Diltiazem during reperfusion preserves high energy phosphates by protection of mitochondrial integrity.
OBJECTIVE
This study evaluates the effects of diltiazem administered during reperfusion on hemodynamic, metabolic, and ultrastructural postischemic outcome.


METHODS
Hearts of 38 adult White New Zealand rabbits underwent 60 min of global cold ischemia followed by 40 min of reperfusion in an erythrocyte perfused isolated working heart model. Hearts were randomly assigned to four groups and received diltiazem (0.1, 0.25, and 0.5 micromol/l) during reperfusion only, or served as control.


RESULTS
The postischemic time courses of heart rate, aortic flow, and external stroke work clearly reflected the dose-dependent negative chronotropic and inotropic efficacy of diltiazem in the two higher concentrations. High energy phosphates (HEP) determined from myocardial biopsies taken after 40 min of reperfusion were significantly better preserved in all treatment groups compared to control hearts. Similarly ultrastructural grading of mitochondria and myofilaments revealed a significant reduction of reperfusion injury in hearts that received diltiazem compared to control.


CONCLUSIONS
Diltiazem protects mitochondrial integrity and function, thereby preserving myocardial HEP levels. Only low dose diltiazem (0.1 micromol/l) during reperfusion combines both, optimal mitochondrial preservation with minimal changes in hemodynamics.
Kröner
A
A
Department of Cardiothoracic Surgery, AKH Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Seitelberger
R
R
Schirnhofer
J
J
Bernecker
O
O
Mallinger
R
R
Hallström
S
S
Ploner
M
M
Podesser
B K
BK
D000227:Adenine Nucleotides / Q000032:analysis*; D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000648:ultrastructure; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D015425:Myocardial Reperfusion / Q000379:methods*; D010725:Phosphocreatine / Q000032:analysis*; D011336:Probability; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000517:prevention & control*; D012680:Sensitivity and Specificity
D000227:Adenine Nucleotides; D010725:Phosphocreatine; D004110:Diltiazem