Pathogenesis Of Neurogenic Pulmonary Edema Research Articles

NEUROGENIC PULMONARY EDEMA: KOMPLIKASI YANG MENGANCAM JIWA AKIBAT KERUSAKAN BERAT SISTEM SARAF PUSAT

ABSTRACT
 Neurogenic Pulmonary Edema (NPE) is one of the complications due to severe damage of the central nervous system (CNS). The incidence is about 2-8% in the world and still rarely reported. Neurogenic pulmonary edema (NPE) commonly found in cases of intracranial hemorrhage such as SDH, SAH, and ICH, in conditions of uncontrolled epilepsy and recurrent seizures, and in some cases of spinal cord trauma. The pathogenesis of Neurogenic Pulmonary Edema (NPE) cannot be fully understood, but there are 2 theories of the occurrence of Neurogenic Pulmonary Edema (NPE), the first namely as theory of hemodynamic changes and the second is NPE trigger zones involving the central control of the brain's autonomic and cardiovascular system. Neurogenic Pulmonary Edema (NPE) has an acute and chronic onset, which is characterized by ARDS-like symptoms such as dyspnea, tachypnea, tachycardia, reddish sputum, crackles in auscultation, and radiological features in the form of diffuse alveolar infiltrat bilateral. Early recognition of signs and symptoms of Neurogenic Pulmonary Edema (NPE) can improve the patient's outcome. Initial treatment of this condition uses two management principles, first overcoming the underlying disease condition and second is supportive therapy, such as mechanical ventilator, ECMO, and transpulmonary thermodilution, the use of diuretics, and controlling fluid therapy.

Vagal Ischemia Induced Lung Immune Component Infarct Following Subarachnoid Hemorrhage: An Experimental Study.

Neurogenic pulmonary edema (NPE) is the most serious complication of subarachnoid hemorrhage (SAH). As vagal nerves have vital roles in lung functions, vagal ischemia may have a causative role in the pathogenesis of NPE. We examined whether there was a relationship between vagal complex ischemia and lung immune complexes occupying the lymph node infarct in SAH. Thirty-two rabbits were divided into three groups: Control (n=5), SHAM (n=5) and SAH group (n=22). SAH was created by autologous blood injection into the cisterna magna and followed-up for 3 weeks. Vasospasm index (VSI) was defined as the ratio of the lung lymph node arteries (LLNA) wall section (wall ring) surface to the lumen surface. Degenerated axon numbers of vagal nerves, neuron densities of the nodose ganglion (NG) and VSIs of LLNA were compared for all groups. The mean degenerated vagal nerve axon density, neuron density of NG, and VSI of LLNA were 26±8/mm < sup > 2 < /sup > , 30±5/mm < sup > 3 < /sup > , and 0.777±0.048 in the control group; 1300±100/mm2, 720±90/mm < sup > 3 < /sup > , and 1.148±0.090 in the animals with slight vasospasm (n=12); and 7300±530/mm < sup > 2 < /sup > , 5610±810/mm3, and 1.500±0.120 in the animals with severe vasospasm (n=10), respectively. Degenerated vagal axon and NG neuron density may be a causative factor in the development of LLNA vasospasm induced lymph node infarct in SAH. Lung lymph node infarct may be an important factor in the prognosis of NPE.

Dynamic changes in serum inflammatory cytokines and their association with neurogenic pulmonary edema in patients with severe hand-foot-mouth disease

Objective To investigate the dynamic changes in the serum inflammatory cytokines and their association with neurogenic pulmonary edema (NPE)in the patients with severe hand-foot-mouth disease (HFMD). Methods Eighty-nine patients with severe HFMD from March 2010 to December 2012 were recruited in the study.The patients were divided into NPE group and central nervous system diseases(CNSD) group according whether they had NPE.The cytokines, including interleukin (IL)-4, IL-6, IL-10, IL-17, tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ)were evaluated by using enzyme-linked immunosorbent assay on day 1, 3 and 5 after admission to hospital.Risk factors for NPE involvement during hospital stay were analyzed with multivariate Logistic regression analysis. Results (1)Compared with the CNSD group, the serum levels of IL-6(Ftime=1.876, P=0.177, Ftime*group=2.192, P=0.145, Fgroup=7.855, P=0.007), TNF-α(Ftime=13.133, P=0.001, Ftime*group=0.291, P=0.592, Fgroup=3.644, P=0.042), IL-10(Ftime=14.580, P=0.001, Ftime*group=2.612, P=0.078, Fgroup=16.823, P=0.000), INF-γ(Ftime=3.093, P=0.045, Ftime*group= 0.513, P=0.600, Fgroup=20.141, P=0.000)were significantly higher than those in NPE group.(2)The serum levels of TNF-α, IL-10, INF-γ rose to the peak on the third day.(3) By using multivariate Logistic regression analysis, age (OR=3.383, 95% CI: 1.173-4.759), days of fever (OR=4.925, 95%CI: 1.758-3.794), hyperglycaemia (OR=3.465, 95%CI: 1.303-5.220), leucocytosis (OR=7.579, 95%CI: 2.530-12.704)and elevation of IL-10 (OR=1.228, 95%CI: 1.007-1.523) were entered into equation.In the risk evaluation model, these variables remained independent predictors for NPE. Conclusions Abnormal cytokine productions appear to be responsible for the pathogenesis of NPE, and might be an effective tool for predicting NPE in infants with severe HFMD. Key words: Hand-foot-mouth disease; Cytokine; Dynamic change; Neurogenic pulmonary edema

Pathogenesis of severe hand-food-mouth disease complicated with neurogenic pulmonary edema

Severe hand-food-mouth disease can be accompanied by neurogenic pulmonary edema, which can rapidly lead to death.The pathogenesis of neurogenic pulmonary edema may be related to the comprehensive influences on neural factors, humoral factors and multiple bioactive substances after the central nervous system is damaged.It is of great impotance to investingate the pathogenesis of neurogenic pulmonary edema, which facilitates timely treatment and prevention of the complications. Key words: Severe hand-food-mouth disease; Enterovirus 71; Neurogenic pulmonary edema; Pathogenesis

Protective effect of an angiotensin-converting-enzyme inhibitor on neurogenic pulmonary edema in rabbits

Neurogenic pulmonary edema (NPE ) was indicative of poor prognosis in the epidemic of enterovirus 71 infections. The pathogenesis of NPE remains poorly understood. The objectives of this experimental study were to explore whether RAS is activated during NPE in rabbit models induced by fibrin and the effects of an angiotensin converting enzyme inhibitor (enalaprilat) on NPE. NPE models were induced by intracisternal injection of fibrinogen and thrombin. According to random number table method, 18 healthy adult New Zealand rabbits were assigned to three groups (with 6 in each) : normal control group (Con group), NPE group and enalaprilat treated (Ena) group. After establishment of NPE models, rabbits in Ena group were given intravenous enalaprilat 0.5 mg/kg. Expression of ACE,ACE2,AT1R mRNA of the lung tissue were evaluated by real-time polymerise chain reaction; and Ang II of the lung tissue was determined by enzyme linked immunosorbent assay ( ELISA ). Meanwhile, histopathological lung injury scores were evaluated. ACE mRNA expression level in NPE group ( 17.2 ± 3.3) appeared an increasing trend in contrast to Con group ( 12.6 ± 5.2 ) and Ena group ( 11.5 ± 2.4, both P > 0.05 ). Compared with Con group (81 ± 22 ), ACE2 mRNA expression levels of NPE group ( 52 ± 6 ) and Ena group ( 45 ± 13 ) both decreased ( both P < 0.05 ) . ACE mRNA/ACE2 mRNA expression levels of NPE group ( 0.33 ± 0.06 ) and Ena group ( 0.26 ± 0.04 ) were higher than those of Con group ( 0.16 ± 0.05, both P < 0.05 ), as well as the ratio of Ena group decreased compared with untreated NPE group ( 0.26 ± 0.04 vs. 0.33 ± 0.06, P < 0.05 ) . There were no statistically significant differences in expression of AT1 mRNA of the lung tissue among three groups, but Ena group ( 4.8 ± 1.1) in contrast to NPE group ( 6.7 ± 1.3) has no significant difference (P > 0.05). Lung AngII level of NPE group [(540 ± 147) pg/ml] was significantly higher than that of Con group [(253 ± 37 ) pg/ml] and Ena group [(309 ± 35 ) pg/ml, both P < 0.05 ]. Gross pathologic examination showed that pink foamy edema fluid appeared in the tracheal tubes in NPE group, but spontaneously appeared in neither Con group nor Ena group; and the level of pulmonary subpleural bleeding in Con group, 12 graded 0; in NPE group, 2 graded II, 10 graded III; in Ena group, 2 graded, 8 grade II, 2 grade III. The histopathologic lung injury scores in Ena group was decreased in contrast to NPE group (1.36 ± 0.26 vs.2.32 ± 0.49, P < 0.05) and mainly for the improvement of alveolar overdistension and interstitial edema. The present study showed that when NPE occurs, a high lung AngII concentration was associated with an imbalance between ACE mRNA to ACE2 mRNA expression level. Activated local RAS in lung tissue resulted in lung injury. Enalaprilat treatment may attenuate lung injury by interventing local RAS in lung tissue with decreased ratio of ACE mRNA to ACE2 mRNA and lung AngII concentration. The result will be significant for the angiotensin converting enzyme inhibitor used in the theatment of NPE.

Abstract 56: Association between Increased Plasma Catecholamine Levels and Neurogenic Pulmonary Edema in Patients with Subarachnoid Hemorrhage

Background: Neurogenic pulmonary edema (NPE) occurs relatively frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been indicated as its principal cause. The objective of this study is to evaluate the relative contribution of each catecholamine in pathogenesis of NPE. Methods: Records of 77 SAH patients (23 men/54 women) whose plasma catecholamine levels were measured within 48 h of SAH onset were retrospectively analyzed. Results: Eight patients (10%) were diagnosed with NPE. Plasma epinephrine (366.9±347.4 vs. 130.3±167.4 pg/mL, p =0.001) and norepinephrine (3481.1±1678.9 vs. 835.5±688.9 pg/mL, p &lt;0.001) levels were significantly higher in the NPE+ group than NPE- group. Demographic comparison revealed that the severity of SAH and cardiac damage/dysfunction was significantly more profound in the NPE+ group. Multivariate logistic regression analysis revealed that increased norepinephrine levels were predictive of NPE (OR, 1.002; 95% CI, 1.001-1.004), but epinephrine levels were not. Linear regression analysis showed that plasma epinephrine and norepinephrine levels were positively correlated. Receiver operating characteristic (ROC) curves showed that threshold values predictive of NPE existed for both catecholamines, and sensitivity/specificity was higher for norepinephrine. After quadrichotomization of patients based on the results of ROC curves, patients whose plasma epinephrine/norepinephrine levels exceeded the threshold values were significantly more likely to experience NPE. Conclusions: Norepinephrine rather than epinephrine appears to play a more active role in pathogenesis of SAH-induced NPE, although both catecholamines may be involved. Since the number of SAH patients complicated by NPE is relatively small, a multi-center study may be required to clarify the issue.

The role of catecholamines in the pathogenesis of neurogenic pulmonary edema associated with subarachnoid hemorrhage

Neurogenic pulmonary edema (NPE) occurs frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been suggested as its principal cause. The objective of this retrospective study is to evaluate the relative contribution of each catecholamine in the pathogenesis of NPE associated with SAH. Records of 63 SAH patients (20 men/43 women) whose plasma catecholamine levels were measured within 48 h of SAH onset were reviewed, and the clinical characteristics and laboratory data of those who developed early-onset NPE were analyzed thoroughly. Seven patients (11 %) were diagnosed with NPE on admission. Demographic comparison revealed that the NPE+ group sustained more severe SAH than the NPE- group. Cardiac dysfunction was also significantly more profound in the former, and the great majority of the NPE+ group sustained concomitant cardiac wall motion abnormality. There was no significant difference in the plasma epinephrine levels between NPE+ and NPE- group (324.6 ± 172.8 vs 163.1 ± 257.2 pg/ml, p = 0.11). By contrast, plasma norepinephrine levels were significantly higher in the NPE+ group (2977.6 ± 2034.5 vs 847.9 ± 535.6 pg/ml, p < 0.001). Multivariate regression analysis revealed that increased norepinephrine levels were associated with NPE (OR, 1.003; 95 % CI, 1.002-1.007). Plasma epinephrine and norepinephrine levels were positively correlated (R = 0.48, p < 0.001). According to receiver operating characteristic curve analysis, the threshold value for plasma norepinephrine predictive of NPE was 2,000 pg/ml, with an area under the curve value of 0.85. Elevated plasma norepinephrine may have more active role in the pathogenesis of SAH-induced NPE compared with epinephrine, although both catecholamines may be involved via multiple signaling pathways.

Postictal pulmonary edema requires pulmonary vascular pressure increases.

The pathogenesis of neurogenic pulmonary edema has been debated for many years. Whether cardiogenic mechanisms and increased pulmonary vascular pressures are primary or even necessary for the production of pulmonary edema has been argued. We used postictal pulmonary edema to study this problem in a sheep model of neurogenic pulmonary edema with bicucullin-induced status epilepticus. Seizure-induced increases in pulmonary vascular pressures were averted with a reservoir system to maintain left atrial pressure (LAP) and pulmonary artery pressure (PAP) at preseizure levels. No increase in lung lymph flow occurred during seizures, in contrast to the doubling of lung lymph flow that occurred during seizures when ictal pulmonary vascular hypertension was not blocked. These data support a primary role of pulmonary vascular pressure increases in the production of neurogenic pulmonary edema.

Neurogenic Pulmonary Edema

Neurogenic pulmonary edema is an anomaly because it cannot be categorized into either of the two major types of pulmonary edema. Both high-pressure and increased-permeability abnormalities may be involved in the pathogenesis of neurogenic pulmonary edema. Furthermore, the mechanisms responsible for these abnormalities appear quite complex. The high-pressure insult appears to be a function of systemic hypertension, pulmonary venoconstriction, negative and positive inotropic factors, and intrinsic myocardial function. Mediators of the pulmonary endothelial permeability defect have not been defined. Although the high-pressure and increased-permeability abnormalities seem to develop through separate mechanisms, their combined effect is probably synergistic on the accumulation of extravascular lung water. The neurologic pathways responsible for initiating neurogenic pulmonary edema remains a mystery. Despite the questions and uncertainties still surrounding neurogenic pulmonary edema, the substantial progress made in understanding the clinical expression, incidence, and pathogenesis of this syndrome does provide a framework for a reasonable approach to its clinical management.

Experimental neurogenic pulmonary edema in cats.

Hemorrhagic pulmonary edema was produced consistently in 19 of 20 anesthetized, paralyzed, ventilated cats when intracranial pressure (ICP) was raised for 30 minutes by intraventricular infusion of mock CSF to 150 mm Hg in 14, or 200 mm Hg in six. However, under identical conditions, except that ICP was raised to only 100 mm Hg, three of seven animals did not develop hemorrhagic edema of the lungs and the remaining four had spotty hemorrhage. Thirteen control animals with normal ICP had normal lungs. Gravimetric lung water analysis by Pearce's method confirmed gross and microscopic appearance of hemorrhagic pulmonary edema. Extravascular lung water (p less than 0.05) and lung blood (p less than 0.05) were significantly greater than control values when ICP was raised to or exceeded 150 mm Hg. Despite hemorrhagic edema, pulmonary gas exchange (O2, CO2) remained unaffected. This animal model allows quantitative measurement of neurogenically-mediated hemorrhagic edema of the lungs before gas exchange is impaired. The model may facilitate clarification of the pathogenesis of neurogenic pulmonary edema and, consequently, refine evaluation of therapy.