Effects of endotoxin on neutrophil-mediated I/R injury in isolated perfused rat hearts

2001 ◽  
Vol 280 (2) ◽  
pp. H802-H811 ◽  
Author(s):  
Brian P. Lipton ◽  
Abraham P. Bautista ◽  
Joseph B. Delcarpio ◽  
Kathleen H. McDonough
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Polymorphonuclear Neutrophils ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Developed Pressure

With the use of a syngeneic model, we demonstrate that rat polymorphonuclear neutrophils (PMNs) exacerbate ischemia-reperfusion injury in the isolated rat heart. However, PMNs (19 × 106cells) from lipopolysaccharide (LPS)-treated rats (LPS-PMNs; 100 mg/kg administered 7 h before exsanguination) induce less reperfusion injury in the isolated heart. Average recovery of left ventricular developed pressure after 20 min of ischemia and 60 min of reperfusion was 51 ± 4% in hearts receiving PMNs from saline-treated control rats (saline-PMNs) versus 78 ± 2% in hearts receiving LPS-PMNs. Ischemic hearts reperfused with LPS-PMNs recovered to the same extent as did hearts reperfused with Krebs buffer only. LPS-PMNs and saline-PMNs showed no difference in basal or phorbol ester-induced superoxide production. Whereas twice the number of LPS-PMNs was positive for nitroblue tetrazolium, the percent positive for L-selectin, a receptor integral in PMN-adhesion to endothelium, was 50% less in LPS-PMNs than in controls. After reperfusion, three-fourths of the saline-PMNs remained within the hearts, whereas only one-fourth of LPS-PMNs were trapped. These data suggest that PMNs from LPS-treated rats do not exacerbate ischemia-reperfusion injury as do control PMNs, possibly, due to impaired PMN adhesion to endothelium as a result of decreased L-selectin receptors.

scholarly journals Hemidesmus indicusandHibiscus rosa-sinensisAffect Ischemia Reperfusion Injury in Isolated Rat Hearts

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Vinoth Kumar Megraj Khandelwal ◽  
R. Balaraman ◽  
Dezider Pancza ◽  
Táňa Ravingerová
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Moderate Increase ◽  
Dependent Manner ◽  
Hemidesmus Indicus ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Developed Pressure

Hemidesmus indicus(L.) R. Br. (HI) andHibiscus rosa-sinensisL. (HRS) are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R). Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure), reperfusion arrhythmias, and infarct size (TTC staining) served as the endpoints. A transient increase in LVDP (32%–75%) occurred at all concentrations of HI, while coronary flow (CF) was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55%) and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions.

Effects of the AT1 Receptor Blocker Candesartan on Myocardial Ischemia/Reperfusion in Isolated Rat Hearts

2014 ◽  
Vol 17 (5) ◽  
pp. 263 ◽  
Author(s):  
C. Murat Songur ◽  
Merve Ozenen Songur ◽  
Sinan Sabit Kocabeyoglu ◽  
Bilgen Basgut
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Relaxation Rates ◽  
Cardioplegic Solution ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Contraction And Relaxation ◽  
Isolated Rat

<p><b>Background:</b> We sought to investigate the effects of the angiotension II receptor blocker candesartan on ischemia-reperfusion injury using a cardioplegia arrested isolated rat heart model.</p><p><b>Methods:</b> Ischemia-reperfusion injury was induced in isolated rat hearts with 40 minutes of global ischemia followed by a 30-minute reperfusion protocol. Throughout the experiment, constant pressure perfusion was achieved using a Langendorff apparatus. Cardioplegic solution alone, and in combination with candesartan, was administered before ischemia and 20 minutes after ischemia. Post-ischemic recovery of contractile function, left ventricular developed pressure, left ventricular end-diastolic pressure and contraction and relaxation rates were evaluated.</p><p><b>Results:</b> In the control group, left ventricular developed pressure, rate pressure product, contraction and relaxation rates and coronary flow significantly decreased but coronary resistance increased following reperfusion. With the administration of candesartan alone, parameters did not differ compared to controls. Contractile parameters improved in the group that received candesartan in combination with the cardioplegia compared to the group that received cardioplegia alone; however, the difference between these two groups was insignificant.</p><p><b>Conclusion:</b> In this study, the addition of candesartan to a cardioplegic arrest protocol routinely performed during cardiac surgery did not provide a significant advantage in protection against ischemia-reperfusion injury compared with the administration of cardioplegic solution alone.</p>

Effects of cadmium on cardiac metallothionein induction and ischemia–reperfusion injury in rats

2009 ◽  
Vol 87 (8) ◽  
pp. 617-623 ◽  
Author(s):  
Sylvie Devaux ◽  
Véronique Maupoil ◽  
Alain Berthelot
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Antioxidant Systems ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Myocardial Ischemia Reperfusion ◽  
Developed Pressure

Myocardial ischemia–reperfusion injury is associated with an imbalance between the formation and the scavenging of reactive oxygen species. In this context, the protective role of the antioxidant metallothionein, a thiol-rich protein that is induced in different organs in response to heavy metals and oxidative conditions, has mainly been investigated in metallothionein-knockout mice or metallothionein-overexpressing mice. The aim of this study was to evaluate whether the administration of cadmium has a protective effect against cardiac ischemia–reperfusion injury and whether this is associated with induction of in vivo cardiac metallothionein. Forty-eight hours after an injection of 0, 1, or 2 mg/kg cadmium, isolated perfused rat hearts were submitted to 30 min of total global ischemia and 30 min of reperfusion.   The ischemia–reperfusion sequence was associated with a significant decrease in cardiac metallothionein levels. Pretreatment with cadmium at a dose of 2 mg/kg (i) prevented this decrease and (ii) improved the postischemic recuperation of the coronary flow, the ventricular developed pressure, and therefore, the global postischemic functional recovery. These results showed that pretreatment of rats with 2 mg/kg cadmium induced cardioprotection against ischemia–reperfusion injuries, perhaps through an in vivo metallothionein induction that may be related to a metal activation of antioxidant systems.

Myocardial reperfusion injury management: erythropoietin compared with postconditioning

2009 ◽  
Vol 297 (6) ◽  
pp. H2035-H2043 ◽  
Author(s):  
Sophie Tamareille ◽  
Nehmat Ghaboura ◽  
Frederic Treguer ◽  
Dalia Khachman ◽  
Anne Croué ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Reperfusion ◽  
Myocardial Reperfusion Injury ◽  
Gsk 3Β ◽  
Developed Pressure

Ischemic postconditioning (IPost) and erythropoietin (EPO) have been shown to attenuate myocardial reperfusion injury using similar signaling pathways. The aim of this study was to examine whether EPO is as effective as IPost in decreasing postischemic myocardial injury in both Langendorff-isolated-heart and in vivo ischemia-reperfusion rat models. Rat hearts were subjected to 25 min ischemia, followed by 30 min or 2 h of reperfusion in the isolated-heart study. Rats underwent 45 min ischemia, followed by 24 h of reperfusion in the in vivo study. In both studies, the control group ( n = 12; ischemia-reperfusion only) was compared with IPost ( n = 16; 3 cycles of 10 s reperfusion/10 s ischemia) and EPO ( n = 12; 1,000 IU/kg) at the onset of reperfusion. The following resulted. First, in the isolated hearts, IPost or EPO significantly improved postischemic recovery of left ventricular developed pressure. EPO induced better left ventricular developed pressure than IPost at 30 min of reperfusion (73.18 ± 10.23 vs. 48.11 ± 7.92 mmHg, P < 0.05). After 2 h of reperfusion, the infarct size was significantly lower in EPO-treated hearts compared with IPost and control hearts (14.36 ± 0.60%, 19.11 ± 0.84%, and 36.21 ± 4.20% of the left ventricle, respectively; P < 0.05). GSK-3β phosphorylation, at 30 min of reperfusion, was significantly higher with EPO compared with IPost hearts. Phosphatidylinositol 3-kinase and ERK1/2 inhibitors abolished both EPO- and IPost-mediated cardioprotection. Second, in vivo, IPost and EPO induced an infarct size reduction compared with control (40.5 ± 3.6% and 28.9 ± 3.1%, respectively, vs. 53.7 ± 4.3% of the area at risk; P < 0.05). Again, EPO decreased significantly more infarct size and transmurality than IPost ( P < 0.05). In conclusion, with the use of our protocols, EPO showed better protective effects than IPost against reperfusion injury through higher phosphorylation of GSK-3β.

scholarly journals Beneficial effect of tetrahydrobiopterin on ischemia-reperfusion injury in isolated perfused rat hearts

2002 ◽  
Vol 124 (4) ◽  
pp. 775-784 ◽  
Author(s):  
Satoshi Yamashiro ◽  
Katsuhiko Noguchi ◽  
Toshihiro Matsuzaki ◽  
Kanako Miyagi ◽  
Junko Nakasone ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Isolated Perfused Rat Hearts

Effects of Endotoxin on Neutrophil-Mediated Ischemia/Reperfusion Injury in the Rat Heart In Vivo

2001 ◽  
Vol 226 (4) ◽  
pp. 320-327 ◽  
Author(s):  
Brian P. Lipton ◽  
Joseph B. Delcarpio ◽  
Kathleen H. McDonough
Keyword(s):  
At Risk ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Necrotic Area ◽  
Area At Risk

We have previously shown that a nonlethal dose of lipopolysaccharide (LPS) decreases L-selectin expression of neutrophils (PMNs), thereby preventing PMN-mediated reperfusion injury in the isolated heart. In the present study we determined whether or not that dose of LPS would protect hearts during in vivo ischemia and reperfusion by preventing PMN-induced reperfusion injury. Rats receiving saline vehicle showed marked myocardial injury (necrotic area/area at risk = 82% ± 2%) and significant depression in left ventricular function as assessed in the isolated isovolumic heart preparation at constant flow rates of 5, 10, 15, and 20 ml/min. The administration of LPS (100 μg/kg body wt) 7 hr prior to ischemia resulted in a reduction in myocardial damage (necrotic area/area at risk = 42% ± 3%) and preservation of function. Myocardial function was similar to that of sham ischemic saline- and LPS-treated rats. Moreover, PMN infiltration as determined by histology was quantitatively more severe in hearts of saline-treated rats than in hearts of LPS-treated rats. Isolated hearts from vehicle- and LPS-treated animals undergoing sham ischemia in vivo recovered to the same extent after in vitro ischemia/reperfusion, suggesting that LPS did not induce protection by altering intrinsic properties of the heart. Our results indicate that LPS-induced protection of the heart from in vivo PMN-mediated ischemia/reperfusion injury may be due to decreased L-selectin expression of PMNs in LPS-treated animals.

Acute effects of 17β-estradiol on myocardial pH, Na+, and Ca2+ and ischemia-reperfusion injury

2005 ◽  
Vol 288 (1) ◽  
pp. C57-C64 ◽  
Author(s):  
Steven E. Anderson ◽  
Dawn M. Kirkland ◽  
Andrea Beyschau ◽  
Peter M. Cala
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Ovariectomized Rats ◽  
Functional Coupling ◽  
Cytosolic Ph ◽  
Thermodynamic Effect ◽  
17Β Estradiol ◽  
Developed Pressure

Evidence suggests that 1) ischemia-reperfusion injury is due largely to cytosolic Ca2+ accumulation resulting from functional coupling of Na+/Ca2+ exchange (NCE) with stimulated Na+/H+ exchange (NHE1) and 2) 17β-estradiol (E2) stimulates release of NO, which inhibits NHE1. Thus we tested the hypothesis that acute E2 limits myocardial Na+ and therefore Ca2+ accumulation, thereby limiting ischemia-reperfusion injury. NMR was used to measure cytosolic pH (pHi), Na+ (Na[Formula: see text]), and calcium concentration ([Ca2+]i) in Krebs-Henseleit (KH)-perfused hearts from ovariectomized rats (OVX). Left ventricular developed pressure (LVDP) and lactate dehydrogenase (LDH) release were also measured. Control ischemia-reperfusion was 20 min of baseline perfusion, 40 min of global ischemia, and 40 min of reperfusion. The E2 protocol was identical, except that 1 nM E2 was included in the perfusate before ischemia and during reperfusion. E2 significantly limited the changes in pHi, Na[Formula: see text] and [Ca2+]i during ischemia ( P < 0.05). In control OVX vs. OVX+E2, pHi fell from 6.93 ± 0.03 to 5.98 ± 0.04 vs. 6.96 ± 0.04 to 6.68 ± 0.07; Na[Formula: see text] rose from 25 ± 6 to 109 ± 14 meq/kg dry wt vs. 25 ± 1 to 76 ± 3; [Ca2+]i changed from 365 ± 69 to 1,248 ± 180 nM vs. 293 ± 66 to 202 ± 64 nM. E2 also improved recovery of LVDP and diminished release of LDH during reperfusion. Effects of E2 were diminished by 1 μM Nω-nitro-l-arginine methyl ester. Thus the data are consistent with the hypothesis. However, E2 limitation of increases in [Ca2+]i is greater than can be accounted for by the thermodynamic effect of reduced Na[Formula: see text] accumulation on NCE.

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