H. A. Menkes

Collateral Ventilation in Man

To determine whether collateral ventilation (defined as the ventilation of alveolar structures through passages or channels that bypass the normal airways) changes with age or emphysema, we compared the mechanics of collateral ventilation in seven young normal subjects, three old normal subjects and five patients with emphysema. In supine normal subjects at the end of a quiet expiration, resistance to airflow was greater through collateral channels than through bronchi and bronchioles. In emphysema, airways resistance could exceed collateral resistance, causing air to flow preferentially through collateral pathways. We conclude that high collateral resistance minimizes collateral airflow in supine normal subjects. When peripheral airways become obstructed or obliterated in emphysema, collateral channels may provide for more even distribution of ventilation.

Protein kinase C regulates smooth muscle tension in guinea-pig trachea and ileum

To explore the function of protein kinase C in smooth muscle, the effects of phorbol esters, potent activators of protein kinase C, were examined in guinea-pig tracheal rings and ileal strips. In tracheal rings, phorbol-12,13-diacetate (PDA) and 12-deoxyphorbol-13-isobutyrate (DPB), both potent stimulants of protein kinase C, produce a concentration dependent, reversible relaxation of resting tracheal tension, whereas phorbol, an inactive analogue is ineffective. PDA also reverses contractions produced by carbachol, serotonin, prostaglandin F2 alpha and prostaglandin D2. In contrast to their ability to inhibit agonist induced contractions, PDA and DPB greatly amplify the constriction produced by a depolarizing concentration of KCl (59 mM). The calcium channel blockers verapamil, nifedipine and diltiazem block the constriction produced by KCl and PDA suggesting that under depolarizing conditions, PDA synergizes with increased intracellular calcium to potentiate muscle contraction. Similar biphasic responses to phorbol esters are elicited in strips of guinea-pig ileum. These results indicate that in addition to enhancing the actions of intracellular calcium in producing contraction, protein kinase C can also activate feedback mechanisms which limit cellular responses.

Effects of positive end expiratory pressure on shunt flow in atelectasis.

We studied the effects of positive end expiratory pressure (PEEP) on vascular pressure flow relationships in atelectatic lobes in the closed-chest pigs and compared our results to measurements we previously obtained in sublobar atelectasis. Regional hemodynamic responses to lung inflation were significantly different between lobes and sublobar regions. PEEP caused marked increase in the fraction of cardiac output perfusing the atelectatic lobe from 16.5 +/- 2.0% (SE) to 32.5 +/- 2.0% at similar pulmonary vascular transmural pressures. In contrast, similar levels of PEEP failed to redistribute blood flow to the atelectatic sublobar regions. We propose that distortion of the sublobar region with inflation of the surrounding lung may be responsible for the failure of redistribution of pulmonary blood flow with application of PEEP.

Diurnal variation of air and helium-oxygen flow-volume curves in asthmatic children

In order to assess diurnal variation of flow-volume curves and to determine whether small airways are involved in the diurnal variation of pulmonary function in asthmatic children, we studied eight asthmatics who were attending an asthma summer camp. Spirometry and maximal expiratory flow-volume curves with air and a helium-oxygen mixture were obtained in the morning and afternoon over a 10-day period. We found that significant increases in maximal expiratory flows at all lung volumes occurred in the afternoon. However, the increase in flows with helium (helium response) was unchanged from morning to afternoon. These results suggest that both large and small airways are involved in the diurnal variation of pulmonary function in asthmatic children.

Characterization and interpretation of forced expiration

Forced expiration is the most widely used test for assessing pulmonary mechanics in man. For clinical purposes, results can be described in terms of the forced vital capacity (FVC) and the forced expiratory volume in 1 sec (FEV1). In order to provide a more complete description of forced expiration, additional parameters have been applied, e.g., flows at various lung volumes (flow volume loops) and the distribution of transit times during lung emptying (moments).In an ongoing epidemiological study we found that age, sex, smoking, socioeconomic status, ABH secretor status, protease inhibitor type, and familial COPD contribute to airways obstruction. We also found that characteristic patterns of obstruction provide insight into risk factors and the pathophysiology of disease.

Perfusion of lung periphery: effects of local exposures to ozone and pressure

Following ozone (O3) exposure, airways reactivity increases. We investigated the possibility that exposure to O3 causes a decrease in pulmonary perfusion, and that this decrease is associated with the increase in reactivity. Perfusion was measured with radiolabeled microspheres. A wedged bronchoscope was used to isolate sublobar segments in the middle and lower lobes of anesthetized dogs. Isolated segments were exposed to either O3 or an elevated alveolar pressure. Although increased alveolar pressure decreased microsphere density, exposure to 1 ppm O3 did not. Collateral system resistance rose significantly following exposure to O3 and to high pressure. These studies do not support the hypothesis that pulmonary perfusion is decreased following O3 exposure and is associated with subsequent increases in reactivity.