G. G. Haddad

Heart rate and heart rate variability during sleep in aborted sudden infant death syndrome

Heart rate and heart rate variability were studied during sleep at monthly intervals in 18 normal infants and 12 infants with aborted sudden infant death syndrome during the first four months of life. At each age studied and in both REM and quiet sleep, the aborted SIDS infants had a 5 to 10% faster heart rate. Moreover, the aborted SIDS infants had a 10 to 45% smaller beat-to-beat and overall heart rate variability. Although the differences in overall variability persisted after normalization by the absolute heart rate, the differences in the beat-to-beat variability narrowed. These findings, when taken in conjunction with our previous observation that aborted SIDS infants have a smaller QT index than normal infants, suggest that infants with aborted SIDS have an increase in sympathetic activity or in circulating levels of catecholamines.

Effect of graded anesthesia on laryngeal-induced central apnea.

To examine the interaction between laryngeal reflex-induced central apnea and anesthesia, we stimulated the superior laryngeal nerves (SLNs) bilaterally in chronically instrumented piglets (N = 18, age 5-17 days) in the presence of various anesthetic dosages. The SLNs were placed in cuff electrodes and wires were exteriorized in the neck for stimulation. A cannula placed in the aorta was used for blood pressure recording and arterial blood sampling. During each experiment, 1-2 days following surgery, ventilation was recorded using whole body plethysmography, and EEG and ECG were recorded using acutely placed subcutaneous electrodes. Following baseline recordings and before administration of anesthesia, the SLNs were electrically stimulated for 15 min. Following recovery from stimulation, pentobarbital (5-15 mg/kg) was infused and the SLN was stimulated with the same variables for 5 min. Before anesthesia, SLN stimulation caused respiratory frequency (Rf) to fall from 44 +/- 5 (mean +/- SEM) to 16 +/- 2 breaths/min; under anesthesia Rf fell from 33 +/- 7 to 9 +/- 1 (pentobarbital dose a = 16 mg/kg) or from 36 +/- 4 to 3 +/- 1 breaths/min (pentobarbital dose b = 28 mg/kg). PaO2 decreased from 110 +/- 4 to 74 +/- 4 mmHg during stimulation before anesthesia and fell from 100 +/- 6 to 40 +/- 4 with dose a or from 98 +/- 10 to 19 +/- 4 mmHg with dose b under pentobarbital anesthesia. Similarly, choloralose/urethane and ketamine anesthesia enhanced SLN-induced respiratory depression. These results suggest that anesthesia impairs the mechanism responsible for initiating breathing during laryngeal reflex activation.

Opposite effects of the δ- and μ-opioid receptor agonists on ventilation in conscious adult dogs

Abstract We studied ventilation and ventilatory pattern in adult unanesthetized dogs after intracisternal adminstration of morphiceptin analogue (MA) (Tyr-Pro-NMePhe- d -Pro-NH2) and morphine sulfate (MS) which are μ-receptor opioid agonists and after d -Ala- d -Leuenkephalin (DADLE), a preferential δ-receptor opioid agonist. DADLE induced a prolongation in expiratory time, Te, and a reduction in instantaneous minute ventilation, Vt/Ttot, which lasted for about 2 h and was dose dependent. In contrast, MA and MS induced a striking decrease in Te and tidal volume with a net increase in Vt/Ttot. Both MA and DADLE increased the number of sighs per unit time while morphine did not. Naloxone increased Vt/Ttot when used after both DADLE or MA but larger doses were required for an observable effect after DADLE than after MA. These data suggest that in the unanesthetized dog: (1) the effect of intracisternal opioids on ventilation and ventilatory pattern is not uniform and (2) the opioid μ-receptor subsystem may involve different neuronal pathways from those of the opioid δ-receptor subsystem to modulate breathing.

Effect of parasympathetic blockade on ventilatory and cardiac depression induced by opioids

We have previously shown that delta-opioid agonists decrease ventilation and heart rate. Because of these results and the known interactions between opioid and acetylcholine metabolism, we hypothesized that opioids induce cardiorespiratory changes via the parasympathetic nervous system. To test this hypothesis, we administered atropine sulfate (systemically) at maximal effect of D-Ala-D-Leu-enkephalin (DADLE; a preferential delta-opioid agonist), injected intracisternally, and examined its effect on cardiorespiratory function. All experiments were performed on chronically instrumented and conscious adult dogs. Mean instantaneous minute ventilation or VT/TTOT decreased and PaCO2 increased after DADLE; atropine had little effect on these changes. Naloxone, even in small doses, reversed opioid effects on VT/TTOT and PaCO2. Atropine, however, reversed the DADLE-induced depression in cardiac rate. In doses that reversed this cardiac depression, atropine had no effect on cardiorespiratory function at rest, i.e., with no prior administration of DADLE. We conclude that DADLE decreases heart rate by increasing parasympathetic activity to the heart and induces hypoventilation by a different mechanism. We speculate that the opioid-induced ventilatory depression is due to either direct opioid action on central respiratory regulation or parasympathetic non-muscarinic or non-cholinergic mediating mechanisms.

Heart rate pattern during sleep in an infant with congenital prolongation of the Q-T interval (Romano-Ward syndrome).

Heart rate and the variability of the heart rate, indices of autonomic control, were studied during sleep in an infant with prolonged Q-T interval (Romano-Ward syndrome) and were compared to the heart rate and variability of heart rate in 18 normal infants studied at monthly intervals during the first four months of life. The overall variability and beat-to-beat variability in the infant with Romano-Ward syndrome were significantly below the median in the normal infants at each age and sleep state. This decrease in overall and beat-to-beat variability persisted after normalization by the absolute heart rate; however, the heart rate in the infant with Romano-Ward syndrome was not different from those in normal infants. These data suggest that the presence of a normal heart rate does not exclude abnormal autonomic activity; and in certain clinical situations, the variability of heart rate may be a more sensitive index of abnormal autonomic function than the heart rate itself.

Breath-to-Breath Control of Ventilation in Normal Infants During Sleep

A variety of clinical problems including apnea of prematurity and the Sudden Infant Death Syndrome (SIDS) may be related to abnormalities in the maturation of the cardiopulmonary control mechanisms. However, even in the normal infant, there is little information concerning maturation of patterns of breathing. In addition, long-term measurements have seldom if ever been made under wholly non-invasive conditions. In this context non-invasive implies the absence of extraneous sensory stimuli especially to the face that may alter the breathing pattern1. Based on a new theoretical analysis of the barometric method of measuring tidal volume, we have developed a chamber that allows us to examine breathing in infants for several hours at a time while avoiding the use of neck seals and face masks.