Na sup + /H sup + Exchanger Inhibitor HOE-642 Improves Cardioplegic Myocardial Preservation Under Both Normothermic and Hypothermic Conditions

Shipolini, Alex R. FRCS
Galinanes, Manuel MD, PhD
Edmondson, Stephen J. FRCS
Hearse, David J. PhD, DSc
Avkiran, Metin PhD

From the Department of Cardiovascular Research, The Rayne Institute, St Thomas' Hospital (A.R.S., M.G., D.J.H., M.A.); and the Cardiothoracic Department, St Bartholomew's Hospital (S.J.E.), London, UK.
Correspondence to Dr Metin Avkiran, Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, Lambeth Palace Rd, London SE1 7EH, UK. E-mail: [email protected].

Circulation 96(9S):p 266II-273II, November 4, 1997.

Background The sarcolemmal Na sup + /H sup + exchanger has been implicated in the pathogenesis of myocardial injury during ischemia/reperfusion.We determined the cardioprotective efficacy of the Na sup + /H sup + exchanger inhibitor HOE-642 (HOE) as an alternative, adjunct, or additive to cardioplegia (CP).

Methods and Results In isolated working rat hearts (n = 6 per group) subjected to 25 minutes of ischemia at 37 [degree sign] Celsius, the postischemic recovery of aortic flow (AF) was 5 +/-3 in controls; this was improved to 18 +/- 4% by the preischemic infusion of 1 micro mol/L HOE (P < .05 versus control) and to 53 +/- 7% by CP (P < .05 versus control and HOE). In hearts subjected to CP and 35 minutes of ischemia at 37 [degree sign] Celsius, AF recovered to 9 +/- 3% with CP alone; this was improved to 18 +/- 3% by the adjunctive administration of HOE during early reperfusion (CP + repHOE, P < .05 versus CP) and to 27 +/- 4% by the use of HOE as an additive to CP (CP + HOE, P < .05 versus CP and CP + repHOE). With 120 minutes of ischemia at 28 [degree sign] Celsius, AF recoveries were 16 +/- 3% in CP, 32 +/- 3% in CP + repHOE (P < .05 versus CP) and to 50 +/- 4% in CP + HOE (P < .05 versus CP and CP + repHOE). With 300 minutes of ischemia at 7.5 [degree sign] Celsius, the corresponding values were 30 +/- 4%, 45 +/- 5% (P < .05 versus CP), and 63 +/- 5% (P < .05 versus CP and CP + repHOE). Improved recovery of pump function was often accompanied by a reduction in creatine kinase leakage during reperfusion.

Conclusions (i) HOE alone affords significant protection at normothermia but is not a superior alternative to CP, and (ii) the use of HOE as an adjunct or additive to CP provides significant benefit at normothermia, moderate hypothermia, and severe hypothermia.(Circulation. 1997;96[suppl II]:II-266-II-273.)