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Biomedical subjects

R Gagnon

Publications and source records attributed to R Gagnon.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of the novel antimigraine agent, frovatriptan, on coronary and cardiac function in dogs.

The effects of frovatriptan (VML 251/SB-209509) on coronary artery function were investigated in isolated coronary arteries from beagle dogs. Low concentrations of frovatriptan produced contraction with -logEC50 7.55 +/- 0.08 (n = 11). The maximal observed contraction attained was 56 +/- 7% of the control 5-hydroxytryptamine (5-HT; 10 microM) response. At high concentrations of frovatriptan (>6 microM), reversal of sumatriptan (10 microM)-induced contractions was noted. In arteries precontracted with the thromboxane mimetic, U46619, frovatriptan produced a bell-shaped concentration-response relation with a maximal response at 600 nM. Concentrations of frovatriptan >2 microM produced marked reversal of tone, with full relaxation of precontracted tissues at 200 microM. In anesthetized, open-chest mongrel dogs, intravenous (n = 5) or intracoronary (n = 5) artery administration of frovatriptan (0.0001-1 mg/kg) had no consistent effect on left ventricular end-diastolic pressure, left end-systolic pressure, cardiac contractility, aortic blood flow, systemic peripheral resistance, coronary blood flow, coronary vascular resistance, mean arterial blood pressure, or heart rate when compared with vehicle (n = 3). Intravenous sumatriptan produced minor effects on blood pressure and heart rate. Intracoronary artery administration of sumatriptan (0.0003 mg/kg) produced an increase in systemic peripheral resistance to 120.5 +/- 8.2% compared with vehicle (97.8 +/- 5.4%; p < 0.05). This dose of sumatriptan also produced a significant increase in coronary blood flow and decrease in coronary vascular resistance. Intravenous administration of sumatriptan produced a dose-related reduction in left ventricular diastolic pressure with a reduction to 58.3 +/- 8.3% and 41.7 +/- 25% of control values observed at 0.3 and 1 mg/kg, respectively; however, administration of sumatriptan by an intracoronary route had no effect. In a model of myocardial infarction, comparable doses of sumatriptan (1.0 mg/kg) or frovatriptan (0.1 mg/kg), in terms of their effect on carotid vascular resistance, had no significant effect on infarct size. Frovatriptan had no effect on coronary blood flow after reperfusion; however, sumatriptan produced a significant reduction in coronary blood flow for < or =3 h. These studies show that frovatriptan has the capability of relaxing coronary arteries in vitro, has no overall effect on cardiac function at rest with no effect on coronary hemodynamics after myocardial infarction, and has a profile superior to that of sumatriptan.

Animals↗
PubMed1997

Prediction of umbilical artery base excess by intrapartum fetal oxygen saturation monitoring.

OBJECTIVE: Our purpose was to evaluate the predictive value of intrapartum fetal oxygen saturation as monitored by reflectance pulse oximetry (SpO2) for metabolic acidosis at birth. STUDY DESIGN: An observational study was carried out on intrapartum patients at > or = 35 weeks' gestation having either a nonreassuring fetal heart rate pattern, intrauterine growth restriction, or thick meconium. Fetal oxygen saturation monitoring was performed with use of the Nellcor N-400 monitor and the FS-14 fetal oxygen sensor. Mean values of SpO2 from the last 30 minutes of monitoring were correlated with umbilical artery base excess and pH at birth, with use of regression analysis, whereas the prediction of acidosis by SpO2 at different thresholds was tested with use of receiver-operator characteristic curve calculations. RESULTS: Fifty-four patients met the criteria for data analysis, with a mean SpO2 monitoring time of 150 +/- 124 minutes (SD) and a mean signal loss of 30% +/- 20%. Mean fetal SpO2 for the last 30 minutes of monitoring averaged 42.1% +/- 9.9% and, for individual patient studies, correlated significantly with calculated oxygen saturation in the umbilical vein (r = 0.52, p < 0.001) and in the umbilical artery (r = 0.34, p = 0.02) as measured at birth. However, the correlation with umbilical artery base excess values at birth was somewhat weaker (r = 0.30, p < 0.05), as was the correlation with umbilical artery pH values (r = 0.26, p = 0.05). Receiver-operator characteristic curve calculations were all nonsignificant when SpO2 from the last 30 minutes of monitoring was used as a diagnostic test for predicting acidosis at birth. CONCLUSIONS: Intrapartum fetal SpO2 as monitored in the current study was of limited use as a diagnostic test for predicting acidosis at birth, regardless of the SpO2 cutoff value used.

Acidosis↗
PubMed1997

Fetal heart rate patterns in growth-restricted fetal sheep induced by chronic fetal placental embolization.

OBJECTIVE: Our purpose was to test the hypothesis that chronic placental insufficiency and intrauterine growth restriction in fetal sheep causes a decrease in the number of fetal heart rate accelerations and fetal heart rate variability. STUDY DESIGN: Chronically catheterized fetal sheep were embolized (n = 6) daily with 15 to 50 microns latex microspheres for 21 days between 0.74 and 0.88 of gestation into the abdominal aorta, until fetal arterial oxygen content was decreased by 40% to 50% of the preembolization value. Control animals (n = 6) received saline solution only. Signals from chest electrodes were analyzed on-line with the Sonicaid System 8000 in 2-hour epochs every 6 hours starting at 8 AM over the first 48 hours of hypoxemia and for 2 hours between 8 and 10 AM every other day from day 3 to day 21 of hypoxemia. Umbilical artery Doppler-derived resistance index and fetal plasma catecholamine concentrations were also measured. RESULTS: Embolized fetuses had asymmetric intrauterine growth restriction and became chronically hypoxemic (p < 0.001) with a progressive increase in the umbilical artery resistance index (p < 0.001). During the first 48 hours of hypoxemia the number of accelerations and decelerations and both short- and long-term fetal heart rate variability increased initially, followed by a return to control levels by 20 hours after the onset of embolization. After 21 days of hypoxemia the number of accelerations was significantly reduced by 30% compared with controls (p < 0.05). Both short- and long-term fetal heart rate variability in control fetuses gradually increased with advancing gestational age (p < 0.001 and p < 0.01, respectively), whereas in embolized fetuses the fetal heart rate variability remained unchanged and was 20% lower than that of controls on day 21 (both p < 0.01). CONCLUSION: Intrauterine growth restriction and long-term hypoxemia in fetal sheep are associated with a decrease in short- and long-term fetal heart rate variability, possibly because of a delay in the normal maturational changes of the autonomic control of fetal heart rate.

Animals↗
PubMed1997

Fetal sheep endocrine responses to sustained hypoxemic stress after chronic fetal placental embolization.

The purpose of this study was to determine the endocrine and circulatory responses of the ovine fetus, near term, to sustained hypoxemic stress superimposed on chronic hypoxemia. Fetal sheep were chronically embolized (n = 7) for 10 days between 0.84 and 0.91 of gestation via the descending aorta until arterial oxygen content was decreased by approximately 30%. Control animals (n = 8) received saline only. On experimental day 10, both groups were embolized over a 6-h period until fetal arterial pH decreased to approximately 7.00. Regional distribution of lower body blood flows was measured on day 10, before and at the end of acute embolization. On day 10, the chronically embolized group had lower arterial oxygen content (P < 0.05), Po2 (P < 0.01), and placental blood flow (P < 0.05) than controls and higher prostaglandin E2 (PGE2) and norepinephrine plasma concentrations (both P < 0.05). In response to a superimposed sustained hypoxemic stress, there was a twofold greater increase in PGE2 in the chronically embolized group than in the control group (P < 0.05). However, the increase in fetal plasma cortisol in response to superimposed hypoxemic stress was similar in both groups, despite significantly lower adrenocorticotropic hormone and adrenal cortex blood flow responses in the chronically hypoxemic group (both P < 0.05). We conclude that PGE2 response to a sustained superimposed reduction in placental blood flow, leading to metabolic acidosis, is enhanced under conditions of chronic hypoxemia and may play an important role for the maintenance of the fetal cortisol response to an episode of superimposed acute stress.

Acute Disease↗
PubMed1997

Cerebral circulatory responses of near-term ovine fetuses during sustained fetal placental embolization.

To test the hypothesis that, in response to an increase in placental vascular resistance and progressive fetal asphyxia, the changes in external carotid blood flow waveforms are directly related to changes in external carotid vascular resistance, we embolized the fetal side of the placenta in pregnant sheep and measured cerebral and external carotid artery circulatory changes in relation to changes in external carotid artery flow waveforms. Chronically catheterized fetal sheep at 0.85 of gestation were embolized (n = 11) in the descending aorta for 6 h, until fetal arterial pH fell to approximately 6.90. Fetuses became rapidly hypoxemic (P < 0.0001) and developed a mixed respiratory and metabolic acidosis (P < 0.0001 for PCO2, pH, and base excess). There was a transient 40% increase in external carotid blood flow at pH approximately 7.25 and a parallel 32% increase in fetal arterial blood pressure (both (P < 0.01), whereas the external vascular resistance remained unaltered. Cerebral blood flow increased by 130% (P < 0.0001), and cerebral vascular resistance decreased by 125% (P < 0.0001) throughout the study. The external carotid resistance index (RI) decreased by 32% (P < 0.0001) at the time external carotid vascular resistance remained unchanged. This fall in external carotid RI was due almost entirely to a 110% increase in external carotid fundamental impedance (P < 0.001). We conclude that the poor relationship between the changes in external carotid vascular resistance and RI indicated that other hemodynamic factors such as vascular impedance to pulsatile flow must be measured for correct interpretation of changes in flow waveform shape under hypoxic conditions. In addition, changes in external carotid blood flow were not proportional to changes in cerebral blood flow in this model.

Animals↗
PubMed1997

Chronic fetal placental embolization and hypoxemia cause hypertension and myocardial hypertrophy in fetal sheep.

To examine the cardiovascular effects on the fetus of an elevated umbilical vascular resistance resulting in fetal hypoxemia, we embolized the fetal side of the placenta in pregnant sheep and measured cardiovascular and hormonal changes and cellular growth in fetal heart. Chronically catheterized fetal sheep were embolized (n = 6) for 21 days between 0.74 and 0.88 of gestation into the descending aorta until arterial oxygen content was decreased by 40-50% of the preembolization value. Control animals (n = 6) received saline only. During embolization, fetuses became chronically hypoxemic (P < 0.001) and hypertensive (P < 0.001), with a progressive increase in umbilical artery resistance index (P < 0.001). There was also an increase in fetal plasma norepinephrine throughout the study period (P < 0.05). On day 21 of embolization, fetuses showed asymmetrical growth restriction, increased heart weight (P < 0.01), and increase in right and left ventricular wall thickness (P < 0.05) compared with control animals. The protein-to-DNA ratio, an index of cell size, increased in the right ventricular myocardium in the embolized group (P < 0.001), suggesting myocardial cell hypertrophy. We conclude that, during chronic placental damage leading to fetal hypoxemia with an increase in umbilical artery resistance index, fetuses developed arterial hypertension and asymmetrical growth restriction and that increases in afterload to the heart and plasma norepinephrine likely caused fetal myocardial hypertrophy.

Animals↗
PubMed1996

Diurnal changes in lumbar intervertebral distance, measured using ultrasound.

STUDY DESIGN: This study measured the distances between the tips of the transverse processes of adjacent lumbar vertebrae (L1-L4) in the same subjects after 1 day of normal activities and again the next morning. OBJECTIVES: To determine the feasibility of directly measuring the lumbar intervertebral distance using ultrasound and to determine the magnitude of the diurnal change in the intervertebral distance. SUMMARY OF BACKGROUND DATA: A diurnal variation in height results from, in part, a decrease in height of the intervertebral discs with loading of the spine during the day. Previous estimates of the diurnal changes in disc height have used radiologic, stereophotographic, and magnetic resonance imaging techniques. No previous study has used ultrasound imaging. METHODS: Ultrasound was used to measure the distance between the tips of adjacent lumbar vertebral transverse processes. Measurements were made on six occasions in each of seven subjects after 6:00 PM in the evening and again the following morning before rising. RESULTS: The distance between the tips of adjacent transverse processes could be measured, within an individual, with a reproducibility of better than +/- 7.5% coefficient of variation. Reproducibility of the measurement of the total distance between L1 and L4 was better than +/- 4%. The intervertebral distances between L1 and L4 were significantly greater in the morning than in the evening. The average diurnal change in the total intervertebral distance L1-L4 was 5.3 mm. CONCLUSIONS: The study confirms the feasibility of using ultrasound to directly measure changes in the distances between the lumbar vertebrae.

Adult↗
PubMed1996

Fetal placental embolization in the late-gestation ovine fetus: alterations in umbilical blood flow and fetal heart rate patterns.

OBJECTIVE: Our goal was to determine the effect of chronic and acute umbilical-placental embolization on placental hemodynamic and fetal heart rate patterns in relation to fetal oxygenation in the near-term ovine fetus. STUDY DESIGN: Daily fetal placental embolization was performed during 10 days in 9 sheep fetuses until fetal arterial oxygen content decreased by approximately 30%. Nine control fetuses received saline solution. Mean and pulsatile umbilical blood flow, perfusion pressure, placental vascular resistance, fundamental impedance, pressure pulsatility index, and umbilical artery resistance index corrected to a fetal heart rate of 160 beats/min were measured. On day 10 both groups were acutely embolized until fetal arterial pH decreased to approximately 7.00. Fetal heart rate was measured with the Sonicaid System 8000 (Oxford Sonicaid, Oxford, United Kingdom). RESULTS: Chronic fetal placental embolization was associated with a progressive reduction in umbilical blood flow (p < 0.00001) and fetal arterial oxygen content (p < 0.001) whereas fetal heart rate patterns remained unaltered. A chronic increase in umbilical artery resistance index corrected to a fetal heart rate of 160 beats/min could be entirely explained only if the changes in umbilical artery pressure pulsatility index and the fundamental impedance were taken into account, in addition to the changes observed in placental vascular resistance. During acute embolization leading to a 50% reduction in umbilical blood flow (p < 0.0002) and a three times increase in placental vascular resistance (p < 0.0001), the most consistent change in fetal heart rate patterns related to progressive metabolic acidosis was an 84% decrease in absolute acceleration frequency (p < 0.0001) whereas short-term fetal heart rate variability remained unaltered. CONCLUSION: Changes in umbilical artery resistance index induced by chronic umbilical-placental embolization resulting in fetal hypoxemia occurred before any changes in fetal heart rate patterns were detectable. A decrease in the absolute acceleration frequency was the only component of fetal heart rate patterns related to progressive metabolic acidosis in the near-term ovine fetus.

Animals↗
PubMed1996

Fetal cerebral, circulatory, and metabolic responses during heart rate decelerations with umbilical cord compression.

OBJECTIVE: The purpose of this study was to determine the cerebral, circulatory, and metabolic responses of the ovine fetus near term to umbilical cord compression with variable-type fetal heart rate decelerations. STUDY DESIGN: Nine fetal sheep, at 0.9 of gestation, were studied before, during, and after umbilical cord occlusion for 1-minute and again after repetitive 1-minute cord occlusions every 5 minutes for 1 hour, with resultant fetal heart rate decelerations of approximately 90 beats/min. Brachiocephalic arterial and sagittal venous blood was analyzed for oxygen content, blood gases and pH, glucose, and lactate. Cerebral and upper body blood flow was measured with the microsphere technique. RESULTS: Umbilical cord occlusion with moderate to severe variable-type fetal heart rate deceleration resulted in an immediate drop in arterial PO2 by approximately 7 torr, an increase in PCO2 by approximately 9 torr, and a small but significant increase in lactate levels. Cerebral oxidative metabolism was well maintained but required an increase in fractional oxygen extraction because the variable change in cerebral blood flow was insufficient to maintain oxygen delivery. A redistribution of upper body blood flow was evident, with that to the bran and heart variably maintained or increased whereas that to muscle tissue was markedly decreased. Repetitive umbilical cord occlusion over 1 hour resulted in a significant drop in fetal arterial pH, with the acidemia mixed as PCO2 increased approximately 6 torr, whereas lactate levels increased almost fourfold. CONCLUSION: Although cerebral oxidative metabolism appears to be well maintained during moderate to severe variable-type fetal heart rate decelerations with umbilical cord occlusion, the need to increase fractional oxygen extraction and the redistribution of blood flow from carcass tissues may contribute to an accumulation of lactic acid both within the brain and systemically when such an insult occurs repeatedly.

Animals↗
PubMed1996

Effects of long-term hypoxemia on pituitary-adrenal function in fetal sheep.

To test the hypothesis that long-term hypoxemia causes premature activation of the fetal pituitary-adrenal function, we embolized the fetal side of the placenta in pregnant sheep and examined the changes in concentrations of immunoreactive adrenocorticotropic hormone (irACTH), cortisol, and prostaglandin E2 (PGE2) in fetal plasma, and levels and localization of proopiomelanocortin (POMC) mRNA in the pars distalis and the pars intermedia of the fetal pituitary. Twelve fetal sheep were studied (6 embolized and 6 control) for 21 days between 0.74 and 0.88 of gestation. Daily injections of nonradiolabeled microspheres were given into the fetal abdominal aorta to decrease fetal arterial oxygen content by 40-50% of the preembolization values. In the embolized group, concentrations of irACTH, PGE2, and cortisol in fetal plasma increased gradually and were significantly (P < 0.05) elevated above those of controls after day 10, day 16, and day 20, respectively. POMC mRNA levels in the pars distalis of the fetal pituitary were not different from those of controls but were significantly reduced in the pars intermedia (P < 0.05). We conclude that levels of POMC mRNA in the pars distalis are unchanged during long-term hypoxemia possibly because of negative feedback effects of elevated cortisol on the pituitary gland. During long-term fetal hypoxemia, there is a differential regulation of POMC mRNA expression in the pars distalis and pars intermedia.

Adrenocorticotropic Hormone↗
PubMed1996

Translabial ultrasonography and placenta previa: does measurement of the os-placenta distance predict outcome?

The aim of this study was to assess the value of the measurement of os-placenta distance by translabial ultrasonography in the evaluation of placenta previa. This method was used in 40 women with suspected placenta previa to measure the distance between the placenta and internal cervical os. Sonographic diagnoses were compared to placental location determined at delivery. Translabial ultrasonography proved superior to the transabdominal route in both diagnosis and exclusion of placenta previa. Measurement of the os-placenta distance can be used as an adjunct to clinical assessment to predict the likelihood of safe vaginal delivery in cases of suspected placenta previa.

Adult↗
PubMed1995

Increased fetal plasma prostaglandin E2 concentrations during fetal placental embolization in pregnant sheep.

OBJECTIVE: The purpose of this study was to examine the effect of chronic fetal placental embolization on fetal plasma prostaglandin E2 concentrations. STUDY DESIGN: Fourteen pregnant sheep were studied (seven embolized and seven controls) for 10 days between 0.84 and 0.91 of gestation. Daily injections of nonradioactive microspheres were made to decrease fetal arterial oxygen content by 30% to 35% of preembolization values. RESULTS: In response to repeated embolization, fetal plasma prostaglandin E2 concentrations increased significantly on day 1, declined to near control levels on days 2 to 6, but were significantly elevated again after day 7. Maternal prostaglandin E2 levels remained unchanged throughout the study. Fetal plasma prostaglandin E2 levels increased significantly with decreasing fetal oxygenation when fetal arterial oxygen content was < 2.0 mmol/L. CONCLUSION: We conclude that there is increased production of prostaglandin E2 by the placenta during progressive fetal hypoxemia induced by fetal placental embolization. We speculate that the progressive increase in prostaglandin E2 may be an important hormonal adaptive mechanism to maintain fetal homeostasis during the development of placental insufficiency.

Animals↗