Abstract
Acute heart failure (AHF) commonly arises from decompensated chronic heart failure or sudden structural and functional breakdown causing a decrease in cardiac contractility and consequently fluid accumulation and systemic congestion. Current treatment for AHF aims at reducing fluid overload and improving hemodynamic which results in quick symptom relief but still poor prognostic outcome. This study utilizes a zebrafish AHF model induced by aristolochic acid (AA) to look for natural products that could attenuate the progression of AHF. The project started off by testing nearly seventy herbal crude extracts. Two of the positive extracts were from Chinese water chestnuts and are further studied in this report. After several rounds of chromatographical chemical fractionation and biological tests, a near pure fraction, named A2-4-2-4, with several hydrophilic compounds was found to attenuate the AA-induced AHF. A2-4-2-4 appeared to inhibit inflammation and cardiac hypertrophy by reducing MAPK signaling activity. Chemical analyses revealed that the major compound in A2-4-2-4 is actually lactate. Pure sodium lactate showed attenuation of the AA-induced AHF and inflammation and cardiac hypertrophy suppression as well, suggesting that the AHF attenuation ability in A2-4-2-4 is attributable to lactate. Our studies identify lactate as a cardiac protectant and a new therapeutic agent for AHF.
Highlights
Acute heart failure (AHF) is defined as new or worsening of symptoms and signs of heart failure
The project designed to use our aristolochic acid (AA)-induced zebrafish AHF model to look for potencompounds from various Chinese herbs which were extracted with different solvents, tial AHF drugs from natural sources
To further compare the mechanisms of lactate with A2-4-2-4 in attenuating AHF, we examined the inflammation in sodium lactate-treated AHF fish embryos by Quantitative RT-PCR (qRT-PCR)
Summary
Acute heart failure (AHF) is defined as new or worsening of symptoms and signs of heart failure. De novo AHF typically occurs in patients who have no previous history of heart failure but develop acute or chronic cardiac pathologies, such as cardiac ischemia, myocardial infarction, inflammatory insults, toxin insults, such as anthracycline [1,2] or chemotherapeutic agent [3], and others. The underlying cardiac pathologies first cause decreased contractility in myocardium followed by activation of several compensatory pathways as in chronic heart failure to briefly bring up the cardiac output but eventually lead to fluid accumulation, systemic congestion and organ dysfunction [4]. ADHF, which accounts for the large majority of AHF cases, occurs in patients with previously diagnosed chronic HF when the abovementioned compensatory physiological systems force the heart to exceed its limit. Many current treatments show quick relief of symptoms, they fail to significantly reduce the mortality of AHF within six months [5]
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