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[The Na+/Ca2+ exchanger as responsible for myocardial stunning]
1Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.
Abstract:
Our objective was to assess the participation of Na+/H+ exchanger (NHE) and Na+/Ca2+ exchanger (NCX) on systolic and diastolic alterations of myocardial stunning. Isolated perfused rat hearts were submitted to 20 min of global ischemia (Is) followed by 30 min of reperfusion (R). This protocol was repeated after treatment before ischemia and/or early in R. with HOE 642 1 microM, a specific blocker of NHE-1 and KB-R7943 1 microM the novel inhibitor of the reverse mode of NCX. In control ischemic hearts the contractility assessed through +dP/dtmax recovered approximately 60%. When the NHE blockade was performed before is or early in R the postischemic recovery reached 100%. The blockade of the reverse mode of NCX only improved significantly the recovery when administered before is and early in R (95 +/- 7%). The ischemic contracture decreased when the treatment with both blockers was performed before Is. During R the increase of end diastolic pressure (EDP) observed in control ischemic hearts (at 30 min of R, EDP value was 44 +/- 4 mmHg) diminished significantly by NHE (24 +/- 6 and 12 +/- 2 mmHg when the blocker was administered before or after Is) and NCX blockade performed before and after is (12 +/- 6 mmHg). These results indicate that the activation of the reverse mode of NCX secondary to the NHE activation during ischemia and reperfusion is the mechanism responsible for the Ca2+ overload involved in the diminution of contractility that characterizes myocardial stunning.
Insights
Blocking Na+/H+ exchanger (NHE) and Na+/Ca2+ exchanger (NCX) significantly improved recovery from myocardial stunning. These exchangers are key to Ca2+ overload and reduced contractility during ischemia and reperfusion.
Area of Science:
- Cardiovascular Physiology
- Cellular Mechanisms of Heart Disease
Background:
- Myocardial stunning, a post-ischemic contractile dysfunction, involves alterations in systolic and diastolic function.
- The roles of Na+/H+ exchanger (NHE) and Na+/Ca2+ exchanger (NCX) in myocardial stunning require further elucidation.
Purpose of the Study:
- To investigate the involvement of NHE and NCX in the systolic and diastolic changes associated with myocardial stunning.
- To assess the therapeutic potential of blocking NHE and NCX in mitigating myocardial stunning.
Main Methods:
- Isolated perfused rat hearts subjected to global ischemia followed by reperfusion.
- Treatment with HOE 642 (NHE-1 blocker) and KB-R7943 (NCX reverse mode inhibitor) before ischemia and/or during early reperfusion.
- Assessment of contractility (+dP/dtmax) and end-diastolic pressure (EDP) to evaluate functional recovery.
Main Results:
- NHE blockade before ischemia or early reperfusion restored post-ischemic contractility to 100%.
- NCX reverse mode blockade before ischemia and early reperfusion significantly improved recovery (95%).
- Both NHE and NCX blockade reduced ischemic contracture and diminished the increase in end-diastolic pressure during reperfusion.
Conclusions:
- NHE activation followed by reverse mode NCX activation during ischemia-reperfusion causes Ca2+ overload, leading to reduced contractility in myocardial stunning.
- Targeting NHE and NCX offers a promising therapeutic strategy for managing myocardial stunning.