Microvascular changes in young hamsters after single heterochronic blood transfusion of one unit of blood

Abstract

Aging is the most significant risk factor for many chronic diseases. Studies of heterochronic blood exchange show that blood and plasma from old-age animals have senescent effects in young mice. However, the underlying mechanisms of how bloodborne factors promote aging remain largely unknown, and studies of blood transfusions' effects on donors of different ages are currently unavailable. This study aimed to compare the microcirculatory effects of blood transfusions from young or old donors in anemic young animals. Blood was collected from anesthetized young (8 weeks old) and older (52-60 weeks old) golden Syrian hamsters via cardiac puncture into CP2D (from an AS-3 blood preparation kit). The supernatant and buffy coat were removed. The AS-3 additive was added according to manufacture instructions, and packed red cells were mixed gently. For microhemodynamic studies, young golden Syrian hamsters instrumented with a dorsal window chamber were subjected to an isovolemic hemodilution of 30% of the animal's blood volume with 5% human serum albumin to induce a normovolemic anemic state. The next day, the anemic animals were randomly assigned to young or older blood and received a transfusion of a volume equivalent to a single unit of red cells. The microhemodynamics in arterioles lower and greater than 60 μm and venules between 20 and 80 μm and functional capillary density (FCD) were measured. Hemodilution acutely reduced hematocrit (Hct) to 60% of the baseline and increased microvascular blood flow in venules and arterioles while decreasing the FCD. Transfusion of young or old donors’ blood increased the Hct. There was no significant change post-transfusion in the diameter or the flow of the arterioles in the young donors' blood group compared to old donors’ blood. The animals transfused with blood from young donors restored venules flow and diameter similarly to baseline (pre-anemia). However, the old donors’ blood group did not show the same recovery. More importantly, the FCD significantly improved after younger donors' blood transfusions compared to the old ones. These results suggest that recovery from anemia is improved when using blood from younger donors, as this ensures higher FCD and supports proper tissue homeostasis. This study intentionally tried to recapitulate how blood is processed in the USA and transfuse only a conservative amount of blood into anemic animals. Studies have shown that heterochronic parabiosis (surgically joining younger and older animals in which blood, organs, and environments are shared) or a blood exchange rejuvenates old tissues. Here using a heterochronic blood transfusion, we show that the donor's age determines the recovery of FCD after transfusion. These deficits could be due to capillary collapse preventing oxygen from arriving uniformly through the tissue, as the FCD determines the microvascular oxygen diffusion field. Future studies will look at the implication of the recovery of FCD after transfusion. This study was supported by National Institutes of Health grants R01HL162120, R01HL159862 and the Department of Defense under grants W81XWH1810059. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.