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S- and P-type cobra venom cardiotoxins differ in their action on isolated rat heart
Alexey S Averin1, Mikhail V Goltyaev1, Tatyana V Andreeva2
1Institute of Cell Biophysics, Federal Research Center Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Pushchino, Russia.
Background:
The cardiovascular system is one of the first systems to be affected by snake toxins; but not many toxins exert a direct effect on the heart. Cobra venom cardiotoxins are among those few toxins that attack the heart. Although the two cardiotoxin types (S and P) differ in their central-loop structure, it is not known whether they differ in their effect on the mammalian heart. We compared the effects of S- and P-type cardiotoxins, CTХ-1 and CTХ-2, respectively, from the cobra Naja oxiana, on the isolated rat heart.
Methods:
An isolated rat heart perfused according to the Langendorff technique was used in this study to investigate the activity of cardiotoxins CTX-1 and CTX-2. The following parameters were registered: the left ventricular developed pressure, calculated as the difference between systolic and diastolic pressure in the left ventricle, the end-diastolic pressure, the heart rate, time to maximal end-diastolic pressure (heart contracture), and time to depression of the heart contraction.
Results:
Both cardiotoxins at the concentration of 5 μg/mL initially produce a slight increase in systolic intraventricular pressure, followed by its rapid decrease with a simultaneous increase in diastolic intraventricular pressure until reaching contracture. CTX-2 blocks cardiac contractions faster than CTX-1; in its presence the maximum diastolic pressure is reached faster and the magnitude of the developed contracture is higher.
Conclusion:
The P-type cardiotoxin CTX-2 more strongly impairs rat heart functional activity than the S-type cardiotoxin CTX-1, as expressed in its faster blockage of cardiac contractions as well as in more rapid development and greater magnitude of contracture in its presence.
Insights
P-type cardiotoxin CTX-2 more severely impacts rat heart function than S-type cardiotoxin CTX-1. CTX-2 causes faster cardiac contraction blockage and more rapid, pronounced contracture.
Area of Science:
- Cardiovascular Physiology
- Toxicology
- Pharmacology
Background:
- Snake venom cardiotoxins directly affect the heart, a rare phenomenon.
- Cobra venom contains S- and P-type cardiotoxins with distinct structures.
- The differential effects of these cardiotoxin types on mammalian hearts remain unclear.
Purpose of the Study:
- To compare the cardiotoxic effects of S-type (CTX-1) and P-type (CTX-2) cardiotoxins from Naja oxiana.
- To investigate the impact of these cardiotoxins on isolated rat heart function.
Main Methods:
- Isolated rat hearts were perfused using the Langendorff technique.
- Key parameters monitored included left ventricular developed pressure, end-diastolic pressure, heart rate, and time to contracture and depression of contraction.
Main Results:
- Both cardiotoxins initially increased systolic pressure, followed by a rapid decrease and increased diastolic pressure leading to contracture.
- CTX-2 induced faster cardiac contraction blockage than CTX-1.
- CTX-2 resulted in a more rapid development and greater magnitude of contracture.
Conclusions:
- P-type cardiotoxin CTX-2 exhibits a more potent cardiotoxic effect on rat hearts compared to S-type CTX-1.
- The functional impairment by CTX-2 is characterized by quicker contraction blockade and more severe contracture development.
