Lidocaine Protects from Myocardial Damage due to Ischemia and Reperfusion in Mice by Its Antiapoptotic Effects

Kaczmarek, Dominik J.; Herzog, Christine; Larmann, Jan; Gillmann, H; Hildebrand, Reinhard; Schmitz, Martina; Westermann, Anik; Harendza, Thomas; Werdehausen, Robert; Osthaus, A.; Echtermeyer, Frank; Hahnenkamp, Klaus; Wollert, Kai C.; Theilmeier, Gregor

doi:10.1097/aln.0b013e31819dabda

Cited by 40 publications

(43 citation statements)

References 47 publications

(48 reference statements)

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“…There is a growing literature indicating that systemic IV lidocaine may have beneficial perioperative effects, including preemptive analgesia, reduced postoperative narcotic requirements, and reduced systemic inflammatory response to surgical trauma. 33,34,[42][43][44][45][46][47] The observation that tumescent infiltration produces a concentration-time profile similar to a constant IV infusion of lidocaine suggests a new hypothesis, to be tested in the future, that local TLA may have desirable systemic effects.…”

Section: Discussionmentioning

confidence: 99%

Estimated Maximal Safe Dosages of Tumescent Lidocaine

Klein

Jeske

2016

Survey of Anesthesiology

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Section: Discussionmentioning

confidence: 99%

Estimated Maximal Safe Dosages of Tumescent Lidocaine

Klein

Jeske

2016

Survey of Anesthesiology

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“…The toe-pinch reflex is the most commonly used index of the depth of anesthesia. Further, to improve the probability for long term survival, some investigators use antiarrhythmic drugs such as lidocaine to reduce the incidence of lethal arrhythmias 19,20 however, it must be taken into account that this has recently been shown to have antiapoptotic properties in an acute model 21 . Also, to reduce post-operative pain, analgesics such as buprenorphine can be administered for the first 48 hours after surgery 3,16,17,22,23 .…”

Section: Discussionmentioning

confidence: 99%

Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction

Virag

Lust

2011

JoVE

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Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo. With the advent of genetic modifications to the whole organism or the myocardium and an array of biological and/or synthetic materials, there is great potential for any combination of these to assuage the extent of acute ischemic injury and impede the onset of heart failure pursuant to myocardial remodeling.Here we present the methods and materials used to reliably perform this microsurgery and the modifications involved for temporary (with reperfusion) or permanent coronary artery occlusion studies as well as intramyocardial injections. The effects on the heart that can be seen during the procedure and at the termination of the experiment in addition to histological evaluation will verify efficacy.Briefly, surgical preparation involves anesthetizing the mice, removing the fur on the chest, and then disinfecting the surgical area. Intratracheal intubation is achieved by transesophageal illumination using a fiber optic light. The tubing is then connected to a ventilator. An incision made on the chest exposes the pectoral muscles which will be cut to view the ribs. For ischemia/reperfusion studies, a 1 cm piece of PE tubing placed over the heart is used to tie the ligature to so that occlusion/reperfusion can be customized. For intramyocardial injections, a Hamilton syringe with sterile 30gauge beveled needle is used. When the myocardial manipulations are complete, the rib cage, the pectoral muscles, and the skin are closed sequentially. Line block analgesia is effected by 0.25% marcaine in sterile saline which is applied to muscle layer prior to closure of the skin. The mice are given a subcutaneous injection of saline and placed in a warming chamber until they are sternally recumbent. They are then returned to the vivarium and housed under standard conditions until the time of tissue collection. At the time of sacrifice, the mice are anesthetized, the heart is arrested in diastole with KCl or BDM, rinsed with saline, and immersed in fixative. Subsequently, routine procedures for processing, embedding, sectioning, and histological staining are performed.Nonsurgical intubation of a mouse and the microsurgical manipulations described make this a technically challenging model to learn and achieve reproducibility. These procedures, combined with the difficulty in performing consistent manipulations of the ligature for timed occlusion(s) and reperfusion or intramyocardial injections, can also affect the survival rate so optimization and consistency are critical. Video LinkThe video component of this article can be found at https://www.jove.com/video/2581/ Protocol 1. Sterile surgical instruments (Table 1) and 3" cotton tipped applicators are placed on a sterile underpad. The bead sterilizer (Germinator 500) is turned on. 2. Mice (age: > 6 weeks; wt: > 18g) are anesthetized with an i.p. injection of 20μl/g BW of tribromoethanol (250mg/kg; duration -approximately 40 minutes). 3. When the mice are unrespon...

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“…32 For potential future clinical applications, the use of peripheral blood mononuclear cells would be an attractive alternative, but their use in this application has yet to be characterized. The adoptively transferred cells constitute only a very small proportion of cells that are recruited to the inflamed site (less than 1% of macrophages in the peritoneal lavages; see Supplemental Digital Content 1, Flow Cytometry Confirms Fluorescencemediated Tomography Measured Cell Recruitment section, http://links.lww.com/ALN/A606) and are therefore unlikely to exert notable biologic effects.…”

Section: Discussionmentioning

confidence: 99%

“…2-6,8 -12 These events have been studied using a wide variety of in vitro assays, intravital microscopy, and in vivo homing assays. 3-5,8 -10,12-14 In the past, homing assays to assess tissue distribution and targeted recruitment of larger populations of leukocytes in response to inflammatory stimuli were carried out in animals, mostly mice, by injecting populations of leukocytes, lymphocytes, 8,12 or macrophages, 31,32,35 and homing was analyzed post mortem on histologic sections or homogenates of lymphatic organs by flow cytometry.…”

Section: Discussionmentioning

confidence: 99%

“…32 In brief, confluent serum-starved endothelial cells were activated with tumor necrosis factor-␣ (100 ng/ml; BioSource International, Camarillo, CA). Double-and single-labeled (eGFP) macrophages or neutrophils were allowed to adhere to endothelium on a rocking plate (20/min) for 30 min before decanting and two buffer washes.…”

Section: Leukocyte Adhesion and Transmigration Assays For Assessment mentioning

confidence: 99%

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In Vivo Fluorescence-mediated Tomography for Quantification of Urokinase Receptor-dependent Leukocyte Trafficking in Inflammation

Larmann

Frenzel

Hahnenkamp³

et al. 2010

Anesthesiology

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Background:Inflammation is characterized by leukocyte recruitment. Macrophages and neutrophils contribute to tissue damage and organ dysfunction. Modulating leukocyte invasion can protect from these adverse effects. Leukocyte recruitment critically depends on the urokinase-type plasminogen activator receptor (u-PAR). We here use a novel technique to longitudinally quantify cell trafficking in inflammatory models in live animals. Methods: Near-infrared fluorophore-labeled leukocytes were adoptively transferred to mice with thioglycollate peritonitis to study leukocyte trafficking to sites of inflammation. Macrophage and neutrophil trafficking was followed with three-dimensional fluorescence-mediated-tomography. u-PARϪ/Ϫ and wild-type macrophage recruitment was studied by cross-over adoptive cell transfer to elucidate the role of leukocytic versus u-PAR expressed on other cells. Endotoxic shock-induced pulmonary inflammation was used to study u-PARs role for pulmonary neutrophil recruitment. Results: Mice experiencing peritonitis showed a significant increase in mean fluorescence intensity because of enhanced macrophage (315%, n ϭ 9-10), P Ͻ 0.05) or neutrophil (194%, n ϭ 6, P Ͻ 0.02) recruitment. Fluorescence-mediated-tomography uncovered a macrophage recruitment defect in the peritonitis model for u-PARϪ/Ϫ mice (147% of baseline) compared with control mice (335% of baseline, n ϭ 8-9, P Ͻ 0.05). When u-PARϪ/Ϫ-macrophages were transferred to wild-type mice fluorescence intensity increased to 145% while wild-type macrophage transfer into u-PARϪ/Ϫ resulted in 192% increase compared with baseline (n ϭ 6, P Ͻ 0.05). Reduced neutrophil recruitment in pulmonary inflammation in u-PARϪ/Ϫ mice was accompanied by improved pulmonary gas exchange. Conclusion: Using noninvasive in vivo fluorescence-mediated tomography to image leukocyte recruitment in inflammatory mouse models, we describe a novel macrophage recruitment defect in u-PARϪ/Ϫ mice. Targeting u-PAR for modulation of leukocyte recruitment is a promising therapeutic strategy to ameliorate leukocyte induced tissue damage.

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Lidocaine Protects from Myocardial Damage due to Ischemia and Reperfusion in Mice by Its Antiapoptotic Effects

Abstract: Lidocaine exerts cardioprotective effects when administered before or after the ischemic insult. This effect is mediated through an antiapoptotic and not through an antiinflammatory pathway and may be therapeutically exploitable.

Cited by 40 publications

References 47 publications

Estimated Maximal Safe Dosages of Tumescent Lidocaine

Estimated Maximal Safe Dosages of Tumescent Lidocaine

Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction

In Vivo Fluorescence-mediated Tomography for Quantification of Urokinase Receptor-dependent Leukocyte Trafficking in Inflammation

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