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

Abstract

New FindingsWhat 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 < 0.005). In the meantime, the LV τe and the LV Ees showed a significant inverse linear correlation (τe = 13.9807 − 0.0068 × Ees; r = 0.6451, P < 0.0005). All these findings suggested that long-term treatment with pyridoxamine might ameliorate myocardial relaxation rate, at least partly through its ability to enhance myocardial contractile performance, increase wave transit time and decrease wave reflection factor in aged rats.

Pyridoxamine improves survival and limits cardiac dysfunction after MI

“…The concomitant reduction in collagen content and LOX expression suggests a reduced collagen cross-linking, resulting in an increased tissue compliance and improved diastolic function. Our data are in line with other studies conducted in animal models of diabetes or in senescent rats 11 , 14 , 37 , 38 . LOX expression is regulated via TGF-β1 by either the PI3K/Akt, Smad3 or MAPK signaling pathway 39 .…”

Influence of biological sex and exercise on murine cardiac metabolism

“…Higher levels of pyridoxamine in female hearts could also underpin the more resilient nature of the female heart. 50 because pyridoxamine has been shown to protect against cardiac dysfunction caused by aging 51 or myocardial infarction. 52 Also markedly higher in female hearts was homoarginine.…”

Defects in Vascular Mechanics Due to Aging in Rats: Studies on Arterial Wave Properties from a Single Aortic Pressure Pulse

“…Statistical significance was assumed at the level of P < 0.05. In cases where the ANOVA results indicated that a hemodynamic variable differed significantly among age groups, Tukey's honest significant difference method was used to determine the groups of rats that exhibited divergent mean values for that variable (Wang et al, 2014b ).…”