Ischemia/reperfusion injury is increased and cardioprotection by a postconditioning protocol is lost as cardiac hypertrophy develops in nandrolone treated rats

Abstract

We hypothesized that Nandrolone (ND)-abuse induces cardiac hypertrophy, increases myocardial susceptibility to ischemia/reperfusion (I/R) injury, and reduces responsiveness to postconditioning (PostC) cardioprotection. Wistar-rats were ND-treated for 2-weeks (short_ND) or 10-weeks (long_ND). Vehicle-treated rats served as controls. Hearts were retrogradely perfused and left ventricular pressure (LVP) was measured before and after 30-min global ischemia. In subgroups of hearts, to induce cardioprotection a PostC protocol (five cycles of 10-s reperfusion and 10-s ischemia) was performed. β-adrenoreceptors, kinases (Akt and GSk-3β) and phosphatases (PP2A sub A and PP2A sub B) were examined by Western blot before and after ischemia. After 120-min reperfusion infarct-size was measured. Short_ND slightly increased cardiac/body weight ratio, but did not affect cardiac baseline nor post-ischemic contractile function or infarct-size when compared to vehicle hearts. However, PostC limited cardiac dysfunction much more in short_ND hearts than other groups. Although cardiac/body weight ratio markedly increased after long_ND, baseline LVP was not affected. Yet, post-ischemic contracture and infarct-size were exacerbated and PostC was unable to reduce infarct-size and ventricular dysfunction. While short_ND increased phosphatases, non-phosphorylated and phosphorylated Akt, long_ND reduced phosphatase-expression and Akt-phosphorylation. Both short_ND and long_ND had no effect on the GSK-3β-phosphorylation but increased the expression of β 2 -adrenoreceptors. In reperfusion, PostC increased Akt-phosphorylation regardless of protective effects, but reduced phosphataseexpression in protected hearts only. In conclusion: short_ND improves post-ischemic myocardial performance in postconditioned hearts. However, long_ND increases myocardial susceptibility to I/R injury and abolishes cardioprotection by PostC. This increased susceptibility might be related to steroid-induced hypertrophy and/or to altered enzyme expression/phosphorylation.

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

“…However, this increase was completely absent in hypertensive, hypertrophied rat hearts . In anabolic steroid-induced cardiac hypertrophy, ischemic postconditioning failed to reduce infarct size after ischemia/reperfusion; postconditioning increased Akt phosphorylation regardless of its protective effects, but reduced expression of protein phosphatase expression was measured in protected hearts (Penna et al, 2011). Chronic captopril treatment significantly reduced left ventricular hypertrophy in hypertensive rats and reduced infarct size after ischemia/reperfusion in isolated hearts from both normotensive and hypertensive rats.…”

Pathophysiology of myocardial reperfusion injury: preconditioning, postconditioning, and translational aspects of protective measures

“…Accordingly, the preconditioning effect of prodromal angina is reportedly attenuated in acute myocardial infarction patients with hypertensive LVH (203). It also seems to be the case with cardioprotection by ischemic (150) and pharmacological (151) postconditioning, although few studies have been published on this point.…”

Neurophysiological Repercussions of Anabolic Steroid Abuse: A Road into Neurodegenerative Disorders

“…Notwithstanding in increasing the susceptibility to myocardial infarction and stroke by the above-mentioned abnormalities, chronic administration of AS has been shown to increase the damage induced by myocardial ischemia and reperfusion, which per se can aggravate the post-infarction prognosis [59][60][61]. Furthermore, recent evidences have demonstrated that therapeutic efficacy of cardioprotective maneuvers against the myocardial ischemia/reperfusion injury can be abolished by chronic exposure to AS [62]. Biochemical and molecular analyses revealed that supraphysiological doses of AS are related to redox imbalance, increased proinflammatory signaling, and overactivation of renin-angiotensin system in the heart, which seems to be closely correlated to the loss of cardioprotection after myocardial ischemia/reperfusion injury [55,60,61,63].…”