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: The endocrine response is an important component of the physiological response to blood loss. There is some variability in reported levels of certain hormones during hemorrhage such as the stress hormone adrenocorticotrophic hormone (ACTH). Therefore, the effect of two anesthetic agents, ketamine and saffan, on ACTH and beta-endorphin levels during hemorrhage was assessed in 12 minipigs. The animals were divided into two groups, group I saffan and group II ketamine (n=6). Pigs were subjected to a continuous fixed volume hemorrhage under one of the above anesthetics while spontaneously breathing. Blood pressure and heart rate responses were recorded together with beta-endorphin and ACTH levels both before and at 10, 20, 30, 40 min after the onset of bleeding. ACTH levels were higher in the ketamine-anesthetized pigs and rose significantly faster with falling blood pressure than ACTH measured in pigs under saffan anesthesia. In contrast, the hemorrhage induced beta-endorphin increase was not significantly different between the two anesthetic groups. These results indicate that choice of anesthetic agent is important when investigating the hormone response to hemorrhage and may account for the variable hormone levels in the published literature to date.
Physiological research / Academia Scientiarum Bohemoslovaca 01/2009; 58(6):799-805. · 1.29 Impact Factor
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