Na(+)/H(+)-exchange inhibition and aprotinin administration: promising tools for myocardial protection during minimally invasive CABG.
OBJECTIVE
Minimally invasive coronary artery bypass grafting (CABG), carried out on the warm beating heart, does not allow conventional myocardial protection. The objective was to investigate the possibility of enhancing tolerance to ischemia during short episodes of coronary artery occlusion, based on a pharmacological approach using a selective Na(+)/H(+)-exchange inhibitor (cariporide) or a serine protease inhibitor (aprotinin).


METHODS
Four groups (n=6 in each group) of sheep were subjected to 20 min of normothermic regional ischemia (first lateral branch of the circumflex artery occlusion) followed by 1 h of reperfusion. Regional wall thickening was measured using sonomicrometry, and expressed as the percentage of thickening fraction compared with baseline. Group I was the control with no treatment, group II received cariporide (1 mg/kg administered over 2 min prior to ischemia), group III was treated with aprotinin (2.10(6) kallikrein inactivation units (KIU) load followed by 500.000 KIU/h). Group IV was treated with a combination of cariporide and aprotinin at the same concentrations as in groups II and III, respectively.


RESULTS
Wall thickening measurements showed that, compared with control, cariporide was largely able to suppress secondary loss of wall thickening after initial recovery during early reperfusion. Wall thickening in the ischemic/reperfused myocardial area improved from 10+/-31 to 51+/-17% at 1 h of reperfusion (P=0.002). Aprotinin improved wall thickening at the end of 1 h of reperfusion to 70+/-13% (P=0.0001). However, in this group, there was a transient loss of regional contractility similar in amplitude and time course to the one observed in the control group. A combination of cariporide and aprotinin suppressed transient contractile loss and resulted in improved wall thickening at the end of 1 h of reperfusion (65+/-22%, P=0.0002 vs. control). This value was not significantly different from the cariporide (P=0.263) or aprotinin (P=0.704) group.


CONCLUSIONS
These data indicate that both Na(+)/H(+)-exchange inhibition and aprotinin administration are promising tools for cardioprotection during minimally invasive CABG. A combination of both treatments is able to adequately suppress loss of contractility during early reperfusion as a consequence of reperfusion injury, and results in significantly improved wall thickening at the end of 1 h of reperfusion.
Hendrikx
M
M
Limburgs Universitair Centrum, Universitaire Campus, 3590, Diepenbeek, Belgium. marc.hendrikx@virgajesse.be
Rega
F
F
Jamaer
L
L
Valkenborgh
T
T
Gutermann
H
H
Mees
U
U
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D007611:Aprotinin / Q000494:pharmacology / Q000627:therapeutic use*; D001026:Coronary Artery Bypass / Q000379:methods; D006146:Guanidines / Q000627:therapeutic use*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D019060:Minimally Invasive Surgical Procedures; D009200:Myocardial Contraction / Q000187:drug effects; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012756:Sheep; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D007611:Aprotinin