Abstract
During myocardial ischemia intracellular acid load increases as a consequence of anaerobic metabolism. Exchange of excessive protons for sodium via the sodium proton exchanger type 1 (NHE1) is supposed to cause intracellular sodium accumulation. The NHE1 inhibitor cariporide has been shown to inhibit ischemia and reperfusion-induced ventricular fibrillation (VF) but the mechanisms are not fully understood. During early reperfusion transient shortening of the action potential has been reported, which renders the heart susceptible to reentrant arrhythmias. In anesthetized pigs subjected to 10 min of left circumflex coronary artery (LCX) occlusion and reperfusion we have investigated whether NHE1 is involved in reperfusion-induced shortening of the monophasic action potential (MAP) taken with an epicardial probe over the ischemic area.
In control pigs (n = 7) a moderate decrease in the duration of the MAP at 50% repolarization (MAPD50) occurred during ischemia reaching 78.8 ± 5.0% of the pre-ischemic duration at 5 min (p < 0.01) and 87.3 ± 7.6% after 10 min. An additional, transient but marked shortening occurred during the first 2 min of reperfusion, which fully recovered after 4 min. At 50 sec of reperfusion MAPD50 fell to 53.1 ± 8.2% of the pre-ischemic value corresponding to 90.1 ± 20.2 msec of reperfusion-induced shortening. Cariporide, 3 mg/kg i. v. 5 min before occlusion (n = 6), totally prevented reperfusion-induced MAP shortening while heaving no effect on MAPD50 during ischemia.
In conclusion, our data suggest that the immediate, transient, but strong action potential shortening during early reperfusion after 10 min of coronary ischemia is due to the activity of the NHE1.
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Received: 16 August 2000, Returned for 1. revision: 8 September 2000, 1. Revision received: 21 September 2000, Returned for 2. revision: 27 September 2000, 2. Revision received: 2 November 2000, Accepted: 7 November 2000
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Wirth, K., Maier, T. & Busch, A. NHE1-inhibitor cariporide prevents the transient reperfusion-induced shortening of the monophasic action potential after coronary ischemia in pigs. Basic Res Cardiol 96, 192–197 (2001). https://doi.org/10.1007/s003950170070
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DOI: https://doi.org/10.1007/s003950170070