Determinação do Tecido Cicatricial do Miocárdio no Fenômeno de Fluxo Coronário Lento e a Relação entre a Quantidade de Tecido Cicatricial e o Nt-ProBNP / Determination of Myocardial Scar Tissue in Coronary Slow Flow Phenomenon and The Relationship Between Amount of Scar Tissue and Nt-ProBNP

Resumo Fundamento A fisiopatologia e o prognóstico não estão claramente determinados nos pacientes com fenômeno do fluxo coronário lento (FCL). Esses pacientes apresentam várias condições clínicas, que variam desde quadro assintomático até internação hospitalar com morte cardíaca súbita. Objetivos Nosso objetivo foi avaliar os achados da ressonância magnética cardíaca (RMC) com o realce tardio pelo gadolínio (RTG), como um indicador de fibrose miocárdica. Também buscamos determinar a relação entre a presença de fibrose miocárdica e os níveis de NT-proBNP em pacientes com FCL na artéria coronária descendente anterior esquerda (DAE). Métodos Ao todo, 35 pacientes, entre 31 e 75 anos de idade, foram incluídos. Os pacientes estudados (n=19) apresentaram artérias coronárias epicárdicas normais na angiografia, mas tinham FCL na DAE. O grupo controle de pacientes (n=16) apresentou artérias coronárias epicárdicas normais e níveis de escore TIMI normais na angiografia. Em ambos os grupos, os pacientes foram examinados com RMC para a detecção de presença de fibrose miocárdica. Além disso, níveis plasmáticos de NT-proBNP foram medidos. Valores de p < 0,05 foram considerados significativos. Resultados A taxa de fibrose miocárdica foi significativamente maior na RMC para os pacientes com FCL (p=0.018). Uma quantidade variável de tecido cicatricial foi detectada no ápice ventricular esquerdo em 7 pacientes e nas regiões inferior e inferolateral em 3 pacientes. Não foram observadas diferenças nos níveis de NT-proBNP nos pacientes com FCL. Entretanto, os níveis de NT-proBNP foram maiores nos pacientes com FCL, que apresentaram fibrose miocárdica na RMC (p=0.022). Conclusões Em suma, o RTG na RMC mostrou que a cicatriz miocárdica isquêmica pode estar presente nos pacientes com FCL. Esses resultados indicam que o FCL pode nem sempre ser inofensivo. (Arq Bras Cardiol. 2020; 114(3):540-551)

Abstract Background Pathophysiology and prognosis are not clearly determined in patients with the coronary slow flow phenomenon (CSFP). These patients present with various clinical conditions ranging from being asymptomatic to being admitted with sudden cardiac death. Objectives We aimed at assessing the findings of late gadolinium enhancement (LGE) in cardiac magnetic resonance imaging (CMR) as an indicator of myocardial fibrosis. We also aimed at determining the relationship between the presence of myocardial fibrosis and NT-proBNP levels in patients with CSFP in the left anterior descending coronary artery (LAD). Methods A total of 35 patients were enrolled within an age range of 31-75. The study patients (n=19) had normal epicardial coronary arteries at angiography, but they presented with CSFP in the LAD. The control group patients (n=16) had normal epicardial coronary arteries and TIMI scores at normal levels in angiography. In both groups, the patients were examined with CMR for the presence of myocardial fibrosis. In addition, plasma NT-proBNP levels were measured. A p-value < 0.05 was considered significant. Results The rate of myocardial fibrosis was significantly higher in CMR in the patients with CSFP (p=0.018). A variable amount of myocardial scar tissue was detected at the left ventricular apex in 7 patients and at the inferior and inferolateral regions in 3 patients. There was no difference in the level of NT-proBNP in patients with CSFP. However, the NT-proBNP levels were higher in patients with CSFP, who had scar tissue in CMR (p=0.022). Conclusions In conclusion, LGE in CMR showed that ischemic myocardial scarring may exist in patients with CSFP. These results indicate that CSFP may not always be innocent. (Arq Bras Cardiol. 2020; 114(3):540-551)

Effect of C-typenatriuretic peptide on paraquat-induced pulmonary fibrosis in mice / 中华麻醉学杂志

Objective To evaluate the effect of C-type natriuretic peptide (CNP) on paraquat-induced pulmonary fibrosis in mice.Methods Fifty-four male Kunming mice,aged 8-10 weeks,weighing 30-35 g,were randomly divided into 3 groups (n=18 each) using a random number table:control group (C group),pulmonary fibrosis group (PF group) and CNP group.Paraquat 10 mg/kg (in 0.1 ml of normal saline) was injected intraperitoneally once every 3 days for 5 times in total in PF and CNP groups,and in addition CNP 3 μg/kg (in 0.1 ml of normal saline) was simultaneously injected via the tail vein once every 2 days for 14 times in total in group CNP.The equal volume of normal saline was given instead of paraquat in group C.On days 1,8 and 15 after the end of administation of paraquat,6 mice were sacrificed,and lungs were removed for determination of wet to dry weight ratio (W/D ratio),hydroxyproline (HYP) content (using alkaline hydrolysis),and transforming growth factor-beta 1 (TGF-β1) content (using enzymelinked immunosorbent assay) in lung tissues.Results Compared with group C,the W/D ratio and contents of HYP and TGF-β1 in lung tissues were significantly increased at each time point after the end of administation of paraquat (P＜0.05),and the pulmonary fibrosis was obvious in group PF.Compared with group PF,the W/D ratio and contents of HYP and TGF-β1 in lung tissues were significantly decreased at each time point after the end of administation of paraquat (P＜0.05),and the pulmonary fibrosis was significantly attenuated in group CNP.Conclusion CNP can reduce paraquat-induced pulmonary fibrosis in mice.

Effect of combined treatment with GnRHa and GH on linear growth in mid-and late pubertal girls at great bone ages with CPP or EFP and rela-tion to CNP signaling pathway / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the effect of combined treatment with gonadotropin-releasing hormone analogue ( GnRHa) and growth hormone ( GH) on the linear growth in mid-and late pubertal girls at great bone ages with central precocious puberty ( CPP) or early and fast puberty ( EFP) , and to determine the relation between C-type natriuretic pep-tide ( CNP) signaling pathway and the accelerative effect of GH on long bone growth in these girls.METHODS:Twenty-two girls were diagnosed as CPP or EFP, whose bone ages were older than 11.5 years with impaired predicted adult height ( PAH) , and divided into GnRHa treatment group ( treated with GnRHa alone, slow-release of triptorelin 60~80 μg/kg every 4 weeks, im) and combined treatment group ( treated with GnRHa and GH, 1 U/kg GH every week for 6~7 times, sc) .The height, weight and pubertal stage were determined every 3 months.At the beginning and after 6 months of the treatment, the bone age was evaluated and the serum concentrations of amino-terminal pro-C-type natriuretic peptide ( NT-proCNP), insulin-like growth factor 1 (IGF-1) and procollagen type 1 amino-terminal propeptide (P1NP) were measured. Height velocity ( HV) , height SD score for bone age ( HtSDSBA ) , PAH and the serum indexes mentioned above were com-pared at the beginning and the end of the treatment.RESULTS: After 6 months of the treatment, HV, ΔHtSDSBA andΔPAH of the girls treated with GnRHa +GH were statistically higher than those of the girls given GnRHa alone ( P <0.01).Serum concentrations of NTproCNP, P1NP and IGF-1 were not significantly different between the beginning and the end of the 6-month combined treatment.The girls treated with GnRHa alone showed a significant decrease in both serum NTproCNP and P1NP levels (P<0.05) and no significant change of serum IGF-1 level after 6 months of the treatment. CONCLUSION:In the CPP or EFP girls who are in mid-and late puberty and at great bone ages, the combined treatment with GnRHa and GH may accelerate linear growth and improve predicted adult height.This effect of GH is not attributed to the change of serum IGF-1 level, and may be related in part to the acceleration of CNP-mediated long bone growth.

The influence of trimetazidine(TMZ) on the cardiac function and neurohormonal of heart failure model in rats / 中国基层医药

Objective To observe the effects of trimetazidine (TMZ) on the cardiac function and neurohormonal of heart failure model in rats.Methods Partially banding abdominal aortic artery to achieve congestive heart failure rats model.Interventricular septum thickness(IVST),left ventricular posterior wall thickness(LVPWT),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter (LVESD),left ventricular ejection fraction(LVEF) and shortening fraction(FS) were measured by echocardiogram,Pathological changes of myocardial cells was observed,B-type natriuretic peptide (BNP)、C-type natriuretic peptide receptor (NPRC),atrial natriuretic peptide (ANP),myosin heavy chain (β-MHC) and angiotensinl (AT1) were measured by Real-Time PCR,superoxide dismutase (SOD) was measured by immunohistochemistry method.Results Trimetazidine treatment of the high-dose group and the model group compare IVST LVPWT,LVESD,LVEDD were (0.63 ± 0.05) mn,(0.73 ± 0.06) mm,(0.73 ±0.05)mm,(0.87 ±0.06)mm and (1.07 ±0.06)mm,(1.13 ±0.06) mm,(0.93 ±0.06)mm,(1.33 ±0.06) mm,was significantly reduced (P ＜ 0.05),LVEF,FS increased to (27.75 ± 1.83) ％,(11.44 ± 0.76) ％ and (11.78 ±0.56)％,(4.27 ± 0.22)％ (P ＜ 0.01),Myocardial cell structure were remarkably improved.The expression of BNP,ANP,NPRC,ATI,β-MHC were remarkably decreased.The expression of SOD was elevated.Conclusion TMZ treatment group can improve the secretion of neurohormonal of heart failure model in rats,and also obviously improve the cardiac contractility.

C-Type Natriuretic Peptide as a Surrogate Marker in Variant Angina Pectoris

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the value of C-type natriuretic peptide (CNP) as a surrogate marker for detection of coronary artery spasm in variant angina pectoris (VAP). SUBJECTS AND METHODS: Sixty-six patients (mean age: 51+/-11 years, M : F=40 : 26) who underwent coronary angiography on suspicion of angina and who were diagnosed with VAP by the acetylcholine-induced spasm provocation test (SPT) were enrolled and divided into a SPT (-) group (n=23) and a SPT (+) group (n=43). Concentrations of CNP and other markers were determined by immunoassay in both groups. RESULTS: Plasma CNP and creatine kinase myoglobin band (CK-MB) concentrations were significantly increased in the SPT (+) group relative to the SPT (-) group (CNP, 5.268+/-1.800 pg/mL vs. 3.342+/-1.150 pg/mL, p=0.002; CK-MB, 2.54+/-1.03 ng/dL vs. 1.86+/-0.96 ng/dL, p=0.019, respectively) while plasma high sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT pro-BNP) concentrations were not significantly different between the SPT (-) group and SPT (+) group (hs-CRP, 2.76+/-4.99 mg/L vs. 3.13+/-4.88 mg/L, p=0.789; NT pro-BNP, 49+/-47 pg/mL vs. 57+/-63 pg/mL, p=0.818, respectively). Plasma CNP concentration was independently associated with the VAP via SPT {odds ratio: 2.014 (95% confidence interval: 1.016-3.992), p=0.045}. A CNP cut-off value of 4.096 pg/mL was found to have a sensitivity of 68.2% and a specificity of 40.0% for predicting the probability of VAP via SPT. CONCLUSION: Increased plasma CNP concentration in patients with VAP may have an impact on the regulation of endothelial function in accordance with the progression of atherosclerosis. Further analysis is warranted to develop clinical applications of this finding.

C-type natriuretic peptide and long bone growth / 国际儿科学杂志

C-type natriuretic peptide (CNP) is an important local regulator of long bone growth. It catalyzes the synthesis of cGMP after binding to its receptor natriuretic peptide receptor-B (NPR-B) ,and regulates long bone growth by activating downstream factors. Though the mechanism of the regulation of CNP signaling remains unclear, it has been demonstrated that CNP signaling has a "cross-talk" with the fibroblast growth factor receptor 3 pathway in cartilate.Heterozygous NPR-B mutations maybe one of the molecular basis of idiopathic short stature. CNP can be used as a biological marker of linear growth, with great importance in growth monitoring, diagnosis and treatment of growth disorders.The research on the mechanism of CNP signaling system in endochondral ossification will contribute to a new medication for bone development disorders in the future.

Clinical investigation of plasma adrenomedullin and C-type natriuretic peptide in the elderly hypertension / 中国基层医药

Objective To investigate the changes of plasma adrenomedullin(ADM) and C-type natriuretic peptide(CNP) levels with elderly hypertension(HPE).Methods The plasma levels of ADM and CNP were measured by radioimmunoassay in 136 cases of the HPE(group A) compared with that of in 40 cases healthy elders(group B).Results The plasma levelsof ADM and CNP increased significantly in group A compared with group B(P

C type natriuretic peptide in femoral atery stenosis in diabetic rabbit models / 中国介入心脏病学杂志

Objective To observe the changes in plasma C type natriuretic peptide(CNP) and C reaction protein(CRP) levels and the preventive effect of exogenous CNP on vascular stenosis in a diabetic rabbit model after femoral artery injury.Methods After setting up an animal model of diabetes,the rabbits were divided into the control group(n=8),artery injury group(n=8) and CNP treatment group(n=8).Enzyme-linked immunosorbent assay was used in determination of plasma CRP and CNP concentration.Histological changes in the femoral artery wall were evaluated by HE staining to determine the degree of stenosis.Results The post operative CRP concentration of the artery injury group compared with CNP treatment group was 13.81?4.30 ?g/mL vs 8.43?0.61 ?g/mL(P

Effect of basic fibroblast growth factor on synthesis of C-type natriuretic peptide in cultured human umbilical vein endothelial cells / 中国病理生理杂志

AIM: To investigate the effect of basic fibroblast growth factor (bFGF) on C-type natriuretic peptide (CNP) production, release and mRNA expression. METHODS: Human endothelial cell cultured; CNP was measured by radioimmunoassay method;CNP mRNA expression was determined by RT-PCR technique. RESULTS: bFGF could augment CNP synthesis in human endothelial cells. Compared with control group,25 ng, 50 ng, 100 ng bFGF increased CNP contents in endothelial cells by 88% (P