PDGF-AB-based functional cardioprotection of the aging rat heart.
Recent studies have demonstrated that targeting of an age-associated impairment in platelet-derived growth factor (PDGF-AB) pathways could reduce histological measures of myocardial infarction in aging rat hearts. To facilitate preclinical developments of this approach, non-invasive measures of cardiac function were investigated in a 24-month-old rat myocardial infarction model employing intramyocardial PDGF-AB (100 ng) or vehicle control pretreatment. Electrocardiographic recordings post-coronary occlusion revealed ST segment elevation-myocardial injury patterns in both groups, which was confirmed histologically 2 weeks later by Masson's trichrome stains (PDGF-AB, 14.6+/-2.8% of left ventricular area (LVA) vs. control, 27.9+/-9.2%; P<0.05). Echocardiographic fractional shortening (FS) measurements revealed greater preservation of cardiac function in PDGF-AB-treated hearts compared with controls (PDGF-AB FS: 27.3+/-3.7% vs. control--16.7+/-4.1% (ANOVA P=0.005) vs. sham operation--34.5+/-6.7%), with a significant inverse relationship between FS and extent of myocardial injury (m=-0.68; r=-0.84). Notably, exercise testing did not correlate with myocardial injury. These findings provide an important functional foundation in preclinical translations of PDGF-AB-based cardioprotective treatment strategies. Moreover, demonstration of respective roles of electrocardiography and echocardiography in the confirmation and correlation of myocardial injury in the aging rat heart may serve to facilitate both PDGF-AB-based and other age-targeted approaches in large animal models of aging and cardiovascular disease.
Chin
Andrew
A
Department of Medicine, Weill Medical College of Cornell University, 520 East 70th Street, Box 161, New York NY 10021, USA.
Zheng
Jingang
J
Duignan
Inga J
IJ
Edelberg
Jay M
JM
D000375:Aging / Q000502:physiology*; D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D017548:Echocardiography, Transesophageal; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006321:Heart / Q000503:physiopathology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D010982:Platelet-Derived Growth Factor / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000627:therapeutic use
D002316:Cardiotonic Agents; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; C095477:platelet-derived growth factor AB