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Biomedical subjects

J Jalonen

Publications and source records attributed to J Jalonen.

At least 19 recordsLinked to original sources

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.

Adrenergic alpha-2 Receptor Agonists↗

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.

Adult↗

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.

Adult↗

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.

Diving↗

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.

Estrogen Antagonists↗

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.

Adult↗

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.

Calcium↗

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.

Adult↗

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.

Aging↗

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.

Aged↗

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.

Analysis of Variance↗

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.

Heart Rate↗

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.

Adult↗

Computer-assisted electrocardiography in structured diagnosis of acute myocardial infarction.

The purpose of this study was to investigate the applicability of computerized electrocardiogram interpretation in classifying patients with suspected acute myocardial infarction. Computerized acquisition and analysis of the 12-lead electrocardiogram can increase the consistency and reduce the workload of patient classification. The serial electrocardiograms of 311 consecutive patients with suspected myocardial infarction were studied and a new computerized myocardial infarction (CMI) electrocardiographic classification was developed and compared with one commercially available and two manual codes. Statistically, there was almost no correlation between the four ECG codes. Compared with the WHO enzymatic criteria, the sensitivity of the CMI code toward detecting definite and possible infarction was 69.2% and 29.8% with a specificity of 62.1% and 79.7%, respectively. In subjects without previous infarction (n = 214) the sensitivity of the CMI code for definite enzymatic infarction was 71.9% and specificity 77.6%. Substituting the CMI for the Minnesota code had no effect on patient classification by the WHO MONICA criteria in 78% of patients with first infarction. Judged by cardiac macromolecular leakage, all electrocardiographic classifications of possible infarction were poorly correlated with myocardial tissue injury. We have developed a new computerized coding system to detect electrocardiographic myocardial infarction. The structure of the code allows interactive redefinition of criteria to meet user-defined needs. However, because of the weak relationship between electrocardiographic and biochemical criteria of myocardial injury, the role of ECG in the diagnostic classification of acute ischemic syndromes should be re-evaluated.

Aged↗

Effect of hyperbaric conditions on plasma stress hormone levels and endothelin-1.

To study a generalized stress reaction as well as endothelin-1 concentrations during moderate hyperbaria and hyperbaric oxygen (HBO2), eight professional divers were exposed to air (O2 21%, AIR) and oxygen (O2 100%, HBO2) at 2.5 atm abs for 60 min in separate sessions. Plasma concentrations of epinephrine, norepinephrine, dihydroxyphenylglycol (metabolite of norepinephrine), cortisol, ADH, renin, aldosterone, pro-ANP, and endothelin-1 were analyzed before, during, and 20 min after the treatments. Endothelin-1 increased significantly (6% during HBO2 and 18% during AIR, and 30 and 34% after the treatments, respectively, P = 0.032). There was no statistically significant difference in the changes of mean norepinephrine and dihydroxyphenylglycol levels between the treatments, although both seemed to change slightly during the treatments, but not over the baseline (time effect P = 0.031 and P = 0.011, respectively). Cortisol levels decreased significantly (P = 0.001) during the treatments. No significant changes were found in other analyzed hormones. The authors concluded that a) HBO2, and hyperbaric air at 2.5 atm abs do not induce a generalized hormonal stress reaction, and b) endothelin-1 increases during HBO2 and hyperbaric air at 2.5 atm abs.

Aldosterone↗

Increased amplitude modulation of continuous respiration precedes sudden infant death syndrome -detection by spectral estimation of respirogram.

The immaturity of the control of the autonomic nervous system has been suggested as one of the key factors in the pathophysiology of sudden infant death syndrome (SIDS). Therefore, the attenuated control of respiration may also cause more slow oscillatory breathing among infants at risk of SIDS. In this study, patterns of respiratory activity (RAV) and heart rate variability (HRV) were examined in Medilog-records prospectively obtained from 22 tape recordings made on 16 babies subsequently suffering from SIDS and from 22 matched control babies. A total of 248 signal segments, 120 s in duration, representing the state of regular breathing were visually selected for further analysis. The digitised signal sets were detrended, Fast-Fourier-transformed and autospectra as well as cross-spectra for the HRV and HRV were computed. The RAV and HRV were examined at two spectral bands: (1) a low frequency (LF) band 0.03-0.17 Hz (1.8-10 cycles/min) and (2) a high frequency (HF) band 0.3-1.3 Hz (18-90 cycles/min). Different parameters of each band were tested in the spectral analysis of cardiorespiratory control. The LF/HF-ratio of the spectral peak area of the respiratory activity and the LF/HF-ratio of the spectral band area of the respiratory activity were greater in the SIDS group when compared to the controls. No significant intergroup differences were found in the parameters of HRV, or the cross-spectral parameters. Interestingly, the technique appeared helpful in displaying that the victims of SIDS had a significantly greater amount of slow oscillation in the continuous respiratory signal (1.05+/-1.89 vs. 0.41+/-0.57, P=0.02). In the victims of SIDS the respiratory control system seems to be less stable and cause more slow oscillatory breathing and this can be detected using spectral analysis of respiratory activity even during breathing that visually seems to be regular.

Autonomic Nervous System↗

Endothelin-1, atrial natriuretic peptide and pathophysiology of pulmonary hypertension in porcine meconium aspiration.

To evaluate the role of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in the development of meconium aspiration-induced pulmonary hypertension, plasma ET-1 and ANP levels were measured serially for 6h after meconium instillation in juvenile pigs. Eleven 10-week-old, anaesthetized and catheterized pigs received intratracheally a bolus of 3 ml kg(-1) 20% human meconium, and five of them were premedicated with 30 mg kg(-1) methylprednisolone i.v. Another six pigs served as controls and were given 3 ml kg(-1) sterile saline intratracheally. Meconium instillation resulted in an increase in plasma ET-1 levels with a significant correlation to the simultaneously increasing PVR (r = 0.72). Methylprednisolone had no effect on the early (0-1 h) ET-1 increase, but prevented significantly the second phase (1-6 h) rise with a concomitant attenuation of the progressive pulmonary hypertension. ANP concentrations were higher in the meconium than in the control group throughout the study and further increased after steroid treatment with a good correlation to ET-1 (r = 0.86). Thus, the postinjury rise in circulating vasoactive peptides, together with the pulmonary hypertensive response, and modulation of the peptide balance and pressor reaction by steroids, suggest a contributory role for ET-1 and ANP in the development of pulmonary hypertension after meconium aspiration.

Animals↗

Transcephalic electrical impedance provides a means for quantifying pulsatile cerebral blood volume changes following head-up tilt.

Transcephalic electrical impedance (delta Z) was used to assess pulsatile cerebral blood volume changes while tilting nine premature (30-34 weeks) infants 20 degrees head up. High-frequency (1.50-4.00 Hz) delta Z variability decreased 27% while heart rate did not show any change. We would like to suggest that the variability of transcephalic electrical impedance analysed with spectral estimation seems to provide a means for quantifying alterations in cerebral circulation.

Blood Volume↗