Rat caval vein myocardium undergoes changes in conduction characteristics during postnatal ontogenesis.

The electrophysiological properties of the superior vena cava (SVC) myocardium, which is considered a minor source of atrial arrhythmias, were studied in this study during postnatal development. Conduction properties were investigated in spontaneously active and electrically paced SVC preparations obtained from 7-60-day-old male Wistar rats using optical mapping and microelectrode techniques. The presence of high-conductance connexin 43 (Cx43) was evaluated in SVC cross-sections using immunofluorescence. It was found that SVC myocardium is excitable, electrically coupled with the atrial tissue, and conducts excitation waves at all stages of postnatal development. However, the conduction velocity (CV) of excitation and action potential (AP) upstroke velocity in SVC were significantly lower in neonatal than in adult animals and increased with postnatal maturation. Connexins Cx43 were identified in both neonatal and adult rat SVC myocardium; however, the abundance of Cx43 was significantly less in neonates. The gap junction uncoupler octanol affected conduction more profound in the neonatal than in adult SVC. We demonstrated for the first time that the conduction characteristics of SVC myocardium change from a slow-conduction (nodal) to a high-conduction (working) phenotype during postnatal ontogenesis. An age-related CV increase may occur due to changes of AP characteristics, electrical coupling, and Cx43 presence in SVC cardiomyocyte membranes. Observed changes may contribute to the low proarrhythmicity of adult caval vein cardiac tissue, while pre- or postnatal developmental abnormalities that delay the establishment of the working conduction phenotype may facilitate SVC proarrhythmia.

Cross talk between vascular smooth muscle cells and monocytes through interleukin-1ß/interleukin-18 signaling promotes vein graft thickening.

OBJECTIVE: Interleukin (IL)-1ß and IL-18 are key proinflammatory cytokines that play important roles in the pathophysiology of vein graft remodeling. However, the mechanism of IL-1ß/IL-18 production and its role in the development of graft remodeling remain unclear. APPROACH AND RESULTS: IL-1ß/IL-18 were rapidly expressed in venous interposition grafts. Vascular smooth muscle cell (VSMC) death and monocytic inflammasome activation occurred in grafted veins. Necrotic VSMCs induced the expression of IL-1ß, IL-18, and other inflammasome-associated proteins in monocytes, which was partially inhibited by their antagonist, recombinant IL-1ra-Fc-IL-18bp. Activated monocytes stimulated proliferation of VSMCs by activating cell growth-related signaling molecules (AKT, STAT3, ERK1/2, and mTOR [AKT/protein kinase B, signal transducer and activator of transcription 3, extracellular signal-regulated kinase 1/2, mammalian target of rapamycin]) and increasing production of platelet-derived growth factor-bb; these effects were suppressed by IL-1ra-Fc-IL-18bp. Activated monocytes also promoted migration of VSMCs, which was independent of IL-1ß/IL-18 signaling. Importantly, administration of IL-1ra-Fc-IL-18bp inhibited activation of cell growth-related signaling molecules, VSMC proliferation, and vein graft thickening in vivo. CONCLUSIONS: Our work identified an interaction among necrotic VSMCs, monocytes, and viable VSMCs through IL-1ß/IL-18 signaling, which might be exploited as a therapeutic target in vein graft remodeling.

Discrepancy between superior vena cava oxygen saturation and mixed venous oxygen saturation can predict postoperative complications in cardiac surgery patients.

OBJECTIVE: To determine if increases in discrepancy between ScvO2 and SvO2 (ScvO2 - SvO2 = ΔSO2) during surgery in cardiac surgery patients can predict postoperative complications. DESIGN: Prospective, observational study. SETTING: University hospital. PARTICIPANTS: One hundred two patients undergoing cardiac surgery were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Central venous oxygen saturation (ScvO2) and mixed venous oxygen saturation (SvO2) values during surgery automatically were collected. The average value of ΔSO2 for every minute was calculated. The area under the receiver operating characteristic curve for prolonged postoperative ICU stay (≥3 days) was 0.745 for ΔSO2, which was significantly different from those of ScvO2 and SvO2 (p<0.05) (ScvO2; 0.584, SvO2; 0.598). The optimal threshold value of ΔSO2 to predict prolonged ICU stay (≥3 days) was 12% (sensitivity: 72.0%, specificity: 76.9%). Postoperative ICU duration, ventilation time, and hospital stay were significantly longer in Group D patients (intraoperative maximum ΔSO2 ≥12%) than those in Group N patients (intraoperative maximum ΔSO2<12%). As for postoperative complications, the number of patients with postoperative use of intra-aortic balloon pumping, delirium, respiratory failure requiring tracheotomy, and severe complications was significantly higher in Group D patients. Multivariate logistic regression models were used to evaluate the independent effects of perioperative variables on the risk of developing prolonged ventilation (>24 hours) and prolonged ICU stay (≥3 days). A discrepancy in intraoperative ΔSO2 was an independent risk factor for prolonged postoperative ventilation and ICU stay. CONCLUSION: The discrepancy between ScvO2 and SvO2 during cardiac surgery is an independent risk factor of postoperative complications such as prolonged ICU stay and ventilation time.

A missense variant at the RAC1-PAK1 binding site of RAC1 inactivates downstream signaling in VACTERL association.

RAC1 at 7p22.1 encodes a RAC family small GTPase that regulates actin cytoskeleton organization and intracellular signaling pathways. Pathogenic RAC1 variants result in developmental delay and multiple anomalies. Here, exome sequencing identified a rare de novo RAC1 variant [NM_018890.4:c.118T > C p.(Tyr40His)] in a male patient. Fetal ultrasonography indicated the patient to have multiple anomalies, including persistent left superior vena cava, total anomalous pulmonary venous return, esophageal atresia, scoliosis, and right-hand polydactyly. After birth, craniofacial dysmorphism and esophagobronchial fistula were confirmed and VACTERL association was suspected. One day after birth, the patient died of respiratory failure caused by tracheal aplasia type III. The molecular mechanisms of pathogenic RAC1 variants remain largely unclear; therefore, we biochemically examined the pathophysiological significance of RAC1-p.Tyr40His by focusing on the best characterized downstream effector of RAC1, PAK1, which activates Hedgehog signaling. RAC1-p.Tyr40His interacted minimally with PAK1, and did not enable PAK1 activation. Variants in the RAC1 Switch II region consistently activate downstream signals, whereas the p.Tyr40His variant at the RAC1-PAK1 binding site and adjacent to the Switch I region may deactivate the signals. It is important to accumulate data from individuals with different RAC1 variants to gain a full understanding of their varied clinical presentations.

A Conceptual Study on the Peripheral Clearance of Brain-Derived α-Synuclein in Humans.

BACKGROUND: Abnormal intracellular expression and aggregation of α-synuclein (α-syn) is the histopathological hallmark of several neurodegenerative diseases especially Parkinson's disease. However, safe and efficient approaches to clear α-syn remain unavailable. OBJECTIVE: This study aimed to investigate the process of peripheral catabolism of brain-derived α-syn. METHODS: Thirty patients with atrioventricular reentrant tachycardia (AVRT) (left accessory pathways) who underwent radiofrequency catheter ablation (RFCA) were enrolled in this study. Blood was collected via catheters from superior vena cava (SVC), inferior vena cava (IVC) proximal to the hepatic vein (HV), the right femoral vein (FV), and femoral artery (FA) simultaneously during RFCA. Plasma α-syn levels of AVRT patients and soluble α-syn levels of the brain samples were measured using enzyme-linked immunosorbent assay kits. RESULTS: The α-syn concentrations in different locations of veins were divided by time-matched arterial α-syn concentrations to generate the venous/arterial (V/A) ratio. The V/A ratio of α-syn from the SVC was 1.204 (1.069-1.339, 95% CI), while the V/A ratio of α-syn from IVC was 0.831 (0.734-0.928, 95% CI), suggesting that brain-derived α-syn in the arterial blood was physiologically cleared while going through the peripheral organs and tissues. And it was estimated that about half of brain soluble α-syn could efflux and be cleared in the periphery. Moreover, the glomerular filtration rate was found correlated with V-A difference (FA-ICV) (p = 0.0272). CONCLUSION: Under physiological conditions, brain-derived α-syn could efflux into and be catabolized by the peripheral system. The kidney may play a potential role in the clearance of α-syn.

Cerebral NIRS as a marker of superior vena cava oxygen saturation in neonates with congenital heart disease.

OBJECTIVES: To investigate the correlation between cerebral near-infrared spectroscopy (NIRS) (rSO2c) and superior vena cava venous oxygen saturation (ScvO2) in newborn patients with congenital heart disease (CHD). BACKGROUND: NIRS is a noninvasive method to monitor hemoglobin oxygen saturation using nonpulsatile oximetry. METHODS: We retrospectively analyzed perioperative data from 100 newborn patients who underwent cardiac surgery for CHD. rSO2c, ScvO2 from 24 h before to 72 h after surgery were recorded. RESULTS: rSO2c had a fair correlation with ScvO2 (r 0.37; P <0.001). The relationship between rSO2c and ScvO2 did not change when analyzed between patients with cyanotic or acyanotic CHD. During the preoperative period, rSO2c levels overestimated ScvO2; in the first 18 postoperative hours, rSO2c underestimated ScvO2; after that period, they showed very close trends. Hypocapnia caused rSO2c to underestimate ScvO2; in normocapnic patients, rSO2c-ScvO2 average differences were close to zero; in hypercapnic neonates, rSO2c tended to overestimate ScvO2. The best performance of rSO2c as a surrogate of ScvO2 was found in the venous saturation ranges from 40% to 60% (r 0.3, P: 0.03). CONCLUSIONS: rSO2c in newborn patients with cyanotic and acyanotic CHD provides a continuous noninvasive information with a fair correlation with ScvO2%: some predictable variables (i.e., time from surgery, carbon dioxide, and venous saturation levels), should guide the operators to adjust rSO2c values in terms of ScvO2. Serial measures of ScvO2 seem recommended to tailor rSO2c information on actual venous saturation percentage.

A case of persistent left and absent right superior caval vein: An anatomical and embryological perspective.

The relatively common persistent left superior caval vein (LSCV) is in most cases associated with doubling of the superior caval vein. A persistent LSCV with absent right superior caval vein (RSCV)-a rather rare event-was found during our course of gross anatomy. The LSCV drained into an enlarged coronary sinus, which was partly accompanied by an apparent "double" sinus of normal size draining into this enlarged coronary sinus. Histological and immunofluorescence studies using antibodies against smooth and cardiac muscle actins were performed. The terminal part of the LSCV near the opening into the right atrium contained cardiac actin as expected for a normal derivative of the left sinus horn. Previously only one case of doubled coronary sinus with LSCV has been reported and this abnormality was explained by splitting of the sinus. In our case, the partly doubled coronary sinus had the structure of coronary veins. Mechanical forces have been invoked for the obliteration of the LSCV. Therefore, we examined thirteen human embryos from 15 mm to 32 mm crown-rump length. In one embryo, we found a persistent LSCV together with an enormously enlarged left atrium. Contrary to previous suggestions our data indicate that during normal development a compression of the left anterior cardinal vein does not sufficiently explain the obliteration of the left and the persistence of the right vein. We therefore believe that beside a left dominated blood flow of head and arm, genes for left-right signaling may have to be taken into consideration.

Cytokeratin-positive interstitial reticulum cell (CIRC) tumor in the lymph node: a case report of the transformation from the epithelioid cell type to the spindle cell type.

BACKGROUND: Cytokeratin-positive interstitial reticulum cells (CIRCs), which are a subgroup of fibroblastic reticular cells (FRCs), are known to be present in the lymph nodes. There have been only a few cases of tumors derived from CIRCs. CASE PRESENTATION: We have reported a new case involving a CIRC tumor in a 75-year-old man and reviewed the literature. The resected mediastinal lymph nodes showed epithelial-like proliferation of large atypical round and polygonal epithelioid cells. The tumor cells expressed CK8, CK18, CAM5.2, AE1/AE3, epithelial membrane antigen, vimentin, fascin, and some FRC markers, which is consistent with the diagnosis of a CIRC tumor. Following chemotherapy, the CIRC tumor was observed to have responded very well and became difficult to confirm on imaging, but a small cell lung carcinoma developed 12 months later. Chemoradiotherapy was performed, but the patient passed away 29 months after the initial diagnosis. The autopsy revealed the recurrence of the CIRC tumor, residual small cell lung carcinoma, and a very small latent carcinoma of the prostate. The relapsed CIRC tumor cells had a spindle shape; they were highly pleomorphic and had invaded the superior vena cava. CONCLUSION: We first reported autopsy findings of CIRC tumors and demonstrated the transformation of the tumor from the epithelioid cell type to the spindle cell type.

Thoracic vein arrhythmias.

The thoracic veins are important foci for the genesis of ectopic atrial tachycardia and play a critical role in the pathophysiology of paroxysmal and permanent atrial fibrillation. The pulmonary veins have the highest arrhythmogenic activity and other venous structures (eg, superior vena cava, coronary sinus and ligament of Marshall) have also been shown arrhythmogenic potential. Thoracic veins contain cardiomyocytes with distinct electrical activities and complex anatomical structures. This review summaries the current understanding of the basic and clinical electrophysiology of thoracic vein arrhythmias.

Intradialytic Central Venous Oxygen Saturation is Associated with Clinical Outcomes in Hemodialysis Patients.

Central venous oxygen saturation (ScvO2) in the superior vena cava is predominantly determined by cardiac output, arterial oxygen content, and oxygen consumption by the upper body. While abnormal ScvO2 levels are associated with morbidity and mortality in non-uremic populations, ScvO2 has received little attention in hemodialysis patients. From 1/2012 to 8/2015, 232 chronic hemodialysis patients with central venous catheters as vascular access had their ScvO2 monitored during a 6-month baseline period and followed for up to 36 months. Patients were stratified into upper and lower two tertiles by a ScvO2 of 61.1%. Survival analysis employed Kaplan-Meier curves and adjusted Cox proportional hazards models. Patients in the lower tertiles of ScvO2 were older, had longer hemodialysis vintage, lower systolic blood pressure, lower ultrafiltration rates, higher leukocyte counts and neutrophil-to-lymphocyte ratios. Kaplan-Meier analysis indicated a shorter survival time in the lower tertiles of ScvO2 (P = 0.005, log-rank test). In adjusted Cox analysis, a 1 percent point decrease in mean ScvO2 was associated with a 4% increase in mortality (HR 1.04 [95% CI 1.01-1.08], P = 0.044), indicating that low ScvO2 is associated with poor outcomes. Research on the relative contributions of cardiac output and other factors is warranted to further elucidate the pathophysiology underlying this novel finding.

Simvastatin ameliorates deep vein thrombosis in rabbits by regulating the fibrinolytic system.

The study aimed to observe the therapeutic effect of simvastatin in a deep vein thrombosis (DVT) animal model and conduct a preliminary study into its mechanism. A total of 72 New Zealand white rabbits were randomly divided into control group (n = 18), low molecular weight heparin (LMWH) group (n = 18), simvastatin group (n = 18), and simvastatin + LMWH group (n = 18). A posterior vena cava thrombus model was established and interventions were administered according to the group procedures. Blood plasma was sampled before and 3, 7, and 14 days after the intervention when the vena cava (including thrombus) specimen was collected. Specimens were weighed, histopathologically examined, and monitored for changes in venous wall inflammation. Concentrations of P-selectin, plasminogen activator inhibitor (PAI-1), and the urokinase plasminogen activator (u-PA) activity were measured with enzyme-linked immunosorbent assay. P-selectin expression in the venous wall was measured with immunohistochemistry, and quantitative PCR detected the changes of local PAI-1/u-PA expression. Simvastatin and LMWH reduced the weight of the thrombus and promoted thrombus dissolution. Simvastatin significantly inhibited the systemic and local expression of P-selectin, whereas LMWH was inhibitory only at the late stage of the acute phase. Plasma active concentration and local gene expression of PAI-1 was inhibited by simvastatin, whereas for u-PA; it was promoted at the early stage of the acute phase, but inhibited in the late stage. Simvastatin inhibited the expression of inflammatory mediators, reduced the DVT inflammatory response, alleviated inflammatory injury and reduced thrombus formation. Simvastatin may provide a beneficial adjuvant therapy for DVT.

Heterogeneity of myocardial sleeve morphology and gap junctions in canine superior vena cava.

BACKGROUND: The myocardial sleeve of the superior vena cava (SVC) has been identified as a potential initiating focus in atrial fibrillation, but information on cell-to-cell linkage at this site is lacking. METHODS AND RESULTS: We examined the SVC in 8 dogs by immunoconfocal and electron microscopy. Cardiomyocytes outlined with vinculin and bearing striations positive for alpha-actinin are found in the proximal segment of the SVC. These cells, grouped in bundles of various orientations according to location, extend cephalically as far as 3 cm from the right atrium (RA)-SVC junction. Comparison between the junctional level and the level 2 cm distal shows that the myocardial layer in the latter is thinner and not as compact and is composed of longer cells (87.3+/-15.7 versus 71.6+/-14.4 micrometer, P<0.01). Gap junctions made of connexin43 (Cx43), Cx40, and Cx45 are aggregated mainly at the intercalated disks, and colocalization of connexins is a common feature throughout the myocardial sleeve. Areas of atypical expression exist, however, characterized by a center of abundant Cx43 labels surrounded by a periphery of scattered tiny Cx40-labeled spots. Although in the ventral subluminal compact myocardial layer, individual cells at both levels are surrounded by similar numbers of cells, the number of aggregation of labeled gap junctions at the distal level is less (2.3+/-0.6 versus 3.7+/-0.9, P<0.01). In addition, electron-microscopic examination demonstrates that the gap junctions at the distal level are smaller in size (0.37+/-0.30 versus 0.55+/-0.34 micrometer, P<0.01). CONCLUSIONS: The myocardial sleeve in the canine SVC is a heterogeneous structure, which could potentially form a substrate for heterogeneity of electrical coupling.

Postoperative management: the role of mixed venous oxygen saturation monitoring.

The results of the Norwood operation have improved considerably over the last decade, due in part to improvement in postoperative care. Mixed venous oxygen saturation (MvO2) monitoring has been an important addition to postoperative management. Our use of MvO2 monitoring in Norwood patients has included 96 infants operated from 1996 to the present. This strategy has proven to be technically straightforward and adds information not provided by monitoring systemic saturation alone. MvO2 has a nadir at 6-12 hours after surgery and below a value of 30% is associated with anaerobic metabolism. It identifies patients at risk for early mortality. It also allows evaluation of management of treatment strategies that evolve over time and of specific interventions in individual patients. Optimizing MvO2 constitutes an important goal of postoperative management after the Norwood procedure.

Impact of Personal Characteristics and Technical Factors on Quantification of Sodium 18F-Fluoride Uptake in Human Arteries: Prospective Evaluation of Healthy Subjects.

UNLABELLED: Sodium 18F-fluoride (18F-NaF) PET/CT imaging is a promising imaging technique for the assessment of atherosclerosis but is hampered by a lack of validated quantification protocols. Both personal characteristics and technical factors can affect quantification of arterial 18F-NaF uptake. This study investigated whether blood activity, renal function, injected dose, circulating time, and PET/CT system affect quantification of arterial 18F-NaF uptake. METHODS: Eighty-nine healthy subjects were prospectively examined by 18F-NaF PET/CT imaging. Arterial 18F-NaF uptake was quantified at the level of the ascending aorta, aortic arch, descending thoracic aorta, and coronary arteries by calculating the maximum 18F-NaF activity (NaFmax), the maximum/mean target-to-background ratio (TBRmax/mean), and the maximum blood-subtracted 18F-NaF activity (bsNaFmax). Multivariable linear regression assessed the effect of personal characteristics and technical factors on quantification of arterial 18F-NaF uptake. RESULTS: NaFmax and TBRmax/mean were dependent on blood activity (ß=0.34 to 0.44, P<0.001, and ß=-0.68 to -0.58, P<0.001, respectively) and PET/CT system (ß=-0.80 to -0.53, P<0.001, and ß=-0.80 to -0.23, P<0.031, respectively). bsNaFmax depended on PET/CT system (ß=-0.91 to -0.57, P<0.001) but not blood activity. This finding was observed at the level of the ascending aorta, aortic arch, descending thoracic aorta, and the coronary arteries. In addition to blood activity and PET/CT system, injected dose affected quantification of arterial 18F-NaF uptake, whereas renal function and circulating time did not. CONCLUSION: The prospective evaluation of 89 healthy subjects demonstrated that quantification of arterial 18F-NaF uptake is affected by blood activity, injected dose, and PET/CT system. Therefore, blood activity, injected dose, and PET/CT system should be considered to generate accurate estimates of arterial 18F-NaF uptake.

Differential expression of connexin43 gap junctions in cardiomyocytes isolated from canine thoracic veins.

We investigated the phenotypic features of cardiomyocytes, including the gap junctions, in the myocardial sleeve of thoracic veins. Single cardiomyocytes, isolated from the canine pulmonary veins (PV) and superior vena cava (SVC) using digestive enzymes, were examined by immunoconfocal microscopy using antisera against connexin43 (Cx43), Cx40, and other cell markers. The results showed that isolated cardiomyocytes displayed rod shapes of various sizes, ranging from <50 microm to >200 microm in length, and all the cells expressed alpha-actinin and vinculin. Gap junctions made of various amounts of Cx43 and Cx40 were found at the cell borders. These two connexins were extensively co-localized. Comparison between the thoracic veins showed that cells of the SVC contained more Cx43 gap junctions (total Cx43 gap junctions area per cell surface area, 4.0 +/- 0.2% vs 1.5 +/- 0.2%; p<0.01). In addition, for single-nucleus cells, those from the PV were longer (103.7 +/- 3.6 vs 85.0 +/- 3.1 microm; p<0.01) but narrower (14.4 +/- 0.5 vs 16.9 +/- 0.9 microm; p<0.01). In conclusion, canine thoracic veins contain cardiomyocytes with differences in shape and gap junctions, suggesting that the electrical conduction properties may be different between the thoracic veins.

Further characterization of the 5-HT receptor mediating vascular relaxation and elevation of cyclic AMP in porcine isolated vena cava.

1. 5-Hydroxytryptamine (5-HT) and 5-carboxamidotryptamine (5-CT) produce both smooth muscle relaxation and elevation of tissue adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels in isolated rings of neonatal porcine vena cava. We now present studies attempting to characterize in more detail the 5-HT receptor mediating these responses. 2. Both 5-HT and 5-CT relaxed porcine isolated vena cava rings (EC50 values 200 nM and 4 nM respectively) and elevated tissue cyclic AMP levels (EC50 values 1500 nM and 16 nM respectively). For both responses 5-CT was approximately 50-100 fold more potent than 5-HT. 3. Both 5-CT-induced smooth muscle relaxation and cyclic AMP elevation were potently and specifically antagonized to a similar extent by methiothepin, methysergide and spiperone. 4. At concentrations up to 1 microM, 8-hydroxy-2-(di-n-propylamino) tetralin, buspirone, ipsapirone, n,n-dipropyl-5-CT, cyanopindolol, RU24969, ketanserin, GR38032 and GR43175 were devoid of both agonist and antagonist activity for both responses. 5. These findings suggest that the same 5-HT1-like receptor mediates both smooth muscle relaxation and elevation of cyclic AMP. This receptor is unlike any known 5-HT1 ligand binding site or adenylate cyclase-coupled 5-HT receptor in brain tissues.

Determination of optimal perfusion flow rate for deep hypothermic cardiopulmonary bypass in the adult based on distributions of blood flow and oxygen consumption.

To determine the optimal perfusion flow in deep hypothermic cardiopulmonary bypass at 20 degrees C in human beings, we studied the relationship of perfusion flow to the whole body and to regional oxygen consumption. In adult patients (n = 11, average age 54 years) with valvular or coronary heart disease, the distributions of perfusion flow rate and oxygen consumption were analyzed by dividing into the superior and inferior vena caval areas. Measurements (n = 39) were made at various perfusion flow rates (perfusion flow rate in the superior vena caval area plus that in the inferior vena caval area equals whole-body perfusion flow rate: 0.4 to 2.2 L/min/m2) in a setting of average hemoglobin levels of 8.1 gm/dl. Between whole-body perfusion flow rate and oxygen consumption (total oxygen consumption equals superior plus inferior vena caval oxygen consumption), there was a hyperbolic correlation (r = 0.73; p less than 0.001; asymptote = 29.0 ml/min/m2). A positive linear correlation was found between whole-body perfusion flow rate and inferior vena caval oxygen consumption (r = 0.75; p less than 0.001), whereas no significant relation was seen between whole-body perfusion flow rate and superior vena caval oxygen consumption. For distributional changes in inferior vena caval perfusion flow rate/whole body perfusion flow rate and inferior vena caval oxygen consumption/whole body oxygen consumption, the broken-line regression analysis showed respective critical points where both parameters started to drop when whole-body perfusion flow rate was gradually reduced: 1.2 L/min/m2 for inferior vena caval perfusion flow rate/whole-body perfusion flow rate and 0.8 L/min/m2 for inferior vena caval oxygen consumption/whole-body oxygen consumption. The results indicate that (1) the oxygen consumption to the superior vena caval area was maintained independent of the perfusion in a relatively wide range in contrast to that for the inferior vena caval area and (2) when the redistribution of oxygen consumption is considered as undesirable under low-flow perfusion, the optimal perfusion flow for 20 degrees C deep hypothermic cardiopulmonary bypass appeared to be 0.8 L/min/m2.

Depopulated vena caval homograft: a new venous conduit.

OBJECTIVE: Completion of the Fontan procedure is frequently performed by using an extracardiac conduit between the inferior vena cava and the pulmonary artery. Most centers use a polytetrafluoroethylene graft for the extracardiac conduit, and because re-endothelialization is unlikely, anticoagulation is used for a variable period. This study explores the use of an alternate large-caliber venous conduit. METHODS: The superior vena cava was replaced in 8 minipigs with either a polytetrafluoroethylene interposition graft (2 pigs) or a depopulated (acellular), cryopreserved superior vena caval homograft (6 pigs). After 6 months, the animals were killed, and the grafts were examined for patency and histology, including immunostaining. No anticoagulation was used. RESULTS: Polytetrafluoroethylene grafts have a cross-sectional luminal narrowing, ranging from 16% to 40%. Histology showed only partial intimal ingrowth, with excessive subendothelial fibrosis and early calcification. In contrast, the depopulated venous homografts showed minimal luminal narrowing, ranging from 2% to 9%. These grafts were completely repopulated by the recipient with an endothelial lining, which stained positively for factor VIII, and a subendothelial region appropriately recellularized by myofibroblasts, which stained positively for smooth muscle actin and procollagen. There was no evidence of an immune response to the venous homografts, as judged by staining for T-cell surface antigen, CD4, and CD8. Thrombus was not seen in any of the grafts. CONCLUSION: Depopulated, cryopreserved vena caval homografts might be superior conduits for cavopulmonary connection during completion of the Fontan operation by using the extracardiac conduit technique.

Measurement of the pulmonary vascular granulocyte pool.

We have developed a technique for measuring the pulmonary granulocyte pool (PGP) as a fraction of the whole body total blood granulocyte pool (TBGP). The technique "captures" a dose of 99mTc-labeled granulocytes in a region of interest (ROI) over the lung during first pass by integrating an input time-activity curve from an ROI over the pulmonary artery, superior vena cava, or right ventricle. The ratio of the estimated first-pass count rate and the count rate in the same lung ROI after equilibration of the cells between the circulating and pulmonary pools (15-30 min) represents the PGP/TBGP. The technique was validated in eight subjects by using 99mTc-labeled macroaggregated human serum albumin. With corrections for background and injected doses, the ratios of first-pass granulocyte-to-macroaggregated human serum albumin count rates given by the three input ROIs were close to unity [superior vena cava 0.98 +/- 0.079 (SD), right ventricle 1.01 +/- 0.070, and pulmonary artery 0.97 +/- 0.073]. Significant increases in PGP/TBGP were demonstrated in systemic inflammation. Thus, in patients with inflammatory bowel disease, it was 0.22 +/- 0.07 (n = 7) compared with 0.08 +/- 0.01 (n = 5) in control subjects. It was also elevated in patients with systemic vasculitis (0.34 +/- 0.07; n = 5), in transplant recipients (0.33 +/- 0.08; n = 5), and in patients with osteomyelitis (0.15 +/- 0.06; n = 4). We conclude that this is a valid technique for quantifying the PGP that is expanded in several conditions associated with systemic inflammation.

Localization of dopamine D1 and D2 receptor mRNAs in the rat systemic and pulmonary vasculatures.

The present study was designed to evaluate the expression of dopamine D1 and D2 receptor mRNAs in systemic and pulmonary vasculatures. Using specific antisense riboprobes for dopamine D1 and D2 receptor cDNAs, in situ hybridization histochemistry was performed in the aorta, common carotid artery, vertebral artery, pulmonary artery, and superior vena cava of the adult male Sprague Dawley rat. In the case of the aorta, common carotid artery, and vertebral artery, dopamine D1 receptor mRNAs localized mainly in the smooth muscle cells of the tunica media. However, the signals of dopamine D2 receptor mRNAs were found in the endothelium and subendothelial layer of tunica intima, and interstitial cells of tunica adventitia. In the case of the pulmonary artery, signals of dopamine D1 receptor mRNAs were detected within the tunica intima, media, and adventitia. Expression of D2 receptor mRNAs was detected in the walls of small blood vessels within the tunica adventitia of the pulmonary artery. There were no detectable signals of dopamine D1 and D2 receptor mRNAs in the vein. The uneven distribution of dopamine D1 and D2 receptor mRNAs in the rat systemic vasculatures and pulmonary artery suggests that dopamine differentially regulates the vasodilation of the systemic and pulmonary arteries through the differential stimulation of dopamine D1 and D2 receptor.