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Updated: Jul 3, 2025
Histological Quantification of Chronic Myocardial Infarct in Rats
Published on: December 11, 2016
Myocardial infarct size is reduced by nitrite and nitrate administration: a systematic review and meta-analysis of
Younes Yassaghi1, Sajad Jeddi1, Khosrow Kashfi2
1Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Insights
Nitrite and nitrate administration effectively reduces myocardial infarct size in animal studies. This finding suggests potential therapeutic benefits for ischemic heart disease, warranting further investigation.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Toxicology
Background:
- Ischemic heart disease (IHD) is a major global cause of mortality.
- Myocardial infarction (MI) is a severe complication of IHD, often leading to cardiac failure.
- Nitric oxide (NO) precursors, inorganic nitrite and nitrate, show cardioprotective potential.
Purpose of the Study:
- To systematically review and meta-analyze animal studies.
- To assess the efficacy of nitrite/nitrate administration in decreasing myocardial infarct size.
Main Methods:
- Systematic search of PubMed, Scopus, and Web of Science databases up to October 2023.
- Inclusion of 15 eligible animal studies (35 in-vivo, 10 in-vitro) published between 1989 and 2023.
- Analysis of infarct size reduction following nitrite/nitrate administration via various routes and durations.
Main Results:
- In-vivo studies demonstrated significant reduction in myocardial infarct size with nitrite (ES=-17.0%) and nitrate (ES=-9.6%).
- In-vitro studies showed nitrite significantly reduced infarct size (ES=-15.8%).
- Sensitivity analysis indicated no significant impact of dose or health conditions on nitrite's effect.
Conclusions:
- Nitrite/nitrate administration effectively reduces myocardial infarct size in animal models.
- These findings highlight the potential therapeutic role of nitrite/nitrate in managing MI.
- Caution is advised due to inherent limitations and heterogeneity in animal studies.
Abstract:
Ischemic heart disease (IHD) is the leading cause of mortality worldwide and can be complicated by myocardial infarction (MI), leading to cardiac failure. Inorganic nitrite and nitrate, which release nitric oxide (NO), can protect the heart against myocardial injury. This animal systematic review and meta-analysis aims to assess whether the administration of nitrite/nitrate decreases myocardial infarct size. We systematically searched PubMed, Scopus, and Web of Science databases until October 2023; 15 eligible animal studies (35 study arms for in-vivo and 10 for in-vitro studies) published between 1989 and 2023 were included. In-vivo studies were conducted on rats, mice, cats, and dogs, and in-vitro studies on rats and mice with an overall exposure of 0.03 to 12713 mg/kg to nitrate/nitrite administrated before, after, or during ischemia mainly by intravenous single bolus or by oral over 270 days. All in-vitro studies used nitrite/nitrate before ischemia, with the concentration ranging between 0.34 to 201 μM. MI was induced by occlusion of the left anterior diagonal or left circumflex arteries in in-vitro studies and by isoproterenol in in-vivo studies. Infarct size was measured by direct staining of the sliced heart sections. In in-vivo studies, nitrite (overall effect size (ES)=-17.0 %, 95 % confidence interval (CI)=-21.3, -12.8, P<0.001) and nitrate (overall ES= -9.6 %, 95 % CI=-15.7, -3.4, P=0.002) reduced myocardial infarct size. In in-vitro studies, nitrite (overall ES=-15.8 %, 95 % CI=-25.5, -6.2, P=0.001) reduced the infarct size. Sensitivity analysis showed that the overall effect of nitrite on myocardial infarct size was unaffected by doses or health conditions in in-vivo and in-vitro studies. In conclusion, our meta-analysis showed that nitrite/nitrate administration can effectively reduce myocardial infarct size. However, these results should be approached with caution because of the limitations of animal studies and the existing high heterogeneity.
