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Indian Journal of Pharmaceutical Education and ResearchAn Official Publication of Association of Pharmaceutical Teachers of India (APTI)
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Ivabradine Enhances its Positive Impact on the Heart Muscle/ (Myocardial Infarction) by Modulating Myocardial Nitric Oxide and ATP-dependent K+ Channels but not by Adenosine and Bradykinin Levels

1, 2, 3

  1. 1PhD Scholar, Department of Pharmacology, Nims Institute of Pharmacy, Nims University Rajasthan, Jaipur, 303121, Rajasthan, INDIA.
  2. 2Professor, Department of Pharmacology, Nims Institute of Pharmacy, Nims University Rajasthan, Jaipur, 303121, Rajasthan, INDIA.
  3. 3Associate Professor, Department of Pharmacology, Nims Institute of Pharmacy, Nims University Rajasthan, Jaipur, 303121 , Rajasthan , INDIA.

CORRESPONDENCE

Mr. Junaid Tantray

PhD Scholar, Department of Pharmacology, Nims Institute of Pharmacy, Nims University Rajasthan, Jaipur, 303121, Rajasthan, INDIA.

junaidtantray22@gmail.com

Received: 05-05-2024; Revised: 14-01-2025; Accepted: 22-02-2025.

Volume 59, Issue 3s (Supplement) · pp. s1026-s1040 · 2025 · DOI: 10.5530/ijper.20251359

ABSTRACT

Background: This study aimed to explore the cardioprotective effects of ivabradine and examine potential secondary mechanisms beyond the established role of If-HCN channel inhibition demonstrated in cellular studies.Objectives: Our hypothesis centered on the idea that Ivabradine could induce responses similar to ischemic preconditioning involving nitric oxide, adenosine, bradykinin, and ATP-dependent potassium channels.Materials and Methods: Ischemia-reperfusion injury was established using Langendroff’s technique. 20 min ischemia and 40 min reperfusion to coronary artery to isolated heart was model of myocardial infarction. There were following groups: Control (Ischeamia-Reperfusion), Ischemic preconditioning, ivabradine (10 µmol/L), ivabradine+L-NAME (30 µmol/L) and ivabradine+Aminoguanidine (30 µmol/L), ivabradine+Theophylline (50 µmol/L), ivabradine+Aminophylline (50 µmol/L), ivabradine+Enalapiril (100 µmol/L), ivabradine+Losartan (50 µmol/L), ivabradine+Gliclazide (30 µmol/L), ivabradine+glimepiride (50 µmol/L) in perfusat.Results: Ivabradine has demonstrated the potential for providing cardiovascular defence. (Infarct Size: 5.334±0.422%; LDH: 101.500±1.147 I.U.; CK-MB: 100.167±1.302 I.U.) Ischemic preconditioning presents significant potential for enhancing cardioprotective effects. Infarct Size: 5.1667±0.478% LDH: 101.667±2.789 I.U.; CK-MB: 97.167±1.721 I.U.). Ivabradine+L-NAME (Infarct size: 64.167±0.872%; LDH: 154.667±1.256 I.U.; CK-MB: 200.167±1.537 I.U.). Ivabradine+Aminoguanidine (Infarct Size: 64.500±0.885%; LDH: 154.833±1.138 I.U.; CK-MB: 198.333±1.145 I.U.). Ivabradine+Theophylline (Infarct Size: 5.333±0.422%; LDH: 102.5±2.923 I.U.; CK-MB: 97.167±1.721 I.U.). Ivabradine+Aminophylline (Infarct Size: 5.667±0.333%; LDH: 102.833±1.515 I.U.; CK-MB: 100.833±1.250 I.U.). Ivabradine+Enalapril (Infarct Size: 5.500±0.428%; LDH: 102.667±1.498 I.U.; CK-MB: 100.667±1.429 I.U.). Ivabradine+Losartan (Infarct Size: 5.333±0.667%; LDH: 102.167±1.751 I.U.; CK-MB: 101.833±1.400 I.U.). Ivabradine+Gliclazide (Infarct Size: 63.833±1.352%; LDH: 154.667±1.054 I.U.; CK-MB: 201.833±1.815 I.U.). Ivabradine+Glimepiride (Infarct Size: 63.667±0.989%; LDH: 155.833±1.352 I.U.; CK-MB: 199.833±1.579 I.U.).Conclusion: Ivabradine and ischemic preconditioning exhibited cardioprotective effects by reducing infarct size, along with Lactate Dehydrogenase isoenzyme (LDH) and Creatine Kinase isoenzyme (CK-MB) levels. In contrast, treatments with L-NAME, Aminoguanidine, Gliclazide, and Glimepiride led to increased infarct size, LDH, and CK-MB levels. Meanwhile, Theophylline, Aminophylline, Enalapril, and Losartan contributed to a reduction in infarct size, LDH, and CK-MB levels. These findings suggest that ivabradine-induced cardioprotection does not involve nitric oxide, adenosine, or bradykinin pathways.

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    Tantray, J., Sharma, A. K., & Sharma, R. K. (2025). Ivabradine Enhances its Positive Impact on the Heart Muscle/ (Myocardial Infarction) by Modulating Myocardial Nitric Oxide and ATP-dependent K+ Channels but not by Adenosine and Bradykinin Levels. Indian Journal of Pharmaceutical Education and Research, 59(3s), s1026-s1040. https://doi.org/10.5530/ijper.20251359

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