title: Pyridoxamine protects against mechanical defects in cardiac ageing in rats: studies on load dependence of myocardial relaxation.
abstract: 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.
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan Department of Surgery, Hsin-Chu Branch of National Taiwan University Hospital, Hsin-Chu, Taiwan.
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: En-Ting
authors.initials: ET
authors.lastname: Wu
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Shiou
authors.initials: MS
authors.lastname: Wu
authors.affiliation: Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Shian
authors.initials: MS
authors.lastname: Tsai
authors.affiliation: Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Ko
authors.affiliation: Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ru-Wen
authors.initials: RW
authors.lastname: Chang
authors.affiliation: Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan kcchang1008@ntu.edu.tw.
authors.forename: Kuo-Chu
authors.initials: KC
authors.lastname: Chang
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D011733:Pyridoxamine / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left; D014803:Vitamin B Complex / Q000627:therapeutic use*
chemical_list: D002316:Cardiotonic Agents; D014803:Vitamin B Complex; D011733:Pyridoxamine