Prenatal cocaine alters diaphragmatic EMG responses to hypoxia in developing swine.

To distinguish pure effects of prenatal cocaine exposure on respiratory control from confounding factors inherent to drug abuse, a porcine model was established. Cocaine was administered at 2 mg/kg 4 times daily during 0.66-1.0 gestation to 5 paired sows. At birth, cocaine-exposed piglets were fostered to the unexposed paired sows and their litters. Respiratory measures were obtained from diaphragmatic electromyographic activity (EMGDI) of 3 to 9 (young) and 21 to 31 (older) day-old, chronically instrumented piglets during 10 min each of normoxia and hypoxia (10% O2 in 90% N2), and compared between cocaine-exposed and unexposed animals. Arterial pH and gas tensions in hypoxia were not altered by cocaine. In the young neonates, only during hypoxia, cocaine preexposure produced a transient elevation of the peak and initial slope of the integrated EMGDI envelope, but did not affect respiratory timing, provided no extensive periodic breathing or apnea had occurred. In the older animals, during hypoxia only, cocaine preexposure increased the peak and initial slope of EMGDI envelope while decreasing summed EMGDI activity, EMGDI duration and Ttot toward levels seen in the young unexposed neonates. These findings suggest that prenatal exposure to cocaine retards the normal maturation of respiratory EMG responses to hypoxia.

Cardiorespiratory and sleep-wake behavior in developing swine: kappa-opioid influence.

Effects of specific kappa-opioid antagonism with norbinaltorphimine (NorBNI) on sleep-wake state, blood pressure and heart rate, and on diaphragmatic and posterior cricoarytenoid electromyographic activities were assessed in 3 to 13 and 23 to 33 day-old, chronically instrumented, unanesthetized piglets. Preliminary experiments established the pharmacodynamics and dose-response for NorBNI. In the main study, each piglet was studied twice daily, once before and once after 3.7 mg kg-1 NorBNI iv, for up to five consecutive days. During each study session, piglets underwent 10 min trials with 21% O2 in 79% N2 followed by 10% O2 in 90% N2 while lying in a sling within a plexiglass box. Sleep-wake distribution and cardiorespiratory functions matured with age. NorBNI produced a modest increase of arterial pressure and heart rate in the older group only, and altered neither state nor respiration at either age. These results suggest that, in the developing piglet model, the kappa-opioid system influences neither breathing nor state, but modulates cardiovascular regulation to a modest degree and later in ontogeny.

Effects of fatigue on the length-tetanic force relationship of the rat diaphragm.

It has been established that the in vivo operating length of the diaphragm corresponds to a wide range of the ascending limb of its length-tetanic force relationship. To investigate the length-dependent effects of fatigue on maximum force production, we constructed length-tetanic force relationships of rat costal diaphragm strips in vitro before and after fatigue induced by repetitive supramaximal electrical field stimulations at optimal length. Two levels of fatigue were studied (i.e., force reductions of 40 and 65% at optimal length). Results indicate that fatigue, when evaluated with high-frequency stimulations, causes a proportionately larger decrease in tetanic force at short muscle lengths as seen by a smaller control force-to-fatigue force ratio and an apparent shift in the length at which active force is zero. A possible explanation for the results obtained is failure of propagation of membrane depolarization into the t-tubule system at short muscle lengths, which is aggravated by fatigue evaluated by high-frequency stimulation.

Contractile responses of rat plantaris muscles following partial denervation, and the influence of daily exercise.

The study was designed to determine the influence of increased daily neuromuscular activity on the sprouting response of motoneurones following partial denervation. Female Sprague-Dawley rats had one hindlimb partially denervated by transecting lumbar radicular nerve L4, and were subsequently subjected to a daily programme of increased activity, including grid climbing and voluntary wheel exercise, for 9 days. Functional sprouting was estimated on day 10 by comparing the L5-evoked plantaris muscle forces, measured in situ, with those of the contralateral L5. Comparisons were made between responses from exercised and non-exercised rats. Tetanic (200 Hz) contribution of L5 axons to plantaris muscle force doubled during the period following partial denervation, but did not attain the equivalent of whole muscle tetanic tension of normal controls. Twitch: tetanic ratios were elevated, and tetanic contractions "fatigued" to a greater extent in partially denervated muscles, signifying limitations on the part of each sprouting motoneurone to tetanically activate its enlarged complement of muscle fibres. No influence of daily exercise following the lesion on any of these functional indices of motoneurone sprouting was evident. Increased daily neuromuscular activity, performed within the restrictions imposed by the neuromuscular deficit, does not influence motoneurone sprouting responses. This is in contrast to the enhancement of sprouting previously reported for motoneurones of rats subjected to intense, prolonged, daily exercise preceding the partial denervation, and when neurones remaining following partial denervation are electrically stimulated for relatively short periods of time (1 h), the day of the lesion.