Influence of antenatal physical exercise on heart rate variability and QT variability.

OBJECTIVE: We sought to characterise the influence of an antenatal exercise programme on ECG-derived cardiac variables. METHODS: Fifity-one healthy pregnant women were recruited and randomly assigned (2 × 2×2 design) to an exercise group or a control group. Exercising groups attended weekly classes from the 20th week of pregnancy onwards. Cardiovascular assessments (heart rate variabiliy (HRV), QT, and the QT variability index (QTVI)) were performed at 12-16, 26-28, 34-36 weeks and 12 weeks following birth, during supine rest and exercise conditions. RESULTS: Advancing gestation was associated with an increased maternal heart rate (p = 0.001), shorter QT interval (p = 0.003), diminished HRV (p = 0.002) and increased QTVI (p = 0.002). Each of these changes was reversed within 12 weeks postpartum (p < 0.004). The Exercise group displayed exaggerated changes for all variables (except QT) but only during supine rest in the third trimester (p < 0.029). CONCLUSION: Advancing gestation is associated with a shift in HRV/QTVI towards values that have been associated with an elevated risk of arrhythmia. A 20-week exercise programme undertaken between mid and late pregnancy exaggerated these changes during rest in the third trimester of pregnancy.

Influence of physical exercise on baroreceptor sensitivity during pregnancy.

BACKGROUND: Baroreceptor sensitivity (BRS) refers to the magnitude of change in the heart rate in response to change in blood pressure (e.g. upon standing). The impact of regular antenatal exercise on maternal BRS is unclear. AIMS: To determine whether supervised weekly exercise influences BRS, and to determine if posture and calculation method are important in antenatal BRS measurement. STUDY DESIGN AND SUBJECTS: Eighty-one healthy pregnant women were randomly assigned to an exercise or control group. The exercise group attended weekly classes from the 20th week of pregnancy onwards. OUTCOME MEASURES: Cardiovascular assessments (beat-to-beat blood pressure, heart rate) were performed at 12-16, 26-28, 34-36 weeks and 12 weeks following birth. BRS was calculated using two methods ("sequence" and "beat-to-beat"). RESULTS: Fifty-one women (63%) completed the study. Mean BRS reduced progressively in all women (p < 0.025) and was lowest in those who exercised (0.046 < p < 0.002). Postnatal increases in BRS were independent of posture. Training-induced BRS (beat-to-beat) reduction occurred earlier than BRS (sequence), and only BRS (sequence) was affected by posture. Heart rate variability reduced with advancing gestation (p < 0.002) and was more pronounced in the exercise group (p < 0.029). CONCLUSIONS: Weekly exercise exaggerated the reductions in BRS and HRV during pregnancy and is likely linked to diminished parasympathetic activity.

Recruitment of pregnant women to an exercise-intervention study.

We share here our experience of recruiting pregnant women into an exercise intervention study. Recruitment challenges were anticipated owing to the study design, which required four hospital visits for cardiovascular assessment, a long-term (nine-month) commitment, and adherence to a 20-week exercise programme. Fifty-three women were assigned to one of three groups (no-exercise, land exercise or water exercise) using a 2 × 2 × 2 flexible randomisation design. Seven hundred forty-four women were screened at an antenatal clinic, of whom 501 were eligible to participate in the study. One hundred forty-five women were subsequently approached: 46 (32%) of whom agreed to participate, 42 (29%) were interested but then declined and 57 (39%) declined outright. Our study design helped recruit pregnant women as it allowed them some choice of group membership. We also noted that the participant-researcher relationship is important in reducing attrition. Our experience provides indications of likely recruitment and attrition rates for future randomised controlled trials of this type.

Changes in heart rate variability and QT variability during the first trimester of pregnancy.

The risk of new-onset arrhythmia during pregnancy is high, presumably relating to changes in both haemodynamic and cardiac autonomic function. The ability to non-invasively assess an individual's risk of developing arrhythmia during pregnancy would therefore be clinically significant. We aimed to quantify electrocardiographic temporal characteristics during the first trimester of pregnancy and to compare these with non-pregnant controls. Ninety-nine pregnant women and sixty-three non-pregnant women underwent non-invasive cardiovascular and haemodynamic assessment during a protocol consisting of various physiological states (postural manoeurvres, light exercise and metronomic breathing). Variables measured included stroke volume, cardiac output, heart rate, heart rate variability, QT and QT variability and QTVI (a measure of the variability of QT relative to that of RR). Heart rate (p < 0.0005, p < 0.0005, p < 0.0005) and cardiac output (p = 0.043, p < 0.0005, p < 0.0005) were greater in pregnant women in all physiological states (respectively for the supine position, light exercise and metronomic breathing state), whilst stroke volume was lower in pregnancy only during the supine position (p < 0.0005). QTe (Q wave onset to T wave end) and QTa (T wave apex) were significantly shortened (p < 0.05) and QTeVI and QTaVI were increased in pregnancy in all physiological states (p < 0.0005). QT variability (p < 0.002) was greater in pregnant women during the supine position, whilst heart rate variability was reduced in pregnancy in all states (p < 0.0005). Early pregnancy is associated with substantial changes in heart rate variability, reflecting a reduction in parasympathetic tone and an increase in sympathetic activity. QTVI shifted to a less favourable value, reflecting a greater than normal amount of QT variability. QTVI appears to be a useful method for quantifying changes in QT variability relative to RR (or heart rate) variability, being sensitive not only to physiological state but also to gestational age. We support the use of non-invasive markers of cardiac electrical variability to evaluate the risk of arrhythmic events in pregnancy, and we recommend the use of multiple physiological states during the assessment protocol.

Parasite manipulation of brain monoamines in California killifish (Fundulus parvipinnis) by the trematode Euhaplorchis californiensis.

California killifish (Fundulus parvipinnis) infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours rendering them more susceptible to predation by avian final hosts. Heavily infected killifish grow and reproduce normally, despite having thousands of cysts inside their braincases. This suggests that E. californiensis affects only specific locomotory behaviours. We hypothesised that changes in the serotonin and dopamine metabolism, essential for controlling locomotion and arousal may underlie this behaviour modification. We employed micropunch dissection and HPLC to analyse monoamine and monoamine metabolite concentrations in the brain regions of uninfected and experimentally infected fish. The parasites exerted density-dependent changes in monoaminergic activity distinct from those exhibited by fish subjected to stress. Specifically, E. californiensis inhibited a normally occurring, stress-induced elevation of serotonergic metabolism in the raphae nuclei. This effect was particularly evident in the experimentally infected fish, whose low-density infections were concentrated on the brainstem. Furthermore, high E. californiensis density was associated with increased dopaminergic activity in the hypothalamus and decreased serotonergic activity in the hippocampus. In conclusion, the altered monoaminergic metabolism may explain behavioural differences leading to increased predation of the infected killifish by their final host predators.

Corticotropin releasing factor influences aggression and monoamines: modulation of attacks and retreats.

Salmonids establish social hierarchies as a result of aggressive social interactions. The establishment of dominant or subordinate status is strongly linked to neuroendocrine responses mediated through the stress axis. In this study, we tested the effects of introcerebroventricular (icv) corticotropin releasing factor (CRF) on the behavioral outcome, plasma cortisol and monoamine function in trout subjected to a socially aggressive encounter. Rainbow trout were treated with an icv injection of artificial cerebrospinal fluid (aCSF), 500 or 2000 ng ovine CRF, or not injected. Fish were allowed to interact with a similarly sized conspecific for 15 min. Following the behavioral interaction, plasma cortisol and central monoamine concentrations were analyzed. Trout treated with CRF were victorious in approximately 66% of the aggressive encounters against aCSF-treated opponents. Trout injected with CRF exhibited a reduction in the total number of attacks and decreased latency to attack. When trout were divided into winners and losers, only victorious CRF-treated fish exhibited a reduced latency to attack and fewer retreats. Social stress increased cortisol levels in both winners and losers of aggressive interaction. This effect was enhanced with the additional stress incurred from icv injection of aCSF. However, icv CRF in addition to social stress decreased plasma cortisol in both winners and losers. While aggression stimulated significant changes in serotonergic and dopaminergic activity, the magnitude and direction were dependent on limbic brain region, CRF dose, and outcome of social aggression. With broad effects on aggressive behavior, anxiety, stress responsiveness, and central monoaminergic activity, CRF plays an important role in modulating the behavioral components of social interaction.

Cure of EMT-6 tumors by X rays or neutrons: effect of mixed-fractionation schemes.

EMT-6 mouse tumors were treated with (a) 1 or 5 fractions of either x rays or neutrons or (b) a mixture of both in which 2 fractions of neutrons (n) plus 3 fraction of x rays (x) were given in 5 days in the sequence n-n-x-x-x or n-x-x-x-n. Using local tumor control as an end point, neutron RBEs of 1.7 for single fractions and 2.6 for 5 fractions were obtained. The two mixed schemes yielded RBEs of 1.5 and 1.4, respectively. Therapeutic gain factors, calculated as the ratio of tumor to skin RBE with neutrons or mixed radiations, were highest for the mixed fractionation schemes. These results are due to an apparent enhancement of the neutron effect in the tumor but not in the skin with these regimens. Other normal tissues must be irradiated with mixed schemes to determine whether this phenomenon is limited to the skin.

Mechanisms underlying reduced growth rate in C3HBA mammary adenocarcinomas recurring after single doses of x-rays or fast neutrons.

C3HBA mammary tumors were irradiated with 3000 rads of 250-kVp X-rays or 1000 rads of 8-MeV neutrons, doses of radiation matched for producing equal growth delay. At 14 days postirradiation, tumors were regrowing at a reduced rate relative to controls. Cell kinetic parameters were examined using percentage of labeled mitoses techniques, and blood vessel spacing and tumor architecture were examined histologically to determine whether the mechanisms underlying growth rate changes were the same after neutron as after photon irradiation. The tumor volume-doubling time at 14 days posttreatment is similar in both irradiated groups (TD=117 hr for neutron-irradiated tumors, 132 hr for X-irradiated tumors) and is approximately twice as long as the doubling time of 61.4 hr in control tumors in the same size range. Control and X-irradiated tumors have median cell cycle durations of 19.3 and 18.5 hr, respectively; the more slowly growing X-irradiated tumors have a reduced growth fraction and increased cell loss factor. Regrowing neutron-irradiated tumors have a median cell cycle of 27.2 hr, with calculated growth fraction and cell loss factor values intermediate between those for control and X-irradiated tumors. Scatter in the percentage of labeled mitoses data makes it difficult to determine whether the cell cycle durations are significantly different. The average distance from tumor parenchymal interphase cells to the nearest recognizable blood vessel is nearly identical in the two irradiated groups and for both groups is significantly greater than interphase to vessel distance in controls. The average distance in irradiated tumors approaches the maximal distance for O2 diffusion in mouse adenocarcinomas of a corded structure surrounding a central blood vessel. Both neutron- and X-irradiated tumors contain more necrosis and fewer viable-appearing parenchymal cells than do control tumors of the same size. The similar growth rate and growth delay in this tumor after 3000 rads of X-rays of 1000 rads of neutrons occur in the face of possibly different cell cycle durations and seem related to similar circulatory system inadequacies which limit growth and are expressed as greater average cell-to-blood-vessel distance and increased cell loss leading to necrosis, indicating oxygen or nutrient deprivation.