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15Kolmykov D.I., Alehin S.A. Ischemia/reperfusion effect on pancreatic volumetrical blood flow velocity. Research result: pharmacology and clinical pharmacology. 2015. Vol. 1, №1(1): 42-46.
Pyc. Eng.
UDC: 611.37:612.172.1 Kolmykov D. I.1
Alehin S.A.
2
DOI: 10.18413/2500-235X-2015-1-4-51-56
ISCHEMIA/REPERFUSION EFFECT ON PANCREATIC VOLUMETRICAL BLOOD FLOW VELOCITY
1) Assistant, Department of Surgery, Kursk State Medical University, K.Marksa str.3, Kursk, 305041, Russia
e-mail: [email protected] 2) Phd in Medical Sciences, assistant, Department of Surgery, Kursk State Medical University K.Marksa str.3, Kursk, 305041, Russia, e-mail: [email protected]
Abstract. We investigate blood flow velocity at ischemia/reperfusion early stages. Transient hyperemia absence after ischemia/reperfusion cased by pancreatic edema development at early stages confirmed by Wet/Dry ratio elevation and morphological changes was determined. Key words: ischemia, reperfusion, blood flow, pancreas.
Ischemia is a trigger and pathogenesis stage in many pathological conditions. Anderson (1961, 1963) was the first who discovered ischemia leading role in acute pancreatitis pathogenesis [5, 6]. This discovery made possible to create vascular model of acute pancreatitis (Hoffmann at all., 1995) later used in domestic and foreign studies [3, 8, 10, 13].
Recent years many authors reveald мetabolic changhes during primary and secondary ischemia are main reasons of pancreatic necrosis formation and spreading even in small primary damage. That was proven by cardiosurgeons found a pancreatitis activation after hypoperfusion during heart surgerys artificial circulation [4, 9, 11, 12, 14].
Thereby pancreatic microvessels blood flow velocity investigation is crucial as it correlates with tissue damage intensity.
Previosely dramatic blood flow decreasing in ductal pancreatitis were proven with minimum at 24 hours folowed by significant stromal changes.
We did't find blood flow investigations at early stages of acute pancreatic damage during blood supply imparement and that was the goal of current research. The latter is of particular importance in assessing the protective effect of ischemic, distant and pharmacologic preconditioning and metabolic effects of drugs [1, 2, 7].
Materials and methods: 30 white (male and female) 280 -300g rates were used. All investiagations were made at the same time under general anesthesia («Zolitel 100» 60 mg/kg with chloral hydrate 125 mg/kg intraperitonealy).
Transient ischemia reproduced by 30 minutes pancreatic arteries compression followed by reperfusion.
Blood flow velocity was measured by Biopaq systems MP150 with TSD144 probe in perfusion units (PU).
Wet/Dry index were measured as ratio between pancreatic weight after section and after drying with weight stabilization at 56°C
Results. Average initial pancreatic perfusion level was 418.09±39.11 PU, draping to undetecteble data during ischemia period. 1 reperfision minute charectorised by arrising blood flow up to 87.15±12.83 PU and 3 minute 99.47±10.74 PU. At 7.5 minute pancreatic blood flow recovered up to 103.749±10.47 PU, and 151.35±12.32 PE at 15 reperfusion minute correspondingly. Microcirculation blood flow velocity were seen up to 30 reperfusion minute 333.21±26.32 PU and were changed by up to 266.69±18.79 PU decreasing at 60 reperfusion minute. Revovery of pancreatic bood flow velocity thus comprised 79.69% of initial level at 30 reperfusion minute and followed by dropping to 63.78% level at 60 blood flow restoration minute (Fig.1).
Recived data contradict with data obtained previously in our laboratory for microcirculatory blood flow velocity in other abdominal organs (liver, small intestine) ischemia and reperfusion so intestinal deep 30 minutes ischemia leads transient hyperperfusion with maximum at 15-20 min exceeding initial level 1.75-2.1 times.
Kolmykov D.I., Alehin S.A Ischemia/reperfusion effect on pancreatic volumetrical blood flow velocity-Research result: pharmacology and clinical pharmacology. 2015. Vol. 1, №1(1): 42-46.
Initial Ischemia 1 3 reperfision 7,5 15 30 60
perfusion reperfusion minure reperfusion reperfusion reperfusion reperfusion
minute minute minute minute minute
Figure 1. Dynamic of blood flow velocity data in pancreatic gland during ischemia/reperfusion
These microcirculation differences in different internal organs response to ischemia couldn't be explained by systemic hemodynamic changes.
Visually we recognize pancreatic edema formation till 30 reperfusion minute following deep 30 minutes long ischemia (Fig. 2).
Figure 2. Edema end dispersion of pancreatic lobules at 30
Most frequently used methods for edema assessment are Wet/Dry ratio counting and Evans blue dye measuring. Wet/Dry ratio expressed early stages changes versus Evans blue dye extraction used for microvessels permeability assessment for large molecules. That helped us to choose W/D ratio rather than Evans blue dye extraction.
In intact group Wet/Dry ratio was 1.72±0.04 increasing up to 2.1±0.02 till 7.5 reperfusion minute and to 2.52±0.02 till 15 minute. 30 reperfusion
min of reperfusion (right) versus against intact group (left)
minute characterized by Wet/Dry ratio at 3.06±0.03 level.
We think such changes were due to severe permeability increasing in ischemia/reperfusion group. Pancreatic edema leads to acinar vessels compression helping necrotizing process spreads through pancreatic tissue, on the other hand interstitial edema decrease the microvessels quantity and subsequently decreased volumetric velocity.
Kolmykov D.I., Alehin S.A. Ischemia/reperfusion effect on pancreatic volumetrical blood flow velocity. Research result: pharmacology and clinical pharmacology. 2015. Vol. 1, №1(1): 42-46.
Figure 3. Morphological changes in pancreatic gland in 30 minutes ischemia group: disorganization of lobular structure, severe diffuse dystrophic acinar cells changes: vacuolization zymogene zones (A), venous hyperemia (E), haemorrhage into intraacinar stroma. Hematoxylin and eosin dye. Microphoto. X100
Interstitial edema was proven standard histological examination. disorganization of lobular structure, severe diffuse dystrophic acinar cells changes: vacuolization zymogene zones, venous hyperemia, haemorrhage into intraacinar stroma also were found (Fig. 3).
Reperfusion leads to tissue injury deepening end exhibits as progression of lobular structure disorganization, severe diffuse dystrophic acinar cells changes, vacuolization of cellular apical parts and interstitial edema (Fig. 4).
Kolmykov D.I., Alehin S.A. Ischemia/reperfusion effect on pancreatic volumetrical blood flow velocity. Research result: pharmacology and clinical pharmacology. 2015. Vol. 1, №1(1): 42-46.
Figure 4. Morphological changes in group with ischemia and 30 minutes of reperfusion: progression of lobular structure disorganization, severe diffuse dystrophic acinar cells changes (A), vacuolization of cellular apical parts (E), interstitial edema.
Hematoxylin and eosin dye. Microphoto. 100 (A, B), x 200 (E). Conclusions. The results obtained in the study showed no evidence of reactive hyperemia in the pancreatic tissue during reperfusion. This is probably due to the rising of interstitial edema, evidenced an increase in Wet/Dry factor and dynamics morphological changes
References
1. Alehin S.A., Emelianov R.A., Pokrovskay T.G. Microcirculation dynamic investigation in rat pancreatic tissue in acute pancreatitis modeling. University science: Look to the future.-collected papers 71 scientific conference KSMU and session Central-Chernozem scientific centre RAMS. V.1 (2006): P. 206.
2. Emelianov R.A., Alehin S.A., Nazarenko D.P. Microcyrculation investigation by lazerdopplerflowmetry method in pancreatic gland during acute experimental pancreatitis. Kuban's scientific bulletin. №1-2 (2007): P. 50-51. [eLIBRARYl
3. Kadyrov R.K. Structural-functional changes in pancreatic gland and it's blood vessels in early stages of experimental ischemia. Bulletin of current clinical medicine. V.5, №3 (2008): P. 15-18. [Full textl
4. Aho H. J., Nevalainen T. J., Aho A. J. Experimental pancreatitis in the rat. Development of pancreatic necrosis, ischemia and edema after intraductal
sodium taurocholate injection. Eur Surg Res. Vol. 15, № 1. (1983): P. 28-36. [PubMedl
5. Anderson M. C. Venous stasis in the transition of edematous pancreatitis to necrosis. JAMA. Vol. 183 (1963): P. 534-7.
6. Anderson M. C., Bergan J. J. Significance of vascular injury as a factor in the pathogenesis of pancreatitis. Ann Surg. Vol. 154. (1961): P. 58-67. [PMCl
7. Dembinski A., Warzecha Z., Ceranowicz P. Pancreatic damage and regeneration in the course of ischemia-reperfusion induced pancreatitis in rats. J Physiol Pharmacol. Vol. 52, № 2. (2001): P. 221-35. [PubMedl
8. Gullo L., Cavicchi L., Tomassetti P. Effects of ischemia on the human pancreas. Gastroenterology. Vol. 111, № 4 (1996): P. 1033-8. [PubMedl
9. Haas G. S., Warshaw A. L., Daggett W. M. Acute pancreatitis after cardiopulmonary bypass. Am J Surg. Vol. 149, № 4. (1985): P. 508-15. [PubMedl
Kolmykov D.I., Alehin S.A. Ischemia/reperfusion effect on pancreatic volumetrical blood flow velocity. Research result: pharmacology and clinical pharmacology. 2015. Vol. 1, №1(1): 42-46.
10. Hoffmann T. F., Leiderer R., Waldner H. Ischemia reperfusion of the pancreas: a new in vivo model for acute pancreatitis in rats. Res Exp Med (Berl). Vol. 195, № 3 (1995): P. 125-44. [PubMedl
11. Kishino T., Nakamura K., Mori H.« et al..». Acute pancreatitis during haemodialysis. Nephrol Dial Transplant. Vol. 20, № 9 (2005): P. 2012-3. [PubMedl
12. Klar E., Messmer K., Warshaw A. L., Herfarth C. Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy. Br J Surg. Vol. 77, № 11. (1990): P. 1205-10. [PubMedl
13. Obermaier R., Benz S., Kortmann B. Ischemia/reperfusion-induced pancreatitis in rats: a new model of complete normothermic in situ ischemia of a pancreatic tail-segment. Clin Exp Med. Vol. 1, № 1 (2001): P. 51-9.
14. Sakorafas G. H., Tsiotos G. G. Intra-abdominal complications after cardiac surgery. Eur J Surg. Vol. 165, № 9 (1999): P. 820-7. [PubMedl
