Major elective abdominal surgery acutely impairs lower limb muscle pyruvate dehydrogenase complex activity and mitochondrial function

Abstract

Summary Background & aims This post hoc study aimed to determine whether major elective abdominal surgery had any acute impact on mitochondrial pyruvate dehydrogenase complex (PDC) activity and maximal mitochondrial ATP production rates (MAPR) in a large muscle group (vastus lateralis -VL) distant to the site of surgical trauma. Methods Fifteen patients undergoing major elective open abdominal surgery were studied. Muscle biopsies were obtained after the induction of anesthesia from the VL immediately before and after surgery for the determination of PDC and maximal MAPR (utilizing a variety of energy substrates). Results Muscle PDC activity was reduced by >50% at the end of surgery compared with pre-surgery (p < 0.05). Muscle MAPR were comprehensively suppressed by surgery for the substrate combinations: glutamate + succinate; glutamate + malate; palmitoylcarnitine + malate; and pyruvate + malate (all p < 0.05), and could not be explained by a lower mitochondrial yield. Conclusions PDC activity and mitochondrial ATP production capacity were acutely impaired in muscle distant to the site of surgical trauma. In keeping with the limited data available, we surmise these events resulted from the general anesthesia procedures employed and the surgery related trauma. These findings further the understanding of the acute dysregulation of mitochondrial function in muscle distant to the site of major surgical trauma in patients, and point to the combination of general anesthesia and trauma related inflammation as being drivers of muscle metabolic insult that warrants further investigation. Clinical trial registration Registered at (NCT01134809).

Nascent to novel methods to evaluate malnutrition and frailty in the surgical patient

“…The metabolic response in combination with the previously mentioned immunologic changes observed in the surgical patient results in loss of fat‐free mass, including skeletal muscle mass 13 . Furthermore, major surgery has also been shown to adversely affect muscle mitochondrial function, which can lead to muscle atrophy 20 …”

“…13 Furthermore, major surgery has also been shown to adversely affect muscle mitochondrial function, which can lead to muscle atrophy. 20 Skeletal muscle is a metabolic organ that accounts for approximately 40% of body mass and serves several functions, including housing the body's largest amino acid reserve, synthesizing and storing glutamine, regulating blood glucose concentrations, and producing myokines. 21 More commonly, skeletal muscle is recognized for its structural functions, including movement, balance, posture, and bodily strength.…”

“… 13 Furthermore, major surgery has also been shown to adversely affect muscle mitochondrial function, which can lead to muscle atrophy. 20 …”

Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids

“…It is rational and expected that on a monolithic view, pyruvate as a novel component in fluid therapy would greatly ameliorate the prognosis of diseases and clinical outcomes, particularly under IGDT, in perioperative fluid management and ICU patients, especially those with diabetes and elders, as the initial clinical indication. For example, clinical studies demonstrate that major abdominal surgery can induce a substantial PDH decrease with glucose metabolic dysregulation in muscles, probably due to an increase in PDK activity and insulin resistance (84,85). Thus, pyruvate-enriched fluids would be an optimal selection to prevent postoperative hyperglycemia, probably due to its preservation of PDH and islet function (30)(31)(32)(33)60).…”