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Pharmacological preconditioning with monophosphoryl lipid A improves post ischemic diastolic function and modifies TNF-alpha synthesis.
Eur J Cardiothorac Surg. 2005 Mar; 27(3):501-7.EJ

Abstract

OBJECTIVE

Pharmacologic preconditioning represents an attractive myocardial protection strategy. Tumor necrosis factor-alpha plays an important role in myocardial ischemia-reperfusion injury. We aimed to determine the effect of Monophosphoryl lipid A-induced delayed preconditioning on diastolic and systolic left ventricular function and tumor necrosis factor-alpha synthesis during ischemia and reperfusion.

METHODS

Rats (n=10) were pretreated with Monophosphoryl lipid A (350 microg/kg) or vehicle (n=9). Twenty-four hours later, the hearts were isolated and perfused on a Langendorff apparatus. Hemodynamic measurements, tumor necrosis factor-alpha mRNA expression and protein content were studied after stabilization (baseline), after 35 min of global ischemia and at 40 min of reperfusion.

RESULTS

Left ventricular developed pressure and peak rate of left ventricular developed pressure (dP/dt) rise were comparable between the animals in the control and Monophosphoryl lipid A treated groups during baseline but were higher in Monophosphoryl lipid A group at reperfusion (74+/-4 vs 51+/-5 mmHg, 3340+/-172 vs 2240+/-156 mmHg/s, respectively, P<0.01). dP/dt fall was significantly lower in the MLA group (2630+/-225v 1580+/-210 mmHg/s, P<0.01) at 40 min of reperfusion as well as end diastolic pressure. Baseline tumor necrosis factor-alpha mRNA (expressed as arbitrary densitometry units) were higher in the Monophosphoryl lipid A group (1.3+/-0.1 vs 0.5+/-0.03, P<0.05) but remained constant after ischemia and reperfusion (1.3+/-0.1 and 1.4+/-0.03, P=0.2), while further increase was observed in the control group (from 1.0+/-0.1 to 1.4+/-0.1, P<0.05). Tumor necrosis factor-alpha protein content from heart effluent in the control group was increased during reperfusion (79+/-30 and 200+/-22pg/ml, P<0.05) but was undetectable in the Monophosphoryl lipid A group. Marked TNF-alpha immunostaining of left ventricular tissue was observed only in the control group but no TNF-alpha staining was evident in the Monophosphoryl lipid A treated group at 40 min of reperfusion.

CONCLUSION

Monophosphoryl lipid A-induced preconditioning renders the heart more tolerant to ischemia-reperfusion in terms of left ventricular diastolic and systolic function, and prevents tumor necrosis factor-alpha production during ischemia, through aborting the translation phase of tumor necrosis factor-alpha synthesis.

Authors+Show Affiliations

Sharony R
Department of Cardiothoracic Surgery, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, 6 Witzman St., Tel Aviv 64239, Israel. sharonyn@netvision.net.il
Frolkis I
No affiliation info available
Froylich D
No affiliation info available
Wildhirt SM
No affiliation info available
Shapira I
No affiliation info available
Reichart B
No affiliation info available
Nesher N
No affiliation info available
Uretzky G
No affiliation info available

MeSH

AnimalsCoronary CirculationGene Expression RegulationHemodynamicsIschemic Preconditioning, MyocardialLipid AMaleMyocardial Reperfusion InjuryOrgan Culture TechniquesRNA, MessengerRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionTumor Necrosis Factor-alphaVentricular Function, Left

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15740963

Citation

Sharony, Ram, et al. "Pharmacological Preconditioning With Monophosphoryl Lipid a Improves Post Ischemic Diastolic Function and Modifies TNF-alpha Synthesis." European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, vol. 27, no. 3, 2005, pp. 501-7.
Sharony R, Frolkis I, Froylich D, et al. Pharmacological preconditioning with monophosphoryl lipid A improves post ischemic diastolic function and modifies TNF-alpha synthesis. Eur J Cardiothorac Surg. 2005;27(3):501-7.
Sharony, R., Frolkis, I., Froylich, D., Wildhirt, S. M., Shapira, I., Reichart, B., Nesher, N., & Uretzky, G. (2005). Pharmacological preconditioning with monophosphoryl lipid A improves post ischemic diastolic function and modifies TNF-alpha synthesis. European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, 27(3), 501-7.
Sharony R, et al. Pharmacological Preconditioning With Monophosphoryl Lipid a Improves Post Ischemic Diastolic Function and Modifies TNF-alpha Synthesis. Eur J Cardiothorac Surg. 2005;27(3):501-7. PubMed PMID: 15740963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological preconditioning with monophosphoryl lipid A improves post ischemic diastolic function and modifies TNF-alpha synthesis. AU - Sharony,Ram, AU - Frolkis,Inna, AU - Froylich,Dvir, AU - Wildhirt,Stephan M, AU - Shapira,Itzhak, AU - Reichart,Bruno, AU - Nesher,Nahum, AU - Uretzky,Gideon, Y1 - 2005/01/19/ PY - 2004/08/09/received PY - 2004/11/25/revised PY - 2004/11/26/accepted PY - 2005/3/3/pubmed PY - 2005/4/26/medline PY - 2005/3/3/entrez SP - 501 EP - 7 JF - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery JO - Eur J Cardiothorac Surg VL - 27 IS - 3 N2 - OBJECTIVE: Pharmacologic preconditioning represents an attractive myocardial protection strategy. Tumor necrosis factor-alpha plays an important role in myocardial ischemia-reperfusion injury. We aimed to determine the effect of Monophosphoryl lipid A-induced delayed preconditioning on diastolic and systolic left ventricular function and tumor necrosis factor-alpha synthesis during ischemia and reperfusion. METHODS: Rats (n=10) were pretreated with Monophosphoryl lipid A (350 microg/kg) or vehicle (n=9). Twenty-four hours later, the hearts were isolated and perfused on a Langendorff apparatus. Hemodynamic measurements, tumor necrosis factor-alpha mRNA expression and protein content were studied after stabilization (baseline), after 35 min of global ischemia and at 40 min of reperfusion. RESULTS: Left ventricular developed pressure and peak rate of left ventricular developed pressure (dP/dt) rise were comparable between the animals in the control and Monophosphoryl lipid A treated groups during baseline but were higher in Monophosphoryl lipid A group at reperfusion (74+/-4 vs 51+/-5 mmHg, 3340+/-172 vs 2240+/-156 mmHg/s, respectively, P<0.01). dP/dt fall was significantly lower in the MLA group (2630+/-225v 1580+/-210 mmHg/s, P<0.01) at 40 min of reperfusion as well as end diastolic pressure. Baseline tumor necrosis factor-alpha mRNA (expressed as arbitrary densitometry units) were higher in the Monophosphoryl lipid A group (1.3+/-0.1 vs 0.5+/-0.03, P<0.05) but remained constant after ischemia and reperfusion (1.3+/-0.1 and 1.4+/-0.03, P=0.2), while further increase was observed in the control group (from 1.0+/-0.1 to 1.4+/-0.1, P<0.05). Tumor necrosis factor-alpha protein content from heart effluent in the control group was increased during reperfusion (79+/-30 and 200+/-22pg/ml, P<0.05) but was undetectable in the Monophosphoryl lipid A group. Marked TNF-alpha immunostaining of left ventricular tissue was observed only in the control group but no TNF-alpha staining was evident in the Monophosphoryl lipid A treated group at 40 min of reperfusion. CONCLUSION: Monophosphoryl lipid A-induced preconditioning renders the heart more tolerant to ischemia-reperfusion in terms of left ventricular diastolic and systolic function, and prevents tumor necrosis factor-alpha production during ischemia, through aborting the translation phase of tumor necrosis factor-alpha synthesis. SN - 1010-7940 UR - https://www.unboundmedicine.com/medline/citation/15740963/Pharmacological_preconditioning_with_monophosphoryl_lipid_A_improves_post_ischemic_diastolic_function_and_modifies_TNF_alpha_synthesis_ DB - PRIME DP - Unbound Medicine ER -