Pyridoxamine protects against mechanical defects in cardiac ageing in rats: studies on load dependence of myocardial relaxation

New Findings What is the central question of this study? This study aimed to investigate the hypothesis that pyridoxamine, one of the three natural forms of vitamin B6, can protect against myocardial relaxation of senescent animals by targeting arterial stiffening and contractile dysfunction of the left ventricle. What is the main finding and its importance? We found that treating the senescent rats with pyridoxamine for 5 months might improve myocardial relaxation rate, at least partly through its ability to enhance myocardial contractile performance, increase wave transit time and decrease wave reflection factor. Our team demonstrated in the past that pyridoxamine attenuated arterial stiffening by targeting the pathogenic formation of glycated collagen cross‐links in aged rats. Herein, we examined whether pyridoxamine therapy can protect against mechanical defects in myocardial relaxation by improving arterial wave properties and cardiac contractile performance in senescent animals. Fifteen‐month‐old male Fisher 344 rats were treated daily with pyridoxamine (1 g l−1 in drinking water) for 5 months and compared with age‐matched untreated control animals (20 months old). Arterial wave properties were characterized by wave transit time (τw) and wave reflection factor (Rf). We measured the contractile status of the myocardium in an intact heart as the left ventricular (LV) end‐systolic elastance (Ees). Myocardial relaxation was described according to the time constant of the LV isovolumic pressure decay (τe). Pyridoxamine therapy prevented the age‐associated prolongation in LV τe and the diminished Ees in senescent rats. The drug also attenuated the age‐related augmentation in afterload imposed on the heart, as evidenced by the increased τw and decreased Rf. We found that the LV τe was significantly influenced by both the arterial τw and Rf (τe = 16.3902 + 8.3123 × Rf − 0.4739 × τw; r = 0.7048, P