Table 1.
Basic characteristics of the TS group and the control group of healthy individuals.
Table 2.
Overview of environmental burden with metals in the TS group and in the control group.
Table 3.
Comparison of a number of patients with positive stimulation index (SI ≥ 3) for individual metals between TS group and healthy controls.
Fig 1.
Suggested hypothesis of pathological immune mechanisms in the Takotsubo syndrome.
TS is associated with increased levels of catecholamines in the acute phase of this condition. Hypersensitivity reactions to environmental burden with metals, which are mediated by antigen/hapten-specific T-lymphocytes, were proved in 96% of our patients with Takotsubo syndrome. Chronic or acute hypersensitivity reactions are accompanied by an inflammatory reaction with the production of many cytokines and free radicals (i.e., an increased oxidative stress). The methionin-homocysteine cycle is one of the main endogenous antioxidant systems. At the same time, the methionine-homocysteine cycle provides methyl groups for the degradation of catecholamines, a process catalysed by catechol-O-methyltransferase (COMT). An “exhaustion” of the methionine-homocysteine cycle as a result of chronic oxidative stress can lead to a decreased degradation of catecholamines; in a subsequent stressful situation, which is generally characterised by an increased production of catecholamines, excessively high levels of catecholamines can occur, such as those typically found in TS patients. TS develops most frequently in postmenopausal women, who have decreased levels of sex hormones, particularly oestrogens. In general, oestrogens have a cardioprotective effect (by reducing the chronotropic and ionotropic effects of catecholamines); additionally, when taking into account the potential hypersensitivity, oestrogens also have anti-inflammatory effects. On top of that, progesterone–of which levels also decrease with age–has immunosuppressive effects.