All Phenotypes Tg(Myh6-Adra1a)A1A1Rmgr MGI Mouse

premature death ( J:108867 )

• 83 of 171 die at a mean age of 155 days with a cumulative mortality of 48.5%

• premature death is sudden with no signs of heart failure

cardiac fibrosis ( J:108867 )

• develop progressive cardiac fibrosis with age, beginning at 2 months of age

increased cardiac muscle contractility ( J:108879 )

• exhibit enhanced contractility as evidenced by a 33% increase in fractional shortening, a 72% decrease in left ventricle (LV) internal dimension at end-systole, an 8% decrease in LV internal dimension at end-diastole, an 80% increase in maximum dP/dt, a 76% increase in dP/dt max/LVPinst, and a 104% increase in dP/dt max:dP/dt min

increased ventricle muscle contractility ( J:108867 )

• 1-month old mutants exhibit enhanced left ventricle contractility with no change or a slight decrease in LV relaxation, resulting in a marked increase in the ratio of dP/dt max to dP/dt min

• cardiac contractility declines with age and diastolic function is reduced, although older mutants still show an increase in dP/dt max compared to wild-type

abnormal cardiac muscle relaxation ( J:108879 )

• time constant of isovolumetric relaxation is prolonged by 40%, indicating impaired relaxation

decreased left ventricle diastolic pressure ( J:108879 )

• LV end-diastolic pressure is significantly lower

increased heart rate ( J:108867 , J:108879 )

• baseline heart rate is increased by 17-27% at 2 months of age, however this difference is no longer seen in older mutants (J:108867)

• heart rate is 16% higher than in controls, however no alterations in systolic or diastolic aortic pressure is seen (J:108879)

decreased QRS amplitude ( J:108867 )

• death is preceded by a marked and progressive decrease in the QRS amplitude