Abstract 116: Loss of T-type Ca 2+ Channels Alters the Cardiac Response to Myocardial Infarction

Rationale: Cav3.1 T-type calcium channels are expressed during development and then re-expressed in ventricular myocytes after pathological stress such as myocardial infarction (MI). Our lab has previously shown that mice with cardiac specific overexpression of Cav3.1 have improved contractility, survival, and preservation of the myocardial mass post-MI. Hypothesis: Loss of the Cav3.1 subunit of the T-type calcium channel reduces the ability of the heart to adapt to MI due to alterations in the wound healing response. Methods and Results: Ischemia reperfusion (IR) injury was induced in 12-16 week old Cav3.1 -/- and wild type (WT) mice. Previously collected data from our groups showed that Cav3.1 -/- mice have decreased survival after permanent occlusion MI. In the present study there was no significant difference in the one week survival of these mice after IR (100% vs 90% for WT vs Cav3.1 -/- , respectively). Cav3.1 -/- mice had significantly increased heart weight to body weight (7.066 vs 5.452) and heart weight to tibia length ratios (9.284 vs 7.594) compared to WT mice at 7 days post IR. Echocardiography performed at baseline showed no significant differences between the two groups. At 1 week post-IR, Cav3.1 -/- mice had significantly lower ejection fraction (11.58% vs 21.77%) and fractional shortening (10.02% vs 17.46%) compared to WT mice. This decrease in function was accompanied by a significantly increased percentage of fibrosis in the Cav3.1 -/- mice (26.42% vs 11.17%) and this was associated with alterations in the infiltration of proliferative inflammatory cells. The left ventricular internal diameter was also significantly increased in Cav3.1 -/- mice compared to WT (4.766 mm vs 4.151 mm). Summary and Conclusions: Cav3.1 -/- mice have decreased cardiac function and increased pathological remodeling at 1-week post-IR. The mechanisms resulting in these pathological changes appear to involve alterations in post MI inflammatory cell infiltration and myocyte survival. These results suggest that loss of Cav3.1 T-type calcium channels alters the behavior of inflammatory responses and myocyte survival after MI.