Perspectives.

Ischemic cholangiopathy

To investigate the effect of nasal cavity expansion surgery on the abnormal blood supply of the cerebral arterial system. Fifty-nine inpatients with abnormal blood supply of cerebral arterial system confirmed by transcranial doppler (TCD) and chronic nasal obstructive diseases were included in this study. All patients accepted nasal cavity expansion surgery and were followed-up with TCD every month after operation until TCD became normal, or up to seven months even if the TCD was still abnormal. SPSS 17.0 software was used to analyze the data. In all 59 patients, there were 164 TCD-abnormal cerebral arteries. Among them, 37 patients(62.71%) with abnormal TCD arteries became normal within 1 to 7 months after operation, 8 patients (13.56 %) got better, but 14 patients (23.73 %) did not improve. Abnormal blood flow of some cerebral arteries was possibly induced by increasing the activation of sympathetic nervous system around the vertebral arterial system, caused by chronic nasal obstruction. Nasal dilatancy surgery can improve the blood supplement of the cerebral arterial system.

Chemoembolization and Radioembolization for Hepatocellular Carcinoma

Background: The study was performed on wild boar (Sus scrofa scrofa) wich is a wild ancestor of the domestic pig and is not part of Brazilian fauna. The arterial blood supply of the encephalus has been studied by some researchers, who have systematized the cerebral blood supply from the rostral and caudal epidural rete mirabile and its sources in wild boar until the blood supply of the base of the brain. The objective was to improve the understanding of the arterial blood supply of the brain, particularly the paleopallium, of the wild boar and to provide a reference for comparative anatomy studies. Materials, Methods & Results: A total of 30 brains were obtained from an officially authorised slaughterhouse and approved by Brazilian Institute of Environment and Natural Renowable Resources. The animals were desensitized, followed by bleending of the jugular veins and common carotid arteries near the entrance of the thorax, according to the slaughter procedure. Finally, the animals were decapitated at the level of axis vertebra. The cerebral arterial system of each animal was rinsed (cooled saline containing 2500 IU of heparin) and drained by the jugular veins, and vessels were filled with latex 603 stained with specific red dye. The heads were submerged for one hour in running water immersed in 20% formaldehyde for fixation; the brains were removed along with a cervical segment of the spinal cord. The duramater was removed, and the arteries were dissected. Schematic drawings of the ventral view of the all preparations were made using magnifying glasses and photographic records. The Nomina Anatomica Veterinaria was used to named the cerebral arteries and their branches, and calculation of pecentages was applied in the statistical analysis. The cerebral carotid artery originating from the rostral epidural rete mirabile emitted a rostral branch and a caudal branch on the side of the hypophysis gland. The rostral branch emitted one to three middle cerebral arteries and continued as rostral cerebral artery. The latter emitted the superficial and perforating central arteries, lateral rhinal artery, ethmoidal artery, medial branch and medial rhinal artery. Discussion: Wild boar is a macrosmatic animal, it presents well-developed areas of the paleopallium that are exclusively olfactory. Its extensive paleopallium was nourished by branches of the rostral cerebral artery and its collateral branches, including the lateral rhinal, ethmoidal, and medial branch and the medial rhinal artery. The rostral cerebral arteries and their collateral branches supplied blood to the olfactory bulb, olfactory peduncle, two-thirds of the lateral olfactory tract, medial olfactory tract, and rostral two-thirds of the olfactory trigone. The medial cerebral arteries within the lateral fossa of the brain, emitted superficial rostral central branches to the paleopallium, perforating central branches (striated) to the lateral fossa of the brain and caudal third of the olfactory trigone and caudal central branches to the piriform lobe. The rostral most two-thirds of a small medial band of the piriform lobe was vascularised by central branches originating mainly from the rostral branch of the cerebral cartotid artery. The paleopallium in the wild boar was nourished by branches of the cerebral rostral, middle and caudal arteries and by the central branches of the cerebral carotid artery. The arterial blood supply of the paleopallium in the wild boar was compared to the chinchilla, nutria, rabbit and pampas fox. Three cerebral vessels were mainly responsable for the emission of the central branches that supplied blood to the paleopallium, namely the middle, rostral, and caudal cerebral arteries. The differences or variations among these species were due to the type of cerebral blood supply in the formation of the cerebral arterial circle.Keywords : anatomy, brain, paleopallia, arteries, Artiodactila, wild boar.

We report the use of a pseudo-random modulated (PRM), low power laser diode based and dual wavelength NIR instrument for non-invasive, time-resolved spectroscopy (TRS) monitoring and quantification of the cerebral tissue blood supply and oxygenation. In vivo experiment have been conducted with dogs under hypoxia, hypercarbia and hemodilution conditions. Cerebral tissue blood supply and oxygenation are monitored through TRS of photon migration at wavelengths of 670 nm and 810 nm respectively. By (chi) <SUP>2</SUP> curve fitting the measured TRS with effective scattering and absorption coefficients as two variables, both effective scattering and absorption coefficients at each wavelength are extracted. It is found that under hypoxia condition, both scattering and absorption coefficients increases with the hypoxic level. This agrees with the physiology that the blood supply increase while the blood oxygenation decreases under hypoxia. Under hypercarbia condition, both scattering and absorption coefficients of 670 nm decreases with the increase of the hypercarbia level whereas those of 810 nm increases. These correspond to the increased blood supply and oxygenation. Under hemodilution condition, both scattering and absorption coefficients at both wavelengths decreases when the anemia level increases. Therefore, the cerebral tissue blood supply and oxygenation can be monitored and quantified in real-time and non-invasive manner.

Increasing precision of liver resection and use of reduced liver grafts stimulated this study of the blood supply of the intrahepatic bile ducts. Corrosion casts of human liver were dissected to study the blood supply of the right and left hepatic ducts. The dissected casts showed that the ducts are surrounded by a vascular plexus supplied from the main right and left hepatic arteries, segmental arteries, gastroduodenal artery and accessory hepatic arteries. This plexus is closely associated with the arteries supplying the caudate lobe. They arise from both right and left in two general patterns. This plexus links the arterial supplies of the right and left livers. Segment i.v. and the central portion of the left hepatic duct are often supplied by the right arterial system. This study provides further insights into bile duct blood supply. The caudate lobe and biliary plexus provide collateral connections between the right and left livers.

To describe the extraosseous blood supply of the tibia and how the blood supply of the distal tibia is influenced by different plating techniques. Microdissection of cadaveric adult hip disarticulation specimens following sequential arterial injections of india ink and Ward's Blue Latex was performed. Readily identifiable arterioles measured approximately 0.5 mm in diameter. Their artery of origin was identified, and their position along the medial, lateral, and posterior aspects of the tibia was documented relative to the tibial plafond. Additionally, six matched pairs of limbs were used to assess the effects of different plating techniques on the extraosseous blood supply along the medial aspect of the distal tibia. University anatomy laboratory. Nine matched pairs ( = 18) of randomly obtained, adult cadaveric hip disarticulation specimens. India ink followed by Ward's Blue Latex was injected into the superficial femoral artery at the level of the inguinal crease after cleansing of the arterial system. The skin, subcutaneous tissue, and muscles were dissected from the leg, exposing the arterial system and the extraosseous vessels of the tibia. MEAN OUTCOME MEASUREMENTS: The extraosseous blood supply of each aspect of the tibial diaphysis was determined. Each extraosseous arteriole was identified, and the locations of each documented relative to the tibial plafond. Changes in the filling of these vessels along the medial aspect of the distal tibia were documented in a separate group of specimens ( = 12), which had undergone two different plating techniques. The proximal metaphysis of the tibia was found to have a rich extraosseous blood supply provided primarily from vessels from the popliteal artery, the anterior tibial artery (ATA) laterally, and the posterior tibial artery (PTA) medially. In comparison, the tibial diaphysis was found to have relatively few extraosseous vessels and a considerably hypovascular region, posteriorly. Branches of the ATA were found to supply the posterior aspect of the diaphysis with these branches passing through the interosseous membrane. The diaphysis also received a variable contribution from the PTA. The lateral aspect of the diaphysis was supplied by branches of the ATA. An anastomotic network of arteries from the ATA and PTA formed the rich extraosseous blood supply of the medial distal aspect of the tibia. Open plating of the medial aspect of the distal tibia caused a statistically significant ( < 0.05) greater disruption of the extraosseous blood supply of the metaphyseal region than did percutaneously applied plates. In each specimen, open plating prevented filling of each periosteal vessel in the region as opposed to percutaneous plates, which permitted filling of the extraosseous vessels up to the edge of the plate. The proximal and distal metaphyseal areas of the tibia have a rich extraosseous blood supply provided primarily by branches of the ATA and the PTA. Open plating of the medial aspect of the distal tibia caused a greater disruption of this extraosseous blood supply than did percutaneously applied plates. Disruption of these extraosseous vessels following fracture and subsequent operative stabilization may slow healing and increase the risk of delayed union and nonunion. These findings support current efforts to develop less invasive methods and implants for operative stabilization of distal tibia fractures.

Objective To investigate the computed tomography (CT) and magnetic resonance imaging (MRI) features of ependymoblastoma in infants and children in order to improve the understanding of the disease. Methods The clinical, pathological and imaging data from 5 children with ependymoblastoma confirmed by surgery and pathology in the Third Affiliated Hospital of Zhengzhou University from January 2008 to January 2019 were retrospectively analyzed. All the 5 patients received MRI plain scan and contrast-enhanced scan before surgery, and 2 of them received CT plain scan before surgery. Results All the 5 patients were infants aged less than 5 years old. All the tumors were solitary and closely related to the ependyma (4 cases were located in the ventricle and 1 case was adjacent to the brain parenchyma). They were mainly solid and rich in blood supply. T1WI, T2WI and T2dark fluid were all dominated by equal or slightly longer T1 and slightly longer T2 signals. Diffusion weighted imaging showed mild to moderate high signals, while apparent diffusion coefficient showed the corresponding low signals.The tumor was significantly enhanced on contrast-enhanced MRI scans, and there was no enhancement in the necrotic area. Conclusions Infantile ependymoblastoma is a solid tumor with rich blood supply, mostly located in the ependyma. CT and MRI can accurately show tumor’s location, range and blood supply, with certain characteristics. Qualitative diagnosis requires pathological examination. Key words: Ependymoblastoma; Tomography, X-ray computed; Magnetic resonance imaging

Balancing Supply and Demand for Blood during the COVID-19 Pandemic.

Regional metabolism of glucose in chicken kidneys was studied in kidneys perfused with either an arterial system or a portal system. Provided that kidneys were perfused with oxygenated buffer solution at a flow rate of 5 ml/min per gram of kidney in both perfusion systems, oxygenation of the kidney was achieved, as judged by the rates of O2 uptake and the formation of lactate, gluconeogenesis, and the ratio of lactate to pyruvate. The rate of formation of lactate and pyruvate during glucose metabolism, in the presence or absence of KCN, was markedly higher with the arterial system than with the portal system. The rate of gluconeogenesis was equal with both perfusion systems but the rate was modulated by the type of substrate used. With succinate as substrate, ouabain inhibited glucose production and O2 uptake in both perfusion systems. With lactate and pyruvate as substrate, ouabain had no effect on glucose production in both perfusion systems, whereas the inhibition of O2 uptake by ouabain was greater with the arterial system than with the portal system. From the viewpoint of the accepted morphological components of the blood supply, these results suggest that chicken renal gluconeogenesis occurs in the cortex and that glycolysis occurs in medullary structures.

Bei der Katze kann der Druckabfall in den extra- und intrakraniellen Anteilen der Hirnarterien unter gewissen Bedingungen genugend gross werden, um die Hirndurchblutung in eindeutiger Weise zu beeinflussen. Schwankungen des Druckgradienten in den Arterien werden durch die arterielle Vasomotorik und Veranderungen der Durchstromung derjenigen Gewebe bedingt, die von den Aa. carotidae externae versorgt werden.

Central diabetes insipidus (CDI) has been linked to vascular central nervous system damage, although the pathophysiology of the mechanism has never been perfectly understood. Indeed, the vascular system of human pituitary gland has rarely been the subject of rigorous investigation except at postmortem. Recently, studies of pituitary gland blood supply have been carried out by means of a time evaluation of pituitary gland enhancement with noninvasive dynamic magnetic resonance (MR) imaging after contrast medium injection. In the present study, we decided to investigate the status of posterior pituitary blood supply by evaluating vascular pituitary patterns in a group of 19 patients with idiopathic CDI in whom previous standard MR imaging had failed to identify causal specific lesions. The control group was composed of 55 subjects with a median age of 12 yr (range, 4.2-17 yr) who had idiopathic isolated GH deficiency and normal pituitary morphology and 15 young adults (18-25 yr) who had normal pituitary gland and no endocrine dysfunction. Nineteen patients (12 females and seven males), ranging in age at the time of diagnosis of CDI from 0.5-14.9 yr (median, 5 yr), were examined with dynamic MR imaging between 1990 and 1997 at a median age of 14.1 yr (range, 5.0-26.3 yr). CDI was diagnosed according to clinical findings of polyuria and polydipsia, water deprivation test, and desmopressin acetate therapeutic trial. All of the patients had permanent CDI and were being treated with satisfactory results with desmopressin, two to three times daily, either intranasally or orally. The previous MR imaging findings of the 19 CDI patients had shown the absence of posterior pituitary hyperintensity, normal pituitary stalk, and normal anterior pituitary size. Enhancement of the straight sinus, representing a temporal reference point and occurring in normal subjects simultaneously to that of the posterior pituitary gland, was observed in all subjects after iv gadopentetate dimeglumine administration, with no substantial differences between patients and controls. However, the enhancement of the posterior pituitary lobe occurred simultaneously with the enhancement of the straight sinus in all of the controls but in only 14 of the 19 patients with CDI. In the remaining five patients, the enhancement of the straight sinus was not associated with the expected contrast enhancement of the posterior pituitary gland, suggesting abnormal blood supply to the posterior pituitary lobe. This is in keeping with vascular impairment of the inferior hypophyseal artery system and suggests that abnormal blood supply to the posterior pituitary gland is associated with what, until now, has been considered idiopathic CDI.

Research about power supplies has been developed for various requirement. The power supply is used to supply electronic devices and laboratory-scale equipment, one of which is electrospinner. Electrospinner is an instrument used to make nanofibers consisting of several components, namely: power supply, high voltage, syringe pump, and collector drum. Electrospinner requires a stable supply of voltage so that the system can work well and requires a lot of voltage supply to supply components from the electrospinner. Arduino-based switching mode power supply (SMPS) is designed in this research. Arduino-based SMPS makes it possible to produce a stable supply with many outputs. Arduino as a PWM generator is used to control the power supply output voltage based on duty cycle. The results of the study addressed the duty cycle affecting the output of the power supply. The output voltage generated by the power supply can be set from 0-100 V with an accuracy of 98.19%, an error of 1.81% and a precision of 0.02% which is stated by the variation of the coefficient. The power supply produced also has an extra output voltage of 15 VCT and 15 V.

Abstract. The report presents the results of the development of the PPU-500, which is part of the SPS-500 electric propulsion system based on the ST-40 Hall thruster. PPU-500 contains all power supplies necessary for the operation of the propulsion system: discharge; electromagnet; cathode heater and keeper; power supplies for valves and heaters of the storage and feeding working substance, as well as a standby power supply that ensures the standby mode of PPU operation.The converter of the discharge power supply is built using a bridge topology with a phase-shifted output power control circuit. The remaining power supplies are built according to the topology of a step-down synchronous converter with current or voltage stabilization. The discharge power supply is a controlled power supply. The power supplies for the cathode heater and electromagnet current sources are. The accuracy of power supplies output parameters in not worse than 1.5%. The valves of the feeding system are controlled in order to stabilize the pressure in the receiver by periodically turning on/turning off the high- and low-pressure valves. For control the valves, signals taken from pressure sensors installed in the receiver are used. The PPU control unit ensures an accuracy of maintaining pressure in the receiver no worse than 2.5%. The control unit of the PPU is built using a microcontroller with an ARM core. It implements the functions of monitoring the condition of the program, restoring the program firmware if an integrity violation is detected, and the ability to remotely flash a new version. To communicate the SPS-500 with the on-board control system, a galvanically isolated CAN interface is used. It can be also the RS485/RS42 interface.During operation of the propulsion system, operating parameters are measured using multi-channel ADCs and DACs. The obtained data, on the one hand, is used to assess the current state of the propulsion system and control Hall thruster operating modes. On the other hand, they are transmitted as telemetry signals reflecting the current state of the SPS-500, operating mode and emerging emergency conditions of the equipment. PPU is possible to alternately control two thrusters. Solid-state switches are used to switch the corresponding power sources.Testing of the PPU-500 as part of the SPS-500 propulsion system with the ST-40 Hall thruster and a flight prototype of the working substance feeding system confirmed the technical solutions adopted. The operating efficiency of PPU-500 for the nominal operating mode of the propulsion system is 94%.

For decades the pulmonary circulation was not considered as important as the systemic ("greater") circulation. However, pulmonary hypertension can arise because of many diseases of the heart and lung. Therefore, increasing efforts in research have been undertaken leading to a profound increase in understanding pulmonary vascular physiology and pathophysiology. This review discusses basic physiology, clinical concepts, and treatment options for pulmonary hypertension and the related right ventricular heart failure focusing on secondary pulmonary hypertension in patients during anesthetic procedures. Physiology of Pulmonary Circulation The pulmonary vascular bed is a high-flow, low-pressure circulation system. Pulmonary vessels have less resistance in comparison to the systemic circulation under normal conditions because of higher compliance of pulmonary precapillary arterioles with a thinner media and less smooth muscle cells (SMCs) compared with the corresponding systemic arterioles. In addition, the cross-sectional area of the pulmonary vascular bed is large and highly distensible with recruitable vessels available to accommodate increase in flow resulting in low pressure and low resistance. In contrast to the systemic arteries, pulmonary vessels constrict with hypoxia (Euler-Liljestrand reflex) and relax in the presence of hyperoxia. Furthermore, changes in cardiac output (CO), airway pressure, and gravity affect the pulmonary more than the systemic circulation. Increases in CO distend open vessels and recruit previously closed vessels. Therefore, the cross-sectional area of pulmonary circulation enlarges and results in a decrease in pulmonary vascular resistance (PVR). An increase in CO has very little effect on pulmonary arterial pressure (PAP) because of the recruitment and distension of pulmonary vessels. An increased PAP or left atrial pressure (LAP) may also distend and recruit pulmonary vessels. Clinically, this means that enhanced CO caused by the administration of inotropic drugs or enlarged blood volume will passively decrease PVR. The contribution of intra- and extraalveolar vessels accounts for the unique U-shaped relationship between lung volume and PVR, which is minimal at functional residual capacity and increased at large and small lung volumes (Fig. 1). Clinically, this may be observed when hyperinflation of the lungs greatly increases PVR.Figure 1: Relationship between lung volume and pulmonary vascular resistance (PVR) (123). RV = residual volume, FRC = functional residual capacity, TLC = total lung capacity.Gravity influences the distribution of blood flow in the pulmonary circulation. Blood flow as well as ventilation increases in the dependent areas of the lung. The relationship between alveolar and hydrostatic pressure implies important clinical consequences. Patients with unilateral lung disease should be positioned with the diseased side up as was already shown by Remolina et al. (1). Lying with the sick lung dependent resulted in the worst gas exchange and the lowest arterial oxygen pressure (1). Application of high levels of positive end-expiratory pressure (PEEP) will narrow the capillaries in the well-ventilated lung areas and divert flow to less well-ventilated or nonventilated areas. Therefore, a decrease in PaO2 is the consequence. Constantly changing hemodynamics, mechanical forces, and hormonal environment influence the vascular endothelium and the underlying SMCs. Under normal circumstances, the interaction between endothelium and SMCs results in a low vascular resistance in the pulmonary circulation. An increasing number of molecules seem to be involved in these biochemical transductions: L-arginine-nitric oxide (NO)-cyclic-3′-5′guanosine monophosphate (cGMP) pathway seems to have a predominant role (2). Physiological agonists such as bradykinin and acetylcholine as well as mechanical stress derived from pulmonary blood flow can activate endothelial cells. This results in oxidation of the guanidino-nitrogen atom of the amino acid L-arginine by the constitutive NO synthase to form and release NO. NO diffuses from endothelial cells to the SMCs, and produces relaxation by activating guanylate cyclase with increasing intracellular cGMP (2). Pulmonary endothelial cells (surface area of 200 m2 in the adult) have a very strategic location: they are exposed to the entire CO, link the pulmonary and systemic circulation, and also regulate SMC tone by signaling to the vascular wall. Endothelial cells both seem to sense local shear stress and to initiate a response (e.g., production of NO) in order to accommodate rapid changes of blood flow. NO and prostacyclin (PGI2) support oxygenation and lung inflation in dilating the pulmonary vasculature after birth, keeping a key regulatory role in the lung because of its prompt, local powerful action compared with a brief half-life time (3). Pathophysiology of Pulmonary Hypertension It is now understood that the balance between vasoconstrictors and vasodilators and mitogenic and antimitogenic factors derived from the endothelium is disturbed in situations with an increase in PAP (4, 5). Endothelial dysfunction is promoted by hypoxia, acidosis, free radicals (6), inflammatory mediators, shear stress caused by increased pulmonary blood flow from left-to-right intracardiac shunt (7), and fibrin from thromboembolism (8). There is no widely accepted range for normal PAP. However, mean PAP >25 mm Hg (normal 15 mm Hg) at rest or >30 mm Hg with exercise is generally accepted as indicative for pulmonary hypertension (9). The enhanced pressure in the pulmonary circulation is associated with an increase in PVR and results in a progressive inability of the right ventricle (RV) to sustain its output leading to RV hypertrophy and RV failure depending from acute or chronic changes (4). In a study by Vizza et al. (10), prevalence of RV dysfunction (defined as RV ejection fraction [RVEF] <45%) was significantly higher in patients with pulmonary hypertension compared with all other groups with end-stage pulmonary disease. Determination of PVR is difficult in clinical settings even if the respective variables such as LAP, mean PAP, pulmonary capillary wedge pressure (PCWP), and thermodilution CO are measured directly because of their intrinsic inaccuracies. Therefore, indirect estimations use the equation: Normal PVR is approximately 1.1–1. 4 Wood units or about 90–120 dynes · s · cm−5, and a PVR >300 dynes · s · cm−5 is indicative of pulmonary hypertension. Pulmonary blood flow and volume are not always equal to or correlated with CO, because of intracardiac or other shunts. Vascular Remodeling Chronic pulmonary hypertension leads to structural alterations of the pulmonary vasculature and to a progression of histological changes known as "vascular remodeling" (11). Under physiological conditions, pulmonary arterioles are thin-walled vessels with the media occupying only 7% of the vessel thickness. The major finding in remodeled vessels caused by a chronic stimulus like hypoxia is the increase in SMCs in already muscularized arteries and extension of SMCs into vessels that are normally thin and nonmuscular (12) and thickening of the adventitial layer (13). Thickening of the adventitial layer is the result of marked proliferation of the fibroblasts, which has been shown to be modulated by protein kinase C and mitogen-activated protein kinase (14). After the proliferative response, there is an increase in adventitial connective tissue including a switch in SMC phenotype to a more synthetic cell that is responsible for deposition of increased connective tissue (12). This deposition of most notably collagen is probably a protective mechanism strengthening the vascular wall against the increase in intravascular pressure (15). Additionally, damage to intimal endothelium as well as intimal hyperplasia and fibrosis can be detected (5). The central regulatory function of the pulmonary endothelium is underlined by the fact that a dysfunctional endothelium can influence the development of pulmonary hypertension at the levels of coagulation control, vasomotor tone, and pulmonary vascular remodeling (16). The major stimulus for remodeling is hypoxia (17). The increase in PVR is predominantly caused by the hypoxic pulmonary vasoconstriction (HPV), which resides primarily distal to lobar arteries and proximal to the capillaries and occurs in resistance arterioles 30–300 μm in diameter (18). Pulmonary arteriolar SMC oxygen-sensitive voltage-dependent potassium channels seem to have an important role for initiating HPV (19). Inhibition of these channels by decreased PO2 inhibits outward potassium current, causing membrane depolarization and calcium entry through voltage-dependent calcium channels (19). The main determinant of HPV is alveolar PO2, but mixed venous PO2 contributes to approximately 20% of the response (19). HPV is inhibited by substances such as substance P, atrial natriuretic peptides, by mediators such as PGI2 and NO, by increased LAP, by increased alveolar pressure, and by alkalosis. Enhanced HPV, however, could be observed with acidosis, by using epidural anesthesia and by inhibition of cyclooxygenase or NO synthase (19). Subsequent increases in PAP are predominantly caused by vascular remodeling as well as secondary polycythemia. Proliferation and differentiation of pericytes and intermediate cells to SMCs are a consequence of chronic exposure to hypoxia followed by elastin and collagen synthesis and deposition (20). In addition, vasomotor function may be altered in these remodeled vessels (20). Among the candidates of biochemical mediators of hypoxia-induced pulmonary hypertension are voltage-gated potassium channels, mitochondrial oxygen sensing, and an imbalance in vasoactive factors (see below) (21). Remodeling also happens in inflammation secondary to sepsis (22) and in patients with chronic lung disease (23) and adult respiratory distress syndrome (ARDS) (24). The inflammation process and increased blood flow lead to vascular remodeling by damaging endothelial cells and disturbs the sensitive balance of pulmonary tone. Under physiological conditions, these cells eliminate factors that initiate SMC proliferation such as angiotensin II, endothelin, thromboxane A2, prostaglandin H2 and O2−(25). Alternatively, damaged endothelial cells may fail to produce inhibitory factors, possible heparin-like substances, which normally decrease SMC proliferation. Removal of the inciting stimulus can lead to reversal of structural changes. Etiology of Pulmonary Hypertension Pulmonary hypertension is caused by a variety of acute and chronic pulmonary diseases with an increase in PAP (Table 1). In contrast to secondary pulmonary hypertension, primary pulmonary hypertension (PPH) is not related to a known underlying disease.Table 1: World Health Organization Diagnostic Classification of Pulmonary Hypertension (1998) (21)PPH PPH is rare (1–2 per million in the general population), affects more women than men (1.7:1), sometimes has a familial link (6% of all cases), and has a poor prognosis (median survival 2–3 yr after diagnosis). PAP usually is >60 mm Hg in these patients (9, 26). PPH is a diagnosis of exclusion, because it is idiopathic. Hypoxemia and increased PVR resulting in an increased PAP can lead to RV failure and death. Altered vasoreactivity alone is not responsible for PPH. Vascular remodeling contributes to the vasculopathic process. However, regression of extensive changes caused by hypertension can occur. Secondary Pulmonary Hypertension Secondary pulmonary hypertension is more common, the increases in PAP are generally less severe (mean PAP <40 mm Hg) (26), and it is also more frequently seen in the perioperative period. Therefore, in this review, we have focused on secondary forms of pulmonary hypertension. Most cases of pulmonary hypertension are secondary to cardiac or pulmonary disease (Table 1) and may be reversible in some cases. Clinical manifestations might be overshadowed by the symptoms of the underlying disease (Table 2). Blood vessel changes are not confined to PPH but are also found in many forms of secondary pulmonary hypertension. Congenital cardiac disease with an atrial or ventricular septal defect causes an increase in pulmonary blood flow. Over time, in response to the increased blood flow, the PVR is increased and eventually will exceed systemic vascular resistance (SVR). Under these conditions, blood flow is shunted from right to left, often referred to as Eisenmenger syndrome. In contrast, high-pressure shunts such as those associated with truncus arteriosus, ventricular septal defects, or patent ductus arteriosus (28) cause pulmonary hypertension much earlier and it is often more severe.Table 2: Common Symptoms and Signs of Pulmonary Hypertension (27)The relevance of pulmonary hypertension in the perioperative period was shown in a study by Reich et al. (29). In patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB), the development of pulmonary hypertension was a significant predictor of increased mortality and perioperative myocardial infarction (29). The severity of the observed vasoconstriction correlates with the extent of CPB-induced endothelial injury (30). Levels of thromboxane A2(31) and endothelin (32) were increased after CPB, whereas PGI2 and NO levels were reduced (33). For a long time, it was thought that CPB did not cause any pulmonary endothelial injury due to ischemia-reperfusion because of the protection via the vasa vasorum of the bronchial circulation. It has been shown, however, that total CPB may cause complete cessation and reestablishment of pulmonary artery flow, with inadequate pulmonary endothelial blood supply by the vasa vasorum, resulting in an ischemia-reperfusion injury (34). The intraoperative injury and postoperative endothelial dysfunction of the pulmonary endothelium is promoted by the following factors (2): Preoperative status of the pulmonary vascular bed, i.e., pulmonary hypertension, valvular pathology; chronic obstructive pulmonary disease, pulmonary thromboembolism, and shear stress caused by increases in pulmonary blood flow and pressure of left-right intracardiac shunt. Bando et al. (35) demonstrated in patients with congenital heart disease that preoperative pulmonary hypertension, absence of mixed venous saturation monitoring, and absence of prophylactic α-blockade significantly increased postoperative pulmonary hypertension. Intraoperative vasospastic stimuli, such as hypoxia, hypercarbia, acidosis, duration of total CPB, ischemia-reperfusion injury, free radical formation, inflammatory mediators, pulmonary leukosequestration, excess thromboxane or endothelin production, and microemboli. Postoperative factors such as adrenergic tone, atelectasis, and HPV. Other examples of pulmonary hypertension during anesthesia are shown in Table 3.Table 3: Occurrence of Pulmonary Hypertension During Anesthesia (36)Symptoms and Diagnosis of Pulmonary Hypertension The most common clinical signs of pulmonary hypertension are dyspnea and fatigue (9) (see also Table 2). These major symptoms might be explained through the associated decrease in CO; however, an exact etiology is still missing. On physical examination, a prominent P2 heart sound, a tricuspid regurgitation murmur, an atrial (S3), or ventricular (S4) heart sound might be heard. The chest radiograph can display an enlarged main pulmonary artery and enlarged hilar vessels, whereas the electrocardiogram shows a right axis deviation suggesting right ventricular hypertrophy. However, the validity of acute changes in the electrocardiogram attributed to right heart insufficiency in the intraoperative period is limited. Transesophageal echocardiography (TEE) as a more advanced technique diagnoses pulmonary hypertension indirectly attributed to RV enlargement, paradoxical interatrial and interventricular movement, partial systolic closure of pulmonary valve, tricuspid regurgitation, and an increased RV systolic pressure (Fig. 2). There are two approaches to obtaining hemodynamic measurements using TEE. By using spatial imaging methods, cardiac chamber volumes can be estimated to obtain both preload and stroke volume. In addition, Doppler-based methods can be used to estimate both right ventricular filling and CO (37). Because of the inherent difficulty in developing a simple geometric model of the RV, regression equations may inaccurately predict ventricular volumes. In addition, TEE measurements are further altered by changing loading conditions, which alter both the size and geometry of the RV. Although TEE evaluation of RV volume can be difficult to determine in adults, high-quality images are routinely obtained in pediatric patients. One of the main limitations on further use of TEE is the availability of equipment as well as costs of echocardiography machines and probes, and expertise (37). The definitive diagnosis is obtained by right heart catheterization with direct measurement of PAP, right atrial pressure (RAP), PCWP, and CO.Figure 2: Transesophageal echocardiography for diagnosis of pulmonary hypertension. Dilated right ventricle (RV) in the midesophageal four chamber view. The figure shows the classical septal (S) interventricular shift to the left side. RA = right atrium, LA = left atrium, LV = left ventricle.RV and Pulmonary Hypertension Like the pulmonary circulation, the RV was not considered as important as the left ventricle (LV) in maintaining normal hemodynamics and counted for a long time as a "quantite negliable" (38). Today it is recognized that RV and LV are interdependent and both have vitally important functions. The RV is a thin-walled, highly compliant, but poorly contractile chamber. Under normal loading conditions and when function is not compromised, RV ejects blood against 25% of the afterload of the LV, resulting in a smaller RV wall thickness (39). The RV is bound by the RV free wall and the interventricular septum. Failure of the septum (e.g., because of ischemia) to contract normally will decrease RV systolic function. Blood supply for the RV and the septum depends mostly on whether a right or left dominant, or a "balanced" coronary circulation is present. Usually the right and the left anterior descending coronary artery supply the septum and parts of the free wall of the RV. The continuous pressure gradient between the aorta and the RV (coronary perfusion pressure) is responsible for the coronary blood flow to the RV free wall throughout systole and diastole (40). Therefore, the RV blood/oxygen supply is proportional to the systemic pressure but inversely proportional to the RV pressure. Systemic hypotension or increased RV pressure results in a decreased RV coronary perfusion pressure (41). Vlahakes et al. (42) previously showed that right heart performance is directly related to systemic pressure during pulmonary hypertension. RV function is very sensitive to increased RV preload or afterload, septic shock, coexistent LV dysfunction, or right coronary artery occlusive disease (43, 44). In a fundamental study, Urabe et al. (45) demonstrated that an increase in the afterload of the RV resulted in a rightward shift of the relationship between perfusion pressure and regional shortening. Also, end-diastolic segment lengths increased significantly after banding of the pulmonary artery. In contrast to LV performance, RV function is relatively sensitive to increases in afterload. Acute increase in mean PAP above approximately 40 mm Hg results in a significant decrease in RVEF even in the presence of a normal RV contractility. However, gradual increases in afterload are well tolerated, because the RV has time to assemble new sarcomeres in parallel to increase wall thickness (39). In the presence of decreased RV contractility, the RV is even more susceptible to acute increases in afterload. The decrease in RVEF results from a disproportionate increase in end-systolic volume compared with end-diastolic volume (41). The RV is less preload-responsive than the LV such that a given increase in preload results in a smaller increase in stroke work. Therefore, attempts at volume loading may be less effective in increasing RV output compared with volume loading of the In addition, volume loading may even the of RV oxygen (41). Vlahakes that two important in the of right heart RV afterload be reduced and systemic pressure be or Normal and are for maintaining normal RV function The of is as important for RV as it is for LV RV performance is by both intrinsic factors of the RV as well as factors afterload, of the pressure, right coronary artery perfusion pressure, LV performance, and the contractile of the interventricular of the LV function like coronary artery disease, heart valvular heart disease, or systemic hypertension influence RV function by ventricular Also, a RV and right can shift the interatrial and interventricular septum and the left and LV end-diastolic volume. venous pressure not on RV filling pressure and volume because it is dependent on the compliance of the RV in the tricuspid methods, and imaging are and more in the RV RV dysfunction caused by increased PAP was demonstrated in patients with chronic pulmonary disease and in patients ventilation can also RV the interventricular septum paradoxical resulting in right heart and decreased LV chamber size In postoperative a decrease in RVEF is observed at levels because of of alveolar vessels and increase in RV afterload significant was between RVEF and increasing of airway pressure by ventilation of the underlying disease has Because symptoms often arise in pulmonary hypertension, the after of signs of RV insufficiency is yr in for lung disease, as well as systemic for chronic lung are of of pulmonary hypertension. of which causes and and for can also definitive of congenital heart diseases can and mortality from postoperative pulmonary hypertension common clinical is the of the right heart because of chronic left heart In this of the LV has of the right heart by means of coronary or coronary artery bypass treatment and should PVR, which can be with the following and factors the pulmonary oxygenation with oxygen of respiratory acidosis, mm Hg) of a to of respiratory of the lung of release caused by stress and of options for RV dysfunction with increased PVR whereas positive inotropic drugs are the treatment of in RV dysfunction with normal PVR. of RV of RV preload should be considered if central venous pressure is mm Hg It is however, that preload of the RV should be estimated by a simple volume in an increase in mean arterial blood pressure and can increase RVEF with volume if RV is normal and PAP is increased only However, administration of volume also can have in patients with right heart treatment in for (defined as patients no increase in to the with central venous pressure mm of RV of the of the pulmonary circulation of CO and RV failure previously or vasodilators should be keeping in to a significant decrease in the decrease in the in RV stroke volume, systemic hypotension can be the consequence. is thought to produce by calcium channels has other such as the to NO synthase activate and release in both endothelial and SMCs. of SMCs is by both release of NO and direct of SMCs has a half-life it is relatively for the pulmonary circulation. It has been shown to be a and of other drugs to produce pulmonary in of patients with PPH a but there are no observed because of the small In contrast to treatment with that to reduced PAP and PVR in patients with secondary pulmonary hypertension treatment did not any This might be explained by the fact that on their to vascular remodeling The angiotensin reduced PAP and PVR in patients with secondary pulmonary hypertension 4 after have been shown to be effective in the treatment of pulmonary hypertension secondary to connective tissue vascular disease but not in patients with treatment was because of the on venous The of with calcium in secondary pulmonary hypertension seems to on the of PAP, i.e., the higher the of PAP, the less effective the of to the of on PAP in patients with pulmonary showed that a in PAP in of The in PAP in patients with the and the in PAP with clinical Although these drugs have shown their they have severe if used it is that calcium treatment should be to to Patients with pulmonary hypertension and severe clinical right heart failure (mean mm CO should be from treatment with calcium because of the inotropic of these by or more responsible for the of monophosphate leading to an increased of these with increased LV and pulmonary given have been used in patients with pulmonary hypertension after cardiac was shown for cardiac patients with increased PVR to pulmonary systemic It also seems to have an pulmonary effect to The PGI2 was in to PAP in PPH It is by the vascular endothelium and via prostaglandin to cyclase with following increase of PGI2 production is in patients with pulmonary hypertension of PGI2 may in to these are an inhibition of both and SMC proliferation from treatment of PGI2 or its also PAP in pulmonary hypertension of the pulmonary hypertension after heart in or pulmonary hypertension secondary to connective tissue diseases in a