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For the past thirty years, hemoglobin-based oxygen carriers (HBOCs) have been under development as a red blood cell substitute. Side-effects such as vasoconstriction, oxidative injury, and cardiac toxicity have prevented clinical approval of HBOCs. Recently, high molecular weight (MW) polymerized human hemoglobin (PolyhHb) has shown positive results in rats. Studies have demonstrated that high MW PolyhHb increased O2 delivery, with minimal effects on blood pressure, without vasoconstriction, and devoid of toxicity. In this study, we used guinea pigs to evaluate the efficacy and safety of high MW PolyhHb, since like humans guinea pigs cannot produce endogenous ascorbic acid, which limits the capacity of both species to deal with oxidative stress. Hence, this study evaluated the efficacy and safety of resuscitation from severe hemorrhagic shock with high MW PolyhHb, fresh blood, and blood stored for 2 weeks. Animals were randomly assigned to each experimental group, and hemorrhage was induced by the withdrawal of 40% of the blood volume (BV, estimated as 7.5% of body weight) from the carotid artery catheter. Hypovolemic shock was maintained for 50 min. Resuscitation was implemented by infusing 25% of the animal’s BV with the different treatments. Hemodynamics, blood gases, total hemoglobin, and lactate were not different before hemorrhage and during shock between groups. The hematocrit was lower for the PolyhHb group compared to the fresh and stored blood groups after resuscitation. Resuscitation with stored blood had lower blood pressure compared to fresh blood at 2 h. There was no difference in mean arterial pressure between groups at 24 h. Resuscitation with PolyhHb was not different from fresh blood for most parameters. Resuscitation with PolyhHb did not show any remarkable change in liver injury, inflammation, or cardiac damage. Resuscitation with stored blood showed changes in liver function and inflammation, but no kidney injury or systemic inflammation. Resuscitation with stored blood after 24 h displayed sympathetic hyper-activation and signs of cardiac injury. These results suggest that PolyhHb is an effective resuscitation alternative to blood. The decreased toxicities in terms of cardiac injury markers, vital organ function, and inflammation following PolyhHb resuscitation in guinea pigs indicate a favorable safety profile. These results are promising and support future studies with this new generation of PolyhHb as alternative to blood when blood is unavailable.

Additional file 1. Representative photomicrographs of gastrocnemius muscle incubated for myofibrillar ATPase activity to determine fiber typing and with Oil red to measure lipid deposition.

This study sought to determine the role of physical training (PT) on body weight (BW), energy balance, histological markers of nonalcoholic fatty liver disease (NAFLD) and metabolic gene expression in the liver of ob/ob mice. Adult male ob/ob mice were assigned into groups sedentary (S; n = 8) and trained (T; n = 9). PT consisted in running sessions of 60 min at 60% of maximal speed conducted five days per week for eight weeks. BW of S group was higher from the 4(th) to 8(th) week of PT compared to their own BW at the beginning of the experiment. PT decreased daily food intake and increased resting oxygen consumption and energy expenditure in T group. No difference was observed in respiratory exchange ratio, but the rates of carbohydrate and lipids oxidation, and maximal running capacity were greater in T than S group. Both groups showed liver steatosis but not inflammation. PT increased CPT1a and SREBP1c mRNA expression in T group, but did not change MTP, PPAR-α, PPAR-γ, and NFKB mRNA expression. In conclusion, PT prevented body weight gain in ob/ob mice by inducing negative energy balance and increased physical exercise tolerance. However, PT did not change inflammatory gene expression and failed to prevent liver steatosis possible due to an upregulation in the expression of SREBP1c transcription factor. These findings reveal that PT has positive effect on body weight control but not in the liver steatosis in a leptin deficiency condition.