Creatine phosphate administration preserves myocardial function in a model of off-pump coronary revascularization.
OBJECTIVE
Off pump coronary artery bypass grafting (OPCAB) involves, and is occasionally impaired by obligatory regional myocardial ischemia, particularly with the use of proximal coronary in-flow occlusion techniques. Intracoronary shunts do not guarantee absence of distal ischemia given their small inner diameter and the presence of proximal coronary stenosis. Additional adjunctive measures to provide short-term myocardial protection may facilitate OPCAB. High-energy phosphate supplementation with creatine phosphate prior to ischemia may attenuate ischemic dysfunction.


METHODS
In a rodent model of a transient coronary occlusion and myocardial ischemia, 36 animals underwent preischemic intravenous infusion of either creatine phosphate or saline, 10 minutes of proximal left anterior descending (LAD) occlusion, and 10 minutes of reperfusion. Rats underwent continuous intracavitary pressure monitoring and cellular ATP levels were quantified using a luciferin/luciferase bioluminescence assay.


RESULTS
Within 2 minutes of ischemia onset, creatine phosphate animals exhibited statistically significant greater preservation of myocardial function compared to controls, an augmentation which persisted throughout the duration of ischemia and subsequent reperfusion. Furthermore, significantly greater cellular ATP levels were observed among creatine phosphate treated animals (344+/-55 nMol/g tissue, n=5) compared to control animals (160+/-9 nMol/g tissue, n=5)(p=0.014).


CONCLUSIONS
A strategy of intravenous high-energy phosphate administration successfully prevented ischemic ventricular dysfunction in a rodent model of OPCAB.
Woo
Y J
YJ
Division of Cardiothoracic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia 19104, USA. wooy@uphs.penn.edu
Grand
T J
TJ
Zentko
S
S
Cohen
J E
JE
Hsu
V
V
Atluri
P
P
Berry
M F
MF
Taylor
M D
MD
Moise
M A
MA
Fisher
O
O
Kolakowski
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D047549:Coronary Artery Bypass, Off-Pump / Q000379:methods*; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood
D002316:Cardiotonic Agents; D019210:Troponin I; D010725:Phosphocreatine; D000255:Adenosine Triphosphate