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R D Gilbert

Publications and source records attributed to R D Gilbert.

85 records · Page 5Linked to original sources

Determinants of venous return in the fetal lamb.

Measurements have been made of the peripheral vascular factors influencing venous return, and hence cardiac output, in the fetus. These measurements show the fetus maintains a high venous return by means of a high mean systemic pressure, or driving pressure for venous return, and a low resistance to venous return. Increases in fetal blood volume cause increases in mean systemic pressure with no change in resistance to venous return and, as a result, venous return is increased. These studies show the possible importance of peripheral vascular factors in the control of cardiac output.

Animals↗

Placental anatomy and diffusing capacity in guinea pigs following long-term maternal hypoxia.

To determine the relation of placental structure to placental diffusing capacity (DPCO), we exposed Hartley guinea pigs to 12 or 14 per cent O2 from day 15 of gestation to near term (64 days). At that time we measured DPCO and fetal body and placental weights. In addition, we used stereological techniques to measure placental parameters important to diffusing capacity. We also used a mathematical model with results from the stereological measurements to predict the diffusing capacity. In the first hypoxic group (E1), measured DPCO decreased 10.1 +/- 3.7 per cent, while that predicted was 2.4 per cent less than control. Total vascular volume decreased 6.6 +/- 3.6 per cent, while tissue volume and mean diffusion distance increased 10.2 +/- 5.6 per cent and 12.9 +/- 7.0 per cent, respectively. In the pair-fed animals, measured DPCO decreased 22.6 +/- 4.6 per cent, while that predicted was 20.0 per cent less than control. There were no significant stereological differences in this group. In the second (E2) hypoxic group, measured DPCO increased 27.2 +/- 7.4 per cent, while that predicted increased 38.2 per cent. For this same group, total vascular volume increased 11.7 +/- 3.0 per cent, and tissue volume and mean diffusion distance decreased 18.2 +/- 4.6 per cent and 17.8 +/- 3.8 per cent, respectively. These results demonstrate the dependence of placental diffusing capacity upon placental structure.

Animals↗

Regional anatomy of the term human placenta.

We have studied regional anatomical variability in four term placentae, comparing both whole placental regions and intralobar zones and plates. In addition, we have emphasized the need for careful selection of the area to be sampled, rather than strictly randomized sampling of the whole placenta. A unique contribution is our quantitative data for a number of structures of the several intralobar zones and plates. The data confirm the hypothesis that the area best suited to physiological exchange is the central region parabasal plate. The relative homogeneity of the intralobar zones in this area make it a representative area for sampling for various placental studies.

Capillaries↗

Ca(2+) sensitivity of fetal coronary arteries exposed to long-term, high-altitude hypoxia.

OBJECTIVE: To determine the contribution of decreased calcium responsiveness of fetal coronary arteries to decreased contractile responses to potassium and the thromboxane A(2) analogue U46619 in these arteries after exposure to chronic hypoxemia. METHODS: Concentration-response curves to Ca(2+) in beta-escin-permeabilized left circumflex (LCx), left anterior descending (LAD), and right coronary artery (RCA) rings from high-altitude (HA) and control (CON) fetuses were measured. In a second set of beta-escin-permeabilized coronary artery rings, the effect of U46619 on Ca(2+) sensitivity was tested. RESULTS: Maximum Ca(2+)-activated force (T(max)) was decreased in HA LCx (CON 0.091+/-0.010 versus HA 0.057+/-0.006 g/cm(2); P<.05) and HA LAD (CON 0.065+/-0.012 versus HA 0.031+/-0.007 g/cm(2); P <.05). No significant difference was observed in the RCA. There was no change in the pD(2) (-log EC(50)) values between CON and HA coronary rings. The Ca(2+) sensitizing effect of U46619 on submaximal Ca(2+)-activated force was lower only in the HA LCx (CON 0.044+/-0.010 versus HA 0.023+/-0.006 g/cm(2) at 10(-5) mol/L; P<.05). CONCLUSION: These results indicate that maximum tension development in response to Ca(2+) was decreased in the HA LCx and LAD but not the RCA; however, Ca(2+) sensitivity of the contractile apparatus was unaltered in all of them. Decreased Ca(2+) responsiveness may partially explain the decreased contractile capability of fetal LCx and LAD during long-term, high-altitude intrauterine hypoxemia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Pearson's syndrome presenting with Fanconi syndrome.

A case of Pearson's marrow-pancreas syndrome is presented. The dominant clinical feature was a generalized disorder of proximal tubule function with severe renal magnesium wasting. Renal and muscle biopsies were performed and showed bizarre giant mitochondria.

Anemia, Sideroblastic↗

Effects of long-term high-altitude hypoxia on isolated fetal ovine coronary arteries.

OBJECTIVE: To examine the effects of long-term high-altitude hypoxia on the contractile properties of isolated fetal coronary arteries. METHODS: Maximal contractile responses (T(max)) to 90 mmol/L KCl and the thromboxane A(2) mimetic U46619 were measured in proximal (PLCx) and distal left circumflex (DLCx), left anterior descending (LAD), and right coronary arterial (RCA) rings from high-altitude and control fetuses. Paired studies were conducted with and without nitric oxide synthase (NOS) inhibitors, Nomega-nitro-L-arginine and Nomega-nitro-L-arginine ester. RESULTS: In high-altitude fetuses, 90 mmol/L KCl T(max) responses in both intact and NOS-blocked rings decreased by approximately 62% in PLCx, approximately 59% in DLCx, approximately 57% in LAD, and approximately 47% in RCA (n = 9-18/group; P <.05). High-altitude vessels also exhibited decreased sensitivity to U46619. NOS blockade potentiated T(max) to U46619 in the high-altitude RCA segments and augmented T(max) to U46619 in high-altitude RCA compared with its treated control counterpart (P <. 05). CONCLUSION: These results suggest that nitric oxide influences the pharmacologic responsiveness of the RCA to U46619. Furthermore, long-term high-altitude hypoxia significantly alters the contractile capabilities of fetal coronary arteries. These observations may partially explain the maintained redistribution of cardiac output to the fetal heart during exposure to long-term high-altitude hypoxia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Oxygen dose-response curve of cardiac papillary muscle from fetal and nonpregnant adult sheep exposed to long-term, high-altitude hypoxemia.

OBJECTIVE: We tested the hypothesis that hearts of fetal and nonpregnant adult sheep exposed to long-term hypoxemia would be able to sustain higher contractile function during exposure to acute hypoxia than hearts from normoxic animals. METHODS: Pregnant and nonpregnant sheep were exposed to high altitude (3820 m) for 100 days. Right and left ventricular papillary muscle strips were obtained from fetuses and nonpregnant adults, mounted in an isolated bath system, stimulated electrically and subjected to acute hypoxia in a dose response manner. Measurements were made of maximum tension production (Tmax), maximum rate of tension development (+dT/dtmax), maximum rate of relaxation (-dT/dtmax), time to peak tension, and duration of contraction. Results were compared to papillary muscle from a normoxic group of animals. RESULTS: Baseline values (95% O2 + 5% CO2 bubbled in the bath) of Tmax and +/- dt/dtmax for each ventricle were greater in adults than fetuses in both normoxic and long-term hypoxemic groups. During hypoxia (at 40 and 20% O2) Tmax and +/- dT/dtmax, were all maintained at significantly higher values in papillary muscle from long-term hypoxemic fetuses than in papillary muscle from normoxic fetuses. Duration of contraction and time to peak tension did not differ between the normoxic and hypoxemic groups. In both ventricles of the long-term hypoxemic adult, Tmax and +/- dT/dtmax, as well as duration and time to peak tension, were significantly higher than in normoxic adults, but only at the lowest level of hypoxia (20% O2). CONCLUSIONS: Contrary to the original hypothesis, heart muscle from both fetal and adult sheep that had been exposed to long-term hypoxemia could maintain contractile function better during acute hypoxia. The responsible mechanisms are not clearly understood.

Animals↗