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Biomedical subjects

G L Irion

Publications and source records attributed to G L Irion.

11 recordsLinked to original sources

Fetal hemodynamic response to maternal intravenous nicotine administration.

OBJECTIVES: Our study was designed to test the hypothesis that maternally administered nicotine has significant effects on fetal hemodynamics and umbilical systolic/diastolic ratios. STUDY DESIGN: Nine pregnant ewes received maternal intravenous infusions of 10, 20, and 30 micrograms/kg/min of nicotine. Maternal and fetal blood pressure, heart rate, and uterine and umbilical blood flow were recorded. RESULTS: Maternal intravenous administration of nicotine (10, 20, and 30 micrograms/kg/min of maternal body weight) produced significant (p < 0.05) increases in fetal blood pressure (2%, 11%, and 25%, respectively), decreases in fetal heart rate (0%, 8%, and 12%), and decreases in umbilical blood flow (0%, 0%, and 19%). Umbilical systolic/diastolic ratios increased slightly at the 30 micrograms/kg/min dose of nicotine, but these changes did not reach significance. Maternal blood pressure increased (10%, 25%, and 53%), and uterine vascular resistance increased (5%, 64%, and 344%) significantly (p < 0.05); uterine blood flow increased at the 10 micrograms/kg/min dose (+5%) and decreased by 23% and 42% at the highest two doses of nicotine. CONCLUSION: Maternal nicotine administration in late-term pregnant sheep produced significant increases in fetal arterial blood pressure and umbilical vascular resistance, decreased fetal heart rate, and umbilical blood flow but did not significantly alter systolic/diastolic ratios.

Animals

Direct determination of the ovine fetal umbilical artery blood flow waveform.

Ultrasonographic umbilical artery blood flow velocity waveform analysis has been proposed as a means of noninvasive assessment of fetal well-being. We computed waveform indices from directly measured umbilical artery blood flow in chronically instrumented ovine fetuses from 109 to 138 days of gestation (term, 145 days). The three waveform indices (systolic/diastolic ratio, pulsatility index, and resistance index) correlated significantly with each other (r = 0.90 to 0.98). These indices progressively decreased with gestation and were significantly correlated with calculated umbilical vascular resistance (r = 0.68 to 0.70, p less than 0.01) and with umbilical blood flow (r = -0.71, p less than 0.01). During the final week of pregnancy, systolic/diastolic ratio could be predicted by the combination of placental size (total cotyledonary mass), fetal size (ponderal index), and either umbilical blood flow or umbilical vascular resistance (multiple linear regression, r2 = 0.94). Fetal heart rate declined from day 109 of gestation to 138 days. Fetal heart rate was significantly correlated with waveform indices only when values exceeded 170 beats/min (r = -0.37 to -0.51). Ovine fetal umbilical artery waveform indices changed at approximately the same rate as those reported for human fetuses in late gestation on the basis of external Doppler ultrasonographic velocity measurements. These results suggest that the sheep is a suitable model for investigations of umbilical artery waveform analysis.

Animals

Fetal hemodynamic and fetoplacental vascular response to exogenous arginine vasopressin.

Fetal hemodynamics and fetoplacental blood flow were measured in chronically instrumented ovine fetuses during intravenous infusion of arginine vasopressin. Vasopressin was infused at rates ranging from 1 to 300 ng/min/kg estimated fetal mass. This range of infusion rates produces plasma arginine vasopressin levels observed throughout a wide range of fetal stress. No maternal effects were observed at any infusion rates used in this investigation. Fetal heart rate declined linearly with the log of the infusion rate. Mean fetal arterial pressure showed a sigmoidal response to log arginine vasopressin infusion rate, reaching a plateau at 30 ng/min/kg. Umbilical vascular resistance increased throughout the entire range of infusion rates. Fetoplacental blood flow decreased with increasing infusion rate but decreased only 4% to 13% throughout the range of infusion rates that produce plasma arginine vasopressin levels commonly observed during fetal stress. Because umbilical vascular resistance continued to rise after arterial pressure reached a plateau, fetoplacental blood flow decreased 31% at the highest infusion rate. However, the plasma vasopressin level associated with this infusion rate is probably in excess of that associated with severe fetal distress. The fetoplacental vascular bed is, therefore, either relatively insensitive to arginine vasopressin, or is capable of autoregulation in the face of high circulating levels of arginine vasopressin.

Animals

Relationship between the ovine fetal umbilical artery blood flow waveform and umbilical vascular resistance.

Ultrasonic umbilical artery blood flow velocity waveform indexes decrease throughout gestation as umbilical blood flow increases. However, it is not known whether the decrease in indexes such as systolic/diastolic ratio is a direct result of a change in umbilical vascular resistance. Umbilical artery blood flow was measured as vasoactive agents angiotensin II, arginine vasopressin, norepinephrine, serotonin, and the thromboxane A2 sympathomimetic agent U-46619 were infused into the inferior vena cava of chronically instrumented ovine fetuses. Angiotensin II, arginine vasopressin, norepinephrine, serotonin, and U-46619 all significantly increased fetal arterial pressure levels. Angiotensin II, arginine vasopressin, and U-46619 significantly reduced umbilical blood flow and fetal heart rate. All five pressor agents increased umbilical vascular resistance. Systolic/diastolic ratios were obtained from pulsatile umbilical blood flow tracings. Systolic/diastolic ratios before infusions were significantly correlated with baseline values of umbilical blood flow (r = -0.55) and umbilical vascular resistance (r = 0.52). Systolic/diastolic ratios decreased with increasing infusion rates of angiotensin II, arginine vasopressin, norepinephrine, and serotonin, and increased with infusion of U-46619. There was no significant correlation between systolic/diastolic ratio and either umbilical blood flow or umbilical vascular resistance during infusion of angiotensin II, arginine vasopressin, or serotonin. Systolic/diastolic ratio decreased with increasing umbilical vascular resistance during norepinephrine infusion (r = -0.44). Systolic/diastolic ratio changed in the predicted direction only when umbilical vascular resistance was increased by infusion of U-46619 (r = 0.80). We conclude that umbilical artery waveform analysis is not an adequate predictor of acute changes in umbilical blood flow or vascular resistance.

Animals

Differential responses of uterine and umbilical vasculatures to angiotensin II and norepinephrine.

Although the uterine vascular responses to endogenous vasoactive substances have been extensively investigated in pregnant sheep, the fetal umbilical responses to angiotensin II (ANG II) and norepinephrine (NE) have not been well characterized. Twenty-five pregnant ewes between 105 and 115 days of gestation were anesthetized and instrumented for hemodynamic measurements, systemic fetal and maternal intravenous infusions, and local maternal uterine arterial infusions of ANG II and NE. Fetal and maternal arterial pressure and heart rate, maternal uterine blood flow (total of left and right middle uterine arteries), and fetoplacental blood flow (common umbilical artery) were measured during continuous infusions of ANG II or NE. Fetal infusions of ANG II (0.03-1.0 micrograms.min-1.kg estimated fetal body wt-1) increased fetal arterial blood pressure by as much as 44% over base-line values, decreased umbilical blood flow by as much as 63%, and increased umbilical vascular resistance by up to 345%. Fetal infusions of NE (0.1-3 micrograms.min-1.kg-1) increased fetal arterial pressure 42% and increased umbilical vascular resistance by up to 38% but did not significantly alter fetoplacental blood flow. No significant maternal changes were observed during fetal infusions. Maternal infusion of ANG II increased maternal arterial pressure by as much as 59% and significantly increased uterine vascular resistance at the two highest doses but significantly decreased uterine blood flow only at the highest dose (17%; P less than 0.05). Maternal infusions of NE increased arterial pressure by as much as 113%, decreased uterine blood flow by as much as 76%, and increased uterine vascular resistance 3- to 10-fold over the base-line value.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II

Computerized stripping method for multiple nuclide microsphere studies.

Radiolabeled microspheres are commonly used to measure cardiac output and regional blood flow distribution in small animals such as rats. By using batches of microspheres labeled with different nuclides, several flow measurements can be made in the same animal. A protocol and computer program for analyzing data from multiple nuclide microsphere experiments are described. This protocol is designed to reduce the amount of arterial blood which must be withdrawn during microsphere distribution and eliminate the potential loss of data due to contamination of reference samples by nuclides used in previous flow measurements.

Animals

Preservation of skeletal muscle hyperemic response to contraction with aging in female rats.

In a previous investigation (Irion et al., 1987), a significant age-related decline in skeletal muscle blood flow during intermittent tetanic contractions was observed in male Fischer 344 rats. This decline in the hyperemic response to muscle contraction was accompanied by an increased fatigability of skeletal muscle of senescent male rats. In the present investigation, anesthetized female adult and senescent Fischer 344 rats were instrumented for stimulation of the plantar flexor muscles in situ, and blood flow measurement by the tracer microsphere technique. After determination of optimum length and maximum tetanic force, muscles were stimulated to contract at the rate of 120 tetani/min. No significant differences could be observed between adult and senescent females in skeletal muscle fatigability or blood flow. The only significant differences observed between senescent and younger females were a decrease in splenic blood flow and an increase in body weight. In contrast to male rats of the same age, no impairment of skeletal muscle blood flow or change in fatigability could be detected in senescent female rats.

Aging

Age-related change in skeletal muscle blood flow in the rat.

Anesthetized adult and senescent male Fischer 344 rats were instrumented for stimulation of in situ plantar flexor muscles and blood flow measurement by the tracer microsphere technique. After determination of optimum length and maximum tetanic force, muscles were stimulated to contract at the rate of 120 tetani/min. Senescent rats displayed significantly lower muscle blood flow and greater muscle fatigue than younger rats. Infusion of a nonspecific vasodilator in resting anesthetized rats also revealed a significantly lower potential to increase muscle blood flow in the senescent rats. Lower muscle blood flow of senescent rats during muscle contractions might be responsible, at least in part, for decreased performance of muscles of senescent male rats.

Aging

Responses of distance runners and sprinters to exercise in a hot environment.

The responses of highly trained distance runners and track sprinters and age-matched untrained men were compared during bicycle ergometry in a 40 degree temperature-controlled environmental chamber. There were no differences among groups in rectal temperature following the 90 min exercise bout. Distance runners had a lower heart rate than either sprinters or untrained subjects. There was no difference in heart rate between sprinters and untrained subjects. Distance runners and sprinters had a much greater sweat rate than untrained subjects and dissipated a greater proportion of their total heat load by evaporation of sweat. Sprinters, however, had a lower sweat rate than distance runners in the hot environment and could only maintain as low a skin temperature as distance runners for 75 min of the 90 min session. Both aerobic training and anaerobic training confer some degree of protection from heat injury during exercise in a hot environment. However, sprinters have a higher heart rate and cannot sustain a low skin temperature as long as distance runners. Sprinters lost their advantage over untrained subjects in skin temperature after 75 min of exercise in a hot environment and did not have a lower heart rate than untrained subjects. Distance runners had a significantly lower heart rate and maintained a lower skin temperature than untrained subjects for the entire 90 min exercise bout.

Acclimatization

Considerations in use of microspheres for flow measurements in anesthetized rat.

The results of single injections of different doses of microspheres (60,000, 100,000, and 375,000) demonstrated a significant reduction in measured heart and kidney blood flows as a function of the number of microspheres injected. Measured flow to other organs was unaffected by a single injection of these doses of microspheres. The injection of microspheres at a faster rate (0.8 ml/min microsphere injection; 1.0 ml/min flush) resulted in higher calculated heart flow when compared with the slow rate (0.2 ml/min microsphere injection; 0.25 ml/min flush). A significant decrease (approximately 21%) in measured blood flow to the right side of the brain that was observed in all the groups is due to the occlusion of the right carotid artery by the cannulation procedure. Intra-aortic injection of microspheres resulted in reduced measured brain blood flow when compared with intraventricular injections. Accurate and reliable heart and brain blood flows were not obtained with intra-aortic injection of microspheres. However, intra-aortic injection of microspheres does provide accurate and reliable flow measurements for more distal organs.

Anesthesia

Age-related changes in regional blood flow in the rat.

The purpose of this investigation was to characterize the changes in regional blood flow and central hemodynamic measures that occur in the rat as a result of the aging process. The isotope-labeled microsphere technique was used to measure cardiac output and regional blood flows in conscious and anesthetized adult (12 mo) and senescent (24 mo) Fischer 344 virgin female rats. No significant changes were observed in central hemodynamic measurements or regional blood flows in conscious rats with the exception of a 25% reduction in splenic blood flow. Pentobarbital anesthesia significantly reduced cardiac index and heart rate but elevated total peripheral resistance and mean arterial blood pressure. There was a decrease in blood flow to skeletal muscle, spleen, duodenum, stomach, and brain tissue samples and increased hepatic arterial blood flow in both age groups. The use of anesthesia caused a greater reduction in the cardiac index and brain blood flow in the senescent anesthetized rats than in the adult rats. Heart and kidney blood flows were decreased by anesthesia in the senescent rats but not in the adult rats. Skeletal muscle blood flow, however, was significantly greater in the senescent anesthetized rats than in the younger anesthetized animals. Although body weight and organ weights of the liver, spleen, kidneys, stomach, heart, and brain were significantly greater for the senescent rats, no differences could be demonstrated in tibial length or lean body mass.

Aging