scholarly journals Experimental parameters and infarct size in closed chest pig LAD ischemia reperfusion models; lessons learned

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Max J. M. Silvis ◽  
Gerardus P. J. van Hout ◽  
Aernoud T. L. Fiolet ◽  
Mirthe Dekker ◽  
Lena Bosch ◽  
...  
Keyword(s):  
Experimental Design ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Balloon Occlusion ◽  
Lessons Learned ◽  
Area At Risk ◽  
Closed Chest ◽  
Occlusion Time ◽  
The Impact

Abstract Background Preclinical models that resemble the clinical setting as closely as possible are essential in translating promising therapies for the treatment of acute myocardial infarction. Closed chest pig left anterior descending coronary artery (LAD) ischemia reperfusion (I/R) models are valuable and clinically relevant. Knowledge on the influence of experimental design on infarct size (IS) in these models is a prerequisite for suitable models. To this end, we investigated the impact of several experimental features (occlusion and follow-up time and influence of area at risk (AAR)) on IS. Methods A total of fifty-one female Landrace pigs were subjected to closed chest LAD balloon occlusion and evaluated in three substudies with varying protocols. To assess the relationship between time of occlusion and the IS, 18 pigs were subjected to 60-, 75- and 90 min of occlusion and terminated after 24 h of follow-up. Influence of prolonged follow-up on IS was studied in 18 pigs after 75 min of occlusion that were terminated at 1, 3 and 7 days. The relation between AAR and IS was studied in 28 pigs after 60 min of occlusion and 24 h of follow-up. The relation between VF, number of shocks and IS was studied in the same 28 pigs after 60 min of occlusion. Results Increasing occlusion time resulted in an increased IS as a ratio of the AAR (IS/AAR). This ranged from 53 ± 23% after 60 min of occlusion to 88 ± 2.2% after 90 min (P = 0.01). Increasing follow-up, from 1 to 3 or 7 days after 75 min of occlusion did not effect IS/AAR. Increasing AAR led to a larger IS/AAR (r2 = 0.34, P = 0.002), earlier VF (r2 = 0.32, P = 0.027) and a higher number of shocks (r2 = 0.29, P = 0.004) in pigs subjected to 60 min of occlusion. Conclusions These experiments describe the association of occlusion time, follow-up duration, AAR and VF with IS in closed chest pig LAD I/R models. These results have important implications for future I/R studies in pigs and can serve as a guideline for the selection of appropriate parameters and the optimal experimental design.

Recombinant Soluble P-Selectin Glycoprotein Ligand-Ig (rPSGL-Ig) Attenuates Infarct Size and Myeloperoxidase Activity in a Canine Model of Ischemia-Reperfusion

2002 ◽  
Vol 88 (07) ◽  
pp. 149-154 ◽  
Author(s):  
Xiaorong Zhou ◽  
Zhongmin Zhou ◽  
Khaldoun Tarakji ◽  
Jian Qin ◽  
Marta Sitges ◽  
...  
Keyword(s):  
Infarct Size ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Balloon Occlusion ◽  
Left Ventricular Ejection ◽  
Myeloperoxidase Activity ◽  
Ventricular Ejection Fraction ◽  
Occlusion Time ◽  
Soluble P

SummaryThe role of P-selectin in the process of reperfusion injury was evaluated using a recombinant soluble P-selectin glycoprotein ligand-Ig (rPSGL-Ig) in a canine coronary artery balloon occlusion model. rPSGL-Ig (1 mg/kg) or saline was given as an intravenous bolus 15 min before balloon deflation. Balloon occlusion time was 90 min followed by either 120 min or 7 days reperfusion. Infarct size was significantly reduced in the treatment group when expressed either as percentage of the area at risk or as absolute infarct size. Histological analysis showed that extensive myocardial injury and neutrophil infiltration were reduced by rPSGL-Ig. Myeloperoxidase activity (MPO) was significantly reduced in the risk area in the rPSGL-Ig group. Left ventricular ejection fraction was significantly less impaired during the first 24 h after reperfusion in the rPSGL-Ig group, although there was no difference by 7-day follow-up. Thus, administration of rPSGL-Ig decreases myocardial injury and inflammatory response for at least 7 days after reperfusion of ischemic myocardium.

Abstract 212: Cd4+ T-cell Activation By T-cell Receptor Engagement Contributes To Myocardial Ischemia-reperfusion Injury

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ulrich Hofmann ◽  
Denise Mathes ◽  
Johannes Weirather ◽  
Niklas Beyersdorf ◽  
Thomas Kerkau ◽  
...  
Keyword(s):  
At Risk ◽  
T Cells ◽  
T Cell ◽  
Infarct Size ◽  
T Cell Receptor ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Receptor ◽  
Area At Risk ◽  
Infarct Area

Background: We have recently shown that CD4 + but not CD8 + T-cells contribute to ischemia-reperfusion injury of the myocardium. We therefore hypothesized that CD4 + T-cells become activated by autoantigen recognition via their T-cell receptor during reperfusion. Methods and Results: Infarct size as percent of the area-at-risk was determined by combined Evans` blue and triphenyltetrazolium (TTC) staining after 30 minutes of in vivo ischemia followed by 24 hours reperfusion in mice. After 24 hours of reperfusion there was a significantly increased population of CD4 + T-cells which expressed the surface protein CD40L in comparison to sham operated mice [n≥7; p<0.05; WT 10.8 ± 0.2% vs. sham 6.4 ± 0.5%]. CD40L is typically expressed in T-cells activated by T-cell receptor engagement. OT-II mice carry a transgenic T-cell receptor with specificity for an ovalbumin-derived peptide. These mice have a limited T-cell receptor repertoire, dominated by specificity for the irrelevant antigen ovalbumin. After 30 minutes of ischemia and 24 hours of reperfusion OT-II mice showed significantly reduction in infarct size [n≥4; p= 0.02; infarct/area at risk: OTII mice 38.9 ± 2.4% vs. WT mice 63.7 ± 6.6 % ]. Administration of a CD40L blocking antibody to wildtype mice also reduced infarct size when compared to administration of isotype-matched antibodies [n≥6; p = 0.03; infarct/ area at risk: anti-CD154 treatment 60.4 ± 3.4% vs. control 75.3 ± 4.1%]. CD4 + CD25 + Foxp3 + T-cells (natural T-regulatory cells) have a low activation threshold and constitute a T-cell subset with reactivity against autoantigens. Depletion of these cells by diphtheria-toxin application in a mouse model expressing the diphtheria-toxin receptor under the Foxp3 promotor also resulted in a significant reduction of infarct size when compared to diphtheria-toxin treated wildtype mice [n≥4; p=0.03; infarct/ area at risk: T reg -depleted DEREG mice 51.9± 3% vs. WT littermates 72.3± 2%]. Conclusion: Our results indicate that CD4 + T-cells that have been activated by an MHC class II/ T-cell receptor dependent mechanism, presumably by autoantigen recognition, contribute to myocardial ischemia-reperfusion injury.

Abstract 300: Topical Application of IcyHot Reduces Myocardial Infarct Size in Rodents by a TRPA1-dependent Mechanism

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Yun Wu ◽  
Yao Lu ◽  
Eric R Gross
Keyword(s):  
Infarct Size ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion Injury ◽  
Calcium Influx ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Sprague Dawley ◽  
Area At Risk ◽  
Reactive Aldehydes

Toxic reactive aldehydes are formed during ischemia-reperfusion. The ion channel transient receptor potential ankryin 1 (TRPA1) is irreversibly modified by reactive aldehydes which can cause calcium influx and cell death. Here we tested whether topically applied creams containing a reversible TRPA1 agonist could reduce myocardial infarct size. Male Sprague-Dawley rats 8-10 weeks age were subjected to an in vivo myocardial ischemia-reperfusion model of 30 minutes of left anterior descending (LAD) coronary artery ischemia followed by 2 hours reperfusion. Prior to ischemia, rats were untreated or had 1g of cream applied to the abdomen. The creams tested were IcyHot, Bengay, Tiger Balm, or preparation H (Fig. 1A). Hearts were negatively stained for the area at risk and the infarct size was determined by using TTC staining (Fig. 1B). A subset of rodents prior to receiving IcyHot also received an intravenous bolus of the TRPA1 antagonist TCS-5861528 (1mg/kg) or AP-18 (1mg/kg). Interestingly, both IcyHot and Bengay reduced myocardial infarct size compared to untreated rodents (Fig. 1C and 1D IcyHot: 41±3%*, Bengay: 50±2%* versus control 62±1%, n=6/group, *P<0.001). Both preparation H and Tiger Balm failed to reduce myocardial infarct size (Tiger Balm: 63±2%, preparation H 59±2%). Giving a TRPA1 antagonist prior to IcyHot also blocked the reduction in infarct size. Our additional data also indicates the methyl salicylate (mint) in IcyHot and Bengay is the agent that limits myocardial infarct size. Since IcyHot and Bengay are safely used by humans, targeting TRPA1 by using products such as these could be quickly translatable and widely used to reduce ischemia-reperfusion injury.

Abstract 223: The Role Of Angiogenesis In The Myocardial Ischemia/reperfusion Injury In Pregnancy

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Jingyuan li ◽  
Zoltan Pierre Arany ◽  
Mansoureh Eghbali
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Angiogenic Factor ◽  
Daily Injection ◽  
Rate Pressure Product ◽  
Ctrl Group ◽  
The Impact ◽  
In Pregnancy

Angiogenesis plays an important role in the pathogenesis of cardiovascular disease. Pro-angiogenic and anti-angiogenic treatments have provided new insights into the impact of angiogenesis-based approaches on coronary artery disease. We have recently reported that the hearts of late pregnant (LP) mice are more prone to ischemia/reperfusion (I/R) injury compared to non pregnant(NP) mice. Provided the significant change of angiogenesis status in pregnancy, here we explored whether stimulating the angiogenesis with VEGF is able to protect the heart against I/R injury in late pregnancy, and whether anti-antigenic treatment with soluble endoglin(sENG), an anti-angiogenic factor, aggravates cardiac I/R injury in NP. Pregnant mice at day 12 either received daily injection of VEGF (100 ug/kg daily subcutaneous injection) or PBS(LP CTRL) for 7 days, and at day 19 the LP mice hearts were subjected to 20 min ischemia followed by 40 min reperfusion in Langendorff. NP mice either received a single adenovirus sENG(2х10 8particles via tail vein injection) or vehicle(NP CTRL), and 10 days later NP mice were subjected to 20 min ischemia followed by 40 min reperfusion in Langendorff. The heart function was recorded throughout the experiments, and the infarct size was measured by TTC staining at the end of experiments. Exogenous VEGF treatment significantly improved the cardiac function of LP mice after ischemia. The rate pressure product (RPP) at the end of reperfusion was improved from 1617±287 mmHg*beats/min (n=6) in LP CTRL to 11287±1783 mmHg*beats/min (n=3) in the VEGF group(p<0.01). The infarct size was also significantly reduced by VEGF treatment to 25.0±4.3% (n=3) from 57.4±5.2%(n=6) in CTRL (p<0.01). While sENG aggravated the cardiac I/R injury in NP, as the RPP at the end of reperfusion in the sENG group (4523±1281 mmHg*beats/min, n=4) was significantly lower compared with NP CTRL group(12818±1213 mmHg*beats/min, n=6)(p<0.01). Furthermore, the infarct size in the sENG group was markedly higher compared with NP CTRL group (34.0±3.3% (n=4) vs. 16.3±1.4%(n=6) in NP CTRL, p<0.05). In conclusion, anti-angiogenic treatment aggravates the cardiac I/R injury in NP, while angiogenic therapy protects the heart against I/R injury in LP.

Ischemic preconditioning in rats: role of mitochondrial KATP channel in preservation of mitochondrial function

2000 ◽  
Vol 278 (1) ◽  
pp. H305-H312 ◽  
Author(s):  
Ryan M. Fryer ◽  
Janis T. Eells ◽  
Anna K. Hsu ◽  
Michele M. Henry ◽  
Garrett J. Gross
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion ◽  
Mitochondrial Protein ◽  
Atp Synthesis ◽  
Area At Risk ◽  
Selective Antagonist ◽  
Mitochondrial Katp Channel

We examined the role of the sarcolemmal and mitochondrial KATPchannels in a rat model of ischemic preconditioning (IPC). Infarct size was expressed as a percentage of the area at risk (IS/AAR). IPC significantly reduced infarct size (7 ± 1%) versus control (56 ± 1%). The sarcolemmal KATP channel-selective antagonist HMR-1098 administered before IPC did not significantly attenuate cardioprotection. However, pretreatment with the mitochondrial KATP channel-selective antagonist 5-hydroxydecanoic acid (5-HD) 5 min before IPC partially abolished cardioprotection (40 ± 1%). Diazoxide (10 mg/kg iv) also reduced IS/AAR (36.2 ± 4.8%), but this effect was abolished by 5-HD. As an index of mitochondrial bioenergetic function, the rate of ATP synthesis in the AAR was examined. Untreated animals synthesized ATP at 2.12 ± 0.30 μmol ⋅ min−1 ⋅ mg mitochondrial protein−1. Rats subjected to ischemia-reperfusion synthesized ATP at 0.67 ± 0.06 μmol ⋅ min−1 ⋅ mg mitochondrial protein−1. IPC significantly increased ATP synthesis to 1.86 ± 0.23 μmol ⋅ min−1 ⋅ mg mitochondrial protein−1. However, when 5-HD was administered before IPC, the preservation of ATP synthesis was attenuated (1.18 ± 0.15 μmol ⋅ min−1 ⋅ mg mitochondrial protein−1). These data are consistent with the notion that inhibition of mitochondrial KATPchannels attenuates IPC by reducing IPC-induced protection of mitochondrial function.

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 Cardioprotective Effect of Novel Matrix Metalloproteinase Inhibitors

2020 ◽  
Vol 21 (19) ◽  
pp. 6990
Author(s):  
Kamilla Gömöri ◽  
Tamara Szabados ◽  
Éva Kenyeres ◽  
Judit Pipis ◽  
Imre Földesi ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Positive Control ◽  
Matrix Metalloproteinase 2 ◽  
Area At Risk ◽  
Triphenyltetrazolium Chloride

Background: We recently developed novel matrix metalloproteinase-2 (MMP-2) inhibitor small molecules for cardioprotection against ischemia/reperfusion injury and validated their efficacy in ischemia/reperfusion injury in cardiac myocytes. The aim of the present study was to test our lead compounds for cardioprotection in vivo in a rat model of acute myocardial infarction (AMI) in the presence or absence of hypercholesterolemia, one of the major comorbidities affecting cardioprotection. Methods: Normocholesterolemic adult male Wistar rats were subjected to 30 min of coronary occlusion followed by 120 min of reperfusion to induce AMI. MMP inhibitors (MMPI)-1154 and -1260 at 0.3, 1, and 3 µmol/kg, MMPI-1248 at 1, 3, and 10 µmol/kg were administered at the 25th min of ischemia intravenously. In separate groups, hypercholesterolemia was induced by a 12-week diet (2% cholesterol, 0.25% cholic acid), then the rats were subjected to the same AMI protocol and single doses of the MMPIs that showed the most efficacy in normocholesterolemic animals were tested in the hypercholesterolemic animals. Infarct size/area at risk was assessed at the end of reperfusion in all groups by standard Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining, and myocardial microvascular obstruction (MVO) was determined by thioflavine-S staining. Results: MMPI-1154 at 1 µmol/kg, MMPI-1260 at 3 µmol/kg and ischemic preconditioning (IPC) as the positive control reduced infarct size significantly; however, this effect was not seen in hypercholesterolemic animals. MVO in hypercholesterolemic animals decreased by IPC only. Conclusions: This is the first demonstration that MMPI-1154 and MMPI-1260 showed a dose-dependent infarct size reduction in an in vivo rat AMI model; however, single doses that showed the most efficacy in normocholesterolemic animals were abolished by hypercholesterolemia. The further development of these promising cardioprotective MMPIs should be continued with different dose ranges in the study of hypercholesterolemia and other comorbidities.

The Functional Endoscopic Approach to Inflammatory Sinus Disease: Current Perspectives and Technique Modifications

1988 ◽  
Vol 2 (3) ◽  
pp. 89-96 ◽  
Author(s):  
David W. Kennedy ◽  
S. James Zinreich
Keyword(s):  
Computed Tomography ◽  
Surgical Techniques ◽  
The United States ◽  
Endoscopic Examination ◽  
Lessons Learned ◽  
Current Status ◽  
Sinus Disease ◽  
Technical Modifications ◽  
The Impact

Endoscopic examination and pleuridirectional polytomography provided some important insights into the pathogenesis of inflammatory sinus disease. These insights have been further refined by the increasing utilization of endoscopy in medical therapy and surgical follow-up, and by the use of computed tomography for diagnosis. The aim of this paper is to review the current status of the diagnosis of chronic inflammatory sinus disease and of functional endoscopic surgical techniques. The impact of this approach on previously held theoretical and diagnostic concepts is evaluated. Technical modifications made since the surgery was first introduced in the United States and the lessons learned from close postsurgical endoscopic examination are presented.

scholarly journals Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression

2010 ◽  
Vol 298 (5) ◽  
pp. H1510-H1517 ◽  
Author(s):  
Wobbe Bouma ◽  
Mio Noma ◽  
Shinya Kanemoto ◽  
Muneaki Matsubara ◽  
Bradley G. Leshnower ◽  
...  
Keyword(s):  
Cell Death ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Apoptotic Cell Death ◽  
Cardiomyocyte Apoptosis ◽  
Myocardial Salvage ◽  
Area At Risk ◽  
Myocardial Area

The female sex has been associated with improved myocardial salvage after ischemia and reperfusion (I/R). Estrogen, specifically 17β-estradiol, has been demonstrated to mediate this phenomenon by limiting cardiomyocyte apoptosis. We sought to quantitatively assess the effect of sex, ovarian hormone loss, and I/R on myocardial Bax, Bcl-2, and apoptosis repressor with caspase recruitment domain (ARC) expression. Male ( n = 48), female ( n = 26), and oophorectomized female ( n = 20) rabbits underwent 30 min of regional ischemia and 3 h of reperfusion. The myocardial area at risk and infarct size were determined using a double-staining technique and planimetry. In situ oligo ligation was used to assess apoptotic cell death. Western blot analysis was used to determine proapoptotic (Bax) and antiapoptotic (Bcl-2 and ARC) protein levels in all three ischemic groups and, additionally, in three nonischemic groups. Infarct size (43.7 ± 3.2%) and apoptotic cell death (0.51 ± 0.10%) were significantly attenuated in females compared with males (56.4 ± 1.6%, P < 0.01, and 4.29 ± 0.95%, P < 0.01) and oophorectomized females (55.7 ± 3.4%, P < 0.05, and 4.36 ± 0.51%, P < 0.01). Females expressed significantly higher baseline ARC levels (3.62 ± 0.29) compared with males (1.78 ± 0.18, P < 0.01) and oophorectomized females (1.08 ± 0.26, P < 0.01). Males expressed a significantly higher baseline Bax-to-Bcl-2 ratio (4.32 ± 0.99) compared with females (0.65 ± 0.13, P < 0.01) and oophorectomized females (0.42 ± 0.10, P < 0.01). I/R significantly reduced Bax-to-Bcl-2 ratios in males. In all other groups, ARC levels and Bax-to-Bcl-2 ratios did not significantly change. These results support the conclusion that in females, endogenous estrogen limits I/R-induced cardiomyocyte apoptosis by producing a baseline antiapoptotic profile, which is associated with estrogen-dependent high constitutive myocardial ARC expression.

scholarly journals Simulated urban carbon monoxide air pollution exacerbates rat heart ischemia-reperfusion injury

2010 ◽  
Vol 298 (5) ◽  
pp. H1445-H1453 ◽  
Author(s):  
G. Meyer ◽  
L. André ◽  
S. Tanguy ◽  
J. Boissiere ◽  
C. Farah ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Environmental Factors ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Urban Pollution ◽  
Epidemiological Studies ◽  
Lactate Dehydrogenase Release ◽  
Intracellular Ca ◽  
The Impact

Myocardial damages due to ischemia-reperfusion (I/R) are recognized to be the result of a complex interplay between genetic and environmental factors. Epidemiological studies suggested that, among environmental factors, carbon monoxide (CO) urban pollution can be linked to cardiac diseases and mortality. The aim of this work was to evaluate the impact of exposure to CO pollution on cardiac sensitivity to I/R. Regional myocardial I/R was performed on isolated perfused hearts from rats exposed for 4 wk to air enriched with CO (30–100 ppm). Functional variables, reperfusion ventricular arrhythmias (VA) and cellular damages (infarct size, lactate dehydrogenase release) were assessed. Sarcomere length shortening and Ca2+ handling were evaluated in intact isolated cardiomyocytes during a cellular anoxia-reoxygenation protocol. The major results show that prolonged CO exposure worsens myocardial I/R injuries, resulting in increased severity of postischemic VA, impaired recovery of myocardial function, and increased infarct size (60 ± 5 vs. 33 ± 2% of ischemic zone). The aggravating effects of CO exposure on I/R could be explained by a reduced myocardial enzymatic antioxidant status (superoxide dismutase −45%; glutathione peroxidase −49%) associated with impaired intracellular Ca2+ handling. In conclusion, our results are consistent with the idea that chronic CO pollution dramatically increases the severity of myocardial I/R injuries.

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