On the pathophysiology of takotsubo syndrome triggered by administered adrenergic agonists, noted in the JADER database

Background: The most serious complication of the acute Takotsubo phase is a myocardial perforation, which is rare, but it usually results in the death of the patient. Methods: In the years 2008–2020, 265 patients were added to the Podlasie Takotsubo Registry. Cardiac rupture was observed in five patients (1.89%), referred to as the Takotsubo syndrome with complications of cardiac rupture (TS+CR) group. The control group consisted of 50 consecutive patients with uncomplicated TS. The diagnosis of TS was based on the Mayo Clinic Criteria. Results: Cardiac rupture was observed in women with TS aged 74–88 years. Patients with TS and CR were older (82.20 vs. 64.84; p = 0.011), than the control group, and had higher troponin, creatine kinase, aspartate aminotransferase, and blood glucose levels (168.40 vs. 120.67; p = 0.010). The TS+CR group demonstrated a higher heart rate (95.75 vs. 68.38; p < 0.0001) and the Global Registry of Acute Coronary Events (GRACE) scores (186.20 vs. 121.24; p < 0.0001) than the control group. In patients with CR, ST segment elevation was recorded significantly more often in the III, V4, V5 and V6 leads. Left ventricular free wall rupture was noted in four patients, and in one case, rupture of the ventricular septum. In a multivariate logistic regression, the factors that increase the risk of CR in TS were high GRACE scores, and the presence of ST segment elevation in lead III. Conclusions: Cardiac rupture in TS is rare but is the most severe mechanical complication and is associated with a very high risk of death. The main risk factors for left ventricular perforation are female gender, older age, a higher concentration of cardiac enzymes, higher GRACE scores, and ST elevations shown using electrocardiogram (ECG).

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Inhibition of Glutamatergic Synaptic Input to Spinal Lamina IIo Neurons by Presynaptic α2-Adrenergic Receptors

Journal of Neurophysiology ◽

10.1152/jn.00575.2001 ◽

2002 ◽

Vol 87 (4) ◽

pp. 1938-1947 ◽

Cited By ~ 86

Author(s):

Yu-Zhen Pan ◽

De-Pei Li ◽

Hui-Lin Pan

Keyword(s):

Receptor Antagonist ◽

Synaptic Input ◽

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Dorsal Root ◽

Primary Afferents ◽

Noradrenergic System ◽

Analgesic Action ◽

Adrenergic Agonists ◽

Excitatory Synaptic Input

Activation of spinal α2-adrenergic receptors by the descending noradrenergic system and α2-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered α2-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina IIo) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic α2-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina IIo neurons. Whole cell voltage-clamp recordings were performed on visualized lamina IIo neurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 μM) significantly decreased the frequency of mEPSCs from 5.8 ± 0.9 to 2.7 ± 0.6 Hz (means ± SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina IIo neurons. Yohimbine (2 μM, an α2-adrenergic receptor antagonist), but not prazosin (2 μM, an α1-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1–20 μM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine ( n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina IIo neurons through activation of α2-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina IIoneurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and α2-adrenergic agonists.

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