Ventilatory responses

Pierce NF, Fedson DS, Brigham KL, et al. The ventilatory response to acute base deficit in humans. Time course during development and correction of metabolic acidosis. Ann Intern Med 1970 72 633-640. 

Chemoreceptor response to decreased arterial P02. Hypoxia has a direct depressant effect on central chemoreceptors as well as on the medullary respiratory center. In fact, hypoxia tends to inhibit activity in all regions of the brain. Therefore, the ventilatory response to hypoxemia is elicited only by the peripheral chemoreceptors. 

Beyond this point, during more severe exercise associated with anaerobic metabolism, minute ventilation increases faster than the rate of oxygen consumption, but proportionally to the increase in carbon dioxide production. The mechanism of the ventilatory response to severe exercise involves metabolic acidosis caused by anaerobic metabolism. The lactic acid produced under these conditions liberates an H+ ion that effectively stimulates the peripheral chemoreceptors to increase ventilation. 

The mechanisms involved with the ventilatory response to exercise remain quite unclear. No single factor, or combination of factors, can fully account for the increase in ventilation during exercise. Therefore, much of this response remains unexplained. Factors that appear to play a role include ... 

Proprioceptors originating in muscles and joints of the exercising limbs provide substantial input to the medullary respiratory center. In fact, even passive movement of the limbs causes an increase in ventilation. Therefore, the mechanical aspects of exercise also contribute to the ventilatory response. The increased metabolism associated with exercise increases body temperature, which further contributes to the increase in ventilation during exercise. (Not surprisingly, ventilation is also enhanced in response to a fever.) Exercise is associated with a mass sympathetic discharge. As a result, epinephrine release from the adrenal medulla is markedly increased. Epinephrine is believed to stimulate ventilation. 

Schaper, M., Thompson, R.D. and Alarie, Y. (1985). A method to classify airborne chemicals which alter the normal ventilatory response induced by C02. Toxicol Appl Pharmacol. 79 332-341. 

Mechanism of Action A central nervous system stimulant that directly stimulates the respiratorycenterinthemedullaorindirectlybyeffectsonthecarotid. TfterflpeMtIc Effect Increases pulmonary ventilation by increasing resting minute ventilation, tidal volume, respiratory frequency, and inspiratory neuromuscular drive, and enhances the ventilatory response to carbon dioxide. 

Nitrous oxide decreases tidal volume and increases the rate of breathing and minute ventilation. Although arterial carbon dioxide partial pressures tend not to be affected the normal ventilatory responses to carbon dioxide and to hypoxia are depressed. Alveolar collapse in structured lung segments may be more rapid in the presence of nitrous oxide than with oxygen due to its greater solubility. Similarly, it depresses mucous flow and chemotaxis. In theory these factors predispose to postoperative respiratoiy complications. 

The respiratory actions of the methylxanthines may not be confined to the airways, for they also strengthen the contractions of isolated skeletal muscle in vitro and improve contractility and reverse fatigue of the diaphragm in patients with COPD. This effect on diaphragmatic performance—rather than an effect on the respiratory center—may account for theophylline s ability to improve the ventilatory response to hypoxia and to diminish dyspnea even in patients with irreversible airflow obstruction. 

Skatrud JB, Dempsey JA, Kaiser DG (1978) Ventilatory responses to medroxyprogesterone acetate in normal subjects time course and mechanism. J Appl Physiol 44 939-944... 

Strohl, K.P., and C.M. Beal (1997). Ventilatory response to experimental hypoxia in adult male and female natives of the Tibetan and Andean plateaus. In Women at Altitude, pp. 154-165, ed. C. Houston, Burlington, Vt. Queen City Printers. 

There has been one case report of reduced ventilatory response to hypercapnia after nortriptyline in a woman with chronic obstructive pulmonary disease (SEDA-18,19). 

Alexander CM, Gross JB. Sedative doses of midazolam depress hypoxic ventilatory responses in humans. Anesth Analg 1988 67(4) 377-82. 

Respiratory effects. Isoflurane causes respiratory depression the respiratory rate increases, tidal volume decreases, and the minute volume is reduced. The ventilatory response to carbon dioxide is diminished. Although it irritates the upper airway it is a bronchodilator. 

In a series of studies of ACE inhibitor-induced improvement in pulmonary function, treatment with aspirin 325 mg/day for 8 weeks in patients with mild to moderate heart failure due to primitive dilated cardiomyopathy did not affect ventilation and peak oxygen consumption during exercise when the patients were not taking an ACE inhibitor but worsened pulmonary diffusion capacity and made the ventilatory response to exercise (tidal volume, ventilation to carbon dioxide production) less effective in those who were, regardless of the duration of ACE inhibition (108). 

Trembath PW, Taylor EA, Varley J, Turner P. Effect of propranolol on the ventilatory response to hypercapnia in man. Clin Sci (Lond) 1979 57(5) 465-8. 

Preterm infants can become apneic during the immediate postoperative period, even if the ventilatory response to CO2 is not depressed after halothane anesthesia (12). In a prospective study in 167 preterm infants after inguinal herniorrhaphy with halothane/nitrous oxide anesthesia, only one had an episode of apnea up to 2 days postoperatively however, the authors recommended careful monitoring until complete recovery from anesthesia has occurred (13). 

Palmisano BW, Setlock MA, Doyle MK, Rosner DR, Hoffman GM, Eckert JE. Ventilatory response to carbon dioxide in term infants after halothane and nitrous oxide anesthesia. Anesth Analg 1993 76(6) 1234-7. 

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