Detrimental effects of acute hyperglycaemia on the rat heart

Abstract

Coordinate NOGP activation in response to acute hyperglycaemia results in contractile dysfunction during ischaemia-reperfusion, allowing for the development of novel cardioprotective agents.

Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways

“…Moreover, a mouse model of diabetes and atherosclerosis lacking RAGE displayed significantly less aortic plaque area (312). Our laboratory and others also found increased AGE levels following ischemia and reperfusion in the absence of atherosclerosis (39,184,192,296), demonstrating more direct effects on rodent hearts. Such detrimental effects of elevated AGEs on cardiac contractile dysfunction are also much more pronounced under hyperglycemic conditions following ischemia-reperfusion (184,192).…”

“…Polyol pathway inhibition also improved cardiac energy metabolism under normoglycemic and hyperglycemic conditions (241,242), attenuated oxidative stress, and restored electrolyte homeostasis (219,281,293,317). Moreover, data from our laboratory revealed that benfotiamine (a vitamin B 1 analog) treatment lowered polyol pathway activation and restored cardiac contractile function following ischemia-reperfusion under hyperglycemic conditions (192). However, the translation of experimental studies is lagging because some synthetic aldose reductase drugs have elicited deleterious side effects in clinical trials without showing significant beneficial effects (32).…”

“…Further in vivo and clinical studies are required to investigate this possibility. Decreased aldose reductase activity also prevents the production of sorbitol and downstream effects such as AGE formation and PKC activation, thereby showing that significant cross talk exists between the various NOGPs (147,192). Together, these data demonstrate that the polyol pathway and especially aldose reductase are important targets for therapeutic interventions to potentially treat hyperglycemia-related CVD onset.…”

“…What about in the context of ischemia-reperfusion? Polyol pathway activation increases severalfold during ischemia-reperfusion and is further upregulated under hyperglycemic conditions (149,192,281). Such activation can mediate ischemiareperfusion injury in several ways.…”

Stress

“…) or metabolic substrate concentration (Mapanga et al . ). Oxidative stress is a major focus of physiological and pathophysiological studies (Heinonen et al .…”