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Eur J Cardiothorac Surg 2006;29:S107-S114
© 2006 Elsevier Science NL

Diastolic dysfunction in stunned myocardium: a state of abnormal excitation–contraction coupling that is limited by Na⁺–H⁺ exchange inhibition

^a Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 62-258 CHS, Los Angeles, CA 90095-1701, USA
^b Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
^c Option on Bioengineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA

Received 17 February 2006; accepted 27 February 2006.

^_* Corresponding author. Address: Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 62-258 CHS, Los Angeles, CA 90095-1701, USA. Tel.: +1 310 206 1027; fax: +1 310 825 5895. (Email: gbuckberg{at}mednet.ucla.edu).

Objective: The systolic and diastolic effects of myocardial stunning were studied to evaluate the contributions of the endocardial and epicardial segments of the ventricular myocardial band, and determine if preconditioning by Na⁺–H⁺ exchange (NHE) inhibition effected post-stunning dysfunction. Methods: Thirteen Yorkshire–Duroc pigs (27.3–38.2 kg) underwent 15 min of mid-LAD clamping. Seven had no protective measures and six were pretreated with IV Cariporide 5 mg/kg 15 min before ischemia. Sonomicrometer crystals evaluated systolic dysfunction (impaired regional shortening) and diastolic dysfunction (contraction extending into early diastole). Results: Before ischemia, contraction started first on the endocardial side followed 82 ± 23 ms later by the subepicardium. Endocardial shortening stopped first, coinciding with negative dP/dt onset, while epicardial shortening phase persisted for 92 ± 33 ms more during occurrence of rapid LVP descent and development of peak negative dP/dt. Ischemia produced paradoxical bulging of both segments. Sixty minutes after ischemia systolic segment shortening recovered 36 ± 24% of baseline values without pretreatment, compared to 75.8 ± 15% with Cariporide (p < 0.05). Global ejection force (maximum dP/dt) fell 32 ± 20% in the unprotected group, but was maintained by Cariporide pretreatment. Diastolic dysfunction always showed continued endocardial contraction into early diastole (occupying 38 ± 16% of diastole in untreated hearts), whereas Cariporide treatment reduced this dysfunction to 5 ± 10% (p < 0.05). Persistent diastolic dysfunction raised left ventricle end diastolic pressure (LVEDP) 4 mmHg in untreated hearts, whereas Cariporide returned LVEDP to normal. Less elevation of creatine kinase MB (CK-MB) and conjugated dienes followed Cariporide pretreatment. Conclusions: Temporary LAD ischemia alters the normal sequential pattern of contraction responsible for ejection and suction by (a) reducing systolic contractile force, and (b) prolonging endocardial contraction into early diastole to disrupt the normal endocardial–epicardial sequence responsible for ventricular suction. NHE inhibition before ischemia limits postischemic systolic and diastolic dysfunction by re-establishing the expected shortening sequences within the ventricular myocardial band model.

Key Words: Cardiac general • Experimental • Myocardial stunning • Systole • Diastole • Sodium–hydrogen exchanger

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