical treatment of traumatic hip fracture. METHODS: After hospital admission and written consent, patients were randomised to conventional analgesic regimen (intramuscular oxycodone, OPI group) or continuous epidural infusion of bupivacaine/fentanyl (EPI group). The analgesic regimens were started preoperatively. Patients were operated under spinal anaesthesia and the treatments were continued three days postoperatively. ECG was continuously recorded. ST segment depression of > or = 0.1 mV or elevation of > or = 0.2 mV lasting > or = 1 min were considered as ischaemic episodes. Nocturnal arterial oxygen saturation (SaO2) was recorded perioperatively, and subjective pain was assessed every morning using a visual analogue scale (VAS). RESULTS: Fifty-nine (OPI 30, EPI 29) patients were evaluable for efficacy. Thirteen patients (43%) in the OPI and 12 patients (41%) in the EPI group had ischaemic episodes (NS). However, significantly more patients in the OPI group had ischaemic episodes during the surgery (8 vs. 0 in the EPI group, P=0.005). The median (quartal deviation) total ischaemic burden (i.e. integral of ST-change vs. time) in patients with ischaemic episodes was ten times larger in the OPI group (340 [342] mm x min) compared with the EPI group (30 [36] mm x min) (P=0.002). There were no significant differences between the groups in average heart rates or in heart rates at the start of ischaemic episodes or in maximal heart rates during the attacks. Average nocturnal SaO2 was similar in the two groups and there were no differences in the number of hypoxaemic (SaO2<90%) episodes. Preoperatively there were no differences in subjective pain, but postoperative and average perioperative VAS scores for pain were almost 40% lower in the EPI group (P=0.006). Perioperative myocardial infarctions were not detected. CONCLUSIONS: Continuous epidural bupivacaine/fentanyl analgesic regimen, started preoperatively, reduces the amount of myocardial ischaemia in elderly patients with hip fracture.

Hyperbaric oxygen increases parasympathetic activity in professional divers.

The role of autonomic nervous system in hyperoxic bradycardia was evaluated by using the power-spectral analysis of heart-rate variability (HRV). Ten professional divers went through two hyperbaric hyperoxic experiments: (1) hyperbaric oxygen (HBO), 100% oxygen at 2.5 ATA, (2) hyperbaric air (HBAIR), O(2) 21% at 2.5 ATA. Four-minute traces of ECG were registered and subjected to power-spectral analysis. Cardiac conduction parameters were evaluated by a diagnostic 12-lead ECG and arrhythmias by a continuous 3-lead ECG. Statistical analysis was made using analysis of variance for repeated measurements. Heart rate decreased (P < 0. 001), but the response was similar during both treatments (P=0.14). Total power increased significantly more during HBO than HBAIR (P=0.003). High-frequency (HF) power (P < 0.001), Hayano's index (P=0.001) and normalized units of HF power (P=0.002) increased and LF/HF index (P < 0.001) decreased more during HBO than HBAIR. There were no changes in cardiac conduction or incidence of arrhythmias. In conclusion, 100% oxygen at 2.5 ATA caused marked increase in parasympathetic tone compared with 21% oxygen at 2.5 ATA.

Comparison of autonomic withdrawal in men with obstructive sleep apnea syndrome, systemic hypertension, and neither condition.

Obstructive sleep apnea syndrome is characterized by obesity, nocturnal breathing abnormalities, arterial hypertension, and an increased number of cardiovascular events. Sympathetic activity is increased during nocturnal apneic episodes, which may mediate the cardiovascular complications of sleep apnea. We studied 15 male subjects with obstructive sleep apnea syndrome and associated hypertension, 54 subjects with mild to moderate essential hypertension, and 25 healthy normotensive men. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability (HRV) during a controlled breathing test and during orthostatic maneuver. Compared with normotensive and hypertensive groups, total power and low- and high-frequency components of HRV during controlled breathing were significantly (analysis of variance, p<0.0001) lower in the obstructive sleep apnea syndrome. During the orthostatic maneuver, the change in total power of HRV was different between the 3 groups (analysis of variance, p = 0.004). The total power of HRV tended to increase in the normotensive (4.11+/-12.29 ms2) and in hypertensive (2.31+/-12.65 ms2) groups, but decreased (1.13+/-1.23 ms2) in the hypertensive group with obstructive sleep apnea syndrome. According to multivariate regression analysis, age and sleep apnea were the major independent determinants of HRV. This study found that an abnormal response to autonomic nervous tests characterizes hypertension in overweight subjects with obstructive sleep apnea syndrome. This could be due to autonomic withdrawal or supersaturation of the end-organ receptors by excessive and prolonged sympathetic stimulation. Our results also show the reduced response of orthostatic maneuver and controlled breathing in the hypertensive group compared with the normotensive group.

Correlation properties and complexity of perioperative RR-interval dynamics in coronary artery bypass surgery patients.

BACKGROUND: Dynamic measures of heart rate variability (HRV) may uncover abnormalities that are not easily detectable with traditional time and frequency domain measures. The purpose of this study was to characterize changes in RR-interval dynamics in the immediate postoperative phase of coronary artery bypass graft (CABG) surgery using traditional and selected newer dynamic measures of HRV. METHODS: Continuous 24-h electrocardiograph recordings were performed in 40 elective CABG surgery patients up to 72 h postoperatively. In one half of the patients, Holter recordings were initiated 12-40 h before the surgery. Time and frequency domain measures of HRV were assessed. The dynamic measures included a quantitative and visual analysis of Poincaré plots, measurement of short- and intermediate-term fractal-like scaling exponents (alpha1 and alpha2), the slope (beta) of the power-law regression line of RR-interval dynamics, and approximate entropy. RESULTS: The SD of RR intervals (P < 0.001) and the ultra-low-, very-low-, low-, and high-frequency power (P < 0.01, P < 0.001, P < 0.001, P < 0.01, respectively) measures in the first postoperative 24 h decreased from the preoperative values. Analysis of Poincaré plots revealed increased randomness in beat-to-beat heart rate behavior demonstrated by an increase in the ratio between short-term and long-term HRV (P < 0.001) after CABG. Average scaling exponent alpha1 of the 3 postoperative days decreased significantly after CABG (from 1.22 +/- 0.15 to 0.85 +/- 0.20, P < 0.001), indicating increased randomness of short-term heart rate dynamics (i.e., loss of fractal-like heart rate dynamics). Reduced scaling exponent alpha1 of the first postoperative 24 h was the best HRV measure in differentiating between the patients that had normal ( 48 h, n = 7) intensive care unit stay (0.85 +/- 0.17 vs. 0.68 +/- 0.18; P < 0.05). In stepwise multivariate logistic regression analysis including typical clinical predictors, alpha1 was the most significant independent predictor (P < 0.05) of long intensive care unit stay. None of the preoperative HRV measures were able to predict prolonged intensive care unit stays. CONCLUSIONS: In the selected group of patients studied, a decrease in overall HRV was associated with altered nonlinear heart rate dynamics after CABG surgery. Current results suggest that a more random short-term heart rate behavior may be associated with a complicated clinical course. Analysis of fractal-like dynamics of heart rate may provide new perspectives in detecting abnormal cardiovascular function after CABG.

Impairment of heart rate variability during paclitaxel therapy.

BACKGROUND: Paclitaxel, which has been reported to be effective in treating metastatic breast carcinoma and advanced ovarian carcinoma, has been associated with cardiac side effects. Therefore, the effect of paclitaxel on cardiovascular autonomic regulation was studied. METHODS: Twenty-four-hour ambulatory electrocardiogram measurements were recorded twice from 14 women with breast or ovarian carcinoma: once before paclitaxel treatment and once on the day after the second chemotherapy course. Heart rate variability (HRV) was assessed with spectral analysis. For the frequency domain analysis, HRV was assessed in the very low (0.005-0.040 hertz [Hz]), low (0.040-0.150 Hz), and high frequency (0.150-0.400 Hz) spectral components. RESULTS: The ratio between low frequency and high frequency HRV decreased (daytime values of 2.7% [standard deviation (SD) 1.6] vs. 1.7% [SD 0.91; P = 0.0098) after 2 courses of paclitaxel. The circadian fluctuation of HRV also decreased in all studied frequency components. CONCLUSIONS: The observed changes in spectral characteristics suggest that autonomic modulation of the heart rate is impaired after paclitaxel therapy. However, from these data it is not clear whether the observed changes are permanent or whether autonomic cardiac function returns to normal some time after treatment. Further studies are needed to examine whether these indices based on HRV can be used to detect those patients at risk for cardiac side effects during chemotherapy.

Efficiency of left ventricular diastolic function increases in healthy full-term infants during the first months of life. A prospective follow-up study.

Postnatal changes in left ventricular diastolic filling and systolic cardiac performance were studied monthly by serial echocardiographic measurements from days 3-5 up to six months in 20 healthy full-term infants. The fractional shortening area (FSA = (left ventricular end-diastolic area - end-systolic area)/end-diastolic area) was assessed for systolic performance, and transmitral pulsed-wave Doppler flow velocity patterns were analysed for diastolic function. FSA remained stationary during the observation. After birth, left ventricular peak early (E) and atrial (A) velocities and the respective integrals were lower than at one month of age (47+/-5 vs. 63+/-6 cm/s and 44+/-6 vs. 57+/-5 cm/s and 3.33+/-0.40 vs. 4.05+/-0.53 cm and 2.74+/-0.40 vs. 3.18+/-0.53 cm; P < 0.05). During the next five months, the early parameters (E velocity and E integral) increased but the atrial indices (A velocity and A integral) did not change. During the whole observation the E/A velocity ratio, the E/A integral ratio and the early filling fraction (EFF) increased. The early filling deceleration time was longer during the first month than later (87+/-10 vs. 72+/-13 ms; P < 0.05). In conclusion, age-related changes were observed in the diastolic but not in the systolic performance in healthy full-term infants during the first six months. The most intensive changes took place in the early and atrial transmitral parameters during the first month of life, suggesting an improvement in both left ventricular relaxation and compliance. During the following five months, the early mitral parameters increased but the atrial diastolic values remained stable. These changes may mainly be determined by the improvement in left ventricular relaxation.

Heart rate variability in healthy volunteers during normobaric and hyperbaric hyperoxia.

Inhaled supranormal partial pressure of oxygen induces bradycardia and peripheral vasoconstriction. The exact mechanism of the decreasing heart rate is not clear, but the autonomic nervous system is partly involved. In the present study the role of the autonomic nervous system in hyperoxic bradycardia was evaluated by using the power spectral analysis of heart rate variability. Ten healthy volunteers participated in four experiments: (i) hyperbaric oxygen treatment (100% oxygen at 2.5 ATA), (ii) hyperbaric air treatment (O2 21% at 2.5 ATA), (iii) oxygen treatment at normal pressure (100% O2, 1 ATA) and (iv) air breathing at normal pressure (21% O2, 1 ATA). During the experiments, ECG was registered and subjected to power spectral analysis. The volunteers rated their perception of temperature, ear discomfort, sweating and excitement on a visual analogue scale. Statistical comparison of the results of the four trials was conducted with a two-way ANOVA for repeated measurements. Heart rate decreased during all interventions, but there were no statistically significant differences between the sessions. High frequency variability of heart rate variability and Hayano's index of HF power increased and LF/HF ratio decreased with increasing partial pressure of oxygen. Our results suggest, that normobaric and hyperbaric hyperoxia increase parasympathetic influence in the regulation of the heart.

Responsiveness of cutaneous vasculature to thermal stimulation during phototherapy in neonatal jaundice.

The present study was performed to measure the vasoregulatory reactions to dynamic changes in local skin temperature during open bed phototherapy. Periodic thermal stimulation using warm and cool air currents was applied to the skin of ten term infants with physiological jaundice, before and during open bed phototherapy. The reactivity of skin blood flow (SBF) and heart rate was measured using laser Doppler flowmetry and power spectral analysis. The baseline SBF increased significantly by 70% (P = 0.008) during phototherapy without any significant change in skin or rectal temperature. Before phototherapy, the rhythmic (0.08 Hz) thermal skin stimulation increased the oscillations of SBF (from 89 +/- 26 au to 213 +/- 37 au, P = 0.02) at the stimulation frequency band. This response was further increased (P = 0.03) during phototherapy (from 198 +/- 54 au to 658 +/- 115 au, P = 0.004). Phototherapy increased SBF in icteric otherwise healthy neonates. The cutaneous vasodilatation augments the cardiovascular responsiveness to thermal stimulation. These results suggest that open bed phototherapy does not inhibit the cardiovascular responsiveness to local thermal skin stimulation in healthy term infants.

Reproducibility of abnormal heart rate variability indices: the case of hypertensive sleep apnoea syndrome.

Before heart rate variability can be used as an investigational tool in the clinical setting, its reproducibility must be known. We studied heart rate variability four times during 44 weeks in 15 hypertensive patients with sleep apnoea syndrome. Time and frequency domain analytical approaches were used during the spontaneous and controlled breathing tests, orthostatic manoeuvre and the cold pressor test. Alterations in resting heart rate were taken into account using the coefficient of component variance. In general, the response of heart rate variability was abnormal and variability was reduced in the hypertensive patients with sleep apnoea syndrome compared with reference data. Time domain measures of heart rate variability demonstrated generally better reproducibility over four recordings than frequency domain measures in these hypertensive patients with sleep apnoea syndrome. On the other hand, the reproducibility of frequency domain measures depended on the specific conditions: during orthostatic manoeuvre and cold pressor test the best reproducibility was found using normalized units. In the reference data set, there were no significant differences between the two heart rate variability recordings during any of the autonomic nervous function tests. In this follow-up study we found that simple procedures such as the controlled breathing test show good reproducibility. More complex tests such as the orthostatic manoeuvre require special attention in order to obtain acceptable reproducibility of heart rate variability measurements. Quantitatively minor changes in the variability indices when the overall variability is reduced exert major effects on the results. Therefore we suggest that reproducibility data obtained in healthy volunteers are not valid for the interpretation of data in patients with damaged cardiovascular autonomic control.