Response of the human myocardium to ischemic injury and preconditioning: The role of cardiac and comorbid conditions, medical treatment, and basal redox status

• Published in: PloS one 2017-04, Vol.12 (4), p.e0174588-e0174588
• Main Authors: Casós, Kelly, Ferrer-Curriu, Gemma, Soler-Ferrer, Paula, Pérez, María L, Permanyer, Eduard, Blasco-Lucas, Arnau, Gracia-Baena, Juan Manuel, Castro, Miguel A, Sureda, Carlos, Barquinero, Jordi, Galiñanes, Manuel
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Absorbance; Aerobic conditions; Aged; AKT protein; Apoptosis; Appendages; Ascorbic acid; ATP; Attenuation; Biology and Life Sciences; Blades; Calcium; Calcium channels (L-type); Calcium-binding protein; Carbon dioxide; Cardiovascular diseases; Cardiovascular system; Catalase - metabolism; Circulation; Comorbidity; Complications; Coronary artery disease; Death; Dehydrogenase; Diabetes mellitus; Disease susceptibility; Estrogens; Female; Females; Gender; Glucose; Health aspects; Health risks; Health services; Heart; Heart diseases; Heart Diseases - complications; Heart surgery; Heart Valve Diseases - complications; Hospitals; Humans; Hydrogen ions; Immunoglobulins; Ischemia; Ischemic Preconditioning, Myocardial - adverse effects; Kinases; Laboratories; Male; Medical treatment; Medicine and Health Sciences; Metabolic disorders; Muscle contraction; Myocardial infarction; Myocardial Ischemia - complications; Myocardial Ischemia - metabolism; Myocardial Ischemia - therapy; Myocardial Reperfusion Injury - complications; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - therapy; Myocardium; Nitric oxide; Nitric Oxide - metabolism; Oxidation-Reduction; Oxidative stress; Oxygen; Patients; Physical Sciences; Population studies; Protein kinase; Restoration; Rheumatic heart disease; Risk Factors; Rodents; Sex Factors; Shaking; Skin; Stresses; Superoxide Dismutase - metabolism; Superoxides - metabolism; Surgery
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174588

The diseased human myocardium is highly susceptible to ischemia/reoxygenation (I/R)-induced injury but its response to protective interventions such as ischemic preconditioning (IPreC) is unclear. Cardiac and other pre-existing clinical conditions as well as previous or ongoing medical treatment may influence the myocardial response to I/R injury and protection. This study investigated the effect of both on myocardial susceptibility to I/R-induced injury and the protective effects of IPreC. Atrial myocardium from cardiac surgery patients (n = 300) was assigned to one of three groups: aerobic control, I/R alone, and IPreC. Lactate dehydrogenase leakage, as a marker of cell injury, and cell viability were measured. The basal redox status was determined in samples from 90 patients. The response to I/R varied widely. Myocardium from patients with aortic valve disease was the most susceptible to injury whereas myocardium from dyslipidemia patients was the least susceptible. Tissue from females was better protected than tissue from males. Myocardium from patients with mitral valve disease was the least responsive to IPreC. The basal redox status was altered in the myocardium from patients with mitral and aortic valve disease. The response of the myocardium to I/R and IPreC is highly variable and influenced by the underlying cardiac pathology, dyslipidemia, sex, and the basal redox status. These results should be taken into account in the design of future clinical studies on the prevention of I/R injury and protection.