Chronic limb-threatening ischemia could benefit from growth hormone therapy for wound healing and limb salvage

Abstract

Revascularization for chronic limb-threatening ischemia (CLTI) is necessary to alleviate symptoms and wound healing. When it fails or is not possible, there are few alternatives to avoid limb amputation in these patients. Although experimental studies with stem cells and growth factors have shown promise, clinical trials have demonstrated inconsistent results because CLTI patients generally need arteriogenesis rather than angiogenesis. Moreover, in addition to the perfusion of the limb, there is the need to improve the neuropathic response for wound healing, especially in diabetic patients. Growth hormone (GH) is a pleiotropic hormone capable of boosting the aforementioned processes and adds special benefits for the redox balance. This hormone has the potential to mitigate symptoms in ischemic patients with no other options and improves the cardiovascular complications associated with the disease. Here, we discuss the pros and cons of using GH in such patients, focus on its effects on peripheral arteries, and analyze the possible benefits of treating CLTI with this hormone.

Cognitive Evolution of a Patient Who Suffered a Subarachnoid Haemorrhage Eight Years Ago, after Being Treated with Growth Hormone, Melatonin and Neurorehabilitation

“…Most likely, if we had been able to treat this patient earlier and without interruptions, the positive results would have been reached sooner; but in any case, our data indicate that there is not a plateau for reaching significant improvements after a brain injury. Moreover, short-term treatments with GH are useful and safe, as we demonstrated previously, even in the case that the patient is not GH-deficient [6,26,27,60]. In addition, although GH replacement therapy has been related to the related to the future development of stroke [61], more recent studies rule out this possibility [62,63].…”

“…Particularly, the hormone plays a significant role at the cognitive level [25][26][27][38][39][40][41][42][43][44], even in the case that no GH-deficiency exists. Moreover, GH is an inducer of endothelial production of the vasodilator NO and recovers endothelial dysfunction [6,37,45]. Therefore, this hormone might be of utility in the prevention of the cascade of deleterious effects subsequent to SAH but also to recover the arteries most likely damaged in the case of our patient.…”

“…Since most brain aneurysms develop throughout adult life [5], it is likely that they are a consequence of arterial affectations produced by the current habits of life (nutrition, smoking, alcohol intake, etc.) [6], factors that also imply a risk for the rupture of an existing aneurysm [1].…”

Why Should Growth Hormone (GH) Be Considered a Promising Therapeutic Agent for Arteriogenesis? Insights from the GHAS Trial

“…GH significantly increases the expression of VCAM, as demonstrated when the serum of healthy patients treated with the hormone is administered to cultured umbilical vein ECs [112]. It has been proposed an indirect mechanism for this action, maybe mediated by VEGF, IGF-I or SDF-1 [16, 92,106,113], that upregulate CAMs [107]. This action is also seen in GHD adults, in which GH replacement therapy significantly increases VCAM-1.…”

“…GH/IGF-I can favor inflammation during collateral enlargement During collateral enlargement two cells will be activated to achieve the great change, both endothelial and SMCs will acquire a proliferative and secretory phenotype after a previous phase of NO-dependent vasodilation, because hemodynamic or short-term compensation always runs first than that which originates from growth factors or long-term compensation. While in physiological situations the flow and metabolism control is done mainly at local level, when a pathological condition as ischemia is present the systemic response is usually required, focused on flow redistribution and microvascular adaptations [106], which will need of the neurohormonal axis effects. In both circumstances, local and systemic GH/IGF-I will be important to regulate short and long-term adaptations.…”