J. A. Decena

Opioid-induced stimulation of fetal respiratory activity by [D-Ala2]deltorphin I.

[D-Ala2]deltorphin I effects on fetal respiratory activity was characterized to determine the role delta-opioid receptors play in modulating fetal respiratory activity. [D-Ala2]deltorphin I, infused at 0.3 or 100 micrograms/h, intracerebroventricularly (i.c.v.), stimulated fetal respiratory activity without changing blood pH, PCO2 or PO2. Stimulation by 0.3 micrograms/h, but not 100 micrograms/h, was blocked by i.c.v. infusion of the delta-opioid receptor antagonist, naltrindole. Stimulation by 100 micrograms/h was blocked by the mu 1-opioid receptor antagonist naloxonazine. These data suggest stimulation of fetal respiratory activity by 0.3 micrograms/h [D-Ala2]deltorphin I are mediated specifically through delta-opioid receptors; while [D-Ala2]deltorphin I at 100 micrograms/h is no longer selective for the delta-opioid receptor, and the stimulation may be mediated through the mu 1-opioid receptor.

The Effects of Selective mu1 Opiate Receptor Blockade on Breathing Patterns in the Fetal Lamb

ABSTRACT: The effects of naloxone and naloxonazine (an irreversible mu1, antagonist) administration on fetal breathing movement (FBM) patterns under control, physiologic conditions were studied in 10 fetal lambs with chronically implanted electromyogram electrodes in the diaphragm. Neither naloxone (6 mg/h) nor naloxonazine (34 mg) had any effect on the total number of diaphragmatic electromyogram bursts per hour, mean instantaneous breathing rate, or incidence of breathing. However, naloxonazine caused a more fragmented FBM pattern, as indicated by a significant increase in both the number of apneas and pauses per hour, along with decreased epoch duration. In addition, naloxonazine caused a significant reduction in the stability or regularity of the breathing rate. Naloxone had no effects on the dynamic pattern of the FBM. These results suggest that endogenous opiate peptides play a tonic role at the mu1 receptor to maintain both the continuity and stability of the FBM pattern in late gestation.

Maternal marijuana smoking alters respiratory timing in the fetal lamb

The effect of single and repeated maternal marijuana smoke exposure on fetal breathing movements (FBMs) was investigated in 13 fetal lambs in the third trimester. These animals were surgically instrumented for long-term intrauterine recording of diaphragmatic electromyogram (EMG). Maternal inhalation of marijuana smoke [1.84% tetrahydrocannabinol (THC)] increased FBMs and resulted in a more continuous and regular breathing pattern. There was a significant increase in the number of breaths/h (p < 0.01) and the incidence of FBMs (p < 0.001) in the second hour. Breathing activity returned to presmoke level by the third hour. Duration of the longest breathing epoch was significantly increased from 16.8 +/- 3.3 min to 31.9 +/- 5.2 min (p < 0.005). Instantaneous breathing rate was much more stable in the second hour after marijuana exposure (p < 0.01). Inhalation of placebo smoke did not result in any significant change in either overall breathing activity or continuity and stability of the breathing rate. The effects of marijuana smoke on fetal breathing were not observed after repeated smoke exposure. These results suggest that tolerance develops rapidly to the respiratory stimulating effect of marijuana smoke in the fetus.

Effects of single and repeated marijuana smoke exposure on fetal EEG

The effect of single and repeated marijuana smoke exposure on fetal EEG was investigated in the chronic fetal lamb model using power spectral analysis. Maternal inhalation of marijuana smoke (n = 9) resulted in a significant reduction in total power and power distribution in the delta (1-4 Hz) band, and an increase in power distribution in the faster frequencies in the first h after smoke inhalation. These EEG changes were not observed following maternal inhalation of placebo smoke (n = 5), nor in animals with 3-5 prior exposures to marijuana smoke (n = 5). These results suggest that the effects of marijuana smoke exposure on fetal EEG is short-lived and tolerance develops rapidly with repeated exposure.

Drug-induced Chances In The Inverse Power-law Distributions And I/F Power Spectra Of Fetal Breathing Dynamics

We have shown that the inverse power-law relationship in the distribution of the interburst intervals and in the power spectrum of fetal breathing dynamics can be effectively changed with drugs. Immature breathing patterns can be made more mature with opiate agonists, while more mature breathing patterns can be made less mature with opiate antagonists. These changes support the hypothesis that the fractal mechanisms involved in the regulation of breathing rate variability can be modulated.

Inverse Power-law Distribution And I/F Power Spectra In Fetal Heart Rate Variability

We have demonstrated that fetal heart rate variability (HRV) demonstrates inverse power-law relationship in the power spectrum. However, the distribution of inter-beat intervals (IBI) is normal. The scaling property of the power spectrum suggests that a fractal mechanism is involved in the control of HRV, but not in the IBI, during early development.