Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury

Abstract

We and others have demonstrated a protective effect of pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury. However, the mechanisms underlying this protection are not completely clear. In the present study, we evaluated the effects of calcium release from the sarcoplasmic reticulum (SR) and the novel intracellular acidic stores (AS). Isolated rat hearts (n = 6 per group) were subjected to coronary occlusion followed by reperfusion using a modified Langendorff system. Cardiac hemodynamics and contractility were assessed using a data acquisition program, and cardiac injury was evaluated by creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Hearts were subjected to 30 min of regional ischemia, produced by ligation of the left anterior descending (LAD) coronary artery, followed by 30 min of reperfusion. The hearts were also subjected to PPC (3 cycles of 30 s of left ventricle (LV) pacing alternated with 30 s of right atrium (RA) pacing) and/or were treated during reperfusion with agonists or antagonists of release of calcium from SR or AS. PPC significantly (P < 0.05) normalized LV, contractility, and coronary vascular dynamics and significantly (P < 0.001) decreased heart enzyme levels compared to the control treatments. The blockade of SR calcium release resulted in a significant (P < 0.01) recovery in LV function and contractility and a significant reduction in CK and LDH levels (P < 0.01) when applied alone or in combination with PPC. Interestingly, the release of calcium from AS alone or in combination with PPC significantly improved LV function and contractility (P < 0.05) and significantly decreased the CK and LDH levels (P < 0.01) compared to the control treatments. An additive effect was produced when agonism of calcium release from AS or blockade of calcium release from the SR was combined with PPC. Calcium release from AS and blockade of calcium release from the SR protect the heart against I/R. Combining calcium release from acidic stores or blockade of calcium release from the SR with PPC produced a synergistic protective effect.

Micronized flavonoid fraction Daflon 500 protects heart against ischemia–reperfusion injury: an old medicine for a new target

“…The thoracic cage was folded back, and the heart was exposed and excised. To limit ischemic injury during the time between excision and the restoration of vascular perfusion, the heart was directly immersed in cold (4°C) Krebs-Hensleit (KH) solution (Khalaf and Babiker 2016).…”

Acute Intravenous Infusion of Immunoglobulins Protects Against Myocardial Ischemia-Reperfusion Injury Through Inhibition of Caspase-3

“…Ischemic preconditioning (repetitive ischemic episodes before the insult) was proposed in attempt to decrease I/R injury [39]. Although this method showed considerable heart protection [28, 40, 41], the likelihood of its use in clinical application is rather limited because of the unexpectedness of most ischemic events. More applicable in clinical practice is ischemic postconditioning (repetitive ischemia at the onset of reperfusion) [42].…”

“…Male Wistar rats weighing 250-300 g were anesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg) with the anticoagulant heparin (1000 U/kg body weight) through the femoral vein. The heart was attached to a modified Langendorff setup for the perfused rat heart, as described previously [28]. Briefly, the hearts were retrogradely perfused with freshly prepared Krebs-Hensleit solution.…”

Two-pore channels and disease

“…Interestingly, extracellular NAADP appears to paradoxically protect hearts against ischemic injury [ 94 , 95 ]. Such effects were reversed by an antagonist of P2Y11 receptors or Ned-19 suggesting NAADP acts on the cell surface or intracellularly upon transport, respectively.…”