Antioxidant Rich Red Palm Oil Reduces Myocardial Infarct Size: the Role of MMP-2, Akt and LDH

A recent study from our laboratory indicated the cardioprotective ability of the tocotrienol-rich fraction (TRF) from red palm oil. The present study compared cardioprotective abilities of different isomers of tocotrienol against TRF as recently tocotrienol has been found to function as a potent neuroprotective agent against stroke. Rats were randomly assigned to one of the following groups: animals were given, by gavage, either 0.35%, 1%, or 3.5% TRF for two different periods of time (2 or 4 wk) or 0.03, 0.3, and 3 mg/kg body wt of one of the isomers of tocotrienol (α, γ, or δ) for 4 wk; control animals were given, by gavage, vehicle only. After 2 or 4 wk, rats were killed, and their hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. Dose-response and time-response experiments revealed that the optimal concentration for TRF was 3.5% TRF and 0.3 mg/kg body wt of tocotrienol given for 4 wk. TRF as well as all the isomers of tocotrienol used in our study provided cardioprotection, as evidenced by their ability to improve postischemic ventricular function and reduce myocardial infarct size. The γ-isoform of tocotrienol was the most cardioprotective of all the isomers followed by the α- and δ-isoforms. The molecular mechanisms of cardioprotection afforded by tocotrienol isoforms were probed by evaluating their respective abilities to stabilize the proteasome, allowing it to maintain a balance between prodeath and prosurvival signals. Our results demonstrated that tocotrienol isoforms reduced c-Src but increased the phosphorylation of Akt, thus generating a survival signal.

Download Full-text

Dietary red palm oil supplementation reduces myocardial infarct size in an isolated perfused rat heart model

Lipids in Health and Disease ◽

10.1186/1476-511x-9-64 ◽

2010 ◽

Vol 9 (1) ◽

pp. 64 ◽

Cited By ~ 22

Author(s):

Dirk J Bester ◽

Krisztina Kupai ◽

Tamas Csont ◽

Gergu Szucs ◽

Csaba Csonka ◽

...

Keyword(s):

Infarct Size ◽

Palm Oil ◽

Rat Heart ◽

Myocardial Infarct ◽

Myocardial Infarct Size ◽

Heart Model ◽

Perfused Rat Heart ◽

Red Palm Oil ◽

Isolated Perfused Rat Heart

Download Full-text

Investigating the role of GSK3beta kinase as a molecular target for myocardial infarct size reduction by using novel pharmacological inhibitors

European Heart Journal ◽

10.1093/eurheartj/eht308.777 ◽

2013 ◽

Vol 34 (suppl 1) ◽

pp. 777-777

Author(s):

I. Andreadou ◽

A. Lazari ◽

S. I. Bibli ◽

N. Gaboriaud-Kolar ◽

A. L. Skaltsounis ◽

...

Keyword(s):

Infarct Size ◽

Myocardial Infarct ◽

Molecular Target ◽

Size Reduction ◽

Myocardial Infarct Size ◽

Infarct Size Reduction

Download Full-text

Abstract 2894: Essential Role of ERK 1/2 in Sildenafil-Induced Early and Delayed Cardioprotection in Mice

Circulation ◽

10.1161/circ.118.suppl_18.s_794-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Anindita das ◽

Lei Xi ◽

Fadi N Salloum ◽

Yuan J Rao ◽

Rakesh C Kukreja

Keyword(s):

South Carolina ◽

Infarct Size ◽

Myocardial Infarct ◽

Ischemia Reperfusion ◽

Critical Role ◽

Heart Association ◽

Myocardial Infarct Size ◽

Western Blots ◽

Delayed Cardioprotection

Background: Sildenafil (SIL), a potent inhibitor of phosphodiesterase-5 induces powerful protection against myocardial ischemia-reperfusion (I-R) injury through activation of protein kinase G (PKG). However, the downstream targets of PKG in SIL-induced cardioprotection remain unclear. We hypothesized that PKG-dependent activation of survival kinase, ERK may play a critical role in SIL-induced cardioprotection in mice. Methods & Results: Ventricular myocytes were isolated from adult male ICR mice and exposed to 40 min of simulated ischemia (SI) with/without 1 hr pre-incubation of SIL (1 μM). Myocyte necrosis and apoptosis were determined after 1 hr or 18 hrs of reoxygenation (RO) using trypan blue or TUNEL assay, respectively. Pretreatment with SIL protected cardiomyocytes after SI-RO (necrosis 18.5±0.5% and apoptosis 6.6±0.7%; n=4, p<0.001) as compared with controls (necrosis 42.1±1.8% and apoptosis 23.3±0.9%). Co-incubation of PD98059 (20 μM), a selective ERK1/2 inhibitor blocked both anti-necrotic and anti-apoptotic protection in cardiomyocytes. Furthermore, intra-coronary infusion of SIL (1 μM) in Langendorff isolated mouse hearts 10 min prior to zero-flow global I (20 min) and R (30 min) significantly reduced myocardial infarct size (from 29.4±2.4% to 16.0±3.0%; p<0.05, n=6). Co-treatment of PD98059 abrogated SIL-induced protection (33.0±5.9; n=4). To evaluate the role of ERK1/2 in delayed cardioprotection, mice were treated with saline or SIL (0.7 mg/kg i.p.) 24 hours before global I-R in Langendorff mode. PD98059 (1 mg/kg) was administered (i.p.) 30 min before the treatment of SIL. Infarct size was reduced from 27.6±3.3% in saline-treated controls to 6.9±1.2% in SIL-treated mice (P<0.05, n=6). The delayed protective effect of SIL was also abolished by PD98059 (22.5±2.3%). Western Blots revealed that SIL significantly increased phosphorylation of ERK1/2 which was blocked by PKG inhibitor, KT5823 in the heart and adult myocytes. Selective knockdown of PKG in cardiomyocytes with short hairpin RNA of PKG also blocked the phosphorylation of ERK1/2. Conclusion: SIL-induced cardioprotection involves the activation and phosphorylation of ERK which appear to be intimately linked with a PKG-dependent survival pathway. This research has received full or partial funding support from the American Heart Association, AHA Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia & Washington, DC).

Download Full-text

Abstract 1568: Loss of Ischemic Postconditioning in the Mouse Hearts Lacking Adenosine A 1 or Bradykinin B 2 Receptors

Circulation ◽

10.1161/circ.116.suppl_16.ii_326-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Lei Xi ◽

Anindita Das ◽

Zhi-Qing Zhao ◽

Vanessa F Merino ◽

Michael Bader ◽

...

Keyword(s):

Infarct Size ◽

G Protein ◽

Contractile Function ◽

Gene Knockout ◽

Myocardial Infarct ◽

Membrane Receptors ◽

Ischemic Postconditioning ◽

Myocardial Infarct Size ◽

G Protein Coupled

Background: Ischemic postconditioning (PostC) is a recently described cardioprotective modality against reperfusion injury, through a series of brief episodes of reperfusion/ischemia at the very onset of reperfusion. It has been well recognized that PostC can activate cellular signaling cascade, in which the role of G protein-coupled membrane receptors serving as upstream triggers of PostC remains to be established. Hence the goal of this study was to determine a definitive role of adenosine A 1 receptors (A1) and bradykinin B 1 or B 2 receptors (B1 or B2) in PostC, using gene knockout (KO) mice. Methods & Results: The hearts isolated from adult male C57BL/6J wild-type mice (C57-WT) or A1, B1, or B2 KO mice (n=7–9 per group) were subjected to 20 min of zero-flow global ischemia and 30 min of reperfusion with or without PostC in a Langendorff isolated, buffer-perfused heart model. PostC, consisted of 6 cycles of 10 sec of reperfusion and 10 sec of ischemia, significantly reduced myocardial infarct size (22.8±3.1%, Mean±SEM) as compared with C57-WT controls (35.1±2.8%, P<0.05). As shown in Figure below, the infarct-limiting protection of PostC was absent in A1-KO (34.9±2.7%) or B2-KO (33.3±1.7%) and was partially attenuated in B1-KO (25.6±2.9%) mice, as compared with the corresponding non-PostC controls under same genetic background (P>0.05). However, cardiac contractile function and coronary flow at the end of reperfusion were not significantly altered by PostC. Conclusion: PostC-induced infarct size reduction in globally ischemic mouse hearts is triggered by activation of multiple G protein-coupled membrane receptors, which include A1, B2, and, to a lesser extent, B1 receptors.

Download Full-text

Myocardial temperature in acute myocardial infarction: protection with mild regional hypothermia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.1.h220 ◽

1997 ◽

Vol 273 (1) ◽

pp. H220-H227 ◽

Cited By ~ 21

Author(s):

S. L. Hale ◽

R. A. Kloner

Keyword(s):

Infarct Size ◽

Myocardial Infarct ◽

Coronary Artery Occlusion ◽

Artery Occlusion ◽

Control Group ◽

Myocardial Infarct Size ◽

Local Cooling ◽

Risk Zone ◽

Myocardial Temperature

This study tests the hypothesis that a 2-4 degrees C reduction in myocardial temperature, obtained by using topical regional hypothermia (TRH), reduces infarct size. Anesthetized rabbits received coronary artery occlusion and reperfusion. We cooled hearts in the TRH group by applying an ice bag directly over the risk zone; the control group received no intervention. Risk zone myocardial temperature (MT) in the TRH group was reduced at occlusion by 2 degrees C from baseline and after 5 min of occlusion by 3.6 degrees C. In the control group, MT in the risk region remained within 0.3 degree C of baseline. The ischemic area was similar in both groups, yet infarct size in the TRH group was reduced by an average of 65% compared with the control group. Infarct size closely correlated with MT in the risk region at the time of occlusion. In a second protocol in which all hearts were paced, infarct size was 21% of the risk region in TRH hearts compared with 44% in controls. These results strongly support the important role of MT in the progression of necrosis and demonstrate that the application of local cooling to the risk region profoundly reduces myocardial infarct size.

Download Full-text