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Anna‐Mari Hekkala Heikki Vnnen Heikki Swan Lasse Oikarinen Matti Viitasalo Lauri Toivonen 《Annals of noninvasive electrocardiology》2006,11(4):318-326
Background: Accurate measurement of the QT interval is important for diagnosing long QT syndrome (LQTS), and in research on determinants of ventricular repolarization time. We tested automatic analysis of QT intervals from multiple ECG leads on chest. Methods: Eleven healthy volunteers and 10 genotyped LQTS patients were tested at rest and during exercise with a bicycle ergometer twice 1–31 months apart. Electrocardiograms were recorded with the body surface potential mapping system, and 12 precordial channels were selected for analysis. Averaged QT peak and QT end intervals were determined with an automated algorithm, and the difference QT end minus QT peak (Tp‐e) was calculated. Repeatability was assessed by coefficient of variation (CV) between measurements. Results: Within one test at rest the QT end intervals were highly repeatable with CV 0.6%. In repeated tests CV was 4.4% for QT end interval and 3.5% when the QT interval was corrected for heart rate. In exercise test at specified heart rates, mean CV was 3.0% for QT end and 2.9% for QT peak interval. The CV of Tp‐e interval was 10.2% at rest, and 9.3% in exercise test. Reproducibility was comparable between healthy subjects and LQTS patients. Conclusions: The BSPM system with automated analysis produced accurate and highly repeatable QT interval measurements. Reproducibility was adequate also over prolonged time periods both at rest and in exercise stress test. The method can be applied in studying duration of ventricular repolarization time in different physiologic and pharmacologic interventions. 相似文献
3.
Jere Paavola Matti Viitasalo P?ivi J Laitinen-Forsblom Michael Pasternack Heikki Swan Ilkka Tikkanen Lauri Toivonen Kimmo Kontula Mika Laine 《European heart journal》2007,28(9):1135-1142
AIMS: Mutations in cardiac ryanodine receptors (RyR2s) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), characterized by risk of polymorphic ventricular tachyarrhythmias and sudden death during exercise. Arrhythmias are caused by gain-of-function defects in RyR2, but cellular arrhythmogenesis remains elusive. METHODS AND RESULTS: We recorded endocardial monophasic action potentials (MAPs) at right ventricular septum in 15 CPVT patients with a RyR2 mutation (P2,328S, Q4,201R, and V4,653F) and in 12 control subjects both at baseline and during epinephrine infusion (0.05 microg/kg/min). At baseline 3 and during epinephrine infusion, four CPVT patients, but none of the control subjects, showed delayed afterdepolarizations (DADs) occasionally coinciding with ventricular premature complexes. In order to study the underlying mechanisms, we expressed two types of mutant RyR2 (P2,328S and V4,653F) causing CPVT as well as wild-type RyR2 in HEK 293 cells. Confocal microscopy of Fluo-3 loaded cells transfected with any of the three RyR2s showed no spontaneous subcellular Ca(2+) release events at baseline. Membrane permeable cAMP analogue (Dioctanoyl-cAMP) triggered subcellular Ca(2+) release events as Ca(2+) sparks and waves. Cells expressing mutant RyR2s showed spontaneous Ca(2+) release events at lower concentrations of cAMP than cells transfected with wild-type RyR2. CONCLUSION: CPVT patients show DADs coinciding with premature action potentials in MAP recordings. Expression studies suggest that DADs are caused by increased propensity of abnormal RyR2s to generate spontaneous Ca(2+) waves in response to cAMP stimulation. Increased sensitivity of mutant RyR2s to cAMP may explain the occurrence of arrhythmias during exercise or emotional stress in CPVT. 相似文献
4.
A rat model of monitoring liver allograft rejection 总被引:5,自引:0,他引:5
Timi Martelius Heikki Mäkisalo Krister Höckerstedt Eero Taskinen Irmeli Lautenschlager 《Transplant international》1997,10(2):103-108
Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection,
monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20
days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation
in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together
with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from
1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1
in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology.
In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental
animals. This saves work, animals, and costs in the study of liver rejection.
Received: 2 July 1996 Accepted: 28 October 1996 相似文献
5.
Tarja A. Soininvaara Hannu J.A. Miettinen Jukka S. Jurvelin Esko M. Alhava Heikki P.J. Kröger 《Journal of clinical densitometry》2004,7(4):424-431
Osteoarthrosis (OA) is often associated with pain and disability, which are relieved after total knee arthroplasty (TKA), but the nature of bone changes associated with OA is controversial. We examined preoperative hip and contralateral knee bone mineral density (BMD) in patients requiring TKA and monitored the BMD changes postoperatively. Sixty-nine patients, scheduled to have TKA for osteoarthrotic knees, had both hips and contralateral knee BMD measured by dual-energy X-ray absorptiometry (DXA) at the time of operation (baseline) and at 1 yr after operation. X-rays of the knee joints were also taken to evaluate the severity of OA. Preoperatively, 27% and 38% of the patients had total hip BMD Z-score more than 1 SD in the operated side and contralateral hips, respectively. In all regions of interest (ROI), the mean baseline BMD of the affected side proximal femur was significantly lower than that of the contralateral side (p < 0.0005-0.019). The severity of OA was not associated with BMD. During 1-yr follow-up, the postoperative knee status and the physical activity of the patients (AKS score) improved. However, neither the hip nor the nonoperated knee BMDs increased. Knee OA is associated with significantly lower BMD values in the affected side compared with the contralateral hip, and these levels remained similar or decreased during a 1-yr follow-up. We conclude that improved mobility after TKA does not improve the effects of preoperative disuse-associated bone loss in the short term. 相似文献
6.
We attempted to find out the role of α2-adrenoceptors of the medullary lateral reticular nucleus (LRN) in antinociception in rats. Spinal antinociception was evaluated using the tail-flick test, and supraspinal antinociception using the hotplate test. Antinociceptive effects were determined following local electric stimulation of the LRN, and following microinjections of medetomidine (an α2-adrenoceptor agonist; 1–10 μg), atipamezole (an α2-adrenoceptor antagonist; 20 μg) or lidocaine (4%) into the LRN. The experiments were performed using intact and spinalized Hannover-Wistar rats with a unilateral chronic guide cannula. Electric stimulation of the LRN as well as of the periaqueductal gray produced a significant spinal antinociceptive effect in intact rats. Medetomidine (1–10 μg), when microinjected into the LRN, produced no significant antinociceptive effect in the tail-flick test in intact rats. However, following spinalization, medetomidine in the LRN (10 μg) produced a significant atipamezole-reversible antinociceptive effect in the tail-flick test in the hot-plate test, medetomidine (10 μg) in the LRN produced a significant atipamezole-reversible increase of the paw-lick latency in intact rats. Microinjection of atipamezole (20 μg) or lidocaine alone into the LRN produced no significant effects in the tail-flick test. The results are in line with the previous evidence indicating brat the LRN and the adjacent ventrolateral medulla is involved in descending inhibition of spinal nocifensive responses. However, α2-adrenoceptors in the LRN do not mediate spinal antinociception but, on the contrary, their activation counteracts antinociception at the spinal cord level. The spinal aninociceptive effect of supraspinally administered medetomidine in spinalized rats can be explained by a spread of the drug (e.g., via circulation) which then directly activates α2-adrenoceptors at the spinal cord level. 相似文献
7.
8.
Kalevi Laitinen David Sinclair Maria Nurmi Reija Hietala Heikki Kröger Kalervo Kiianmaa Mikko Salaspuro 《Alcoholism, clinical and experimental research》1992,16(5):875-880
Previous work has shown that calcitonin inhibits eating by rats and that it affects several neurotransmitter systems suspected to play a role in alcohol consumption. The present study was an initial test of whether calcitonin does affect voluntary alcohol consumption by male Wistar rats with prolonged alcohol experience. Calcitonin (20 IU/kg) or saline was injected subcutaneously on 10 consecutive days when the rats (n = 20) had continual access to 10% (v/v) ethanol solution, and to food and water. Using a cross-over design, the effects of 40 IU/kg calcitonin vs. saline were then examined in a second 10-day treatment period. Similar patterns of effects were obtained with both calcitonin doses, but the patterns differed with alcohol, food, and water intake. Alcohol drinking showed biphasic changes with both doses, producing highly significant Treatment x Day interactions (p < 1E-10 and p = 6E-7): it was significantly reduced on the first day of calcitonin treatment and significantly increased on the last few days. Food intake was reduced on all calcitonin days although most markedly on the first. Water drinking was not altered on the first calcitonin day, but was greatly increased on the second, then gradually returned toward the baseline. In a second experiment, the animals were switched to 1 hr of alcohol access per day, and calcitonin (20 IU/kg) was administered periodically to one group 4 hr before the alcohol access. Alcohol drinking was significantly reduced in all cases when the calcitonin injection was preceded by at least 1 day without calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
Heikki Wuorela 《Basic & clinical pharmacology & toxicology》1992,71(5):376-382
Abstract: The effects of calcium supplementation on blood pressure, intracellular free calcium concentration ([Ca2+],) and rate of Na+-H+ exchange were studied in DOC-NaCl-hypertensive rats. All the animals were uninephrectomized and divided into two main groups: the first group received deoxycorticosterone (DOC) (25 mg/kg, s.c.) once a week and had 0.7% NaCl as drinking fluid while the other received equal volumes of saline and tap water to drink. The animals were further divided according to dietary calcium intake: in the Control and DOC groups the chow contained 1.1% calcium, in the Calcium and DOC + Calcium groups, 2.5%. After 6 and 8 weeks, blood pressure in the DOC group was higher than in the Control group; on the other hand, the development of hypertension was attenuated in the DOC + Calcium compared with the DOC group. The Control and Calcium groups did not differ from each other. Platelets and lymphocytes were used as experimental models to study changes in the regulation of [Ca2+]i, evaluated by fluorescent indicators indo-1 and quin-2. In lymphocytes, basal [Ca2+]i was highest in the DOC group, but similar in DOC + Calcium and Control groups. In platelets, both basal and thrombin-stimulated [Ca2+]i were higher in the DOC and DOC + Calcium groups than in the Control group. In both cell types [Ca2+]i was similar in Control and Calcium groups. In addition, platelets were used to study the ability of the cells to recover from intracellular acidification by first blocking the Na+ -H+ exchange in a Na+-free medium and then restarting the exchange mechanism by increasing the extracellular Na+ concentration at constant speed. Changes in [pH]i were monitored by fluorescent indicator BCECF. The rate of Na+-H+ exchange in the recovery phase did not reveal differences between the experimental groups. Vascular smooth muscle function was examined by determining concentration-response curves for noradrenaline in mesenteric arterial rings and a shift to the left was observed in the DOC and DOC + Calcium groups compared with the Control group. The present data indicate that high calcium intake attenuates the development of mineralocorticoid-salt hypertension. The DOC-induced elevation of blood pressure is associated with higher [Ca2+]i in platelets and lymphocytes, evidencing disturbances in cellular calcium handling. However, possibly due to differing characteristics in regulatory mechanisms between these cell types, supplementary calcium reduced [Ca2+]i only in lymphocytes. The assumed elevation in intracellular sodium did not cause detectable changes in the Na+-H+ exchange rate in platelets. Enhanced vascular responses to noradrenaline observed in the DOC group were not altered by high calcium intake. 相似文献
10.
Arto J. Turunen José A. Fernández Leena Lindgren Kaija T. Salmela Lauri E. Kyllönen Heikki Mäkisalo John H. Griffin Sanna M. Siitonen Jari Petäjä Eero J. Pesonen 《American journal of transplantation》2005,5(9):2204-2212
We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L-selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Delta) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88-144]% before infusion vs. 232 [85-1246]% after infusion, p<0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Delta=-72 [-567 to 12]%, p<0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L-selectin r=0.7, p=0.01; lactoferrin r=-0.6, p=0.02; CD11b r=-0.8, p=0.001), and with both warm (r=0.6, p=0.01) and cold ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation. 相似文献