Brain Natriuretic Peptide (BNP), also known as B-type Natriuretic Peptide, is another member of the natriuretic peptide system after ANP, which was first isolated from porcine brain by Sudoh et al. in 1988. BNP has important pathophysiological implications, as it can promote sodium excretion and urination, has strong diastolic effects, and can counteract the vasoconstrictive effects of the renin-angiotensin-aldosterone system (RAAS), and is a major endocrine system, like ANP, in the body to counteract volume overload and hypertension. Cardiac dysfunction can greatly activate the natriuretic peptide system, and increased ventricular load leads to BNP release. 1.1 Structure, synthesis and secretion of BNP: BNP, like ANP, has a ring structure consisting of 17 amino acids through a pair of disulfide bonds, which is necessary for receptor binding, and the disulfide bond is important for the biological activity of BNP. The human BNP gene fragment is located at the distal end of the short arm of chromosome 1 and is linked to its upstream ANP fragment, whose reverse transcribed deoxyribonucleic acid (cDNA) consists of 1900 nucleotides, and the messenger ribonucleic acid (mRNA) of BNP consists of 900-1000 nucleotides, which can be expressed as BNP precursor pro, and the signal peptide at the N-terminal end is removed to become the BNP precursor containing BNP precursor (proBNP) containing 108 amino acids is not stored in the secretory granules, but is mainly secreted from the ventricles and is broken down into biologically active BNP (C-terminal fragment containing 32 amino acids) and N-terminal fragment (NT-BNP, as shown in the figure) during its secretion or into the blood. Left ventricular extension and ventricular wall tension regulate the release of BNP basally. 1.2 Distribution, receptors and degradation of BNP: BNP is widely distributed in brain, spinal cord, heart and lung tissues, with the highest content in heart. BNP content in the brain is the highest in the medulla oblongata, and BNP content in the central nervous system is higher than that in ANP, and BNP content in the brain and spinal cord is about 13 times higher than that in ANP. The BNP content in the heart is mainly found in the left and right atria, with the right atrium containing more than three times that of the left atrium, while the BNP content in the ventricle is less than 1/20 of that in the atrium. The septum, atrioventricular valve, aorta, hepatic artery and pulmonary vein also contain small amounts of BNP. The natriuretic peptide system has three types of receptors, A, B and C, all of which are transmembrane receptors. BNP is cleared by two main pathways: first, endocytosis of BNP into the cytosol mediated by C receptors and then degradation by lysosomal enzymes; second, degradation of BNP by neutral peptide chain endonucleases, which are more concentrated in the lung and kidney. The affinity of ANP for neutral peptide chain endonuclease is much greater than that of BNP, but the second pathway is still the main pathway of BNP metabolism, and the affinity of C receptor for ANP is also higher than that of BNP, which results in a longer biological half-life of BNP (20 min) than that of ANP (about 3 min). 1.3 BNP determination: The determination of plasma BNP concentration can provide many useful clinical information, and the commonly used methods are: radioimmunoassay (IRA), immunoradiometric assay (IRMA), electrochemiluminescence assay (ECLA). This assay system uses two anti-human BNP monoclonal antibodies, one recognizing the C-terminal sequence of BNP and the other recognizing its ring structure, which means that the plasma BNP concentration can be measured by the sandwich method with a minimum measurement of 2 pg/ml and inter- and intra-batch coefficients of variation (CV) of 5.9% and 5.3%, respectively, which is more sensitive, accurate and easy to operate. This method is more sensitive, accurate and easy to operate, while ECLA is more sensitive and accurate, with inter- and intra-batch coefficients of variation (CV) of only 5.8% and 3%, but it is costly. Recently, BNP rapid test and enzyme immunoassay (ELISA) for POCT have been used in clinical practice, which are fast, easy and inexpensive. 2.1 Cardiovascular effects of BNP and clinical applications 2.1 Cardiovascular effects of BNP: BNP and ANP are both natural antagonists of renin-angiotensin-aldosterone system (RAAS), and also resist the sodium and water retention and hypertension effects of posterior lobe pressor and sympathetic nerve. BNP and ANP together participate in the regulation of blood pressure, blood volume and water-salt balance, increase glomerular filtration rate, sodium and diuresis, dilate blood vessels, and reduce the vascularity of body circulation. BNP is different from ANP in that it is mainly synthesized in the atria, and its secretion increases when the atria are overloaded or dilated, and its plasma concentration rises, mainly reflecting changes in pulmonary vascular pressure. BNP is mainly synthesized in the ventricle and increases when the ventricle is overloaded or dilated; therefore, it is more sensitive and specific to reflect changes in ventricular function because BNP precursors are not stored in the secretory granules and the rapid regulation of BNP synthesis and secretion is performed at the level of gene expression. 2.2 Diagnostic value of BNP on cardiac function: Heart failure is the end stage of many diseases, and heart failure can be divided into acute heart failure and chronic heart failure (CHF), and CHF is classified into grade I, II, III and IV according to the New York Heart Association (NYHA) cardiac function classification. Class I heart function is actually without clinical heart failure symptoms and can be referred to as left ventricular dysfunction (LVD). Symptoms in chronic heart failure with acute decompensation are similar to those in acute heart failure. The reliability of clinical diagnosis of heart failure is poor, especially in primary care settings. Cardiac ultrasound is the most useful and reliable non-invasive method of diagnosing cardiac insufficiency. There are 120,000 new cases of suspected heart failure in the UK each year. It is difficult to diagnose such a large number of patients with cardiac ultrasound. Based on the close relationship between BNP and cardiac function, much work has been done by many researchers to explore its clinical application. The importance of BNP in the pathophysiological changes and diagnosis of CHF has been confirmed. Mukoyama et al. reported that plasma BNP concentration was higher than normal in patients with CHF and was proportional to the severity of heart failure. Comparing cardiac and plasma BNP levels between normal and CHF groups, it was found that ventricular BNP levels were 7.2% of the atria and 30% of the whole heart in normal subjects, and rose to 22% and 52% in CHF patients, respectively. plasma BNP concentration in normal subjects was about 0.9± 0.07fmol/ml, BNP/ANP value is about 0.16±0.02, while BNP concentration in patients with different degrees of CHF (NYHA classification I~IV): grade I is about 14.3±1.8fmol/ml; grade II is about 68.9±37.9fmol/ml; grade III is about 155.4±39.1fmol/ml; grade IV is about 267.3± Plasma BNP/ANP values were 1.44 and 1.72 in class III and IV patients, respectively, with BNP increasing 200-300 times more than normal and ANP only 20-30 times, thus suggesting that increased ventricular synthesis and secretion of BNP in CHF patients is partly responsible for the elevated plasma BNP, which increases with the severity of heart failure.Selvais et al. concluded that BNP is superior to ANP in the diagnosis of CHF and its severity. They compared ANP and BNP concentrations in normal subjects, coronary artery disease patients with normal left ventricular ejection fraction (LVEF), and patients with different degrees of CHF and found that BNP concentrations in severe heart failure (NYHA class III-IV) (205±143 pg/ml) were significantly higher than those in mild heart failure (NYHA~II) (51±28pg/ml) (p<0.001), BNP was better than ANP in distinguishing CHF from normal subjects and coronary patients with normal LVEF (p<0.01), and the correlation between BNP concentration and LVEF was better than ANP (rBNP=-0.59, rANP=-0.30, p<0.05), and stronger than ANP in determining the degree of CHF (p<0.05), suggesting that BNP can be used for the diagnosis of outpatients with cardiovascular disease. Current clinical studies on BNP have focused on left ventricular dysfunction (LVD), where left ventricular function refers to systolic function. In both normal and LVD patients, BNP is mainly synthesized and secreted by left ventricular cardiomyocytes, and enters the small vein to return to the septal vein and enter the circulation through the coronary sinus, and its secretion is mainly regulated by the tension of the left ventricular wall. At present, moderate and severe LVD are easier to diagnose based on clinical examination, while mild LVD (NYHA class I) is difficult to do, but it is important for the confirmation of LVD diagnosis, especially for those patients who recovered from myocardial infarction, plasma BNP, ANP and other peptide hormones and cGMP concentrations measured at rest or 3 minutes after exercise are higher than normal controls, but only BNP has a statistically significant The area under the curve was 0.70 and 0.75 at rest and after exercise, respectively, and the ability to discriminate normal from LVD was significantly better than that of ANP and cGMP, and it was the best marker of LVD by the natriuretic peptide system. They screened patients with LVD and CHF by radionuclide gated cardiac blood pool imaging, and selected healthy individuals with normal cardiac function as controls. were significantly higher than those in the control group (39.06±18.20ng/L and 422.06±255.38ng/L, respectively, p<0.05 and p>0.001), but significantly lower than those in the CHF group (150.90±83.66ng/L and 4020.43±2090.95ng/L, respectively, p<0.05 and p>0.001); plasma BNP >75.00ng/L had a sensitivity of 91% and specificity of 94% for the diagnosis of LVD; plasma N-ANP >923.00ng/L had a sensitivity of 75% and specificity of 94% for the diagnosis of LVD, and it was considered that BNP and N-ANP could be used to diagnose LVD, and BNP >75.00ng/L and N-ANP >923.00ng/L were suitable as diagnostic indicators. L as a diagnostic index-like fit. There is a growing body of literature supporting the determination of BNP after myocardial infarction (MI), which not only identifies the presence or absence of left ventricular systolic insufficiency, but also may be superior to cardiac ultrasound in determining the risk of left ventricular remodeling and death. In clinical practice, BNP also helps to distinguish shortness of breath due to heart failure from other causes of shortness of breath. A normal BNP can almost always exclude shortness of breath due to left heart insufficiency. 2.3 The role of BNP in assessing the prognosis of heart disease: The traditional long-term monitoring of patients with heart failure is very imperfect. It would be advantageous to have an inexpensive biochemical marker to monitor heart failure. is BNP such a marker? If a bedside BNP test were available, it would be possible to monitor heart failure patients in the same way as diabetic patients. This is an area where BNP has great potential. Tsutamoto et al. compared BNP with ANP and cGMP in the prognostic assessment of CHF in 85 patients with CHF (EF <45%) followed for two years and found that plasma BNP was superior to ANP and cGMP in estimating morbidity and mortality in patients with chronic CHF and that the prognostic information provided was not dependent on other hemodynamic The prognostic information provided is not dependent on other hemodynamic parameters such as PCWP and LVEF. In the elderly population, elevated plasma BNP concentrations are significantly associated with morbidity and mortality in the entire population, and mortality can be predicted by measuring plasma BNP regardless of definite cardiovascular disease. Plasma BNP levels are positively correlated with the degree of LVD after AMI, and studies have demonstrated that the increased secretion of BNP is mainly concentrated in the marginal area at the junction of the infarct and non-infarct regions, where the mechanical tension of the ventricular wall is greatest, so BNP can accurately reflect changes in local ventricular wall tension in the infarct, which is influenced by the infarct size, altered left ventricular morphology, and myocardial mechanical stress, and so on, in patients after myocardial infarction. Measurement of plasma BNP can predict both infarct size and left ventricular function. Several reports have suggested that plasma BNP measurement is a simple, accurate, and useful biochemical index for predicting the progression of left ventricular remodeling after myocardial infarction, and because left ventricular remodeling is not easily detected by clinical manifestations or echocardiography, BNP measurement is a valuable and good screening method for risk classification after myocardial infarction. Cowei concluded that BNP is an important marker of prognosis in heart failure patients, and theoretically, plasma BNP concentration and survival are closely related. Preliminary results from a large population-based heart failure survey suggest that plasma BNP and NT-BNP concentrations are associated with survival and rehospitalization. Adapting angiotensin-converting enzyme inhibitor therapy with a series of BNP tests better inhibits the renin-angiotensin-aldosterone system and reduces mortality compared with empirical therapy. 2.4 Role of BNP in the treatment of LVD: BNP has clinical application because of its natriuretic, diuretic, and vasodilatory effects and antagonistic effect with activation of the renin-angiotensin-aldosterone system. In some studies, BNP was injected into normal subjects and patients with congestive heart failure, and it was found that BNP reduced PCWP, systemic vascular resistance and increased per beat volume, thus reducing cardiac preload and afterload and increasing cardiac output: it also increased urine volume, sodium and chloride excretion, and reduced plasma aldosterone concentration, suggesting that BNP input to heart failure patients can improve left ventricular function through its diastolic effect, especially its natriuretic effect. Hopbbs et al. administered different doses of synthetic BNP (0.3, 1, 3, 10 and 15ug/kg) as intravenous drug alone to heart failure patients and found that doses of 10 and 15ug/kg significantly reduced PCWP (-73%, p<0.001), mean pulmonary artery pressure (-41%, p<0.001), mean atrial pressure (-28%, p<0.001), and mean atrial pressure (-28%, p<0.001). (-28%, p<0.001), systemic vascular resistance (-53%, p<0.001), and significant increases in cardiac index (68%, p<0.001) and stroke volume (72%, p<0.001), suggesting that BNP may improve cardiac function when used as a single intravenous agent in patients with heart failure, but further studies are needed to determine whether long-term use in patients with CHF is beneficial. In addition, given that BNP is a neuropeptide mainly found in the central nervous system, it may also have some effects on the nervous system, such as the effect on pain. The relationship between BNP and hemodynamic alterations has been widely recognized. BNP plasma concentration is closely related to cardiac function status, and normal BNP concentration can negate the existence of impaired cardiac function to a great extent. A large number of studies have shown that BNP can be used to diagnose LVD caused by a variety of diseases, however, due to different laboratory conditions, different methods of measurement and different research methods, the normal values obtained vary and need to be improved. Moreover, it should be noted that BNP is not a specific diagnostic tool, because elevated plasma BNP concentrations are not necessarily caused by heart failure; some cardiopulmonary diseases, renal failure, and cirrhosis can also increase plasma BNP concentrations, and should be differentiated by clinical data. Despite the limitations, BNP has shown good promise for diagnosing cardiac function, determining prognosis, and guiding treatment. In particular, it has shown significant superiority in screening for LVD and in the evaluation of risk after myocardial infarction. In future applications, strict testing and judgment criteria need to be developed. In conclusion, with further studies, plasma BNP concentration measurement is likely to become a simple and easy routine test as an important supplement to assess cardiac function.