scholarly journals Effect of Maturation on the Resistance of Rat Hearts Against Ischemia. Study of Potential Molecular Mechanisms

2015 ◽  
pp. S685-S696 ◽  
Author(s):  
L. GRIECSOVÁ ◽  
V. FARKAŠOVÁ ◽  
I. GÁBLOVSKÝ ◽  
V. K. M. KHANDELWAL ◽  
I. BERNÁTOVÁ ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Molecular Mechanisms ◽  
Contractile Function ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Cellular Mechanisms ◽  
Area At Risk ◽  
Mature Adult

Reduced tolerance to ischemia/reperfusion (IR) injury has been shown in elder human and animal hearts, however, the onset of this unfavorable phenotype and cellular mechanisms behind remain unknown. Moreover, aging may interfere with the mechanisms of innate cardioprotection (preconditioning, PC) and cause defects in protective cell signaling. We studied the changes in myocardial function and response to ischemia, as well as selected proteins involved in “pro-survival” pathways in the hearts from juvenile (1.5 months), younger adult (3 months) and mature adult (6 months) male Wistar rats. In Langendorff-perfused hearts exposed to 30-min ischemia/2-h reperfusion with or without prior PC (one cycle of 5-min ischemia/5-min reperfusion), we measured occurrence of reperfusion-induced arrhythmias, recovery of contractile function (left ventricular developed pressure, LVDP, in % of pre-ischemic values), and size of infarction (IS, in % of area at risk size, TTC staining and computerized planimetry). In parallel groups, LV tissue was sampled for the detection of protein levels (WB) of Akt kinase (an effector of PI3-kinase), phosphorylated (activated) Akt (p-Akt), its target endothelial NO synthase (eNOS) and protein kinase Cε (PKCε) as components of “pro-survival” cascades. Maturation did not affect heart function, however, it impaired cardiac response to lethal IR injury (increased IS) and promoted arrhythmogenesis. PC reduced the occurrence of malignant arrhythmias, IS and improved LVDP recovery in the younger animals, while its efficacy was attenuated in the mature adults. Loss of PC protection was associated with age-dependent reduced Akt phosphorylation and levels of eNOS and PKCε in the hearts of mature animals compared with the younger ones, as well as with a failure of PC to upregulate these proteins. Aging-related alterations in myocardial response to ischemia may be caused by dysfunction of proteins involved in protective cell signaling that may occur already during the process of maturation.

scholarly journals Inhibition of Myocardial Ischemia/Reperfusion Injury by Exosomes Secreted from Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Heng Zhang ◽  
Meng Xiang ◽  
Dan Meng ◽  
Ning Sun ◽  
Sifeng Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Left Ventricle ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Area At Risk

Exosomes secreted by mesenchymal stem cells have shown great therapeutic potential in regenerative medicine. In this study, we performed meta-analysis to assess the clinical effectiveness of using exosomes in ischemia/reperfusion injury based on the reports published between January 2000 and September 2015 and indexed in the PUBMED and Web of Science databases. The effect of exosomes on heart function was evaluated according to the following parameters: the area at risk as a percentage of the left ventricle, infarct size as a percentage of the area at risk, infarct size as a percentage of the left ventricle, left ventricular ejection fraction, left ventricular fraction shortening, end-diastolic volume, and end-systolic volume. Our analysis indicated that the currently available evidence confirmed the therapeutic potential of mesenchymal stem cell-secreted exosomes in the improvement of heart function. However, further mechanistic studies, therapeutic safety, and clinical trials are required for optimization and validation of this approach to cardiac regeneration after ischemia/reperfusion injury.

Abstract 042: Radiation-Associated Cardiovascular Risks for Future Deep-Space Missions

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Xinhua Yan ◽  
Sharath P Sasi ◽  
Hannah Gee ◽  
Juyong Lee ◽  
Yongyao Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Dose ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Heart Function ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Cardiovascular Risks ◽  
Compensatory Mechanisms ◽  
Negative Effect

During the future Moon and Mars missions astronauts will be exposed to space radiation (IR) for extended time. The effect of cosmic IR during and after space flights on cardiovascular (CV) system is unknown. Nine-month old C57BL/6N male mice were IR once with proton 50 cGy or 56Fe 15 cGy, both at 1 GeV/nucleon. We evaluated IR-induced biological responses - underlying molecular mechanisms, calcium handling, signal transduction and gene expression. Cardiac function was assessed by echocardiography and hemodynamic measurements. Left ventricular end diastolic pressure (LVEDP) was increased in 56Fe mice 1 and 3 months post-IR (p<0.001). One month post-IR, compared to control, proton- and 56Fe-IR sarcolemmal Na+-Ca2+ exchanger (NCX) (p<0.007) and sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a, p<0.02) were both increased more than 200% and p-p38 was decreased 400% (p<0.05), suggesting activation of compensatory mechanisms in [Ca2+]i handling in these hearts. By 3 months, compared to control, proton- and 56Fe-IR hearts SERCA2a and p-Creb1 was decreased 200-500% (p<0.02), suggesting reduced capacity in intracellular [Ca2+]i handling, suggesting that [Ca2+]i handling dysfunction combined with LVEDP increase in 56Fe-IR may be due to prolonged activation of compensatory mechanisms that lead to changes in SERCA2a and p-Creb1 levels. By 10 months, compared to control, LVESP was decreased in proton- and 56Fe-IR (p<0.03), suggesting IR-associated decrease in contractile function. However, compared to age-matched controls (18 months), the LVEDP was increased (p<0.05) and dP/dt Min was decreased (p<0.02) in proton-IR but not 56Fe-IR mice. This data suggests that after 10 months proton- but not 56Fe-IR affects considerably contractile and relaxation functions during aging. Our longitudinal 1, 3 and 10 months studies reveal that a single full body low dose proton- and 56Fe-IR have long-lasting negative effect on heart homeostasis during aging. The divergent effects of low dose proton vs. 56Fe-IR on heart function during aging suggest significantly different biological mechanisms responsible for this ion-dependent dichotomy over 10 months post-IR and necessitate further studies into underlying molecular mechanisms.

scholarly journals Impact of Maturation on Myocardial Response to Ischemia and the Effectiveness of Remote Preconditioning in Male Rats

2021 ◽  
Vol 22 (20) ◽  
pp. 11009
Author(s):  
Lucia Kindernay ◽  
Veronika Farkasova ◽  
Jan Neckar ◽  
Jaroslav Hrdlicka ◽  
Kirsti Ytrehus ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ventricular Arrhythmias ◽  
Glycogen Synthase ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Age Groups ◽  
Left Ventricular ◽  
Male Rats ◽  
Mature Adult ◽  
Survival Proteins

Aging attenuates cardiac tolerance to ischemia/reperfusion (I/R) associated with defects in protective cell signaling, however, the onset of this phenotype has not been completely investigated. This study aimed to compare changes in response to I/R and the effects of remote ischemic preconditioning (RIPC) in the hearts of younger adult (3 months) and mature adult (6 months) male Wistar rats, with changes in selected proteins of protective signaling. Langendorff-perfused hearts were exposed to 30 min I/120 min R without or with prior three cycles of RIPC (pressure cuff inflation/deflation on the hind limb). Infarct size (IS), incidence of ventricular arrhythmias and recovery of contractile function (LVDP) served as the end points. In both age groups, left ventricular tissue samples were collected prior to ischemia (baseline) and after I/R, in non-RIPC controls and in RIPC groups to detect selected pro-survival proteins (Western blot). Maturation did not affect post-ischemic recovery of heart function (Left Ventricular Developed Pressure, LVDP), however, it increased IS and arrhythmogenesis accompanied by decreased levels and activity of several pro-survival proteins and by higher levels of pro-apoptotic proteins in the hearts of elder animals. RIPC reduced the occurrence of reperfusion-induced ventricular arrhythmias, IS and contractile dysfunction in younger animals, and this was preserved in the mature adults. RIPC did not increase phosphorylated protein kinase B (p-Akt)/total Akt ratio, endothelial nitric oxide synthase (eNOS) and protein kinase Cε (PKCε) prior to ischemia but only after I/R, while phosphorylated glycogen synthase kinase-3β (GSK3β) was increased (inactivated) before and after ischemia in both age groups coupled with decreased levels of pro-apoptotic markers. We assume that resistance of rat heart to I/R injury starts to already decline during maturation, and that RIPC may represent a clinically relevant cardioprotective intervention in the elder population.

Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling

2007 ◽  
Vol 293 (5) ◽  
pp. H3014-H3019 ◽  
Author(s):  
Cécile Moro ◽  
Marie-Gabrielle Jouan ◽  
Andry Rakotovao ◽  
Marie-Claire Toufektsian ◽  
Olivier Ormezzano ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Ventricular Remodeling ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Cellular Mechanisms ◽  
Artery Ligation ◽  
Tnf Α

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-α occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-α can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-α, IL-1β, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3α was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.

Abstract P293: Endogenous Lats2 Plays an Important Role in Mediating Myocardial Injury Caused by Ischemia/Reperfusion Through Inhibition of FoxO3

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Dan Shao ◽  
Peiyong Zhai ◽  
Junichi Sadoshima
Keyword(s):  
Oxidative Stress ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Dominant Negative ◽  
Area At Risk ◽  
Perfused Heart ◽  
Developed Pressure

Lats2 is a tumor suppressor and a serine/threonine kinase, acting downstream of mammalian sterile 20 like kinase1 (Mst1), which stimulates apoptosis and inhibits hypertrophy in cardiomyocytes (CM). We investigated the role of Lats2 in mediating myocardial injury after ischemia/reperfusion (IR). Phosphorylation of YAP, an in vivo substrate of Lats2, was increased after 45 minutes ischemia followed by 24 hours reperfusion in control mouse hearts compared with sham, but not in dominant negative (DN) Lats2 transgenic mouse (Tg) hearts, suggesting that Lats2 is activated by IR. The size of myocardial infarction (MI)/area at risk was significantly smaller in Tg mice than in NTg mice (19% and 49%, p<0.01). And there were fewer TUNEL positive cells in Tg than in NTg mice (0.04% and 0.11%, p<0.05). Following 30 min of global ischemia and 60 min of reperfusion in Langendorff perfused heart preparations, left ventricular (LV) systolic pressure (100 vs 71mmHg, p<0.05) and LV developed pressure (79 vs 47 mmHg, p<0.05) were significantly greater in Tg than in NTg mice, indicating that suppression of Lats2 induces better functional recovery after IR. Oxidative stress, as evaluated by 8-OHdG staining, was attenuated in Tg mice. In cultured CMs, DN-Lats2 significantly decreased H 2 O 2 -induced cell death. Overexpression of Lats2 significantly downregulated (51% and 75%, p<0.05), whereas that of DN-Last2 upregulated (100 and 70%, p<0.05), MnSOD and catalase, suggesting that Lats2 negatively regulates expression of antioxidants. Reporter gene assays showed that overexpression of Lats2 significantly inhibits (−70%), whereas knocking down Lats2 by sh-Lats2 increases (+60%), FoxO3-mediated transcriptional activity. Overexpression of Lats2 in CMs inhibited FoxO3 expression, whereas that of DN-Lats2 significantly inhibited FoxO3 downregulation after IR in vivo, suggesting that Lats2 negatively regulates FoxO3 protein expression, which may lead to the downregulation of MnSOD and catalase. Taken together, these results suggest that endogenous Lats2 plays an important role in mediating myocardial injury in response to IR, In part through downregulation of FoxO3 and consequent downregulation of antioxidants and increased oxidative stress in the heart.

scholarly journals PPARα augments heart function and cardiac fatty acid oxidation in early experimental polymicrobial sepsis

2017 ◽  
Vol 312 (2) ◽  
pp. H239-H249 ◽  
Author(s):  
Stephen W. Standage ◽  
Brock G. Bennion ◽  
Taft O. Knowles ◽  
Dolena R. Ledee ◽  
Michael A. Portman ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Mouse Models ◽  
Heart Function ◽  
Left Ventricular ◽  
Cardiac Response ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Regulatory State ◽  
Peroxisome Proliferator Activated Receptor

Children with sepsis and multisystem organ failure have downregulated leukocyte gene expression of peroxisome proliferator-activated receptor-α (PPARα), a nuclear hormone receptor transcription factor that regulates inflammation and lipid metabolism. Mouse models of sepsis have likewise demonstrated that the absence of PPARα is associated with decreased survival and organ injury, specifically of the heart. Using a clinically relevant mouse model of early sepsis, we found that heart function increases in wild-type (WT) mice over the first 24 h of sepsis, but that mice lacking PPARα ( Ppara−/−) cannot sustain the elevated heart function necessary to compensate for sepsis pathophysiology. Left ventricular shortening fraction, measured 24 h after initiation of sepsis by echocardiography, was higher in WT mice than in Ppara−/− mice. Ex vivo working heart studies demonstrated greater developed pressure, contractility, and aortic outflow in WT compared with Ppara−/− mice. Furthermore, cardiac fatty acid oxidation was increased in WT but not in Ppara−/− mice. Regulatory pathways controlling pyruvate incorporation into the citric acid cycle were inhibited by sepsis in both genotypes, but the regulatory state of enzymes controlling fatty acid oxidation appeared to be permissive in WT mice only. Mitochondrial ultrastructure was not altered in either genotype indicating that severe mitochondrial dysfunction is unlikely at this stage of sepsis. These data suggest that PPARα expression supports the hyperdynamic cardiac response early in the course of sepsis and that increased fatty acid oxidation may prevent morbidity and mortality. NEW & NOTEWORTHY In contrast to previous studies in septic shock using experimental mouse models, we are the first to demonstrate that heart function increases early in sepsis with an associated augmentation of cardiac fatty acid oxidation. Absence of peroxisome proliferator-activated receptor-α (PPARα) results in reduced cardiac performance and fatty acid oxidation in sepsis.

Abstract 1008: A Protective Role for Cardiac Specific Muscle Ring Finger-1 (MuRF1) in Ischemia/Reperfusion Injury In Vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monte S Willis ◽  
Mauricio Rojas ◽  
Pamela Lockyer ◽  
Thomas G Hampton ◽  
Luge Li ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Ring Finger ◽  
Left Ventricular ◽  
Ex Situ ◽  
Histological Evaluation ◽  
Area At Risk ◽  
Fractional Shortening

We previously identified a critical role for MuRF1 in suppressing pathologic cardiac hypertrophy. To extend these observations to other pathologic processes, we tested the role of MuRF1 in cardiac ischemia reperfusion (I/R) injury. We challenged MuRF1 transgenic (Tg) mice to I/R injury both ex situ and in vivo. First, we examined isolated MuRF1 Tg and age-matched sibling wild-type (WT) hearts after global ischemia (15 min) followed by reperfusion (20 min) in a Langendorff apparatus. Baseline function of MuRF1 Tg hearts did not significantly differ from WT hearts (mean left ventricular developed pressure (LVDP) 88.5 +/− 18 vs. 82.5 +/− 6.7, respectively; n = 4/group). Mean LVDP of hearts from MuRF1 Tg mice after reperfusion was 76.0 +/− 22.9% of baseline function compared to 27.2 +/− 13.3% in WT hearts (N = 5/group, P< 0.05)). To confirm that MuRF1 is cardioprotective in vivo, we subjected MuRF1 Tg and WT mice to a 30 minute ligation of the left anterior descending coronary artery, followed by 24 hours reperfusion. Mice underwent conscious echocardiography at baseline and after 24 hours; cardiac function was further interrogated by Millar pressure volume catheterization at 24 hours. Additionally, hearts underwent a histological evaluation of area at risk and infarct size. By echocardiography, a ~7% decrease in fractional shortening was identified in MuRF1 Tg mice after 24 hours reperfusion compared to baseline. This was in striking contrast to WT mice, which exhibited ~48% decrease in fractional shortening. Steady state catheterization measurements showed a significantly higher ejection fraction in MuRF1 Tg compared to WT mice after I/R injury (81.6 ± 2.3% vs. 49.0 +/− 4.0%, P < 0.05). Contractility reflected by +dP/dt max was better preserved in MuRF1 Tg compared to WT mice after I/R injury (12,614 +/− 776 vs. 7,448 +/−752, N = 3–12/group, P < 0.05). Histologically, the area of infarct in MuRF1 Tg mice was significantly smaller (10.0 +/− 0.8%) than in WT mice (25.5 +/− 2.5%, N = 4/group, P < 0.05). We demonstrate here for the first time that cardiac MuRF1 expression preserves function after I/R injury in vivo. Since MuRF1 is known to interact with metabolic and structural targets, this model will allow us to identify mechanisms by which MuRF1 modifies cardiac pathophysiology.

Abstract 405: Inhibition of Class I Histone Deacetylases at Reperfusion Attenuates Ischemia-reperfusion Injury and Modifies Mitochondrial Acetylation

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Daniel J Herr ◽  
Sverre E Aune ◽  
Donald R Menick
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Class I ◽  
Mass Spectrometry Analysis ◽  
Rate Pressure Product ◽  
Lv Function ◽  
Mitochondrial Enzymes ◽  
Reperfusion Phase

Although rapid reperfusion of ischemic tissue is the treatment of choice for myocardial infarction, much of the resultant damage occurs as a consequence of reperfusion itself. Previously, we have shown that pretreatment with MS-275, a selective class I histone deacetylase (HDAC) inhibitor, preserves left-ventricular (LV) function and substantially reduces the area of infarcted tissue in isolated rat hearts subjected to ischemia-reperfusion (IR) injury. Here, we tested the hypothesis that MS-275 treatment at reperfusion reduces LV tissue damage and improves post-ischemic LV contractile function. To do this, hearts from male Sprague-Dawley rats were isolated and perfused ex vivo on a Langendorff perfusion apparatus. A saline-filled balloon was inserted into the left ventricle of the heart to monitor ventricular pressure development throughout the experiment. Hearts were subjected to 30 minutes of ischemia, followed by 60 minutes of reperfusion. MS-275 was administered during the entire reperfusion phase, and resultant functional data were compared to untreated hearts. There was no difference in any metric of pre-ischemic contractile function between groups. 10nM MS-275 administered at reperfusion significantly improved multiple measures of LV function, including dP/dtmax, -dP/dtmax, developed pressure and rate pressure product. We also observed a significant reduction in infarct area of treated hearts compared to control, as measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Unexpectedly, mass spectrometry analysis revealed significant changes in acetylation state of multiple mitochondrial enzymes. Administration of MS-275 during the reperfusion phase of IR is sufficient to partially rescue LV function from reperfusion-induced damage. This study emphasizes the importance of exploring class I HDAC inhibitors for protection against ischemia-reperfusion.

Role of endogenous testosterone in myocardial proinflammatory and proapoptotic signaling after acute ischemia-reperfusion

2005 ◽  
Vol 288 (1) ◽  
pp. H221-H226 ◽  
Author(s):  
Meijing Wang ◽  
Ben M. Tsai ◽  
Ajay Kher ◽  
Lauren B. Baker ◽  
G. Mathenge Wairiuko ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Functional Recovery ◽  
Caspase 3 ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Acute Ischemia ◽  
Caspase 1 ◽  
Tnf Α

Myocardial ischemia is the leading cause of death in both men and women; however, very little information exists regarding the effect of testosterone on the response of myocardium to acute ischemic injury. We hypothesized that testosterone may exert deleterious effects on myocardial inflammatory cytokine production, p38 MAPK activation, apoptotic signaling, and myocardial functional recovery after acute ischemia-reperfusion (I/R). To study this, isolated, perfused rat hearts (Langendorff) from adult males, castrated males, and males treated with a testosterone receptor blocker (flutamide) were subjected to 25 min of ischemia followed by 40 min of reperfusion. Myocardial contractile function (left ventricular developed pressure, left ventricular end-diastolic pressure, positive and negative first derivative of pressure) was continuously recorded. After reperfusion, hearts were analyzed for expression of tissue TNF-α, IL-1β, and IL-6 (ELISA) and activation of p38 MAPK, caspase-1, caspase-3, caspase-11, and Bcl-2 (Western blot). All indices of postischemic myocardial functional recovery were significantly higher in castrated males or flutamide-treated males compared with untreated males. After I/R, castrated male and flutamide-treated male hearts had decreased TNF-α, IL-1β, and IL-6; decreased activated p38 MAPK; decreased caspase-1, caspase-3, and caspase-11; and increased Bcl-2 expression compared with untreated males. These results show that blocking the testosterone receptor (flutamide) or depleting testosterone (castration) in normal males improves myocardial function after I/R. These effects may be attributed to the proinflammatory and/or the proapoptotic properties of endogenous testosterone. Further understanding may allow therapeutic manipulation of sex hormone signaling mechanisms in the treatment of acute I/R.

Lipid peroxidation contributes to cardiac deficits after ischemia and reperfusion of the small bowel

1993 ◽  
Vol 264 (5) ◽  
pp. H1686-H1692 ◽  
Author(s):  
J. W. Horton ◽  
D. J. White
Keyword(s):  
Lipid Peroxidation ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Contractile Function ◽  
Langendorff Preparation ◽  
Cardiac Contractile ◽  
Intestinal Ischemia Reperfusion

Our previous studies showed that intestinal ischemia-reperfusion (IR) impairs cardiac contractile function. The present study examined the contribution of oxygen free radicals and lipid peroxidation of cardiac cell membrane to cardiac dysfunction after intestinal IR in a rat model of superior mesenteric artery (SMA) occlusion (atraumatic clip for 20 min) and collateral arcade ligation. Controls were sham operated (group 1, n = 25). In group 2, 30 rats with SMA occlusion were killed 3-4 h after reperfusion without treatment. Aminosteroid (U-74389F), a pharmacological agent known to inhibit lipid peroxidation of membranes, was given 1 min before occlusion of the SMA (group 3, n = 19). All rats were killed 3-4 h after reperfusion of the ischemic intestine, and the hearts were harvested for in vitro assessment of cardiac function (Langendorff preparation). Cardiac contractile depression occurred in the untreated group as indicated by a fall in left ventricular pressure (from 76 +/- 3 to 64 +/- 3 mmHg, P = 0.01), maximum +dP/dt (from 1,830 +/- 60 to 1,577 +/- 64 mmHg/s, P = 0.05), and maximum -dP/dt (from 1,260 +/- 50 to 950 +/- 60 mmHg/s, P = 0.005). Lipid peroxidation of cardiac membranes occurred after untreated IR as indicated by the rise in cardiac malondialdehyde levels (MDA) (from 0.203 +/- 0.046 to 0.501 +/- 0.044 nM/mg protein, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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