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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.

We have described whole body oxygen (O2) extraction ratio (ER) as a reliable indicator of transfusion need in acute normovolemic anemia. In normal hearts, myocardial lactate production (-LACT), indicating anaerobic metabolism, does not occur until the ER greater than 50% and Hct less than 10%. It is not known if the ER is valid in the setting of limited coronary vascular reserve. This study assesses the effect of a critical left anterior descending (LAD) coronary stenosis on the compensation to acute blood loss anemia. Adult dogs were anesthetized, paralyzed, and mechanically ventilated. A critical LAD stenosis was created in seven animals (STEN). There were seven controls (CON). Animals underwent isovolemic exchange transfusion with 6% HES until cardiac failure (CF). Catheters were placed in the aorta, pulmonary artery, and anterior interventricular coronary vein. Cardiac failure occurred at Hct = 8.6% +/- 0.4% in the CON and 17.0% +/- 0.5% in the STEN animals. Cardiac output increased in the CON, but not in the STEN animals. Blood flow in the LAD increased in the CON but not the STEN animals. -LACT began in the CON and STEN animals at Hct less than 20% and coincided with an ER greater than 50% in both groups. We conclude that CF occurs at a higher hematocrit with a critical LAD stenosis. The whole body ER greater than 50% remains a valid indicator of myocardial metabolism in anemia in the presence of limited coronary vascular reserve. The ER may be a useful guide to transfusion therapy.

Risks inherent in the administration of blood products have increased efforts to avoid homologous transfusion. Although this has increased interest in autologous transfusion and intraoperative salvage, little attention has been focused on efforts to enhance endogenous erythropoiesis as a method of minimizing exposure to homologous blood. Recombinant human erythropoietin (rHuEPO) has been shown to enhance erythropoiesis. The purpose of this study is to evaluate the effect of rHuEPO, administered postoperatively, on a model of acute blood loss. Eleven adult male baboons were randomized into two groups. All animals underwent a laparotomy and an exchange transfusion, with 6% hetastarch, to a final hematocrit of 15%. Group I (N = 6) received 1,000 units/kg of recombinant human erythropoietin daily for the first 14 postoperative days. Group II (N = 5) received an equivalent volume of placebo. All animals were given supplemental vitamin B12, folate and 200% of shed iron, as iron dextran IV, after exchange transfusion. Response was observed for a period of 35 days. All animals survived the protocol. There were no adverse reactions to rHuEPO or surgical complications. The hematocrits were similar between groups at baseline and after exchange transfusion. The maximal rate of erythropoiesis was significantly faster in the rHuEPO group (2.1 vs. 1.3%/day; p less than 0.01). The time required to return to hematocrits of 30% (9.9 vs. 17.4 days, p less than 0.001) and to baseline hematocrits (11.9 vs. 32.1 days, p less than 0.01) were both significantly shorter in the rHuEPO group. The data show that rHuEPO accelerates the recovery from anemia in the postoperative setting. Acceleration of erythropoiesis represents another alternative to homologous transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

We have prepared a polymerized pyridoxylated hemoglobin solution (Poly SFH-P) with a normal [Hb] of 14 gm/dl and a normal COP of 20 torr. Although this normal [Hb] is a significant improvement over prior products, the P50 of 16-20 torr raises a concern about the ability of Poly SFH-P to effectively transport O2 in the presence of red cells with their normal P50 of 26 torr. This study quantitatively assessed the contribution of Poly SFH-P to total O2 delivery and consumption in the clinically relevant range of hematocrits. The results document that Poly SFH-P supports life at zero hematocrit, and makes significant contributions to total O2 delivery and consumption in the presence of red cells. Poly SFH-P permits a higher plasma [Hb], and has a longer intravascular persistence than any unpolymerized hemoglobin solution. Poly SFH-P is thus an effective O2 carrier, and offers greater potential than prior products as a clinically useful red cell substitute.

Stroma-free hemoglobin (SFH) and Fluosol-DA (FL-DA) are the two acellular oxygen carriers that represent potential red cell substitutes. Although both can support life at zero hematocrit, their effectiveness as O2 carriers at intermediate hematocrits has been unclear. In the presence of red cells, the efficacy of an acellular O2 carrier can be assessed by its contribution to O2 delivery and O2 consumption. This study evaluated the efficacy of SFH and FL-DA in the presence of red cells at hematocrits less than or equal to 10%. The results illustrate that SFH and FL-DA do contribute to O2 delivery and O2 consumption in the presence of red cells. The data indicate that SFH and FL-DA are both effective acellular O2 carriers.

We have previously reported on the efficacy of a 20% fluorocarbon emulsion (Fluosol-DA, 20%) as an acellular O2 carrier at an FIO2 = 1.0. We are concerned, however, about the potential O2 toxicity that may result from extended exposure to FIO2 = 1.0. The O2 content of the fluorocarbon phase is linearly related to both the FIO2 and the fluorocarbon concentration (Fct). It should therefore be possible to maintain the same O2 content by raising the Fct using a higher fluorocarbon concentration and lowering the FIO2. The purpose of this report is to assess the ability of a 35% fluorocarbon emulsion (Fluosol-DA, 35%) at an FIO2 = 0.6 to support hemodynamics and O2 transport. Five adult baboons were paralyzed, anesthetized, intubated, and mechanically ventilated at FIO2 = 0.6. An isovolemic total exchange transfusion (E.T.) with Fluosol-DA, 35% was performed. Measurements were made at Hct's of 20, 10, 5, and less than 2%. All animals survived the exchange. Total arterial O2 content fell from 17.4 +/- 0.7 to 3.3 +/- 0.2 vol% (p less than 0.01), and O2 delivery decreased from 21.8 +/- 2.2 to 5.1 +/- 0.7 cc/min-kg (p less than 0.01) during the exchange. There was no significant change in MAP, H.R., C.O., or VO2 during the exchange transfusion. Fluosol-DA, 35% maintains normal hemodynamics and O2 transport despite a marked fall in arterial O2 content and total O2 delivery. Fluosol-DA, 35% is thus an effective O2 carrier at the safe FIO2 of 0.6.

Pulmonary dysfunction is a well-recognized sequela of sepsis, which has been quantitated by calculation of intrapulmonary shunt (Qs/Qt) and, more recently, by measurement of extravascular lung water (EVLW). We sought to demonstrate the relationship between Qs/Qt and EVLW in sepsis. Nine pigs were given live E. coli infusions and five control pigs received only crystalloid. Pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), arterial blood gases (ABG), and mixed venous blood gas levels were measured serially and Qs/QT calculated. EVLW was measured simultaneously using the thermal-green dye technique. The septic group showed increases from baseline in PAP (2.4 X), EVLW (2x), and Qs/Qt (1.6x). Regression analysis of Qs/Qt or EVLW yielded a correlation coefficient of r = 0.48. We concluded that while sepsis can result in both increased EVLW and Qs/Qt, the correlation is not sufficiently strong to account for the increased Qs/Qt on the basis of elevated EVLW alone. The possible relationships of arterial hypoxemia and pulmonary edema, ventilation-perfusion mismatch, and alterations in the normal hypoxic vasoconstrictive response in sepsis are considered.