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Effect of Hyperpolarization-Activated Current Blockade on the Isolated Rat Heart during Long-Term Consequences of
A M Kuptsova1, N I Ziyatdinova1, A V Krylova1
1Kazan (Volga Region) Federal University, Kazan, Russia.
Insights
Blocking hyperpolarization-activated currents (If) with ZD7288 affected left ventricular pressure differently in healthy and myocardial infarction rats. Heart rate and coronary flow decreased with If blockade in both groups.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Hyperpolarization-activated currents (If) play a crucial role in cardiac function.
- Understanding the effects of If blockade is essential for developing new cardiovascular therapies.
Purpose of the Study:
- To investigate the effects of If blockade using ZD7288 on cardiac function in sham-operated (SO) rats and rats with long-term consequences of myocardial infarction (lcMI).
- To evaluate the dose-dependent effects of If blockade on left ventricular developed pressure, heart rate, coronary flow, and contraction/relaxation dynamics.
Main Methods:
- Isolated rat hearts from SO and lcMI models were perfused and subjected to varying concentrations of ZD7288 (10-9 M and 10-5 M).
- Measurements included left ventricular developed pressure, heart rate, coronary flow, contraction duration, relaxation duration, and contraction cycle duration.
Main Results:
- If blockade demonstrated multidirectional effects on left ventricular developed pressure, varying with concentration and cardiac condition (SO vs. lcMI).
- Heart rate and coronary flow generally decreased with If blockade in both groups.
- If blockade altered contraction and relaxation durations, with notable effects on relaxation duration in SO rats.
Conclusions:
- The effects of If blockade on cardiac function are complex and depend on the concentration of the blocker and the underlying cardiac state.
- ZD7288 exhibits differential impacts on myocardial function in healthy and post-infarction hearts, suggesting potential therapeutic applications or contraindications.
Abstract:
Hyperpolarization-activated currents blockade (If) (ZD7288, 10-9 M) had a multidirectional effect on the left ventricular developed pressure in sham-operated (SO) rats and decreased this parameter in rats with long-term consequences of myocardial infarction (lcMI). The If blocker (10-5 M) increased the left ventricular developed pressure in SO rats and decreased it in the lcMI group. Heart rate of the isolated heart after If blockade decreased in both experimental groups. If blockade (10-9 M) produced multidirectional changes in coronary flow (CF) in the lcMI group and decreased CF in the SO group. The maximum concentration of the blocker reduced CF in both experimental groups. The duration of contraction of the isolated heart decreased after addition of If blocker at a minimum concentration, while the maximum concentration of If blocker increased this parameter in both groups. The If blocker increased the duration of relaxation of the isolated heart at both concentrations in all groups, the greatest changes were observed in the SO group. The duration of the contraction cycle during If blockade (10-9 M) increased in the SO group and did not change significantly in the lcMI group. At a concentration of 10-9 M, the blocker increased the duration of the contraction cycle in both groups.
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