Pyridoxamine protects both cardiac function and improves glycaemic control in a rat model of diabetic cardiomyopathy: a pilot study

Abstract

Conclusions: DGM is an automatic and fast tool to identify the mechanism underlying ATs and VTs from electroanatomical mapping data. DGM reduces subjectivity and aides the electrophysiologist in choosing the correct ablation target, therefore our software is capable of decreasing the time electrophysiologists spend on treating each case. DGM is still under development and rapidly improving in collaboration with electrophysiologists from multiple centres. Background/Introduction: Individuals with type 2 diabetes mellitus are at increased risk of diabetic cardiomyopathy (DCM), a major cause of death within this population. The underlying mechanisms of DCM are unclear and clinical care is suboptimal. Pyridoxamine (PM), a form of vitamin B6 and glycated protein inhibitor, has shown to prevent cardiac dysfunction in preclinical models. Whether PM can be beneficial in DCM is unknown. Purpose: We hypothesized that PM improves glycaemic control and limits cardiac dysfunction in DCM. Methods: Healthy male Sprague Dawley rats received a control chow diet (N ¼ 7) or Western diet (N ¼ 4) for 18 weeks to induce DCM. At onset of diet, one Western diet group received in addition PM (1 g/L, N ¼ 8) via drinking water. Blood glucose levels were determined with a 1h oral glucose tolerance test. Echocardiographic measurements were performed to asses cardiac function. Left ventricular (LV) tissue was stained for interstitial fibrosis. Data were compared by one-way ANOVA or two-way ANOVA test. p < 0.05 was considered statistically significant. Results: Total blood glucose levels and fasting glucose levels were significantly increased in rats undergoing Western diet for 18 weeks. PM tended to improve these parameters. Animals fed Western diet displayed cardiac impairment characterized by significantly increased systolic and diastolic LV volumes and areas, associated with a tendency towards reduced global ejection fraction. Interestingly, PM treatment tended to prevent alterations in cardiac morphology and function. Moreover, the increased LV interstitial collagen content observed with Western diet was significantly prevented by PM. Conclusions: Our data confirm that 18 weeks of Western diet induces DCM in rats, characterized by impaired glucose tolerance and LV dilation. Changes in cardiac function and morphology were accompanied by increased interstitial cardiac fibrosis. As it could limit progression of this adverse phenotype, PM offers promise for preventing worse cardiac outcome in DCM patients.