Increased susceptibility of hypertrophied hearts to ischemic injury.
Cardiac hypertrophy is an adaptive response that compensates for increased workload by normalizing wall stress and preserving cardiac contractile function. In advanced stages, however, clinical and experimental studies have shown that when the high workload is maintained, hypertrophy progresses to ventricular dilatation, contractile dysfunction, and decreased tolerance to ischemia/reperfusion. Development of hypertrophy is accompanied by distinct qualitative and quantitative changes in contractile protein expression and isoform switching, cytosolic calcium regulation, and substrate delivery and use. We have focused our investigations on changes in substrate delivery and capillary density in pressure overload hypertrophy and on the effects that these changes have on tolerance to ischemia/reperfusion. This report summarizes our work in this area using a model of aortic banding in 10-day-old rabbits, which exhibits the same pattern of concentric hypertrophy early, followed by ventricular dilatation and contractile dysfunction that is clinically apparent.
Friehs
Ingeborg
I
Department of Cardiac Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
del Nido
Pedro J
PJ
D000818:Animals; D000831:Animals, Newborn; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004730:Endothelium, Vascular / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D009004:Monosaccharide Transport Proteins / Q000502:physiology; D009124:Muscle Proteins; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits; D020257:Ventricular Remodeling / Q000502:physiology
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D005947:Glucose