Stress-induced takotsubo syndrome: dynamic changes in regional cerebral metabolism revealed by quantitative PET imaging

Abstract

Stress significantly contributes to cardiovascular diseases such as Takotsubo syndrome (TTS), which mimics an acute coronary syndrome without coronary obstruction. TTS is triggered by surgery, trauma, and emergency treatments in patients, and is reproduced in animal models by a catecholamine surge that impacts cardiac sympathetic innervation. The action of catecholamines on energy metabolism is well documented in the heart, less so in the brain. We investigated the effects of acute catecholaminergic stress on regional cerebral glucose metabolism and interregional metabolic organization in a TTS rat model using FDG-PET and quantitative two- tissue compartment modeling. Adult female rats received a single intraperitoneal injection of isoprenaline (ISO) (50 mg/kg). Dynamic FDG-PET imaging was performed at baseline, 2 hours (acute phase), and 7 days (recovery phase) post-injection. Kinetic parameters, namely glucose inflow (K1) and glucose phosphorylation (k3), were quantified in 58 brain regions. Interregional metabolic coordination, defined as statistically significant linear correlations between regional kinetic parameters, was assessed across functional brain areas. During the acute phase, the catecholaminergic surge induced widespread reductions in glucose inflow and regional decreases in phosphorylation, particularly in the limbic and sensorimotor areas. During the recovery phase, most regions remained below baseline. Metabolic coordination increased for glucose inflow in both phases but declined for phosphorylation, especially during recovery, indicating a disruption of metabolic synchronization. Persistent changes in brain metabolism imply that mid-to-long-term changes in regional cerebral metabolism may contribute to long-term TTS consequences.