Abstract 14873: Mouse Model of Takotsubo Cardiomyopathy: The Role of Coronary Metabolic Blood Flow Regulation in Apical Ballooning
Takotsubo cardiomyopathy, also known as “transient apical ballooning” mimics acute coronary syndrome and is characterized by transient systolic ballooning of the apex in the absence of significant coronary disease. The exact mechanism of transient apical ballooning is still unknown, but it is speculated that impaired microvascular metabolic dilation produces the pathology. Previously we studied potassium voltage gated (Kv 1.5-/-) channel null mice and found that resting blood flow was not different between wild type (WT) and Kv1.5-/-; however, at increased metabolic demands, flow in the null mice was significantly less than in WT. The level of flow in the null mice was insufficient to meet the metabolic demands of the myocardium and acute ischemia with cardiac dysfunction ensued.
Accordingly, we hypothesized that Kv1.5-/- mice, with impaired coronary metabolic dilation, develop transient apical ballooning when subjected to a chronic metabolic challenge. Transaortic constriction (TAC) was performed to increase afterload in Kv 1.5 -/- male and WT mice. 10 days after TAC the constriction was released (debanding). Cardiac function was measured at 7 days after TAC and after de-banding using echocardiography.
Results: About 50 % of Kv 1.5 -/- mice developed apical ballooning 7 after days after TAC. M-mode echocardiography was performed at the apex and at the base of the heart (Panels A and B). At the base left ventricular (LV) internal diameter at diastole was 3.85±0.05mm and at the apex was 6.8±0.03mm. The apex was significantly dilated compare to the base and it was dilated eccentrically (P<0.05). Du ring the systole the base contracted, but the apex dilated (ID=7.45±0.04) (Panel C). 7 days after de-banding apical ballooning was absent (Panel D). Cardiac function was decreased, but apex demonstrated contraction during systole. Based on these data, we conclude that alterations in the coupling of myocardial blood flow to cardiac work leads to “Takotsubo” cardiomyopathy.
- © 2013 by American Heart Association, Inc.