Does Ischemic Preconditioning Require Reperfusion Before Index Ischemia?

B. Korbmacher; T. Schmidt; U. Schwanke; R. Schulz; G. Heusch; J. D. Schipke

doi:10.1055/s-2000-8890

The Thoracic and Cardiovascular Surgeon, Table of Contents

Thorac Cardiovasc Surg 2000; 48(1): 15-21
DOI: 10.1055/s-2000-8890

Original Cardiovascular

Does Ischemic Preconditioning Require Reperfusion Before Index Ischemia?[∗]

B. Korbmacher¹ , T. Schmidt² , U. Schwanke^2,3 , R. Schulz³ , G. Heusch³ , J. D. Schipke²

¹Department of Thoracic and Cardiovascular Surgery,
²Institute of Experimental Surgery, Düsseldorf University, Düsseldorf, Germany
³Institute of Pathophysiology, Essen University, Essen, Germany

Abstract

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Background: Ischemic preconditioning (IP) is initiated through one or several short bouts of ischemia and reperfusion which precede a prolonged ischemia. To test whether a reperfusion must precede the prolonged index ischemia, a series without reperfusion (intraischemic preconditioning: IIP) and a series with gradual onset of ischemia, i.e. ramp ischemia (RI), which is possibly related to the development of hibernation, was compared to conventional IP (CIP). Method: Experiments were performed an 27 blood-perfused rabbit hearts (Langendorff apparatus) that were randomized into one of four series: (1) control (n = 7): 60 min normal flow → 60 min low flow (10 %) ischemia → 60 min reperfusion. (2) CIP (n = 7): 4 times 5 min zero flow with 10 min reperfusion each → 60 min low flow (10 %) → ischemia 60 min reperfusion. (3) IIP (n = 7): 50 min normal flow → 10 min no flow → 60 min low flow (10 %) ischemia → 60 min reperfusion. (4) RI (n = 6): gradual reduction to 10 % flow during 60 min → 60 min low flow (10 %) ischemia → 60 min reperfusion. At the end of each protocol, the infarcted area was assessed. Results: The infarct area in control hearts was 6.7 ± 1.4 % (means ± SEM) of LV total area, in CIP hearts 2.6 ± 0.8 %, in IIP hearts 3.1 ± 0.5 %, and in RI hearts 3.0 ± 0.3 % (all p < 0.05 vs. control). The differences between the three protection protocols were statistically not significant, and no protective protocol reduced post-ischemic myocardial dysfunction. Conclusion: The preconditioning effect (infarct size reduction) appears not to depend on intermittent reperfusion. Thus, the protective mechanism of IP develops during the initial ischemia that precedes the index ischemia. Alternatively, low-flow ischemia is effectively a sort of reperfusion.

Key words:

Ischemic Preconditioning - Cardiac Surgery - Cardioprotection - Rabbit

Full Text

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1 Presented in part at the 64th Meeting of the German Cardiac Society, Mannheim, April 1998

FESC PhD J. D. Schipke

Institut für Experimene Chirurgie Universität Düsseldorf

D-40225 Düsseldorf

Germany

Email: schipkej@uni-duesseldorf.de