Arterial-mixed Venous Oxygen Difference Research Articles

Body size and V.O2peak: a new perspective?

The purpose of this paper was to show how dimensional analysis and biological similarity theory can be used to define and derive extensive (size-dependent) and intensive (size-independent) variables. The method was then used to analyze the peak rate of oxygen consumption (V.O2peak) data of children, adolescents, and adults to determine if size-independent increases in V.O2peak occur during growth and development. The results indicated growth and development is accompanied by a substantial increase in size-independent V.O2peak, which was associated with improvements in size-independent peak heart rate ( HR(peak)). When differences in fat free mass (FFM) were considered, size-independent HR(peak) was similar in boys and girls within each age-group, but was greater in men than in women. In contrast, when differences in FFM were accounted for, size-independent peak oxygen pulse (O2P(peak)) was independent of age, although males tended to have greater values than females at all ages. Because O2P(peak) is proportional to the product of stroke volume ( SV) and arterial mixed-venous oxygen difference (a-vO2peak), when differences in FFM were considered, the size-independent nature of O2P(peak) indicated the combined effects changes in SV(peak) and (a-vO(2)peak) played a secondary role in improving aerobic capacity. In conclusion, during normal growth and development improvement in HR(peak), not stroke volume and arterial mixed-venous oxygen difference, appears to increase aerobic capacity.

Oxygen delivery-consumption relationship in septic adult respiratory distress syndrome patients: The effects of positive end-expiratory pressure

The oxygen consumption/ delivery relationship (VO2/602) was studied in 18 sedated, paralyzed, septic adult respiratory distress syndrome patients. Different levels (0 to 15 cm H2O) of positive end-expiratory pressure (PEEP) were applied. DO 2 was calculated from cardiac index (thermodilution technique) and arterial oxygen content measurements. VO 2 was calculated using Fick's equation. Regression lines were obtained for each patient. The following results were obtained. First, patients with DO 2 at zero end-expiratory pressure ≤ 640 mL/min/m 2 showed a highly significant relationship between changes in DO 2 and VO 2 with PEEP (supply dependency). In all these patients PEEP decreased DO 2 by reducing cardiac index without significant changes in arterial oxygen saturation. All these patients developed multiple organ system failure and died. Second, changes in DO 2 and VO 2 with PEEP were not correlated in patients with a DO 2 on zero end-expiratory pressure ≥ 686 mL/min/m 2 (nonsupply dependency). As PEEP was applied, changes in DO 2 were compensated by changes in oxygen extraction ratio such as to keep VO 2 constant. On average, DO 2 decreased with PEEP, while oxygen extraction ratio and arterial-mixed venous oxygen difference increased as PEEP was applied. Only three of these patients developed multiple organ system failure and died (70% survivors).

Oxygen transport in adult respiratory distress syndrome and other acute circulatory problems

To evaluate the evidence that oxygen consumption (VO2) is pathologically dependent on oxygen delivery (DO2). Studies published since 1972 with their relevant bibliographies and computerized search of MEDLINE. All clinical papers reporting the relationship of: VO2 to DO2 in the adult respiratory distress syndrome (ARDS), sepsis, other critically ill patients, and normal individuals; cardiac output determined by measured VO2 to calculated VO2 from the arterial-mixed venous oxygen difference; blood lactate to DO2; and selected basic science studies. Study quality was assessed and all pertinent data were summarized. RESULTS OF DATA EXTRACTION: Normal individuals display physiologic dependence of VO2 at very low levels of DO2 (330 mL/min.m2). Pathologic dependence of VO2 on DO2 entails two concepts: a) VO2 varies directly with DO2 over a wide range of DO2 and b) of particular import, tissue oxygen extraction is compromised. This pathologic supply dependence was initially identified in patients with ARDS; subsequently, it has been demonstrated in patients with sepsis and in a variety of other critically ill individuals. There are substantial, but not uniform, data documenting this dependence of VO2 on DO2 in ARDS. In some studies, this relationship correlates best with increased lactate concentrations. However, increased blood lactate concentrations do not accurately track other evidence of tissue hypoxia. Some researchers have attributed the finding of this supply dependency to artifact, when VO2 is determined by the arterial-mixed venous oxygen difference. However, when these methods are compared, the correlation is excellent. Others have raised the concern that appreciable changes in VO2, even over short periods of time, may result in physiologic increases in DO2. However, when "control" groups have been contemporaneously compared with patients with ARDS using the same methodology, they have not shown supply dependency. Interwoven throughout the studies reviewed is overwhelming and uniform evidence that both mixed venous oxygen tension (PVO2) and mixed venous oxygen content (CVO2) correlate poorly with cardiac output, DO2, or VO2. The inconsistencies in identifying pathologic DO2 dependency may well reflect the unknown variables that exist in patients with ARDS, perhaps better labeled, multiple organ system failure. Pathologic dependence of VO2 on DO2, especially the inability to increase tissue oxygen extraction, is present in most patients with ARDS and many other critically ill individuals. PVO2 and CVO2 are both unreliable indicators of cardiac output, DO2, or VO2.

Effects of feeding on muscle blood flow during prolonged exercise in miniature swine

Eight exercise-trained miniature swine were studied during prolonged treadmill runs (100 min) under fasting and preexercise feeding conditions. Each animal ran at identical external work loads that corresponded to 65% of the heart rate reserve (210-220 beats/min) for the two exercise bouts. Cardiac outputs and stroke volumes were higher and heart rates lower for fed than for fasting runs (P less than 0.05). Preexercise feeding did not alter oxygen consumption, core temperature, mean arterial pressure, and arterial-mixed venous oxygen difference during prolonged exercise; however, mixed venous lactate concentration was lower at end exercise than during fasting conditions (1.2 vs. 2.6 mM, P less than 0.05). Microsphere measurements of regional blood flow revealed significantly higher total gastrointestinal flow (23%) for fed than for fasting conditions. Throughout the exercise bout, blood flow to the biceps femoris, semitendinosus, and tibialis anterior muscles was lower in fed than in fasted animals (P less than 0.05). Combined hindlimb muscle blood flow averaged 15 ml.min-1.100 g-1 (18%, P less than 0.05) lower under feeding than fasting run conditions. These findings provide further evidence that cardiovascular reflexes originate in the gut after feeding to increase cardiac output and redistribute a portion of the blood flow away from active muscle to the gastrointestinal tract during prolonged exercise.

Arterial blood gas derived variables as estimates of intrapulmonary shunt in critically ill children.

Oxygen transport data, prospectively collected from 52 critically ill children, were analyzed to determine whether any derived variable accurately estimated intrapulmonary shunt (Qsp/Qt). Arterial hemoglobin saturation was more closely correlated with Qsp/Qt than was PaO2, alveolar-arterial oxygen gradient, arterial mixed venous oxygen difference (C[a-v]O2), arterial/alveolar oxygen ratio, and the ratio of PaO2 to inspired oxygen (FIO2) (r = 0.8, p less than .0001). When C(a-v)O2 was normal, hemoglobin saturation became a very accurate (r = 0.96) assessment of Qsp/Qt. We conclude that various arterial blood gas derived variables do not accurately reflect Qsp/Qt in critically ill children. In these patients, a pulmonary artery catheter is needed to accurately assess intrapulmonary shunt.

Cardiorespiratory alterations consequent to endurance exercise training during chronic beta-adrenergic blockade with atenolol and propranolol

A study was undertaken to determine if normal healthy subjects can increase their endurance capacity consequent to endurance training during chronic β-adrenergic blockade. Forty-seven subjects, 17 to 34 years of age, were randomly assigned to 1 of 3 treatments (placebo, propranolol, 160 mg/day, and atenolol, 100 mg/day) and then completed a 15-week aerobic exercise training program. All groups reduced their submaximal steady-state heart rates consequent to training; submaximal oxygen uptake was slightly reduced; submaximal stroke volume was increased only in the placebo and atenolol groups; submaximal cardiac output was generally lower; and arterial-mixed venous oxygen difference was increased after training in all 3 groups, suggesting decreased muscle blood flow and increased oxidative capacity. Maximal oxygen uptake, and maximal treadmill time were increased in all 3 groups after training. However, while still on medication the atenolol group had significantly greater increases In maximal oxygen uptake and maximal treadmill time compared with the propranolol group. Because most patients will remain on medication, these results suggest a distinct advantage for cardloselective blocking agents. It is concluded that β-adrenergic blockade does not reduce the ability of normal healthy subjects to gain the benefits associated with cardiorespiratory endurance training.

Maximal cardiac output during upright exercise: Approximate normal standards and variations with coronary heart disease

The observed normal ranges for age- and weight-adjusted maximal oxygen uptake and age-adjusted maximal heart rate measured during the Bruce protocol are shown for 99 normal sedentary men. On the basis of observations in 10 normal men, the relation between oxygen uptake and cardiac output (measured with the direct Fick principle) was used to estimate normal limits of maximal cardiac output and stroke volume for the 99 normal sedentary men. These normal standards were then used to evaluate the results of 77 studies in patients with coronary heart disease who had various clinical and angiographic findings and who performed symptom-limited upright exercise while cardiac output was measured using the direct Fick principle. Patients with angina and infarction showed the greatest impairment of age- and weight-adjusted maximal oxygen uptake and age-adjusted maximal cardiac output, maximal heart rate and maximal stroke volume when compared with patients with angina or healed infarction alone. Arterial-mixed venous oxygen difference at maximal exercise was comparable in the three groups. The surgical cohort (studled after aortocoronary vein bypass grafting) had significantly higher maximal heart rates. Patients with an ejection fraction of less than 50 percent had significantly impaired age-adjusted maximal cardiac output and stroke volume.

Acute effects of oral propranolol on hemodynamic responses to upright exercise

Noninvasive measurements of maximal oxygen intake and invasive measurement of systemic and pulmonary arterial pressures, arterial and mixed venous oxygen contents and direct Fick cardiac output are reported for 3 healthy men and 14 men with coronary heart disease. Observations were obtained at supine and sitting rest, during graded levels of upright exercise on a treadmill up to symptom-limited maximal effort and in two periods of recovery. The effects of 40 mg of propranolol orally were ascertained by repeating the measurements 1 to 1 1 2 hours later. The most consistent effect of propranolol was reduction of pressure-rate products at all phases; slowing of heart rate was significant only during exercise and recovery, and the greater slowing was accompanied by a significant increase in stroke volume. These changes were similar in patients with and without evidence of left ventricular impairment greater than 15 percent on exercise testing. Maximal oxygen intake decreased in healthy subjects and decreased slightly in patients with coronary heart disease with less than 15 percent left ventricular impairment or percent deviation of pressure-rate product from age-predicted normal values during the control study. Maximal oxygen intake increased in patients with more than 15 percent left ventricular impairment. Arterial-mixed venous oxygen difference increased after propranolol because of a reduction of mixedvenous oxygen content attributed to greater peripheral extraction of oxygen.

Acute hemodynamic effects of an alpha- and beta-receptor blocking agent (AH 5158) on the systemic and pulmonary circulation at rest and during exercise in hypertensive patients

The acute hemodynamic effects of 50 mg. of the alpha- and beta-receptor blocking agent AH 5158, administered intravenously, on the systemic and pulmonary circulation were studied in 13 hypertensive patients at rest in the supine and erect positions, and during exercise, with right heart and brachial artery catheterization. AH 5158 induced a significant fall of systemic blooc pressures under all conditions, whereas the pulmonary systolic and mean pressures were lower at rest and unaltered during exercise. The left ventricular filling pressure largely remained unchanged. Blood pressure was lowered predominantly by a reduction in systemic vascular resistance together with a reduction in cardiac output. These effects were particularly pronounced in the erect position and during exercise. Cardiac output was lowered solely by the reduction of heart rate; stroke volume was unchanged or even increased. The arterial-mixed venous oxygen difference increased in the erect position and during exercise. The pattern of AH 5158-induced hemodynamic adaptation comprising a reduction of both vascular resistance and cardiac output, without evidence of significant negative inotropic action, offers a novel basis for treating hypertension with a single drug. Its pharmacological and hemodynamic profile suggests considerable potential in the treatment of hypertensive patients.

Cardiovascular mechanisms of functional aerobic impairment in patients with coronary heart disease.

Maximal oxygen uptake V O O2 max ) and functional aerobic impairment (FAI) were determined by treadmill test in 42 men with coronary heart disease and in 11 slightly older healthy men. Patients were separated according to occurrence or nonoccurrence of angina with exercise. At rest and at four levels of submaximal exercise on a bicycle ergometer, cardiac output (Q), using the direct Fick principle, heart rate (HR), mean systemic and pulmonary arterial pressures, and arterial-mixed venous oxygen difference (A-V O 2 D) were evaluated in relation to relative aerobic requirement (% V o o2 max ). Q was highly correlated with V o o2 , and both the level and the rate of change of Q were lower in patients with angina at all submaximal workloads. Stroke volume (SV) and HR were significantly restricted at the higher workloads. Although peripheral resistance was increased, there was no compensatory increase in A-V O 2 D. Both restricted SV and reduced HR are responsible for cardiovascular components of the abnormal FAI found in patients with myocardial ischemia due to coronary arterial disease.

Reproduction of maximal exercise performance in patients with angina pectoris despite ouabain treatment.

Eight patients with a diagnosis of atherosclerotic heart disease and a history of typical angina pectoris, uncomplicated by cardiac dilatation or heart failure, were studied by means of standardized, symptom-limited treadmill exercise test. Repeatability of such testing was determined during two control tests 1-1.5 hours apart. From two to six days later, the same patients performed two treadmill tests after pulmonary and brachial arterial catheterization. The study design allowed evaluation of the effects of 0.005 mg/kg of ouabain at rest-both supine and standing-and during submaximal and maximal exercise. Measurements were made of oxygen uptake, arterial-mixed venous oxygen difference, heart rate, systemic arterial pressures and pulmonary arterial mean pressure. The ratio of mean systemic to mean pulmonary arterial pressure relative to cardiac output indicated that acute left ventricular dysfunction limited aerobic work. Treatment with ouabain did not significantly change performance or capacity and angina was not alleviated.

COMPARISON OF THE HEMODYNAMIC EFFECTS OF MERCURIAL DIURETICS AND DIGITALIS IN CONGESTIVE HEART FAILURE.

The non-xanthine-containing mercurial diuretic mercaptomerin (Thiomerin), a noncardiotonic agent, was given repeatedly to 14 patients with congestive heart failure until all edema fluid had been eliminated. There resulted relief of subjective symptoms and removal of the characteristic physical signs of circulatory congestion to the point where subjects were considered in "cardiac compensation"; reduction of the elevated intracardiac pressures, in the right atrium, right ventricle, and pulmonary artery; variable changes in cardiac function (cardiac output) and cardiocirculatory (arterial-mixed venous oxygen difference) function, with improvement toward normal in half of the patients and no change in the other half. In subjects in whom full mercurial diuresis alone improved the cardiac and cardiocirculatory functions, subsequent digitalization produced no further improvement in these functions. These patients were in a first or second episode of cardiac decompensation. In subjects in whom full diuresis alone did not alter the cardiac and cardiocirculatory dynamics, subsequent digitalization produced an increase in cardiac output and a decrease in A-V oxygen difference toward normal values. These subjects usually had had one or several previous episodes of congestive failure. When there was persistent chronic congestive heart failure, neither mercurial diuretic nor digitalis therapy altered the low cardiac output or the high A-V oxygen difference. Removal of the edema and vascular congestion by diuresis alone nevertheless produced subjective improvement. In those patients in whom an increase in cardiac output occurred as the mercurial diuretic eliminated edema and lowered the elevated intracardiac pressures, the response may be considered consistent with Starling's law of the heart in man in congestive heart failure. The data clearly make the point that it is the circulatory congestion that produces the symptoms and the physical signs traditionally considered characteristic of congestive heart failure. Removal of the circulatory congestion, however accomplished, relieves the symptoms and physical signs of congestive heart failure, regardless of whether or not cardiac function is improved toward the normal. Circulatory congestion does not necessarily indicate, nor correlate with, the status of cardiac function.

Effects of khellin on coronary blood flow and related metabolic functions.

Khellin, a drug employed as a coronary dilator, was tested to determine its effects on the cardiovascular system of the dog. Ten mongrel dogs were anesthetized with Nembutal and, after control observations were made, given an intravenous administration of 1 mg/kg body weight of khellin. Coronary blood flow and cardiac output samples were drawn during the control period and at 10, 40 and 80 minutes after administration of the drug Cardiac output was calculated by the direct Fick principle and coronary blood flow by the nitrous oxide method. There was a significant (5%) increase in the arterial oxygen content during the 10- and 40-minute intervals, but no change was observed at 80 minutes. An increase in arterial-mixed venous oxygen difference occurred at 40 and 80 minutes. No change in systemic arterial pressure or cardiac output was noted at any time. Coronary blood flow had decreased slightly at 80 minutes. A significant decrease in carbon dioxide content of the arterial, pulmonary arterial and coronary sinus blood was observed, possibly as a consequence of hyperventilation. Khellin appeared to alter the metabolism of the myocardial and splanchnic tissues.