The action of tetrodotoxin on the heart

Effects of Tetrodotoxin on the Mammalian Cardiovascular System

“…Toxin dilution on the way to the heart should be much less pronounced, when injecting the drug bolus i.v. within a few seconds [43]. For example, application of 0.5–1.0 MLD into the jugular vein within seconds could result in such a high TTX concentration in the heart that already blocks a portion of Na v 1.5 channels.…”

“…A direct negative inotropic or chronotropic action of TTX in intoxicated animals was excluded also in most if not all subsequent studies. For example, Cheng and colleagues [43,46] found that the blood flow in the ascending aorta was not measurably altered when injecting a dose of 0.25 MLD into right external jugular vein (Table 2), demonstrating that the simultaneously observed arterial hypotension was caused by peripheral vasodilatation only.…”

“…Microinjection of the same TTX dose into the nucleus tractus solitarii (NTS), a well known vasodepressive and cardio-inhibitory area, caused an increase in blood pressure. Secondly, vasodilatation resulted mainly from a conduction block in sympathetic fibers [27,35,37,39,41,43,46]. Thirdly, low doses of TTX may directly affect vascular smooth muscles [39].…”

“…Thirdly, low doses of TTX may directly affect vascular smooth muscles [39]. Several authors, however, did not observe any effect of TTX on smooth muscle tone [27,37,43]. …”

“…showed no signs of ECG alterations shortly before respiratory failure and death, despite a substantial drop in blood pressure [45]. In pithed rats, heart rate fell about 10% after injection of 1–2 MLD, but also soon regained the pre-injection state, in contrast to the long-lasting blood pressure reduction [43]. In another study, a 30–40% reduction in heart rate was observed in intoxicated rats (20 μg/kg).…”