Hemoglobin-based oxygen carrier (HBOC) resuscitation has been associated with increased systemic and pulmonary vascular resistances (SVR, PVR), which may result in reduced blood flow and severe pulmonary hypertension. The physiologic and immunologic properties of 7.5% hypertonic saline solution (HTS), such as reduction of SVR and PVR, as well as inhibition of neutrophil and endothelial activation may be beneficial in reducing some of these undesirable effects of HBOCs. The aim of this study was to evaluate the hemodynamic effects of the HBOC and HBOC-201 suspended in 7.5% hypertonic saline solution (HT-HBOC) when compared with standard HBOC resuscitation.
Thirty-two domestic crossbred pigs (50-60 kg) were hemorrhaged to a mean arterial pressure (MAP) of 35 mm Hg +/- 5 mm Hg for 45 minutes and resuscitated to a baseline mean arterial pressure using the following groups: (1) sham, no hemorrhage; (2) shed blood + lactated Ringer's solution; (3) standard HBOC-201; (4) hypertonic saline 7.5%; (5) hypertonic 7.5% HBOC-201. After resuscitation, observation was continued for 4 hours. Hemodynamic variables, oxygen consumption, and arterial blood gases were monitored continuously. Data were analyzed using analysis of variance.
SVR (p = 0.001), PVR (p = 0.001), and MPAP (p = 0.01) were significantly reduced in the HT-HBOC group compared with the standard HBOC group.
In this model of hemorrhagic shock, hypertonic HBOC-201- resuscitated pigs had significantly reduced SVR and PVR, as well as mean pulmonary artery pressure (MPAP) and increased cardiac output. HT-HBOC may be beneficial in reducing the undesirable effects of standard HBOC-201. The mechanisms of these beneficial effects need to be investigated.
[Show abstract][Hide abstract] ABSTRACT: Hypertonic saline may be administered in the setting of lung transplantation but may affect the development of ischemia-reperfusion lung injury. This study investigated the effects of the pre-treatment by intravenous hypertonic saline in a pig model of single lung ischemia-reperfusion.
Forty-three pigs (34 +/- 4 kg) under mechanical ventilation were randomly assigned to a left lung ischemia-reperfusion alone or preceded by 4-ml/kg 7.5% hypertonic saline, 33-ml/kg normal saline, or by the infusion of the vasodilator nicardipine. Animals without ischemia served as controls. After euthanasia, the left lung was sampled for histologic analysis and measurement of lung water and alveolar-capillary permeability.
Ischemia-reperfusion resulted in high-permeability pulmonary edema, hypoxemia, and increased interleukin-6 serum level. Hypertonic saline pre-treatment worsened pulmonary edema of the left lung (6.6 +/- 0.7 vs 4.8 +/- 0.8 ml/kg of body weight, p < 0.05) and resulted in a higher ratio of the protein level in the alveolar fluid to the serum protein level (0.41 +/- 0.04 vs 0.21 +/- 0.09, p < 0.05) and in a higher histologic damage score (11 [range, 9-11.75] vs 6.5 [range, 4.5-7.5], p < 0.05) without promoting pulmonary or systemic inflammation. Lung injury was affected neither by normal saline nor by nicardipine pre-treatment. Nicardipine did not influence the deleterious effect of hypertonic saline.
Pre-treatment by intravenous hypertonic saline worsened ischemia-reperfusion lung injury independently of its effects on the cardiac index or pulmonary circulation but probably through a direct effect of hyperosmolarity on endothelial permeability.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2008; 27(9):1023-30. DOI:10.1016/j.healun.2008.07.004 · 6.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemoglobin-based oxygen-carrying solutions (HBOC) provide emergency alternatives to blood transfusion to carry oxygen to tissues without the risks of disease transmission or transfusion reaction. Two primary concerns hampering the clinical acceptance of acellular HBOC are the occurrence of systemic and pulmonary vasoconstriction and the maintenance of the heme-iron in the reduced state (Fe2+). We recently demonstrated that pretreatment with inhaled nitric oxide prevents the systemic hypertension induced by HBOC-201 (polymerized bovine hemoglobin) infusion in awake mice and sheep without causing methemoglobinemia. However, the impact of HBOC-201 infusion with or without inhaled nitric oxide on pulmonary vascular tone has not yet been examined.
The pulmonary and systemic hemodynamic effects of breathing nitric oxide both before and after the administration of HBOC-201 were determined in healthy, awake lambs.
Intravenous administration of HBOC-201 (12 ml/kg) induced prolonged systemic and pulmonary vasoconstriction. Pretreatment with inhaled nitric oxide (80 parts per million [ppm] for 1 h) prevented the HBOC-201--induced increase in mean arterial pressure but not the increase of pulmonary arterial pressure, systemic vascular resistance, or pulmonary vascular resistance. Pretreatment with inhaled nitric oxide (80 ppm for 1 h) followed by breathing a lower concentration of nitric oxide (5 ppm) during and after HBOC-201 infusion prevented systemic and pulmonary vasoconstriction without increasing methemoglobin levels.
These findings demonstrate that pretreatment with inhaled nitric oxide followed by breathing a lower concentration of the gas during and after administration of HBOC-201 may enable administration of an acellular hemoglobin substitute without vasoconstriction while preserving its oxygen-carrying capacity.
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