Biallelic mutations in mitochondrial tryptophanyl-tRNA synthetase cause Levodopa-responsive infantile-onset Parkinsonism.

Mitochondrial aminoacyl-tRNA synthetases (mtARSs) are essential, ubiquitously expressed enzymes that covalently attach amino acids to their corresponding tRNA molecules during translation of mitochondrial genes. Deleterious variants in the mtARS genes cause a diverse array of phenotypes, many of which involve the nervous system. Moreover, distinct mutations in mtARSs often cause different clinical manifestations. Recently, the gene encoding mitochondrial tryptophanyl tRNA synthetase (WARS2) was reported to cause 2 different neurological phenotypes, a form of autosomal recessive intellectual disability and a syndrome of severe infantile-onset leukoencephalopathy. Here, we report the case of a 17-year-old boy with compound heterozygous mutations in WARS2 (p.Trp13Gly, p.Ser228Trp) who presented with infantile-onset, Levodopa-responsive Parkinsonism at the age of 2 years. Analysis of patient-derived dermal fibroblasts revealed decreased steady-state WARS2 protein and normal OXPHOS content. Muscle mitochondrial studies suggested mitochondrial proliferation without obvious respiratory chain deficiencies at the age of 9 years. This case expands the phenotypic spectrum of WARS2 deficiency and emphasizes the importance of mitochondrial protein synthesis in the pathogenesis of Parkinsonism.

Essential fatty acid profiling for routine nutritional assessment unmasks adrenoleukodystrophy in an infant with isovaleric acidaemia.

We report a 16-month-old asymptomatic male with enzyme confirmed isovaleric acidaemia (IVA; isovaleryl-CoA dehydrogenase deficiency; OMIM 243500) who, upon routine nutritional follow-up, presented evidence of peroxisomal dysfunction. The newborn screen (2 days of life) revealed elevated C(5)-carnitine (2.95 µmol/L; cutoff <0.09 µmol/L) and IVA was subsequently confirmed by metabolic profiling and in vitro enzymology. Plasma essential fatty acid (EFA) analysis, assessed to evaluate nutritional status during protein restriction and L: -carnitine supplementation, revealed elevated C(26:0) (5.0 µmol/L; normal <1.3). Subsequently, metabolic profiling and molecular genetic analysis confirmed X-linked adrenoleukodystrophy (XALD). Identification of co-inherited XALD with IVA in this currently asymptomatic patient holds significant treatment ramifications for the proband prior to the onset of neurological sequelae, and critically important counselling implications for this family.

Potentiation of radiation therapy by vinorelbine (Navelbine) in non-small cell lung cancer.

Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France), a semisynthetic vinca alkaloid that is a potent inhibitor of mitotic microtubule polymerization, was recently approved for the treatment of non-small cell lung cancer. Radiotherapy also has been widely used to treat this malignancy. Since other antitumor agents that act on microtubules, such as paclitaxel and estramustine, have been shown to act as radiosensitizers, we studied the ability of vinorelbine to potentiate radiation. The in vitro activity of this combination was evaluated in the human lung carcinoma cell lines NCI-H460 and A549. when NCI-H460 cells were exposed to vinorelbine for 24 hours and then irradiated (1 to 6 Gy) the drug potentiated radiation in a dose-dependent manner, with the ratio of fractional survival (radiation) to fractional survival (drug plus radiation) ranging from 1.7:1 at 1 Gy to 5.5:1 at 6 Gy. When the treatment sequence was reversed (ie, radiation was followed by drug exposure), similar survival ratios were obtained at concentrations of vinorelbine that were five to 10 times lower. In this cell line radiation produced a block in the G2/M phase of the cell cycle, with the maximum block (60% to 70%) occurring 10 hours after treatment. The greatest potentiation was seen when irradiated cells were exposed to vinorelbine after they had plateaued in the G2/M phase of the cycle. Vinorelbine given early after irradiation, when only 10% to 30% of the cells were in G2/M, produced survival ratios similar to those of controls treated with radiation alone. In A549 cells radiation induced a G1 block. In this case, vinorelbine was unable to potentiate the effects of radiation. These studies show that vinorelbine can potentiate the antitumor effects of radiation and that the potentiation is cell cycle-dependent, with the maximal effect being obtained when the cells are in the G2 phase.

An in vitro analogue of immune dysfunction with altered immunoglobulin production in the aged.

The consequences of aging of the immune system include impaired T-lymphocyte responsiveness and aberrant immunoglobulin production. Although T cells from elderly individuals have a well-described defect in lymphoblastic transformation in response to some polyclonal mitogens, immunoglobulin abnormalities have lacked a clear in vitro model. Peripheral blood mononuclear cells from 13 young and 13 old healthy donors were cultured with phytohemagglutinin (PHA) or pokeweed mitogen (PWM). Old-donor-cell phytohemagglutinin (PHA), but not PWM, cultures had significantly lower lymphoblastic transformation compared with young donor cultures. IgG, IgA, and IgM production tended to be lower in old- versus young-donor PWM cell cultures. By contrast, despite lower lymphoblastic transformation in old-donor PHA cell cultures, immunoglobulin production was higher for old- versus young-donor cell cultures. No significant age differences were present in initial lymphocyte counts, percent B cells, T cells or monocytes, or helper/suppressor ratios to explain this enhancement in immunoglobulin production. PHA-stimulated mononuclear cell cultures in the aged demonstrate not only a defect in proliferation but also increased immunoglobulin production. This in vitro system may be useful to characterize further the pathogenesis of altered immunoglobulin production in the elderly.

Plasma acid-base regulation above and below ventilatory threshold in late gestation.

Stewart's physicochemical approach was used to study the effects of pregnancy on acid-base regulation in arterialized blood. Responses of 15 healthy pregnant women (PG; gestational age, 37.1 +/- 0.2 wk) were compared with those of 15 nonpregnant controls (CG) at rest and during cycling at 70 and 110% of the ventilatory threshold (T(vent)). Hydrogen ion concentration ([H(+)]) was lower in the PG vs. CG at rest and during exercise (P < 0.05 at rest and 70% T(vent)). Exercise-induced changes in [H(+)] were similar between groups. Lower resting [H(+)] values in the PG vs. CG resulted from lower values for arterialized PCO(2) (Pa(CO(2))) and total weak acid ([A](tot)), which were partly offset by a lower strong-ion difference ([SID]). Reductions in [A](tot) and [SID] at rest were primarily the result of reductions in albumin [Alb] and sodium [Na(+)], respectively. In the transition from rest to 70% T(vent), small increases in Pa(CO(2)) and [A](tot) contributed to moderate increases in [H(+)] in both groups, however [SID] increased in the PG and decreased in the CG (P < 0.05 between groups). In the transition from rest to 110% T(vent), decreases in [SID] made a significantly greater contribution to changes in [H(+)] in the CG vs. PG. Exercise-induced increases in [H(+)] are similar in the pregnant vs. nonpregnant state, but there is a reduced contribution of [SID] both above and below T(vent) during pregnancy.

Maximal exercise testing in late gestation: fetal responses.

OBJECTIVE: To determine the fetal response to and safety of maximal maternal exercise in the third trimester. METHODS: Twenty-three active women with uncomplicated pregnancies (singleton gestations) underwent maximal exercise testing in late gestation using a progressive maximal cycle ergometer protocol. Fetal heart rate (FHR) responses were monitored and classified using National Institute of Child Health and Human Development guidelines. Statistical analyses involved use of the Student t test, repeated measures analysis of variance with Tukey-Kramer multiple comparisons posttest, and the chi(2) test. RESULTS: There was an increase in baseline FHR in the 20-minute posttest period compared with the 20-minute pretest period. There were significantly fewer accelerations in the second posttest 10-minute segment compared with the second pretest 10-minute segment. Variability was reduced in both posttest periods compared with the first 10-minute pretest period. Time to reactivity increased after testing. Mild tachycardia was noted in two tracings and bradycardia occurred in a fetus with previously undiagnosed growth restriction. There were no abnormal neonatal outcomes. CONCLUSION: Maximal exercise testing in late gestation led to minimal changes in FHR. Fetal bradycardiac responses were not seen in appropriate for gestational age fetuses, suggesting that brief maximal maternal exertion for research or diagnostic purposes is safe in this group.

Effects of pregnancy and chronic exercise on respiratory responses to graded exercise.

Effects of cycle ergometer conditioning (heart rate 143 +/- 2 beats/min, 25 min/session, 3 sessions/wk) during the second and third trimesters of pregnancy were studied in 18 healthy previously sedentary women. A nonexercising control group (n = 9) was also studied. Graded exercise tests were conducted for both groups at approximately 17, 27, and 37 wk of gestation and at 20 wk postpartum. Both groups exhibited augmented ventilatory responses to exercise throughout pregnancy. Significant aerobic conditioning effects observed in the exercised group between entry and third trimester of pregnancy testing included a 17% increase in oxygen pulse at peak exercise, reduction in the respiratory exchange ratio during standard submaximal exercise, and an increase in work rate at the onset of blood lactate accumulation. Onset of blood lactate accumulation did not change significantly in the control group. Respiratory exchange ratio at peak exercise was higher in postpartum tests compared with those conducted in late gestation in both groups. Peak postexercise lactate levels were also significantly lower in second and third trimesters of pregnancy testing compared with postpartum in the control group. This effect appeared to be prevented by physical conditioning in the exercised group. The study results support the hypothesis that moderate aerobic conditioning increases maximal aerobic power and the capacity for sustained submaximal exercise. Chronic exercise also appeared to help to preserve anaerobic working capacity in late gestation.

Maximal exercise testing in late gestation: maternal responses.

OBJECTIVE: To study the effects of human pregnancy on metabolic and respiratory responses to maximal cycle ergometer testing and to test the hypothesis that the respiratory exchange ratio at maximal exercise and peak postexercise lactate concentration are lower in the pregnant compared with the nonpregnant state and that these effects are associated with lower excess postexercise oxygen consumption during pregnancy. METHODS: The pregnant (n = 14, mean gestational age 34.7 +/- 0.4 weeks) and nonpregnant control group (n = 14) included healthy, physically active women. Groups were matched for age, height, parity, prepregnant body mass and body mass index (BMI), and aerobic fitness. Breath-by-breath gas exchange was measured at rest, during exercise, and 15 minutes after exercise. The minimum sample size to detect a statistically significant result for a reasonable difference (0.25 L/min) in the ventilatory threshold was calculated to be ten subjects per group; thus, 14 was considered adequate. RESULTS: Maximal oxygen uptake, the ventilatory threshold, the point of respiratory compensation, and calculated work efficiency did not differ significantly between groups. However, the respiratory exchange ratio at maximal exercise, peak postexercise lactate, and excess postexercise oxygen consumption were significantly lower in the pregnant group. Peak lactate was significantly correlated with the respiratory exchange ratio and excess postexercise oxygen consumption. CONCLUSION: The capacity for weight-supported work is preserved in late gestation, and work efficiency is unchanged. However, carbohydrate utilization might be blunted at high levels of exertion. Blunted respiratory responses were attributed to reduced lactate production and/or dilution of lactate in an expanded blood volume.

Effects of acute and chronic maternal exercise on fetal heart rate.

Maternal-fetal effects of cycle ergometer conditioning (heart rate of 145 beats/min at 25 min/day for 3 days/wk) were studied during the second and third pregnancy trimesters. Subjects were 22 previously sedentary women and 16 nonexercising pregnant control women. Fetal heart rate (FHR) characteristics were studied before, during, and after 15 min of upright cycling at a maternal heart rate target of 145 beats/min at the end of both the second and third trimesters. Despite higher cycling power outputs in the exercised group, mean FHR responses were similar in both groups and conformed to 1) gradual increase in FHR baseline during exercise, 2) normal variability, and 3) normal reactivity. Fetal bradycardia was observed during (n = 1) and after (n = 2) exercise in three isolated tests. The timing of these events suggested that the likelihood of significant fetal hypoxia is highest in the immediate postexercise period. These results also support the hypothesis that physically conditioned women can perform at higher exercise power outputs than sedentary women without inducing fetal hypoxic stress. Further study is recommended to examine possible fetal and placental adaptations to maternal aerobic conditioning.

Acid-base regulation after maximal exercise testing in late gestation.

This study employed Stewart's physicochemical approach to quantify the effects of pregnancy and strenuous exercise on the independent determinants of plasma H+ concentration ([H+]). Subjects were nine physically active pregnant women [mean gestational age = 33 +/- 1 (SE) wk] and 14 age-matched nonpregnant controls. Venous blood samples and respiratory data were obtained at rest and during 15 min of recovery from a maximal cycle ergometer test that involved 20 W/min increases in work rate to exhaustion. Mean values for [H+], PCO2, and total protein increased, whereas those for bicarbonate concentration ([HCO-3]) and the strong ion difference ([SID]) decreased in the transition from rest to maximal exercise within both groups. At rest and throughout postexercise recovery, the pregnant group exhibited significantly lower mean values for PCO2, [HCO-3], and total protein, whereas [SID] was significantly lower at rest and early recovery from exercise. [H+] was also lower at all sampling times in the pregnant group, but this effect was significant only at rest. Our results support the hypothesis that reduced PCO2 and weak acid concentration are important mechanisms to regulate plasma [H+] and to maintain a less acidic plasma environment at rest and after exercise in late gestation compared with the nonpregnant state. These effects are established in the resting state and appear to be maintained after maximal exertion.

Chronic exercise and left ventricular structure and function in healthy human subjects.

Twelve healthy well-trained participants in a supervised exercise program (mean age, 41.3 yr) were compared with 12 sedentary control subjects (mean age, 38.9 yr) with physical characteristics similar to the exercised group (EG) before training. Resting echocardiograms revealed significantly lower heart rates (HR) in the EG compared with control group (CG) but no evidence for cardiac structural differences between groups. Radionuclide angiograms performed at rest and during two levels of supine cycling (HR targets: 120 and 140 beats X min-1) resulted in increases in background-corrected end-diastolic counts [EDC(bc)] and confirmed use of the Frank-Starling mechanism in the majority of subjects. Mean values (+/- SD) for ejection fraction (EF) and normalized peak systolic ejection rate (PSER) (P greater than 0.05 between groups) were the following. (Formula: see text) The results suggested that fitness training does not induce significant cardiac enlargement as apparent from measurements at rest or important changes in contractile state during exercise. Increases in exercise stroke volume with such training may be the result of an increased end-diastolic volume.

Effects of human pregnancy on cardiac autonomic function above and below the ventilatory threshold.

This study examined the effects of human pregnancy on heart rate variability (HRV), spontaneous baroreflex (SBR) sensitivity, and plasma catecholamines at rest and during exercise. Subjects were 14 healthy, physically active pregnant women (PG; mean gestational age = 33.9 +/- 1.0 wk). Results were compared with an age-matched nonpregnant control group (NPG; n = 14) with similar characteristics. The electrocardiographic R-wave-R-wave interval and systolic blood pressure (via finger plethysmograph) were measured on a beat-to-beat basis at rest and during upright cycling at 60 and 110% of the ventilatory threshold (T(vent)). Parasympathetic nervous system (PNS) modulation (as reflected by HRV high-frequency/total power and SBR slope) was significantly reduced at rest in the PG vs. the NPG. During exercise, PNS modulation decreased significantly in both groups, but the magnitude of PNS withdrawal from rest to 110% T(vent) was smaller in the PG vs. NPG. Sympathetic nervous system (SNS) modulation (reflected by the low-frequency power-to-high-frequency power ratio) increased above resting values at 60 and 110% T(vent) in the NPG. SNS modulation at 110% T(vent) was significantly lower in the PG compared with the NPG. Plasma norepinephrine and epinephrine levels were also lower at 110% T(vent) in the PG. It was concluded that healthy pregnant women exhibit lower PNS modulation at rest and blunted SNS modulation during exercise above T(vent) in late gestation.

The 'athletic heart syndrome'. A critical review.

Cardiological findings in athletes are often similar to those observed in clinical cases. Electrocardiographic and cardiac imaging abnormalities as well as physical findings may be the same in both of these groups. Bradycardia and rhythm disturbances are the most common abnormalities in athletes. Most athletes with abnormal electrocardiograms are asymptomatic and numerous investigators have failed to detect heart disease in association with such electrocardiograms. In contrast to cardiac dysfunction observed in clinical cases, enhanced or normal ventricular systolic and diastolic function have been reported in athletes. In endurance athletes, this is associated with very high values for maximal aerobic power (VO2max). Absolute and body size-normalised cardiac dimensions in most athletes do not approach values from chronic disease states, and may not exceed echocardiographic normal limits. In addition, pathological and physiological enlargement appear to be biochemically and functionally different. Myosin ATPase enzyme expression and calcium metabolism are different in rats with pathologically or physiologically induced enlargement. The reported biochemical differences underlie systolic and diastolic dysfunction in pathological enlargement. Conversely, trained rodents and humans have demonstrated enhanced systolic and diastolic function. It is important to note that cardiac enlargement observed in athletes is the result of normal adaptation to physical conditioning and/or hereditary influences. Conversely, pathological changes result from disease processes which can lead in turn to reduced function, morbidity and mortality. Since the mid 1970s echocardiography has been used to compare cardiac dimensions in male endurance- and resistance-trained athletes. A sport-specific profile of eccentric and concentric enlargement has been documented in endurance and resistance athletes, respectively. Subsequent studies of athletes have examined factors such as age, sex and degree of competitive success to determine their contribution to these sport-specific cardiac profiles. Unique athletic subgroups have also been analysed and have included ballet dancers, rowers, basketball players and triathletes. However, there is a paucity of data on cardiac dimensions in female athletes. Finally, physical conditioning studies have also examined echocardiographic dimensions before and after endurance and resistance training. Significant enlargement of internal dimensions, wall thickness or left ventricular mass have been reported but such increases are relatively small and by no means universal. Several conflicting explanations for enlarged cardiac dimensions appear in the literature. Chronic volume and pressure haemodynamic overloading during physical conditioning has been proposed to explain eccentric and concentric cardiac enlargement in endurance- and resistance-trained athletes respectively. However, twin studies suggest that hereditary factors may be important determinants of cardiac dimensions and/or the degree of cardiac adaptability to physical conditioning.(ABSTRACT TRUNCATED AT 400 WORDS)

Prescription of aerobic exercise during pregnancy.

Available evidence supports the existence of both risks and benefits of aerobic conditioning during human pregnancy. During intensive exertion, maternal skeletal muscle and the fetus may compete for blood flow, oxygen delivery and essential fuel substrates. Hence, the most important hypothetical risks include acute fetal hypoxia, hyperthermia and malnutrition. If exercise is repeated on a chronic basis, teratogenic effects, fetal growth retardation or altered fetal development may result if maternal/fetal adaptive reserve is exceeded. A dose-response relationship for such effects has been demonstrated in laboratory animals, but specific findings may have limited applicability to voluntary exercise in pregnant women. Although further investigation is needed, the majority of published studies suggest that fitness-type conditioning does not jeopardise fetal well-being in healthy well-nourished women. Benefits of such exercise appear to include increases in maximal aerobic power (VO2max, L/min) and enhanced cardiopulmonary reserve. It has also been proposed that exercise prevents accumulation of excess body fat, promotes psychological well-being, helps to prevent gestational diabetes and low back pain and may facilitate labour. However, these benefits remain to be confirmed by objective scientific study. Due primarily to a lack of scientific data, existing medical guidelines for exercise during pregnancy are conservative and follow a common sense approach. Good agreement exists on the need for preparticipation medical screening and continuing surveillance to verify the existence of maternal/fetal adaptive reserve. Women are advised to select safe, non-ballistic exercise modalities and to avoid thermal or hyperbaric environmental stress during exercise. Exercise in the supine position is also prudent to avoid, particularly in late gestation. The usefulness of heart rate in prescribing and monitoring exercise intensity has been questioned, with use of conventional perception of exertion scales being the most logical alternative. Prediction of maximal aerobic power (VO2max) from submaximal work rate/heart rate relationships is also problematic during pregnancy. Other areas of debate include the advisability of initiating a new exercise programme during pregnancy, methods for prevention of fetal hyperthermia, the safety of weight-training/isometric exercise and optimal methods for training of pre/postnatal fitness instructors.

Physical conditioning attenuates respiratory responses to steady-state exercise in late gestation.

PURPOSE: To study the ventilatory effects of closely monitored cycle ergometer conditioning (HR target, 145-150 beats x min(-1); 25 min/session; three sessions per week) during the second and third pregnancy trimesters (TMs) in healthy human pregnancy. METHODS: Subjects were 27 previously sedentary pregnant women (exercised group, EG). A sedentary control group (CG, N = 20) was also studied. Subjects were tested at rest and during upright cycle ergometry at three steady-state power outputs (approximately 20, 45, and 65 W) at the start of the second TM (ENTRY), at the end of the second and third TMs (post-training), and 3 months postpartum (PP, nonpregnant control). RESULTS: Significant reductions in exercise HR were observed in the EG at each exercise level, confirming achievement of an aerobic conditioning effect. In both groups the ventilatory equivalent for oxygen (VE/O2) was significantly higher at all work rates during pregnancy compared with that during PP. This effect was caused by significantly higher exercise tidal volumes (VT) at each work rate in both groups during pregnancy versus PP. Respiratory sensitivity as reflected by the ventilatory equivalent for carbon dioxide (E/VECO2) and calculated arterial carbon dioxide tension (PaCO2) was significantly increased at all three work rates in late gestation versus PP and increased slightly with advancing gestational age in both groups. The main effects of physical conditioning were attenuation of increases in VE/VO2 observed at all exercise levels between the end of TM2 and TM3 and reductions in respiratory perception of effort (RPEr) between ENTRY and the end of TM3. Attenuation of increases in VE/VO2 during TM3 in the EG was attributed to the combined effects of enhanced fat versus carbohydrate utilization (resulting in reduced CO2 output and drive to ventilate) and attenuation of pregnancy-induced increases in dead space ventilation in late gestation. CONCLUSION: The study results support the hypothesis that physical conditioning reduces both ventilatory demand and respiratory perception of effort in late gestation.

Acute effects of exercise intensity on appetite in young men.

This study investigated the acute effects of two exercise intensities on three measures of appetite. Fifteen, 12-h-fasted, college-age males completed three experimental sessions in counterbalanced orders: no-exercise control; cycle exercise performed at 35% VO2max; and cycle exercise performed at 68% VO2max. Both exercise conditions involved a total energy expenditure of 4.1 kcal.kg-1 body weight. Dependent measures were intermittent hunger and sucrose palatability ratings, and food intake at a test meal given approximately 1 h post-exercise. Hunger was briefly suppressed in the high-intensity exercise condition compared to low-intensity exercise and control, while intake of liquid-source kilocalories and carbohydrates was higher after the exercise sessions. Total caloric intake remained stable. Sucrose palatability did not vary across sessions. Intensity is inferred to be an important variable mediating exercise effects on appetite. Relations between appetite measures are discussed, and validity of sucrose palatability ratings and common methods of measuring food intake questioned. Exercise, while not decreasing food intake, does not appear to increase it, and the benefits of exercise for body fat reduction are not immediately offset by compensatory caloric intake.

Electrocardiographic and echocardiographic characteristics of female athletes.

This study examined electrocardiographic and echocardiographic characteristics of endurance- and resistance-trained female athletes. The subjects were 10 varsity caliber endurance-trained athletes, 10 resistance-trained athletes, and 10 nonathletes. Data collection included anthropometric measurements, VO2max, standard 12-lead ECGs and left ventricular dimensions measured by M-mode and two-dimensional echocardiography. For endurance-trained athletes, absolute left ventricular end-diastolic volume and values normalized for lean body mass were significantly greater than in nonathletes. An interstudy comparison of female vs male endurance-trained athletes from the same population also revealed significantly lower values for M-mode left ventricular mass expressed per kilogram of lean body mass in the former. Absolute and normalized wall thicknesses were not significantly greater in resistance-trained athletes compared to the other two groups. Wall thickness indexed for lean body mass was similar for the three groups. Sinus bradycardia was observed in all endurance athletes and in four resistance-trained athletes. ECG criteria were unreliable for the prediction of left ventricular enlargement. It appears that both female resistance- and endurance-trained athletes exhibit a lesser degree of enlargement of left ventricular wall thickness and mass than male athletes. A close relationship between skeletal and cardiac muscularity in resistance-trained athletes of both genders also was supported.

Physical conditioning effects on fetal heart rate responses to graded maternal exercise.

PURPOSE: This study examined the effects of advancing gestational age and maternal aerobic conditioning (stationary cycling) on fetal heart rate (FHR) responses to strenuous non-steady-state maternal exercise. METHODS: Subjects chose to participate in either an exercise group (EG) or control group (CG). Fourteen healthy, previously sedentary pregnant women participated in the exercise group, and six pregnant controls remained sedentary. Stationary cycling (heart rate target: 145 beats x min(-1)) was performed 3 d x wk(-1) by the exercised group. Exercise duration was increased from 14 to 25 min x session(-1) during the second trimester and was maintained at 25 min x session(-1) throughout the third trimester. FHR was monitored before, during, and after a progressive submaximal cycle ergometer test (peak heart rate = 170 beats x min(-1)) performed at approximately 27 and 37 wk gestation. RESULTS: Mean FHR increased significantly (P < 0.05) during exercise, followed by a modest suppression and then a delayed rise during the recovery period at both observation times. Fetal bradycardia was not observed in any of the exercise tests. Effects of advancing gestational age included a lower FHR baseline both at rest and in response to maternal exercise and a lower incidence of exercise-induced tachycardia. Maternal physical conditioning did not significantly alter FHR response to maternal exercise. CONCLUSION: Our results support the hypothesis that FHR responses to strenuous exercise are altered by advancing gestational age and a brief progressive exercise test terminated at a maternal heart rate of 170 beats x min(-1) does not induce fetal distress during a healthy pregnancy.

The value of combining noninvasive techniques in exercise testing.

A 3-stage cycle ergometer exercise test which combines the noninvasive measurement of systolic time intervals (STI's), stroke volume (SV), mean systolic ejection rate (MSER) and blood pressure was administered to 2 groups of middle-aged men. Group 1 included 15 healthy men. Group 2 consisted of 20 men with coronary artery disease (CAD), confirmed by a proven myocardial infarction. The groups were matched for age, weight and height. Over the range of heart rates (HR's) encountered (70--173 beats min-1) the STI's described an inversely linear relationship with HT. At all exercise HR's, group 2 displayed higher values for total electromechanical systole (QS2), left ventricular ejection time (LVET) and the pre-ejection period (PEP), and lower values for SV and MSER. Statistical comparison of all variables at a common HR of 100 beats min-1 indicated that QS2 and MSER best discriminated between the groups. It was concluded that this test is sufficiently sensitive to detect differences in cardiac performance in groups of subjects, but not for the diagnosis of CAD in individual patients.

Recent advances in understanding maternal and fetal responses to exercise.

In the past decade, physical health fitness has become increasingly more important in the lives of women of child-bearing age. Many have made regular, and sometimes vigorous commitments to exercise programs. In 1985, the American College of Obstetricians and Gynecologists (ACOG) developed a set of guidelines for women who plan to exercise during pregnancy. Recommendations were based on available, but somewhat limited, scientific data and common sense. Since that time, researchers have learned a significant amount of new information about how a pregnant woman and her fetus respond to aerobic activity. The objective of this communication is to review recent investigations in this area. Specific topics include a) maternal responses to exercise, b) fetal responses to maternal exercise, c) animal research models, and d) pregnancy and physical conditioning. Our objectives are to present information that will a) stimulate new and innovative research designs for exercise and pregnancy studies, and b) add significantly to our knowledge and ability to develop safe and effective exercise programs for women who wish to remain physically active throughout a normal-term pregnancy.