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

Date Published: April 5, 2017

Publisher: Public Library of Science

Author(s): Kelly Casós, Gemma Ferrer-Curriu, Paula Soler-Ferrer, María L Pérez, Eduard Permanyer, Arnau Blasco-Lucas, Juan Manuel Gracia-Baena, Miguel A Castro, Carlos Sureda, Jordi Barquinero, Manuel Galiñanes, Tobias Eckle.


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 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.

Partial Text

Cardiovascular diseases are the most prevalent health problem worldwide and the major cause of morbidity and mortality [1]. According to the WHO, in 2012 ischemic heart diseases caused 17.5 million deaths. Prolonged ischemia, such as occurs during myocardial infarction, causes lactate accumulation, alterations in ion-transport mechanisms, and eventually cardiomyocyte death through apoptosis and necrosis. However, oxygen restoration during reperfusion creates a large burst of reactive oxygen species production and calcium overload [2], causing additional myocardial damage. In fact, ischemic/reperfusion (I/R) injury is one of the main risk factors during heart surgery [3–5], especially in older patients and those with underlying comorbidities (e.g., diabetes) [6]. Over the last three decades, major efforts have been aimed at understanding the mechanisms of I/R-induced injury and developing strategies to protect the human myocardium. Nonetheless, much remains to be learned.

Table 1 summarizes the demographic data from the donor patients (n = 300).

In this study, in vitro preparations of right atrial appendages from a very large cohort of patients undergoing elective heart surgery were examined with respect to I/R and IPreC. The results demonstrated that: (1) the response of the human myocardium to I/R is highly variable, with tissue from patients with aortic valve disease being more susceptible to injury than tissue from patients with other cardiac pathologies. By contrast, the myocardial tissue of patients with dyslipidemia was the least susceptible to I/R injury. (2) The response to IPreC was also highly variable. The myocardium from females was significantly better protected than that from males and, the myocardium from patients with mitral valve disease was less responsive to IPreC-mediated protection than tissues from patients without mitral valve disease. (3) The redox status of the myocardium under basal conditions (prior to ischemia) may be relevant to the degree of I/R-induced injury and to the response to IPreC in patients with heart valve pathologies.

The response of the myocardium from patients with heart diseases to I/R and IPreC varies widely and may be influenced by specific cardiac pathologies and the sex of the patient. Our results do not support the broad clinical use of IPreC; rather, they emphasize the need for research into both the molecular basis of I/R-induced injury and the cardioprotective interventions in human myocardium that will lead to clinical success. Whether the basal redox status of the myocardium plays a role in the degree of I/R-induced injury and the response to IPreC remains to be determined. Our results are an important contribution to the design of future clinical studies on I/R injury and IPreC.




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