Diaspirin-crosslinked hemoglobin reduces mortality of severe hemorrhagic shock in pigs with critical coronary stenosis

Häbler, O.; Kleen, M.; Pape, Andreas; Meisner, Franz; Kemming, Gregor; Meßmer, K.

doi:10.1097/00003246-200006000-00034

Cited by 34 publications

(36 citation statements)

References 23 publications

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“…In addition, the myocardial blood flow values as well as the ratio of sub-endocardial to subepicardial blood flow were found in good agreement with the data obtained in previous studies [12][13][14][15][16][17].…”

Section: Discussionsupporting

confidence: 90%

Comparison of Regional Blood Flow Values Measured by Radioactive and Fluorescent Microspheres

Thein¹,

Raab²,

Harris³

et al. 2002

Eur Surg Res

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Fluorescent microspheres (FM) have become an attractive alternative to radioactive microspheres (RM) for the measurement of regional blood flow (RBF). The aim of the present study was to investigate the comparability of both methods by measuring RBF with FM and RM. Eight anaesthetised pigs received simultaneous, left atrial injections of FM and RM with a diameter of 15 µm at six different time points. Blood reference samples were collected from the descending aorta. RBF was determined in tissue samples of the myocardium, spleen and kidneys of all 8 animals. After radioactivity of the tissue samples was determined, the samples were processed automatically for measuring fluorescence using a recently developed filter device (SPU). RBF was calculated with both the isotope and spectrometric data of both methods for each sample resulting in a total of 10,512 blood flow values. The comparison of the RBF values yielded high linear correlation (mean r² = 0.95 ± 0.03 to 0.97 ± 0.02) and excellent agreement (bias 5.4–6.7%, precision 9.9– 16.5%) of both methods. Our results indicate the validity of MS and of the automated tissue processing technique by means of the SPU.

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Section: Discussionsupporting

confidence: 90%

Comparison of Regional Blood Flow Values Measured by Radioactive and Fluorescent Microspheres

Thein¹,

Raab²,

Harris³

et al. 2002

Eur Surg Res

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“…Parts of the results of this extensive study have already been published [6,16]. Briefly, it was demonstrated that all animals treated with DCLHb survived the observation period after completion of fluid resuscitation, whereas 5 out of 10 HSA-treated animals died of acute LV failure within 20 min after termination of resuscitation.…”

Section: Resultsmentioning

confidence: 96%

“…appendix). The myocardial perfusion was assessed by the radioactive microsphere technique which has already been described in detail elsewhere [6,15,16].…”

Section: Parametersmentioning

confidence: 99%

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Diaspirin Cross-Linked Hemoglobin Fails to Improve Left Ventricular Diastolic Function after Fluid Resuscitation from Hemorrhagic Shock

et al. 2001

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In severe hemorrhagic shock, left ventricular (LV) diastolic dysfunction is an early sign of cardiac failure due to compromised myocardial oxygenation. Immediate fluid replacement or, in particular, administration of a hemoglobin-based oxygen carrier (diaspirin cross-linked hemoglobin; DCLHb) improves myocardial oxygenation; therefore, positive effects on LV diastolic function could be expected. The effects of fluid resuscitation from severe hemorrhagic shock with DCLHb were investigated in 20 anesthetized domestic pigs. After generation of a critical left anterior descending coronary artery stenosis (narrowing of the artery until disappearance of reactive hyperemia after a 10-second complete vessel occlusion), hemorrhagic shock (mean arterial blood pressure 45 mm Hg) was induced within 15 min by controlled blood withdrawal and maintained for 60 min. Fluid resuscitation consisted of replacement of the plasma volume withdrawn during hemorrhage by infusion of either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). After completion of resuscitation, an observation period of 60 min elapsed. Measurements of central hemodynamics, myocardial oxygenation, and LV diastolic function were performed at baseline, after induction of critical coronary artery stenosis, after 60 min of hemorrhagic shock, immediately after resuscitation, and 60 min later. While 5 out of 10 animals treated with HSA died within the first 20 min after fluid resuscitation from acute LV pump failure, all DCLHb-treated animals survived until the end of the protocol (p < 0.05). Despite superior myocardial oxygenation due to augmentation of the arterial O₂ content as well as of coronary perfusion pressure, no beneficial effects on LV diastolic function were observed after infusion of DCLHb. Peak velocity of LV pressure decrease (dp/dt_min) did not reveal significant differences between the two groups. Immediately after completion of fluid resuscitation with DCLHb, the time constant of LV diastolic relaxation (τ) was prolonged when compared with HSA-treated animals (p < 0.05), indicating retardation of early LV diastolic relaxation. Our data suggest that DCLHb fails to improve LV diastolic function after fluid resuscitation from severe hemorrhagic shock. However, positive effects on myocardial perfusion and oxygenation result in a significant reduction of the mortality of severe hemorrhagic shock.

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“…26 In experimental studies on severe shock, resuscitation using HBOCs consistently stabilized the hemodynamics and tissue oxygenation. 27 The potential uses for HBOCs in the future include cases of shock, organ ischemia, red blood cell incompatibility, acute lung injury, transplant organ preservation, sickle cell anemia, tumor therapy and air embolism. 6 The potential advantages offered by oxygen carriers include universal compatibility, one to three years of shelf life compared with 42 days for blood cells, the ability to be produced in large quantities, a manufacturing process that can reduce the risk of infectious agents, reduced dependence on donor blood supplies and an alternative for patients who will not accept transfusions of red blood cells, such as Jehovah's Witnesses.…”

Section: Final Considerationsmentioning

confidence: 99%

Artificial oxygen carriers as a possible alternative to red cells in clinical practice

et al. 2009

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Fluid resuscitation is intended to eliminate microcirculatory disorders and restore adequate tissue oxygenation. The safety limits for a restrictive transfusion policy are given by patients' individual tolerance of acute normovolemic anemia. Artificial oxygen carriers based on perfluorocarbon or hemoglobin are attractive alternatives to allogenic red blood cells. There are many risks involved in allogenic blood transfusions and they include transmission of infections, delayed postoperative wound healing, transfusion reactions, immunomodulation and cancer recurrence. Regardless of whether artificial oxygen carriers are available for routine clinical use, further studies are needed in order to show the safety and efficacy of these substances for clinical practice.

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Diaspirin-crosslinked hemoglobin reduces mortality of severe hemorrhagic shock in pigs with critical coronary stenosis

Abstract: Fluid resuscitation with 10% DCLHb solution completely reverses hemorrhagic shock-induced subendocardial ischemia and hypoxia in the presence of compromised coronary circulation and thereby prevents early death after resuscitation.

Cited by 34 publications

References 23 publications

Comparison of Regional Blood Flow Values Measured by Radioactive and Fluorescent Microspheres

Comparison of Regional Blood Flow Values Measured by Radioactive and Fluorescent Microspheres

Diaspirin Cross-Linked Hemoglobin Fails to Improve Left Ventricular Diastolic Function after Fluid Resuscitation from Hemorrhagic Shock

Artificial oxygen carriers as a possible alternative to red cells in clinical practice

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