The present invention relates to the prevention of cardiovascular and central nervous system side effects in mammals who receive transfusions of hemoglobin based oxygen carriers (HBOC) or stored blood products containing a concentration of hemoglobin sufficient to induce vasoconstriction, by adding a vasoactivity reducing effective amount of one or more phosphodiesterase inhibitors in combination with a calcium channel blocker and/or an alpha agonist, to the circulation, or alternatively to the HBOC or stored blood, thereby preventing the manifestation of vasoactivity attributable to the presence of free tetrameric hemoglobin (Hb).