Serological Alterations Enables Hemin to Preserved Cardiac Function in Response to Pressure Overload

We reported previously that hemin, a substrate for erythropoiesis and an agonist of HO‐1 activity, not only reduces the hypertrophic response to chronic pressure overload (PO) in rat, but also enhances cardiac performance. Here, we investigated whether serological changes and alterations in hemoglobin:oxygen binding may be associated with beneficial effects of hemin. Animals were subjected to banding of the ascending aorta and treated with hemin (75 μg/Kg) for 2 consecutive days prior‐ and every 3 days after banding. Hemin treated rats showed a 15% increase in hematocrit compared to untreated banded rats (47 vs 55% P < 0.001, respectively). The hemoglobin oxygen dissociation curve for the hemin banded shows significant leftward shift (at isocapnic and isohydric) thus enabling enhanced unloading of oxygen (PO 2 50 42.2 mmHg) compared to sham and untreated banded animals (PO 2 50 34.6 and 35.2 mmHg, respectively). Analysis of sera consistently revealed lower levels of LDL and triglycerides in the banded animals treated with hemin but not in the sham or buffer‐treated control animals. Taken together, our data suggests the enhanced oxygen unloading may enable the myocardium to utilize more fat to chronically maintain higher levels of cardiac performance. Supported by grants from CIHR and HSFO to LG Melo and CA Ward.