Growth Hormone Treatment Improves Peripheral Muscle Oxygen Extraction-Utilization during Exercise in Patients with Human Immunodeficiency Virus-Associated Wasting: A Randomized Controlled Trial

Abstract

The arteriovenous oxygen difference (a-vO(2) difference), a measure of peripheral muscle oxygen extraction-utilization during exercise, is reduced in antiretroviral-treated patients with human immunodeficiency virus (HIV), thus causing a shift in the cardiac output-oxygen consumption (Q-VO(2)) relationship. We investigated the impact of recombinant human GH (rhGH) treatment on a-vO(2) difference and the Q-VO(2) relationship during submaximal exercise by randomizing 12 HIV-infected patients (mean +/- sem: age, 43.3 +/- 1.5 yr; body mass, 69.5 +/- 2.9 kg; body mass index, 22.4 +/- 0.9 kg/m(2); maximum oxygen consumption, 33.6 +/- 1.5 ml/kg x min), with documented unintentional weight loss (>or=10% within the preceding 12 months) despite antiretroviral therapy, to receive 3 months of rhGH (6 mg/d) in a double-blind, placebo-controlled, cross-over trial. We assessed Q (determined noninvasively using CO(2) rebreathing), and subsequently a-vO(2) difference, from Q-VO(2) relationships. At study entry, the mean slope (8.1 +/- 1.0 liters/min x 1-liter increase in VO(2)) and intercept (3.1 +/- 1.3 liters/min), generated from each patient's Q-VO(2) relationship, were greater and lower, respectively, than those reported for healthy individuals (6.0 and 4.0, respectively), thereby indicating a deficit in the a-vO(2) difference. After 3 months of rhGH treatment, the slope decreased to 7.0, and the intercept increased to 3.5. After 1 month of rhGH treatment, the a-vO(2) difference (at a VO(2) of 1250 ml/min) significantly (P < 0.05) increased (17.1 +/- 8.9%) from baseline (9.92 +/- 0.51 ml/dl) and remained elevated (10.39 +/- 0.48 ml/dl) after 3 months of treatment. No significant changes were seen with placebo. Therefore, treatment with rhGH leads to an improvement in peripheral muscle oxygen extraction-utilization and the Q-VO(2) relationship during exercise in patients with HIV-associated wasting despite antiretroviral therapy.

Anabolic growth hormone action improves submaximal measures of physical performance in patients with HIV-associated wasting

“…Therefore, we extend our previous findings (20) and herein present a randomized, double-blinded, placebo-controlled study. The primary purpose of the study was to assess the ability of submaximal measures of exercise physiological performance obtained from sophisticated gas exchange methodology and functional measurements of the simple 6-min walk test (6MWT) to reflect the impact of rhGH-induced changes in body composition and subjective perception of fatigue in patients with HIV-associated wasting.…”

“…Although that study and ours attribute improvement of physical performance to rhGH anabolic action, other potential physiological mechanisms (improved regional distribution of peripheral blood flow, increased numbers of muscle mitochondria, and/or improved respiratory enzyme activity) may concurrently contribute to this improvement. We (20) have recently demonstrated that rhGH treatment transiently increases peripheral muscle oxygen extraction and utilization, yet it is unclear whether this improvement is dependent on or independent of the increased LBM.…”

“…Using cardiopulmonary exercise testing and the gas exchange analyses thereof, we have recently demonstrated that rhGH treatment transiently increases peripheral muscle oxygen extraction and utilization during exercise in male patients with HIV-associated wasting (20), thereby providing insight into one of the mechanisms responsible for improved exercise performance after rhGH treatment in these patients. However, there have been no studies using cardiopulmonary exercise testing in tandem with functional walk tests to determine their ability to measure the impact of rhGH treatment on physical performance in patients with HIV-associated wasting.…”

Uptodate on GH/IGF-1 axis actions

“…GH/IGF-I axis functionality is important in protein synthesis and to preserve normal muscular mass. GH and IGF-I could increase the retention of nitrogenous and induce protein synthesis (200). Moreover, in some cases, GH/IGF-I function could have an important role in the nutritional status and body composition which are impaired in HIV infected patients.…”

O papel do hormônio de crescimento no tratamento dos distúrbios endócrino-metabólicos do paciente com a síndrome da imunodeficiência adquirida (Aids)

“…O principal estudo clínico com hrGH realizado até o momento com pacientes com a síndrome do emaciamento (n = 757; controles = 199) incluiu 88% de pacientes em uso de HAART e, além dos resultados esperados em relação à composição corporal, também demonstra mudança muito significativa da capacidade física dos pacientes tratados (8,54). À semelhança de outros estudos (8,49,(52)(53)(54)(55), os efeitos colaterais incluem artralgias (36,4%), mialgia (30,4%), edema periférico (26,1%), cefaléia (12,6%), artrose (10,7%), náusea (9,1%) e parestesia (7,9%). Além dos efeitos adversos já relatados, entre os pacientes com HAART e emaciamento, houve aparecimento de um caso de diabetes melito tipo 2 e hiperglicemia em pacientes previamente diabéticos (n = 2) (54).…”