Immunohistochemical expression of HIF-1alpha in response to early myocardial ischemia.

ABSTRACT

This study aims to evaluate the effects of ischemia on the myocardial fibers and the expression of the transcriptional factor for angiogenesis hypoxia-inducible factor-1 alpha (HIF-1alpha) in human heart specimens. We have prospectively analyzed the HIF-1alpha expression in human ischemic hearts with the ABC-inmunohistochemistry technique and amplification by biotinylated tyramide. The relationship between the expression of HIF-1alpha and the temporal evolution of ischemia has also been evaluated. As pathomorphological diagnosis of early myocardial ischemia has many problems in human autopsy material with less than 4 to 6 h after clinical onset, we suggest that HIF-1alpha is helpful in the early acute myocardial infarction diagnosis, so it stains necrotic areas within the first 2 h. The amplification procedure provides a higher intensity of the final staining without losing specificity. It is concluded that in normal cardiac fibers, basal expression of HIF-1alpha is not appreciable, but it steadily increases after ischemia. With regard to the practical applicability in forensic field, our observations suggest that positive immunohistochemical expression of HIF-1alpha on heart samples may be used as a reliable indicator of myocardial damage in cases without cardiac lesion evidence, using conventional microscopy. This method is especially useful and may provide definitive proof of myocardial ischemia in unexpected deaths without previous symptoms, or in forensic cases with a short period of clinical manifestations. In addition, it may have been involved in possible future cardiovascular therapies.