scholarly journals Timing of adenosine 2A receptor stimulation relative to reperfusion has differential effects on infarct size and cardiac function as assessed in mice by MRI

2008 ◽  
Vol 295 (6) ◽  
pp. H2328-H2335 ◽  
Author(s):  
Zequan Yang ◽  
Joel Linden ◽  
Stuart S. Berr ◽  
Irving L. Kron ◽  
George A. Beller ◽  
...  
Keyword(s):  
Infarct Size ◽  
Coronary Occlusion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Triphenyltetrazolium Chloride ◽  
Adenosine 2A Receptor ◽  
Treatment Window

The activation of adenosine 2A receptors before reperfusion following coronary artery occlusion reduces infarct size and improves ejection fraction (EF). In this study, we examined the effects of delaying treatment with the adenosine 2A receptor agonist ATL146e (ATL) until 1 h postreperfusion. The infarct size and EF were serially assessed by gadolinium-diethylenetriaminepentaacetic acid-enhanced MRI in C57BL/6 mice at 1 and 24 h postreperfusion. The infarct size was also assessed by 2,3,5-triphenyltetrazolium chloride staining at 24 h. Mice were treated with ATL (10 μg/kg ip) either 2 min before reperfusion (early ATL) or 1 h postreperfusion (late ATL) following the 45-min coronary occlusion. The two methods used to assess infarct size at 24 h postreperfusion (MRI and 2,3,5-triphenyltetrazolium chloride) showed an excellent correlation ( R = 0.96). The risk region, determined at 24 h postreperfusion, was comparable between the control and ATL-treated groups. The infarct size by MRI at 1 versus 24 h postreperfusion was 25 ± 1 vs. 26 ± 1% of left ventricular mass (means ± SE) in control mice, 16 ± 2 versus 17 ± 2% in early-ATL mice, and 24 ± 2 versus 25 ± 2% in late-ATL mice (intragroup, P = not significant; and intergroup, early ATL vs. control or late ATL, P < 0.05). EF was reduced in control mice but was largely preserved between 1 and 24 h in both early-ATL and late-ATL mice ( P < 0.05). In conclusion, after coronary occlusion in mice, the extent of myocellular death due to ischemia-reperfusion injury is 95% complete within 1 h of reperfusion. The infarct size was significantly reduced by ATL when given just before reperfusion, but not 1 h postreperfusion. Either treatment window helped preserve the EF between 1 and 24 h postreperfusion.

scholarly journals Metoprolol blunts the time-dependent progression of infarct size

2020 ◽  
Vol 115 (5) ◽  
Author(s):  
Manuel Lobo-Gonzalez ◽  
Carlos Galán-Arriola ◽  
Xavier Rossello ◽  
Maribel González‐Del‐Hoyo ◽  
Jean Paul Vilchez ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Primary Angioplasty ◽  
Primary Outcome Measure ◽  
Artery Occlusion ◽  
Area At Risk ◽  
Perfusion Computed Tomography ◽  
Myocardial Ischemia Reperfusion

Abstract Early metoprolol administration protects against myocardial ischemia–reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.

scholarly journals Administration of a CO-releasing molecule at the time of reperfusion reduces infarct size in vivo

2004 ◽  
Vol 286 (5) ◽  
pp. H1649-H1653 ◽  
Author(s):  
Yiru Guo ◽  
Adam B. Stein ◽  
Wen-Jian Wu ◽  
Wei Tan ◽  
Xiaoping Zhu ◽  
...  
Keyword(s):  
At Risk ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Effective Means ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Water Soluble ◽  
Arterial Blood

Although carbon monoxide (CO) has traditionally been viewed as a toxic gas, increasing evidence suggests that it plays an important homeostatic and cytoprotective role. Its therapeutic use, however, is limited by the side effects associated with CO inhalation. Recently, transition metal carbonyls have been shown to be a safe and effective means of transporting and releasing CO groups in vivo. The goal of the present study was to test whether a water-soluble CO-releasing molecule, tricarbonylchloro(glycinato) ruthenium (II) (CORM-3), reduces infarct size in vivo when given in a clinically relevant manner, i.e., at the time of reperfusion. Mice were subjected to a 30-min coronary artery occlusion followed by 24 h of reperfusion and were given either CORM-3 (3.54 mg/kg as a 60-min intravenous infusion starting 5 min before reperfusion) or equivalent doses of inactive CORM-3, which does not release CO. CORM-3 had no effect on arterial blood pressure or heart rate. The region at risk did not differ in control and treated mice (44.5 ± 3.5% vs. 36.5 ± 1.6% of the left ventricle, respectively). However, infarct size was significantly smaller in treated mice [25.8 ± 4.9% of the region at risk ( n = 13) vs. 47.7 ± 3.8% ( n = 14), P < 0.05]. CORM-3 did not increase carboxyhemoglobin levels in the blood. These results suggest that a novel class of drugs, CO-releasing molecules, can be useful to limit myocardial ischemia-reperfusion injury in vivo.

scholarly journals Comparative Effects of Verapamil, Nicardipine, and Nitroglycerin on Myocardial Ischemia/Reperfusion Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Hitoshi Yui ◽  
Uno Imaizumi ◽  
Hisashi Beppu ◽  
Mitsuhiro Ito ◽  
Munetaka Furuya ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rabbit Model ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Control Group ◽  
Area At Risk ◽  
Group A

The aim of this experiment was to establish whether verapamil, nicardipine, and nitroglycerin have (1) infarct size-limiting effects and (2) antiarrhythmic effects inin vivorabbit hearts during ischemia/reperfusion. Rabbits received regional ischemia by 30 min of left anterior descending coronary artery occlusion followed by 3 hours of reperfusion under ketamine and xylazine anesthesia. The animals were randomly assigned to the following 4 treatment groups: a control group, a verapamil group, a nicardipine group, and a nitroglycerin group. A continuous infusion of verapamil, nicardipine, or nitroglycerin was initiated 5 min prior to ischemia. Infarct size/area at risk decreased in verapamil, and nitroglycerin. The incidence of ischemia-induced arrhythmia decreased in nicardipine, verapamil and nitroglycerin. The incidence of reperfusion-induced arrhythmias decreased in verapamil and nitroglycerin. From the present experimental results, verapamil and nitroglycerin rather than nicardipine did afford significant protection to the heart subjected to ischemia and reperfusion in a rabbit model.

Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits

2006 ◽  
Vol 291 (3) ◽  
pp. H1345-H1350 ◽  
Author(s):  
Nicolas Couvreur ◽  
Laurence Lucats ◽  
Renaud Tissier ◽  
Alain Bize ◽  
Alain Berdeaux ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Infarct Size ◽  
Myocardial Stunning ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Segment Length ◽  
Wall Thickening ◽  
Area At Risk

Postconditioning, i.e., brief intermittent episodes of myocardial ischemia-reperfusion performed at the onset of reperfusion, reduces infarct size after prolonged ischemia. Our goal was to determine whether postconditioning is protective against myocardial stunning. Accordingly, conscious chronically instrumented dogs (sonomicrometry, coronary balloon occluder) were subjected to a control sequence (10 min coronary artery occlusion, CAO, followed by coronary artery reperfusion, CAR) and a week apart to postconditioning with four cycles of brief CAR and CAO performed at completion of the 10 min CAO. Three postconditioning protocols were investigated, i.e., 15 s CAR/15 s CAO ( n = 5), 30 s CAR/30 s CAO ( n = 7), and 1 min CAR/1 min CAO ( n = 6). Left ventricular wall thickening was abolished during CAO and similarly reduced during subsequent stunning in control and postconditioning sequences (e.g., at 1 h CAR, 33 ± 4 vs. 34 ± 4%, 30 ± 4 vs. 30 ± 4%, and 33 ± 4 vs. 32 ± 4% for 15 s postconditioning, 30 s postconditioning, and 1 min postconditioning vs. corresponding control, respectively). We confirmed this result in anesthetized rabbits by demonstrating that shortening of left ventricular segment length was similarly depressed after 10 min CAO in control and postconditioning sequences (4 cycles of 30 s CAR/30 s CAO). In additional rabbits, the same postconditioning protocol significantly reduced infarct size after 30 min CAO and 3 h CAR (39 ± 7%, n = 6 vs. 56 ± 4%, n = 7 of the area at risk in postconditioning vs. control, respectively). Thus, contrasting to its beneficial effects on myocardial infarction, postconditioning does not protect against myocardial stunning in dogs and rabbits. Conversely, additional episodes of ischemia-reperfusion with postconditioning do not worsen myocardial stunning.

Abstract 17348: Necrostatin 7 Limits Myocardial Infarct Size and Reduces Cardiac Remodeling After Permanent Coronary Occlusion in Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuri Dmitriev ◽  
Sarkis Minasian ◽  
Anna Dracheva ◽  
Andrey Karpov ◽  
Svetlana Chefu ◽  
...  
Keyword(s):  
Infarct Size ◽  
Rat Model ◽  
Coronary Occlusion ◽  
Ventricular Remodeling ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Morphological Characteristics ◽  
Left Ventricular ◽  
Myocardial Infarct Size

Background: Reduction of irreversible myocardial ischemia-reperfusion injury (IRI) remains important. One of the promising strategies aimed at myocardial IRI alleviation is modulation of programmed cell death (PCD) pathways. PCD mode displaying morphological characteristics of necrosis, and amenable to pharmacological manipulation is referred to as necroptosis. Necroptosis inhibitor necrostatin-1 has been shown to exert cardio- and neuroprotective effects. In the present work, the effect of necrostatin-7 (Nec-7) on myocardial injury in the rat model of permanent coronary occlusion was studied. Methods: Male Wistar rats (n = 19) were anesthetized with pentobarbital. The animals were subjected to permanent coronary occlusion (PCO) and intraperitoneal (i.p.) Nec-7 administration 1 h prior to PCO at a dose of 14.5 mg/kg in dimethyl sulfoxide (DMSO) or DMSO alone at a dose of 3.1 g/kg. Control rats were treated with saline. Three weeks after PCO, serum levels of NT-proBNP were measured, and histological outcomes were assessed. The infarct size (IS, %) and infarct length (IL, mm) were analyzed morphometrically. Results: DMSO caused significant reduction in serum NT-proBNP level vs. Control (0.3 ± 0.19 vs. 0.5 ± 0.22 ng/ml, p = 0.001), while Nec-7 further decreased NT-proBNP level in comparison with DMSO (0.2 ± 0.14 ng/ml, p = 0.008 vs. DMSO). Compared with Control, DMSO reduced adverse left ventricular remodeling, as evidenced by reduction in IS (16.0 ± 2.92 and 12.9 ± 1.72%, p = 0.015) and IL (6.2 ± 0.89 and 3.8 ± 0.35 mm, p = 0.008). Nec-7 treatment resulted in additional reduction of both IS and IL vs. DMSO group (9.0 ± 4.91 % and 2.9 ± 1.62 mm, respectively; p = 0.013 and p = 0.011 vs. DMSO, respectively). Conclusion: Nec-7 has cardioprotective properties, reducing myocardial wall stress and myocardial remodeling in the rat model of myocardial infarction.

KATPchannels mediate the beneficial effects of chronic ethanol ingestion

2000 ◽  
Vol 279 (5) ◽  
pp. H2574-H2579 ◽  
Author(s):  
Paul S. Pagel ◽  
Wolfgang G. Toller ◽  
Eric R. Gross ◽  
Meir Gare ◽  
Judy R. Kersten ◽  
...  
Keyword(s):  
Infarct Size ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Ethanol Ingestion ◽  
Protective Effects ◽  
Area At Risk ◽  
Triphenyltetrazolium Chloride ◽  
Beneficial Effects ◽  
Dry Food

Chronic ingestion of low doses of ethanol protects the myocardium from ischemic injury by activating adenosine receptors and protein kinase C. We tested the hypothesis that ATP-dependent potassium (KATP) channels mediate these beneficial effects. Dogs were fed with ethanol (1.5 g/kg) or water mixed with dry food twice per day for 12 wk. After they were acutely instrumented for measurement of hemodynamics, dogs received saline (vehicle) or glyburide (0.1 mg/kg iv) and were subjected to 60 min of coronary artery occlusion followed by 3 h of reperfusion. Infarct size (through triphenyltetrazolium chloride staining) was significantly ( P < 0.05) reduced to 14 ± 1% of the left ventricular area at risk in ethanol-pretreated dogs compared with controls (25 ± 2%). Glyburide alone did not affect infarct size (25 ± 3%) but abolished the protective effects of ethanol pretreatment (28 ± 3%). No differences in hemodynamics or coronary collateral blood flow (through radioactive microspheres) were observed among groups. The results indicate that KATPchannels mediate the protective effects of chronic consumption of ethanol.

Ebselen protects against ischemia-reperfusion injury in a canine model of myocardial infarction

1994 ◽  
Vol 267 (6) ◽  
pp. H2342-H2347 ◽  
Author(s):  
S. Hoshida ◽  
T. Kuzuya ◽  
M. Nishida ◽  
N. Yamashita ◽  
M. Hori ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Ischemic Myocardium ◽  
Regional Myocardial Blood Flow

We investigated the infarct-limiting effect of a selenoorganic compound, ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], in a canine coronary artery occlusion-reperfusion model of myocardial infarction. Ebselen, administered 1 h before coronary artery occlusion (50 mg/kg po), significantly reduced infarct size resulting from 90-min coronary artery occlusion followed by 5-h reperfusion (P < 0.05). When we examined the relation between infarct size and plasma ebselen level, infarct size in dogs with plasma ebselen level > 5 microM before reperfusion was significantly smaller (P < 0.05) than that in dogs with plasma ebselen level < or = 5 microM or in the control dogs. This infarct limitation produced by ebselen treatment was associated with an increase in reduced glutathione content and a reduction in myeloperoxidase activity in the ischemic myocardium. No differences between the control and treated groups were found in hemodynamic parameters or regional myocardial blood flow in the course of the experiment. The findings of this study demonstrate that ebselen effectively reduced the myocardial ischemia-reperfusion injury associated with preservation of the glutathione redox state and a reduction in neutrophil infiltration into the ischemic myocardium.

Abstract 2320: Long Acting Erectile Dysfunction Drug Tadalafil Limits Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Function through Protein Kinase G Dependent Pathway

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Fadi N Salloum ◽  
Ramzi A Ockaili ◽  
Antonio Abbate ◽  
Nicholas N Hoke ◽  
Vinh Q Chau ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Corpus Cavernosum ◽  
Coronary Artery Occlusion ◽  
Left Ventricular ◽  
Therapeutic Modality ◽  
Lv Function ◽  
Long Acting

Tadalafil (TAD) is a novel long acting inhibitor of phosphodiesterase-5, which enhances erectile function in men through accumulation of cGMP in the corpus cavernosum. Since cGMP-dependent protein kinase (PKG) signaling plays a key role in cardioprotection, we hypothesized that TAD would limit myocardial infarction (MI) following ischemia/reperfusion (I/R) through a mechanism involving PKG. Additionally, we contemplated that TAD would preserve left ventricular (LV) function following 30 min ischemia and 24 hr reperfusion. TAD (1 mg/kg, ip) or 10% DMSO (vehicle) was administered in ICR mice 1 hr prior to 30 min of regional ischemia by coronary artery occlusion followed by 24 hr reperfusion. In another subset of mice, KT5823 (KT), a specific PKG inhibitor (1 mg/kg, ip), was administered 10 min before TAD or 10% DMSO. Infarct size was measured at the end of reperfusion using TTC and LV function was assessed using transthoracic echocardiography. Infarct size was reduced in TAD-treated mice as compared to controls. KT abolished TAD-induced protection and KT alone had no effect on infarct size in controls (Figure ). All groups did not present with significant LV dilatation at 24 hr post infarction. However, TAD preserved fractional shortening (FS:31 ± 1.5%) as compared to control mice (FS: 22 ± 4.8%, P ± 0.05). Baseline FS was 44 ± 1.7%. KT abrogated the preservation of LV function with TAD by a marked decline in FS to 17 ± 1%. TAD is a powerful cardioprotective agent which limits MI and preserves LV function through activating PKG. Therefore, this drug may be a useful therapeutic modality to suppress I/R injury in patients with cardiovascular disease.

Abstract 449: Myristic Acid Conjugated Protein Kinase C Beta II Peptide Inhibitor Elicits Robust Cardioprotective Effects in Rat Myocardial Ischemia-Reperfusion Injury

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Alison M Baker ◽  
Melinda Beale ◽  
Daphne Metellus ◽  
Ian Madison ◽  
Sunit Singh ◽  
...  
Keyword(s):  
Infarct Size ◽  
Organ Transplantation ◽  
Myristic Acid ◽  
Untreated Control ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Peptide Inhibitor ◽  
Triphenyltetrazolium Chloride ◽  
Cardioprotective Effects

Reactive oxygen species (ROS) induced ischemia-reperfusion (I/R) injury is a phenomenon causing paradoxical myocardial damage after cardio-angioplasty, coronary bypass and organ transplantation. Previous studies show that a cell-permeable myristic acid (myr-) conjugated PKCβII peptide inhibitor given at reperfusion prevents PKCβII translocation (N - myr-SLNPEWNET; myr-PKCβII-) and significantly attenuates ROS mediated I/R injury. We included a scrambled myr-PKCβII- (N-myr-WNPESLNTE; myr-PKCβII-scram) to examine the effects of myr separately. We hypothesize that myr-PKCβII- will improve and myr-PKCβII activator peptide (N-myr-SVEIWD; myr-PKCβII+) will exacerbate infarct size and post-reperfused cardiac function compared to myr-PKCβII-scram and untreated controls. Hearts isolated from male Sprague-Dawley rats (~300g) were perfused with Krebs’ buffer at a constant pressure of 80mmHg and subjected to 30 min of global ischemia and 50 min reperfusion. Myr-PKCβII-, myr-PKCβII+, myr-PKCβII-scram (all 20μM), or untreated control were given during the first five minutes of reperfusion. Left ventricular (LV) dP/dt max and dP/dt min (mmHg/s) were measured using a pressure transducer, and infarct size was determined using 1% triphenyltetrazolium chloride staining comparing infarcted tissue vs. total tissue weight. Data were evaluated using ANOVA with Student-Newman-Keuls post-hoc analysis. Myr-PKCβII- (n=17) significantly improved LV dP/dt max and dP/dt min to 1535±107 and 1063±83 at 50 min post-reperfusion compared to untreated control (815±107 and 722±89; n=15); myr-PKCβII-scram (513±78 and 433±66; n=12), and myr-PKCβII+ (860±118 and 694±81; n=14) (all p<0.05). Myr-PKCβII- significantly reduced infarct size (%) to 13±2 compared to untreated control (24±4); myr-PKCβII-scram (22±2), and myr-PKCβII+ (21±3) (all p<0.05). Unexpectedly, myr-PKCβII-scram significantly depressed post-reperfused LV dP/dt max and LV dP/dt min compared to untreated control and other treated groups (p<0.05). Results suggest that myr-PKCβII- exerted significant cardioprotective effects compared to untreated controls, myr- PKCβII+ and myr-PKCβII-scram and would improve clinical outcomes after cardio-angioplasty or organ transplantation.

Rosuvastatin reduces experimental left ventricular infarct size after ischemia-reperfusion injury but not total coronary occlusion

2005 ◽  
Vol 288 (4) ◽  
pp. H1802-H1809 ◽  
Author(s):  
Ellen O. Weinberg ◽  
Marielle Scherrer-Crosbie ◽  
Michael H. Picard ◽  
Boris A. Nasseri ◽  
Catherine MacGillivray ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Myocardial Protection ◽  
Coronary Occlusion ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Saline Group ◽  
Left Ventricular ◽  
Deficient Mice

This study compared the effects of rosuvastatin on left ventricular infarct size in mice after permanent coronary occlusion vs. 60 min of ischemia followed by 24 h of reperfusion. Statins can inhibit neutrophil adhesion, increase nitric oxide synthase (NOS) expression, and mobilize progenitor stem cells after ischemic injury. Mice received blinded and randomized administration of rosuvastatin (20 mg·kg−1·day−1) or saline from 2 days before surgery until death. After 60 min of ischemia with reperfusion, infarct size was reduced by 18% ( P = 0.03) in mice randomized to receive rosuvastatin ( n = 18) vs. saline ( n = 22) but was similar after permanent occlusion in rosuvastatin ( n = 17) and saline ( n = 20) groups ( P = not significant). Myocardial infarct size after permanent left anterior descending coronary artery occlusion ( n = 6) tended to be greater in NOS3-deficient mice than in the wild-type saline group (33 ± 4 vs. 23 ± 2%, P = 0.08). Infarct size in NOS3-deficient mice was not modified by treatment with rosuvastatin (34 ± 5%, n = 6, P = not significant vs. NOS3-deficient saline group). After 60 min of ischemia-reperfusion, neutrophil infiltration was similar in rosuvastatin and saline groups as was the percentage of CD34+, Sca-1+, and c-Kit+ cells. Left ventricular NOS3 mRNA and protein levels were unchanged by rosuvastatin. Rosuvastatin reduces infarct size after 60 min of ischemia-reperfusion but not after permanent coronary occlusion, suggesting a potential anti-inflammatory effect. Although we were unable to demonstrate that the myocardial protection was due to an effect on neutrophil infiltration, stem cell mobilization, or induction of NOS3, these data suggest that rosuvastatin may be particularly beneficial in myocardial protection after ischemia-reperfusion injury.

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