Noninvasive Serial Evaluation of Myocardial Mechanics in Pressure Overload Hypertrophy of Rabbit Myocardium

Abstract

This novel noninvasive method for determination of myocardial mechanics allows for serial evaluation of cardiac function and the determination of the time course from compensated hypertrophy to myocyte failure.

Inhibition of Glycogen Synthase Kinase-3β Improves Tolerance to Ischemia in Hypertrophied Hearts

“…Details of this model have been published previously [6,7,22]. This model results in severe concentric hypertrophy by 4 to 5 weeks of age, and ventricular dilatation and dysfunction by 7 weeks.…”

“…Lithium has been shown to compete with magnesium for binding to GSK-3β and thereby blocks enzyme activity, then, inorganic phosphate attaches to the enzyme, further inactivating it [11,14,15,[17][18][19][32][33][34]. Chemical agents of the indirubin family can also inhibit GSK-3β, such as indirubin-3′-monoxime, 5-iodo-(IMI), a specific inhibitor of the enzyme, which inhibits GSK-3β by competing with ATP for binding to the catalytic site [22]. In preliminary studies perfusing hearts with different concentrations of Li (0.1 mmol/L to 3 mmol/L) or IMI (0.5 µmol/L to 50 µmol/L), we have found that the concentrations chosen in this study (0.1 mmol/L Li and 1 µmol/L IMI) had no effect on contractile function when administered to nonischemic control and hypertrophied hearts (data not shown).…”

Vascular endothelial growth factor delays onset of failure in pressure–overload hypertrophy through matrix metalloproteinase activation and angiogenesis

“…Pressure-overload hypertrophy was achieved by banding the descending aorta in ten-day-old New Zealand White rabbits as previously described [8,19]. While still in the compensated phase of hypertrophy (4 weeks of age in this model), the animals were treated with an intrapericardial administration of either 2 μg/kg VEGF 165 dissolved in PBS/0.1% rabbit serum or vehicle only via sub-xyphoid exposure of the heart.…”

“…Measurements of LV dimensions, wall thickness, and cavity volume were taken with transthoracic echocardiography with simultaneous blood pressure monitoring as we have previously described [8,19]. Measurements of LV mass to LV volume ratio (M/V ratio) were used as an index for progression of hypertrophy.…”

“…As a measure of cardiac performance, midwall contractility was determined. Calculation of midwall contractility Z-scores is based on previous experiments where serial echocardiography was performed in non-hypertrophied control animals between the ages of 3 and 7 weeks [19].…”