cardiovascular system
• mice challenged with isoproterenol exhibit altered cardiac gap junctions
• rapid pacing of isolated hearts induces changes in connexin 43 protein expression, solubility, and isoform distribution and results in accumulation of dephosphorylated connexin 43 isoform P0 in cardiac tissue
• cardiac tissue after isoproterenol challenge shows a reduction in junctional connexin 43 and regions of connexin 43 isoform P0 accumulation
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• small decrease in heart weight to body weight ratio
• mice do not exhibit cardiac hypertrophy
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• rapid pacing of isolated hearts increases anisotropy ratio, with transverse conduction velocity reduced by more than 20%
• after rapid pacing challenge, the myocardium, in areas of connexin 43 isoform P0 accumulation, is energetically compromised as indicated by an increase in activated AMP-dependent kinase in these areas resulting in ATP depletion
• following pacing, Lucifer yellow dye spread through intact cardiomyocytes is reduced indicating reduced gap junctional intercellular coupling
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• 25% of mice challenged with the catecholamine isoproterenol exhibit ventricular tachycardia
• rapid pacing of isolated hearts induces ventricular tachycardia in more than 50% of mice
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• 56% of mice challenged with the catecholamine isoproterenol exhibit ventricular ectopy
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• mice treated with isoproterenol exhibit progressive prolongation of QRS duration
• rapid pacing of isolated hearts causes progressive QRS prolongation
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• papillary muscle fibers exhibit increased calcium sensitivity of steady state force development in both sedentary and exercised groups
• maximal steady state force developed by muscle fibers is decreased in both sedentary and exercised groups
• muscle fibers show an increased rate of force activation and moderately increased rate of relaxation
• cardiac muscle is less sensitive to acidic pH and shows a smaller decrease in calcium-sensitivity of force development indicating a loss of sensitivity to pH-induced shifts in calcium dependence of force
• large increase in the calcium sensitivity of the ATPase activity and force development in skinned fibers
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mortality/aging
N |
• mice exhibit normal survival and chronic swimming exercises do not affect survival
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
hypertrophic cardiomyopathy 2 | DOID:0110308 |
OMIM:115195 |
J:213305 |