Efficacy and Safety of Early Systemic Anticoagulation for Preventing Splanchnic Thrombosis in Acute Necrotizing Pancreatitis.

OBJECTIVES: Splanchnic venous thrombosis (SVT) is a relevant complication in patients with acute necrotizing pancreatitis. So far, no specific treatment for preventing development of SVT exists, and the effect of systemic anticoagulation (SAC) is unclear. METHODS: Patients with acute necrotizing pancreatitis admitted to our center within 7 days from onset of abdominal pain were screened. In the historic group, during which period, most patients received no SAC. Patients in the study group received SAC therapy considering the risk of deep vein thrombosis and SVT. The primary outcome measure was the incidence of SVT. RESULTS: Splenic vein was involved in 71% of all 84 SVT patients. Compared with the historic cohort, patients who received SAC experienced lower incidence of SVT (P < 0.001), especially for splenic venous thrombosis (P = 0.002). Patients in the study group also showed lower mortality (P = 0.04) and incidence of new-onset organ failure (P = 0.03). The incidence of bleeding shows no statistical significance between 2 groups. CONCLUSIONS: Application of SAC seems to reduce the incidence of SVT and improve clinical outcomes without increasing the risk of bleeding. Randomized clinical trials are needed to confirm our findings.

Successful intravenous administration of argatroban in the management of heparin-resistant and surgery-resistant mesenteric vein thrombosis.

A 78-year-old woman visited the emergency department with complaints of progressively worsening abdominal pain for a week. Nausea and vomiting started at the time of the visit. An abdominal contrast-enhanced CT (CECT) revealed a filling defect of portal vein, splenic vein and superior mesenteric vein (SMV) which was diagnosed as portal vein and mesenteric venous thrombosis (MVT). Intravenous administration of unfractionated heparin was initiated. However, her symptoms did not improve, and she underwent surgical thrombectomy on the second day of hospitalisation. On the sixth day, CECT revealed the recurrence of thrombi in the portal vein, SMV and along the central venous catheters. We switched heparin to argatroban on the eighth day. After administering argatroban, CECT revealed that the thrombi had almost disappeared by the 40th day. In this case, argatroban was considered effective for heparin-resistant and surgery-resistant portal vein and MVT.

How I treat splanchnic vein thrombosis.

Antithrombotic treatment of splanchnic vein thrombosis (SVT) is a clinical challenge. Depending on the site of thrombosis, patients are at risk of developing liver insufficiency, portal hypertension, or bowel infarction and may experience recurrence in both the splanchnic veins and other vein segments. To prevent recurrence, anticoagulant therapy should be started as soon as possible after diagnosis and is often continued for an indefinite period of time. However, active bleeding is not infrequent at the time of SVT diagnosis, and major risk factors for bleeding, such as esophageal varices or a low platelet count, are frequently present in these patients. In real-world clinical practice, a proportion of SVT patients are left untreated because the risks associated with anticoagulant therapy are felt to exceed its benefits. However, the majority of patients receive anticoagulant drugs, with heterogeneous timing of initiation, drug choice, and dosages. Evidence to drive treatment decisions is limited because no randomized controlled trials have been carried out in these patients. This review provides practical guidance for the use of anticoagulant drugs in patients presenting with SVT, including symptomatic as well as incidentally detected events.

Synergistic effect of lidocaine with pingyangmycin for treatment of venous malformation using a mouse spleen model.

AIMS: To explore whether lidocaine has the synergistic effect with pingyangmycin (PYM) in the venous malformations (VMs) treatment. METHODS: The mouse spleen was chosen as a VM model and injected with different concentration of lidocaine or PYM or jointly treated with lidocaine and PYM. After 2, 5, 8 or 14 days, the mouse spleen tissues were acquired for hematoxylin-eosin (HE) staining, transmission electron microscopy (TEM) analysis, TUNEL assay and quantitative RT-PCR analysis to examine the toxicological effects of lidocaine and PYM on splenic vascular endothelial cells. RESULTS: 0.4% of lidocaine mildly promoted the apoptosis of endothelial cells, while 2 mg/ml PYM significantly elevated the apoptotic ratios. However, the combination of 0.2% lidocaine and 0.5 mg/ml PYM notably elevated the apoptotic ratios of splenic cells and severely destroyed the configuration of spleen, compared to those of treatment with 0.5 mg/ml PYM alone. CONCLUSION: Lidocaine exerts synergistic effects with PYM in promoting the apoptosis of mouse splenic endothelial cells, indicating that lidocaine possibly promotes the therapeutic effects of PYM in VMs treatment via synergistically enhancing the apoptosis of endothelial cells of malformed venous lesions.

Thrombosis of the portal venous system following blunt abdominal trauma.

A 60-year-old man presented to the accident and emergency department with a 4-day history of abdominal pain following blunt abdominal trauma. An initial CT scan showed thickened walls of the proximal jejunum and thromboses in the portal, splenic and superior mesenteric veins. He was given warfarin and the abdominal pain resolved. A repeat CT scan 1 week later revealed significant resolution of the mural thickening and the portal vein thrombosis. A subsequent thrombophilia screen was negative and he continued taking oral anticoagulants for a total of 6 months. A repeat CT scan 3 months after presentation revealed complete recanalisation the portal venous system.

[Effect of umbilical sticking therapy with qitou xiaogu plaster in treating liver cirrhosis patients with portal hypertension].

OBJECTIVE: To observe the effect of umbilical sticking therapy (UST) with Qitou Xiaugu Plaster (QXP) on hemodynamics of portal system in patients with liver cirrhosis. METHODS: One hundred and twenty patients of liver cirrhosis with portal hypertension were assigned to two groups. On the basis of conventional therapy, UST was applied in the 66 patients in treated group, which was exchanged once every 3 days with an interval of 1-day rest. The 54 patients in the control group were orally administered with propanolol. The therapeutic course for both groups was 1 month. Before and after treatment, the hemodynamic changes in portal or splenic veins were observed by color Doppler ultrasonograph, and the changes of liver function, blood coagulation and patients' subjective symptoms were observed as well. RESULTS: After treatment, portal vein diameter and splenic vein diameter significantly decreased (P < 0.05, portal venous flow velocity and splenic venous flow velocity apparently increased (P < 0.05), and portal venous flow apparently decreased in both groups (P < 0.05), while no significant change was found in the splenic venous flow (P > 0.05). The liver function and blood coagulation indexes in both groups were improved. The improvement of clinical symptoms in the treated group was superior to that in the control group. CONCLUSION: UST with QXP could decrease the portal vein pressure in a short time, with the therapeutic effect comparable to propanolol, and with no adverse reaction.

Prostacyclin causes splenic dilation and haematological change in dogs.

1. The effect of vasodilators on spleen volume and the blood storage function is not yet well elucidated. To this end, in the present study the effects of prostacyclin, a potent vasodilator, on splenic diameter and blood cell concentrations in arterial and splenic venous blood were evaluated in anaesthetized dogs. 2. The main splenic artery and vein were dissected for measurement of splenic arterial blood flow and intra-arterial administration and for sampling of splenic venous blood, respectively. The diameter of the spleen was measured continuously by sonomicrometry. Counts of white blood cells (WBC), red blood cells (RBC) and platelets in blood sampling from the aorta and splenic vein were estimated by an automatic blood cell counter. 3. Bolus injections of prostacyclin (1-100 ng/kg) into the splenic artery produced dose-dependent increases in splenic arterial blood flow and splenic diameter associated with significant decreases in splenic venous concentrations of WBC, RBC and platelets. When splenic blood flow was kept constant, similar changes in splenic diameter and blood cell counts were observed with prostacyclin injection. 4. Splenic dilation and haematological changes induced by prostacyclin were relatively more potent than those induced by prostaglandin E(2), acetylcholine, nitroglycerin or isoproterenol when doses producing a comparable increase in splenic blood flow were compared. 5. Infusion of prostacyclin (100 ng/kg per min) into the splenic artery caused a marked increase in splenic diameter, with immediate reductions in splenic venous concentrations of WBC, RBC and platelets, followed by significant reductions in these cell counts in the general circulation. 6. These results indicate that prostacyclin produces potent and flow-independent splenic dilation that may contribute to a decrease in circulating blood cell concentrations.

Guanylyl cyclase mediates ANP-induced vasoconstriction of murine splenic vessels.

We have previously shown that ANP causes differential constriction of the splenic vasculature of the rat (veins greater than arteries), which may be inhibited by blocking the production of cGMP with A7195. In this paper, we report experiments done on vessels derived from guanylyl cyclase (GC)-A knockout mice. Small splenic arteries ( approximately 150-microm diameter) and veins ( approximately 250-microm diameter) were dissected from male GC-A-deficient 129sv mice or age-matched wild-type controls and mounted in a wire myograph. In the wild-type mice, ANP exhibited higher potency in the veins than in the arteries (EC(50) values wild-type mice: artery, 8 +/- 3 x 10(-9) M, n = 5 vs. vein, 6 +/- 4 x 10(-10) M, n = 5; P < 0.05). The concentration-response curve for ANP-induced vasoconstriction was also shifted leftward in denuded compared with intact arteries (EC(50) values: denuded artery: 5 +/- 3 x 10(-10) M, n = 5 vs. intact artery, 8 +/- 3 x 10(-9) M, n = 5; P < 0.05), i.e., the denuded vessels were more reactive. By contrast, ANP caused no significant change in tension from baseline in intact splenic arteries, intact splenic veins, or denuded splenic arteries derived from the GC-A-deficient mice, although these vessels did show normal concentration-dependent increases in tension to phenylephrine. We conclude that ANP causes vasoconstriction in the splenic vasculature by an endothelium-independent mechanism, mediated via guanylyl cyclase.

Increased splenic capacity in response to transdermal application of nitroglycerine in the dog.

This study was conducted to determine if application of transdermal 2% nitroglycerine ointment (TDNG) to dogs anesthetized with alpha chloralose would produce splenic dilatation by relaxation of venous smooth muscle. Sonomicrometer crystals were applied to the spleen in each of 15 dogs, and a pressure-measuring catheter was inserted into a splenic vein. The sonomicrometer crystals permitted measurement of splenic dimension, which is known to correlate with splenic volume. Ten dogs were given 2.5 cm TDNG/10 kg, and 5 dogs (vehicle controls) were given only petrolatum, both applied to the inner surface of the auricular pinna. Splenic dimension in all dogs receiving TDNG increased significantly (P < .05) by 7.0 +/- 4.8%, whereas splenic dimension in dogs receiving petrolatum did not increase. Splenic venous pressures did not change significantly in either group. Spleens began to dilate 482 +/- 652 seconds after application of TDNG and achieved maximal dilatation at 861 +/- 632 seconds. Splenic dilatation occurred in the absence of elevation of splenic venous pressure, indicating that the dilatation probably resulted from relaxation of splenic smooth muscle. TDNG was absorbed transdermally and produced splenic dilatation in health dogs anesthetized with alpha chloralose. If the spleen is a sentinel for peripheral veins, then TDNG may increase venous capacity, retaining blood from the lungs and thereby functioning to reduce pulmonary congestion and edema in dogs with left-sided heart failure.

Effects of adrenergic and cholinergic drugs on splenic arteries and veins from hooded seals (Cystophora cristata).

Isolated ring preparations of arteries and veins from hooded seal spleens were subjected in vitro to adrenaline (A), noradrenaline (NA), isoprenaline (Iso), and acetylcholine (ACh), alone or in combination with the blockers phentolamine (Phe), propranolol (Pro), and atropine (Atr). Both arteries and veins constricted in response to A (the estimated effective dose required for half-maximal response (ED50) was 3.3 and 0.2 microM, for arteries and veins, respectively) and NA (estimated ED50 was 1.5 and 0.6 microM, for arteries and veins, respectively), but these effects were abolished when the drugs were given in combination with the alpha-adrenoceptor blocker Phe. The responses of arteries and veins to ACh and the beta-adrenoceptor agonist Iso were minor and inconsistent, and were completely abolished when combined with their respective blockers (Atr and Pro, respectively). The ED50 for both A and NA are quite high in relation to normal plasma levels of A and NA in seals. This implies that these vessels (and, hence, the supply of blood to the spleen) primarily are subjected to neurogenic, rather than humoral physiological control.

Effect of verapamil on portal and splanchnic hemodynamics in patients with advanced posthepatitic cirrhosis using duplex Doppler ultrasound.

PURPOSE: To assess the effect of verapamil (80 mg) oral administration on portal and splanchnic hemodynamics in patients with advanced posthepatitic cirrhosis using duplex Doppler ultrasound (US). METHODS: Fourteen patients with post-hepatitic liver cirrhosis were included in the study. Duplex Doppler sonographic examinations were performed before, and 2-3 h after, 80 mg verapamil oral administration. Portal and splanchnic hemodynamics including vessel diameters (mm), mean flow velocities (cm/s), blood flows (ml/min), Doppler indices such as pulsatility and resistive indices (PI and RI), were investigated before and after verapamil administration. RESULTS: After verapamil administration; diameter of portal vein, splenic vein, and superior mesenteric artery (SMA) showed increase of 8%, 10%, and 7% (P < 0.05 to < 0.001), respectively. Increases of 20%, 38%, and 47% were found in blood flows (P < 0.05 to < 0.0001) with respect to the above vessels. Decreases of 17%, 10%, 11%, and 7% were found in SMA PI, SMA RI, splenic artery (SA) PI, and SA RI, respectively (P < 0.05 to < 0.0001). CONCLUSIONS: Verapamil appears to have splanchnic, portal, splenic, portocollateral and probably intrahepatic vasodilator effects in patients with advanced posthepatitic liver cirrhosis. Verapamil should be further investigated in the treatment of patients with advanced liver cirrhosis with prospective studies measuring portal and wedged hepatic pressure.

Comparison of the acute influence of neuropeptide Y and sympathetic stimulation on the composition of blood cells in the splenic vein in vivo.

The acute influence of exogenous transmitters and sympathetic nerve stimulation on the composition of blood cells in the splenic vein in relation to the splenic vascular effects was investigated in anaesthetized pigs. Intra arterial bolus injections of 720 pmol neuropeptide Y (NPY), 4.9 nmol noradrenaline (NA) and 20 nmol alpha,beta-methylene adenosine triphosphate (mATP) in the spleen were given and these doses caused arterial vasoconstriction in the same range, and increase in splenic venous haematocrit. NPY administration evoked a decrease in splenic venous blood flow and an unchanged leukocyte outflow from the spleen. mATP and NA, on the other hand, evoked increases in splenic venous blood flow and leukocyte outflow. Sympathetic nerve stimulation caused increases in haematocrit and leukocyte outflow in control pigs as well as in pigs with reserpine-induced depletion of tissue NA, although these effects, as well as the vascular effects, were significantly reduced after reserpine treatment. For comparison, the vasodilator calcitonin gene-related peptide increased leukocyte outflow without change in haematocrit. It is concluded that haematocrit and leukocyte concentration in the splenic venous blood are acutely modulated in different ways by vascular changes evoked by different sympathetic mediators. Furthermore, the capacitance function seems to be regulated by adrenergic and possibly purinergic transmission, whereas the non-adrenergic mediator NPY seems to be involved mainly in splenic arterial vasoconstriction.

Effects of adrenergic stimulants on the splenic diameter, haemoglobin content and haematocrit in anaesthetized dogs: determination of the adrenoceptor subtype responsible for changes in the splenic diameter.

Changes in splenic diameter measured by sonomicrometry in response to various adrenergic stimulants were estimated together with simultaneously measured arterial haemoglobin content (HGB) and haematocrit (HCT) in anaesthetized dogs. Splenic diameter decreased following intravenous injections (i.v.) of adrenaline, noradrenaline and phenylephrine and splenic nerve stimulation associated with increases in arterial HGB and HCT, which were significantly attenuated by prazosin i.v. After prazosin i.v., adrenaline i.v. increased splenic diameter significantly, but noradrenaline i.v. did not. Isoprenaline i.v. increased splenic diameter transiently, followed by a decrease that was abolished by prazosin i.v. During occlusion of splenic arteries and veins, adrenaline i.v. and phenylephrine i.v. did not cause any change in arterial HGB and HCT. Injection to splenic artery (i.a.) of phenylephrine induced a significant decrease in splenic diameter that was attenuated by prazosin i.a. but not by yohimbine i.a. Clonidine i.a. did not change splenic diameter. The present results indicate that splenic contraction, which is mediated through alpha 1-adrenoceptor activation, causes a significant increase in arterial HGB and HCT.

Effects of vasopressin on left gastric venous flow in cirrhotic patients with esophageal varices.

To assess vasopressin control of esophageal variceal bleeding, we investigated the effect of vasopressin on the left gastric venous flow, portal venous flow, superior mesenteric venous flow, and splenic venous flow in seven cirrhotic patients with esophageal varices, using a duplex system consisting of a real-time ultrasonograph and an echo-Doppler flowmeter. Infusion of vasopressin (0.3 U/min) significantly decreased the blood flow in the left gastric vein (-56%), portal trunk (-54%), superior mesenteric vein (-54%), and splenic vein (-56%) as a result of decrease of blood velocity in these vessels. Thus, vasopressin seems to control esophageal variceal bleeding, in part, by reducing blood velocity and blood flow in the left gastric vein following reduction of blood velocity and blood flow in the superior mesenteric vein and splenic vein.

Relationship between splenic and superior mesenteric venous circulation.

We took advantage of routine hemodynamic examinations to determine the relationship between splenic and intestinal circulation by infusing prostaglandin E1 into the superior mesenteric artery and observing the portal hemodynamic changes in patients with chronic liver disease. Relative blood flow rate in various vessels of the portal system were measured percutaneously using an ultrasonic duplex system, while portal venous pressure was measured directly using a transducer. The superior mesenteric venous blood flow increased significantly as did the portal venous blood flow and pressure, though the degree of change of portal venous blood flow was less than was expected from the change of portal venous blood flow in the superior mesenteric venous blood flow. Splenic venous blood flow decreased significantly. This decrease is perhaps due to a mechanism that acts to compensate for the increase induced in the superior mesenteric venous blood flow to maintain portal flow at approximately the same level. The measured changes suggest a relationship between splenic and intestinal blood flows that is regulated according to the hepatic circulatory condition. The regulatory mechanism should be considered when designing the treatment of portal hypertension.

Venous complications of sclerotherapy for esophageal varices.

Although endoscopic sclerotherapy is effective in controlling bleeding from esophageal varices, the effects of sclerosing agents on the extrahepatic portal and splenic veins have not previously been investigated. This study of 21 men with portal hypertension and variceal bleeding compares the morphology of the portal and splenic veins in 11 who had received endoscopic sclerotherapy versus 10 patients who did not. The mean number of injections per patient was 11 +/- 5, the mean volume of 1.5 percent sodium tetradecyl injected was 23 +/- 15 ml, and the interval between the last injection and surgery was 15 +/- 6.5 days. Among the 11 patients who had endoscopic sclerotherapy, portal vein thrombosis occurred in 4 (36 percent). Two of these patients died from acute liver failure; the other two had shunt procedures. Histologic changes included intimal thickening and medial fibrosis in seven patients, thrombus in four patients, and destruction of the venous architecture in two patients. Of the 10 patients with portal hypertension who did not have endoscopic sclerotherapy, all had medial fibrosis of the portal vein, with thrombus and intimal thickening present in only 1. These findings suggest that endoscopic sclerotherapy for esophageal varices should be used cautiously in patients who may later require a shunt. Moreover, further studies are necessary to evaluate the long-term effects of injecting sclerosing agents into the portal circulation before widespread use of prophylactic sclerotherapy can be recommended.

Distinctive characteristics of the splenic vein in the dog. Its morphological and pharmacological discontinuities with the portal vein and splenic capsule.

Vascular characteristics of the splenic vein are entirely different from the portal vein in the dog. We compared the responsiveness of the splenic capsule, which contains abundant smooth muscle with the portal and splenic veins. With respect to potentiation of acetylcholine-induced contraction by neostigmine, the relaxation response to isoproterenol and the contractile response to 5-hydroxytryptamine, the splenic capsule differed from the splenic vein, but was rather similar to the portal vein. A site of morphological and pharmacological discontinuity between the portal vein and the splenic vein occurred at the junction of the splenic vein and the left gastric vein to form the gastrosplenic vein. This junction may coincide with the site of connection of the embryonic splenic vein, a newly formed efferent vein of the spleen, with the portal vein, which was reported by Miki [cf. Bevan et al.: 4th Int. Symp. on Vascular Neuroeffector Mechanisms; Raven Press, New York 1983]. On the splenic side, histological examination revealed that smooth muscle of the splenic capsule and trabeculae are interconnected, but did not extend to the splenic vein. At openings of the trabecular veins into the 'intrasplenic' portion of the splenic vein the trabecular smooth muscle continued to the extended capsule. The site of change in pharmacological responses was also found to be located between the trabeculae and the intrasplenic portion of the splenic vein. Thus the splenic vein can be regarded as a distinct segment of vessel inserted between the portal vein and the spleen. This may reflect differences in embryogenesis of their smooth muscle.

Effect of xylazine hydrochloride on canine splenic weight: an index of vascular capacity.

Splenic weight, an index of changes in vascular capacity, was used to assess the effects of xylazine hydrochloride in anesthetized dogs. Intravenous xylazine (0.01, 0.1, and 1 mg/kg) produced dose-dependent decreases in vascular capacity as assessed by decreases in splenic weight which were significant (P less than 0.05) at the 1 mg/kg dose. Phenoxybenzamine, an alpha-adrenergic receptor blocking drug, prevented the splenic contractile response to xylazine. Propranolol, a beta-adrenergic receptor blocking drug, did not alter the splenic contractile response to xylazine. Intravenous xylazine (0.1 and 1 mg/kg) produced significant (P less than 0.05) decreases in heart rate, splenic arterial flow, and systolic, mean, and diastolic blood pressures. Central venous pressure increased significantly (P less than 0.05) in dogs given the 1 mg/kg dose.