Intrahepatic Portal Research Articles

Acute abdominal compartment syndrome

Acute abdominal compartment syndrome can be an elusive clinical diagnosis for which critical care physicians must exercise a high index of suspicion in the differential diagnosis of hemodynamic compromise and hemorrhagic shock. The purpose of these Rounds is to describe a case of abdominal compartment syndrome and to summarize the pathophysiology, differential diagnosis, etiology, and treatment of this entity. The Research Ethics Committee of the Montreal Heart Institute granted approval for use of the related images for publication purposes. A middle-aged male was admitted to the intensive care unit (ICU) for management of lower gastro-intestinal bleeding and hemorrhagic shock. His medical history was remarkable for cirrhosis (Child-Pugh Stage C) secondary to hepatitis C, with previous ligature of esophageal varices. He also had undergone a colonoscopy with a cecal polyp resection five days earlier. The initial blood work-up showed a 6.0 g decrease in hemoglobin. The patient was mechanically ventilated and transfused with six units of packed red blood cells. Despite blood transfusion and aggressive resuscitation with crystalloids, noradrenaline was required at an infusion rate of 15 lg min to maintain a mean arterial pressure (MAP) [65 mmHg. Esophagogastric endoscopy showed no active bleeding. A colonoscopy was planned, and 4 L of an oral preparation (Golytely) were to be administered via a nasogastric tube (NGT). After 30 min and 1 L of the oral preparation had been administered, the patient’s blood pressure decreased to 50 mmHg and the noradrenaline infusion was increased to 53 lg min (Fig. 1a). The patient’s abdomen became increasingly tense and he developed anuria. His intravesical pressure at this time was 28 mmHg (Fig. 1b). A diagnosis of acute compartment syndrome (ACS) was made, and ultrasound-guided paracentesis (Figs. 2 and 3a, b) and nasogastric aspiration were performed. Two and one-half litres of ascitic fluid and 1 L of the enteral solution were removed through aspiration. Shortly after this intervention, the noradrenaline requirements decreased to 10 lg min to maintain the MAP [65 mmHg. On angiography, an intracecal bleeding site was identified and the cecal artery was embolized. The bleeding stopped and the patient later stabilized. A review of computed tomography scans of the abdomen performed one week prior to this acute event revealed signs of liver cirrhosis with portal hypertension and ascitis (Fig. 4 [videos #1 and #2 online at www.springerlink.com]). Note was made of the fact that the inferior vena cava was significantly narrowed in its intrahepatic portion. Abdominal compartment syndrome is defined as a sustained abdominal pressure [20 mmHg with evidence of organ dysfunction relieved by abdominal decompression. Electronic supplementary material The online version of this article (doi:10.1007/s12630-009-9140-8) contains supplementary material, which is available to authorized users.

The posterior intrahepatic approach to the left portal pedicle using the ligamentum venosum: anatomical basis

Prevention of blood loss in liver resections is essential for reducing postoperative morbidity. The main method to control bleeding during surgery of the left hemiliver is occlusion of the left portal pedicle. This may be accomplished by hilar, fissural or posterior intrahepatic techniques. However, these techniques may injure transposed vessels or bile ducts from the right portal pedicle to the left. The purpose of this study was to describe the anatomical aspects of the posterior intrahepatic ligamentum venosum approach to the left portal pedicle. Anatomical study was carried out on 215 isolated adult livers. In 57 specimens, sections of the extra- and intrahepatic portions of the left portal pedicle were prepared under stereoscopic microscopy. The ligamentum venosum is the anatomical landmark between the medial and lateral portions of the left portal vein. The convergence of the ligamentum venosum along the left portal pedicle is where the left portal sheath reaches its maximal thickness and these connections are tight. In 8-12%, the medial portion of the left portal pedicle includes a transposed right paramedian vein or right-sided bile ducts. According to our anatomical study, we believe that it is possible to use the ligamentum venosum as an anatomical guide to achieve a controlled approach of the left portal pedicle during left-sided hepatectomies. Moreover, ligation of the left portal pedicle at its convergence with the ligamentum venosum may prevent erroneous injury of transposed right paramedian vessels or bile ducts.

Findings in multi-detector row CT with portal phase enhancement in patients with mesenteric venous thrombosis

There exists no systematic evaluation on the findings in multi-detector row computed tomography (MDCT) with portal phase enhancement in patients with mesenteric venous thrombosis (MVT). Patients with MVT between 2004 and 2006 were identified at Malmö University Hospital, Sweden. Thirty patients had MVT. Median age was 58 years (interquartile range, 46-72), and 57% (17) were men. MDCT with portal phase enhancement showed MVT in 19 out of 20 investigated patients at first evaluation, even though there was clinical suspicion in only one, and conservative management was possible in 19 (95%). Central and peripheral MVT was seen in 20 (100%) and six (30%) cases, respectively. Extra-hepatic and intra-hepatic portal and splenic vein thrombosis was seen in 17 (85%), nine (45%) and 15 (75%) cases, respectively. Venous collaterals were visible in 12 (60%) cases. The most frequent extra-vascular pathologies were mesenteric oedema (50%), ascites (40%), small bowel wall oedema (25%) and local small bowel wall dilatation (20%). The vascular findings in MVT are more pronounced than the intestinal findings in MDCT with portal phase enhancement, and evaluation of the mesenteric vessels should be included in routine MDCT scans for unclear acute abdomen.

Mesoatrial shunt in Budd-Chiari syndrome

Budd-Chiari syndrome (BCS) represents partial or total occlusion of the hepatic veins with or without simultaneous obstruction of vena cava inferior (VCI). The symptoms of BCS are abdominal pain, hepatomegaly, ascites, varices of the abdominal wall, sometimes bleeding from the upper part of gastointestinal tract (GIT), lower limbs swelling and jaundice. Primary BSC is a relatively rare condition occuring in one per 100,000 of the population worldwide. A male patient, 25-year-old, facing tooth postextraction complications, was presented with acute BCS. On admission, physical examination revealed pale-grayish complexion, more pronounced veins over the thorax and abdomen, ascites, enlarged liver rising 8 cm below the right costal arch and having a minor pleural effusion by the right side. The patient was submitted to Doppler sonography and computed tomography (CT) that verified the right leg deep veins thrombosis, as well as the presence of a thrombus in the intrahepatic portion of the VCI. Multislice computed tomography (MSCT) showed occlusion of hepatic veins (Budd-Chiari syndrome) and thrombosis of the VCI in the retrohepatic part 6 cm long. Also, increased values of transaminases and gamma GT and reduced values of albumines and serum ferrum were registered. Molecular examination revealed Factor V Leiden mutation--heterozygote. After preoperative preparations a mesocaval shunt was made using Gore-Tex ring graft of 12 mm. Intraoperatively, the blue enlarged liver was found with almost black zones of tense capsule. After a graft making, liver congestion decreased followed by the change of colour and volume. Within postoperative course metabolic and synthetic liver functions were obvious. In patients with BCS medicamentous treatment does not yield adequate results, but even causes worsening of general condition. Surgical therapy in the presented patient was performed timely regarding the stage of the disease due to which irreversible liver changes were prevented while decompression of the portal system provided time overbridging up to liver transplantation.

Idiopathic Non-Cirrhotic Intrahepatic Portal Hypertension Is Associated with Sustained ADAMTS13 Deficiency.

Idiopathic non-cirrhotic portal hypertension (NCPH) is caused by obliterative venopathy affecting the terminal radicals of the hepatic portal vein. It has been associated with areas of low socio-economic development. We observed a long history of thrombocytopenia and association with enteric disorders in a Caucasian population presenting with NCPH and postulated that the underlying mechanism could be deficiency of ADAMTS13, leading to the circulation of ultra large molecular weight von Willebrand factor (VWF) multimers and consequent platelet aggregate formation, causing occlusion of hepatic portal venules. ADAMTS13 activity was measured in all patients by a collagen binding assay, while antigen and IgG antibody were measured using ELISA kits (American Diagnostica Inc), normal ranges: 66–126%, 485–1242ng/ml and <11AU/ml, respectively. Plasma ADAMTS13 activity and antigen levels were measured in 14 patients with NCPH and 25 control patients with miscellaneous liver diseases associated with portal hypertension and Model for End Stage Liver Disease (MELD) scores indicating similar disease severity, median 12 (IQR 10–14) and 11 (8–16), for NCPH cases and controls. The platelet count was reduced in 13/14 NCPH cases median 69 x109/L (IQR 40–97) and 123 (85–193) in cases and controls, but did not correlate with MELD score or ADAMTS13 activity. ADAMTS13 activity was very low in 13/14 NCPH cases (median 12% (IQR <5–20)) and significantly lower than controls (59% (4–84), p<0.0001). In 4 cases, serial samples over several months revealed consistently low ADAMTS13 levels. There was a corresponding reduction in ADAMTS13 antigen, median 238ng/ml (IQR 186–361) and 584 (442–831), although NCPH cases showed a small excess of antigen over activity (antigen:activity ratio: median 25.7 (IQR 11.3–32.6) and 9.4 (8.1–13.8), in cases and controls, p<0.001), suggesting that an abnormal molecular species could be present. An inhibitor was not detected, although 10 cases and 15 controls had IgG anti-ADAMTS13: median levels 14.8AU/ml (8.8–20.0) and 13.4 (9.0–22.6), but these IgG levels did not correlate with activity. Non-inhibitory IgG antibodies to ADAMTS13 have been previously observed in certain other clinical groups (eg. coronary syndromes, sepsis, etc.). In NCPH, there was no correlation between ADAMTS13 level and either VWF antigen or VWF collagen binding activity. Increased very high molecular weight VWF multimers were observed in 4/11 NCPH cases and 0/22 controls. CD31 positive platelet aggregates were observed in the hepatic vessels of 7/20 (35%) NCPH cases and 1/15 (7%) controls. Our results suggest that sustained deficiency of ADAMTS13 associated with thrombocytopenia is characteristic of NCPH. It differs from other hepatic pathologies, where the decrease in ADAMTS13 has been reported to correlate with the severity of liver disease. NCPH also differs from thrombotic thrombocytopenic purpura because there is a chronic disease process, there is an absence of obvious red cell fragments and the primary organ affected is the liver. Since the predominant plasma source of ADAMTS13 appears to be hepatic stellate cells, the portal microcirculation is most at risk from pathological interactions of VWF and platelets if enteric factors further deplete circulating levels of ADAMTS13. The cause of the decreased ADAMTS13 remains to be elucidated, but could be due to decreased expression and synthesis, immune depletion (IgM and IgA anti-ADAMTS13 have not been investigated), or consumption in the circulation.

Hepatic Venous Pressure Gradient: Worth Another Look?

Portal hypertension is one of the most important complications of chronic liver disease and accounts for significant morbidity and mortality. Measurement of the hepatic venous pressure gradient (HVPG) is a simple, invasive, and reproducible method of assessing portal venous pressure. Measurement of HVPG provides the clinician an estimate of the degree of intrahepatic portal flow resistance, guides therapy for variceal bleeding (primary and secondary prophylaxis), assesses feasibility of resection in patients with hepatocellular cancer, and predicts response to therapy of patients with chronic hepatitis C. Achieving hemodynamic targets of reducing the HVPG to <10 mmHg or a 20% reduction from baseline virtually eliminates complications related to portal hypertension from chronic liver disease. This review explores the role of HVPG measurement in the contemporary treatment of patients with cirrhosis and portal hypertension.

Intrahepatic Portal Venopathy and Related Disorders of the Liver

Intrahepatic portal venopathy leads to various entities that are important causes of portal hypertension. Noncirrhotic portal fibrosis (NCPF) occurs in the Indian subcontinent, whereas idiopathic portal hypertension (IPH) occurs in Japan although the pathogenesis and presentation of both are similar. NCPF presents mainly with upper gastrointestinal bleeding; IPH presents with massive splenomegaly. The liver functions are preserved. Wedged hepatic venous pressure is normal, but portal venous pressure is high indicating a presinusoidal block. Patients are best managed with endoscopic therapy or surgery, with better results than in patients with cirrhosis. Nodular regenerative hyperplasia is a histological diagnosis characterized by development of nodules in the liver due to uneven perfusion of the portal venous blood. These patients may develop portal hypertension and if they bleed would require treatment as in NCPF/IPH. Schistosomiasis produces portal hypertension by the development of fibrous tissue around the portal veins as a response to schistosome eggs. Gratifying results have been reported with praziquantel therapy. Rarely sarcoidosis and chronic biliary obstruction may also produce portal venopathy.

QS269. Outcome of Laparoscopic Hepatic Cyst Resection in 48 Patients

Background: Hepatic cysts occur in 4-7% of the population. Laparoscopy has emerged as an effective management tool. We sought to evaluate the safety and usefulness of laparoscopic resection of symptomatic cysts in a large series of patients. Methods: Between August 2001 and August 2007, 48 patients underwent laparoscopic resections for symptomatic hepatic cysts. In each case, attempts were made to remove as much cyst wall as possible, typically 70-80%, leaving the remnant back wall overlaying the intra-hepatic portal and hepatic veins.

Portal–systemic encephalopathy in a non-cirrhotic patient

We report a rare case of non-cirrhotic intrahepatic portal–systemic venous shunt. The patient presented with repeated neuropsychiatric symptoms. Our case reminds us that such portal–systemic encephalopathy should be considered even...

Hepatic Computed Tomography for Simultaneous Depiction of Hepatocellular Carcinoma, Intrahepatic Portal Veins, and Hepatic Veins in Real-time Virtual Sonography

The aim of this study was to examine a double-step injection of contrast material in hepatic computed tomography (CT) for the simultaneous depiction of hepatocellular carcinoma (HCC), intrahepatic portal veins, and hepatic veins in real-time virtual sonography. This study consisted of 6 patients with solitary HCC nodules with early enhancement on dynamic contrast-enhanced CT. Computed tomographic scanning was performed in a combined late arterial/hepatic phase after 2 sequential contrast material injections. In all 6 patients, the solitary HCC nodule, intrahepatic portal veins, and hepatic veins were simultaneously visualized with enhancement, for which CT values were appreciably higher than that of the liver parenchyma. In virtual sonography, HCC nodules and intrahepatic vessels were simultaneously shown, and the HCC lesions were treated by radio frequency ablation without vascular injury. A double-step injection of contrast material in hepatic CT was helpful in the identification of the relationship between the HCC nodule and intrahepatic vessels under virtual sonography and contributed to the accurate and safe performance of radio frequency ablation for HCC.

Computer Simulation of Hemodynamic Changes After Right Lobectomy in a Liver with Intrahepatic Portal Vein Aneurysm

Intrahepatic portal vein aneurysm is rare and its natural history is unknown. A 22-year-old healthy man, who wished to donate part of his liver to his diseased father, was incidentally diagnosed to have an intrahepatic portal vein aneurysm. The surgical decision of performing live donor hepatectomy for such a patient is normally difficult. We combined modern imaging reconstruction technologies with scientific computing as a new modality to foresee the risks of surgical complications. Cross-sectional computed tomography images were used to reconstruct the three-dimensional image of portal vein distribution using the 3D-Doctor v3.5 software. The reconstructed images were further employed to generate surface and interior meshes with CFX software. Simulated hemodynamic changes in velocity, pressure, and wall stress were determined for the right lobectomy case pre- and postoperatively. The simulation results indicated that aneurismal pressure would be elevated significantly to 12.03 mmHg after operation. The left segmental portal venous blood flow would increase from 2.95- to 4.25-fold. The area near the branch point of one left segmental portal vein, which supplies blood to liver segment 4, and the portal vein aneurysm would endure high shear stress gradient. The resulting elevated aneurismal pressure may cause the thin wall to enlarge and rupture, while the high shear stress gradient would lead to vascular endothelial cell injury. Living donor surgery was not recommended hemodynamically based on the simulated results. Scientific computing and modern imaging technologies can be applied together to aid surgeons to make the best decision in difficult clinical situations.

Adenosquamous Carcinoma of Extrahepatic Bile Duct: A Case Report

Most malignant tumors originating from the biliary tract are adenocarcinomas, and adenosqamous carcinoma of Klatskin's tumor is a very rare finding. An 83-yr-old man was admitted to our hospital because of jaundice. The abdominal computed tomography and magnetic resonance cholangiopancreatography revealed wall thickening and luminal stenosis of both the intrahepatic duct confluent portion and the common hepatic duct. These findings were compatible with Klatskin's tumor, Bismuth type III. Considering the patient's old age, palliative combined modality therapy was performed. After percutaneous transhepatic biliary drainage, biopsy was performed via percutaneous transhepatic cholangioscopy. The histopathologic findings showed adenosquamous carcinoma. External radiotherapy and intraluminal brachytherapy through the endobiliary Y-type stent were then done. Nine months after the radiotherapy, the laboratory findings and the abdominal computed tomography revealed biliary obstruction and progressive hepatic metastasis. The combined modality therapy of external radiotherapy, intraluminal brachytherapy and stenting assisted him to live a normal life until he finally experienced biliary obstruction.

Cardiac Perforation and Tamponade: A Potentially Fatal Complication During Transjugular Intrahepatic Portosystemic Shunt Placement

Transjugular intrahepatic portosystemic shunt (TIPS) is a low-resistance channel between the hepatic vein and the intrahepatic portion of the portal vein. This is an important addition to the therapeutic armamentarium against portal hypertension. Complications are either technical or due to the creation of a shunt. Procedure-related mortality is about 0 to 2%. Cardiac perforation, one of the rarest complications during TIPS, can occur while traversing the catheter from the jugular vein past the right atrium to enter the hepatic vein. We are reporting the case of a 50-year-old woman who became acutely hypotensive with cardiovascular compromise during the TIPS procedure. A stat echocardiogram confirmed cardiac tamponade and emergency pericardiocentesis resulted in improvement of hemodynamic status with complete recovery.

Endovascular treatment of obliterative hepatocavopathy with inferior vena cava occlusion and renal vein thrombosis

We describe the endovascular treatment of an occlusion of the inferior vena cava (IVC) due to obliterative hepatocavopathy with renal and iliac vein thrombosis. A 34-year-old man with nephrotic syndrome and hepatic dysfunction presented to the hospital after a 3-month history of lower extremity swelling with an acute deterioration in his condition. Magnetic resonance venography diagnosed a massive IVC occlusion with thrombosis of the entire IVC, iliac veins, and renal vein. He was treated with thrombolysis, and a chronic occlusion of the infrahepatic IVC was discovered. After venous stenting of the IVC and iliac veins, he dramatically improved. After 24 months, he remains symptom-free with a patent IVC and iliac veins.

Case 15-2006

A 46-year-old woman had rapid onset of ascites, right upper abdominal discomfort, nausea, and vomiting. The serum–ascites albumin gradient was 1.2 g per deciliter. Venography demonstrated narrowing of the intrahepatic portion of the inferior vena cava; hepatic veins could not be visualized. Additional diagnostic procedures were performed.

Biliary cystic disease

Biliary cystic disease, though uncommon, can present at a wide range of ages with a wide range of symptoms. Choledochal cysts are associated with the development of both cholangiocarcinoma and gallbladder cancer. Thus, most biliary cystic disease is best managed operatively. Many factors should be considered when performing surgery on patients with choledochal cysts, including age, presenting symptoms, cyst type, associated biliary stones, prior biliary surgery, intrahepatic strictures, hepatic atrophy/hypertrophy, biliary cirrhosis, portal hypertension, and associated biliary malignancy. When feasible, surgical treatment should consist of cholecystectomy and complete surgical excision of extrahepatic cysts with Roux-en-Y reconstruction. Because the risk of recurrent cholangitis is significant and additional symptoms and problems are common, the use of long-term soft Silastic biliary stents (Dow Corning Corp., Midland, MI) should be considered when complex intrahepatic and extrahepatic cystic disease is present. Alternatively, the Roux-en-Y jejunal limb can be marked at the fascia for future percutaneous access. Reconstruction via hepaticoduodenostomy and jejunal interposition has been associated with increased postoperative pain due to bile reflux gastritis. Thus, hepaticojejunostomy reconstruction is recommended. For choledochal cysts involving the distal bile duct, the bile duct should be excised at the intrapancreatic portion. Resection of the pancreatic head should be reserved for patients with established malignancies. Surgical excision of the intrahepatic portion of the bile duct should be individualized to include preservation of hepatic parenchyma when the liver is not cirrhotic. If cirrhosis is advanced, hepatic transplantation may be indicated, but this is rare. Oncologic principles should be followed in the presence of a malignancy. Lifelong follow-up is required because of the possibility of a "field" defect increasing susceptibility to cancer throughout the biliary tract epithelium.

An Audit of Outcome in Intravascular Transfusions Using the Intrahepatic Portion of the Fetal Umbilical Vein Compared to Cordocentesis

Introduction: Maternal red cell alloimmunization is a potential cause of perinatal morbidity and mortality. The outcome of severe disease has been transformed by the use of in-utero and particularly, fetal intravascular transfusion. In the majority of instances this is performed by cordocentesis. However, this cohort study represents the experience in a large tertiary referral centre in performing fetal intravascular transfusions via the intrahepatic vein (IHV). Methods: Over an 8-year period, 1997–2004, 221 in-utero transfusions (IUT) were performed for rhesus disease in 66 pregnancies. 86% had severe fetal anaemia caused by anti-D, 10.6% by anti-Kell and 3.4% by anti-c. The median maternal age of the cohort was 31 years (range 19–43). The median gestation at initial IUT was 25 weeks (interquartile range (IQR) 23–29 weeks). Results: A median number of three IUT were performed in each fetus (IQR 2–5) with a median haemoglobin at first fetal blood sampling of 7.3 g% (IQR 4.6–8.8 g%) (73% ≤5 SD and 27% ≤2 SD). Of the total intravascular transfusions, 170 were performed via the IHV (71.7%), 33 via cordocentesis (13.9%) and 1 by intracardiac puncture (0.5%). There were ‘transient’ bradycardias complicating 4.1% of all transfusions and amniorrhexis following 1.4%. 92% of babies were live born at a median gestation of 34 weeks (range 21–38) with a birth weight centile of 50 (range 3–90). There was no significant difference in intravascular transfusion complication rate when the procedure was performed via the IHV (7.6%) as compared to cord root puncture (3.0%) (Fisher’s exact test, p < 0.47). Conclusion: IUT performed by fetal IHV puncture is safe and carries no excess morbidity when performed for severe rhesus disease.

Anomaly of the Portal Vein With Total Ramification of the Intrahepatic Portal Branches From the Right Umbilical Portion

To describe CT findings of portal vein anomaly with total ramification of the intrahepatic portal branches from the right umbilical vein. Retrospective analysis was performed in 6 patients with portal vein anomaly with total ramification of the intrahepatic portal branches from the right umbilican vein. We analyzed the position of the umbilical portion of the portal vein and ligamentum teres, and determined the intrahepatic branching pattern of the portal vein. The umbilical portion and ligamentum teres were deviated to the right and seen above the gallbladder fossa in all 6 patients. All major braches of the portal vein ramified from the right umbilical vein in all 6 patients. The possibility of this portal vein anomaly should be kept in mind when hepatic resection or partial liver transplantation is required.

Stable multilineage chimerism across full MHC barriers without graft-versus-host disease following in utero bone marrow transplantation in pigs

Stable engraftment of hematopoietic progenitors and multilineage chimerism following in utero bone marrow transplantation could be a promising modality for treatment of prenatally diagnosed blood dyscrasias. For treatment of these diseases, stable chimerism in the myeloid and erythroid lineages is important because it is anticipated that donor-derived cells will compensate for defects in these host lineages. In the present study, a preparation of bone marrow that includes fresh, unmanipulated marrow mixed with T-cell-depleted marrow to achieve 1.5% T-cell content, was injected into the intrahepatic portion of the umbilical vein of porcine fetuses at mid-gestation. Donor hematopoietic progenitor cell engraftment was assessed in fetal liver and recipient bone marrow postnatally by donor-specific polymerase chain reaction of colony-forming units. Chimerism was assessed in lymphoid tissues and peripheral blood by flow cytometry. Graft-versus-host disease (GVHD) was assessed by histological analysis of biopsies of skin, bone marrow, liver, and intestine. In this report, we demonstrate that stable multilineage chimerism across a full major histocompatibility complex disparity can be achieved without GVHD through in utero bone marrow transplantation.

Mechanisms Involved in the Contraction of Intrahepatic Portal Vein Branches by Clomipramine and Oxethazaine in Isolated Perfused Rat Livers

Clomipramine (CLM) and oxethazaine (OXZ) were previously reported to increase portal pressure by contracting portal vein branches (PVBs) in isolated perfused rat liver. In the present study, to characterize the contractile mechanisms, the effects of Y27632, HA1077, staurosporine, papaverine, SKF96365, and sulindac sulfide on the portal pressure increase induced by CLM and OXZ were examined comparatively with those induced by endothelin-1. The results suggest that 1) intrahepatic PVBs employ a Rho-kinase-dependent pathway for sustained contraction, 2) CLM contracts PVBs by activating a Rho-kinase pathway and Ca2+-channels, and 3) OXZ acts primarily by promoting Ca2+ entry through its ionophore-like action.