Potential limitation of angiogenic therapies is the potential effect of the treatment on neural networks of the heart. It is entirely possible that the pro-angiogenic therapies also induce alterations in nerves producing arrhythmias. As a result, potential sudden deaths and other potential arrhythmia-based problems should be carefully monitored. Also, large animals do not have comorbidities that the patients might possess. For instance, reactions to angiogenic stimuli significantly vary in the ischemic and normoxic myocardium. Rapid growth of heart also causes challenges, as relatively young tissue is more resistant to injury and can regenerate better than tissues in elderly patients.