Gap junction blockade does not alter eupnea or gasping in the juvenile rat.

The role of gap junctions in the brainstem respiratory control system is ambiguous. In the present study, we used juvenile rats to determine whether blocking gap junctions altered eupnea or gasping in the in situ, arterially perfused rat preparation. Blockade of gap junctions with 100 microM carbenoxolone or 300 microM octanol did not produce any consistent changes in the timing or amplitude of integrated phrenic discharge or in the peak frequency in the power spectrum of phrenic nerve discharge during eupnea or ischemic gasping beyond those changes seen in time-control animals. These findings do not rule out a role for gap junctions in the expression of eupnea or gasping, but they do demonstrate that these intermembrane channels are not obligatory for either rhythm to occur.

Cardiovascular effects of the respiratory muscle metaboreflexes in dogs: rest and exercise.

In awake dogs, lactic acid was injected into the phrenic and deep circumflex iliac arteries to elicit the diaphragm and abdominal muscle metaboreflexes, respectively. At rest, injections into the phrenic or deep circumflex iliac arteries significantly increased mean arterial blood pressure 21 +/- 7% and reduced cardiac output 6 +/- 2% and blood flow to the hindlimbs 20 +/- 9%. Simultaneously, total systemic, hindlimb, and abdominal expiratory muscle vascular conductances were reduced. These cardiovascular responses were not accompanied by significant changes in the amplitude or timing of the diaphragm electromyogram. During treadmill exercise that increased cardiac output, hindlimb blood flow, and vascular conductance 159 +/- 106, 276 +/- 309, and 299 +/- 90% above resting values, lactic acid injected into the phrenic or deep circumflex iliac arteries also elicited pressor responses and reduced hindlimb blood flow and vascular conductance. Adrenergic receptor blockade at rest eliminated the cardiovascular effects of the respiratory muscle metaboreflex. We conclude that the cardiovascular effects of respiratory muscle metaboreflex activation are similar to those previously reported for limb muscles. When activated via metabolite production, the respiratory muscle metaboreflex may contribute to the increased sympathetic tone and redistribution of blood flow during exercise.

Carotid body denervation eliminates apnea in response to transient hypocapnia.

We determined the effects on breathing of transient ventilatory overshoots and concomitant hypocapnia, as produced by pressure support mechanical ventilation (PSV), in intact and carotid body chemoreceptor denervated (CBX) sleeping dogs. In the intact dog, PSV-induced transient increases in tidal volume and hypocapnia caused apnea within 10-11 s, followed by repetitive two-breath clusters separated by apneas, i.e., periodic breathing (PB). After CBX, significant expiratory time prolongation did not occur until after 30 s of PSV-induced hypocapnia, and PB never occurred. Average apneas of 8.4 +/- 1-s duration after a ventilatory overshoot required a decrease below eupnea of end-tidal Pco(2) 5.1 +/- 0.4 Torr below eupnea in the intact animal and 10.1 +/- 2 Torr in the CBX dog, where the former reflected peripheral and the latter central dynamic CO(2) chemoresponsiveness, as tested in the absence of peripheral chemoreceptor input. Hyperoxia when the dogs were intact shortened PSV-induced apneas and reduced PB but did not mimic the effects of CBX. We conclude that, during non-rapid eye movement sleep, carotid chemoreceptors are required to produce apneas that normally occur after a transient ventilatory overshoot and for PB.

Effect of ventilatory drive on carbon dioxide sensitivity below eupnea during sleep.

We determined the effects of changing ventilatory stimuli on the hypocapnia-induced apneic and hypopneic thresholds in sleeping dogs. End-tidal carbon dioxide pressure (PET(CO2)) was gradually reduced during non-rapid eye movement sleep by increasing tidal volume with pressure support mechanical ventilation, causing a reduction in diaphragm electromyogram amplitude until apnea/periodic breathing occurred. We used the reduction in PET(CO2) below spontaneous breathing required to produce apnea (DeltaPET(CO2)) as an index of the susceptibility to apnea. DeltaPET(CO2) was -5 mm Hg in control animals and changed in proportion to background ventilatory drive, increasing with metabolic acidosis (-6.7 mm Hg) and nonhypoxic peripheral chemoreceptor stimulation (almitrine; -5.9 mm Hg) and decreasing with metabolic alkalosis (-3.7 mm Hg). Hypoxia was the exception; DeltaPET(CO2) narrowed (-4.1 mm Hg) despite the accompanying hyperventilation. Thus, hyperventilation and hypocapnia, per se, widened the DeltaPET(CO2) thereby protecting against apnea and hypopnea, whereas reduced ventilatory drive and hypoventilation narrowed the DeltaPET(CO2) and increased the susceptibility to apnea. Hypoxia sensitized the ventilatory responsiveness to CO2 below eupnea and narrowed the DeltaPET(CO2); this effect of hypoxia was not attributable to an imbalance between peripheral and central chemoreceptor stimulation, per se. We conclude that the DeltaPET(CO2) and the ventilatory sensitivity to CO2 between eupnea and the apneic threshold are changeable in the face of variations in the magnitude, direction, and/or type of ventilatory stimulus, thereby altering the susceptibility for apnea, hypopnea, and periodic breathing in sleep.

Diaphragm plasticity following intrinsic laryngeal muscle denervation in rats.

PURPOSE: During inspiration, recruitment of the intrinsic laryngeal muscles (ILM) reduces the inspiratory load on the ventilatory pump muscles. The purpose of our study was to determine 1) whether the diaphragm adapts to denervation of the ILM, and 2) whether the additional stimulus of exercise training affects the degree to which the diaphragm adapts to ILM denervation. METHODS: Thirty-six male Sprague-Dawley rats (2 months) were randomly divided into sedentary control (SC), sedentary-denervated (SD), and exercise-denervated (ED) groups. Control animals underwent sham operations, whereas ILM-denervated animals underwent bilateral transection of the recurrent laryngeal nerves. Three weeks after surgery, animals in the ED group performed a treadmill training protocol for a period of 6 wk. RESULTS: Denervation (SD and ED animals) of the ILM significantly increased diaphragm citrate synthase activity (20%), in vitro endurance, and time to peak twitch tension (15%), and reduced (13%) peak tetanic tension (Po, N x cm(-2)). No independent training effect over and above the effects attributed to denervation of ILM were noted in ED animals. CONCLUSION: The results highlight the role of vocal cord dilator function during both eupnea and exercise-induced hyperpnea.