Arterial Blood Gas Tensions and pH in Acute Asthma in Childhood

Studies of the arterial blood gas tensions and pH in 21 children during 24 acute attacks of asthma showed that all were hypoxic on admission to hospital, and in 10 there was evidence of carbon dioxide retention. Cyanosis, invariably present when the So₂ was below 85%, and restlessness in patients breathing air were the most reliable indices of the severity of hypoxia. There were no reliable clinical guides to the Pco₂ level. Conventional oxygen therapy in tents (25–40%) did not always relieve hypoxia, and in three cases the administration of oxygen at a concentration of 40% or over failed to produce a normal arterial oxygen tension. Uncontrolled oxygen therapy may aggravate respiratory acidosis, and three of our patients developed carbon dioxide narcosis while breathing oxygen. The necessity for blood gas measurements in the management of severe acute asthma in childhood is emphasized.     

Changes in haemoglobin binding curve and oxygen transport in chronic hypoxic lung disease.

Direct measurements of the factors determining blood oxygen transport in 10 patients with chronic hypoxic respiratory failure led to the conclusion that wide differences in the position of their oxygen binding curves, due to spontaneous differences in red-cell 2, 3-diphosphoglycerate, had little effect on oxygen delivery to the tissues, as assessed by the mixed venous oxygen tension when they were breathing air. This result arises from the shape of the oxygen binding curve. A drug which could shift the curve to the right would help tissue oxygenation in cardiogenic and other forms of shock, when a low cardiac output can not be improved though arterial blood can be well oxygenated.     

Circulatory and Metabolic Effects of Oxygen in Myocardial Infarction

The circulatory and metabolic effects of inhalation of oxygen in high concentration were investigated in 50 patients with acute myocardial infarction. The heart rate, arterial blood pressure, cardiac out-put, blood gas tensions, pH, and lactate and pyruvate levels were measured. In general, oxygen inhalation produced a fall in cardiac output and stroke volume and a rise in blood pressure and systemic vascular resistance. In a small number of patients with very low cardiac out-puts there was a rise in output. A substantial rise in arterial oxygen tension was obtained even in patients with low initial values. The raised arterial blood lactate levels which were frequently present were reduced after oxygen. The therapeutic implications of these effects are discussed.     

Mixed Venous Oxygen Saturation in Relation to Cardiac Output in Myocardial Infarction

Mixed venous oxygen saturations derived from measurement of mixed venous oxygen tension were compared with dye dilution cardiac output determinations in 26 patients with acute myocardial infarction. Mixed venous oxygen saturation was greatly reduced in patients with shock or failure complicating myocardial infarction. The level of oxygen saturation correlated with cardiac output determinations. The measurement of mixed venous oxygen saturation, which is relatively simple and does not require elaborate equipment, should be an important aid to the rational treatment of patients with low output states complicating acute myocardial infarction.     

Respiratory Insufficiency in Acute Myocardial Infarction

Arterial blood gases and pH were assessed in 115 patients who had suffered a myocardial infarction, with or without complicating cardiogenic shock or cardiac standstill. In 11 of the 78 uncomplicated cases and in 16 of the 37 complicated cases, the arterial O₂ tension was much lower than would be expected on the basis of a three-fold drop in cardiac output, indicating considerable right to left shunting. The death rate in the patients with uncomplicated myocardial infarction was 32% and that of the complicated cases 65%. In both groups it was greatest when the arterial pH was low, indicating that correction of the acidosis is essential. In many instances administration of 100% oxygen is inadequate to restore the oxygen tension to normal levels, and controlled ventilation may be necessary to maintain adequate alveolar ventilation. The findings indicate the necessity for repeated assessment of the arterial blood gas tensions and pH in any patient who has suffered a myocardial infarction. If the management of such patients is designed to provide adequate oxygenation, to maintain adequate alveolar ventilation and to correct the acid-base disturbances, the patient may be tided over the stage of “cardiac pump failure”.     

Effect of Controlled Oxygen Therapy on Arterial Blood Gases in Acute Respiratory Failure

Seven patients in acute exacerbation of chronic respiratory failure were given 24·5% and later 28% oxygen through Ventimasks. The mean increases in arterial PO₂ were 11 and 21 mm. Hg while breathing 24·5% and 28% oxygen respectively compared with control values while breathing air. Associated increases in arterial PCO₂ were 4 and 8 mm. Hg, respectively. In five of the patients these increases in inspired oxygen concentration resulted in useful increases in tissue oxygen supply without significant deterioration in ventilation, but in two patients arterial PCO₂ rose excessively and artificial ventilation was required.     

Effect of increased gas density on pulmonary gas exchange in man.

Pulmonary gas exchange was measured in seven resting supine subjects breathing air or a dense gas mixture containing 21% O2 in sulfur hexafluoride (SF6). The mean value of the alveolar-arterial oxygen difference (AaDO2) decreased from 12.4 on air to 7.0 on SF6 (P less than 0.01), and increased again to 13.4 when air breathing resumed (P less than 0.01). No differences occurred between gas mixtures for O2 consumption, respiratory quotient, minute ventilation, breathing frequency, heart rate, or blood pressure, and the improved oxygen transfer could not be attributed to changes in cardiac output or mixed venous oxygen content in the one subject in which they were measured. These results are best explained by an altered distribution of ventilation during dense gas breathing, so that the ventilation-perfusion ratio (VA/Q) variance was reduced. Of several considered mechanisms, we favor one in which SF6 promotes cardiogenic gas mixing between peripheral parallel units having different alveolar gas concentrations. This mechanism allows for observed increases in arterial carbon dioxide tension and dead space-to-tidal volume ratio during dense gas breathing, and suggests that intraregional VA/Q variance accounts for at least one-half of the resting AaDO2 in healthy supine young men.     

Acute alterations in stroke volume during exercise at 3,100 m altitude.

Following 3 weeks exposure to an altitude of 3,100 m, the cardiac output response to upright submaximal exercise was examined in 3 healthy subjects breathing ambient air and breathing 60% oxygen. The procedure allowed acute alteration of the 2 conditions within a single testing period of 30 min, 60% oxygen breathing either preceding or following breathing ambient air. Cardiac output was also measured in two of the subjects during maximal exercise under these two conditions. Administration of the high oxygen inspirate during exercise had little effect on the level of cardiac output but resulted in an immediate bradycardia and a dramatic increase of approximately 16% in stroke volume. Stroke volumes during maximal exercise were also increased by approximately 10% by the administration of high oxygen. It is suggested that the condition of decreases exercise stroke volume which develops with chronic exposure to altitude may be largely the result of diminished myocardial contractility stemming from a condition of myocardial hypoxia.     

Negative arterial-mixed expired PC02 gradient during acute and chronic hypercapnia.

In resting conscious dogs physiological dead space was calculated using the Bohr equation and measurements of arterial and mixed expired carbon dioxide tension. Whenever dogs inhaled carbon dioxide mixtures (5-10%) that had normal or low oxygen concentrations, the calculated dead space became negative. This paradox was based on the fact that the mixed expired carbon dioxide tension in resting hypercapnic dogs. Under these circumstances carbon dioxide was produced from the lung as measured by gas analyses and blood analyses. By the lung as measured by gas analyses and blood analyses. By reasoning this implies that "alveolar" carbon dioxide tension was higher than pulmonary venous carbon dioxide tension. The negative carbon dioxide gradient persisted at 14 days of chronic hypercapnia and reverted to normal within 10 min of breathing air after chronic hypercapnia. These findings suggest that the exchange of carbon dioxide in the lung cannot be explained solely on the basis of passive diffusion.     

New Trends in the Treatment of Angina Pectoris

Traditionally when considering the pharmacologic basis of therapy in angina pectoris, attention is focussed on alterations of coronary blood flow. Yet the diseased coronary arteries in these patients often do not appear to be capable of responding to vasodilatory drugs. Since the pain of myocardial ischemia is relieved by a number of interventions without an increase in coronary blood flow, the concept herein considered is that angina pector is best viewed as an unfavorable relation between myocardial oxygen requirements and availability. Thus, the clinical value of the major antianginal agents is thought to be based importantly upon their actions to reduce myocardial oxygen consumption rather than to increase coronary blood flow.Sublingual nitroglycerin possesses a powerful dilator effect on veins which reduces venous return and thereby the size of the heart and intra-myocardial tension; thus myocardial oxygen requirements are diminished.The beta-adrenergic receptor blocking drug, propranolol (Inderal®), inhibits sympathetic stimulation of the heart at rest and during exercise. Thus, myocardial oxygen requirements are diminished by the reduction in heart rate and diminished contractility. As a result of this latter action, cardiac output is reduced and thereby arterial pressure and intramyocardial tension is lowered. In patients with advanced heart disease and borderline cardiac compensation, propranolol is hazardous because it removes the availability of one of the important reserve mechanisms for maintaining cardiac compensation—the sympathetic support of the failing heart.The introduction of electrical stimulation of the carotid sinus nerves as a means of therapy in patients with angina pectoris has provided a powerful tool for the treatment of patients with refractory ischemic pain.     

A Theoretical Study of Pulmonary Capillary Gas Exchange and Venous Admixture

A model of pulmonary capillary gas exchange and venous admixture is presented and the inclusion of this model into a model of the entire respiratory system is discussed. Partial pressure and concentration gradients for nitrogen, helium, oxygen, and carbon dioxide are predicted. The cases of breathing room air and 10% oxygen are studied. In both of these studies the Bohr and Haldane effects are included, and the “physiological” dissociation curves of oxygen and carbon dioxide are predicted for the normal case as blood flows from the venous blood end of the capillary to the arterial blood end. Venous admixture effects are also calculated for both of these cases. The effects of emphysema, pulmonary congestion, and altered cardiac function on the gradients are studied.     

Effects of pirbuterol and sodium nitroprusside on pulmonary haemodynamics in hypoxic cor pulmonale.

The acute haemodynamic effects of oral pirbuterol (a beta-agonist) were contrasted with those of sodium nitroprusside, a vasodilator, in six patients with hypoxic chronic bronchitis and emphysema. Sodium nitroprusside (1-5 mg/kg intravenously) reduced mean pulmonary arterial pressure and total pulmonary vascular resistance significantly (p less than 0.01) without change in cardiac output or right ventricular ejection fraction, measured by radionuclide ventriculography. Oral pirbuterol (22.5 mg) produced a greater reduction in total pulmonary vascular resistance than sodium nitroprusside, largely as a result of increasing cardiac output. Right ventricular ejection fraction also increased significantly after pirbuterol (p less than 0.01). Pirbuterol in a lower dosage (15 mg by mouth) in six further patients with hypoxic chronic bronchitis and emphysema produced similar changes in total pulmonary vascular resistance and right ventricular ejection fraction. Nine of the patients who were studied acutely thereafter received pirbuterol 15 mg thrice daily for six weeks, which produced a significant fall in systolic pulmonary arterial pressure and a rise in right ventricular ejection fraction (p less than 0.01), without a significant fall in arterial oxygen tension. Pirbuterol acts as a vasodilator on the pulmonary circulation in these patients and may in addition improve right ventricular performance by an inotropic action.     

Atelectasis affects the rate of arterial desaturation during obstructive apnea

Chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange (low arterial PO2) is present. Previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation (dSaO2/dt) in obstructive sleep apnea. We postulated that abnormal gas exchange in the form of atelectasis would steepen dSaO2/dt and thereby lower nadir arterial oxyhemoglobin saturation (SaO2) for the same duration of apnea. Apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons. Apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung. SaO2 and mixed venous O2 saturation were continuously monitored, and cardiac output was calculated. Worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10.5 +/- 0.8 to 25.0 +/- 0.7% (P less than 0.001). The dSaO2/dt was independent of apnea duration at 30, 45, and 60 s. During endobronchial occlusion, apnea dSaO2/dt increased 20%, and nadir SaO2 was significantly lower. Possible mechanisms for steepening of dSaO2/dt during atelectasis are discussed.     

The Acid-Base Status in Cyanotic Congenital Heart Disease

The relation between oxygen consumption, metabolic status and prognosis was studied in two infants with identically low arterial oxygen tensions (20 mm. Hg) due to cyanotic congenital heart disease. The first patient had low oxygen consumption, arterial blood acidosis and increased arterial lactate, and died at the age of 36 hours. The second had normal oxygen consumption, arterial acid-base balance, lactate and pyruvate, and survived. Since arterial oxygen tensions were similar in both, it was concluded that compensatory factors, such as cardiac output, pulmonary and systemic blood flow and increased oxygen saturation at normal pH levels (Bohr effect), are important in maintaining tissue oxidation and preventing anaerobiosis and lactate production. The importance of a knowledge of acid-base status in the immediate prognosis of cyanotic congenital heart disease is stressed. The treatment of acidosis by buffer therapy may be an important palliative, improving cardiac output and tissue oxidation, and should be undertaken as soon as possible before irreversible cellular damage has occurred.     

Decreased O2 consumption and cardiac output during normobaric hyperoxia in conscious dogs

Recent reports indicate that under certain restricted conditions hyperoxia may decrease tissue O2 consumption. However, this effect has not been established for whole body O2 consumption in the intact healthy conscious state. The goal of the present study was to document the effect of hyperoxia on resting whole body O2 consumption and hemodynamics under these latter more general physiological conditions. The inspired gas was delivered by mask to six fasted resting conscious dogs and alternated hourly between air and O2-enriched air (hyperoxia) for 5 h, while hemodynamics and blood gas data were obtained every 20 min. Compared with air breathing, hyperoxia increased the mean arterial O2 tension from 95 to 475 Torr and decreased heart rate, cardiac output, pulmonary vascular resistance, and right and left ventricular work rates and thus, presumably, myocardial O2 consumption. Hyperoxia also increased systemic vascular resistance and right atrial pressure but did not change stroke volume or systemic arterial pressure. The increase in arterial O2 content during hyperoxia was counterbalanced by the decrease in cardiac output, so that O2 delivery was unchanged by hyperoxia. Surprisingly, hyperoxia decreased the arterial-to-mixed venous difference in O2 content; this decrease together with the decrease in cardiac output produced a decrease in resting whole body O2 consumption from 5.88 +/- 0.68 to 4.80 +/- 0.62 ml O2.min-1.kg-1 (P = 0.0002). It is concluded that under physiological conditions normobaric hyperoxia may decrease metabolic rate in addition to cardiac output, which may have important implications for the metabolic regulation of O2 utilization as well as for the medical and nonmedical uses of O2.     

Acute hypoxic pulmonary vasoconstriction in conscious dogs decreases renin and is unaffected by losartan.

Acute hypoxic pulmonary vasoconstriction (HPV) may be mediated by vasoactive peptides. We studied eight conscious, chronically tracheostomized dogs kept on a standardized dietary sodium intake. Normoxia (40 min) was followed by hypoxia (40 min, breathing 10% oxygen, arterial oxygen pressures 36 +/- 1 Torr) during both control (Con) and losartan experiments (Los; iv infusion of 100 microg. min-1. kg-1 losartan). During hypoxia, minute ventilation (by 0.9 l/min in Con, by 1.3 l/min in Los), cardiac output (by 0.36 l/min in Con, by 0.30 l/min in Los), heart rate (by 11 beats/min in Con, by 30 beats/min in Los), pulmonary artery pressure (by 9 mmHg in both protocols), and pulmonary vascular resistance (by 280 and 254 dyn. s. cm-5 in Con and Los, respectively) increased. Mean arterial pressure and systemic vascular resistance did not change. In Con, PRA decreased from 4.2 +/- 0.7 to 2.5 +/- 0.5 ng ANG I. ml-1. h-1, and plasma ANG II decreased from 11.9 +/- 3.0 to 8.2 +/- 2.1 pg/ml. The renin-angiotensin system is inhibited during acute hypoxia despite sympathetic activation. Under these conditions, ANG II AT1-receptor antagonism does not attenuate HPV.     

Non-invasive mechanical ventilation for acute respiratory failure.

The value of mechanical ventilation using intermittent positive pressure ventilation delivered non-invasively by nasal mask was assessed in six patients with life threatening exacerbations of chronic respiratory disease. Median (range) arterial oxygen and carbon dioxide tensions were 4.4 (3.5-7.2) kPa and 8.7 (5.5-10.9) kPa respectively, with four patients breathing air and two controlled concentrations of oxygen. The arterial oxygen tension increased with mechanical ventilation to a median (range) of 8.7 (8.0-12.6) kPa and the carbon dioxide tension fell to 8.2 (6.5-9.2) kPa. Four patients discharged after a median of 10 (8-17) days in hospital were well five to 22 months later. One died at four days of worsening sputum retention and another after five weeks using the ventilator for 12-16 hours each day while awaiting heart-lung transplantation. This technique of mechanical ventilation avoids endotracheal intubation and can be used intermittently. Hypercapnic respiratory failure can be relieved in patients with either restrictive or obstructive lung disease in whom controlled oxygen treatment results in unacceptable hypercapnia. Respiratory assistance can be tailored to individual need and undertaken without conventional intensive care facilities.     

The aetiology of hypoxaemia in chickens selected for rapid growth

In comparison to other classes of chickens, broilers selected for rapid growth tend to be hypoxaemic, and many develop congestive heart failure (CHF). In order to explain the physiological mechanisms associated with hypoxaemia in fast-growing broiler chickens (Gallus gallus), this study examined several basic physiological parameters including the blood gas profile in arterial [left atrial (LA)] and mixed venous [right atrial (RA)] blood, systemic oxygen extraction ratio, and intrapulmonary shunt fraction. These parameters were further studied in the context of blood flow in the pulmonary circulation, structural characteristics of the lungs, and cardiac function [measured as cardiac index (CI)]. Overall, broilers had lower arterial and mixed venous blood pO(2) levels and higher pCO(2) levels compared to leghorns. The cardiac index was lower in fast-growing and CHF broilers compared to leghorn chickens or feed-restricted broilers. Systemic oxygen extraction ratio (ER) and intrapulmonary shunt fraction were significantly higher in fast-growing broilers and birds with CHF (all P<0.01). Lungs of all broilers, but not leghorns, contained ectopic, irregular nodular formations located within air spaces. Broilers with clinical signs of hypoxaemia revealed the highest number of these formations in their lung. Taken together, the present findings indicate that key factors associated with the development of hypoxaemia in fast-growing broilers include: (1) high demand for oxygen as evidenced by high oxygen ER; (2) inadequate cardiac output (CO) to fulfill the higher oxygen demands, leading to severe depletion of O(2) in mixed venous blood; and (3) elevated intrapulmonary shunt fraction and possibly dead space associated with specific pathological and anatomical characteristics within the lung.     

Pulmonary and circulatory changes in conscious sheep exposed to 100% O2 at 1 ATA

We have measured the effects of normobaric hyperoxia on arterial and mixed venous gas tensions, cardiac output, heart rate, right atrial, pulmonary, and aortic pressures in 12 conscious chronically instrumented sheep. Regional blood flow to brain, heart, kidney, intestines, and respiratory muscles was assessed in five sheep by injecting 15-micrometers microspheres labeled with gamma-emitting isotopes. Survival time ranged from 60 to 120 h (mean = 80 h). All variables except arterial O2 partial pressure (PaO2) and mixed venous O2 partial pressure remained at base-line level during the first 40 h of exposure, after which PaO2 decreased gradually but remained above 200 Torr at death. After this there was a progressive uncompensated respiratory acidosis with terminal arterial CO2 partial pressure values exceeding 90 Torr. There was a considerable rise in the brain blood flow, whereas flow to the other organs either remained unchanged or increased in proportion to cardiac output. Our experiments also showed that systemic hyperoxic vasoconstriction did not occur, and any local changes were not of sufficient magnitude to affect perfusion.     

An improved rebreathing method for measuring mixed venous carbon dioxide tension and its clinical application.

The mixed venous carbon dioxide tension (PVCO2) can be measured at the bedside by a rebreathing equilibrium technique that is quick, simple and noninvasive. Only one brief period of rebreathing is required. The technique is accurate even when the lungs are not normal, and gives a graphic record that allows verification of the accuracy of the estimate. The PVCO2 is affected mainly by changes in alveolar ventilation and cardiac output. It can be measured instead of the arterial carbon dioxide tension (PACO2) to follow changes in alveolar ventilation when the cardiac output is normal (PaCO2 = 0.8 PVCO2). When the cardiac output is abnormal, measurement of both PaCO2 and PvCO2 is useful in determining how much the cardiac output is reduced. Consideration of the relation between oxygen consumption and carbon dioxide production suggests that the equation PaCO2 = 0.8 PVCO2 - 12 indicates a reduction in cardiac output that may impair the oxygen supply to tissues. Simple corrections can be applied to allow for variations in arterial oxygen saturation and hemoglobin concentration that will affect this relationship.