The relationship between oxygen delivery and consumption in the conscious rat before and after expansion of body fluid volumes

Oxygen consumption and delivery (defined as the product of cardiac output, haemoglobin concentration and arterial oxygen saturation) and haemodynamic variables were examined in the conscious resting rat throughout the day and after the expansion of body fluid volumes. Cardiac output was measured in arbitrary units by electromagnetic flowmetry and oxygen consumption by respirometry. The variability of blood pressure in the basal state was significantly less than that of cardiac output. Oxygen consumption was significantly correlated with cardiac output and oxygen delivery. In studies undertaken throughout the day, both oxygen consumption and delivery fell in the afternoon and there was evidence that the relationship between these two variables was curvi- rather than recti-linear. During oral sodium chloride administration for 7 days, blood pressure rose and some evidence was found for an alteration in the relationship between oxygen consumption and delivery, with an excess of delivery relative to consumption, particularly on the first day of salt loading. Intravenous injection of sodium chloride solution (0.171 mol/l) did not alter the relationship between oxygen consumption and delivery. Expansion of blood volume, while the packed cell volume was maintained nearly constant, raised oxygen delivery transiently and evidence was obtained that the relationship between oxygen consumption and delivery was altered, with oxygen delivery rising relatively more than oxygen consumption. The findings are discussed in relation to the autoregulatory hypothesis of circulatory control and for the role of autoregulation in hypertensive states. The importance of relating oxygen delivery to metabolic requirements in studies of the role of autoregulation is emphasized.     

Low cardiac output syndrome: identification and management

Low cardiac output syndrome (LCOS) is a clinical condition that is caused by a transient decrease in systemic perfusion secondary to myocardial dysfunction. The outcome is an imbalance between oxygen delivery and oxygen consumption at the cellular level which leads to metabolic acidosis. Although LCOS is observed most commonly in patients after cardiac surgery, it may present in various disease processes resulting in cardiac dysfunction. This article provides an overview of the determinants involved in oxygen transport, the physiologic factors influencing cardiovascular function, the assessment of hemodynamic variables, the etiology of LCOS, and management strategies, including a brief review of some pharmacologic agents that are used in the treatment of low cardiac output.     

Comparison of Cardiac Output Responses to 2,4-Dinitrophenol-Induced Hypermetabolism and Muscular Work

Both electrically induced exercise and infusion of 2,4-dinitrophenol (DNP) increased oxygen consumption and tissue metabolism in chloralose-anesthetized dogs. Cardiac output increased with oxygen consumption at the same rate in both experimental conditions. The increase in cardiac output induced by exercise was, as expected, accompanied by increases in both lactate-to-pyruvate ratio and "excess lactate" in arterial blood. However, these parameters did not increase after DNP infusion until the rate of oxygen consumption had increased four- to fivefold, perhaps due to facilitation of mitochondrial electron transport by DNP. Anaerobic tissue metabolism therefore probably did not contribute significantly to increased cardiac output during the mild-to-moderate tissue hypermetabolism induced by DNP. The increased cardiac output may have been the result of metabolic changes common to both exercise and DNP infusion; muscular activity alone may not have been the primary determinant of the cardiac output response during exercise.     

Oxygen kinetics during liver transplantation: The relationship between delivery and consumption

In anesthetized humans, oxygen consumption is independent of oxygen delivery above a critical threshold. Below this critical level, lactic acid is a marker of anaerobic metabolism and tissue oxygen debt, and heralds a supply dependency of oxygen consumption. The goal of this study was to determine whether a threshold value for oxygen delivery below which oxygen consumption becomes supply dependent can be identified in patients with normal, impaired, or absent liver function. Measurements were made in 34 surviving patients (group 1) and in 16 nonsurvivors with sepsis and postoperative liver graft failure (group 2). Hemodynamic measurements and blood samples were taken 10 minutes after introduction of anesthesia, 10 minutes after cross-clamping, and 10 minutes after reperfusion of the new liver. At these time points, we measured blood lactate, cardiac output, and arterial and mixed venous oxygen contents in order to calculate oxygen consumption and oxygen delivery. In both groups, cardiac output, oxygen delivery, and oxygen consumption decreased during the anhepatic phase and increased after unclamping of the inferior vena cave. Lactate increased in both groups during surgery, but was significantly higher in nonsurvivors (6.6 ± 0.4 mmol/L) than in survivors (4.6 ± 0.1 mmol/L) (P <.05). With similar changes for oxygen delivery and oxygen consumption during increased lactate levels we could not identify a clear supply dependency of oxygen consumption in survivors and nonsurvivors during liver transplantation. We conclude that the interpretation of blood lactate levels during circulatory shock can be biased due to a reduced lactate clearance in patients with impaired liver function, unrelated to the status of the relationship between oxygen delivery and consumption. Moreover, elevated blood lactate after liver transplantation predicts postoperative complications and death.     

Adaptation during surgical stress. A reevaluation of the role of glucocorticoids.

Pharmacologic doses of glucocorticoids are administered to patients with adrenal insufficiency during operative procedures to prevent hemodynamic instability, cardiovascular collapse, and death. Since these supraphysiologic doses might not be necessary and might have adverse effects, we examined the effects of different doses of glucocorticoids on hemodynamic adaptation during surgical stress in adrenalectomized primates. Sham-adrenalectomized placebo-treated animals served as controls. Adrenalectomized monkeys were maintained for 4 mo on physiologic glucocorticoid and mineralocorticoid replacement. The adrenalectomized monkeys were then stratified into three groups receiving, respectively, subphysiological (one-tenth the normal cortisol production rate), physiological, or supraphysiological (10 times the normal cortisol production rate) cortisol (hydrocortisone) treatment. 4 d later a cholecystectomy was performed. The intraoperative hemodynamic and metabolic parameters, perioperative survival rates, and postoperative wound healing were compared. The subphysiologically treated group was hemodynamically unstable before, during, and after surgery and had a significantly higher mortality rate than control. In this group, arterial blood pressure was low, and the cardiac index, systemic vascular resistance index, and left ventricular stroke work index were all reduced, suggesting decreased cardiac contractility and blood vessel tone. In contrast, the physiologically replaced group was indistinguishable from either supraphysiologically treated animals or sham-operated controls. All groups had similar metabolic profiles and normal wound healing. These findings suggest that the permissive actions of physiologic glucocorticoid replacement are both necessary and sufficient for primates to tolerate surgical stress. Supraphysiological glucocorticoid treatment has no apparent advantage during this form of stress in the primate.     

The physiologic sequelae of chronic dynamic exercise

The physiologic results of acute dynamic exercise include complex neurologic, hormonal, pulmonary, and cardiovascular adjustments that provide an integrated response perfectly matching oxygen supply with oxygen demands. Long-term repeated bouts of dynamic exercise of sufficient intensity and duration yield predictable changes in anatomy and physiology. These changes affect active skeletal muscle and the heart. Changes in skeletal muscle include an increased capillary blood volume, increased mitochondrial density, increased oxidative pathway enzymes, and more efficient regulation of blood flow. These adaptations result in an increased oxidative capacity and more favorable fuel utilization. Oxygen extraction increases, accounting for up to 50 per cent of the increased maximal oxygen consumption, and endurance improves. Following chronic dynamic exercise the heart beats slower and has a larger stroke volume at rest and throughout a broad range of work intensities. The maximal cardiac output increases substantially, accounting for up to 50 per cent of the increased maximal oxygen consumption. The metabolic and biochemical changes found in skeletal muscle are not found in cardiac muscle. Changes found in isolated cardiac muscle do not always correlate with heart performance. The separation of central and peripheral factors in assessing heart performance is difficult because preload and afterload are major determinants of heart function and are altered by chronic dynamic exercise. Ischemia is a major stimulus for the development of coronary collateral vessel development in animals. Because dynamic exercise does not induce ischemia in normal humans, collateral vessel development may only occur in those with coronary heart disease. However, there is no convincing evidence that chronic dynamic exercise results in physiologically important coronary collateral vasculature in patients with angina. Improved work capacity is predictable following chronic dynamic exercise in patients with coronary heart disease. Although the rate pressure product that produces angina does not change following training, heart rates are lower at matched absolute workloads and the maximal consumption of oxygen increases. Changes in heart function are largely secondary to peripheral changes in these patients.     

Oxygen consumption is increased in the postanesthesia period after burn excision

We studied the intraoperative and postoperative effects of anesthesia and wound excision on oxygen delivery and oxygen consumption after burn injury. Twenty adult sheep were studied: six had halothane anesthesia alone and 14 had anesthesia and third-degree burns over 15% of the total body surface. Body temperatures were maintained within 1 degree C of baseline value during the operations. The burns on six sheep were totally excised and hide from donor sheep was grafted 3 hours after injury; in eight sheep, excision and grafting were done 5 days after injury. We found that 3 hours of anesthesia in controls decreased oxygen delivery (DO2) by 22% +/- 6% and oxygen consumption (VO2) by 30% +/- 7% from waking baseline values primarily because of a decrease in cardiac output as oxygen (O2) extraction from hemoglobin also decreased. However, no base deficit developed. DO2 and (VO2) transiently increased to 9% +/- 3% above baseline value on the sheeps' return to the waking state. Anesthesia and wound excision, which began 3 hours after the burns were formed, decreased DO2 and VO2 by 25% +/- 4% and 32% +/- 4%, respectively, despite baseline filling pressures. However, a base deficit of -3 +/- 1 mEq/L developed during the two-hour operations, which began with the administration of anesthesia alone. Oxygen consumption increased to 25% +/- 6% above the waking baseline value upon each subject's return to the waking state. In the sheep treated 5 days after burn injury, DO2 decreased by 35% +/- 6% and VO2 decreased by 42% +/- 6% below the value during the waking hypermetabolic state when the sheep were under anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maximizing oxygen delivery when resuscitating patients from shock. Clinical guidelines as well as some practical pointers

In patients with shock and evidence of hypoperfusion, target therapy at increasing oxygen delivery and decreasing oxygen consumption. To augment delivery, increase arterial oxygenation (with mechanical ventilation and high levels of inspired oxygen), hemoglobin level to at least 10 g/dL (with transfusions of red blood cells), and cardiac output (with hydration and inotropic support). Avoid vasopressors because they increase afterload and thereby decrease cardiac output and oxygen delivery. To reduce oxygen consumption, consider antipyretics (to lower metabolic demand) and mechanical ventilation plus sedatives or paralytics (to decrease the work of breathing). Continue therapy until oxygen consumption is no longer coupled to delivery.     

Cardiovascular effects of various colloidal solutions during major abdominal surgery

We examined the effects of various colloidal solutions on cardiovascular and oxygen transport variables for 26 patients undergoing gastrectomy under general anesthesia. Fluosol-DA, whole blood, 3% Dextran-40 (Saviosol), and 6% hydroxyethyl starch (hetastarch, Hespan) affected the right side of heart, but only whole blood and Fluosol-DA significantly increased cardiac output and oxygen delivery (DO2). Fluosol-DA may prove useful for critical care of hemorrhagic shock during operation or resuscitation in the immediate postoperative period.     

Circulatory mechanisms of shock and their mediators

Traditional concepts of shock therapy have been based on conventional monitoring. However, the availability of invasive monitoring systems has provided the means to describe the patterns of oxygen transport in various acute life-threatening illnesses. Surgical trauma provides a useful model for investigation of other shock syndromes, because measurements may be made in the preoperative control period, during the hemodynamic crisis intraoperatively, and sequentially throughout the postoperative period for survivors and nonsurvivors. This provides a time-related pattern of physiologic events that may form the basis for the physiologic evaluation of mechanisms operative in survivors and nonsurvivors. Physiologic alterations which are compensatory may be identified from the survivor pattern and differentiated from decompensations associated with the lethal course. The DO2 pattern reflects circulatory functional changes which may limit body metabolism as reflected by VO2. The body compensates for tissue hypoxia and increased metabolic needs by increased flow and DO2 in sepsis and trauma, and by increased oxygen extraction in hemorrhagic and cardiogenic shock where flow is limited. The interactions of survivors' hemodynamic and oxygen transport patterns define compensatory responses which primarily are increased cardiac output, DO2, and VO2. Inadequate compensations and decompensations of shock are clearly manifest by the nonsurvivor pattern. Therapeutic goals may be defined by the values of the survivor patterns; reduced mortality and morbidity result when these goals are vigorously applied prospectively (17-19).     

Exercise tolerance and cardiorespiratory response to exercise before and after the Fontan operation

To determine the effect of the Fontan operation on exercise tolerance and cardiorespiratory response to exercise, we compared the preoperative and postoperative responses to graded exercise to maximal effort in 20 patients who underwent a modified Fontan procedure. The mean interval between preoperative and postoperative exercise testing was 1.8 years. Postoperatively, total work performed, duration of exercise, and maximal oxygen uptake were significantly increased. Although cardiac output increased during exercise, the response was subnormal, and stroke volume was unchanged. The heart rate and systolic blood pressure during maximal exercise were not significantly changed from preoperative values, but the diastolic blood pressures during rest and maximal exercise were significantly increased postoperatively. Systemic arterial blood oxygen saturation increased after the modified Fontan operation, but during exercise, a mild but significant desaturation occurred (93% compared with 90%). The ventilatory equivalent for oxygen decreased toward normal during exercise. The respiratory rate and oxygen consumption during resting remained unchanged from preoperative values. For this subset of patients, these data indicate that exercise tolerance improves, cardiac output and stroke volume responses to exercise are subnormal, and ventilatory response to exercise decreases toward normal after the modified Fontan operation.     

Sequential physiologic interactions in pediatric cardiogenic and septic shock

We report that the pediatric cardiogenic shock and septic shock populations show similar hemodynamic and oxygen utilization physiologic relationships during aggressive intensive care therapy. We examined the mathematical relationships between vascular tone and flow, and oxygen utilization and oxygen delivery (DO2) in the early and middle stages of cardiogenic and septic shock. The fitted curves between cardiac index and systemic vascular resistance, and oxygen consumption (VO2) and DO2 were clinically and statistically similar in both shock populations. We found no evidence for decreased oxygen extraction in sepsis as compared to the cardiogenic shock population. In addition, it appears that the major determinant of VO2 in these populations is DO2, not oxygen extraction. We suggest that patients with cardiogenic or septic shock can be treated according to similar physiologic principles.     

Pentoxifylline in resuscitation of experimental hemorrhagic shock

BACKGROUND: Pentoxifylline improves survival in animal models of hemorrhagic shock. The purpose of this study was to determine the physiologic effects of pentoxifylline in hemorrhagic shock that may be responsible for improved survival. METHODS: Randomized, prospective, blinded trials in Sprague-Dawley rats subjected to hemorrhage and resuscitation, with or without pentoxifylline. RESULTS: Pentoxifylline had no effect on BP or cardiac output. However, tissue oxygenation and oxygen consumption were increased with pentoxifylline resuscitation. Pentoxifylline resuscitation also significantly decreased polymorphonuclear leukocyte adhesiveness. CONCLUSIONS: Pentoxifylline improves tissue oxygenation and oxygen consumption posthemorrhage and this effect is not due to increased cardiac output. Therefore, it must be due to improved microcirculatory blood flow. This effect may be due to decreased polymorphonuclear leukocyte adhesiveness induced by pentoxifylline resuscitation.     

Understanding hyperbaric oxygen therapy and its use in the treatment of compromised skin grafts and flaps.

Nonhealing wounds represent a problem involving inadequate oxygenation of the tissues that can lead to hypoxic injury. Hyperbaric oxygen therapy can be used as an adjunctive therapy for compromised grafts and flaps that have failed to show improvement with standard wound therapy and offer additional physiologic benefits in the reversal of wound hypoxia and hypoperfusion. A literature review confirms the efficacy of hyperbaric oxygen therapy in nonhealing wounds and compromised skin grafts and flaps. The purpose of this article is to review the role of oxygen and physiological effects of hyperbaric oxygen therapy in wound healing and to provide an overview of the hyperbaric oxygen therapy experience including indications, types of chambers, patient preparation, complications, and treatment protocols. This article is intended to provide nurses working in plastic surgery the information necessary to consider the benefits that hyperbaric oxygen therapy can offer to improve the healing potential of patients with compromised skin grafts and flaps.     

Effect of vasoactive treatment on the relationship between mixed venous and regional oxygen saturation

OBJECTIVE: To evaluate the relationship between the mixed venous (SvO2), hepatic, and femoral venous oxygen saturations before and during sympathomimetic drug infusions. DESIGN: Case series. SETTING: Tertiary care center. PATIENTS: Twenty-four ICU patients: postoperative open-heart surgery patients (n = 12), patients with septic shock (n = 8), and patients with acute respiratory failure (n = 4). INTERVENTIONS: In postoperative open-heart surgery patients and patients with respiratory failure, cardiac output was increased by at least 25% following therapy with either dobutamine or dopamine. Patients with septic shock were treated with either dopamine or norepinephrine to correct hypotension. MEASUREMENTS AND MAIN RESULTS: Vasoactive drug infusions increased cardiac index and oxygen delivery by 34% and oxygen consumption by 8%. SvO2 increased (62.6 +/- 6.7% vs. 69.5 +/- 6.0%, p less than .001). Although cardiac index was the most important determinant of SvO2, the correlation between cardiac index and SvO2 was weak (r2 = .32). The hepatic and femoral venous saturations also increased (49.0 +/- 12.1% vs. 59.4 +/- 9.8%, p less than .01, and 51.9 +/- 16.6% vs. 63.4 +/- 9.8%, p less than .001, respectively) in response to vasoactive treatment. The mean gradient between SvO2 and hepatic venous saturation was 11.9 +/- 8.7% and was independent of the clinical condition and baseline SvO2. The hepatic venous oxygen saturation increased in parallel with SvO2 regardless of the initial SvO2 value. CONCLUSIONS: The individual values of SvO2 have no predictive value concerning regional oxygen transport. The parallel increase in SvO2 and hepatic venous oxygen saturation suggests that the vasoactive treatment did not compromise splanchnic oxygenation.     

Hemodynamic, blood volume, and oxygen transport responses to albumin and hydroxyethyl starch infusions in critically ill postoperative patients

Hemodynamic, plasma volume, and oxygen transport effects were measured after administration of 500 ml of 5% albumin or 6% hydroxyethyl starch (HES) in hypovolemic postoperative patients using a prospectively randomized crossover design. Both agents produced marked and significant improvement in plasma volume and flow as well as small transient increases in arterial and venous pressures, urine output, colloidal osmotic pressure (COP), and oxygen transport. The authors conclude that HES is a safe, inexpensive, effective plasma expander that has hemodynamic effects similar to those of other colloids. It was apparent from these and other studies that clinically stable postoperative patients may have appreciable blood volume deficits. Routine vital signs correlated poorly with the preinfusion control hemodynamic values or the changes in blood volume status after volume loading. Normal cardiac output, central venous pressure (CVP), and pulmonary arterial wedge pressure (WP) values are commonly seen in critically ill postoperative patients who, nevertheless, may be hypovolemic. Measurement of changes in these variables after a fluid challenge is a useful way to assess plasma volume status.     

Photoacoustic microscopy of vascular adaptation and tissue oxygen metabolism during cutaneous wound healing

Cutaneous wounds affect millions of people every year. Vascularization and blood oxygen delivery are critical bottlenecks in wound healing, and understanding the spatiotemporal dynamics of these processes may lead to more effective therapeutic strategies to accelerate wound healing. In this work, we applied multi-parametric photoacoustic microscopy (PAM) to study vascular adaptation and the associated changes in blood oxygen delivery and tissue oxygen metabolism throughout the hemostasis, inflammatory, proliferation, and early remodeling phases of wound healing in mice with skin puncture wounds. Multifaceted changes in the vascular structure, function, and tissue oxygen metabolism were observed during the 14-day monitoring of wound healing. On the entire wound area, significant elevations of the arterial blood flow and tissue oxygen metabolism were observed right after wounding and remained well above the baseline over the 14-day period. On the healing front, biphasic changes in the vascular density and blood flow were observed, both of which peaked on day 1, remained elevated in the first week, and returned to the baselines by day 14. Along with the wound closure and thickening, tissue oxygen metabolism in the healing front remained elevated even after structural and functional changes in the vasculature were stabilized. On the newly formed tissue, significantly higher blood oxygenation, flow, and tissue metabolism were observed compared to those before wounding. Blood oxygenation and flow in the new tissue appeared to be independent of when it was formed, but instead showed noticeable dependence on the phase of wound healing. This PAM study provides new insights into the structural, functional, and metabolic changes associated with vascular adaptation during wound healing and suggests that the timing and target of vascular treatments for wound healing may affect the outcomes.     

Regulation of myocardial oxygen delivery

In most organs, oxygen consumption is maintained at relatively constant levels as oxygen delivery decreases, until a critical level is reached. This biphasic action is not observed in the heart. Myocardial oxygen consumption is supply dependent at all levels of myocardial oxygen delivery, because changes in myocardial oxygen delivery modify ventricular loading conditions and hence myocardial oxygen consumption. Since the oxygen content of coronary sinus blood is very low, only limited increases in oxygen extraction are possible. Therefore, coronary dilation is the primary mechanism for increasing myocardial oxygen delivery. Four- to sixfold increases in coronary blood flow can occur in several animal species and in human beings. Apart from metabolic control mechanisms, the regulation of myocardial oxygen delivery is multifaceted; major factors include extravascular compressive forces, autoregulation, neural controls, and humoral factors. In situations of decreased myocardial oxygen delivery, coronary vessels dilate to increase flow, and as coronary flow reserve falls to zero, flow becomes exquisitely dependent on perfusion pressure. With onset of supply dependency, contractility falls in an effort to maintain cardiac output at a given myocardial oxygen consumption.