Is High-Dose Catecholamine Administration in Small Animals an Appropriate Model for Takotsubo Syndrome?
Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp (rats and mice) has been in the range of 15-40%. 1-3 This is not comparable to the mortality rate in human patients with TTS (1-3%). This difference suggests that the doses used experimentally are in the toxic range. (e) Experimental models may have some echocardiographic and/or electrocardiographic resemblance to TTS, but it is difficult to assess those features (apical ballooning) in a small
... l heart, beating at more than 300 beats/min (see Figure 1 1 ). 2. The review article 1 concludes that clinical TTS must be a product of catecholamine overload, but TTS more closely resembles "stunned myocardium" (severe, localized reversible dysfunction). The authors quickly dismiss coronary spasm, the usual explanation for stunning, as an explanation for TTS; however, there is recent human evidence (although only from pilot studies) to suggest that endothelial dysfunction with coronary spasm may indeed play an essential, causal role in TTS. Recent studies even show the experimental reproduction of TTS in recovering patients, as assessed by acetylcholine (ACh) testing of endothelial function. 6,7 Systematic use of ACh testing in the recovery phase of TTS has shown repeatedly that ACh induces intense spasm of the related territories, accompanied by reproduction of TTS in the myocardial segments originally affected. 6 This spasm (and left ventricular dysfunction) is promptly and consistently eliminated by intracoronary administration of nitroglycerine. An appropriate experimental animal model of TTS must address these important features of TTS. Toxic doses of catecholamines are not likely to be helpful in creating such a model, as they seem to cause more sustained and profound myocardial changes than those associated with TTS.