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Biomedical subjects

J F Clapp

Publications and source records attributed to J F Clapp.

At least 19 recordsLinked to original sources

Uterine blood flow during supine rest and exercise after 28 weeks of gestation.

OBJECTIVE: To test the null hypothesis that, after 28 weeks of gestation, uterine blood flow during supine rest and supine exercise is no different than uterine blood flow at left-lateral rest. DESIGN: In vivo experimental study in pregnant women. SETTING: Department of Obstetrics, MetroHealth Medical Center, Cleveland, OH, USA. POPULATION: Fourteen, physically active, late-pregnant women who continued supine exercise throughout gestation. METHODS: Studies were carried out between 29 and 38 weeks of gestation. Maternal blood pressure, maternal heart rate, and ultrasound estimates of volume blood flow in the right ascending branch of the uterine artery were obtained serially at rest in the left-lateral position, at rest in the supine position, during and immediately after 10 minutes of supine exercise, and again at rest in the left-lateral position. Exercise sessions included alternating 60- to 90-second periods of abdominal crunches and leg exercise at moderate/high intensity (Borg's rating of perceived exertion 14 +/- 1). MAIN OUTCOME MEASURES: Blood pressure, heart rate, and uterine artery volume flow. RESULTS: Data are presented as the mean +/- SD. Maternal heart rate and blood pressure were unchanged at supine rest but increased during supine exercise (heart rate increased from 76 +/- 9 to 98 +/- 12 beats per minute, mean arterial pressure increased from 81 +/- 6 to 102 +/- 12 mmHg). Volume flow fell from 410 +/- 93 to 267 +/- 73 cc/minute after 5 minutes of supine rest and then, during supine exercise, increased to 355 +/- 125 cc/minute. Uterine artery luminal diameter and blood flow correlated directly with tissue weights at birth (r(2) values between 0.32 and 0.59). CONCLUSIONS: In physically active women, uterine blood flow decreases during both supine rest and supine exercise but the decrease in the former is twice that seen in the latter.

Adult↗

Influence of endurance exercise and diet on human placental development and fetal growth.

The delivery of oxygen and substrate to the maternal-fetal interphase is the major maternal environmental stimulus which either up- or down-regulates feto-placental growth. During pregnancy, sustained exercise sessions cause an intermittent reduction in oxygen and substrate delivery to the interphase that may exceed 50% during the exercise but, it is probable that regular bouts of sustained exercise or exercise training may improve oxygen and substrate delivery at rest. The type of maternal carbohydrate intake (low- versus high-glycemic sources) and food intake frequency also influence substrate availability through their effects on maternal blood glucose levels and insulin sensitivity. As a result, different exercise regimens and/or different types of carbohydrate intake modify feto-placental growth. The magnitude and direction of the effect is determined by their average 24-h effect on oxygen and substrate availability at different time-points in pregnancy. In general, exercise in early and mid pregnancy stimulates placental growth while the relative amount of exercise in late pregnancy determines its effect on late fetal growth. Low-glycemic food sources in the diet decrease growth rate and size at birth while high-glycemic food sources increase it. Thus, it may be possible to improve pregnancy outcomes in both healthy, low-risk women and a variety of high-risk populaces by simply modifying maternal physical activity and dietary carbohydrate intake during pregnancy.

Adult↗

Fetal cerebellum: US appearance with advancing gestational age.

PURPOSE: To evaluate the change in ultrasonographic (US) appearance of the fetal cerebellum with advancing gestation. MATERIALS AND METHODS: A total of 291 normal fetuses of uncomplicated pregnancies were evaluated at gestational ages (GAs) between 15 and 41 weeks with a 3.75-MHz transabdominal curvilinear probe. After the transcerebellar view was obtained, the transverse cerebellar diameter (TCD) was measured and the images were stored. On hard-copy US images, cerebella were assigned three grades of appearance. These grades were analyzed in relation to GA and TCD. Inter- and intraobserver variations were assessed in 91 randomly selected cases. RESULTS: Cerebella in 137 (47.1%), 71 (24.4%), and 83 (28.5%) of 291 subjects were classified as grade I (hypoechoic, "eyeglass" shape), grade II (intermediate echogenicity, "dumbbell" outline), and grade III (hyperechoic, "fan" shape), respectively. With advancing gestation, the dominant grade changed from I to III gradually and progressively. The median GA and TCD, respectively, were 22 weeks and 22 mm for grade I, 29 weeks and 35 mm for grade II, and 36 weeks and 46 mm for grade III. These differences were statistically significant (P <.001). The agreements within inter- and intraobserver estimations were 96% (87 of 91) and 95% (86 of 91), respectively. CONCLUSION: A gradual change in US appearance of the fetal cerebellum is seen with advancing gestation.

Adult↗

Matrix-assisted laser desorption/ionization mass spectrometric quantification of the mu opioid receptor agonist DAMGO in ovine plasma.

The synthetic opioid peptide analog Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol (DAMGO), which is a mu opioid receptor-selective agonist, was quantified in ovine plasma samples with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), using delayed extraction and a reflectron. The internal standard was pentadeuterated DAMGO. Timed-ion selection was used to select the precursor ion. The analysis of the post-source decay fragments improved the detection sensitivity, and the use of the precursor-product ion relationship optimized the specificity. For plasma samples, the inter-assay variability of this method was 6.4% (n = 79) and the intra-assay variability was 6.0% (n = 10). The variability for controls was 3.4% (n = 43). The profile of DAMGO amount versus time was determined in sheep plasma, and the corresponding pharmacokinetic data were calculated.

Analysis of Variance↗

Effects of pregnancy and exercise on concentrations of the metabolic markers tumor necrosis factor alpha and leptin.

OBJECTIVE: Pregnancy and exercise have opposite effects on fat mass and insulin resistance. We therefore designed this study to test the hypotheses that exercise during pregnancy alters the pregnancy- associated increases in the levels of tumor necrosis factor alpha and leptin and that the changes in tumor necrosis factor alpha and leptin concentrations during pregnancy continue to reflect changes in fat mass. STUDY DESIGN: The levels of tumor necrosis factor alpha and leptin were measured longitudinally in a control group of physically active women, a group of women who performed endurance exercises >/=4 times a week throughout pregnancy, and a group of women who initially performed endurance exercises but then stopped exercising during midpregnancy. Exercise was monitored, and longitudinal estimates of maternal total mass and fat mass were obtained. RESULTS: Tumor necrosis factor alpha levels were lower during pregnancy in the women who exercised, and the same was true for leptin levels. When women stopped exercising, however, both tumor necrosis factor alpha and leptin concentrations rose at rates comparable to those seen in the physically active control group. Changes in leptin concentration but not those in tumor necrosis factor alpha concentration correlated with the pregnancy-associated increases in total body and fat mass. CONCLUSIONS: Regular weight-bearing exercise during pregnancy suppresses the pregnancy-associated changes normally seen in both tumor necrosis factor alpha and leptin. The decrease in leptin reflects decreased fat accretion, and we speculate that the changes in tumor necrosis factor alpha may reflect a change in insulin resistance.

Adult↗

Cardiovascular responses of perimenopausal women to hormonal replacement therapy.

OBJECTIVE: This study was undertake to test the hypothesis that hormone replacement therapy alters cardiovascular function during the first several months of therapy. STUDY DESIGN: Serial estimates of blood pressure, heart rate, stroke volume, and venous capacitance were obtained before and at 1, 5, 9, and 21 weeks after the beginning of hormone replacement therapy with daily estradiol and intermittent norethindrone. Measurements were performed by means of electrocardiography, automated blood pressure measurement (Dynamap; Critikon Company LLC, Tampa, Fla), echocardiography, and plethysmography. RESULTS: Hormone replacement therapy did not alter heart rate, blood pressure, or venous capacitance. End-diastolic volume and stroke volume were unchanged after 1 week of hormone replacement therapy but rose thereafter. After 5 weeks of hormone replacement end-diastolic volume and stroke volume were increased by 13 +/- 5 mL and 9 +/- 2 mL, respectively, and after 9 weeks the increases totaled 23 +/- 5 mL and 17 +/- 3 mL, respectively. As a result cardiac output rose progressively to a level 1.1 +/- 0.3 L/min (18%) greater than pretreatment values and systemic vascular resistance fell 15%. These changes were associated with a 3-fold increase in serum estradiol levels. CONCLUSION: The studied regimen of hormone replacement therapy produces progressive cardiac remodeling and peripheral vasodilatation during the first 2 months of therapy.

Blood Pressure↗

Exercise during pregnancy. A clinical update.

Research dealing with exercise during pregnancy continues to demonstrate marked benefits for mother and fetus. The type, intensity, frequency, and duration of the exercise seem to be important determinants of its beneficial effects. Maternal benefits include improved cardiovascular function, limited weight gain and fat retention, improved attitude and mental state, easier and less complicated labor, quick recovery, and improved fitness. Fetal benefits may include decreased growth of the fat organ, improved stress tolerance, and advanced neurobehavioral maturation. Currently, the offspring are leaner at 5 years of age and have a slightly better neurodevelopmental outcome. Postpubertal effects are still unknown. In the absence of medical contraindications, women should be encouraged to maintain their prepregnancy activity level.

Bicycling↗

Portal vein blood flow-effects of pregnancy, gravity, and exercise.

OBJECTIVE: We sought to test the hypotheses that pregnancy increases portal vein blood flow and that regular exercise training during pregnancy limits the flow redistribution away from the splanchnic and uterine circulations in response to either gravitational or exercise-induced hemodynamic stress. STUDY DESIGN: Portal vein blood flow, which probably reflects changes in uterine blood flow, was estimated with ultrasonography in 6 regularly exercising and 6 physically active control subjects before and during pregnancy after 15 minutes of rest in the left lateral recumbent position, after 5 minutes of standing rest, and immediately and 5 minutes after 20 minutes of treadmill exercise at 55% +/- 3% of maximal aerobic capacity. RESULTS: Portal vein blood flow rose significantly during early and mid pregnancy at recumbent rest (from 660 +/- 110 to 1090 +/- 120 mL/min), standing rest (580 +/- 70 to 790 +/- 120 mL/min), immediately after exercise (160 +/- 30 to 360 +/- 60 mL/min), and at 5 minutes of recovery (520 +/- 60 to 760 +/- 110 mL/min). Before pregnancy, exercise training did not blunt the decremental effects of either gravity or exercise on portal vein blood flow. During mid and late pregnancy, exercise training had no effect on the fall in portal vein blood flow with gravitational stress, but it markedly reduced the decremental effects of exercise (average for the 2 time points, -510 +/- 80 vs -840 +/- 100 mL/min) and improved recovery at 5 minutes after exercise (940 +/- 140 vs 600 +/- 130 mL/min). CONCLUSIONS: Portal vein blood flow rises significantly during pregnancy, and flow redistribution away from the splanchnic and uterine circulations in response to severe hemodynamic stress is reduced by exercise training in mid and late pregnancy.

Adult↗

Beginning regular exercise in early pregnancy: effect on fetoplacental growth.

OBJECTIVE: Our purpose was to test the null hypothesis that beginning regular, moderate-intensity exercise in early pregnancy has no effect on fetoplacental growth. STUDY DESIGN: Forty-six women who did not exercise regularly were randomly assigned at 8 weeks either to no exercise (n = 24) or to weight-bearing exercise (n = 22) 3 to 5 times a week for the remainder of pregnancy. Outcome variables included antenatal placental growth rate and neonatal and placental morphometric measurements. RESULTS: The offspring of the exercising women were significantly heavier (corrected birth weight: 3.75 +/- 0.08 kg vs 3.49 +/- 0.07 kg) and longer (51.8 +/- 0.3 cm vs 50.6 +/- 0.3 cm) than those born to control women. The difference in birth weight was the result of an increase in both lean body mass and fat mass. In addition, midtrimester placental growth rate was faster (26 +/- 2 cm(3)/wk vs 21 +/- 1 cm(3)/wk) and morphometric indexes of placental function were greater in the exercise group. There were no significant differences in neonatal percentage body fat, head circumference, ponderal index, or maternal weight gain. CONCLUSIONS: These data indicate that beginning a moderate regimen of weight-bearing exercise in early pregnancy enhances fetoplacental growth.

Birth Weight↗

A peripheral site of action for the attenuation of baroflex-mediated bradycardia by intravenous mu-opioid agonists.

We previously reported that i.v. DAMGO (Tyr-D-Ala-Gly-NMePhe-Gly-ol), a selective mu-opioid agonist, causes an increase in blood pressure with no change in heart rate in unanesthetized sheep and subsequently demonstrated that DAMGO attenuates baroreflex-mediated bradycardia. To determine the site and mechanism by which mu-agonists inhibit baroreflex sensitivity, we have carried out further investigations by using DAMGO and another mu-agonist, DALDA (Tyr-D-Arg-Phe-Lys-NH2). The bradycardic response to norepinephrine (NE) was significantly blunted after i.v. DAMGO or DALDA in both nonpregnant and pregnant sheep. In contrast, the tachycardic response to sodium nitroprusside (SNP) remained unchanged in the presence of DAMGO or DALDA. In view of the highly restricted distribution of DALDA across the blood-brain barrier (BBB), we hypothesized that the blunting of reflex-mediated bradycardia by mu-opioid agonists can occur peripherally. Pretreatment with the quaternary opioid antagonist, naloxone methiodide (NM), completely blocked the attenuation of baroreflex sensitivity by DAMGO and DALDA in both nonpregnant and pregnant animals. These data suggest that in addition to central mechanisms, mu-opioid agonists can inhibit baroreflex sensitivity at a peripheral site, most likely by inhibiting vagal influence on heart-rate control rather than by acting directly at baroreceptors.

Animals↗

Neonatal behavioral profile of the offspring of women who continued to exercise regularly throughout pregnancy.

OBJECTIVE: The objective of the study was to test the hypothesis that continuing regular exercise throughout pregnancy alters early neonatal behavior. STUDY DESIGN: The offspring of 34 women who exercised were compared with those of 31 demographically similar control subjects. All women had normal antenatal courses. Behavior was assessed at 5 days after birth with the Brazelton Scales. RESULTS: The offspring of the exercising women performed better in 2 of the 6 behavioral constellations when examined at 5 days after birth. The scores reflecting their ability to orient to environmental stimuli were (mean +/- SEM) 7.6 +/- 0.1 and 6.5 +/- 0. 3, respectively, and the scores reflecting their ability to regulate their state or quiet themselves after sound and light stimuli were 6. 6 +/- 0.2 and 4.9 +/- 0.3, respectively. The scores reflecting habituation (7.9 +/- 0.2 and 8.0 +/- 0.1, respectively), motor organization (5.7 +/- 0.1 and 5.5 +/- 0.1, respectively), autonomic stability (5.9 +/- 0.2 and 5.5 +/- 0.3, respectively), and behavioral state range (4.1 +/- 0.2 and 4.5 +/- 0.3, respectively) were not significantly different. CONCLUSIONS: These data indicate that the neonates born of exercising mothers have a different neurobehavioral profile as early as the fifth day after birth.

Adult↗

Respiratory depression after intravenous administration of delta-selective opioid peptide analogs.

We compared the effects of three micro-(DAMGO, DALDA, TNPO) and three delta-(DPDPE, DELT, SNC-80) opioid agonists on arterial blood gas after IV administration in awake sheep. None of the mu agonists altered pO2, pCO2 or pH. All three mu agonists decreased pO2 increased pCO2 and decreased pO2, and this effect was not sensitive to naloxone or TIPPpsi, a delta-antagonist, suggesting that it is not mediated by beta-opioid receptors. When administered to pregnant animals, there were significant changes in fetal pCO2 and pH. It may be possible to develop delta-selective opioid agonists which do not produce respiratory depression.

Analgesics↗

The one-year morphometric and neurodevelopmental outcome of the offspring of women who continued to exercise regularly throughout pregnancy.

OBJECTIVE: Our purpose was to test the hypothesis that continuing regular exercise throughout pregnancy alters morphometric and neurodevelopmental outcome at 1 year. STUDY DESIGN: The offspring of 52 women who exercised were compared with those of 52 control subjects who were similar in terms of multiple prenatal and postnatal variables known to influence outcome. All women were enrolled before pregnancy and had clinically normal antenatal and postnatal courses. Neurodevelopment was assessed by blinded examiners at 1 year of age, and morphometrics were obtained at birth and at 1 year of age. RESULTS: At birth, the offspring of the exercising women weighed less (3.38 +/- 0.06 kg vs 3.58 +/- 0.07 kg) and had less body fat (9.5% +/- 0.8% vs 12.6% +/- 0.6%). However, at 1 year, all morphometric parameters were similar, and no clinically significant between-group differences were observed in performance on either the Bayley psychomotor (108 +/- 1 vs 101 +/- 2) or mental (120 +/- 1 vs 118 +/- 1) scales. CONCLUSIONS: These data indicate that the offspring of exercising mothers have normal growth and development during the first year of life.

Adult↗

Baroreflex-mediated bradycardia but not tachycardia is blunted peripherally by intravenous mu-opioid agonists.

OBJECTIVE: We sought to test the hypothesis that an intravenous dose of H-Tyr-D-Arg-Phe-Lys-NH2, a highly mu-receptor selective opioid peptide, suppresses baroreflex sensitivity through a peripheral mechanism. STUDY DESIGN: A transient change in mean arterial pressure was produced in chronically instrumented pregnant ewes by norepinephrine or sodium nitroprusside in the absence or in the presence of H-Tyr-D-Arg-Phe-Lys-NH2, a highly mu-selective opioid peptide. In some studies naloxone methiodide, a peripheral opioid antagonist, was infused starting 60 minutes before the administration of H-Tyr-D-Arg-Phe-Lys-NH2 and maintained for a total of 90 minutes. Linear plots were obtained when the changes in mean arterial pressure during the pressure rise were plotted against the changes in heart rate and the sensitivity of the baroreflex was derived as the slope of the linear regression line. RESULTS: We observed (1) lower baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypertensive stimulus; (2) unchanged baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypotensive stimulus; and (3) unchanged baroreflex sensitivity after H-Tyr-D-Arg-Phe-Lys-NH2 administration with a hypertensive stimulus in the presence of naloxone methiodide. CONCLUSION: H-Tyr-D-Arg-Phe-Lys-NH2 suppresses the hypertensive but not the hypotensive arm of the baroreflex through peripheral opioid receptors. These results suggest that mu-opioid receptors are present in the vagus nerves and that the activation of these opioid receptors inhibits reflex bradycardia in pregnant sheep.

Animals↗

Cardiovascular and metabolic responses to two receptor-selective opioid agonists in pregnant sheep.

OBJECTIVE: Our purpose was to assess the effects of an intravenous dose of a highly selective mu-(DALDA) and delta-(DPDPE) opioid peptide to determine which class of peptide has the best clinical potential. STUDY DESIGN: Chronically instrumented pregnant ewes received a 0.3 mg/kg intravenous bolus of each peptide with and without opioid receptor blockade by means of a randomized prospective design. RESULTS: Intravenous DALDA produced only mild hypertension and a loss of heart rate variability, whereas DPDPE produced respiratory depression, maternal hypertension, and a fall in heart rate in both mother and fetus. Uterine blood flow, oxygen uptake, and glucose uptake were unchanged with both drugs. The effects of DALDA but not DPDPE were reversed by opioid receptor blockade. CONCLUSION: The delta-selective agonist had multiple nonopioid adverse effects, whereas the mu-selective agonist was well tolerated by the pregnant ewe, suggesting that mu-selective agonists have better potential for clinical use as an analgesic in pregnancy.

Animals↗

Self-selected recreational exercise has no impact on early postpartum lactation-induced bone loss.

UNLABELLED: Although exercise is known to positively impact bone mineral density (BMD), its effect on lactation-induced BMD loss has not been previously evaluated in a case-control study. PURPOSE: The purpose of this study was to compare lactation-induced bone changes in women who engaged in regular, self-selected, recreational exercise versus those who refrained from such during early postpartum. METHODS: Subjects were 20 healthy, lactating women who either exercised regularly (exercise, E; N = 11) or refrained from such (control, C; N = 9) during the first 3 months postpartum. Although preconception VO2max was significantly higher in E than C (E = 54.1, C = 36.9 mL.min-1.kg-1), no significant group differences were observed for parity, age, height, weight (WT), % body fat, dietary calcium intake, lactation calcium loss, and serum estradiol. Total body (TB), lumbar spine (LS), and femur neck (FN) BMD were measured within 2 wk of parturition and repeated at 3 months postpartum by dual energy x-ray absorptiometry. RESULTS: Although TB was unchanged, BMD decreased significantly from baseline in both groups at LS (C = -5.4, E = -4.1%) and FN (C = -2.7, E = -2.8%). WT decreased significantly over time but was not significantly correlated with BMD loss. No significant group by time interactions were observed for WT or BMD changes. CONCLUSION: These results suggest that regular, self-selected, recreational E has no impact on early postpartum lactation-induced BMD loss.

Adult↗

In vivo disposition of dermorphin analog (DALDA) in nonpregnant and pregnant sheep.

Although synthetic opioid peptide analogs have been used extensively to study the functional roles of opioid receptors, little is known about their in vivo disposition. Our goal was to develop novel opioid drugs with limited transfer across the placenta. DALDA (Tyr-D-Arg-Phe-Lys-NH2) is a potent and highly selective mu agonist that is quite polar because of its 3+ charge at physiological pH. It can therefore be expected that the distribution of DALDA across the placenta would be highly restricted. In this study, we determined the pharmacokinetics and placental transfer of DALDA after systemic administration in sheep. DALDA was infused intravenously to four nonpregnant and four pregnant sheep at a dose of 0.6 mg/kg/hr for 4 hr. Steady state plasma levels of DALDA were 5436 +/- 464 ng/ml in nonpregnant sheep and 5214 +/- 661 ng/ml in pregnant sheep. A one-compartment open model provided an excellent fit for nonpregnant and pregnant plasma data. The apparent volume of distribution was estimated to be 45.6 +/- 4.4 and 59.2 +/- 7.9 ml/kg in nonpregnant and pregnant animals, respectively. There was no difference in the elimination half-life of DALDA in nonpregnant (1.4 +/- 0.1 hr) and pregnant (1.7 +/- 0.2 hr) animals, and clearance was also similar in nonpregnant (23.1 +/- 1.7 ml/kg/hr) and pregnant (23.7 +/- 1.3 ml/kg/hr) animals. These data suggest that the distribution of DALDA is restricted to plasma volume and that its disposition is not altered in pregnancy. DALDA was not detected in any of the fetal plasma samples (< 50 ng/ml), indicating that fetal plasma concentration is < 1% of maternal concentration. The highly restricted placental distribution of DALDA suggests that it may be a promising opioid drug for obstetrical use.

Analgesics↗

Effect of dietary carbohydrate on the glucose and insulin response to mixed caloric intake and exercise in both nonpregnant and pregnant women.

The objective of this study was to test the hypothesis that a woman's dietary carbohydrate mix modifies the glucose and insulin response to both mixed caloric intake and exercise. Either a prospective randomized or a prospective randomized crossover design was used to examine the effects of two isocaloric, high-carbohydrate diets on the whole-blood glucose and insulin responses to mixed caloric intake and exercise in healthy nonpregnant (n = 14) and pregnant (n = 12) women. The diets differed only in the type of carbohydrate ingested. Those in one had low glycemic indexes and those in the other had high glycemic indexes. In nonpregnant women, the blood glucose response to a meal containing low-glycemic carbohydrate was half that seen with high-glycemic carbohydrate, and the effect of exercise on blood glucose was more pronounced while eating the high-glycemic carbohydrate diet. During pregnancy, women on the low-glycemic carbohydrate diet experienced no significant change in their glycemic response to mixed caloric intake, whereas those who switched to the high-glycemic carbohydrate diet experienced a 190% increase in their response. In conclusion, the type of dietary carbohydrate in a healthy, physically active woman's diet influences both her postprandial blood glucose profile and her blood sugar response to exercise.

Adult↗