In mice with acute myocardial infarction, cardiac-directed AC(VI) expression increased survival compared to controls (74% vs 41%; P=0.004) and attenuated adverse left ventricular remodeling.
Does increased cardiac adenylyl cyclase type VI expression improve survival after acute myocardial infarction in mice?
In a mouse model of acute myocardial infarction, increased cardiac AC(VI) expression attenuates adverse LV remodeling, preserves contractile function, and improves survival.
Absolute Event Rate: 74% vs 41%
p-value: p=0.004
BACKGROUND: Cardiac-directed expression of adenylyl cyclase type VI (AC(VI)) in mice results in structurally normal hearts with normal basal heart rate and function but increased responses to catecholamine stimulation. We tested the hypothesis that increased left ventricular (LV) AC(VI) content would increase mortality after acute myocardial infarction (MI). METHODS AND RESULTS: Transgenic mice with cardiac-directed AC(VI) expression and their transgene-negative littermates (control) underwent coronary ligation, and survival, infarct size, and LV size and function were assessed 1 to 7 days after MI. Mice with increased AC(VI) expression had increased survival (control 41%, AC(VI) 74%; P = 0.004). Infarct size and myocardial apoptotic rates were similar in AC(VI) and control mice; however, AC(VI) mice had less LV dilation (P < 0.001) and increased ejection fractions (P < 0.03). Three days after MI, studies in isolated perfused hearts showed that basal LV +dP/dt was similar, but graded dobutamine infusion was associated with a more robust LV contractile response in AC(VI) mice (P < 0.05). Increased LV function was associated with increases in cAMP generation (P = 0.0002), phospholamban phosphorylation (P < 0.04), sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) affinity for calcium (P < 0.015), and reduced AV block (P = 0.04). CONCLUSIONS: In acute MI, increased cardiac AC(VI) content attenuates adverse LV remodeling, preserves LV contractile function, and reduces mortality.
Takahashi et al. (2006) studied Acute myocardial infarction. Cardiac-directed adenylyl cyclase type VI (AC(VI)) expression vs. Transgene-negative littermates (control) was evaluated on Survival (p=0.004). In mice with acute myocardial infarction, cardiac-directed AC(VI) expression increased survival compared to controls (74% vs 41%; P=0.004) and attenuated adverse left ventricular remodeling.