Inhibition of PLC improves postischemic recovery in isolated rat heart

The Ca2+-dependent PLC converts phosphatidylinositol 4,5-bisphosphate to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Because these products modulate Ca2+ movements in the myocardium, PLC may also contribute to a self-perpetuating cycle that exacerbates cardiomyocyte Ca2+-overload and subsequent cardiac dysfunction in ischemia-reperfusion (I/R). Although we have reported that I/R-induced changes in PLC isozymes might contribute to cardiac dysfunction, the present study was undertaken to examine the beneficial effects of the PLC inhibitor, U-73122, as well as determining the role of Ca2+ on the I/R-induced changes in PLC isozymes. Isolated rat hearts were subjected to global ischemia 30 min, followed by 5 or 30 min of reperfusion. Pretreatment of hearts with U-73122 (0.5 μM) significantly inhibited DAG and Ins(1,4,5)P3 production in I/R and was associated with enhanced recovery of cardiac function as indicated by measurement of left ventricular (LV) end-diastolic pressure (EDP), LV diastolic pressure (LVDP), maximum rate of pressure development (+dP/d tmax), and maximum rate of LV pressure decay (−dP/d tmax). Verapamil (0.1 μM) partially prevented the increase in sarcolemmal (SL) PLC-β1 activity in ischemia and the decrease in its activity during the reperfusion phase as well as elicited a partial protection of the depression in SL PLC-δ1 and PLC-γ1 activities during the ischemic phase and attenuated the increase during the reperfusion period. Although these changes were associated with an improved myocardial recovery after I/R, verapamil was less effective than U-73122. Perfusion with high Ca2+ resulted in the activation of the PLC isozymes studied and was associated with a markedly increased LVEDP and reduced LVDP, +dP/d tmax, and −dP/d tmax. These results suggest that inhibition of PLC improves myocardial recovery after I/R.

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Lack of the effect of superoxide dismutase and catalase on Na+,K+-ATPase activity in stunned rabbit hearts

Physiological Research ◽

10.33549/physiolres.931553 ◽

2008 ◽

pp. S61-S66

Author(s):

P Kaplán ◽

M Matejovičová ◽

P Herijgers ◽

W Flameng

Keyword(s):

Superoxide Dismutase ◽

Antioxidant Enzymes ◽

Atpase Activity ◽

Cardiac Dysfunction ◽

Myocardial Stunning ◽

Diastolic Pressure ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Significant Loss ◽

Protective Effects

Reactive oxygen species (ROS) have been implicated in the mechanism of postischemic contractile dysfunction, known as myocardial stunning. In this study, we examined protective effects of antioxidant enzymes, superoxide dismutase (SOD) and catalase, against ischemia/reperfusion-induced cardiac dysfunction and inhibition of Na+,K+-ATPase activity. Isolated Langendorff-perfused rabbit hearts were subjected to 15 min of global normothermic ischemia followed by 10 min reperfusion. The hearts treated with SOD plus catalase did not show significant recovery of left ventricular (LV) end-diastolic pressure compared with untreated ischemic reperfused hearts. Treatment with antioxidants had no protective effects on developed LV pressure or its maximal positive and negative first derivatives (+/-LVdP/dt). Myocardial stunning was accompanied by significant loss in sarcolemmal Na+,K+-ATPase activity and thiol group content. Inhibition of enzyme activity and oxidation of SH groups were not prevented by antioxidant enzymes. These results suggest that administration of SOD and catalase in perfusate do not protect significantly against cardiac dysfunction in stunned rabbit myocardium.

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Acute Exercise Attenuates Cardiac Dysfunction After Ischemia/Reperfusion in Isolated Rat Heart

Juntendo Medical Journal ◽

10.14789/jmj.62.s80 ◽

2016 ◽

Vol 62 (Suppl.1) ◽

pp. 80-80

Author(s):

RYO KAKIGI ◽

MAKINO WATANABE ◽

HISASHI NAITO ◽

TAKAMASA TSUZUKI ◽

HIROTO TSUJIKAWA ◽

...

Keyword(s):

Cardiac Dysfunction ◽

Rat Heart ◽

Acute Exercise ◽

Ischemia Reperfusion ◽

Isolated Rat Heart ◽

Isolated Rat

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Mechanical Postconditioning Promotes Glucose Metabolism and AMPK Activity in Parallel with Improved Post-Ischemic Recovery in an Isolated Rat Heart Model of Donation after Circulatory Death

International Journal of Molecular Sciences ◽

10.3390/ijms21030964 ◽

2020 ◽

Vol 21 (3) ◽

pp. 964 ◽

Cited By ~ 1

Author(s):

Maria Arnold ◽

Natalia Méndez-Carmona ◽

Patrik Gulac ◽

Rahel K Wyss ◽

Nina Rutishauser ◽

...

Keyword(s):

Glucose Metabolism ◽

Glucose Uptake ◽

Rat Heart ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Isolated Rat Heart ◽

Donation After Circulatory Death ◽

Heart Model ◽

Circulatory Death ◽

Isolated Rat

Donation after circulatory death (DCD) could improve donor heart availability; however, warm ischemia-reperfusion injury raises concerns about graft quality. Mechanical postconditioning (MPC) may limit injury, but mechanisms remain incompletely characterized. Therefore, we investigated the roles of glucose metabolism and key signaling molecules in MPC using an isolated rat heart model of DCD. Hearts underwent 20 min perfusion, 30 min global ischemia, and 60 minu reperfusion with or without MPC (two cycles: 30 s reperfusion—30 s ischemia). Despite identical perfusion conditions, MPC either significantly decreased (low recovery = LoR; 32 ± 5%; p < 0.05), or increased (high recovery = HiR; 59 ± 7%; p < 0.05) the recovery of left ventricular work compared with no MPC (47 ± 9%). Glucose uptake and glycolysis were increased in HiR vs. LoR hearts (p < 0.05), but glucose oxidation was unchanged. Furthermore, in HiR vs. LoR hearts, phosphorylation of raptor, a downstream target of AMPK, increased (p < 0.05), cytochrome c release (p < 0.05) decreased, and TNFα content tended to decrease. Increased glucose uptake and glycolysis, lower mitochondrial damage, and a trend towards decreased pro-inflammatory cytokines occurred specifically in HiR vs. LoR MPC hearts, which may result from greater AMPK activation. Thus, we identify endogenous cellular mechanisms that occur specifically with cardioprotective MPC, which could be elicited in the development of effective reperfusion strategies for DCD cardiac grafts.

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Effect of Hydrogen Sulfide on Reactions of Isolated Rat Heart under Volume Load and Ischemia-Reperfusion

International Journal of Physiology and Pathophysiology ◽

10.1615/intjphyspathophys.v4.i3.30 ◽

2013 ◽

Vol 4 (3) ◽

pp. 201-212

Author(s):

Tetyana V Shimanskaya ◽

Yulia V. Goshovska ◽

Olena M. Semenykhina ◽

Vadim F. Sagach

Keyword(s):

Hydrogen Sulfide ◽

Rat Heart ◽

Ischemia Reperfusion ◽

Isolated Rat Heart ◽

Volume Load ◽

Isolated Rat

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Dobutamine responsiveness, PET mismatch, and lack of necrosis in low-flow ischemia: is this hibernation in the isolated rat heart?

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00906.2002 ◽

2003 ◽

Vol 285 (1) ◽

pp. H316-H324 ◽

Cited By ~ 10

Author(s):

Richard Southworth ◽

Pamela B. Garlick

Keyword(s):

Rat Heart ◽

Recovery Of Function ◽

Electron Microscopic Examination ◽

Left Ventricular ◽

Isolated Rat Heart ◽

Low Flow ◽

Hibernating Myocardium ◽

Heart Model ◽

Electron Microscopic ◽

Isolated Rat

The clinical hallmarks of hibernating myocardium include hypocontractility while retaining an inotropic reserve (using dobutamine echocardiography), having normal or increased [18F]fluoro-2-deoxyglucose-6-phosphate (18FDG6P) accumulation associated with decreased coronary flow [flow-metabolism mismatch by positron emission tomography (PET)], and recovering completely postrevascularization. In this study, we investigated an isolated rat heart model of hibernation using experimental equivalents of these clinical techniques. Rat hearts ( n = 5 hearts/group) were perfused with Krebs-Henseleit buffer for 40 min at 100% flow and 3 h at 10% flow and reperfused at 100% flow for 30 min (paced at 300 beats/min throughout). Left ventricular developed pressure fell to 30 ± 8% during 10% flow and recovered to 90 ± 7% after reperfusion. In an additional group, this recovery of function was found to be preserved over 2 h of reperfusion. Electron microscopic examination of hearts fixed at the end of the hibernation period demonstrated a lack of ischemic injury and an accumulation of glycogen granules, a phenomenon observed clinically. In a further group, hearts were challenged with dobutamine during the low-flow period. Hearts demonstrated an inotropic reserve at the expense of increased lactate leakage, with no appreciable creatine kinase release. PET studies used the same basic protocol in both dual- and globally perfused hearts (with 250MBq18FDG in Krebs buffer ± 0.4 mmol/l oleate). PET data showed flow-metabolism “mismatch;” whether regional or global,18FDG6P accumulation in ischemic tissue was the same as (glucose only) or significantly higher than (glucose + oleate) control tissue (0.023 ± 0.002 vs. 0.011 ± 0.002 normalized counts · s-1· g-1· min-1, P < 0.05) despite receiving 10% of the flow. This isolated rat heart model of acute hibernation exhibits many of the same characteristics demonstrated clinically in hibernating myocardium.

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Abstract P237: Is Ischemia/Reperfusion an Efficient Method for Producing Heart Failure in Rats?

Hypertension ◽

10.1161/hyp.68.suppl_1.p237 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Ana Carolina M Omoto ◽

Fábio N Gava ◽

Mauro de Oliveira ◽

Carlos A Silva ◽

Rubens Fazan ◽

...

Keyword(s):

Heart Failure ◽

Diastolic Pressure ◽

Histopathological Examination ◽

Ischemia Reperfusion ◽

Mitral Annulus ◽

Mortality Rates ◽

Tissue Doppler ◽

Left Ventricular ◽

Coronary Artery Ligation ◽

Artery Ligation

Myocardium infarction (MI) elicited by coronary artery ligation (CAL) is commonly used to induce chronic heart failure (HF) in rats. However, CAL shows high mortality rates. Given that ischemia-reperfusion (IR) may cause the development of HF, this approach may be useful for obtaining a model of HF with low mortality rates. Therefore, it was compared the model of CAL vs. IR in rats, evaluating the mortality and cardiac morphological and functional aspects. The IR consisted of 30 minutes of cardiac ischemia. Wistar rats were assigned into three groups: CAL: n=18; IR: n=7; SHAM (fictitious IR): n=7. After four weeks of CAL, the subjects were evaluated by echocardiography and ventriculography as well. The statistical analysis consisted of ANOVA combined with Tukey’s posthoc test (p<0.05). There were no deaths in the IR and SHAM groups, whereas in the CAL group the mortality rate was 33.33% (6 out of 18). In the CAL group echocardiography showed increased left ventricular (LV) cavity during systole (8.3 ± 1mm) and diastole (10.5 ± 1mm); decreased LV free wall during systole (1.4 ± 0.5 mm); increased left atrium/aorta (2.3 ± 0.4) ratio. These changes were not significant in IR (4.8 ± 0.5mm, 7.6 ± 0.6mm, 2.6 ± 0.3 mm, 1.6 ± 0.2) and SHAM (4.6 ± 0.6 mm, 7.7 ± 0.8mm, 2.8 ± 0.4mm, 1.5 ± 0.2) groups. There was also the reduction in the ejection fraction in the CAL group (41 ± 12 %) when compared with IR (65 ± 9%) and SHAM (69 ± 7%) groups. The tissue Doppler analysis from the lateral mitral annulus showed reduction in E′ in CAL (-29 ± 8 mm/s) and IR (-31± 9 mm/s) groups when compared with the SHAM (-48 ± 11 mm/s) group. The ventriculography in the CAL group showed smaller maximum dP/dt (6519 ± 1062) and greater end-diastolic pressure (33 ± 8 mmHg) when compared with IR (8716 ± 756 mmHg/s; 9 ± 9 mmHg) and SHAM (7989 ± 1230 mmHg/s; 9 ± 7 mmHg) groups. The CAL group presented transmural infarct size of 40% of the left ventricular wall, measured under histopathological examination. In conclusion, IR for 30 minutes caused only small changes in LV diastolic function, assessed by tissue Doppler; however, the IR was not effective for promoting HF, as observed with CAL. Thus, it is possible that prolonged IR is necessary for promoting significant HF in rats.

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Networking Antioxidants in the Isolated Rat Heart are Selectively Depleted by Ischemia-Reperfusion

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(98)00066-5 ◽

1998 ◽

Vol 25 (3) ◽

pp. 329-339 ◽

Cited By ~ 82

Author(s):

Nobuya Haramaki ◽

Daphne B Stewart ◽

Sarita Aggarwal ◽

Hisao Ikeda ◽

Abraham Z Reznick ◽

...

Keyword(s):

Rat Heart ◽

Ischemia Reperfusion ◽

Isolated Rat Heart ◽

Isolated Rat

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Dose-dependent Effects of Perfluorocarbon Based Blood Substitute Perftoran on Cardyodinamics in Animal Model of Ischemia-reperfusion Injury

10.21203/rs.3.rs-784611/v1 ◽

2021 ◽

Author(s):

Vladimir Jakovljevic ◽

Sergey Vorobyev ◽

Sergey Bolevich ◽

Elena Morozova ◽

Stefani Bolevich ◽

...

Keyword(s):

Growth Rate ◽

Reperfusion Injury ◽

Rat Heart ◽

Ex Vivo ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Isolated Rat Heart ◽

Ischemic Reperfusion Injury ◽

Ischemic Reperfusion ◽

Isolated Rat

Abstract The main goal of this study was to investigate the cardioprotective properties in terms of effects on cardiodynamics of perfluorocarbon emulsion in ex vivo-induced ischemic-reperfusion injury of an isolated rat heart. The first part of the study aims to determine the dose of 10% perfluoroemulsion (PFT) that will show the best cardioprotective effect in rats on ex vivo-induced ischemic / reperfusion injury of an isolated rat heart. Depending on whether the animals received saline or PFT, the animals were divided into a control or experimental group, and depending on the application of a dose (8, 12, 16 ml / kg body weight) of saline or PFT. At a dose of 8 ml / kg, the results indicate statistically significantly lower values of the maximum pressure growth rate in the group treated with 10% PFT compared to the control group treated with saline at R5 and R25 points. At a dose of 12 ml / kg, the maximum left ventricular pressure growth rate differed statistically significantly in the PFT group, ie there was an increase in this parameter at points R25 and R30, and the minimum left ventricular pressure growth rate in R15-R30 compared to saline-treated group. At a dose of 16 ml / kg, PFT also had a statistically significant effect on the change in cardiodynamic parameters in an isolated rat heart organ. Based on all the above, we can conclude that Peftoran administered immediately before ischemia (1 hour) has less positive effects on myocardial function in a model of an isolated rat heart compared to earlier administration (10 and 20 hours). Also, the effects of 10% peftoran solution are more pronounced if there is a longer period of time from application to ischemia, ie immediate application of peftoran before ischemia (1 hour) gave the weakest effects on the change of cardiodynamics of isolated rat heart.

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Effects of Eurycoma Longifolia Extract on the Isolated Rat Heart

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v13i1.489 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Mokhtar RH ◽

Abdullah N ◽

Ayob A

Keyword(s):

Isolated Heart ◽

Water Extract ◽

Left Ventricular ◽

Isolated Rat Heart ◽

Maximum Effect ◽

Coronary Perfusion ◽

No Donor ◽

Eurycoma Longifolia ◽

Cardiovascular Side Effects ◽

Isolated Rat

Introduction: Eurycoma longifolia (E. longifolia) which is better known locally as Tongkat Ali is an indigenous plant in Malaysia. It belongs to the family of Simaroubaceae and is popular as a traditional medicine for its aphrodisiac properties. Throughout the years, several studies have been conducted to prove its effect on aphrodisiac action, antimalarial, antibacterial and anxiolytic properties but its effect to the cardiovascular system had not been fully explored. This study was aimed to demonstrate the changes that take place in the isolated heart following the injection of the extract. Methods: Three parameters that were measured included the coronary perfusion pressure (CPP), the left ventricular developed pressure (LVDP) and the heart rate (HR). Eighteen isolated rat hearts were used and were divided equally into three groups. The first group was to observe the effect of Isoprenaline, a β agonist while the second group was to see the effect of sodium nitroprusside (SNP), a nitric oxide (NO) donor. The dose which gave the maximum effect for these two positive controls was used to compare with the effect of E. longifolia water extract in the third group of rats. Isolated heart was mounted using the Langendorff apparatus and perfused with modified Krebs-Henseleit buffer. Doses of controls and the extract were instilled through an injection port, and the effect of each dose was monitored. Results: E. longifolia extract was found to reduce the CPP in normotensive rat at two of the highest doses. A dose of 1.0 mg of the extract reduced the CPP significantly from 34.52 ± 4.99 mmHg of the baseline value to 31.99 ± 4.93 mmHg while the dose of 10.0 mg of the extract reduced the CPP significantly to 32.67 ± 3.89 mmHg. However, there were no significant changes of effect of the extract on the LVDP and HR as compared to control. Conclusion: These early findings suggest that E. longifolia extract may have vasodilatory property, which supports its traditional usage with minimum cardiovascular side effects.

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