Preservation of Endothelial Vascular Function of Saphenous Vein Grafts after Long-Time Storage with a Recently Developed Potassium-Chloride and N-Acetylhistidine Enriched Storage Solution

Wilbring, Manuel; Tugtekin, Sems Malte; Zatschler, Birgit; Ebner, Annette; Reichenspurner, Hermann; Kappert, Utz; Matschke, Klaus; Deußen, Andreas

doi:10.1055/s-0032-1311549

Cited by 9 publications

(5 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vessel preparation was performed according to a slightly modified method as previously described (Wilbring et al, 2013; Kopaliani et al, 2014; Bosche et al, 2016). In brief, male CD57 mice 10 weeks of age (Charles River Laboratories, Sulzfeld, Germany) were sacrificed by cutting off the upper cervical spinal cord under deep anesthesia.…”

Section: Methodsmentioning

confidence: 99%

“…Vessel function was assessed according to the method of Mulvany and Halpern (1977) as described previously (Wilbring et al, 2013; Kopaliani et al, 2014; Bosche et al, 2016). Briefly, aortic and cerebral vessel grafts (2 mm in length and 0.5–0.6 or 1.2–1.4 mm internal width, respectively) were transferred to carbogen equilibrated phosphate saline solution (PSS; in mmol/L: 119 NaCl, 4.7 KCl, 2.5 CaCl 2 , 1.17 MgSO 4 , 1.18 KH 2 PO 4 , 25 NaHCO 3 , 5.5 glucose, 0.027 EDTA) and equilibrated for 30 min at 37°C and subsequently mounted in a myograph (DMT-610 M, Power Laboratory/400; AD-Instruments, Spechbach, Germany) for isometric force measurements.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Low-Dose Lithium Stabilizes Human Endothelial Barrier by Decreasing MLC Phosphorylation and Universally Augments Cholinergic Vasorelaxation Capacity in a Direct Manner

et al. 2016

View full text Add to dashboard Cite

Lithium at serum concentrations up to 1 mmol/L has been used in patients suffering from bipolar disorder for decades and has recently been shown to reduce the risk for ischemic stroke in these patients. The risk for stroke and thromboembolism depend not only on cerebral but also on general endothelial function and health; the entire endothelium as an organ is therefore pathophysiologically relevant. Regardless, the knowledge about the direct impact of lithium on endothelial function remains poor. We conducted an experimental study using lithium as pharmacologic pretreatment for murine, porcine and human vascular endothelium. We predominantly investigated endothelial vasorelaxation capacities in addition to human basal and dynamic (thrombin-/PAR-1 receptor agonist-impaired) barrier functioning including myosin light chain (MLC) phosphorylation (MLC-P). Low-dose therapeutic lithium concentrations (0.4 mmol/L) significantly augment the cholinergic endothelium-dependent vasorelaxation capacities of cerebral and thoracic arteries, independently of central and autonomic nerve system influences. Similar concentrations of lithium (0.2–0.4 mmol/L) significantly stabilized the dynamic thrombin-induced and PAR-1 receptor agonist-induced permeability of human endothelium, while even the basal permeability appeared to be stabilized. The lithium-attenuated dynamic permeability was mediated by a reduced endothelial MLC-P known to be followed by a lessening of endothelial cell contraction and paracellular gap formation. The well-known lithium-associated inhibition of inositol monophosphatase/glycogen synthase kinase-3-β signaling-pathways involving intracellular calcium concentrations in neurons seems to similarly occur in endothelial cells, too, but with different down-stream effects such as MLC-P reduction. This is the first study discovering low-dose lithium as a drug directly stabilizing human endothelium and ubiquitously augmenting cholinergic endothelium-mediated vasorelaxation. Our findings have translational and potentially clinical impact on cardiovascular and cerebrovascular disease associated with inflammation explaining why lithium can reduce, e.g., the risk for stroke. However, further clinical studies are warranted.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Low-Dose Lithium Stabilizes Human Endothelial Barrier by Decreasing MLC Phosphorylation and Universally Augments Cholinergic Vasorelaxation Capacity in a Direct Manner

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Saphenous vein segments were studied in a four chamber Myograph as published previously [16]. Vessel rings of 2 mm length were placed on stainless steel hooks (diameter 200 m) in a 5 ml tissue bath with physiological saline solution (PSS: in mmol/l: Glucose 5.5, Na + 144, Cl − 128.7, H 2 PO 4 − 1.18, SO 4 2− 1.17, HCO 3 − 25, K + 5.9, Mg 2+ 1.17, Ca 2+ 2.5, EDTA 0,027.))…”

Section: Vasomotor Function Analysismentioning

confidence: 99%

“…For fluororescence detection of nucleotides derivatisation with chloracetaldehyd to their 1,N 6 -etheno-analouges was performed as described previously (16). 143 l neutralized sample were mixed with 51 l of citrate-phosphate-buffer (0.1 mol/l Na-citrate, 0.2 mol/l Na 2 HPO 4 ) for pH adjustment to pH = 4.…”

Section: Determination Of Energy Chargementioning

confidence: 99%

Heparinized blood better preserves cellular energy charge and vascular functions of intraoperatively stored saphenous vein grafts in comparison to isotonic sodium-chloride-solution

Wilbring¹,

Ebner

Schoenemann

et al. 2013

Clinical Hemorheology and Microcirculation

Self Cite

View full text Add to dashboard Cite

OBJECTIVE: Several studies have addressed the optimal storage conditions for vascular grafts during surgery. The results remain contradictionary. This may be attributed to the fact, that the various vascular beds have a different sensitivity to storage. We analyzed the impact of storage in isotonic saline solution (NaCl) or heparinized blood the vascular functions of human saphenous vein grafts. Special care was taken to choose storage conditions which are relevant for intraoperative storage of a saphenous vein graft in a setting of coronary artery bypass grafting with vein and internal mammary artery as grafts. METHODS: Intraoperatively isolated V. saphena-segments (n = 36) were stored in NaCl or heparinized blood for approximately 30 minutes at room temperature. Subsequently, the segments were examined in a Mulvany-myograph. Following preconstriction with norepinephrine, concentration-relaxation curves were assessed for bradykinin and sodium-nitroprusside to assess developed vessel-wall tension as well as endothelium-and smooth-muscle-cell dependent vasorelaxation. The availability of adenosintriphosphate (energy charge) was determined based on liquid chromatography measurements of nucleotide tissue levels. RESULTS: Mean storage time was 27.4 ± 2.4 min in NaCl-and 26.3 ± 2.7 min in blood-group, respectively. After this period, receptor-dependent and-independent maximum of developed vessel wall tension was significantly reduced in NaCl-group (p = 0.05 and p = 0.045, respectively). Furthermore, the energy charge was significantly (p = 0.046) better preserved after blood storage (74 ± 1%) in comparison to NaCl-group (68 ± 2%). Endothelium-induced vasodilatation in response to bradykinin reached only 12.3 ± 2.5% in NaCl-group, but 19.3 ± 5.2% in blood-group (p = 0.033). Alike, EC 50 -concentration of bradykinin for half-maximal relaxation was significantly lower in blood-than in NaCl-group (log EC 50 −7.08 ± 0.3 and −5.91 ± 0.4; respectively; p = 0.046). Endothelium-independent smooth muscle relaxation in response to sodium-nitroprusside was not different between both groups. CONCLUSION: Heparinized blood better preserves vascular contractile and endothelial functions of the saphenous vein graft. Storage in NaCl rapidly compromises vascular functions and impaires cellular energy. NaCl should no longer be recommended for intraoperative storage of harvested V. saphena grafts.

show abstract

“…Although Gundry et al 12 showed that storage in a saline solution had deleterious effects on endothelial function compared with preservation in autologous blood, other studies 13-18 aiming to substantiate these findings have shown conflicting results. Other studies 9,15,16,19-23 have investigated the effect of storage in various buffered saline solutions on vessel wall tension and endothelial function in discarded vein graft segments and overall have shown improved endothelial function after preservation in a buffered saline storage solution compared with saline- and/or blood-based media.…”

Section: Discussionmentioning

confidence: 99%

Vein Graft Preservation Solutions, Patency, and Outcomes After Coronary Artery Bypass Graft Surgery

et al. 2014

View full text Add to dashboard Cite

IMPORTANCE In vitro and animal model data suggest that intraoperative preservation solutions may influence endothelial function and vein graft failure (VGF) after coronary artery bypass graft (CABG) surgery. Clinical studies to validate these findings are lacking. OBJECTIVE To evaluate the effect of vein graft preservation solutions on VGF and clinical outcomes in patients undergoing CABG surgery. DESIGN, SETTING, AND PARTICIPANTS Data from the Project of Ex-Vivo Vein Graft Engineering via Transfection IV (PREVENT IV) study, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that enrolled 3014 patients at 107 US sites from August 1, 2002, through October 22, 2003, were used. Eligibility criteria for the trial included CABG surgery for coronary artery disease with at least 2 planned vein grafts. INTERVENTIONS Preservation of vein grafts in saline, blood, or buffered saline solutions. MAIN OUTCOMES AND MEASURES One-year angiographic VGF and 5-year rates of death, myocardial infarction, and subsequent revascularization. RESULTS Most patients had grafts preserved in saline (1339 [44.4%]), followed by blood (971 [32.2%]) and buffered saline (507 [16.8%]). Baseline characteristics were similar among groups. One-year VGF rates were much lower in the buffered saline group than in the saline group (patient-level odds ratio [OR], 0.59 [95% CI, 0.45-0.78; P < .001]; graft-level OR, 0.63 [95% CI, 0.49-0.79; P < .001]) or the blood group (patient-level OR, 0.62 [95% CI, 0.46-0.83; P = .001]; graft-level OR, 0.63 [95% CI, 0.48-0.81; P < .001]). Use of buffered saline solution also tended to be associated with a lower 5-year risk for death, myocardial infarction, or subsequent revascularization compared with saline (hazard ratio, 0.81 [95% CI, 0.64-1.02; P = .08]) and blood (0.81 [0.63-1.03; P = .09]) solutions. CONCLUSIONS AND RELEVANCE Patients undergoing CABG whose vein grafts were preserved in a buffered saline solution had lower VGF rates and trends toward better long-term clinical outcomes compared with patients whose grafts were preserved in saline- or blood-based solutions.

show abstract

Preservation of Endothelial Vascular Function of Saphenous Vein Grafts after Long-Time Storage with a Recently Developed Potassium-Chloride and N-Acetylhistidine Enriched Storage Solution

Cited by 9 publications

References 18 publications

Low-Dose Lithium Stabilizes Human Endothelial Barrier by Decreasing MLC Phosphorylation and Universally Augments Cholinergic Vasorelaxation Capacity in a Direct Manner

Low-Dose Lithium Stabilizes Human Endothelial Barrier by Decreasing MLC Phosphorylation and Universally Augments Cholinergic Vasorelaxation Capacity in a Direct Manner

Heparinized blood better preserves cellular energy charge and vascular functions of intraoperatively stored saphenous vein grafts in comparison to isotonic sodium-chloride-solution

Vein Graft Preservation Solutions, Patency, and Outcomes After Coronary Artery Bypass Graft Surgery

Contact Info

Product

Resources

About