Afferent baroreceptor discharge in pregnant rats.

The baroreflex function curve is shifted to lower operating pressures, efferent sympathoexcitatory responses are attenuated, and sympathoinhibitory responses are potentiated in pregnant compared with virgin rats. It has been proposed that during pregnancy, elevated levels of 3 alpha-hydroxy-dihydroprogesterone (3 alpha-OH-DHP), a major metabolite of progesterone, may contribute to this difference, because acute intravenous administration of 3 alpha-OH-DHP to virgin female rats mimics the effects of pregnancy on the baroreflex. To determine whether changes in the afferent limb might contribute to these baroreflex responses, the effects of pregnancy and 3 alpha-OH-DHP on aortic depressor nerve activity were assessed in the current study. Baroreceptor discharge curves were obtained in Inactin-anesthetized rats by recording aortic nerve activity during ramp increases and decreases in mean arterial pressure (MAP) [intravenous phenylephrine and nitroprusside infusion] before [(control, C) 15 min (E1), and 30 min (E2) after 3 alpha-OH-DHP (220 microg/kg bolus + 22 microg x kg(-1) x min(-1) infusion iv)]. Baseline blood pressure was significantly lower in pregnant (109 +/- 4.4 mmHg) compared with virgin (122 +/- 2.8 mmHg) rats. The only significant difference in the baroreceptor discharge curves was a decrease in curve midpoint in pregnant rats (virgin = 140 +/- 2.7 vs. pregnant = 124 +/- 3.6 mmHg). 3 alpha-OH-DHP had no effect on afferent baroreceptor discharge curves in either virgin or pregnant groups. These results suggest that pressure-dependent baroreceptor resetting may contribute to a shift in the baroreflex curve to lower operating pressures, but cannot completely explain differences in baroreflex function between virgin and pregnant animals.

Diaphragm dimensions of the healthy preterm infant.

BACKGROUND: The diaphragm is the major inspiratory muscle in the neonate; however, human neonatal diaphragm development has not been extensively studied. We hypothesized that diaphragm thickness (t(di)) would be positively related to postmenstrual age (PMA), body weight, body length, head circumference, and nutritional intake. OBJECTIVES: To evaluate the evolution of diaphragm growth and motion in the healthy, preterm infant. METHODS: We used ultrasound to measure t(di) at the zone of apposition to the rib cage and diaphragm excursion (e(di)) during inspiration. Thirty-four stable, preterm infants (16 males and 18 females) between 26 and 37 weeks' PMA were studied during quiet sleep at weekly intervals until the time of discharge or transfer from the neonatal intensive care unit. All infants were clinically stable and not receiving ventilatory support. RESULTS: We found that 1) t(di) increased from 1.2 +/- 0.1 to 1.7 +/- 0.05 mm between 26 to 28 and 35 to 37 weeks' PMA; 2) t(di) was positively correlated with PMA (r = 0.40), body weight (r = 0.52), body length (r = 0.53), and head circumference (0.49), but not with postnatal nutritional intake (r = 0.09); and 3) e(di) decreased with increasing PMA. CONCLUSIONS: Our findings suggest that diaphragm development in premature infants scales with body dimensions. We speculate that the increase in t(di) with age is likely attributable to increased diaphragm muscle mass, and the reduced e(di) with age may be resulting from a reduction in chest wall compliance.

Effects of continuous positive airway pressure on diaphragm dimensions in preterm infants.

OBJECTIVE: The use of continuous positive airway pressure (CPAP) in the treatment of a variety of neonatal respiratory conditions is associated with improvement in arterial oxygen saturation, decreased long-term morbidity, and an overall improvement in infant survival. We reasoned that CPAP might change diaphragm length by increasing end-expiratory lung volume (EEV), but the extent to which this occurs has not been assessed. This study was designed to evaluate (1) the extent to which CPAP shortens the diaphragm and (2) the relationship of diaphragm thickness and excursion with arterial oxygen saturation in spontaneously breathing preterm infants. STUDY DESIGN: Ultrasonographically (7.5 MHz transducer), diaphragm thickness and diaphragm excursion were measured in 12 stable preterm infants [birth weight 1120+/-225 g (mean+/-SD); study weight 1187+/-400 g; gestational age 29+/-1 week; postnatal age 10+/-8 days, six males and six females] at three levels of CPAP [1-3, 4-6, and 7-9 cm H(2)O (low, medium, and high, respectively)]. Heart rate, respiratory rate, and arterial oxygen saturation were simultaneously recorded. RESULTS: We found that diaphragm thickness and arterial oxygen saturation increased, and diaphragm excursion decreased significantly at higher levels of CPAP (p<0.05). The shortening of the diaphragm at the high levels of CPAP, calculated from the increase in diaphragm thickness, was 36% at EEV and 31% at end-inspiratory volume. CONCLUSION: We conclude that the improvement in arterial oxygen saturation with CPAP occurred despite the presence of a shorter and a less mobile diaphragm, and that other physiological and mechanical alterations accompanying the application of CPAP offset its negative effects on diaphragm function. We speculate that with excessive CPAP, however, diaphragm dysfunction along with the previously described adverse hemodynamic effects may outweigh its benefits on oxygenation.

Neurosteroid modulation of arterial baroreflex-sensitive neurons in rat rostral ventrolateral medulla.

The major metabolite of progesterone, 3 alpha-OH-dihydroprogesterone (3 alpha-OH-DHP), is the most potent endogenous positive modulator of central nervous system GABAA receptors. Acute intravenous administration of 3 alpha-OH-DHP to virgin female rats potentiates arterial baroreflex sympathoinhibitory responses. The current experiments tested the possibility that circulating 3 alpha-OH-DHP potentiates central GABAergic influences in the rostral ventrolateral medulla (RVLM). The unit activity of spontaneously active, spinally projecting, and arterial pressure-sensitive neurons was recorded in the RVLM of urethan-anesthetized rats. Arterial pressure sensitivity of RVLM neurons was tested before (control) and 10 min after bolus injection (44 microliters i.v.) of 3 alpha-OH-DHP (1.12 micrograms/kg, n = 19) or vehicle (40% beta-cyclodextrin, n = 8). Both threshold pressure and saturation pressure for inhibition of RVLM neurons were decreased after acute administration of a physiological dose of 3 alpha-OH-DHP (1.12 micrograms/kg i.v.), which produces plasma concentrations similar to those seen during pregnancy (20-30 ng/ml), suggesting potentiated responsiveness to endogenously released GABA. Following suppression by 3 alpha-OH-DHP, high doses of the inactive stereoisomer 3 beta-OH-DHP (112-224 micrograms/kg i.v.; n = 8) restored unit activity, presumably by displacing 3 alpha-OH-DHP from the neurosteroid binding site on GABAA receptors.