Abstract
BackgroundThis study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points.MethodsIn normal isolated rat hearts, coronary flow, left ventricular developed pressure, heart rate, and functional recovery were measured using the Langendorff preparation. Hearts were perfused with either (i) Krebs-Henseleit (normal) solution, (control), or with 30, 100 μg/ml B. monnieri ethanolic extract (30 min), or (ii) with normal solution or extract for 10 min preceding no-perfusion ischemia (30 min) followed by reperfusion (30 min) with normal solution. Infarct volumes were measured by triphenyltetrazolium staining. L-type Ca2+-currents (ICa, L) were measured by whole-cell patching in HL-1 cells, a mouse atrial cardiomyocyte cell line. Cytotoxicity of B. monnieri was assessed in rat isolated ventricular myocytes by trypan blue exclusion.ResultsIn normally perfused hearts, B. monnieri increased coronary flow by 63 ± 13% (30 μg/ml) and 216 ± 21% (100 μg/ml), compared to control (5 ± 3%) (n = 8–10, p < 0.001). B. monnieri treatment preceding ischemia/reperfusion improved left ventricular developed pressure by 84 ± 10% (30 μg/ml), 82 ± 10% (100 μg/ml) and 52 ± 6% (control) compared to pre- ischemia/reperfusion. Similarly, functional recovery showed a sustained increase. Moreover, B. monnieri (100 μg/ml) reduced the percentage of infarct size from 51 ± 2% (control) to 25 ± 2% (n = 6-8, p < 0.0001). B. monnieri (100 μg/ml) reduced ICa, L by 63 ± 4% in HL-1 cells. Ventricular myocyte survival decreased at higher concentrations (50–1000 μg/ml) B. monnieri.ConclusionsB. monnieri improves myocardial function following ischemia/reperfusion injury through recovery of coronary blood flow, contractile force and decrease in infarct size. Thus this may lead to a novel cardioprotectant strategy.
Highlights
This study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points
We aimed to show that an extract of B. monnieri could improve myocardial perfusion in normally beating isolated rat hearts and to show that it produces an independent acute recovery in cardiac function after I/R while at the same time not creating cellular toxicity in isolated ventricular myocytes
Application of 30 or 100 μg/ml B. monnieri for 30 min produced a concentration-dependent increase in coronary flow (Fig. 1b) and left ventricular developed pressure (LVDP) (Fig. 1c)
Summary
This study explored Bacopa monnieri, a medicinal Ayurvedic herb, as a cardioprotectant against ischemia/reperfusion injury using cardiac function and coronary flow as end-points. Mitochondrial Ca2+ homeostasis fails, leading to disruption of the electron transport chain, cytochrome C release and initiation of apoptosis. These changes are slow during sustained occlusion [2] but most damage begins on reperfusion. Reperfusion is accompanied by excessive superoxide production [3] and leads to other reactive species which increase cell damage and to further cytosolic Ca2+ loading [4]. Endothelial cells generate further superoxide via adherent xanthine oxidase, cytokine activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and oxidised nitric oxide (NO) synthase [5]. We have a potent cytotoxic combination of Ca2+, superoxide, inflammation and vasoconstriction, all of which conspire over the ensuing minutes-hours in myocardial cell death
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