Journal of applied physiology
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Comparative Study
Depression of cough reflex by microinjections of antitussive agents into caudal ventral respiratory group of the rabbit.
We have previously shown that the caudal nucleus tractus solitarii is a site of action of some antitussive drugs and that the caudal ventral respiratory group (cVRG) region has a crucial role in determining both the expiratory and inspiratory components of the cough motor pattern. These findings led us to suggest that the cVRG region, and possibly other neural substrates involved in cough regulation, may be sites of action of antitussive drugs. To address this issue, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30-50 nl) of some antitussive drugs into the cVRG of pentobarbital-anesthetized, spontaneously breathing rabbits. [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) and baclofen at the lower concentrations (0.5 mM and 0.1 mM, respectively) decreased cough number, peak abdominal activity, and peak tracheal pressure and increased cough-related total cycle duration (Tt). ⋯ The neurokinin-1 (NK(1)) receptor antagonist CP-99,994 (10 mM) decreased cough number, peak abdominal activity, and peak tracheal pressure, without affecting baseline respiration. The NK(2) receptor antagonist MEN 10376 (5 mM) had no effect. The results indicate that the cVRG is a site of action of some antitussive agents and support the hypothesis that several neural substrates involved in cough regulation may share this characteristic.
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The relationship between changes in absolute end-expiratory lung volume (EELV) and collapsibility has not been rigorously quantified. We hypothesized that pharyngeal collapsibility varies inversely with absolute lung volume in sleeping humans during 1) conventional and 2) isovolume measurements of passive critical pressure (Pcrit). Eighteen healthy subjects (11 male, 7 female) slept in a negative pressure ventilator for measurements of pharyngeal collapsibility (Pcrit) during non-rapid eye movement sleep. ⋯ Nevertheless, men and women differed significantly in FRC (2.63 ± 0.16 vs. 1.88 ± 0.13 liters, P <0.05) and FRC isovolume Pcrit (-2.3 ± 0.8 vs. -7.2 ± 1.2 cmH(2)O, P < 0.05), implying that the men had larger lungs and more collapsible airways than the women. The ΔPcrit/ΔEELV response was independent of sex, conventional Pcrit, body mass index, and neck, waist, and hip circumferences. We conclude that Pcrit varies inversely with absolute EELV, which may lead to 1) an underestimation of the magnitude of quantitative differences in Pcrit across the spectrum from health (negative Pcrit) to disease (positive Pcrit) and 2) increases in sleep apnea susceptibility in obesity.
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The effects of full lung inflation on respiratory conductance (Grs) and reactance (Xrs) were measured in 15 subjects with moderate to severe chronic obstructive pulmonary disease (COPD) and 11 matched healthy control subjects. Airway distensibility was estimated from the ratio of the difference of Grs between functional residual capacity and total lung capacity to the relevant changes in lung volume (ΔGrs/ΔVl) or transpulmonary pressure (ΔGrs/ΔPtp). Similar analysis was applied to Xrs to estimate lung volume recruitment (ΔXrs/ΔVl or ΔXrs/ΔPtp). ⋯ Moreover, ΔGrs/ΔPtp and ΔXrs/ΔPtp with lung inflation were no longer correlated with each other, suggesting that airway distensibility and volume recruitment were affected differently by airway smooth muscle tone. Assuming that Grs mainly reflects airway caliber and Xrs the number of ventilated lung units, we conclude that airway smooth muscle contributes to airway stiffness and ventilation inhomogeneities in COPD subjects with prevailing bronchitis but only to the latter in those with more emphysema. We suggest that changes of airway distensibility and volume recruitment with a bronchodilator may be useful for disease phenotyping.
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Criteria for diagnosing cachexia in adults include unintentional loss in body weight, decreased strength, fatigue, anorexia, and low muscle mass. Cachexia is also associated with systemic inflammation, altered metabolism, and anemia. The Apc(Min/+) mouse is a model of cachexia directly related to intestinal tumor burden and subsequent chronic inflammation. ⋯ In sedentary Apc(Min/+) mice at 26 wk of age anemia was present, and markers of apoptosis were induced in severely cachectic muscle. Proapoptotic protein expression was induced in both red and white portions of gastrocnemius muscle as well as in soleus muscle of severely cachectic mice compared with mildly cachectic mice. These data demonstrate that decrements in wheel running performance precede loss of body mass and that inherent muscle oxidative capacity is not protective against muscle apoptosis.
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Pulmonary hypertension on heart failure (HF) limits exercise capacity and survival probably because of associated right ventricular (RV) failure. This study investigated the mechanisms of RV function adaptation to early pulmonary hypertension in experimental HF. Seven weeks of rapid ventricular pacing in six dogs induced a HF characterized by cardiomegaly and decreased left ventricular ejection fraction. ⋯ Inhaled nitric oxide, 40 ppm or 5 μg·kg(-1)·min(-1) nitroprusside i.v., did not affect Ees/Ea. Fifty milligrams (i.v.) of milrinone increased Ees/Ea to 1.6 ± 0.2 by an isolated increase in Ees. We conclude that overpacing-induced HF is accompanied by a borderline pulmonary hypertension but profound RV-arterial uncoupling explained by the failure of RV systolic function to adapt combined effects of increased pulmonary arterial resistance and elastance.