GSTM1 and stroke disorder: Unfortunately, while many of these HBOCs showed promise in early clinical trials [15,28,30,31], they eventually failed Phase III clinical trials due to severe adverse effects, such as hypertension, myocardial infarction, stroke, renal damage and tissue toxicity, which are caused by rapid Hb oxidation and scavenging of the vasodilator nitric oxide by Hb [28,32,33,34].