The Role of Microcirculation in Takotsubo Syndrome

Objective: In a murine model of Takotsubo Syndrome (Kv1.5 null mice [TTS]), myocardial blood flow (MBF) is less in the apex than the base of the left ventricle (LV). Because of these differences, we performed RNA DeepSeq on vessels from the apex and base of the LV and found 197 differentially expressed genes with some of the most significant comprising neuroactive-receptor ligand interactions, including the endothelin pathway. To examine if endothelin could play a role in the differences in MBF in TTS we determined vascular reactivity in coronary arterioles from the LV base and apex in the TTS model. Hypothesis: We hypothesized that changed vascular reactivity in coronary arterioles may contribute to reduced coronary perfusion in TTS. Methods: Coronary arterioles were isolated from the heart apex of Wild Type (WT) and TTS mice. Vessels were cannulated, pressurized, and exposed to the NO-donor, sodium nitroprusside (SNP), acetylcholine (ACh), and endothelin. (ET-1). Results: Arterioles from TTS mice exhibited reduced responses to Acetylcholine (ACh) compared to WT, indicating impaired endothelium-dependent responses in TTS. However, there were no differences to ACh in base and apex microvessels in TTS or WT. SNP-induced vasodilation was unaltered in both groups, suggesting preserved smooth muscle responsiveness to NO donors. In contrast, constrictor responses to ET-1 were markedly enhanced in TTS mice and arterioles from the apex showed much more sensitivity than those from the base ( p < 0.01). The findings indicate that TTS parallels vascular dysfunction, characterized by diminished dilator effects of nitric oxide (NO), while the increased sensitivity to ET-1 in the apex arterioles (vs base) may explain base/apex differences in MBF in TTS. Conclusion: Coronary arterioles from TTS mice exhibit impaired vasodilation and enhanced vasoconstriction, likely contributing to reduced coronary perfusion. These alterations may exacerbate the cardiac dysfunction observed in TTS. NIH-RO1 HL161512 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.