John C. Mithoefer

Effect of intravenous NaHCO3 on ventilation and gas exchange in normal man

Sodium bicarbonate was administered intravenously (1.3 meq per kg) over a 5-minute period to six normal subjects. The bicarbonate concentration of the solution was 892 meq per liter, its pH 7.6 and Pco2 929 mm Hg. Ventilation, expired gas volume and composition and arterial Pco2 pH and Po2 were measured at intervals up to one hour. During infusion, alveolar ventilation increased in association with a rise in Paco2, Vco2, Vo2, pH and plasma bicarbonate concentration. All of these values returned rapidly toward normal following infusion. Eleven per cent of the injected dose was eliminated by the lungs within 5 min after injection. Within 15 min, the volume of distribution of the remainder (excluding renal excretion) was 20% of body weight, indicating rapid equilibration with interstitial fluid; by 60 min, 20% of the injected dose appeared to have been distributed to cells or tissue. n nIt is concluded that the rise in Pco2 resulting from the formation and dissociation of carbonic acid and the inclusion of some dissolved CO2 in the administered dose stimulates ventilation in spite of a fall in interstitial hydrogen ion concentration.

The in vivo carbon dioxide titration curve in the presence of hypoxia.

Abstract Three types of CO2 titration curves were studied in the dog: (l) In vivo, arterial Pco, was increased by CO2 breathing in the presence of high inspired oxygen. (2) In vivo, Pco2 was increased by hypoventilation, while breathing air, producing hypoxia in association with respiratory acidosis. (3) In vitro, by equilibration of whole blood with CO2 mixtures in oxygen. CO2 titration curves obtained by Methods 1 and 3 confirm the findings of others that the in vivo curve differs from that found in vitro primarily because of the equilibration of CO2 with interstitial fluid which has a lower buffering capacity than blood. The curve obtained by Method 2 differs from that of Method 1 since, beyond a Pco2 of 60 mm Hg, bicarbonate concentration becomes progressively depressed, largely as a result of lactic acid formation secondary to hypoxia. This curve represents the effect of hypoxia on in vivo CO2 titration and describes a relationship which must exist when severe respiratory acidosis develops during air breathing.

GAS EXCHANGE DURING REBREATHING

An understanding of the regulation of respiration implies an appreciation of the behavior of multiple receptor systems in response to a variety of stimuli. There is no agreement as to the nature or location of all the receptor mechanisms. Therefore, it must follow that there can be no unanimity regarding the true nature of the stimuli to which they are sensitive. For example, there is no doubt that an increase in carbon dioxide tension a t some specific anatomical site will stimulate ventilation, but it is by no means clear, under all circumstances, whether this stimulus is the carbon dioxide tension of arterial blood, the tension that exists in some specialized tissue, as for example the brain, the P C O ~ along a capillary system or whether it is more nearly reflected by the P ~ o , of cerebral venous blood. Although there is evidence of varying strength for all of these possibilities, the measurement most often made to represent the stimulus from COz is the alveolar or arterial carbon dioxide tension. This measurement is not necessarily used in the belief that it represents the true stimulus, but simply because it is a convenient index. Most of the available information regarding the ventilatory response to COz comes from observations made in a relatively steady state after prolonged periods of C02 breathing. While such studies give valuable information regarding the net ventilatory effect, they do not describe the response to a COZ stimulus in its pure form since secondary, modifying effects develop during adaptation to the new steady state. For this resson it has become increasingly clear that ventilatory response to a single stimulus can be seen in purer form under unsteady conditions. When a gas mixture is rebreathed from a confined space, there ensues a progressive accumulation of C 0 2 and consequent unsteady state during which alveolar COz tension and ventilation can be measured and related. Rebreathing is now widely used as a technique for the study of the regulation of respiration. It is, therefore, the purpose of this communication to review some fundamental concepts which apply to rebreathing and to emphasize some recent studies relating to gas exchange which are perti-

Myocardial potassium exchange during respiratory acidosis: The interaction of carbon dioxide and sympathoadrenal discharge

Abstract The myocardial exchange of K + was studied under the following conditions: acute respiratory acidosis, respiratory acidosis when acidemia was prevented by an organic buffer, catecholamine administration, cardio-accelerator nerve stimulation and during respiratory acidosis following adrenergic blockade. Application of the Stibitz extension of the Fick equation allowed calculation of myocardial K + uptake in the unsteady state. During respiratory acidosis, the myocardium takes up K + as a result of the rise in P CO 2 , independent of direct change in extracellular [H + ]. Catecholamines, both exogenously and endogenously, result in a sudden, short-lived uptake of K + by the heart. When sympatho-adrenal discharge is prevented during respiratory acidosis, there is a biphasic response consisting of an initial loss of myocardial K + , followed by a gain. These findings are discussed in terms of the Fenn hypothesis. The net effect of respiratory acidosis on myocardial K + exchange is interpreted as being the result of the interaction of increased P CO 2 and sympatho-adrenal discharge.

Acid-base balance and the effect of oxyhemoglobin reduction on CO2 transport

Abstract The CO2 content and [H+] of oxygenated and reduced whole blood of the dog were measured in vitro at constant PCO2 but at varying levels of [H+]. The magnitude of increase in CO2 content and decrease in hydrogen ion concentration at constant PCO2, which results from oxyhemoglobin reduction (Cue5f8Due5f8H effect), is a decreasing linear function of the [H+] at which reduction takes place. The relationship is expressed by the equation Cue5f8Due5f8H effect = −0.0034 [H+] + 0.518 and is similar at PCO2s of 43 and 60 mm Hg. This effect is presumably the result of the influence of hydrogen ion concentration on formation of carbamino-bound CO2 and explains the variations in the magnitude of the C-D-H effect which have been previously reported. The decreases in hydrogen ion concentration which accompanied oxyhemoglobin reduction were small and consistent with the hypothesis that carbamino-bound CO2 is derived from oxylabile α-NH2 groups with pKs between 6.5 and 8. Since carbamate formation results in the release of hydrogen ion, the relationship between its formation and the existing hydrogen ion concentration represents a mechanism for hydrogen ion homeostasis.