title: Diaspirin cross-linked hemoglobin fails to improve left ventricular diastolic function after fluid resuscitation from hemorrhagic shock.
abstract: 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 Fluid resuscitation consisted of replacement of the plasma volume withdrawn during hemorrhage by infusion of either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10).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 O(2) 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 (tau) 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.
authors.affiliation: Clinic of Anaesthesiology, Ludwig Maximilians University, Munich, Germany. andreas.page@helios.med.uni-muenchen.de
authors.forename: A
authors.initials: A
authors.lastname: Pape
authors.forename: G
authors.initials: G
authors.lastname: Kemming
authors.forename: F
authors.initials: F
authors.lastname: Meisner
authors.forename: M
authors.initials: M
authors.lastname: Kleen
authors.forename: O
authors.initials: O
authors.lastname: Habler
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D001802:Blood Substitutes / Q000627:therapeutic use*; D023921:Coronary Stenosis / Q000503:physiopathology; D003971:Diastole; D005260:Female; D005440:Fluid Therapy; D006454:Hemoglobins / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D012151:Resuscitation; D012709:Serum Albumin / Q000627:therapeutic use; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy*; D013552:Swine; D017211:Treatment Failure; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D012709:Serum Albumin; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin