title: Homocysteine Exposure Impairs Myocardial Resistance to Ischaemia Reperfusion and Oxidative Stress.
abstract: OBJECTIVE
  Hyperhomocysteinaemia is recognised as a strong independent risk factor for developing cardiovascular disease. This study investigated how an acute homocysteine dose affected cardiac performance during ischaemia reperfusion and cardiomyocyte contractility and morphology under normal conditions and during oxidative stress.
  
  
  METHODS
  Cardiac function was measured in isolated and perfused rat hearts before and after 40 minutes' global normothermic ischaemia. Where used, 0.1 mM L-homocysteine was present prior to, and throughout ischaemia, before wash out after 10 minutes' reperfusion. Calcium transients under normal conditions and changes in contractile synchronicity during oxidative stress (exposure to 0.2 mM H2O2) were measured in freshly isolated rat cardiomyocytes incubated for 60 minutes ± 0.1 mM L-homocysteine.
  
  
  RESULTS
  During ischaemia reperfusion 0.1 mM L-homocysteine significantly reduced the rate pressure product during reperfusion (10,038 ± 749 vs. 5955 ± 567 mmHg bpm, p < 0.001), but did not affect time to ischaemic contracture. Incubation of freshly isolated cardiomyocytes with 0.1 mM L-homocysteine significantly decreased the amplitude of the calcium transient and slowed the time to half relaxation.
  
  
  CONCLUSIONS
  These findings suggest that homocysteine exposure affected myocardial recovery from ischaemia and contractile homeostasis although the exact mechanisms for these changes remain to be determined.
authors.forename: Amer
authors.initials: A
authors.lastname: Almashhadany
authors.forename: Dareuosh
authors.initials: D
authors.lastname: Shackebaei
authors.forename: Thomas
authors.initials: T
authors.lastname: Van der Touw
authors.forename: Graham L
authors.initials: GL
authors.lastname: Jones
authors.forename: M-Saadeh
authors.initials: MS
authors.lastname: Suleiman
authors.forename: Nicola
authors.initials: N
authors.lastname: King
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006710:Homocysteine / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D006710:Homocysteine