Non-oncotic properties of albumin. A multidisciplinary vision about the implications for critically ill patients.

INTRODUCTION: Effective resuscitation with human albumin solutions is achieved with less fluid than with crystalloid solutions. However, the role of albumin in today's critical care unit is also linked to its multiple pharmacological effects. Areas covered: The potential clinical benefits of albumin in select populations of critically ill patients like sepsis seem related to immunomodulatory and anti-inflammatory effects, antibiotic transportation and endothelial stabilization. Albumin transports many drugs used in critically ill patients. Such binding to albumin is frequently lessened in critically ill patients with hypoalbuminemia. These changes could result in sub-optimal treatment. Albumin has immunomodulatory capacity by binding several bacterial products. Albumin also influences vascular integrity, contributing to the maintenance of the normal capillary permeability. Moreover, the albumin molecule encompasses several antioxidant properties, thereby significantly reducing re-oxygenation injury, which is especially important in sepsis. In fact, most studies of albumin administration are a combination of a degree of resuscitation with a degree of maintenance or supplementation of albumin. Expert commentary: The potential clinical benefits of the use of albumin in selected critically ill patients such as sepsis seem related to its immunomodulatory and anti-inflammatory effects, antioxidant properties, antibiotic transportation and endothelial stabilization. Additional studies are warranted to further elucidate the underlying physiologic and molecular rationale.

Therapeutic Approaches in Mitochondrial Dysfunction, Proteolysis, and Structural Alterations of Diaphragm and Gastrocnemius in Rats With Chronic Heart Failure.

Patients with chronic heart failure (CHF) experience exercise intolerance, fatigue and muscle wasting, which negatively influence their survival. We hypothesized that treatment with either the antioxidant N-acetyl cysteine (NAC) or the proteasome inhibitor bortezomib of rats with monocrotaline-induced CHF may restore inspiratory and limb muscle mass, function, and structure through several molecular mechanisms involved in protein breakdown and metabolism in the diaphragm and gastrocnemius. In these muscles of CHF-cachectic rats with and without treatment with NAC or bortezomib (N = 10/group) and non-cachectic controls, proteolysis (tyrosine release, proteasome activities, ubiquitin-proteasome markers), oxidative stress, inflammation, mitochondrial function, myosin, NF-κB transcriptional activity, muscle structural abnormalities, and fiber morphometry were analyzed together with muscle and cardiac functions. In diaphragm and gastrocnemius of CHF-cachectic rats, tyrosine release, proteasome activity, protein ubiquitination, atrogin-1, MURF-1, NF-κB activity, oxidative stress, inflammation, and structural abnormalities were increased, while muscle and cardiac functions, myosin content, slow- and fast-twitch fiber sizes, and mitochondrial activity were decreased. Concomitant treatment of CHF-cachectic rats with NAC or bortezomib improved protein catabolism, oxidative stress, inflammation, muscle fiber sizes, function and damage, superoxide dismutase and myosin levels, mitochondrial function (complex I, gastrocnemius), cardiac function and decreased NF-κB transcriptional activity in both muscles. Treatment of CHF-cachectic animals with NAC or bortezomib attenuated the functional (heart, muscles), biological, and structural alterations in muscles. Nonetheless, future studies conducted in actual clinical settings are warranted in order to assess the potential beneficial effects and safety concerns of these pharmacological agents on muscle mass loss and wasting in CHF-cachectic patients.