Major alterations in relaxation during cardiac hypertrophy induced by aortic stenosis in guinea pig.
Left ventricular hypertrophy (LVH) was produced in guinea pigs after aortic stenosis (AS). The percentage of LVH in AS was determined by normalizing left ventricular (LV) weight by the mean LV weight of sham-operated controls (n = 12). After 3 weeks of cardiac overload, a mild LVH (30 +/- 3%) was induced in 17 animals and a relatively severe LVH (56 +/- 3%) was induced in 7 animals. LV papillary muscles were rapidly excised for mechanical studies. No significant differences were observed between control and mild hypertrophy groups. In contrast, a marked decrease in myocardial performance was seen in the more severe cardiac hypertrophy group and was expressed as a percentage of sham-operated levels (Vmax, 22%; active isometric force/mm2, 23%; +dF/dt max/mm2, 26%). Relaxation in this group was still more impaired than contraction (peak lengthening velocity, 14%; -dF/dt max/mm2, 19%). Moreover, the load sensitivity of relaxation was present in both sham-operated controls and mild hypertrophy but almost disappeared in more severe hypertrophy. Isometric relaxation was delayed in the latter group, as shown by the 15% increase of the half-time of the decline of isometric relaxation (t 1/2). On the other hand, acute hypoxia (95% N2-5% CO2 for 20 minutes) also induced a fall in contractility and the disappearance of the load sensitivity of relaxation but with a 67% decrease of t 1/2. Thus, the mechanical analysis of relaxation allows the effects of chronic overload in relatively severe cardiac hypertrophy to be separated from those of acute hypoxia. Moreover, in severe cardiac hypertrophy, the impairment of the load sensitivity of relaxation with increased t 1/2 strongly suggests alterations of the sarcoplasmic reticulum, especially since the moderate decrease in the myofibrillar ATPase activity, which has been observed previously in guinea pig pressure overload, cannot account completely for the marked fall in myocardial performance.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications* / Q000503:physiopathology; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D009210:Myofibrils / Q000201:enzymology; D010101:Oxygen Consumption; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology
D000251:Adenosine Triphosphatases