The effect of altered hemoglobin-oxygen affinity on oxygen transport by hemoglobin solution

Oxygen dynamics were evaluated in eight baboons following total exchange transfusion with either stripped (SFH) or pyridoxylated (SFH-P) stroma-free hemoglobin solution. Oxygen consumption and circulatory dynamics were maintained with both hemoglobin solutions. The oxygen extraction ratio increased in each group from 0.15 to 0.47, with no change in cardiac output or arteriovenous oxygen content difference. The major finding was the significantly higher mixed venous PO₂ (Pv?O₂) values observed with pyridoxylated hemoglobin at hematocrits below 20. At hematocrits of 5%, the SFH-P animals had a Pv?O₂ of 31.3 Torr, while the group receiving SFH had a Pv?O₂ of 13.8 Torr. The data suggest that SFH-P is more likely to minimize tissue hypoxia than SFH. Finally, the physiology of oxygen transport with hemoglobin solution appears to be different from that of erythrocytic hemoglobin.     

Oxygen Transport to Tissue under Normovolemic Moderate and Extreme Hemodilution during Coronary Bypass Operation

Oxygen transport to tissue was studied in 12 patients undergoing coronary bypass operation under normovolemic moderate and extreme hemodilution. Normovolemic moderate hemodilution (15 ml per kilogram of body weight), carried out immediately after induction of anesthesia, decreased the mean hematocrit from 0.43 to 0.33. Simultaneously, the cardiac index and the left ventricular filling pressure increased slightly but the systemic oxygen transport was reduced by 20%. The subcutaneous tissue oxygen tension (Po₂) was approximately 40 mm Hg after induction of anesthesia and underwent a transient increase during moderate hemodilution. During cardiopulmonary bypass and extreme hemodilution, the mean hematocrit declined to 0.16. Concurrently, the mean tissue Po₂ fell sharply and reached a minimum of 14 mm Hg at deepest hypothermia. After decannulation and reinfusion of autologous blood, the Po₂ rose to 30 mm Hg. In general, total-body oxygen consumption changed along with tissue Po₂. Blood lactate concentration underwent a clear increase in the early phase of extracorporeal circulation and remained rather stationary thereafter. No perioperative myocardial infarctions were encountered, and each patient made an uneventful recovery.     

Improved Anesthesia for Deep Surface-Induced Hypothermia: The Halothane-Diethyl Ether Azeotrope

The halothane-diethyl ether azeotrope was evaluated in dogs as the anesthetic agent for deep surface hypothermia with total circulatory arrest for open-heart operation. All 10 animals given azeotrope in 100% oxygen (O₂) experienced atrial arrhythmias during cooling, and 1 had ventricular fibrillation prior to the completion of cooling at 18° to 20°C. After only 30 minutes' arrest, 8 of the 10 dogs had postoperative motor disturbances. Administering the azeotrope in 95% O₂ and 5% carbon dioxide (CO₂) yielded markedly improved results characterized by a rapid, smooth cooling course, easy resuscitation following circulatory arrest, and rapid rewarming, and 3 out of 10 dogs experienced mild motor disturbance after 60 minutes of circulatory arrest.This method, when compared with our standard method of ether in 100% O₂, resulted in reduced blood lactates and a striking improvement in clinical status on the first postoperative morning. In limited clinical trials, infants undergoing repair of congenital cardiac defects have done well and responded as expected based on the laboratory experience. Since the results with the azeotrope in 95% O₂ and 5% CO₂ were at least as good as, and in several instances better than, those with the standard method employing ether, the nonexplosive characteristic of the azeotrope warrants continued evaluation of this agent.     

Oxygen Consumption during Surface-Induced Deep Hypothermia under Halothane Anesthesia

The effect of halothane-100% oxygen anesthesia on oxygen consumption was studied in 10 dogs subjected to surface-induced deep hypothermia with 30 minutes of circulatory arrest. The results were compared with previous oxygen consumption data under ether-100% oxygen anesthesia.Low cardiac output, especially during the rewarming period, low Pa02, and a large arteriovenous oxygen difference during rewarming were significantly different in the halothane group, despite identical oxygen consumption in both groups. These differences could not elucidate the exact cause of postoperative motor disturbances associated with 30 minutes of circulatory arrest in the halothane group. The possibility that there was higher oxygen consumption under halothane anesthesia is discussed.     

Souffrance de la muqueuse intestinale au cours du choc endotoxinique expérimental

To ascertain tissue oxygenation during conversion from hypo to hyperdynamic state with vascular volume expansion, venous outflow from a segment of ileum was isolated in anesthetized and pump-ventilated endotoxic dogs to measure gut oxygen uptake (V̇o₂), lactate metabolism, intramucosal Pco₂ and tissue Po₂ (Ptio₂). Tissue Po₂ was measured by multipoint surface Mehrdraht Dortmund Oberfläche electrodes placed on mucosal and serosal surfaces of gut. Six dogs were infused with 2 mg · kg⁻¹ E. coli lipopolysaccharide (LPS) in one hour followed by a two hour 0.5 mL · kg⁻¹ · min⁻¹ dextran infusion. Two dogs were used as controls and received dextran infusion in order to assess time and hemodilution-dependent effects. LPS infusion resulted in an hypodynamic sepsis with supply limited V̇o₂, increased arterial lactate and increased lactate output by gut. Resuscitation resulted in an hyperdynamic sepsis with improvement of whole-body V̇o₂. In the gut, V̇o₂ remained low and intramucosal Pco₂ as well as lactate output remained high, despite increased flow. Gut Ptio₂ results suggested blood flow maldistribution with tissue hypoxia in the mucosa despite increased total flow to the gut. Gut V̇o₂, lactate flux, intramucosal Pco₂, and tissue Po₂ were consistent with regulatory responses that shut down mucosal perfusion and oxygenation in spite of increased blood flow to gut.     

The oxygen transporting capability of neo red cells (NRC) evaluated under total cardiopulmonary bypass

The oxygen transporting capability of an artificial oxygen carrier NRC was evaluated by employing it as a perfusate for total cardiopulmonary bypass. NRC is a type of liposome encapsulated hemoglobin. It has a particle size of approximately 220 nm, with a hemoglobin concentration of 5.6 g/dl and its P₅₀ is controlled to 45 Torr. Male beagles were used in the experiment. Approximately 80% of the estimated circulatory volume was exchanged with NRC and total cardiopulmonary bypass was initiated. Arterial oxygen tension and carbon dioxide tension were controlled to 400 Torr and 40 Torr respectively. The perfused we heated to 37°C. The rate of flow was altered during the experiment. Oxygen consumption reached a plateau at 9.3 ml/kg/min where oxygen delivery was 14.9 ml/kg/min. At this point the oxygen consumed per gram of hemoglobin from NRC was equivalent to that from dog red blood cells. This indicated that almost an equal amount of oxygen was consumed from NRC in comparison to red blood cells. Regarding oxygen transporting capability, NRC could be considered a candidate for perfusate in cardiopulmonary bypass.     

Ischemia may be less detrimental than anemia for O2 transport because of CO2 transport: A model analysis

We analyzed the relationship between oxygen delivery (Do₂) and Pto₂ (tissue Po₂). We found an important factor which has not been specified before. In the previous O₂ transport model, Do₂ was a dependent variable, calculated from hemoglobin, blood flow, Pao₂, and the oxygen dissociation curve (ODC). In this study, the model was modified slightly so that the Do₂ can be an independent variable. We allowed, instead, one of the three parameters, hemoglobin, blood flow, and Pao₂ to be a dependent variable. We compared the brain tissue Po₂ under three conditions, hypoxemia, ischemia and anemia, at the same Do₂. To further elucidate the mechanism produced by the effect of CO₂ transport on the ODC, we studied the effect of the Bohr factor (d log Po₂/d pH) and of the gas exchange ratio (Vco₂/Vo₂) on the O₂ transport. Ischemia maintains a slightly higher tissue Po₂ than anemia at the same Do₂ level. In ischemia the CO₂ transport is disturbed, leading a higher draining venous Pco₂, which in turn maintains a higher Po₂ the capillary, resulting in a higher gradient for Po₂ between capillary and the tissue. Between ischemia and anemia, ischemia is less detrimental than anemia. In ischemia, the CO₂ transport is disturbed, which in turn maintains a higher Po₂ at the capillary.     

The effect of hemodilution on capillary blood flow and arteriovenous shunt after resuscitation in dogs

The present study was designed to elucidate the adverse effects of temporary circulatory arrest upon the capillary blood flow and arteriovenous shunt and additionally to observe how hemodilution may improve such microcirculatory deterioration. The organ capillary blood flow and organ fraction of cardiac output were measured by the microsphere (phi 9 microns) trapping method in 14 organs. Simultaneously, the arteriovenous shunt rate was measured by continuous collection of drained venous blood at 4.8 ml.min-1 for two minutes from the brain, kidney, liver, splanchnic organs, skeletal muscle of the pelvic limb and all systemic circulatory organs. In five non-hemodiluted dogs (C group), the capillary blood flows decreased in the thyroid gland and pancreas at 30 minutes after circulatory arrest, and in these organs as well as in the brain and stomach at 90 minutes after the arrest. Change in the fraction of cardiac output was similar to that in the capillary blood flow. The arteriovenous shunt rate was unchanged after circulatory arrest. The remaining ten dogs were hemodiluted with dextran-70 solution either before (Pre group, five dogs) or after (Post group, five dogs) circulatory arrest. Both groups of hemodilution maintained the capillary blood flow and showed no alteration of the arteriovenous shunt rate after circulatory arrest, except for an increase in the systemic arteriovenous shunt rate in the Pre group. These results suggest that hemodilution maintains the capillary blood flow at a normal level and ameliorates the oxygen supply into organs after circulatory arrest.     

Cardiopulmonary Dynamics during Arteriovenous Perfusion: Cardiac Output,Pulmonary Arterial Resistance,and Right Ventricular Stroke Work

The effects of arteriovenous perfusion on myocardial performance, pulmonary circulatory dynamics, and organ preservation were studied in dogs in order to evaluate the applicability of arteriovenous extracorporeal membrane oxygenation for partial respiratory support. Studies were made on normally oxygenated dogs, on dogs made hypoxic by oxygen deprivation and ventilatory depression, and on dogs with pulmonary injury and moderate pulmonary hypertension induced by injection of oleic acid into the right ventricle. The latter two groups were included to assess the changes that occur in cardiopulmonary dynamics in the presence of hypoxia and pulmonary hypertension. A micro-channel membrane oxygenator was employed to provide partial respiratory support to the group of animals with pulmonary injury. The results indicate that no deleterious hemodynamic changes occurred in any of the groups of animals with arteriovenous flow for periods of up to 5 hours at rates corresponding to 20 to 35% of the total cardiac output. Adequate systemic oxygenation was provided by the microchannel oxygenator at these rates of arteriovenous perfusion.     

Techniques de ventilation artificielle sur un seul poumon en cours de thoracotomie

Different means of limiting the fall in arterial Po₂ produced by single lung artificial ventilation were studied in 60 patients during thoracotomy. Changing from ventilating both lungs to the one healthy lung in the lateral recumbent position, without modifying tidal volume and frequency, brought about a fall in arterial Po₂ from 180±56 to 67±40 mmHg. The alveolar to arterial oxygen gradient increased to 110±45 mmHg (the alveolar oxygen pressure being calculated). Reducing the tidal volume so as to keep the inflation pressure at its initial level did not improve the arterial Po₂ but slightly increased the arterial Pco₂ (2.3 mmHg). The use of 6 to 8 cm H₂O positive end-expiratory pressure did not significantly modify the arterial Po₂ or Pco₂. Increasing the inspired oxygen fraction from 0.5 to 0.7 increased the arterial Po₂ from 100±89 mmHg to 165±59 mmHg, whilst the alveolar to arterial oxygen gradient increased to 118±60 mmHg. Clamping the pulmonary artery increased the arterial Po₂ and dual lung ventilation restored it to its initial value. Therefore, the only effective means of increasing oxygenation was to increase the inspired oxygen fraction. Unilateral continuous positive airway pressure was not used so as not to impair surgery. Dual lung ventilation may be necessary if the arterial Po₂ remains low.     

Circulatory dynamics during surface-induced hypothermia under halothane-ether azeotrope anesthesia

Circulatory dynamics during surface- induced deep hypothermia using the halothane-diethyl ether azeotrope in 100% oxygen (O2) without circulatory arrest and 95% O2 and 5% carbon dioxide (CO2) with and without 60 minutes of arrest were evaluated in 15 adult mongrel dogs. Mean arterial pressure was lower in animals given 5% CO2 than in animals given 100% O2 during cooling. Cardiac output in the 5% CO2 groups increased until 30 degrees C cooling and then gradually decreased to 29% of control at 20 degrees C. Cardiac output in the 100% O2 group progressively decreased to 16% of control at 20 degrees C cooling and was 51 to 77% of the output in the 5% CO2 animals at comparable temperatures throughout the hypothermia procedure. The differences in cardiac output were attributed primarily to changes in stroke volume since heart rates were not significantly different. These changes were probably secondary to differences in systemic vascular resistance, which had increased sixfold in the animals given 100% O2 and had only doubled in the 5% CO2 groups at 20 degrees C during cooling. Hemodynamic variables in animals given 5% CO2 did not reveal significant differences in arrested versus nonarrested animals during early rewarming. However, with further warming, cardiac output, stroke volume, left ventricular stroke work, and mean pulmonary arterial and pulmonary artery wedge pressures were lower, and systemic and pulmonary vascular resistances were higher in the arrest group. We conclude that the improved results with halothane-diethyl ether azeotrope in 95% O2 and 5% CO2 during surface hypothermia are due to a greater cardiac output and reduced peripheral vascular resistance.     

Evaluation de l'hématose dans l'insuffisance respiratoire aiguë: Mesure de la différence alvéolo-artérielle d'oxygène ou calcul du shunt ?

Information provided by computation of shunt and alveolar arterial oxygen differences have been compared in 58 épisodes of acute respiratory failure. In order to demonstrate the role of hemodynamic factors on pulmonary gas exchange, we compared blood gas measurements made in 29 patients with a high cardiac output and a reduced arteriovenous oxygen difference {C(a - v?)O₂ < 3.5 ml}, with 33 measurements corresponding to a low cardiac output and a widened C(a - v?)O₂ (> 6.5 ml). When the data was pooled together, the same P(A - a)O₂ corresponded to many different shunt values, depending on the level of mixed venous oxygenation (Pv?O₂). Q?s/Q?tot and P(A - a)O₂ were quasi linearly correlated only when they corresponded to patients with the same C(a - v?)O₂. For the same value of shunt, the PaO₂ was always raised when the Pv?O₂ was raised. As far as pulmonary gas exchange is concerned, shunt calculation in acute respiratory failure is preferable to P(A - a)O₂, especially when some hemodynamic disturbance is present.     

Functional preservation of the mammalian kidney. V. pharmacokinetics of dimethyl sulfoxide (1.4M) in kidneys (rabbit and dog) perfused at 37, 25, or 10 degrees C followed by transplantation (dog).

Rabbit and dog kidneys were perfused for 30 min at 37°C with 1.4 M [³H]Me₂SO in a K⁺-Mg²⁺?rich perfusate. Subsequently the kidneys were perfused for 30 min with Me₂SO-free perfusate. The rate of Me₂SO uptake and washout as well as Me₂SO distribution in the tissue were determined. It was found that equilibrium conditions were achieved within 30 min for both uptake and washout with $\text{T}\text{M}$ ratios approaching 1.0. The amount of Me₂SO in the cortex and medulla of rabbit kidneys was not significantly different. The same experiment was repeated with dog kidneys at 25 and 10°C. At these lower temperatures the rate of uptake and washout was significantly less, but the final concentration achieved within 30 min was the same as at 37°C. Dog kidneys flushed with a K⁺?Mg²⁺?rich solution, with or without 1.4 M dimethyl sulfoxide (Me₂SO), were kept at 10°C, then reimplanted in the autologous host, and an immediate contralateral nephrectomy was performed. Of the dogs receiving kidneys treated with Me₂SO-free solution, 86% survived; of the dogs receiving Me₂SO-treated kidneys, 75% survived. Dog kidneys were perfused for 30 min with a K⁺?Mg²⁺?rich solution, with or without 1.4 M Me₂SO, at 25 or 37°C. All kidneys were then perfused for 30 min with a Me₂SO-free solution at the same temperature used for the first perfusion. All kidneys were then reimplanted in the autologous host and an immediate contralateral nephrectomy was performed. Of the dogs receiving kidneys perfused at 25°C with Me₂SO-free solution, 43% survived; of the dogs receiving kidneys perfused with Me₂SO, 42% survived. Dog kidneys were also treated at 37°C in a manner similar to those at 25°C. Of the dogs receiving kidneys perfused at 37°C with Me₂SO-free solution, 80% survived; of the dogs receiving kidneys perfused with Me₂SO, 67% survived. Other results indicate that perfusion with a closed circuit is superior to perfusion with an open circuit. Also, gradual administration and washout of Me₂SO gives better renal survival than rapid changes in Me₂SO concentration.     

Mild Hypothermia Impairs Left Ventricular Diastolic but Not Systolic Function

Hypothermia is a component of myocardial protection during cardiopulmonary bypass (CPB) and cardioplegic arrest (CA). Patients in the early post CPB period often show mild hypothermia and cardiac dysfunction. We sought to investigate the impact of hypothermia on left ventricular (LV) function. Anesthetized dogs (n = 12) were instrumented with myocardial ultrasonic crystals and LV micromanometer. Systolic function was measured by preload recruitable stroke work (PRSW). Diastolic function was measured by ?dP/dt_max and tau. In six dogs (Norm group), body temperature was maintained at baseline levels. In another six dogs (Hypo group), body temperature dropped gradually over the time course of the experiment. The body temperature in the Hypo group decreased from 37.0 ± 0.3°C to 35.2 ± 1.0°C. ?dP/dt_max decreased and tau increased significantly with hypothermia but were stable in the Norm group. Both tau and ?dP/dt_max showed a linear relationship to the body temperature (r =.91 and r =. 93, respectively). PRSW did not change and cardiac output decreased with hypothermia. Thus, even mild hypothermia impairs LV diastolic but not systolic function. Cardiac output is temperature sensitive and therefore rewarming of patients post-CPB has priority.     

Hemorrhagic shock in dogs. Comparison of treatment with shed blood alone versus shed blood plus Ringer's lactate: intravascular pressures, cardiac output, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO2, electrolyte changes, and survival rates.

The purpose of our study of hemorrhagic shock in dogs was to examine the efficacy of adding Ringer's lactate to shed blood replacement in increasing animal rates. The standard Wiggers' hemorrhagic shock technic was used in two groups of ten animals each. Intravascular pressures, cardiac outut, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO2 and pH, electrolyte changes, and survival rates were determined. There was a positive correlation between changes in cardiac output, central venous oxygen content, and PO2 and extracellular fluid PO2 as measured using subcutaneously implanted Silastic tubing and perforated plastic balls. Four of the dogs that received shed blood alone survived, whereas five of the dogs that received shed blood plus Ringer's lactate survived. This difference was not statistically significant.     

Protective Effect of Continuous Retrograde Cerebral Perfusion on the Brain During Deep Hypothermic Systemic Circulatory Arrest

Deep hypothermic circulatory arrest has been widely used as an adjunct for surgery of the aortic arch to protect the brain and other vital organs. We introduced the use of continuous retrograde cerebral perfusion via the superior vena cava during deep hypothermic circulatory arrest in 1987 and have used it in 33 patients. Continuous retrograde cerebral perfusion times ranged from 10 to 89 minutes (mean 40.2 ± 22.5), and minimal nasopharyngeal temperatures ranged from 14 to 25°C (mean 17.4 ± 2.0). Two patients with a ruptured aneurysm died during operation due to bleeding and two other patients, with continuous retrograde cerebral perfusion time of 24 and 35 minutes, died 1 month postoperatively due to preoperative liver cirrhosis and sepsis. Two patients suffered from stroke. The remaining 27 patients, including 6 with from 60 to 82 minutes of continuous retrograde cerebral perfusion, had no complications related to continuous retrograde perfusion. During continuous retrograde cerebral perfusion, 66 pairs of blood samples from the perfusate and from the drainage back to the arch vessels were obtained. Analysis of these samples revealed that partial pressure of oxygen, saturation of oxygen, and oxygen content significantly decreased (p < 0.001), and partial pressure of carbon dioxide (CO₂) and CO₂ content significantly increased (p < 0.001). The nasopharyngeal temperature gradually increased at the rate of 0.01 to 0.03°C/min, but was maintained below 20°C. These results reflect the fact that the aerobic metabolism of the brain is maintained during continuous retrograde cerebral perfusion due to oxygen and substrate availability. This technique offers the potential of metabolic support to the brain during deep hypothermic circulatory arrest and prolongs the safe time limits of deep hypothermic circulatory arrest in surgery of the aortic arch. (J Card Surg 1994;9:584–595)     

THE INFLUENCE OF CARDIAC OUTPUT ON ARTERIAL OXYGENATION: A THEORETICAL STUDY

Recent measurements of cardiac output have shown that, duringanaesthesia, departures from normality are of common occurrence.In the presence of pulmonary venous admixture, such changesof cardiac output may affect the arterial Po₂ to a considerableextent. This paper explores the nature of the theoretical relationshipbetween cardiac output, percentage pulmonary venous admixture,and (A-a) Po₂ difference, and from the results draws certainconclusions: (1) Appreciable reductions in arterial Po₂ duringand after anaesthesia may be caused largely by reductions ofcardiac output. (2) When allowance is made for the probablechanges of cardiac output, it appears that the percentage pulmonaryvenous admixture during anaesthesia may not be greatly increasedabove the normal range. (3) Since with certain anaesthetic techniquesthere is a linear relationship between Pa_co2 and cardiac output,an increase of alveolar ventilation may under such circumstancescause a paradoxical decrease of the arterial Po₂.     

Effect of graded hemorrhage on renal cortical perfusion in dogs

Renal cortical tissue gas tensions, systemic oxygen supply and some features of energy metabolism and central hemodynamics were recorded in splenectomized dogs during graded hemorrhage and subsequent reinfusion of shed blood. Renal cortical partial pressure of oxygen and carbon dioxide responded rapidly to changes in blood volume and cardiac output. Lowest cortical partial pressure of oxygen values and highest cortical partial pressure of carbon dioxide levels were achieved at a maximal 50 percent blood loss. The decrease in arterial pressure, blood hemoglobin and hematocrit as well as the increase in blood lactate concentration lagged behind blood loss. Renal cortical partial pressure of oxygen, arterial pressure and cardiac output responded rapidly to reinfusions of withdrawn blood, while the cortical partial pressure of carbon dioxide, heart rate, arterial pH and blood lactate concentration returned to initial levels more slowly. Arterial blood gases remained normal throughout the observation period and did not provide an adequate index of tissue oxygenation. In contrast, the partial pressure of oxygen of the renal cortex proved an excellent and sensitive indicator of renal perfusion during hemorrhagic shock and its management.     

Long-term studies of hemoglobin-oxygen affinity in hypoxemic dogs with a right-to-left cardiac shunt

Long-standing hypoxemia was surgically created in dogs by inserting an aortic homograft between the inferior vena cava and right atrium. Ligation of the caval—atrial junction resulted in a right-to-left cardiac shunt. Arterial p O₂ fell immediately and P₅₀ increased within 20 min. The 2,3-diphosphoglycerate concentration rose in 4 hr following surgery, while hemoglobin concentration increased within 7 days. Alterations in hemoglobin—oxygen affinity can occur rapidly and may be beneficial compensatory responses to acute and chronic hypoxemia caused by a right-to-left cardiac shunt.     

Circulation in profound hypothermia

Circulation was maintained in dogs at 5°C using a noninvasive pulsatile pumping system (MVA) and studied using ^99mTechnetium-labeled microspheres. Cardiac output, blood pressure, and stroke volume decreased as temperature fell and peripheral resistance increased.Seven of eight dogs were successfully resuscitated after rewarming but cardiac output and blood pressure remained low and peripheral resistance remained high.The distribution of cardiac output increased to the heart (×3) and brain (×2) and decreased or remained the same in other organs at 5°C.Blood flow in the heart and brain remained high at 5°C, despite a low cardiac output. After rewarming, blood flow was normal in the heart but remained low in the brain, kidney, and gastrointestinal tract. Circulation in profound induced hypothermia may be similar to circulation in deep hibernation.