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Biomedical subjects

M K McLaughlin

Publications and source records attributed to M K McLaughlin.

62 records · Page 4Linked to original sources

Effects of indomethacin on sheep uteroplacental circulations and sensitivity to angiotensin II.

Indomethacin, a prostaglandin synthetase inhibitor, injected simultaneously into the abdominal aorta of the ewe and her fetus at 125 days' gestation causes vasoconstriction of both the uterine and umbilical circulations. There is no change in these hemodynamic effects of indomethacin in the presence of phenoxybenzamine, an alpha-adrenergic antagonist. When the indomethacin experiment is repeated seven to 10 days later, a uterine vasoconstriction 10 per cent greater than that found earlier occurs, but there is no change from control umbilical vascular resistance. The mean maternal arterial pressure response (20 mm. Hg) to angiotensin II with and without indomethacin also was examined at the same time in gestation. Indomethacin infusion to the ewe significantly reduces the pressor dose (nanograms per kilogram per minute) by 42 +/- 4 per cent. Thus, in pregnant sheep in the third trimester, endogenous prostaglandins appear to be: (1) partial determinants of basal blood flow in both the uterine and umbilical circulations and (2) modulators of the vasoconstrictive effects of angiotensin II in the ewe.

Angiotensin II↗

Vasoconstrictive effects of prostaglandins in sheep placental circulations.

Changes in the uterine and umbilical circulations after intra-aortic injection of prostaglandin E2 (PGE2) or protaglandin F2alpha (PGF2alpha) to either the fetus or the mother have been examined in 13 ewes at late gestation. PGF2alpha vien to either the fetus or the mother is vasoconstrictive in both uterine and umbilical circulations. PGE2 given to the fetus results in a dissociated response with vasodilation of the uterine circulation and vasoconstriction of the umbilical circulation. PGE2 given to the mother causes a uterine contraction that precludes specific hemodynamic analysis. Therefore, exposure of either maternal or fetal ovine circulation to exogenous prostaglandins in associated with acute changes in both placental circulations. Similar responses to pertubations in endogenous prostaglandin levels may exist in pregnant sheep.

Animals↗

Effects of prolonged infusion of beta-adrenergic agonists on uterine and umbilical blood flow in pregnant sheep.

We have extended our evaluation of the effects of three beta-adrenergic agents in near-term pregnant sheep to include a period of infusion three times longer than previously studied. This extension has provided the following information: (1) Initial depression of uterine blood flow and mean arterial pressure associated with administration of ritodrine or salbutamol abate with time despite continued drug infusion; (2) the uterine hyperemia associated with salbutamol and fenoterol are drug-related rather than postinfusion-related phenomena; (3) increased uterine vascular resistance is found with ritodrine, and decreased uterine vascular resistance occurs with salbutamol and fenoterol.

Adrenergic beta-Agonists↗

24-hour rhythms in uterine and umbilical blood flows of conscious pregnant sheep.

The possibility that 24-hour rhythms exist in uterine blood flow (UtBF) and umbilical blood (UmBF) was investigated in 5 days postoperative chronically instrumented near-term pregnant sheep acclimated to a controlled environment. UtBF, UmBF and pressure measurements were made at 15-min intervals over 24 h beginning at 0800 h. Each data series was examined for the presence of significant rhythms of a 24-hour period using a method of Fourier analysis. UtBF 24-hour rhythms were found in all ewes; UmBF 24-hour rhythms were found in 4 of 5 lambs. A consistent reciprocal phase relationship between UtBF and UmBF was evident within animals. There were no associated rhythms in maternal arterial, fetal arterial, or amniotic fluid pressures. These results indicate that the presence of circadian rhythms must be considered as a possible variable when long-term uteroplacental hemodynamic studies are planned.

Amniotic Fluid↗

Effect of ritodrine infusion on uterine and umbilical blood flow in pregnant sheep.

The effect of ritodrine upon uterine artery blood flow (UtBF) and umbilical vein blood flow (UmBF) was investigated in near-term chronic sheep preparations. During intravenous ritodrine infusions to the ewe in sequential dose rates from 100 to 800 mug per minute, UtBF fell progressively to 43 per cent below control levels and mean maternal arterial pressure (MMAP) declined 20 per cent. During constant infusions of 100, 400, or 800 mug per minute of ritodrine to the ewe for 120 minutes,, UtBF decreased 10, 37, and 31 per cent, respectively, and MMAP decreased 6, 20 and 25 per cent respectively. Dose-related maternal tachycardia and hyperglycemia occurred. There were no significant changes in UmBF, mean fetal arterial pressure, or fetal heart rate. During all infusions, maternal and fetal arterial pH, PCO2, and PO2 remained within normal physiologic limits. Simultaneous infusion of ritodrine (400 mug per minute) and propranolol (100 mug per minute) blocked the maternal tachycardia, but decreases in UtBF, MMAP, and UmBF were observed. Ritodrine infusions to the fetus (25 mug per minute) resulted in fetal tachycardia and a variable increase in UmBF.

Animals↗

Low-density lipoprotein particle size decreases during normal pregnancy in association with triglyceride increases.

OBJECTIVE: To characterize the changes in low-density lipoprotein (LDL) peak particle diameter (diameter of the predominant LDL subclass) in relation to changes in serum triglyceride concentration during successive stages of normal gestation and postpartum. METHODS: Nonfasting venous blood was obtained longitudinally during and after uncomplicated primiparous pregnancy from 10 nonsmoking women with no history of metabolic disorders. Plasma LDL diameter was determined by nondenaturing polyacrylamide gel electrophoresis. Serum concentrations of total cholesterol, triglyceride, apolipoprotein B, apolipoprotein A-I, and LDL-cholesterol were measured. Gestational changes were analyzed by one-way repeated-measures analysis of variance and the paired multiple comparison Student-Newman-Keuls test. Pearson coefficients were computed for correlation of serum lipids and LDL diameter. RESULTS: Low-density lipoprotein diameter decreased progressively with advancing gestation, evident by 16-20 weeks relative to 5-12 weeks. Seven of 10 cases were subclass pattern B (diameter less than 255 A) by term, indicating that small, dense particles predominated. The average diameter decrease from early to late gestation was 13 A. All subjects reverted to subclass pattern A (diameter 255 A or more) by 6-12 weeks postpartum, indicating prevalence of large, buoyant LDL. Low-density lipoprotein diameter correlated inversely with concentrations of serum triglyceride (r = -.61, P < .0001), apo B (r = -.66, P < .0001), cholesterol (r = -.53, P < .001), LDL cholesterol (r = -.45, P < .005), and apo A-I (r = -.39, P < .02). CONCLUSION: Gestational triglyceride increases are accompanied by progressive decreases in LDL diameter in a majority of cases. These changes undergo reversal postpartum and therefore are transient. Small, dense LDL particles have a number of properties capable of altering vascular function. However, the consequences of the gestational LDL size decrease for maternal and fetal metabolism remain unknown.

Apolipoprotein A-I↗

[Direct assessment of mesenteric vein compliance in the rat during pregnancy].

This study was designed for two purposes. The first was to establish an in-vitro technique for the comparative study of isolated capacitance veins during pregnancy. Secondly, to test the hypothesis that pregnancy is associated with an increase in venous compliance and the unstressed volume of the veins. Capacitance-size mesenteric veins were mounted in a pressurized myograph system equipped with a video dimension analyzing system and a servo pressure control unit, which was modified for venous studies. After equilibration, the transmural pressure was changed from 2 to 10 mmHg in 2 mmHg increments every 15 minutes. The calculated change in volume over this pressure range consisted of both a change in vessel diameter and in axial length. The veins from the nonpregnant rats exhibited a greater change in axial length than those from the pregnant rats (21% vs. 14%). Unexpectedly, the compliance (change in volume/change in pressure) of the veins from the pregnant rats was significantly less (42%) than those from the nonpregnant rats. However, the basic component of the change in vascular capacitance, the unstressed volume, was significantly greater in the veins from the pregnant rats (100%). We conclude that pregnancy causes alterations in the wall of the capacitance veins, which results in an apparent increase in volume at the expense of wall compliance. Secondly, the pressurized myograph system is a valuable tool for studying the physiology of the capacitance veins during pregnancy under rigorously controlled conditions.

Animals↗