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PubMed2006

Nitric oxide and liver microcirculation during autoregulation and haemorrhagic shock in rabbit model.

BACKGROUND: Direct evidence of nitric oxide (NO) involvement in the regulation of hepatic microcirculation is not yet available under physiological conditions nor in haemorrhagic shock. METHODS: A laser Doppler flowmetry was used to measure liver perfusion index and a specific NO-sensitive electrode was inserted into liver parenchyma of anaesthetized rabbits. Hepatic autoregulation during moderate hypovolaemia {mean arterial pressure at 50 mm Hg without liver perfusion alteration; blood withdrawal 17.7 (4.2) ml [mean (SD)]} or haemorrhagic shock [mean arterial pressure at 20 mm Hg associated with liver perfusion impairment and lactic acidosis; blood withdrawal 56.0 (6.8) ml] were investigated over 60 min and were followed by a rapid infusion of the shed blood. Involvement of NO synthases was evaluated using a non-specific inhibitor, NAPNA (Nomega-nitro-L-arginine P-nitro-anilide). RESULTS: In the autoregulation group, a decrease [30.0 (4.0) mm Hg] of mean arterial pressure did not alter liver perfusion index, whereas the liver NO concentration increased and reached a plateau [125 (10)%; compared with baseline; P<0.05]. This NO concentration was reduced to zero by the administration of NO synthase inhibitor. Haemorrhagic shock led to a rapid decrease in liver perfusion index [60 (7)%; compared with baseline; P<0.05] before an immediate and continuous increase in NO concentration [250 (50)%; compared with baseline; P<0.05]. Infusion of NO inhibitor before haemorrhagic shock reduced the NO concentration to zero and hepatic perfusion by 60 (8)% (P<0.05) of the baseline. Mean arterial pressure increased simultaneously. In these animals, during haemorrhage, a continuous increase in NO concentration still occurred and liver perfusion slightly increased. In all groups but NAPNA+haemorrhagic shock, blood replacement induced recovery of baseline values. CONCLUSIONS: NO plays a physiological role in the liver microcirculation during autoregulation. Its production is enzyme-dependent. Conversely, haemorrhagic shock induces a rapid increase in hepatic NO that is at least partially enzyme-independent.

Anilides↗

PubMed2003

Leukocyte behaviour and permeability in the rat mesenteric microcirculation following induction of ovulation.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS), a highly dangerous and incompletely understood complication of ovulation induction with exogenous gonadotrophins, can include haemoconcentration, hypovolaemia, hypotension, acute renal insufficiency, thromboembolism and ultimately death. Using intravital microscopy, we examined microvascular permeability and leukocyte-endothelial cell interactions in the rat mesenteric microcirculation associated with induction of ovulation. METHODS: In female rats treated with hMG and hCG, mesenteric venules were observed by intravital microscopy assisted by a video imager. Erythrocyte velocity was monitored, and rolling and adhesion of leukocytes were studied by transmission video images. Transvascular leakage of fluorescein isothiocyanate-labelled albumin was assessed by epi-illumination. RESULTS: Administration of hMG and hCG significantly increased vascular protein leakage within a few hours, and also reduced rolling velocities of leukocytes in venules and increased numbers of leukocytes adherent to endothelium at 16 h following hCG injection. The administration of antibodies against intracellular adhesion molecule (ICAM)-1 inhibited these reactions. CONCLUSION: By induction of ovulation, vascular permeability is increased not only at the surface of the ovary but also in the mesentery. Alteration of leukocyte behaviour in the microcirculation through mechanisms involving ICAM-1 is one likely cause of the protein leakage.

Animals↗

PubMed1997

Dietary copper in the physiology of the microcirculation.

Dietary copper has long been known to be essential for cardiovascular homeostasis. However, the role of copper and cuproenzymes in the normal control of vascular physiology is not well understood. Most studies in the cardiovascular system have focused on copper deficiency-induced defects in the heart or large vessels. Recently, attention has also focused on the effects of copper deficiency in the microcirculation or the small blood vessels that control blood flow, nutrient and waste exchange, and peripheral vascular resistance. Studies in the microcirculation demonstrate that copper is important in mechanisms of macromolecular leakage, platelet-endothelial interactions and vascular smooth muscle reactivity. There is a significantly greater leakage of proteins from postcapillary venules in copper-deficient rats in response to mast cell-released histamine. This response appears to be the result of increased numbers of mast cells and thereby increased available histamine. Copper deficiency also causes an inhibition of in vivo thrombogenesis, which appears to be related to an inhibition of platelet adhesion. Subsequent studies have demonstrated that this is probably caused by a diminished concentration of the adhesion molecule von Willebrand factor. Nitric oxide (NO)-mediated arteriole vasodilation is also compromised in copper-deficient rats. This functional deficit to NO can be reversed by the addition of Cu, Zn-superoxide dismutase (SOD), suggesting that degradation of NO by superoxide anion occurs during copper deprivation. These observations demonstrate that dietary copper is necessary for several microvascular control mechanisms affecting inflammation, microhemostasis and regulation of peripheral blood flow.

Animals↗

PubMed2002

Hydroxyethyl starch (130 kD), but not crystalloid volume support, improves microcirculation during normotensive endotoxemia.

BACKGROUND: Increased leukocyte-endothelial cell interaction (LE) and deterioration of capillary perfusion represent key mechanisms of septic organ dysfunction. The type of volume support, however, which may be used during septic disorders, remains controversial. Using intravital microscopy, the authors studied the effect of different regimens of clinically relevant volume support on endotoxin-induced microcirculatory disorders, including the synthetic colloid hydroxyethyl starch (HES, 130 kD) and a crystalloid regimen with isotonic saline solution (NaCl). METHODS: In Syrian Golden hamsters, normotensive endotoxemia was induced by intravenous application of Escherichia coli lipopolysaccharide (LPS, 2 mg/kg). The microcirculation was analyzed in striated muscle of skinfold preparations. HES 130 kD (Voluven(R), 16 ml/kg, n = 7) or isotonic saline (NaCl, 66 ml/kg, n = 6) were infused 3 h after LPS exposure over a 1-h period (posttreatment mode). Animals receiving LPS without volume therapy served as control subjects (n = 8, control). LE, functional capillary density (FCD), and macromolecular leakage were repeatedly analyzed in the awake animals during a 24-h period using intravital fluorescence microscopy. RESULTS: HES 130 kD significantly reduced LPS-induced arteriolar and venular leukocyte adherence (P < 0.05), whereas NaCl resuscitation had no effect when compared with nontreated control animals. The LPS-induced decrease in FCD and increase in macromolecular leakage were also significantly attenuated by HES 130 kD but not by NaCl. Improvement of LPS-induced microcirculatory disorders by HES was unlikely the result of macro- and microhemodynamic changes because arterial blood pressure, heart rate, and venular wall shear rate did not differ between HES- and NaCl-treated animals. CONCLUSIONS: Thus, our study provides microhemodynamic and cellular mechanisms of HES 130 kD-mediated protection on microcirculation during endotoxemia, even when used in a clinically relevant posttreatment mode during normotensive conditions.

Animals↗

PubMed1995

Calcitonin gene-related peptide increases microcirculation after mechanically induced ischemia in an experimental island flap.

Vasoconstriction, as a result of mechanical manipulation of blood vessels during microsurgery, may produce a decrease in blood supply and endanger flap viability. A study was undertaken to determine the effects of the topical vasodilator calcitonin gene-related peptide on the microcirculation of flaps after mechanically induced ischemia. A neurovascular island flap based on the superficial epigastric vessels was raised in 42 rats. Blood cell flux in the flap was recorded continuously with a laser Doppler flux meter. The feeding artery was pinched to induce vasospasm, and different concentrations of calcitonin gene-related peptide (10(-7), 10(-8), 10(-9), 10(-10) mol) or a control of sodium chloride 0.9% was applied topically to relieve the ischemia. Results showed that calcitonin gene-related peptide at a concentration of 10(-7) mol significantly shortened the time to reach 50% of the original blood cell flux values (270 +/- 123 seconds) and significantly increased the number of flaps in which the blood cell flux values were restored to prestress levels within 30 minutes. The data support the conclusion that, in this model, topical calcitonin gene-related peptide at the concentration of 10(-7) mol was effective in promoting recovery of the microcirculation after mechanically induced ischemia, without the adverse effects associated with other commonly used vasodilators.

Animals↗

PubMedDate not supplied

A new apparatus for chronic observation of the microcirculation in situ to evaluate artificial organ performance.

Chronic study of the peripheral circulation and metabolism is very important in evaluation of artificial organ performance. However, there has been no way to observe the microcirculation in situ, chronically and continuously, without restriction. In this study, the authors developed a new apparatus that could be implanted and connected to an artificial organ that would allow continuous observation of the microcirculation while the subject is awake. The apparatus uses a charge coupled device (CCD) under a new principle: thin living tissue, such as mesentery, is put directly on a highly integrated CCD and transilluminated with a light emitting diode (LED). The vascular nets in the tissue are projected onto the CCD like a contact photograph, which is sent to a television screen and can be analyzed for motion and function. A 0.5 inch CCD with 25K pixels was used in this study. The cover glass of the CCD was removed so the tissue would be able to directly contact the CCD surface. The CCD, as well as LED, were molded with hard polyurethane as electrical insulation. The apparatus is 35 mm in diameter and 10 mm high with a micro stand for lighting with the LED, which is easy to implant in a goat or calf. The resolution of this apparatus was tested by putting a micro scale on the CCD surface. Several tenths of micrometers could be seen. In an animal experiment with a rabbit, configurations of arterioles and venules and their motions could be observed continuously for a night until the electrical insulation was broken. This method might be a strong weapon in artificial organs research.

Animals↗

PubMedDate not supplied

Distinctive microcirculation of the brain during cerebral perfusion by observation with a CCD microscope.

Establishment of safer cerebral protection remains an important issue in reducing cerebral complications during aortic arch repair. Various cerebral perfusion techniques have been used. Recently, the usefulness of retrograde cerebral perfusion (RCP) combined with hypothermia was reported. The authors evaluated the cerebral microcirculation during RCP by direct observation with a charge-coupled device (CCD) microscope. In six craniotomied, anesthetized swine, cardiopulmonary bypass was established by arterial perfusion through the femoral artery and venous drainage from the right atrium. The authors observed cerebral arteriolae and venulae on the brain surface. Each swine was cooled to a brain temperature of 20 degrees C. Perfusion was stopped, RCP was initiated with oxygenated blood through the superior vena cava, and cerebral perfusion pressure (CPP) was gradually increased. During antegrade cerebral perfusion (ACP), homogeneous vascular flow was observed in all models. During RCP, retrograde vascular flow was generated in four of the six models, but homogeneous retrograde vascular flow was achieved in arteriolae and venulae in only two models at a CPP of greater than 20 mmHg. It is suggested that homogeneous and effective retrograde perfusion may not be achieved at a CPP of less than 20 mmHg, and that RCP causes uneven microcirculation of the brain with a disadvantageous effect on cerebral protection when compared with ACP.

Animals↗

PubMedDate not supplied

The role of pulsatility in end-organ microcirculation after cardiogenic shock.

To estimate the effectiveness of pulsatility in end-organ microcirculation after cardiogenic shock, experimental studies using swine were done. Cardiogenic shock was produced in 14 pigs by ligating the left anterior descending branches so that mean aortic pressure dropped to 60% of the control value. After inducing shock, left atrial to ascending Ao bypass was initiated. A pneumatic pulsatile pump (Zeon Medical Inc, Tokyo, Japan) was used in seven pigs (Group P) and a centrifugal pump (BP-80, BioMedicus Inc, Minneapolis, MN) in seven (Group NP). In both groups, about half the usual cardiac output was supported for 3 hr, maintaining mean aortic pressure at approximately 100 mm Hg. The pulse pressure was 36.6 +/- 4.6 mm Hg in Group P, and 14.3 +/- 1.5 mm Hg in Group NP. Epicardial and endocardial regional flows recovered after assist in both groups. There were no significant differences between the two groups. However, liver tissue flow, renal cortex flow, and stomach mucous flow in Group P was significantly higher than those of Group NP after support (p < 0.05). In addition, arterial blood ketone ratio in Group P was 0.61 +/- 0.13 vs 0.39 +/- 0.06 in Group NP, a significant difference (p < 0.05). These results suggest that in uneven blood flow distribution of end organs after cardiogenic shock, pulsatility was effective in improving and maintaining function and microcirculation of end organs, preventing multiorgan failure.

Animals↗

PubMed1998

Improved outcome after severe head injury with a new therapy based on principles for brain volume regulation and preserved microcirculation.

OBJECTIVE: To assess the new "Lund therapy" of posttraumatic brain edema, based on principles for brain-volume regulation and improved microcirculation. DESIGN: A prospective, nonrandomized outcome study over a 5-yr period on severely head-injured patients with increased intracranial pressure, comparing the results with a historical control group with the same selection criteria for patients who were treated according to conventional principles. SETTING: General intensive care unit of a university hospital. PATIENTS: Fifty-three consecutive head-injured patients with a Glasgow Coma Score of <8, and with increased intracranial pressure (>25 mm Hg), despite conventional treatment. INTERVENTIONS: Interstitial fluid resorption was obtained by lowering intracapillary hydrostatic pressure, by preserving normal colloid osmotic pressure, and by maintaining a normovolemic (normal albumin/serum and hemoglobin/serum), not overtransfused patient. Intracapillary pressure was reduced by the combination of precapillary vasoconstriction (low-dose thiopental, dihydroergotamine) and reduction of mean arterial pressure, the latter attained with a beta1-antagonist (metoprolol 0.2 to 0.3 mg/kg/24 hrs iv) and an alpha2-agonist (clonidine 0.4 to 0.8 microg/kg x 4 to 6 iv). Clonidine, in combination with normovolemia, also improves microcirculation by reducing catecholamines in plasma. Intracranial blood volume was reduced by arterial (low-dose thiopental sodium and dihydroergotamine) and large-vein (dihydroergotamine) vasoconstriction. The start dose of dihydroergotamine (maximum 0.9 microg/kg/hr) was successively reduced toward discontinuation within 4 to 5 days. MEASUREMENTS AND MAIN RESULTS: There were 8% of patients who died and the neurologic conditions of 13% remained severely damaged, compared with 47% and 11%, respectively, for the control group. CONCLUSIONS: The low mortality compared with previous outcome studies strongly indicates that this therapy improves outcome for severe head injuries. However, a randomized, controlled study is needed to reach general acceptance of this new therapy.

Acute Disease↗

PubMed1992

Nailfold microcirculation in normotensive and essential hypertensive subjects, as assessed by video-microscopy.

OBJECTIVE: To compare morphological and hemodynamic parameters of skin microcirculation in the fingertip in patients with essential hypertension and normotensive control subjects. DESIGN: Consecutive sample of patients. METHODS: Digital capillary blood flow measurements under normal and cooled conditions were assessed by nailfold video capillaroscopy using the technique of flying spot. RESULTS: There was a significant reduction in capillary density in hypertensive patients, compared with normotensive subjects. There was a correlation between capillary density and mean diastolic blood pressure. After local cooling the frequency of the blood flow stop was significantly higher in hypertensive patients. CONCLUSION: The finding of abnormal vasoconstriction in finger microcirculation in essential hypertension suggests a vasospastic tendency in the disease.

Blood Flow Velocity↗

PubMed1996

Effect of atrial natriuretic factor on skin microcirculation versus skeletal muscle blood flow.

The response of the skin microcirculation and of forearm skeletal muscle blood flow to infusion of alpha-human (99-126) atrial natriuretic factor (ANF) into the brachial artery was investigated in 15 young (18-25 years) healthy volunteers in a double-blind, randomized, placebo-controlled study. The forearm blood flow (FBF) was measured with venous occlusion plethysmography, and the skin flux was measured by using laser Doppler fluxmetry (LDF). Dose-response curves were made using increasing dosages of ANF: 1, 10, and 100 ng/min/dl forearm volume. The FBF showed a significant, dose-dependent increase during ANF infusion, averaging 107 + 22% during the highest ANF dosage, as compared with -5 +/- 9% during placebo (p < 0.001). For the LDF, these numbers were 34 +/- 21 and -6 +/- 10%, respectively (NS). In two subgroups of subjects, the effect of ANF on microvascular reactivity was assessed by registering the vasoconstrictor response to cold exposure (n = 7) and the vasodilator response to arterial occlusion (n = 7). ANF did not change the microvascular response to these stimuli. ANF induces a dose-dependent increase in skeletal muscle BF without a relevant response in the skin microcirculation. ANF does not play an important role in the regulation of skin perfusion.

Adult↗

PubMed1990

Persistent arteriolar constriction in microcirculation of the terminal ileum following moderate hemorrhagic hypovolemia and volume restoration.

A stable in vivo preparation of moderate hypovolemia with prompt volume restoration was produced in anesthetized rats. The microcirculation of the terminal ileum was observed in vivo videomicroscopy, and changes in mean arterial pressure (MAP) as well as arteriolar diameters were recorded after a 30-min period in which the MAP was reduced by 50% by bleeding. Volume was restored with shed blood alone (control); dextran 70 alone (dextran); or dextran + hypertonic (7.5%) saline (dextran + HS). A final group of rats was pretreated with allopurinol 5 mg/kg and then treated identically to the control group to assess the role of the xanthine oxidase system in microcirculation changes following hemorrhage. MAP was restored to normal by return of shed blood in control animals, but inflow arterioles (A1) remained significantly constricted. MAP was significantly higher and A1 arteriolar dilation was observed in the dextran + HS group. Responses in allopurinol-pretreated animals were not different from the responses seen in control animals. We conclude that persistent arteriolar constriction is produced by moderate hypovolemia and this effect is ameliorated by volume restoration with dextran + HS.

Allopurinol↗

PubMed1999

In vivo rat closed spinal window for spinal microcirculation: observation of pial vessels, leukocyte adhesion, and red blood cell velocity.

OBJECTIVES: An in vivo closed spinal window technique in rats was designed for observing the spinal microcirculation, such as the change of vessel diameter, leukocyte adhesion, and red blood cell (RBC) velocity, which has been very rarely examined in vivo in the spinal cord. METHODS: We made a very precise closed spinal window with a laminectomy at the C5 level using a dental acrylic resin and a cover glass (7 mm in diameter). Through this closed window, the dorsal surface of the rat cervical cord was observed with a video microscope, and the fluorescent images of rhodamine 6G-labeled leukocytes and fluorescein isothiocyanate-labeled RBCs were recorded and analyzed with a silicon-intensified target tube camera (30 frames/s) and an image-intensified high-speed video camera system (1000 frames/s). RESULTS: During CO2 inhalation, the pial arterioles responded with vasodilation of 12.4+/-10.4% (P<0.01) in 11 arterioles of seven rats. The adhering leukocytes significantly increased in 41 venular segments of seven rats after superfusion of the neutrophil chemoattractant, N-formyl-methionine-leucine-phenylalanine solution for 15 minutes (P<0.001) but not after superfusion of only artificial cerebrospinal fluid for 15 minutes. During these experiments, no adhering leukocyte was seen in the pial arterioles. Fluorescein isothiocyanate-labeled RBCs look like shooting stars in arterioles with silicon-intensified target tube camera processing at 30 frames per second, but individual fluorescein isothiocyanate-labeled RBCs could be recognized frame by frame with the image-intensified high-speed video camera system. In 13 arterioles of four rats, the RBC velocity was 5.3+/-2.0 mm per second. CONCLUSION: This closed spinal window technique in rats is available and applicable for the study of the spinal microcirculation, such as the pathophysiology of a secondary injury.

Animals↗

PubMed1997

Effect of low dose aspirin on thrombus formation at arterial and venous microanastomoses and on the tissue microcirculation.

In free flap/replantation surgery, failure is usually associated with thrombotic occlusion of a microvascular anastomosis (risk zone I) or, on occasion, flow impairment in the microcirculation of the transferred or replanted tissue (risk zone II). The objective of this study is to describe the effect of low dose aspirin on blood flow at both risk zones in microvascular surgery. Risk zone I: In rat femoral arteries and veins, thrombus formation was measured at the anastomoses using transillumination and videomicroscopy. Forty male Wistar rats were assigned in equal numbers to four groups: either arterial or venous injury with either aspirin (5 mg/kg systemically) or saline treatment. We found that aspirin significantly reduces thrombus formation at the venous anastomosis (p = 0.001). Risk zone II: In the isolated rat cremaster muscle downstream from an arterial anastomosis, we measured capillary perfusion, arteriolar diameters, and the appearance of platelet emboli for 6 hours in the muscle microcirculation. Sixteen male Wistar rats in two equal groups received either aspirin (5 mg/kg systemically) or saline. We found that in aspirin-treated animals, capillary perfusion is significantly (p = 0.002) improved, whereas arteriolar diameters and emboli only slightly increased. In conclusion, low dose aspirin inhibits anastomotic venous thrombosis and improves microcirculatory perfusion in our rat model. These studies provide quantitative data confirming and clarifying the beneficial effects of low dose aspirin in microvascular surgery.

Anastomosis, Surgical↗

PubMed2003

Noninvasive in vivo assessment of the pancreatic microcirculation: orthogonal polarization spectral imaging.

INTRODUCTION: Capillary perfusion failure of the pancreatic microcirculation is characteristic in the pathogenesis of acute pancreatitis and ischemia-reperfusion damage after pancreas transplantation. Up to now, no logistic suitable method for analyzing pancreatic capillary perfusion during operations in humans has been established without the use of fluorescent dyes. AIM: To compare the well-established technique of intravital epifluorescence microscopy with the novel noninvasive method of orthogonal polarization spectral (OPS) imaging for measurement of the pancreatic functional capillary density. METHODOLOGY: In eight anesthetized rats, six identical capillary regions of interest per animal were measured by both methods, and the results were compared. RESULTS: Absolute values from the capillary perfusion data were not significantly different between the two methods (fluorescence microscopy: 394 +/- 44 cm/cm2; OPS imaging: 385 +/- 45 cm/cm2). Correlation parameters were significant, and Bland-Altman analyses showed good agreement with a mean difference (bias) between the two methods of 6.9 cm/cm2, indicating that slightly smaller values are measured with OPS imaging. CONCLUSION: OPS imaging is a valid noninvasive method that analyzes the pancreatic microcirculation as accurately as the established intravital microscopy technique and therefore could be useful for clinical research and diagnosis during transplantation and operations.

Animals↗

PubMed2004

A new experimental pancreatitis by incomplete closed duodenal loop: the influence of pancreatic microcirculation on the development and progression of induced severe pancreatitis in rats.

OBJECTIVES: We developed a new model of reversible pancreatitis, as an incomplete closed duodenal loop (ICDL) model. This permitted us to demonstrate the process of progressing severity of pancreatitis and the influence of tissue microcirculation impairment on the morphologic changes of pancreatitis. METHODS: An ICDL model was prepared in Wistar rats according to the following procedure. The duodenum was ligated over half its circumference at 2 cm on either side of the duodenal entry of the biliopancreatic duct. RESULTS: The pancreatic wet weight ratio in the ICDL was higher than that of the control after model preparation. The survival rate in the ICDL group was significantly longer than that in the CDL group. Blood flow in the pancreas and duodenal loop decreased over time after model preparation, and the decline in ICDL occurred and remained at a plateau in chronic pancreatitis phase. Histopathologic alterations of the pancreas in the ICDL group consisted of edema, parenchymal necrosis, thrombosis, and hemorrhage. From 1 week onward, periductal fibrosis spread to the parenchyma, the regenerative activity of the acinar cell presenting the clinical features of chronic pancreatitis. CONCLUSION: Impairment of microcirculation due to tissue ischemia played a role in the increasing severity of pancreatitis.

Acute Disease↗

PubMed1992

The impact of arterialization on hepatic microcirculation and leukocyte accumulation after liver transplantation in the rat.

This study investigated the influence of hepatic arterialization on early graft function, microcirculation, and leukocyte-endothelial interaction after syngeneic orthotopic liver transplantation in Lewis rats. Livers were preserved for 17 hr in UW solution and transplanted without rearterialization (group 1: n = 10) or with immediate arterial reconstruction (group 2: n = 10). Graft function was analyzed by bile flow; microcirculation was assessed by laser Doppler flowmetry (LDF) and intravital microscopy (IVM). In addition, flow behavior of leukocytes was quantified by IVM after i.v. injection of the WBC marker acridine orange. Improved graft function in group 2 was indicated by increased bile production during the observation period of 90 min after reperfusion (7.18 +/- 0.62 vs. 3.63 +/- 0.63 ml/100 g liver [mean +/- SEM] P < 0.001). In arterialized grafts LDF values increased by 22.9 +/- 3.8% upon reperfusion of the hepatic artery (P = 0.004). Arterialization increased WBC velocities in sinusoids (group 1: 0.29 +/- 0.02 mm/sec, group 2: 0.34 +/- 0.01 mm/sec, P < 0.001) and postsinusoidal venules (0.43 +/- 0.05 vs. 0.64 +/- 0.05 mm/sec, P = 0.029). In addition, the number of nonperfused midzonal sinusoids decreased significantly (8.5 +/- 2.2% of all sinusoids analyzed vs. 4.2 +/- 1.3%, P = 0.048). However, the marked sinusoidal and venular WBC adherence observed 1 hr after reperfusion was not altered by arterialization. It is concluded that arterial reconstruction in rat liver transplantation improves microvascular perfusion and graft function but this improvement does not relate to WBC accumulation within the graft. We propose that studies on hepatic preservation and postischemic reperfusion in the rat should be based on the physiological model of dual vascularization.

Animals↗

PubMed2001

Improved hepatic microcirculation by human soluble urinary thrombomodulin in the xeno-perfused porcine liver.

PURPOSE: Both the protein C/thrombomodulin system and the heparin/anti-thrombin III system are major physiological anticoagulant systems, which may also play a major role in preserving the hepatic microcirculation in xenogeneic liver transplantation. To compensate for the functional incompatibilities of the porcine thrombomodulin (TM)-cofactor activity beyond species for human thrombin, soluble human TM protein was tested in xenogeneic perfusion of the porcine liver. MATERIALS AND METHODS: The livers were harvested from adult female pigs and perfused through the portal vein (PV) and hepatic artery (HA) for 2 hr, with fresh human blood in group 1 (n=5), fresh porcine blood (10 units/ml) in group 2 (n=5), and fresh human blood with TM (50,000 units/1.5 l) in group 3 (n=5). The tissue PO2 level, tissue blood flow, PV and HA pressures were all continuously monitored. Circulating perfusate and liver tissue samples were periodically obtained for blood chemistry and histologic analyses. RESULTS: The activated protein C (aPC) level was significantly elevated in the TM-treated group 3 (47.5%+/-3.5% at preperfusion and 51%+/-2.8% after 120 min of perfusion) in comparison to group 1 (32.3%+/-7.2% and 35.3+/-12.0%). The hepatocyte enzyme release of aspartate aminotransferase (AST) was suppressed significantly more in group 3 (238.2+/-107 IU/l), than in group 1 (672.3+/-160 IU/l) at 2 hr after reperfusion. In group 3, the tissue PO2 levels and tissue blood flow also remained significantly higher throughout the perfusion. The platelet counts in the perfusate remained significantly higher in group 3 (37.1% to 74.3% of the preperfusion level) than in group 1 (4.4% to 14.7%), after 0 to 80 min of perfusion. According to the histologic findings, the degree of interlobular hemorrhaging and congestion decreased remarkably more in group 3 than in group 1. CONCLUSION: These findings thus indicated that soluble thrombomodulin protein extracted from human urine remarkably improved hepatic microcirculation in the xenoperfused porcine liver. The thrombomodulin/protein C system might, thus, play an important role in restoring the physiological anticoagulant system in the xenoperfused porcine liver.

Animals↗