Diabetes, perioperative ischaemia and volatile anaesthetics: consequences of derangements in myocardial substrate metabolism

Abstract

Volatile anaesthetics exert protective effects on the heart against perioperative ischaemic injury. However, there is growing evidence that these cardioprotective properties are reduced in case of type 2 diabetes mellitus. A strong predictor of postoperative cardiac function is myocardial substrate metabolism. In the type 2 diabetic heart, substrate metabolism is shifted from glucose utilisation to fatty acid oxidation, resulting in metabolic inflexibility and cardiac dysfunction. The ischaemic heart also loses its metabolic flexibility and can switch to glucose or fatty acid oxidation as its preferential state, which may deteriorate cardiac function even further in case of type 2 diabetes mellitus.Recent experimental studies suggest that the cardioprotective properties of volatile anaesthetics partly rely on changing myocardial substrate metabolism. Interventions that target at restoration of metabolic derangements, like lifestyle and pharmacological interventions, may therefore be an interesting candidate to reduce perioperative complications. This review will focus on the current knowledge regarding myocardial substrate metabolism during volatile anaesthesia in the obese and type 2 diabetic heart during perioperative ischaemia.

Figure 1

Glucose and fatty acid metabolism in the cardiomyocyte. Glucose uptake into the cell occurs through the glucose transporters GLUT1 and GLUT4. Once inside, glucose is broken down into pyruvate by glycolysis. Pyruvate is subsequently transported into the mitochondria and decarboxylated to acetyl-CoA. Non-esterified fatty acids are taken up through fatty acid transporter (FAT)/CD36, fatty acid transport protein (FATP) and plasma membrane fatty acid binding protein (FABPpm). Intracellular fatty acids form fatty acyl-CoA and can either be esterified into triglycerides (TG) or enter the mitochondria via carnitine palmitoyl transferase (CPT-1). Fatty acyl-CoA enters the β-oxidation pathway, forming acetyl-CoA. Glucose or fatty acid-derived acetyl-CoA enters the tricarboxylic acid (TCA) cycle with entry of reducing equivalents to the electron transport chain and oxidative phosphorylation, and finally ATP is formed.

Figure 2

(Hypothetical) Glucose and fatty acid metabolism under different conditions. Glucose and fatty acid metabolism in the healthy heart (A), during volatile anaesthesia (B), in the metabolic altered heart (C), in the ischaemic heart (D), during volatile anaesthesia in the ischemic heart (E) and during volatile anaesthesia in the ischemic metabolic altered heart (F). The healthy heart utilises 70% of fatty acids and 30% of glucose for ATP generation (A). We hypothesise that one of the mechanisms of volatile anaesthesia is the effect on increased glucose metabolism (B). In the metabolic altered heart it is suggested that myocardial substrate metabolism is shifted to increased fatty acid metabolism (C), whereas it is suggested that the ischaemic heart is shifted to increased glucose metabolism, however, also contrasting results exist (D). We hypothesise that exposure of volatile anaesthetics in the ischaemic heart might increase myocardial glucose metabolism even more (E), which is disturbed in the ischaemic and metabolic altered heart (F).