HMOX1 and ischemia: The tissue protective capacity of HO-1 is underscored by observations that isolated myocardium from homozygous knockout mice for the gene encoding the protein for this enzyme (HO-1−/−) exhibited significantly higher cellular damage and incidence of ventricular fibrillation in comparison with myocardium from heterozygous (HO-1+/−) and wild-type mice (HO-1+/+) in studies using isolated mouse hearts mounted in the Langendorf apparatus and subjected to ischemia followed by reperfusion, thus demonstrating the cytoprotective capacity of this major mechanism for clearance of unreacted heme [74,75].