Eugene D. Robin

Pulmonary Mechanics during Pregnancy

Previously reported changes in static lung volumes during pregnancy have been confirmed. Measurements of lung compliance (C(L)) and total pulmonary resistance (R(L)) were made in 10 women in the last trimester of pregnancy and 2 months postpartum, employing an esophageal balloon and recording spirometer. C(L) was unaffected by pregnancy, but R(L) was 50% below normal during pregnancy. Measurements of airway conductance (C(A)) were made, employing the constant pressure body plethysmograph on 14 nonpregnant and 13 pregnant women. Specific airway conductance was increased during pregnancy. Serial measurements of C(A) indicated a progressive increase beginning at about 6 months of gestation and a return to normal by 2 months postpartum. The mechanism of the increased C(A) during pregnancy is not known. It may be related to changes in bronchial smooth muscle tone and conceivably explains the tolerance of certain patients with lung resections to pregnancy.

INTRACELLULAR ACID‐BASE RELATIONS AND INTRACELLULAR BUFFERS

The classical work of Henderson and Hasselbalch established firmly the theoretical basis of defining acid-base relationships of plasma and extracellular fluid. Methods based on this theoretical foundation have been widely used by biologists to develop present knowledge of this area. Implicit in an interpretation of the results of investigations of extracellular acid-base balance has been the assumption that a given change of extracellular PH is accompanied by a similar change both in direction and magnitude of intracellular pH. During the past 40 years, however, a large amount of evidence has accumulated indicating that hydrogen ion concentrations across cell membranes do not obey the Donnan relationship and that, under many circumstances, intracellular pH may be independent of extracellular pH. On this basis, any evaluation of the effect of a given substance upon acidbase metabolism should include an estimate of the effect of the substance on intracellular pH. Such evaluation is obviously a complex matter. Intracellular water is not a homogeneous unit, and there is undoubtedly considerable variation in pH from cell to cell as well as nonuniformity of H+ ion concentration within individual cells. Despite these variations, it is theoretically possible to develop a technique for approximating a value that reflects the mean or average H+ concentration inside cells throughout the body.* Such a technique has the disadvantage of providing no exact information about regional or single-cell pH values but does have the advantage of providing data in the intact animal and further, of being a reflection of pH changes in the great bulk of cells. The method to be described is based on work originally performed by Waddell and Butler, who utilized the same general approach for the measurement of the internal pH of muscle cells. I t uses the weak acid 5,5-dimethyl-2,4 oxazolidinedione (DMO) as a pH indicator. The theoretical basis of the method is as follows: In extracellular water un-ionized DMO (HDMO) dissociates to form H+ ion and ionized DMO-.

Relationship of cytochrome oxidase activity to vertebrate total and organ oxygen consumption

Abstract 1. 1. Cytochrome oxidase activity shows a precise exponential relationship to total O 2 consumption among various vertebrate species with different O 2 , consumptions. A similar relationship between cytochrome oxidase activity and organ O 2 consumption has been demonstrated in a single species (rabbit). 2. 2. These findings suggest that cytochrome oxidase activity may represent a quantitative biochemical marker for functional mitochondrial mass. 3. 3. The regulation of cytochrome oxidase activity may represent a long-term regulatory mechanism involving mitochondrial O 2 uptake in different species and different tissues.

Arterial constrictor response in a diving mammal

Angiograms were obtained in the harbor seal, Phoca vitulina, in air and during diving. During diving there is arterial constriction of the vascular beds of muscle, skin, kidney, liver, spleen, and presumably of all vascular beds except those perfusing the brain and heart. There is sudden constriction and narrowing of muscular arteries close to their origin from the aorta. Constriction of small arterial branches is so intense that blood flow is essentially lost in all involved organs.

Survival during prolonged anaerobiosis as a function of an unusual adaptation involving lactate dehydrogenase subunits.

Abstract 1. 1. The pond turtle ( Pseudemys scripta elegans ) is able to survive for prolonged periods utilizing anaerobic glycolysis as the sole energy source, with approximately constant blood pyruvate concentrations and increasing blood lactate concentrations. 2. 2. The turtle possesses lactate dehydrogenase tetramers with apparently similar M and H subunit polypeptides. 3. 3. This enzyme may represent an important mechanism permitting survival under anaerobic conditions.

Bioenergetic Pattern of Isolated Type II Pneumocytes in Air and during Hypoxia

The bioenergetic pattern of a cell clone derived from rat lung with ultrastructural and biochemical characteristics like those of type II pneumocytes (T-II-P), has been studied in a tissue culture system. During air cultivation, these cells have a high rate of aerobic and anaerobic glycolysis associated with high activities of two rate-limiting enzymes in glycolysis (pyruvate kinase [PyKi] and phosphofructokinase [PFK]). This is present despite the rates of oxygen consumption and activities of cytochrome oxidase (CyOx) similar to other lung cells. Presumably the high rate of aerobic glycolysis explains the substantial lactate production previously described in lung slices and in the intact perfused lung. Hypoxic cultivation results in a decrease in CyOx. Acute re-exposure to air does not restore the oxygen consumption to normal, presumably as a result of decreased mitochondrial O(2) utilization associated with decreased CyOx activity. As a result, hypoxically cultivated T-II-P cells have a decreased capacity for mitochondrial ATP generation in air as compared to air-cultivated cells. During hypoxia, aerobic and anaerobic glycolysis are further increased as well as the activities of PyKi and PFK. The high rate of glycolysis and high activities of PyKi and PFK in cultivated T-II-P appear to reflect intrinsic genetic regulation. The decreased CyOx activity and increased PyKi and PFK activities in hypoxic T-II-P appear to reflect alterations in enzyme biosynthesis/biodegradation regulated by O(2) availability.

Ion and macromolecular transport in the alveolar macrophage

Abstract 1. 1. Some aspects of Na+, K+, Cl− and macromolecular transport have been studied in isolated rabbit alveolar macrophages. Steady-state intracellular concentrations in Ringers solution (pH 7.4) were as follows: Na+, 83 ± 7.1 (S.E.); K+, 75 ± 13.2 ; Cl, 59 ± 4.1 mequiv/kg cell water. Cl− is rapidly and completely lost from the cell in Cl−-free media suggesting rapid thermodynamic equilibrium between intracellular and extracellular phases. 2. 2. Na+ efflux has two rate constants (rapid phase 636 ± 302 (S.D.); slow phase 329 ± 125 mequiv/kg cell water per h). It appears that this cell has high permeability for Na+ and the high leak down the electrochemical gradient requires a high rate of active transport. Thermodynamic considerations suggest that the major energy source for active Na+ transport is derived from oxidative phosphorylation. 3. 3. Classical relatively high molecular weight extracellular markers are excluded from cell water. However, ferritin (mol. wt. 465000) influx is rapid with intracellular/extracellular concentrations greater than 1.0 within 3 min. Ferritin efflux is exceedingly slow so that there is essentially unidirectional transport. Simultaneous exposure of cells to both ferritin and dextran leads to no measurable increase in cellular dextran uptake suggesting high specificity for ferritin uptake.

Dissociation of bradycardia and arterial constriction during diving in the seal Phoca vitulina.

Bradycardia associated with diving in the harbor seal has been dissociated from the arterial constrictor response by intracardiac pacing. Development of arterial constriction does not depend upon the development of bradycardia. During pacing, arterial constriction continues in the absence of bradycardia. Increases in heart rate to values greater than 120 beats per minute during a dive produce a progressive decrease in mean aortic pressure, which suggests that one major function of bradycardia is to reduce cardiac output, thus matching left ventricular output to the restricted vascular bed and decreased venous return associated with diving.

UREA: APPARENT CARRIER-MEDIATED TRANSPORT BY FACILITATED DIFFUSION IN DOGFISH ERYTHROCYTES.

The exposure of erythrocytes from the elasmobranch, Squalus acanthias, to solutions isosmotic with plasma (IM) but containing urea or hydroxyurea as the sole solute does not produce hemolysis. Exposure of these cells to IM methylurea, thiourea and acetamide does produce hemolysis. Low concentrations of urea, which are associated with hemolysis, protect dogfish red cells against hemolysis by methylurea and thiourea. Dogfish red cells exposed to mediums containing high concentrations of urea, or no urea, reach 95 percent of their equilibrium concentration in less than 5 minutes.

Humoral agent from calf lung producing pulmonary arterial vasoconstriction.

Saline washings obtained in vivo from the lung of young calves produce pulmonary hypertension upon intrayascular (systemic or pulmonary) injection into either the dog or the calf. This pulmonary hypertension is produced by vasoconstriction of small, precapillary pulmonary vessels. The active agent, pulmonary arterial constrictor substance, differs chemically and physiologically from other substances which have been investigated with respect to vasomotor activity in the pulmonary circulation. Although the chemical nature of the active agent is not known it appears to have a relatively large molecular weight. Whether this agent plays a role in the physiological regulation of the pulmonary circulation is not known.