Synthetic human adrenomedullin and ADM15-52 have potent short-lasting vasodilator activity in the pulmonary vascular bed of the cat.

Responses to synthetic human adrenomedullin, a novel hypotensive peptide localized in several organ systems, including the lung, and the carboxy terminal 15-52 amino acid fragment of adrenomedullin (ADM15-52) were investigated in the pulmonary vascular bed of the intact-chest cat. Under constant flow conditions when baseline tone in the pulmonary vascular bed was raised to a high steady level, injections of adrenomedullin and ADM15-52 into the perfused lobar artery in doses of 0.1-1 nmol, caused significant dose-related decreases in lobar arterial pressure. Since left atrial pressure was unchanged, the decreases in lobar arterial pressure reflect decreases in pulmonary lobar vascular resistance. Adrenomedullin and ADM15-52 exhibited similar vasodilator activity and were approximately 3-fold more potent than bradykinin in the pulmonary vascular bed of the cat. Pulmonary vasodilator responses to adrenomedullin and ADM15-52 were rapid in onset and lasted for 150-200 sec, depending on the dose of the peptide injected. The present results demonstrate that synthetic human adrenomedullin and ADM15-52 possess potent, short-lasting vasodilator activity in the pulmonary vascular bed of the cat and suggest that amino acids 15-52 in the peptide are important for the expression of vasodilator activity in the pulmonary vascular bed of the cat.

Frequency spectra of normal breath sounds in childhood.

Clinicians who auscultate the chest of normal children note that the frequency content of their breath sounds appears to vary with age. Because these changes have not been systematically documented before, we recorded and analyzed inspiratory breath sounds in 35 children (0 to 13 years) and five adults (34 to 43 years). Our objective was to determine if the frequency content of normal breath sounds differed with age. Using a Fast Fourier Transform program, we calculated an average amplitude frequency spectrum from the inspiratory portion of the breath sounds of each subject (n = 10 breaths), and we compared the shape of the AFS and the values of selected frequency parameters. We found that the shape of the AFS of the youngest children differed most from the AFS of adults. Three of four selected frequency parameters (F25, F50, F95) differed significantly between children and adults (p less than 0.05), and one parameter (F75) did not (p = 0.11). The F25, F50, and F75 parameters of children (but not F95) were correlated (p less than 0.001) with increasing height and age. These results suggest that differences in the frequency content of the normal breath sounds of children and adults contribute to the differences that clinicians detect during clinical auscultation.

Influence of SK&F 95587 and BN 50730 on bronchoconstrictor responses in the cat.

The effects of SK&F 95587 (4[2-(benzenesulfonamido)-ethyl] phenoxyacetic acid), a thromboxane (TX) receptor blocking agent, on bronchoconstrictor responses were investigated in paralyzed, anesthetized, mechanically ventilated cats. Intravenous injections of the TXA2 receptor mimics, U-46619 [(15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta5Z,13E-dienoic acid] and U-44069 (9,11-dideoxy-11 alpha,9 alpha-epoxymethano PGF2 alpha), produced dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic compliance. After administration of SK&F 95587, 5 mg/kg i.v., bronchoconstrictor responses to U-46619 and U-44069 were reduced markedly, whereas airway responses to prostaglandin (PG)F2 alpha, serotonin, PGD2 or the PGD2 metabolite, 11 beta-PGF2 alpha, were not altered. The duration of action of SK&F 95587 was greater than 3 hr, and the blockade was overcome when 10-fold larger doses of the TXA2 mimics were administered. Bronchoconstrictor responses to platelet-activating factor (PAF) were blocked by SK&F 95587 and by the novel PAF receptor antagonist, BN 50730. BN 50730 also blocked the fall in systemic arterial pressure in response to PAF. However, BN 50730 did not influence airway responses to U-46619, PGF2 alpha, PGD2 or serotonin and had no effect on baseline bronchomotor tone or arterial pressure. The PAF receptor antagonism with BN 50730 was overcome when 10-fold larger doses of PAF were administered and the dose-response curves for changes in lung resistance and dynamic compliance were shifted to the right in a parallel manner. The present data suggest that SK&F 95587 has selective TX receptor blocking activity, and that BN 50730 has selective PAF receptor blocking properties in the airways of the cat. The present data also provide support for the hypothesis that bronchoconstrictor responses to PAF are mediated by specific receptors, which are coupled to a phospholipase and, when activated, result in the release of TXA2 and contraction of airway smooth muscle.

Effects of OKY 1581 on bronchoconstrictor responses to arachidonic acid and PGH2.

The influence of OKY 1581, a thromboxane synthase inhibitor, on airway responses to arachidonic acid and endoperoxide, [prostaglandin (PG) H2], were investigated in anesthetized, paralyzed, mechanically ventilated cats. Intravenous injections of arachidonic acid and PGH2 caused dose-related increases in transpulmonary pressure and lung resistance and decreases in dynamic and static compliance. OKY 1581 significantly decreased airway responses to arachidonic acid but not to PGH2. Sodium meclofenamate, a cyclooxygenase inhibitor, abolished airway responses to arachidonic acid but had no effect on airway responses to PGH2. OKY 1581 or meclofenamate has no effect on airway responses to PGF2 alpha, PGD2, or U 46619, a thromboxane mimic. In microsomal fractions from the lung, OKY 1581 inhibited thromboxane formation without decreasing prostacyclin synthesis or cyclooxygenase activity. These studies show that OKY 1581 is a selective thromboxane synthesis inhibitor in the cat lung and suggest that a substantial part of the bronchoconstrictor response to arachidonic acid is due to thromboxane A2 formation. Moreover, the present data suggest that airway responses to endogenously released and exogenous PGH2 are mediated differently and that a significant part of the response to exogenous PGH2 may be due to activation of an endoperoxide/thromboxane receptor, since responses to PGH2 are blocked by the thromboxane receptor antagonist SQ 29548.

A comparison of tracheal breath sounds, airflow, and impedance pneumography in the detection of childhood apnea.

Impedance respiratory monitoring is not capable of detecting obstructive apneas. We compared a microphone breath sound detector, coupled to the chest wall, with a standard impedance device in 10 sleeping infants and children in order to determine the ability of the breath sound detector to detect normal respirations and central and obstructive apneas. Airflow was used as a standard for all measurements. No difference was found between the breath sound detector and impedance device techniques in the detection rate of either normal respirations or central apneic intervals. There was no statistically significant difference between breath sounds and airflow in the ability of either technique to detect obstructive apnea. The use of a breath sound detector avoids unnecessary stimulation of a sleeping child, whose monitoring would otherwise require that two or three airflow sensing devices be taped on the face. Breath sound monitoring may represent an alternative to impedance and airflow techniques for evaluation of apnea in closely observed infants and children.

Frequency spectra of flow and volume events for forced vital capacity.

We determined the frequency content of forced expiratory flow-time (FT) and volume-time (VT) curves by a fast Fourier transform to determine the dynamic responses required of devices to reproduce these curves. We analyzed 304 FT and VT curves from 15 normal (N) subjects (ages 8-34 yr), 15 cystic fibrosis (CF) patients (ages 7-36 yr), and 9 smokers (S, ages 20-63 yr). The highest frequency (HF) with significant amplitude content, defined as the highest frequency with 5% or more amplitude of the fundamental, for FT curves in N (mean +/- SD, 5.06 +/- 0.7 Hz) was significantly (P less than 0.05) lower than in CF (6.43 +/- 0.9 Hz) and S (6.49 +/- 1.8 Hz). These differences were due predominantly to flow transients at high lung volumes in CF and S. No significant differences in HF of VT curves were noted among N (3.0 +/- 1.4 Hz), CF (2.9 +/- 1.4 Hz), and S (1.7 +/- 1.5 Hz). All subjects had HF for FT of 12 Hz or less and for VT of 6 Hz or less. For spirometric recordings our results suggest that the amplitude response of flow- and volume-measuring devices should be flat (+/- 5%) up to 12 Hz for flow signals and up to 6 Hz for volume signals.

Tracheal breath sounds for detection of apnea in infants and children.

Impedance respiratory monitoring is the standard technique for detecting apnea in infants. A miniature microphone/amplifier system has been used to sense breath sounds over the trachea in order to detect both central and obstructive apnea episodes in infants and children. The tracheal microphone has several advantages over other devices that sense airflow (thermistors, CO2 sampling catheters) because it is not easily dislodged during restless sleep. This simple device may be used in monitoring of neonates and infants; it may eventually replace impedance monitoring.

Within-subject variability and per cent change for significance of spirometry in normal subjects and in patients with cystic fibrosis.

We studied 15 normal subjects and 15 patients with cystic fibrosis (CF), to determine the within-subject variability of spirometry, moment analysis, and slope ratios, and to calculate the per cent change for significance. Common sources of variability, such as patient and technician training, equipment errors, lung volume history, posture, and circadian variation, were controlled. Flow-time curves were analyzed with a digital computer. The coefficient of variations of spirometry were smallest for forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak flow (PF), and were largest for root moments (M) and slope ratios (SR) in both normal subjects and patients with CF. The coefficient of variations of all tests, except PF, were larger in patients with CF than in normal subjects. Significant change was calculated from the sample variance, mean, and the number of trials using a modified equation for sample size. This calculation estimated the degree of change for significance for each participant that was required in subsequent testing.

Method for respiratory sound analysis.

A system is described for the analysis of respiratory sounds by means of a dual-channel sound envelope detector and a real-time spectrum analyzer. A three-dimensional spectral analyzer display for frequency, amplitude, and time has been utilized. Respiratory sounds have been observed with intensities up to 0.5 N/m2 and with normal frequencies in the range of 0 to 1.5 kHz. This system can extract useful information from the sounds of respiration, information which is not available by conventional auscultation.

Effects of arachidonic acid and prostaglandins on lung function in the intact dog.

The effects of the prostaglandin (PG) precursor, arachidonic acid (AA), and the primary PG's, PGF2alpha, and PGD2, on lung function were compared in 39 intact-chest, paralyzed, artificially ventilated dogs. Intravenous AA decreased dynamic compliance (Cdyn) and functional residual capacity and increased airway resistance (Rl) and transpulmonary pressure at end-passive expiration. The decrease in Cdyn correlated closely with a rise in pulmonary arterial pressure (Ppa). Indomethacin abolished airway and vascular responses to AA, but did not attenuate responses to the PG's. The effects of AA, PGD2, and PGF2alpha on lung function and Ppa were similar, whereas PGE2 had little effect. Vagotomy attentuated the RL increase in response to AA, PGE2alpha, and PGD2 and the Cdyn decrease in response to the PG's. The effects of the PG's on compliance were greater than those produced by mechanically increasing pulmonary venous pressure. The present studies suggest that the PG precursor is rapidly converted to agents that have marked effect on both pulmonary vessels and airways, particularly peripheral airways, in the dog.