PERFADEX® Plus

PERFADEX® Plus

THE GOLD STANDARD IN LUNG PRESERVATION MADE READY AND EASY TO USE

PERFADEX® Plus is an extracellular, low potassium, dextran-based electrolyte preservation solution for rapid cooling, perfusion and cold static storage of donor lungs – pre-supplemented with calcium ions and THAM so that it is ready to use whenever you need it.

PERFADEX® Plus with Click Port

– a new ready to use solution for optimal cold static preservation of donor lungs

XVIVO Perfusion have developed PERFADEX® Plus, a new generation of PERFADEX®. To save you time and effort, we have pre-supplemented the solution with calcium ions and THAM, so it is always ready to use. Calcium ions have been added to further mimic the composition of plasma. PERFADEX® Plus has several design fetures that make it even easier to handle.

  • Strong, reinforced hanger – for safety and convenience.
  • Free from PVC, latex and phthalates – for patient safety.
  • New double, twist-off sterile portsare easy to grip and easy to open.
  • Ports are made of stronger plastic no risk of perforating the bag during injection.
  • New easy to use click port – connect tubing spike free to the bag with one simple click using the XVIVO Click Adapter. Once connected, the tubing can rotate on its own axis for flexibility during handling.

PERFADEX® Plus is indicated for the flushing, cold static storage and transportation of isolated lungs after removal from the donor in preparation for eventual transplantation into a recipient. The colloid component, dextran 40, protects the microvasculature against post-ischemic reperfusion injury, primarily by preventing pathological leukocyte-endothelial interaction.12, 13 It also prevents edema formation during preservation.14,15,20 Calcium is important to maintain endothelial and epithelial cell integrity and endothelial contractility.23  It is also crucial to maintain tight junctions between cells (to avoid cell disintegration).22,24
Numerous studies have shown that PERFADEX® enables safe preservation of lungs up to 12 hours, depending of status of the organ during retrieval.1 ,2 ,3 ,4 ,5 ,6 ,7 ,8, 9, 10, 11

The colloid component, dextran 40, particularly protects the microvasculature against post-ischemic reperfusion injury, primarily by preventing pathological leukocyte endothelial interaction.12, 13

The endothelium - a vulnerable tissue

The lung is primarily composed of endothelial cells which line the enormous surface area of the capillaries (equivalent to an entire tennis court) and a similar surface area of types I and II epithelial cells which line the alveoli and secrete surfactant respectively. The endothelium is the most vulnerable tissue and plays a critical role for the structure and function of a normal vessel wall. Endothelial cells produce a variety of biologically active substances that control vascular permeability, vessel tone, coagulation, fibrinolysis and inflammatory responses. Some of these substances, such as proteins which seal the junctions between cells (adhesion molecules), are integral parts of the cell structure. Others, such as nitric oxide (NO), prostacycline, chemokines,or factors involved in coagulation and fibrinolysis, are produced and then released by the endothelial cells either luminally or abluminally.16

What causes damage to the endothelium?

A number of factors can injure the pulmonary endothelium during the manipulation and temporary storage involved in the retrieval of donor lungs;

  • Traumatic manipulation during retrieval, evaluation and transplantation
  • Excessive pressure
  • Low temperature – particularly below 2 ⁰C
  • Storage solution – e.g. intracellular type (high K+) solutions
  • Prolonged cold ischemia
  • Ischemia-reperfusion – free radical injury

Consequences of an injured endothelium

Injured endothelium can induce platelet and leukocyte adhesion which triggers a number of inflammatory cascades. These process induces further endothelial damage resulting in ischemic reperfusion injury IRI. A well preserved endothelium is antithrombogenic, yet promotes platelet aggregation and coagulation if injured.17,18

The importance of an intact endothelium

Experimental and clinical evidence indicates that early ischemia-reperfusion injury to the endothelium, within the very first few hours of reperfusion, is a key trigger in initiating immune reactions that might subsequently result in graft failure often months or years later.18

This early injury can be prevented or mitigated by minimizing physical injury (manipulation) and storing the lungs in a protective solution under optimal temperature conditions.19

Current best practice

According to Munshi et al, 2013 21

Current best practice based on the latest research on potential lung donor and lung-preservation techniques advises the use of an extracellular, dextran-based solution.

Lung preservation techniques

  • Extracellular solution consisting of dextran-40, glucose and low potassium
  • Anterograde and retrograde flushing of 60 ml/kg and max 30 cm height
  • Temperature during lung preservation 2-8 ⁰C
  • Inflation to 50% of total lung capacity, fraction of inspired oxygen 50%
  • Pharmacological additives: prostaglandin E1, heparin, glucocorticoids
  • Cold ischemic times generally less than 8 h
  • Normothermic ex-vivo lung perfusion based on lung assessment and therapeutics.

 

USING PERFADEX® PLUS

PERFADEX® Plus is pre-supplemented and ready to use whenever you need it. Must not be supplemented with calcium ions or THAM.

Intended use: PERFADEX® Plus solution for lung perfusion is indicated for flushing, cold static storage and transportation of isolated lungs after removal from the donor in preparation for eventual transplantation into a recipient.

Storage temperature between 2-25°C (36-77°F). Once opened the solution should be kept chilled and used within 24 hours.

PERFADEX® Plus is supplied in 1000ml and 3000ml bags and comes together with the XVIVO Click Adapter.

Sterility: PERFADEX® Plus is supplied sterile.

Supply and order information:

Available outside of US:
PERFADEX® Plus 1000 ml (with Click Port and XVIVO Click Adapter)
REF 19811
Content: 
10 x PERFADEX® Plus 1000 ml
10 x XVIVO Click Adapter
Packaging:
10 pcs/box

PERFADEX® Plus 3000 ml (with Click Port and XVIVO Click Adapter)
REF 19911
Content: 
2 x PERFADEX® Plus 3000 ml
2 x XVIVO Click Adapter
Packaging:
2 pcs/box

Available in US:
PERFADEX® Plus 1000 ml (with Click Port and XVIVO Click Adapter)
REF 19850
Content: 
10 x PERFADEX® Plus 1000 ml
10 x XVIVO Click Adapter
Packaging:
10 pcs/box

PERFADEX® Plus 3000 ml (with Click Port and XVIVO Click Adapter)
REF 19950
Content: 
2 x PERFADEX® Plus 3000 ml
2 x XVIVO Click Adapter
Packaging:
2 pcs/box

Regulatory approvals:
PERFADEX® Plus is CE marked and 510(k) cleared by the FDA in US.

REFERENCES

  1. Muller C, et al, transplantation, 1999. 68(8):1139-43.
  2. Fischer S, et al, J Thorac. Cardiovasc Surg. 2001. 121(3):594-6
  3. Struber M, et al, Eur. J. Cardiothorac. Surg. 2001. 19 (2):190-4.
  4. Rabanal J M, et al, Transplant Proc. 2003. ;35(5):1938-9
  5. Sakamaki F, et al, Am J Respir Crit Care Med. 1997:156:1073-81
  6. Struber M, et al, J Heart Lung Transplant. 1999:18:1:87
  7. Struber M, et al, J Thorac Cardiovasc Surg. 2000, 120 (3); 566-72.
  8. Oto T et al. Ann Thorac Surg. 2006 Nov;82(5):1842-8.
  9. Gamez P et al Arch Bronconeumol. 2005 Jan;41(1):16-19.
  10. Okada Y et al. Ann Thorac Cardiovasc Surg. 2006 Feb;12(1):10-4
  11. Arnaoutakis GJ et al. J Heart Lung Transplant. 2010 Dec; 29(12): 1380-7
  12. Menger M D. Transplant Proceed. 1995, 27; 5: 2863-65
  13. Hoffman h et al. Z. Hertz-, Thorax-, Gefässchir. 1997, 11: 108-14
  14. Frost -Arner L et al. Microsurgery. 1995, 16: 357-361
  15. Keshavjee SH et al. J Thorac Cardiovascular Surg. 1992; 103:314-25
  16. Toborek M, JKaisers S. Basic Res Cardiol 1999; 94: 295-314
  17. Zilla P et al. J Card Surg 1993; 8: 32-60
  18. Davis S.F. et al. Circulation. 1996; 93: 457-462
  19. Steen S. Scand Cardiovasc J. 2001; 35: 297-301
  20. Arfors K-E,  Buckley, PB, Bailliere´s Clinical Anaesthesiol. 1997;11,1,15-47
  21. Munshi L et al. Lancet Rspeir Med 2013; 1;318-28
  22. Cardella et al. J Appl Physiol, 2000, 89:1553-1560
  23. Ingemansson et al. Ann Thorac Surg. 1996 Apr;61(4):1158-62
  24. Volberg et al The Journal of Cell Biology 1986;102:1832-42