Platelet-derived growth factor improves cardiac function in a rodent myocardial infarction model.
OBJECTIVE
The translation of cardioprotective therapies for myocardial infarction requires a preclinical demonstration of improved cardiovascular function following acute coronary occlusion. We previously showed that pretreatment of rodent hearts with platelet-derived growth factor (PDGF) promotes angiogenesis and decreases the extent of myocardial injury measured by histology. The present study aimed to determine the correlation of these histological findings with noninvasive measures of improvement in cardiac function.


METHODS
Rats were treated with intramyocardial injections of PDGF (100 ng) or phosphate buffer solution (PBS) (n = 6 per group) 24 h prior to acute, permanent ligation of the left anterior descending artery and the extent of myocardial injury was assessed by Masson's trichrome staining 14 days later. To assess the physiological effects of PDGF pretreatment after coronary occlusion, cardiac function was assessed noninvasively by electrocardiography, exercise testing and echocardiography and correlated with direct histological measures.


RESULTS
Physiological studies demonstrated that PDGF resulted in lower ST-segment elevation at the time of coronary occlusion (0.12 +/- 0.02 mV above baseline) than in PBS control rats (0.35 +/- 0.05 mV; P < 0.05). Exercise testing 14 days after coronary occlusion revealed that PDGF pretreatment resulted in faster maximal exercise speeds (28.54 +/- 3.98 m/min) than in control rats (24.98 +/- 3.13 m/min; P < 0.05). Echocardiography also revealed that the left ventricular factional shortening in the PDGF-pretreated rats was significantly greater (18.47 +/- 12.21%) than in control animals (4.91 +/- 7.21%; P<0.05).


CONCLUSIONS
These studies demonstrate that PDGF pretreatment improves cardiac function following acute coronary occlusion. Strategies based on the cardioprotective actions of PDGF may provide a significant advance in the treatment of myocardial infarction.
Zheng
Jingang
J
Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Shin
Jin H
JH
Xaymardan
Munira
M
Chin
Andrew
A
Duignan
Inga
I
Hong
Mun K
MK
Edelberg
Jay M
JM
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004452:Echocardiography; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005080:Exercise Test; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D013223:Statistics as Topic
D002316:Cardiotonic Agents; D010982:Platelet-Derived Growth Factor