Variable Heart Research Articles

Outbreak of dysautonomia (Key-Gaskell syndrome) in a closed colony of pet cats

Six of eight pet cats in a closed colony developed overt signs of dysautonomia over a period of seven days; two of them died and one was euthanased. Dysautonomia was...

A maximum likelihood approach for estimating the QT correction factor using mixed effects model.

Assessment of QT interval prolongation is often used for assessing the cardiac safety of a new drug. However, the correction of the QT interval for varying heart rates has potential bias due to various different correction factors. This article proposes a maximum likelihood (ML) approach for calculating the appropriate individual correction factor using the data. The data come from a study with 24 subjects participating in a 10 day multiple dose (NEW RX) placebo-controlled cross-over trial with repeat ECGs obtained at baseline and at day 10. ML techniques were used to fit a random-effects model to observed QT and HR values for estimating the pooled and individual correction factors. QT(c) values using four correction factors (Bazett, Friderecia, pooled and individual) were investigated. The relative performance of the various correction factors are given in terms of variability and graphical techniques. The pooled correction factor was estimated to be 0.292 and the individual correction factors ranged from 0.19 to 0.41. The assessment of the treatment effect on QT(c) yielded inconsistent results. Bazett's factor indicated prolongation (6.55+/-1.20), Friderecia's factor indicated no change, while the pooled (-2.92+/-0.94) and individual (-2.82+/-1.00) factors showed a significant decrease. Graphical examination of individual QT(c) data showed a significant advantage in the use of individual correction factors versus Bazett's factor both in terms of sensitivity as well as reduction in bias. Use of individual correction factors is advocated for the assessment of possible drug-induced QT(c) prolongation.

Heart rate responses of male orienteers aged 21-67 years during competition

Orienteering is a sport in which it is common for most participants to be aged over 40 years, but research into the demands of the sport has focused almost exclusively on elite participants aged 21–35 years. The aim of the present study was to examine the heart rate responses of older male orienteers. Thirty-nine competitive male orienteers were divided into three groups: group 1 (international competitive standard, n=11, age 21–67 years), group 2 (national competitive standard, n=15, age 24–66 years) and group 3 (club competitive standard, n=13, age 23–60 years). Each participant had his heart rate monitored during two orienteering races of contrasting technical difficulty. The results were analysed using analysis of covariance, with age as a covariate, and Pearson product-moment correlation coefficients to determine whether age was related to the observed heart rate responses. The groups did not differ in their peak (175±12 beats · min−1, P=0.643) or mean (159±13 beats · min−1, P=0.171) heart rates during the races. There was a decline of 6 beats · min−1 · decade−1 (P=0.001) for peak heart rate and 5 beats · min −1·decade−1 (P<0.001) for mean heart rate. Mean heart rates were 86±6% of the participants' maximal heart rates and were not associated with age. The orienteers in group 1 displayed a lower (P<0.005) within-race standard deviation in heart rate (6±2 beats · min−1) than those in groups 2 and 3 (10±3 and 10±4 beats · min−1, respectively). In conclusion, the mean heart rates indicated that all three groups of orienteers ran at a relative high intensity and the international competitive standard orienteers displayed a less variable heart rate, which may have been related to fewer instances of slowing down to relocate and being able to navigate while running at relatively high speeds.

Antepartum amnioinfusion: a review

Objective: Antepartum amnioinfusion is a relatively recent procedure introduced with fetal medicine techniques. It is usually indicated for severe oligohydramnios in order to avoid the related complicationssuch as pulmonary hypoplasia, the deforming effects of oligohydramnios, variable fetal heart rate decelerations and intraventricular hemorrhage. Antepartum amnioinfusion is also employed to improve ultrasoundvisualization in cases with oligohydramnios. Our objective was to evaluate the benefits and complications related to this procedure which is still less commonly used compared to intrapartum amnioinfusion,and whose risks are therefore not well established.Study design: Reports of study designs identified from searches of MEDLINE, PUBMED, the Cochrane Collaboration, specialized databases and bibliographiesof review articles were identified. Studies in women who underwent amnioinfusion between 1987 and 2002 were included.Results and conclusions: Amnioinfusion seems to offer several benefits, interms of both prenatal diagnosis and favorable perinatal outcome. Most clinical experiences report that amnioinfusion is safe, both for the mother and for the fetus. However, randomized control-group studiessubdivided on the basis of the cause of oligohydramnios (e.g. premature rupture of membranes, fetal growth restriction, obstructive uropathy and renal agenesis) could help to determine the advantages andrisks linked to this procedure. Prospective randomized studies should therefore be encouraged, to clarify any possible doubts regarding the procedure, before it can be introduced into routine practice inthe management of oligohydramnios.

Meconium-Stained Amniotic Fluid in Labor: A Randomized Trial of Prophylactic Amnioinfusion

Puertas, Alberto; Paz Carrillo, M.; Moltó , Luis; Álvarez, Margarita; Sedeño, Salvador; Miranda, José

Amnioinfusion for meconium-stained liquor in labour.

Amnioinfusion aims to prevent or relieve umbilical cord compression during labour by infusing a solution into the uterine cavity. It is also thought to dilute meconium when present in the amniotic fluid and so reduce the risk of meconium aspiration. However it may be that the mechanism of effect is that it corrects oligohydramnios (reduced amniotic fluid), for which thick meconium staining is a marker. The objective of this review was to assess the effects of amnioinfusion for meconium-stained liquor on perinatal outcome. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched. Randomised trials comparing amnioinfusion with no amnioinfusion for women in labour with moderate or thick meconium-staining of the amniotic fluid. Eligibility and trial quality were assessed by one reviewer. Ten studies, most involving small numbers of participants, were included. Under standard perinatal surveillance, amnioinfusion was associated with a reduction in the following: heavy meconium staining of the liquor (relative risk 0.03, 95% confidence interval 0.01 to 0.15); variable fetal heart rate deceleration (relative risk 0.47, 95% confidence interval 0.24 to 0. 90); and a trend to reduced caesarean section overall (relative risk 0.83, 95% confidence interval 0.69 to 1.00). No perinatal deaths were reported. Under limited perinatal surveillance, amnioinfusion was associated with a reduction in the following: meconium aspiration syndrome (relative risk 0.24, 95% confidence interval 0. 12 to 0.48); neonatal hypoxic ischaemic encephalopathy (relative risk 0.07, 95% confidence interval 0.01 to 0.56) and neonatal ventilation or intensive care unit admission (relative risk 0.56, 95% confidence interval 0.39 to 0.79); there was a trend towards reduced perinatal mortality (relative risk 0.34, 95% confidence interval 0.11 to 1.06). Amnioinfusion is associated with improvements in perinatal outcome, particularly in settings where facilities for perinatal surveillance are limited. The trials reviewed are too small to address the possibility of rare but serious maternal adverse effects of amnioinfusion.

Meconium-stained amniotic fluid in labor: a randomized trial of prophylactic amniofusion

Objectives: To investigate the effect of amnioinfusion in women with meconium-stained amniotic fluid on the rate of cesarian sections and on neonatal morbidity. Study design: A randomized controlled trial. A total of 206 women with meconium-stained amniotic fluid were assigned to receive amnioinfusion via two-way catheter or no amnioinfusion (control group). The catheter was inserted and other treatment was the same in both groups. Results: Amnioinfusion decreased the rate of cesarian sections for fetal distress (RR 0.23, 95% CI 0.07–0.79) and increased mean pH at birth (7.24±0.1 versus 7.21±0.1, P<0.05). It also decreased the frequency of variable fetal heart rate decelerations (RR 0.74, 95% CI 0.59–0.92), and of meconium below the vocal cords in neonates (RR 0.37, 95% CI 0.19–0.69). Conclusions: Amnioinfusion improves the neonatal outcome and reduces the frequency of cesarian sections.

Enhanced cardiac thermal dilution measurement of cardiac output, volumes, regurgitation, valve effective diameters, ventricular power and efficiency – Feasibility analysis using digital simulation

Cardiac output is measured by the thermal dilution method which uses a quadruple lumen catheter, with a thermistor on the tip, through the right atrium, right ventricle and into the pulmonary artery. Cold saline is injected into the right atrium and the resulting pulmonary artery temperature profile is integrated. The same procedure performed with three thermistors and three pressure sensors located on the catheter to measure temperature and pressure in the atrium, ventricle and artery respectively will produce a set of temperature and pressure curves with shapes determined by injectate temperature, injectate volume, heart rate, systolic time interval, body temperature, cardiac output, volumes, flow rates and valve openings. A digital computer program has been developed to optimize the fit of a lumped parameter model to the thermodilution curves in order to determine heart rate, systolic time as a fraction of cardiac cycle, right atrial systolic and diastolic volumes, ventricular systolic and diastolic volumes, cardiac output, inflow valve forward and reverse flow rates and effective diameters, outflow valve forward and reverse flow rates and effective diameters, ventricular power and efficiency. The program has been tested over a range of operating conditions including noise in the temperature and pressure signals, randomly varying heart rate and cardiac cycle. All of the data for the tests were produced by a digital computer simulation of a pulsatile artificial heart. The results of these tests indicate that the enhanced thermal dilution analysis method is feasible.

The effect of variable heart rate decelerations on intraventricular hemorrhage and other perinatal outcomes in preterm infants.

We investigated the hypothesis that repetitive variable heart rate decelerations in labor are associated with an increased incidence of neonatal complications in premature infants. This was a retrospective case-control study. Singleton fetuses weighing between 750 and 2500 g at 25-35 weeks' gestation were considered for the study. Fetuses delivered by Cesarean section prior to labor were excluded. Heart rate traces were retrieved from an electronic archive and were assessed for the presence of variable decelerations. Cases had at least three variable decelerations in the hour prior to delivery and were matched 1:1 with controls for gestation, sex and birth weight. A review of 6500 deliveries yielded 41 matched pairs. The groups were compared for the following outcomes. Measures of acute morbidity were cord pH at delivery, 5-min Apgar score and resuscitation; measures of chronic morbidity were intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis and death. There was no difference in measures of acute morbidity between the groups. The incidence of chronic morbid outcome measures in the cases was six (15%) vs. one (2.5%) in controls (p = 0.01). This study suggests that variable decelerations in preterm infants are associated with chronic morbidity, particularly intraventricular hemorrhage through a mechanism independent of fetal acidemia. Further study is required to determine whether these infants would benefit from early Cesarean section.

Molecular Basis of the Delayed Rectifier Current IKsin Heart

J. Kurokawa, H. Abriel and R. S. Kass. Molecular Basis of the Delayed Rectifier Current IKsin Heart. Journal of Molecular and Cellular Cardiology (2001) 33, 873–882. Electrical activity underlies the control of the frequency, strength, and duration of contraction of the heart. During the cardiac cycle, a regular rhythmic pattern must be established in time-dependent changes in ionic conductances in order to ensure events that underlie normal cardiac function. This pattern must be tightly regulated by sympathetic nervous activity to ensure a physiologically relevant relationship between diastolic filling and ejection times with variable heart rate. The duration of the ventricular action potential is controlled in part by a slowly activated potassium channel current, IKs. The molecular identity of the subunits that comprise the channels conducting this current is important, not only for understanding the fundamental mechanisms that control electrical activity in healthy individuals, but also for understanding the molecular basis of at least one inherited human disease, LQTS-1. This brief review summarizes key points of information regarding the molecular determinants of the activity of these channels, their relationship to human disease, and what is known, and yet to be discovered, about the molecular determinants of the regulation of this channel by sympathetic nervous activity.

Direct biologically based biosensing of dynamic physiological function.

Dynamic regulation of biological systems requires real-time assessment of relevant physiological needs. Biosensors, which transduce biological actions or reactions into signals amenable to processing, are well suited for such monitoring. Typically, in vivo biosensors approximate physiological function via the measurement of surrogate signals. The alternative approach presented here would be to use biologically based biosensors for the direct measurement of physiological activity via functional integration of relevant governing inputs. We show that an implanted excitable-tissue biosensor (excitable cardiac tissue) can be used as a real-time, integrated bioprocessor to analyze the complex inputs regulating a dynamic physiological variable (heart rate). This approach offers the potential for long-term biologically tuned quantification of endogenous physiological function.

Lack of relationship between variable decelerations during reactive nonstress tests and oligohydramnios.

We sought to prospectively determine the value of variable and lambda decelerations noted during nonstress tests in predicting oligohydramnios and perinatal outcome. On the same day as having had reactive nonstress tests, 651 women underwent obstetrical ultrasound examinations for amniotic fluid index (AFI). Lambda and variable fetal heart rate decelerations were identified on sets of otherwise-reactive nonstress tests. Those with variable decelerations composed group 1; those without variable decelerations composed group 2. Demographic, perinatal outcome, and AFI data were compared, and group 1 inclusion criteria were varied. There were 200 nonstress tests in group 1 and 490 in group 2. There was a small difference between groups in maternal age (1.2 years, p = 0.02) and gestational age (0.8 weeks, p = 0.01), but no differences in gravidity, parity, race, or indications for testing (p >0.05). Oligohydramnios was present in 14.5% in group 1 and in 13.3% of group 2 (p = 0.68). In the cases of amniotic fluid index <8 cm, depth and duration of the variable decelerations did not correlate with AFI (R2 = 0.11, p = 0.09). Variable decelerations were associated with intrapartum "fetal distress," but lambda decelerations did not correlate with any outcome. Variable decelerations on an otherwise-reactive nonstress test did not correlate with amniotic fluid volume and were not cause for intervention in this study.

The effect of variable heart rate decelerations on intraventricular hemorrhage and other perinatal outcomes in preterm infants

Objective: We investigated the hypothesis that repetitive variable heart rate decelerations in labor are associated with an increased incidence of neonatal complications in premature infants. Methods: This was a retrospective case-control study. Singleton fetuses weighing between 750 and 2500 g at 25-35 weeks' gestation were considered for the study. Fetuses delivered by Cesarean section prior to labor were excluded. Heart rate traces were retrieved from an electronic archive and were assessed for the presence of variable decelerations. Cases had at least three variable decelerations in the hour prior to delivery and were matched 1 : 1 with controls for gestation, sex and birth weight. Results: A review of 6500 deliveries yielded 41 matched pairs. The groups were compared for the following outcomes. Measures of acute morbidity were cord pH at delivery, 5-min Apgar score and resuscitation; measures of chronic morbidity were intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis and death. There was no difference in measures of acute morbidity between the groups. The incidence of chronic morbid outcome measures in the cases was six (15%) vs. one (2.5%) in controls ( p = 0.01). Conclusions: This study suggests that variable decelerations in preterm infants are associated with chronic morbidity, particularly intraventricular hemorrhage through a mechanism independent of fetal acidemia. Further study is required to determine whether these infants would benefit from early Cesarean section.

Delayed rectifier K currents have reduced amplitudes and altered kinetics in myocytes from infarcted canine ventricle.

The rapid (I(Kr)) and slow (I(Ks)) components of delayed rectifier currents play an important role in determining the cardiac action potential configuration. Abnormalities in their function may contribute to arrhythmogenesis under pathological conditions. We studied the effects of myocardial infarction on I(Kr) and I(Ks) in canine ventricular myocytes and their molecular basis. Infarct zone myocytes (IZs) were isolated from a thin layer of surviving epicardium overlying an infarct 5 days after a total occlusion of the left anterior descending (LAD) coronary artery. Normal myocytes (NZs) were isolated from the corresponding region of control hearts for comparison. Currents were recorded under the whole-cell patch clamp conditions. Both I(Kr) and I(Ks) current densities were reduced in IZs versus NZs. Kinetic analysis further suggests an acceleration of I(Kr) activation and I(Ks) deactivation. RNase protection assays were used to quantify the mRNA levels of I(Kr) and I(Ks) channel subunits (dERG, dIsK and dKvLQT1) in tissue immediately adjacent to the region where myocytes were isolated. mRNA levels of all three subunits were reduced 2 days after LAD occlusion (by 48+/-9%, 68+/-5%, and 45+/-4% for dERG, dIsK and dKvLQT1, respectively, n=8 each). By day 5, the dKvLQT1 message returned to control while those of dERG and dIsK remained reduced (by 52+/-7% and 76+/-6%, respectively). The decrease in I(Kr) and I(Ks) amplitudes and changes in their kinetics in infarcted tissue might be due to a decrease in functional channels and/or changes in their subunit composition. Heterogeneous changes in I(Kr) and I(Ks) in infarcted hearts may impact on the effects of varying heart rate or neurohumoral modulation on repolarization.

Social subordination stress, behavior, and central monoaminergic function in female cynomolgus monkeys

Background: Social subordination in female cynomolgus monkeys is stressful and activates the hypothalamic–pituitary–adrenal axis. In a previous experiment behavioral depression was observed in a subset of subordinates. Methods: In the experiment reported here behavioral and physiological indicators of stress were evaluated in dominant and subordinate female cynomolgus monkeys, and brain dopaminergic activity was assessed, as reflected in the prolactin response to haloperidol, a dopamine 2 (D 2) receptor antagonist. Results: Subordinates were aggressed more, spent more time in fearful scanning of the social environment, spent less time as the recipients of the active affiliative behavior of being groomed, had more variable heart rates in response to a novel environment, and were hypercortisolemic compared to dominants. Prolactin responses to haloperidol challenge were lower in subordinates than dominants, an observation consistent with the hypothesis that subordinate females have decreased D 2 receptor function. Conclusions: These observations suggest that social subordination is stressful and may alter brain dopaminergic function in primates. The neurophysiological characteristics of social subordinates may contribute to their susceptibility to depression.

Randomized, blinded, placebo-controlled trial of tissue factor pathway inhibitor in porcine septic shock.

This study tested the hypothesis that tissue factor pathway inhibitor (TFPI) would improve mortality and morbidity evoked by peritonitis-induced bacteremia in pigs. Secondarily, it sought to determine if TFPI treatment would attenuate cardiodynamic abnormalities produced by this septic model. 32 pigs were chronically instrumented with intracardiac transducers to measure left ventricular pressure and diameter, pulmonary and aortic pressures, and cardiac output. At least 5 days after surgery to implant transducers, basal cardiovascular readings and blood samples were obtained. Using a randomized, blinded study design, either purified, reconstituted TFPI (1 mg/kg bolus, 10 mg/kg/min for 48 h), placebo (arginine buffer), or saline was administered to pigs immediately after Escherichia coli 0111.B4 (3.0-11 x 10(9) colony-forming U/kg)-laden fibrin clots were implanted intraperitoneally, producing peritonitis and bacteremia. Pigs did not receive antibiotics or supportive therapy. No significant differences in primary or secondary endpoints were noted between the arginine and saline groups, so these data were combined into a control group (N = 20). 5 of 12 TFPI pigs survived (42%), while 5 of 20 control pigs survived (25%); this difference was not significant (p = .714, Fisher's exact test). TFPI treatment augmented cardiac output in surviving pigs, but did not affect any other cardiovascular performance variable (heart rate, % diameter shortening, or systemic and pulmonary vascular resistance). In controls, peritonitis induced rapid increase in plasma tumor necrosis factor-alpha (428 +/- 771 to 5,933 +/- 559 pg/mL at 2 h) and interleukin-8 (180 +/- 153 to 1,393 +/- 145 pg/mL at 2 h). TFPI treatment significantly attenuated cytokine responses to sepsis, reducing peak tumor necrosis factor-alpha to 2,103 +/- 813 pg/mL and reducing peak interleukin-8 levels to 534 +/- 211 pg/mL at 2 h (p < .05, Tukey test, two-way ANOVA). In conclusion, TFPI treatment attenuated important mediator components of the inflammatory response but did not provide significant survival benefit.

Amnioinfusion for umbilical cord compression in labour.

Amnioinfusion aims to prevent or relieve umbilical cord compression during labour by infusing a solution into the uterine cavity. The objective of this review was to assess the effects of amnioinfusion on maternal and perinatal outcome for potential or suspected umbilical cord compression or potential amnionitis. The Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register were searched. Randomised trials of amnioinfusion compared with no amnioinfusion in women with babies at risk of umbilical cord compression; and women at risk of intrauterine infection. Eligibility and trial quality were assessed by the reviewer. Twelve studies were included. Transcervical amnioinfusion for potential or suspected umbilical cord compression was associated with the following reductions: fetal heart rate decelerations (relative risk 0.54, 95% confidence interval 0.43 to 0.68); caesarean section for suspected fetal distress (relative risk 0.35, 95% confidence interval 0.24 to 0.52); neonatal hospital stay greater than 3 days (relative risk 0.40, 95% confidence interval 0. 26 to 0.62); maternal hospital stay greater than 3 days (relative risk 0.46, 95% 0.29 to 0.74). Transabdominal amnioinfusion showed similar results. Transcervical amnioinfusion to prevent infection in women with membranes ruptured for more than 6 hours was associated with a reduction in puerperal infection (relative risk 0.50, 95% confidence interval 0.26 to 0.97). Amnioinfusion appears to reduce the occurrence of variable heart rate decelerations and lower the use of caesarean section. However the studies were done in settings where fetal distress was not confirmed by fetal blood sampling. The results may therefore only be relevant where caesarean sections are commonly done for abnormal fetal heart rate alone. The trials reviewed are too small to address the possibility of rare but serious maternal adverse effects of amnioinfusion.

Transcervical intrapartum amnioinfusion: a simple and effective technique

Objective: To test a simple method of intrapartum amnioinfusion to replace amniotic fluid during labor in cases of prolonged labor and severe variable fetal heart rate decelerations or thick meconium. Study design: We conducted a prospective study of intrapartum amnioinfusion in sixteen consecutive patients. A simple transcervically placed Foley bladder catheter was used for intrauterine infusion of saline solution, while monitoring was performed by external cardiotocography. Results: In twelve patients, catheter placement was easily performed; the remaining four required stabilization by a mandrel for insertion. Amnioinfusion was effective in ten out of thirteen patients for relief of fetal heart rate anomalies. No complications were observed; all had good neonatal outcome. Conclusions: In our small, uncontrolled study, this amnioinfusion method proved to be a simple, inexpensive, effective and safe technique for the relief of severe heart rate anomalies in prolonged labor.

Effect of variable heart rate decelerations on perinatal outcome in low birthweight infants

Effect of variable heart rate decelerations on perinatal outcome in low birthweight infants

Amnioinfusion for the prevention of meconium aspiration during labour.

The aim of this observational study is to review the outcome of prophylactic intrapartum amnioinfusion (AI) in pregnancies complicated by moderate to thick meconium-stained liquor (MSL). The labour and neonatal outcome of all 298 AIs performed over a 3-year period were compared to a matched-control group of patients whose labour was complicated by moderate or thick MSL but without AI. The incidence of moderate or thick meconium below the vocal cords of the neonate were significantly lower in the AI group (6.4% and 3.4%) compared with the control group (15.4% and 6.7%). The incidence of meconium aspiration syndrome in the AI group was half (1.7%) that of the control group (3.7%), although the difference did not reach statistical significance. There was a significant higher incidence of cardiotocographic abnormalities in the AI group (30.5% versus 14.7%), with higher incidences of Caesarean section and operative vaginal deliveries. The reduction in the incidence and thickness of meconium after AI was not accompanied by any statistically significant reduction in adverse fetal outcomes such as low Apgar scores, cord pH values, admissions to and duration of admission to the neonatal unit, or the incidence of meconium-aspiration syndrome.