Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular–pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.

PURPOSE:The failure of small-caliber vascular grafts still means a serious problem. Concerning the early postoperative complications we aimed to investigate the hemostaseological and hemorheological aspects of this issue in a canine model. METHODS:In the Control group only anesthesia was induced. In the Grafted group under general anesthesia a 3.5-cm segment was resected unilaterally from the femoral artery and replaced with a PTFE graft (diameter: 3 mm). On the 1 st -3 rd -5 th -7 th and 14 th postoperative days the skin temperature of both hind limbs was measured, and blood sampling occurred for hematological, hemostaseological and hemorheological tests. RESULTS:The skin temperature of the operated versus intact limbs did not differ. In the Grafted group leukocyte count was elevated by the 1 st postoperative day, while platelet count increased over the entire follow-up period. Fibrinogen concentration rose on the 1 st -5 th days, activated partial thromboplastin time increased on the 3 rd -7 th days. Erythrocyte aggregation was enhanced significantly on the 1 st -5 th days. In specimens taken on the 14 th day, histologically we found matured thrombus narrowing the graft lumen. CONCLUSIONS:Small-caliber PTFE graft implantation into the femoral artery caused significant changes in several hemostaseological and hemorheological parameters. However, better clarifying the factors leading to early thrombosis of these grafts needs further studies.Key words: Vascular Grafting. Graft Occlusion, Vascular. Erythrocyte Aggregation. Blood Coagulation. Models, Animal. Dogs. Early postoperative changes in hematological, erythrocyte aggregation and blood coagulation parameters after unilateral implantation of polytetrafluoroethylene vascular graft in the femoral artery of beagle dogs

Previously we have investigated the cerulein-induced acute pancreatitis and provided data on its micro-rheological impact in the rat. We hypothesized that non-steroid anti-inflammatory agent flunixin, the xanthine-derivate pentoxifylline and the low molecular weight heparin enoxaparin may have various beneficial effects improving microcirculatory and rheological parameters. In female rats, under general anesthesia, 10 g/kg cerulein s.c. was administered and 2 hours afterwards microcirculation was tested by laser Doppler flowmetry on the tongue and after performing laparotomy on the small intestine, liver and pancreas prior to terminal blood sampling. From blood samples hematological parameters, blood pH, lactate concentration, erythrocyte deformability, osmoscan parameters and erythrocyte aggregation were tested. Compared to normal control in acute pancreatitis group we found severe deterioration in tissue microcirculation together with impaired erythrocyte deformability and enhanced aggregation, accompanied by acidic pH and increasing lactate concentration. Improvement was found when using flunixin (s.c.), pentoxifylline (i.p.) or enoxaparin (s.c.). These drugs could partly improve the blood flux on the surface of the investigated organs, and the flunixin had the most expressed improving effects on micro-rheological parameters. Surprisingly, the improving effect of pentoxifylline on micro-rheological parameters was not obvious (red blood cell deformability did not improved better than in the other treated groups), however, microcirculatory parameters improved.

PURPOSE:To examine how the ischemia-reperfusion injury of latissimus dorsi-cutaneous maximus (LDCM) musculocutaneous flap affects the microcirculatory (flap's skin surface) and hemorheological parameters, and whether an intraoperative deterioration would predictively suggest flap failure in the postoperative period. METHODS:Ten healthy male rats were subjected to the study. In Group I the left flap was sutured back after 2-hour, while the contralateral side was right after its elevation. In Group II the same technique was applied, but the pedicle of the left flap was atraumatically clamped for 2-hour. The contralateral side was left intact. On the flap skin surface laser Doppler tissue flowmetry measurements were done before and after and during the protocols applied in the groups. Microcirculatory and hemorheological examinations were done postoperatively. RESULTS:The microcirculatory parameters significantly decreased during immobilization and ischemia. Afterwards, all the regions showed normalization. In the retrospective analysis there was a prominent difference between the microcirculatory parameters of necrotic and survived flap during the early postoperative days (1-3) in Group II. Erythrocyte aggregation and deformability showed only slight differences.CONCLUSIONS: Two-hour ischemia and reperfusion caused deterioration in latissimus dorsi-cutaneous maximus flap microcirculation.Predicting the possible postoperative complication, the intraoperative laser Doppler measurement can be informative.

No abstract

Ischemia-reperfusion-caused hemorheological alterations have been widely studied but the effect of testicular ischemia-reperfusion has not so far. In this study 14 Sprague-Dawley rats were involved. In the ischemia-reperfusion group under general anaesthesia the left testis was explored by opening the scrotum then the deferent duct and vasculature were clamped for 30 minutes. Testicular microcirculation was monitored by laser Doppler flowmetry. The right testis was untouched. In the control group: only anaesthesia was induced. Blood sampling occurred before and after ischemia, at the 60th minute of reperfusion and on the 1st postoperative day for determining hematological parameters (microcell-counter), erythrocyte deformability (slit-flow ektacytometer) and erythrocyte aggregation (light-transmission aggregometer). After the last blood sampling, testicles were removed for histological examination. Hematological parameter changes reflected inflammatory response. Erythrocyte deformability showed a worsening already at the 60th minute of reperfusion compared to base and control values. By the 1st postoperative day further decrease was observed. Erythrocyte aggregation significantly enhanced with great magnitude versus base and control values (p < 0.001). However, conventional histological examinations did not show marked testicular injury. The experienced changes can attract attention to the testicular ischemia-reperfusion causing significant effects on hemorheological parameters, which can lead to further harmful microcirculatory consequences.

Testicular torsion may lead to serious ischemia, and the viability depends on the duration of torsion and the effect of ischemia-reperfusion. Testicular decompression and tunica vaginalis flap application technique were introduced in 2008 by Kutikov et al. We aimed to examine the impact of this method on the testicular microcirculation and hemorheological parameters in a rat model. Six adult rats underwent bilateral scrotal exploration. Intravaginal torsion of the testis was created by 720° rotation on both sides for 2 h. After detorsion, the right testes underwent tunica albuginea incision and tunica vaginalis flap application. Testicular microcirculation was monitored and hematological parameters, erythrocyte deformability, and aggregation were determined. Measurements were performed before and after torsion, directly after detorsion, on the 1st–2nd and 8th postoperative day. After the last sampling, testicles were removed to determine their volume for histological examinations. The microcirculatory parameters demonstrated slight differences between testicles. Apical zone of the left (nondecompressed) testicles had elevated compared to the middle zone (P < 0.05). On the 2nd and 8th day, the microcirculation of the testes normalized but not equally. The erythrocyte aggregation and deformability decreased by the 8th day. Both testicles underwent atrophy and epithelial necrosis, but the volume of the decompressed ones was lower (1.07 ± 0.08 vs 1.25 ± 0.31). Histologically, there was no significant difference in epithelial damage score between decompressed and nondecompressed testes. In conclusion, 2-h ischemia led to alteration in testicular microcirculation, reduction in volume, changes in hemorheological parameters and serious epithelial necrosis both in decompressed and nondecompressed testicles without remarkable differences.

Investigation of regional hemorheological properties are important in ischemia-reperfusion experimental surgical and microsurgical research models, however, the physiological arterio-venous as well as porto-caval differences in erythrocyte deformability and aggregation are still controversial. In this study, besides measuring blood pH, blood gases, lactate concentration and hematological parameters we determined erythrocyte deformability (rotational ektacytometer) together with osmoscan data as well as erythrocyte aggregation (light transmittance aggregometer) in blood samples taken from the portal vein, caudal caval vein and abdominal aorta of rats. Blood pH, partial blood gas pressures showed the anticipated physiological differences. Leukocyte count was lower in arterial blood; hematocrit, erythrocyte and platelet count was higher in systemic and portal venous blood. The lowest elongation index values were measured in arterial blood, the highest in venous and portal venous blood showed values in between. The osmoscan data did not show important differences. Erythrocyte aggregation M index 5 s showed the lowest values in arterial, higher in systemic venous and portal venous blood samples. M index 10 s showed significantly low values in systemic venous blood. M1 values were slightly higher in arterial blood compared to venous blood but the highest were in portal venous blood. Erythrocyte deformability and aggregation may show aorto-porto-caval differences in the rat. The appropriate control examinations thus are important in experimental surgical and microsurgical research models.