Ventilatory instability during sleep: new insights from the computational model.

We developed a computational model of the human respiratory system and its chemoreflex control during sleep [1] [2] Our model, which is an extension of the model of Grodins et al. [3], combines an accurate description of a plant with a novel controller design. The controller consists of two feedback loops (central and peripheral) each with its own delay and gain. The overall minute ventilation is a sum of central and peripheral components. The model was employed to develop a new graphical method for stability analysis of the respiratory control system similar in concept to the phase plane. The relative chemosensitivities of the peripheral and central loops serve as the plane's coordinates. A region of stability exists with the normal operating point for the system lying well inside its boundaries. Changes to the sensitivities of either loop, caused by known pathologies, displace the operating point toward the border of the stability region. Furthermore, the shape and area of the stability region is significantly influenced by changes in the cerebral blood flow.

Analysis of respiratory and muscle activity by means of cross information function between ventilatory and myographic signals.

Analysis of respiratory muscle activity is a promising technique for the study of pulmonary diseases such as obstructive sleep apnea syndrome (OSAS). Evaluation of interactions between muscles is very useful in order to determine the muscular pattern during an exercise. These interactions have already been assessed by means of different linear techniques like cross-spectrum, magnitude squared coherence or cross-correlation. The aim of this work is to evaluate interactions between respiratory and myographic signals through nonlinear analysis by means of cross mutual information function (CMIF), and finding out what information can be extracted from it. Some parameters are defined and calculated from CMIF between ventilatory and myographic signals of three respiratory muscles. Finally, differences in certain parameters were obtained between OSAS patients and healthy subjects indicating different respiratory muscle couplings.

Dynamic ventilatory response to CO(2) in congestive heart failure patients with and without central sleep apnea.

Nonobstructive (i.e., central) sleep apnea is a major cause of sleep-disordered breathing in patients with stable congestive heart failure (CHF). Although central sleep apnea (CSA) is prevalent in this population, occurring in 40-50% of patients, its pathogenesis is poorly understood. Dynamic loop gain and delay of the chemoreflex response to CO(2) was measured during wakefulness in CHF patients with and without CSA by use of a pseudorandom binary CO(2) stimulus method. Use of a hyperoxic background minimized responses derived from peripheral chemoreceptors. The closed-loop and open-loop gain, estimated from the impulse response, was three times greater in patients with nocturnal CSA (n = 9) than in non-CSA patients (n = 9). Loop dynamics, estimated by the 95% response duration time, did not differ between the two groups of patients. We speculate that an increase in dynamic gain of the central chemoreflex response to CO(2) contributes to the genesis of CSA in patients with CHF.

The role of angiotensin in arterial blood pressure regulation in the toad Bufo marinus.

Little is known about the role of the renin-angiotensin system in anuran amphibians, although they appear to possess the functional components of such a system. We investigated the role of angiotensin (ANG) in arterial blood pressure regulation in the conscious toad Bufo marinus using the angiotensin-converting enzyme blocker captopril. We found that conversion of endogenous ANG I to ANG II made a significant contribution to mean arterial pressure in undisturbed animals. The vascular tone contributed by ANG II was not mediated via &agr ; adrenergic mechanisms because increases in pressure in response to ANG infusion were unaffected by the presence of the &agr ; antagonist phentolamine. Angiotensin-induced vasoconstriction was shown to be an important mechanism in arterial blood pressure regulation in the face of an acute hypotensive perturbation of pressure brought about by sodium nitroprusside. Blockade of the conversion of ANG I to ANG II significantly delayed the recovery of mean arterial pressure after sodium nitroprusside-induced hypotension. This suggests that the renin-angiotensin system may play an important role in the initial responses to hypotension in anurans, whether brought about by haemorrhage or dehydration.

Hypoxemic threshold for lung ventilation in the toad.

The relationship between the activity of the buccal force pump, expressed as the time integral of positive buccal pressure, and PaO2 was investigated in conscious toads, Bufo marinus, unidirectionally ventilated at a high flow rate (240-260 ml/min). The high ventilatory flow rate meant that PaO2 was largely independent of the animal's ventilatory activity so that the relationship between pulmonary ventilation and PaO2 was effectively open-loop. The hypoxemic threshold (PaO2) for lung ventilation was 54.2 mm Hg in hypocapnia (PaCO2 = 4.7 +/- 0.3 mm Hg), 82.6 mm Hg in normocapnia (PaCO2 = 11.6 +/- 0.2 mm Hg), and 137.9 mm Hg in hypercapnia (PaCO2 = 20.1 +/- 0.1 mm Hg). Unidirectional ventilation with 20% O2 in N2, a condition in which the toads were normoxic but hypocapnic, stopped pulmonary ventilation cycles. Taken with existing evidence that hyperoxia stops pulmonary ventilation even under conditions in which PaCO2 is elevated this suggests that hypoxic and hypercapnic stimuli summate to drive lung ventilation in the toad. Bilateral denervation of the carotid labyrinths decreased pulmonary ventilation in absolute terms, but did not reduce the proportionate increase in pulmonary ventilation in response to normocapnic hypoxia, suggesting that chemoreceptors within the carotid labyrinth may contribute to, but are not solely responsible for, the hypoxemic ventilatory drive.