Blood transfusion and lung function in chronically anemic patients with severe chronic obstructive pulmonary disease

OBJECTIVE: To study in anemic patients with chronic obstructive pulmonary disease (COPD) whether blood transfusion reduces minute ventilation and work of breathing (WOB). DESIGN: We prospectively evaluated the minute ventilation and WOB in 20 anemic adults (hemoglobin of <11 g/dL). Ten patients had severe COPD and ten patients were without lung disease. Measurements were made before and after receiving red blood cell transfusion; post-transfusion measurements were made 24 to 36 hrs after the last transfusion. SETTING: The study was performed in the intensive care unit of a tertiary referral center for home mechanical ventilation and for patients considered difficult to wean from mechanical ventilation. PATIENTS: Twenty clinically stable patients (12 female, eight male) with chronic anemia were studied. Ten patients with COPD (mean forced expiratory volume in 1 sec: 0.55+/-0.1 [SD] L) were compared with ten patients without lung disease. All participants had adequate renal and left ventricular function. INTERVENTIONS: Patients received 1 unit of packed red blood cells for each g/dL that their hemoglobin value was less than an arbitrarily defined target value of 11.0 to 12.0 g/dL. Each unit was transfused over 2 hrs and < or =3 units in total was given. MEASUREMENTS AND MAIN RESULTS: Esophageal pressure was measured from a catheter which was positioned in the middle of the esophagus. Flow was measured using a pneumotachygraph connected to a mouthpiece while a nose clip closed the nostrils during the measurements. From these data, respiratory rate, minute ventilation, and inspiratory resistive WOB were computed. Arterial blood gas values, oxygen saturation, hemoglobin, and hematocrit were also measured, and oxygen content was calculated before and 24 to 36 hrs after transfusion. In patients with COPD, hemoglobin increased from 9.8+/-0.8 to 12.3+/-1.1 g/dL due to a mean transfusion of 2.2+/-0.4 (SD) units of red blood cells. There was a reduction in the mean minute ventilation from 9.9+/-1.0 to 8.2+/-1.2 L/min (p < .0001); correspondingly, WOB decreased from 1.03+/-0.24 to 0.85+/-0.21 WOB/L (p< .0001). The capillary P(CO2) increased from 38.1+/-6.0 to 40.7+/-6.8 torr (5.1+/-0.8 to 5.8+/-0.9 kPa) (p < .05). Similarly, capillary P(O2) changed from 56.9+/-8.9 to 52.8+/-7.0 torr (7.6+/-1.2 to 7.0+/-0.9 kPa) (p < .05). In anemic patients without lung disease, minute ventilation, WOB, and the capillary blood gas values did not change after increase of the hemoglobin by a similar degree. CONCLUSIONS: We conclude that red blood cell transfusion in anemic patients with COPD leads to a significant reduction of both the minute ventilation and the WOB. In these patients, transfusion may be associated with unloading of the respiratory muscles, but it may also result in mild hypoventilation.     

Perfluorocarbons are effective oxygen carriers in cardiopulmonary bypass

Intravascular perfluorochemical (PFC) emulsions together with a high oxygen (O2) tension may increase the delivery of dissolved O2 to useful levels. A severely anemic model of cardiopulmonary bypass (CPB) was used to test the hypothesis that a novel PFC emulsion (PFCE; Oxygent [Alliance Pharmaceutical Corp., San Diego, CA] 90% w/v perflubron) used at a high PO2 during bypass delivers sufficient O2 to ameliorate hypoxic myocardial contractile dysfunction. Acutely anemic dogs (N = 42; hematocrit = 15.8 +/- 0.6% [mean +/- SEM] before CPB and 10.9 +/- 0.1% during CPB) were divided into four groups. Group 1 was a control (n = 12). As CPB was initiated, groups 2 (n = 10), 3 (n = 10), and 4 (n = 10) had 1.35 g PFC.kg-1, 2.7 g PFC.kg-1, or 5.4 g PFC.kg-1 added via the venous return cannula. Pre-CPB and post-CPB cardiac function was measured by the first derivative of left ventricular pressure (dP/dtmax). The dP/dtmax on separation from CPB was: group 1, 619 +/- 96; group 2, 738 +/- 56; group 3, 782 +/- 101; and group 4, 828 +/- 100 (p < 0.05 groups 3 and 4 versus group 1). Mortality during the first hour after separation from CPB was higher in group 1 than in PFCE treated dogs; however, this trend did not attain statistical significance (p < 0.065). The PFC dose was higher in survivors than in nonsurvivors (2.6 +/- 0.4 g PFC.kg-1 versus 1.2 +/- 0.5 g PFC.kg-1; p < 0.05). A PFCE used at a high PO2 provides sufficient physically dissolved O2 to relieve myocardial hypoxic injury in a severely anemic model of CPB. Current PFCEs are effective O2 carriers. This finding suggests that they can be used as a temporary erythrocyte substitute to diminish the need for allogeneic transfusions during cardiac operations.     

The importance of accurate lesion placement in posteroventral pallidotomy. Report of two cases

OBJECTIVES: The effects of anemia of prematurity during bronchopulmonary dysplasia (BPD) as well as on the metabolic and erythropoietic functions were determined before and after a transfusion. Fourteen anemic (Hb range: 65-88 gm/L), oxygen dependent (fraction of inspired oxygen < or = 35%), nonventilated, preterm infants with BPD were studied at a postnatal age of 6 +/- 2 weeks. STUDY DESIGN: Cardiac output, heart rate, mean velocity of circumferential fiber shortening, shortening fraction (SF), and stroke volume were assessed by pulsed and continuous wave Doppler echocardiography. Values for resting oxygen consumption, carbon dioxide production, and energy expenditure were obtained by indirect calorimetry. The affinity of oxygenated hemoglobin was determined by a blood oxygen dissociation analyzer. RESULTS: An increased hemoglobin level resulted in a suppression of erythropoietin secretion (p < 0.001), whereas heart rate, cardiac output, stroke volume, and SF decreased (p < 0.05). Weight gain before and after transfusion were similar. Plasma lactate levels decreased from 1.6 +/- 0.3 to 1.2 +/- 0.3. Oxygen consumption, carbon dioxide production, and energy expenditure were not affected. CONCLUSIONS: Anemia of prematurity and BPD increase heart rate, cardiac output, stroke volume, and SF. These hemodynamic compensatory responses are normalized by transfusion.     

Effect of sodium ortho-iodobenzoate on oxygen transport and erythropoiesis in hypoxemic dogs with a right-to-left cardiac shunt

Eight dogs were made hypoxemic by surgical construction of a right-to-left cardiac shunt; and they were given sodium ortho-iodobenzoate (OISB) before and for 3 months after operation. The P(50) at 50% saturation) rose from 27.2 +/- 0.7 to 31.2 +/- 0.6 mm Hg (p less than 0.001) during OLSB treatment before operation and increased further to 32.2 +/- 0.8 mm Hg 3 months after creation of hypoxemia. The P(50) remained elevated for an additional 3 months after OISB was stopped. Administration of OISB before operation did not alter the red blood cell 2,3-diphosphoglycreate concentration. Hypoxemia caused an increase of this metabolite from 0.91 +/- 0.21 to 1.50 +/- 0.28 moles/moles of hemoglobin (p less than 0.05); the rise was not as great as that observed in hypoxemic dogs without OISB treatment. In spite of significant hypoxemia, hematocrit rose only slightly during the period of OISB infusion. OISB increased P50 and prevented the compensatory polycythemia regularly seen when dogs are made hypoxemic. Altering oxygen transport in this fashion may increase tissue oxygen delivery in patients with conditions which result in tissue hypoxia.     

Does airway pressure release ventilation alter lung function after acute lung injury?

BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject-controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.     

Effect of hematocrit variations on coronary hemodynamics and oxygen utilization

Twenty-five closed-chest pentobarbitalized dogs were used for studying coronary flow dynamics and myocardial oxygen utilization following variations of hematocrit (Hct) by isovolumetric exchange of blood with plasma or packed red cells. Coronary blood flow (133Xe washout) and cardiac output varied inversely with Hct. Coronary systemic, and pulmonary flow resistances varied in the same direction with Hct. Blood viscosity played a significant role in determining the flow resistances in these three regions. Analysis of vascular hindrance (vascular resistance/blood viscosity) suggested that coronary vasodilation occurred following Hct changes beyond the range of 20-60%. In systemic and pulmonary circulations, however, there was vasoconstriction following hemodilution. The range of optimum Hct for maximum O2 transport (blood flow X arterial O2 content) was much wider in coronary (20-60% Hct) than in systemic circulation (40-60% Hct). The O2 consumptions in total body and in myocardium were essentially constant over a wide range of Hct (20-60%). The maintenance of total body O2 consumption over the Hct range of 20-40% was attributable to an increase in A-V O2 extraction. The O2 extraction ratio in the coronary circulation was constant over the entire range of Hct studied, suggesting that the myocardial O2 consumption was primarily determined by the coronary O2 transport.     

High-density lipoprotein subclasses and esterification rate of cholesterol in children: effect of gender and age

OBJECTIVE: To investigate the gas exchange and pulmonary haemodynamic responses to two different intravenous fat emulsions in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Intensive care unit in a university-affiliated hospital. PATIENTS: 21 patients with ARDS [mean age, 57 +/- 3 (SEM) years; Acute Physiology and Chronic Health Evaluation II, 20 +/- 3; Murray's score, 2.85 +/- 0.12] consecutively admitted. INTERVENTIONS: Patients were assigned to three groups (n = 7 each): group A (LCT) received long-chain triglycerides (20% LCT), group B (MCT/LCT), medium-chain triglycerides/long-chain triglycerides (20% MCT/LCT: 50/50) and group C placebo (0.9% sodium chloride, NaCl). The infusion was always given at the rate of 2 mg/kg min over a total period of 12 h, with a volume infusion of 500 ml in each group. MEASUREMENTS: Data were collected before, immediately after and 12 h after infusion ceased. Pulmonary and systemic haemodynamic and gas exchange variables were measured at each time point. Serum triglyceride cholesterol, and non-esterified fatty acids levels were measured. RESULTS: During LCT infusion, cardiac output, oxygen consumption and oxygen delivery increased (all p < 0.05), whereas pulmonary haemodynamics, arterial oxygen tension, mixed venous partial pressure of oxygen and venous admixture ratio remained essentially unaltered. No changes were observed following MCT/LCT infusion. CONCLUSIONS: The administration of LCT emulsion given at a slow rate did not alter arterial oxygenation because of the beneficial effect of a high cardiac output, hence offsetting the detrimental effect of increased O2 consumption.     

Defining the critical limit of oxygen extraction in the human small intestine

Although animal models have been used to characterize the relation between oxygen consumption and blood flow, reliable data have not been generated in the human small intestine. We perfused segments of human small intestine by using an ex vivo perfusion circuit that allowed precise manipulation of blood flow and perfusion pressure. Our goal was to define the critical level of intestinal blood flow necessary to maintain the metabolic needs of the tissue. Human small intestine (n = 5) tissue obtained at transplantation harvest was transported on ice to the laboratory. A 40-cm mid-jejunal segment was selected for perfusion, and appropriate inflow and outflow vessels were identified and cannulated. Perfusion with an autologous blood solution was initiated through an extracorporeal membrane oxygenation circuit. After a 30-minute equilibration period, arterial and venous blood gases were measured at varying flow rates while maintaining a constant hematocrit level. Arterial and venous oxygen content, arteriovenous oxygen difference (A-VO2 diff), and oxygen consumption (VO2) were then calculated. Our results demonstrated that at blood flows > 30 ml/min/100 g, VO2 is independent of blood flow (1.6 +/- 0.06 ml/min/100 g), and oxygen extraction is inversely related to flow. Below this blood flow rate of 30 ml/min/100 g, oxygen extraction does not increase further (6.3 +/- 0.3 vol%), and VO2 becomes flow dependent. This ex vivo preparation defines for the first time a threshold value of blood flow for small intestine below which oxygen consumption decreases (30 ml/min/100 g). Previous animal studies have correlated such a decrease in oxygen consumption with functional and histologic evidence of tissue injury. This "critical" flow rate in human intestine is similar to that found previously in canine and feline intestine, but lower than that of rodent species.     

Acute dilutional anemia and critical left anterior descending coronary artery stenosis impairs end organ oxygen delivery

OBJECTIVE: Limited cardiac reserve, secondary to coronary disease, may be associated with end organ morbidity. In this study, we investigate the significance of anemia in the pathogenesis of this phenomenon. DESIGN: Nonrandomized controlled animal trial. SETTINGS: Animal laboratory in a university hospital. SUBJECT: Anesthetized dogs. INTERVENTIONS/MEASUREMENTS: Fourteen anesthetized dogs underwent isovolemic hemodilution with 6% hetastarch from a baseline hematocrit of 40 to 20%. Radioactive microspheres were used to evaluate regional blood flow and cardiac index. Systemic oxygen delivery, consumption, serum lactate, and systemic vascular resistance were recorded during each experiment. Arterial venous oxygen difference was determined from arterial and mixed venous blood. Seven dogs had an iatrogenic critical stenosis of their left anterior descending coronary artery (experimental group); seven dogs did not (control). MAIN RESULTS: Only in the control animals, the cardiac index increased by 35% with hemodilution to 20%. Systemic oxygen delivery decreased in both the control and the experimental animals. Systemic oxygen consumption and lactate levels were unchanged in both groups. In the renal cortex, spleen, distal colon, ileum, gallbladder, and stomach body, regional O2 delivery was significantly decreased with hemodilution to 20% in both groups. This finding was also observed in the left ventricle and cervical spinal cord in the experimental group. In addition, regional O2 delivery was reduced in the spleen, distal colon, and gallbladder with hemodilution to only 30%. Regional blood flow in the stomach body, gallbladder, ileum, renal cortex, and distal colon, in both groups, and the spleen in the control group was unchanged from baseline with hemodilution to 20%. However, regional blood flow under all other circumstances (control or experimental) was significantly increased with hemodilution to 20% with the exception of the spleen, which showed significant regional blood flow decrease in the experimental group only. CONCLUSIONS: These data suggest that with limited cardiac reserve, anemia may compromise aerobic splanchnic circulation. These observations may further our understanding of the pathogenesis of cholecystitis, gastric stress ulcers, ileal endotoxin translocation, and ischemic colitis in critically ill patients with coronary artery disease.     

Overcoming right ventricular failure with left ventricular assist devices

BACKGROUND: Right ventricular failure can lead to circulatory collapse while on left ventricular assist device support. By shunting blood from the femoral vein to the left ventricular assist device, cardiac output can be increased, but arterial oxygen saturation will decrease. METHODS: To determine the effects on O2 delivery, a model was developed on the basis of O2 uptake in the lungs and whole body O2 consumption. An equation was derived that related cardiac output, pulmonary venous O2 saturation, O2 consumption, and the ratio of shunt-to-systemic blood flow to systemic O2 delivery. RESULTS: When total cardiac output increases, the shunt will increase systemic O2 delivery while decreasing arterial O2 saturation and leaving systemic venous O2 saturation unaltered. When total output does not increase, the shunt will decrease systemic O2 delivery, arterial O2 saturation, and systemic venous O2 saturation. CONCLUSIONS: The analysis suggests that measuring systemic venous oxygen saturation may be a useful way to monitor patient safety. A decrease in systemic venous O2 saturation when creating the shunt implies an inadequate increase in cardiac output.     

Noninvasive determination of cardiac output in patients with severe airflow limitation

The noninvasive measurement of cardiac output (Q) by the Indirect Fick CO2-rebreathing technique requires mixed venous P CO2 (P CO2) to be determined by the rebreathing maneuver, and Pa CO2 to be estimated from end-tidal P CO2 (PET CO2). Previous work has suggested that although P CO2 can be determined, Pa CO2 cannot be accurately estimated in patients with significant airflow limitation. Nineteen patients with cystic fibrosis who had severe airflow limitation (%FEV1, 29.3 +/- 7.12 SD) were studied during steady-state exercise at 50% of their measured maximal work capacity. Estimated Pa CO2 was slightly lower than Pa CO2 measured from blood samples obtained from an indwelling arterial catheter (measured: 45.2 +/- 4.92; estimate: 42.7 +/- 5.68 mm Hg). To calculate arterial blood content, the values derived from Pa CO2, pH, hemoglobin (Hb), and O2 saturation were compared with those derived from PET CO2 and O2 saturation, where (1) pH was assumed to be 7.40 and Hb was measured, and (2) pH was assumed to be 7.40 and Hb was assumed to be 15 g/dl (measured mean pH, 7.34; Hb, 14.4 g/dl). No difference in arterial CO2 content was seen between the three methods (measured: 47.53 +/- 5.17; estimate 1: 49.57 +/- 6.58; estimate 2: 49.12 +/- 6.61 ml/100 ml). As pH and Hb can also affect mixed venous CO2 content, the effect on Q was also assessed. Both estimates fit closely with measured Q (r2=0.77 and 0.76), with intercepts not different from zero and slopes not different from 1, and coefficients of variation of 13.5 and 14.6%. When viewed with regard to the confidence intervals for Q as a function of O2 consumption, Q was altered to a minor extent. We conclude that the use of PET CO2 to estimate Pa CO2 can give reasonable values for Q determined noninvasively in patients with severe airflow limitation.     

Mechanisms facilitating oxygen delivery during exercise in patients with chronic heart failure

The aim of the study was to estimate the relative importance of the Bohr effect and redistribution of blood from the non-exercising tissues on the arterial-venous oxygen content differences across the exercising extremities and the central circulation in patients with chronic heart failure; the relationship among femoral vein, systemic and pulmonary artery oxygen partial pressure and hemoglobin saturation was determined. It has been reported that the maximal reduction in femoral vein pO2 precedes peak oxygen consumption and lactic acidosis threshold in patients with chronic heart failure and normal subjects during exercise. The increase in oxygen consumption at work rates above lactic acidosis threshold, therefore, must be accounted for by increase in blood flow in the exercising muscles and right-ward shift on the oxyhemoglobin dissociation curve. Since the total cardiac output increase is blunted in patients with chronic heart failure, diversion of blood flow from non-exercising to exercising tissues may account for some of the increase in muscle blood flow. Ten patients with chronic heart failure performed a progressively increasing leg cycle ergometer exercise test up to maximal effort while measuring ventilation and gas concentration for computation of oxygen uptake and carbon dioxide production, breath-by-breath. Blood samples were obtained, simultaneously, from systemic and pulmonary arteries and femoral vein at rest and every minute during exercise to peak oxygen consumption. At comparable levels of exercise, femoral vein pO2, hemoglobin saturation and oxygen content were lower than in the pulmonary artery. PCO2 and lactate concentration increased steeply in femoral vein and pulmonary artery blood above lactic acidosis threshold (due to lactic acid build-up and buffering), but more steeply in femoral vein blood. These increases allowed femoral vein oxyhemoglobin to dissociate without a further decrease in femoral vein pO2 (Bohr effect). The lowest femoral vein pO2 (16.6 +/- 3.9 mmHg) was measured at 66 +/- 22% of peak VO2 and before the lowest oxyhemoglobin saturation was reached. Artero-venous oxygen content difference was higher in the femoral vein than in the pulmonary artery; this difference became progressively smaller as oxygen consumption increased. "Ideal" oxygen consumption for a given cardiac output (oxygen consumption expected if all body tissues had maximized oxygen extraction) was always higher than the measured oxygen consumption; however the difference between the two was lost at peak exercise. This difference positively correlated with peak oxygen consumption and cardiac output increments at submaximal but not at maximal exercise. In conclusion, femoral vein pO2 reached its lowest value at a level of exercise at or below the lactic acidosis threshold. Further extraction of oxygen above the lactic acidosis threshold was accounted for by a right shift of the oxyhemoglobin dissociation curve. The positive correlation between increments of cardiac output vs "ideal" and measured oxygen consumption suggests a redistribution of blood flow from non-exercising to exercising regions of the body. Furthermore the positive correlation between exercise capacity and the difference between "ideal" and measured oxygen consumption suggests that patients with the poorer function have the greater capability to optimize blood flow redistribution during exercise.     

Straightening out the renal tubule: advances in the molecular basis of the inherited tubulopathies

OBJECTIVE: To assess the left ventricular determinants of cardiac output in 12 chronically instrumented fetal lambs, six of which where made anemic. METHODS: Twelve, singleton pregnant ewes were instrumented between 123-126 days gestation and chronic catheters placed in-situ. In six fetal lambs, isovolemic fetal anemia was induced (reducing the hematocrit from a mean of 35% to 20%). In a prospective study, absolute 'beat-to-beat' LV volumes and pressures were obtained (gestational age 131-134 days) using a conductance catheter method and a comparison made with non-anemic fetal lambs. RESULTS: The group of anemic fetuses (n = 6) had a significantly reduced hematocrit as compared to the control group (37% decrease: mean difference--13.4%; P < 0.001). The arterial blood gases of the two groups were not statistically different, with the exception of the pO2 and oxygen content which were significantly lower in the anemic group (P < 0.05). There was no significant change in fetal heart rate, LV preload (as assessed by venous pressure, end-diastolic volume and pressure) or mean arterial pressure between the anemic and control groups. However, a 75% increase in LV stroke volume was observed in the anemic fetal lambs (P < 0.05), secondary to a 61% fall in LV afterload (P < 0.05). There was no significant change in inherent myocardial contractility of the LV, although this did increase to approach statistical significance in the anemic group (P = 0.056). The diastolic time interval was increased by 22% in the anemic fetus, possibly allowing prolonged LV filling time. The indices measuring LV relaxation (Tau and dP/dtmin) were not significantly different in either group. CONCLUSIONS: This is the first study to report absolute left ventricular volumes in the anemic ovine fetus and the relationship of these data to LV pressure during the cardiac cycle. The model used produces a state of moderately severe, non-hydropic, isovolemic, fetal anemia consistent with those previously described. Although the anemic state was not prolonged, an observed increase in LV stroke volume (which is predominantly due to a decrease in afterload) has been described.     

Safe hemoglobin or hematocrit levels in surgical patients

The terminology and fundamental aspects of the delivery, consumption, and deficits of oxygen are recalled. In chronic and acute, nonseptic states, red blood cell (RBC) transfusion is capable of increasing oxygen consumption (VO2). In acute septic states, the response of VO2 to RBC transfusion is variable and unpredictable, but attempts to increase oxygen delivery (DO2) should be made if the clinical picture raises the suspicion of a potentially lethal oxygen deficit. Therapeutic interventions raising the cardiac index to "supranormal" values in critically ill patients improve their chances of survival; and maintenance of hemoglobin or hematocrit values around 11 g/dl or 33%, respectively, is one part of such interventions. Opinions differ on the general tolerance of anemia, as witnessed by postulated "critical levels" of the hemoglobin concentration between approximately 11 and 4 to 5 g/dl or hematocrit values between 33% and 12% to 15%, respectively. The common denominator underlying these vastly different opinions is the variable behavior of several "non-Hb variables," which influence the venous oxygen tensions apart from the hemoglobin or hematocrit. Abnormalities of these non-Hb variables-typically encountered in the critically ill-increase the dependence of patients on hemoglobin or hematocrit levels that suffice to protect them against an oxygen deficit. For this reason, the "critical" hemoglobin or hematocrit is an individual value, and a generally valid "transfusion trigger" does not exist. Finally, the entity now known as silent myocardial ischemia (SMI) is a decisive factor for the tolerance of anemia. Solid clinical evidence is now available to support the concept that patients over age 40 should not, as an elective procedure, be subjected to levels < 10 g/dl or < 30%, respectively, without prior exclusion of SMI by appropriate investigations.     

Effect of ortho-iodo sodium benzoate on hemoglobin-oxygen affinity in normal and ischemic myocardium

The effect of ortho-iodo sodium benzoate (OISB) on the oxyhemoglobin dissociation curve of coronary venous blood was studied in an isolated canine heart preparation perfused at a constant coronary blood flow. Changes in P-50 (millimeters of mercury) [the oxygen tension (pO2) at which hemoglobin is 50% saturated], were used to express hemoglobin-oxygen affinity. Intracoronary infusion of OISB (200, 400 and 800 mg/min) produced a dose-related increase in coronary venous P-50 and a concurrent increase in coronary venous pO2. In addition, OISB produced a significant decrease in heart rate and increase in coronary artery perfusion pressure. During cardiac pacing at 150, 190 and 230 beats/min, OISB (400 mg/min) significantly increased coronary venous P-50, myocardial oxygen exrraction (O2E) and oxygen consumption (MVO2) whereas coronary venous PO2 was not changed. Furthermore, a 5-minute intracoronary infusion of OISB (200 mg/min) during myocardial ischemia produced an increase in O2E, MVO2 and myocardial contractility with little change in coronary venous pO2. These results suggest that acute pharmacological manipulation of the oxyhemoglobin dissociation curve may enhance oxygen release to the myocardium while maintaining the effective driving pressure (as reflected in coronary venous pO2) for diffusion of oxygen to the myocardium.     

Mechanisms of worsening gas exchange during acute exacerbations of chronic obstructive pulmonary disease

This study was undertaken to investigate the mechanisms that determine abnormal gas exchange during acute exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen COPD patients, hospitalized because of an exacerbation, were studied after admission and 38+/-10 (+/-SD) days after discharge, once they were clinically stable. Measurements included forced spirometry, arterial blood gas values, minute ventilation (V'E), cardiac output (Q'), oxygen consumption (V'O2), and ventilation/perfusion (V'A/Q') relationships, assessed by the inert gas technique. Exacerbations were characterized by very severe airflow obstruction (forced expiratory volume in one second (FEV1) 0.74+/-0.17 vs 0.91+/-0.19 L, during exacerbation and stable conditions, respectively; p=0.01), severe hypoxaemia (ratio between arterial oxygen tension and inspired oxygen fraction (Pa,O2/FI,O2) 32.7+/-7.7 vs 37.6+/-6.9 kPa (245+/-58 vs 282+/-52 mmHg); p=0.01) and hypercapnia (arterial carbon dioxide tension (Pa,CO2) 6.8+/-1.6 vs 5.9+/-0.8 kPa (51+/-12 vs 44+/-6 mmHg); p=0.04). V'A/Q' inequality increased during exacerbation (log SD Q', 1.10+/-0.29 vs 0.96+/-0.27; normal < or = 0.6; p=0.04) as a result of greater perfusion in poorly-ventilated alveoli. Shunt was almost negligible on both measurements. V'E remained essentially unchanged during exacerbation (10.5+/-2.2 vs 9.2+/-1.8 L x min(-1); p=0.1), whereas both Q' (6.1+/-2.4 vs 5.1+/-1.7 L x min(-1); p=0.05) and V'O2 (300+/-49 vs 248+/-59 mL x min(-1); p=0.03) increased significantly. Worsening of hypoxaemia was explained mainly by the increase both in V'A/Q' inequality and V'O2, whereas the increase in Q' partially counterbalanced the effect of greater V'O2 on mixed venous oxygen tension (PV,O2). We conclude that worsening of gas exchange during exacerbations of chronic obstructive pulmonary disease is primarily produced by increased ventilation/perfusion inequality, and that this effect is amplified by the decrease of mixed venous oxygen tension that results from greater oxygen consumption, presumably because of increased work of the respiratory muscles.     

Mild hypothermia after cardiac arrest in dogs does not affect postarrest cerebral oxygen uptake/delivery mismatching

PURPOSE: To compare measurements of cerebral arteriovenous oxygen content differences (oxygen extraction ratios, oxygen utilization coefficients) in dogs after cardiac arrest, resuscitated under normothermia vs. mild hypothermia for 1-2 h or 12 h. METHODS: In 20 dogs, we used our model of ventricular fibrillation (no blood flow) of 12.5 min, reperfusion with brief cardiopulmonary bypass, and controlled ventilation, normotension, normoxemia, and mild hypocapnia to 24 h. We compared a normothermic control Group I (37.5 degrees C) (n = 8); with brief mild hypothermia in Group II (core and tympanic membrane temperature about 34 degrees C during the first hour after arrest) (n = 6); and with prolonged mild hypothermia in Group III (34 degrees C during the first 12 h after arrest) (n = 6). RESULTS: In Group I, the cerebral arteriovenous O2 content difference was 5.6 +/- 1.6 ml/dl before arrest; was low during reperfusion (transient hyperemia) and increased (worsened) significantly to 8.8 +/- 2.8 ml/dl at 1 h, remained increased until 18 h, and returned to baseline levels at 24 h after reperfusion. These values were not significantly different in hypothermic Groups II and III. The cerebral venous (saggital sinus) PO2 (PssO2) was about 40 mmHg (range 29-53) in all three groups before arrest and decreased significantly below baseline values, between 1 h and 18 h after arrest; the lowest mean values were 19 +/- 19 mmHg in Group I, 15 +/- 8 in Group II (NS), and 21 +/- 3 in Group III (NS). Postarrest PssO2 values of < or = 20 mmHg were found in 6/8 dogs in Group I, 5/6 in Group II and 4/6 in Group III. Among the 120 values of PssO2 measured between 1 h and 18 h after arrest, 32 were below the critical value of 20 mmHg. CONCLUSIONS: After prolonged cardiac arrest, critically low cerebral venous O2 values suggest inadequate cerebral O2 delivery. Brief or prolonged mild hypothermia after arrest does not mitigate the postarrest cerebral O2 uptake/delivery mismatching.     

The effect of hypoxia on the regional distribution of cardiac output in the dog

Twenty-one dogs were studied under conditions of normal oxygenation and hypoxia with the microsphere distribution method to determine the effect of arterial oxygen saturation on the regional distribution of cardiac output. The dogs were anesthetized and artifically ventilated. Cannulas were placed in the left ventricle to administer microspheres and in a peripheral artery to determine cardiac output. Each dog received two microsphere injections: (1) while normally oxygenated (room air), and (2) under hypoxia (10% oxygen-90% nitrogen in 10 dogs and 5% oxygen-95% nitrogen in 11 dogs). Absolute cardiac output increased from 87 +/- 15 ml/min per kg to 101 +/- 14 ml/min per kg during mild hypoxia (10% oxygen) (P less than 0.05), and from 73 +/- 17 ml/min per kg to 120 +/- 24 ml/min per kg during severe hypoxia (5% oxygen) (P less than 0.01). Absolute blood flows increased to all organs except skin and muscle during hypoxia, although there were decreases in the fractional distribution of cardiac output to the splanchnic bed and kidney. Striking changes were found in coronary, hepatic, and cerebral circulation, and the organ with, greatest response to hypoxia was the heart, with increased coronary flow of 37% and 285% during exposure to 10% and 5% oxygen, respectively. Hence, low oxygen levels in blood cause redistribution of cardiac output and arterial content plays an important role in blood flow regulation.     

Anemia increases gastric blood flow in noncirrhotic and cirrhotic patients

BACKGROUND: Previous studies in rats have demonstrated that anemia induces a significant increment in gastric mucosal blood flow. In the present study, we investigated whether chronic anemia induces similar changes in gastric blood perfusion in humans, and if this effect is also present in cirrhotic patients in whom gastric blood flow is usually increased in basal conditions. METHODS: Gastric mucosal blood perfusion was assessed by means of laser-Doppler flowmetry and reflectance spectrophotometry applied through the endoscope. RESULTS: Anemia significantly increases laser-Doppler signal in cirrhotic (2.3 +/- 0.11 vs 2.9 +/- 0.22 volts, p < 0.05) and noncirrhotic patients (1.71 +/- 0.15 vs 2.24 +/- 0.17, p < 0.05). In anemic patients the index of hemoglobin concentration of the gastric mucosa, assessed by reflectance spectrophotometry, was significantly decreased in cirrhotic patients (107.6 +/- 4.7 vs 95.5 +/- 3.3, p < 0.05) and noncirrhotic patients (93.9 +/- 4.1 vs 76.1 +/- 4.2, p < 0.01), whereas the index of oxygen saturation was increased (36.7 +/- 0.7 vs 40.4 +/- 1.4, p = 0.05; and 36.4 +/- 1.1 vs 43.2 +/- 1.9, p < 0.01, respectively). CONCLUSIONS: In conclusion, chronic anemia is associated with an enhanced gastric blood perfusion reflected by an increased laser-doppler signal and gastric mucosal oxygen index despite a decrease in gastric hemoglobin concentration. In cirrhotic patients, anemia promotes a further increment in its basal gastric hyperemia.     

Capillary oxygen transport during severe hypoxia: role of hemoglobin oxygen affinity

The efficacy of an increased hemoglobin oxygen affinity [decreased oxygen half-saturation pressure of hemoglobin (P50)] on capillary oxygen transport was evaluated in the hamster retractor muscle under conditions of a severely limited oxygen supply resulting from the combined effects of a 40% reduction in systemic hematocrit and hypoxic ventilation (inspired oxygen fraction 0.1). Two groups of hamsters were utilized: one with a normal oxygen affinity (untreated; P50 = 26.1 +/- 2.4 Torr) and one with an increased oxygen affinity (treated; P50 = 15.7 +/- 1.4 Torr) induced by the chronic short-term administration of sodium cyanate. Using in vivo video microscopy and image analysis techniques, we determined oxygen saturation and associated hemodynamics at both ends of the capillary network. During hypoxic ventilation, the decrease in oxygen saturation across the network was 3.6% for untreated animals compared with 9.9% for treated animals. During hypoxia, estimated end-capillary PO2 was significantly higher in the untreated animals. These data indicate that, at the capillary level, a decreased P50 is advantageous for tissue oxygenation when oxygen supply is severely compromised, because normal oxygen losses in capillaries are maintained in treated but not in untreated animals. The data are consistent with the presence of a diffusion limitation for oxygen during severe hypoxia in animals with a normal hemoglobin oxygen affinity.