Expression of atrial natriuretic polypeptide in ventricles of heart with hypertrophic cardiomyopathy: an immunohistochemical study of endomyocardial specimens]

To investigate the ventricular expression of atrial natriuretic polypeptide (ANP) in human hypertrophic heart, we conducted an immunohistochemical study using endomyocardial biopsy specimens obtained from the right side of the interventricular septum (RVB), left ventricular free wall (LVB), or both of 39 patients with hypertrophic cardiomyopathy (HCM), and 9 control subjects without hypertrophy. No HCM patients had apparent congestive heart failure. ANP was not present in control subjects' RVB or LVB specimens, but was found in HCM patients', showing its characteristic distribution patterns (RVB > LVB, p < 0.05); it was present in 15 of 36 RVB (42%) and 2 of 25 LVB (8%). No clinical data, including echocardiographic, hemodynamic and angiographic data, were directly related to ventricular ANP expression in HCM. According to histological data, however, ANP-present RVB specimens of HCM had larger myocytes, severer fibrosis and myofiber disarray than the specimens without ANP. This indicates that a failing state may not be a prerequisite for ANP expression in human hypertrophic ventricles, but that ventricular ANP expression may occur concomitantly with myocyte hypertrophy as an adaptive response to focal stress due to "histological overloads" such as disarray and fibrosis in HCM, which may be reflected in the characteristic distribution patterns of intraventricular ANP.     

Appearance of atrial natriuretic peptide in the ventricles in patients with myocardial infarction

To study whether atrial natriuretic peptide (ANP) is present in the ventricles in patients with myocardial infarction, we have examined ventricular tissues from five patients with myocardial infarction and five control subjects without cardiovascular diseases by the indirect immunoperoxidase method using monoclonal antibody to alpha-human ANP. Immunoreactivity for ANP was observed in the subendocardial cardiac cells of infarcted as well as noninfarcted segments of the left ventricles in all patients with myocardial infarction. In a case of biventricular infarcts, the subendocardial cardiac cells of the right ventricle were also stained. In a case of ventricular aneurysm, the viable hypertrophied cardiac cells were immunoreactive for ANP throughout the wall of the aneurysm. Immunoreactivity for ANP, however, was not detected in the working ventricular cardiac cells in any of the control subjects. Because ANP improves left ventricular function by reducing both preload and afterload, the appearance of ANP in the ventricles in patients with myocardial infarction may be one of the manifestations of the compensatory mechanism.     

Coronary aneurysm and silent myocardial infarction in an adolescent secondary to undiagnosed childhood Kawasaki disease

The majority of coronary artery aneurysms in young adults and children are caused by Kawasaki disease. A case of undiagnosed childhood Kawasaki disease presenting as silent myocardial infarction during adolescence, which was successfully treated with coronary artery bypass grafting, is described. The present case is followed by a review of the literature.     

Clinicopathologic study of abnormal Q waves in Kawasaki disease (mucocutaneous lymph node syndrome): An infantile cardiac disease with myocarditis and myocardial infarction

A correlative study of abnormal Q waves and pathologic findings was performed on 15 hearts from children with Kawasaki disease. Gross pathologic study revealed acute angiitis with pericarditis, acute myocarditis and coronary heart disease as the result of angiitis.Three hearts in infants with abnormal Q waves in leads I and aVL and chest leads had gross transmural fibrosis in the anteroseptal-lateral walls of the left ventricle. Coagulation necrosis (acute myocardial infarction) or fibrosis, or both, in more than 30 percent of the wall thickness in the posterior ventricular wall was found in four of five hearts in infants with abnormal Q waves in leads II, III and aVF. Seven of the 15 infants had no abnormal Q waves, and only 2 of the 7 had myocardial damage in over 30 percent of the wall thickness.In 9 of the 15 hearts there were 11 gross areas of fibrosis; in these hearts there was a corresponding severe stenosis of more than 90 percent due to organization in the major coronary arteries supplying these areas. In three hearts with coagulation necrosis, the coronary occlusion was caused by fresh large thrombi. In the six hearts without sizable fibrosis, the grade of stenosis due to organization was less than 75 percent in each of the major coronary arteries.Coronary aneurysm due to angiitis was seen in 12 of the 15 hearts, and at autopsy fresh large thrombi were seen in each aneurysm. Ten of the 12 hearts exhibited sizable areas of myocardial damage. Three hearts without aneurysm manifested angiitis with mild stenosis of less than 25 percent, but there were no macroscopic fresh thrombi in any of the major coronary arteries.Thus, abnormal Q waves in children with Kawasaki disease almost always reflect myocardial damage in over 30 percent of the wall thickness of the left ventricle. Electrocardiograms are useful to determine the anterior or posterior localization of the damage. Nevertheless, the possibility of transmural and nontransmural areas of damage cannot be excluded in the absence of abnormal Q waves.     

慢性心力衰竭患者心钠素水平及与心功能关系的观察

目的探讨心钠素(ANP)在慢性心力衰竭发生与发展过程中的意义及与心功能的关系。方法选择35例慢性心力衰竭患者和32例正常对照,采用放射免疫法测定其血浆ANP水平,应用彩色多普勒超声心动图测定左心室收缩末期内径(LVSd)、左心室舒张末期内径(LNDd)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)及心动周期中二尖瓣舒张晚期心室充盈峰速度(A)与二尖瓣舒张早期心室充盈峰速度(E)的比值(A／E),观察ANP水平与心功能之间的关系。结果心力衰竭患者血浆ANP水平比健康对照组明显升高(P<0．001),且随着心功能程度的不断加重,ANP水平逐渐升高．依次为心功能Ⅱ级<心功能Ⅲ级<心功能Ⅳ级(P<0．05-0．001)。ANP水平与LVEF、LVFS呈负相关,r值分别为0．76(P<0．01)、-0．72(P<0．01);与LVSd、LVDd及A／E呈正相关,r值分别为0．65(P<0．01)、0．79(P<0．01)、0．72(P<0．01)。结论慢性心力衰竭进展中,ANP水平与心力衰竭的严重程度密切相关,能够反映不同的心功能状态,为慢性心力衰竭的诊断与治疗提供参考依据。     

Plasma atrial natriuretic peptide in patients with acute myocardial infarction: effects of streptokinase

Plasma concentrations of immunoreactive atrial natriuretic peptide (mean (SEM] were measured in 135 patients admitted to two coronary care units with myocardial infarction, ischaemic chest pain, or non-ischaemic chest pain. Concentrations were significantly higher in patients with acute myocardial infarction not treated with systemic thrombolysis (60.4 (14.3) pg/ml) than in patients with non-ischaemic chest pain (21.1 (4.3) pg/ml). Patients with ischaemic chest pain had intermediate values (39.3 (7.1) pg/ml). Patients with acute myocardial infarction treated with intravenous streptokinase had normal concentrations of plasma atrial natriuretic peptide (20.2 (3.6) pg/mg), which were significantly lower than those in patients with myocardial infarction not given streptokinase. These changes could not be explained by factors such as age, pre-existing hypertension, renal dysfunction, or cardiac failure, nor treatment other than streptokinase. Raised plasma concentrations of atrial natriuretic peptide in acute myocardial infarction may be a homoeostatic response acting to reduce atrial pressures by natriuresis, diuresis, and venodilatation. The lower concentrations of atrial natriuretic peptide in patients with acute myocardial infarction treated with streptokinase may reflect a short term beneficial haemodynamic effect of streptokinase.     

Plasma atrial natriuretic peptide in patients with acute myocardial infarction: effects of streptokinase.

Plasma concentrations of immunoreactive atrial natriuretic peptide (mean (SEM] were measured in 135 patients admitted to two coronary care units with myocardial infarction, ischaemic chest pain, or non-ischaemic chest pain. Concentrations were significantly higher in patients with acute myocardial infarction not treated with systemic thrombolysis (60.4 (14.3) pg/ml) than in patients with non-ischaemic chest pain (21.1 (4.3) pg/ml). Patients with ischaemic chest pain had intermediate values (39.3 (7.1) pg/ml). Patients with acute myocardial infarction treated with intravenous streptokinase had normal concentrations of plasma atrial natriuretic peptide (20.2 (3.6) pg/mg), which were significantly lower than those in patients with myocardial infarction not given streptokinase. These changes could not be explained by factors such as age, pre-existing hypertension, renal dysfunction, or cardiac failure, nor treatment other than streptokinase. Raised plasma concentrations of atrial natriuretic peptide in acute myocardial infarction may be a homoeostatic response acting to reduce atrial pressures by natriuresis, diuresis, and venodilatation. The lower concentrations of atrial natriuretic peptide in patients with acute myocardial infarction treated with streptokinase may reflect a short term beneficial haemodynamic effect of streptokinase.     

Association of the ScaI atrial natriuretic peptide gene polymorphism with nonfatal myocardial infarction and extent of coronary artery disease

Background There is growing evidence from recent studies that atrial natriuretic peptide (ANP) plays an important part in coronary blood flow regulation and in atherosclerosis. Transition T2238→C in the atrial natriuretic peptide (ANP) precursor gene, which leads potentially to the translation of ANP with 2 additional arginines, has been suggested to be associated with salt-sensitive hypertension. According to our knowledge, this study is the first to look for the potential association of the ScaI ANP gene polymorphism with the history of nonfatal myocardial infarction and the extent of coronary artery disease (CAD).Methods The study was performed in 847 consecutive, white patients (719 men and 128 women) with significant coronary artery stenosis confirmed by means of elective coronary angiography (at least 1 coronary artery with ≥50% lumen narrowing). Screening for the T2238→C substitution was performed by means of polymerase chain reaction of genomic DNA, followed by ScaI digestion and agarose gel electrophoresis.Results We found a significant association of the A2A2 ScaI ANP genotype with a higher incidence of positive history of nonfatal myocardial infarction (odds ratio 1.85, 95% CI 1.33-2.58) and multiple-vessel CAD (odds ratio 1.45, 95% CI 1.02-2.06). The ScaI ANP genotype distribution did not differ with age, sex, body mass index, plasma lipids, hypertension, diabetes mellitus, and family history of CAD in studied groups.Conclusions Our results suggest that the ScaI ANP polymorphism may be associated with nonfatal myocardial infarction and the extent of CAD. However, the precise mechanism of this association remains to be determined. (Am Heart J 2003;145:125-31.)     

Plasma concentrations of alpha-human atrial natriuretic polypeptide and cyclic GMP in patients with heart disease

Plasma concentrations of immunoreactive alpha-human atrial natriuretic polypeptide (i alpha-hANP) and cyclic guanosine monophosphate (cGMP) were measured in 70 patients with heart disease. Plasma concentrations of i alpha-hANP were directly related to the severity of heart disease (F = 29.61, p less than 0.001). Plasma concentrations of i alpha-hANP were well correlated with pulmonary capillary wedge pressure (PCWP; r = 0.64, p less than 0.001), mean pulmonary arterial pressure (PAP; r = 0.62, p less than 0.001), and mean right atrial pressure (RAP; r = 0.75, p less than 0.001). Plasma concentrations of cGMP were also directly related to the severity of heart disease (F = 13.61, p less than 0.001) and highly correlated with plasma concentrations of i alpha-hANP (r = 0.73, p less than 0.001). Plasma concentrations of cGMP were also closely correlated with PCWP (r = 0.69, p less than 0.001), mean PAP (r = 0.61, p less than 0.001), and mean RAP (r = 0.60, p less than 0.001). The i alpha-hANP concentrations of plasma samples obtained from the coronary sinus were approximately fourfold higher than those of samples obtained from the pulmonary artery, whereas cGMP concentrations were comparable in plasma samples obtained from either site. Elevation of cGMP concentrations following intravenous infusion of synthetic alpha-hANP was comparable in plasma samples obtained from the coronary sinus and the pulmonary artery. These findings suggest that elevated plasma concentrations of i alpha-hANP in cardiac patients result from an increase in the secretion of ANPs, which is probably accelerated by elevation of right or left atrial pressure, and that plasma concentrations of cGMP reflect circulating levels of alpha-hANP.     

Acute and sustained release of the atrial natriuretic factor prohormone N-terminus with acute myocardial infarction

This investigation was designed to determine if acute ischemic cardiac injury causes the release of the 98 amino acid (aa) N-terminus of the 126 aa atrial natriuretic factor prohormone (pro ANF). Seventeen patients with acute myocardial infarction, but without clinical evidence of congestive heart failure, had their circulating concentrations of the whole N-terminus (ie, pro ANF 1-98), the midportion of the N-terminus of the ANF prohormone (consisting of aa 31-67; pro ANF 31-67) and creatine phosphokinase (CPK) monitored daily for 14 days. All seventeen patients had elevated plasma pro ANF 1-98 and pro ANF 31-67 concentrations at the time of presentation. Maximal increase on day three post-infarction correlated with the size of infarction estimated by the maximal CPK (r = 0.675; p less than 0.05) but did not correlate with the amount of left ventricular dysfunction. Another three patients with acute myocardial infarction were treated with tissue plasminogen activator (tPA). The measured pro ANF 1-98 and pro ANF 31-67 levels in these patients were within our normal range and significantly lower (p less than 0.001) than seen in patients with acute myocardial infarction not given thrombolytic therapy. Six patients with unstable angina, likewise, had normal circulating pro ANFs 1-98 and 31-67 concentrations during prolonged episodes of chest pain. These data suggest that myocardial necrosis but not ischemia triggers the release of the entire 126 aa prohormone.     

Influence of exercise on plasma atrial natriuretic factor levels in patients with myocardial infarction

The influence of dynamic exercise on plasma atrial natriuretic factor (ANF) levels was studied in a group of 10 patients with myocardial infarction (MI) and five patients with atypical chest pain (control group). Exercise protocol consisted of three fixed workloads (25, 50, and 75 watts) every 4 minutes with the use of a supine bicycle ergometer. Plasma ANF levels and hemodynamic indices were measured before, during, and 10 minutes after exercise. In the MI group, plasma ANF levels significantly increased at the 75-watt workload and significantly decreased at 10 minutes after exercise, whereas in the control group, the increase in plasma ANP levels after a 75-watt workload, compared with those at rest, was not significant. Significant correlations of pulmonary artery wedge pressure, right atrial pressure, mean arterial pressure, and heart rate to plasma ANF levels were observed at four points obtained before and during each stage of exercise in the MI group. Furthermore, a significant correlation between maximal creatine kinase levels and plasma ANF levels at a 75-watt workload and a significant inverse correlation between left ventricular ejection fraction and plasma ANF levels at a 75-watt workload were observed. These results suggest that the increase in the circulating ANF level during exercise in MI is associated with elevated atrial pressure resulting from left ventricular dysfunction and that measurement of ANF during exercise may be an indication of the severity of MI and associated left ventricular dysfunction.     

Augmented expression of atrial natriuretic polypeptide gene in ventricles of spontaneously hypertensive rats (SHR) and SHR-stroke prone

Tissue levels of atrial natriuretic polypeptide (ANP) and ANP messenger RNA (mRNA) in the atrium and ventricle were measured simultaneously in spontaneously hypertensive rats (SHR) and its substrain, SHR-stroke prone (SHRSP), and these levels were compared with those in control Wistar-Kyoto rats (WKY). At 27 weeks of age with established hypertension and ventricular hypertrophy, ANPmRNA levels in ventricles from SHR and SHRSP were markedly increased, and total contents of ventricular ANPmRNA in SHR and SHRSP were approximately 50% and 250%, respectively, of the corresponding atrial contents. However, levels and total contents of atrial ANPmRNA in SHR and SHRSP were similar to those of WKY, and the total content of ventricular ANPmRNA in WKY was only 6% of the content of atrial ANPmRNA. ANP concentrations in ventricles of SHR and SHRSP were increased in association with the augmentation of ANPmRNA levels. During the prehypertensive stage at 6 weeks of age, slight increases in levels and total contents of ANPmRNA and ANP in the ventricle were observed only in SHRSP. These results demonstrate that the expression of the ANP gene is markedly augmented in ventricles of SHR and SHRSP, especially of SHRSP, at the stage of established hypertension and ventricular hypertrophy, and they also suggest that these genetically hypertensive rats are one of the best animal models to investigate the biosynthesis, storage, and secretion of ventricular ANP.     

Transmural distribution of myocardial infarction: difference between the right and left ventricles in a canine model

The evolution of myocardial infarction 24 hours after ligating both the right coronary artery and the obtuse marginal branch of the left circumflex coronary artery was examined in 33 anesthetized dogs. Postmortem coronary angiography and a tracer microsphere technique were used to determine risk areas and their collateral blood flows, respectively. The mean weight of the risk areas was 11.3 +/- 0.5 g (mean +/- SEM) in the right ventricle and 10.5 +/- 0.9 g in the left ventricle (NS). The weight of infarcted tissue was 5.7 +/- 0.7 g in the right ventricle and 5.2 +/- 0.9 g in the left ventricle (NS). In both ventricles, infarct weight was linearly related to risk area size, and the percent of risk area necrosis was inversely correlated with the extent of collateral flow at 24 hours of coronary ligation, defined as the mean myocardial blood flow inside the central risk area. Ratios of infarct to risk area between the subendocardial and subepicardial layers were 0.76 +/- 0.06 and 0.28 +/- 0.05 in the right and left ventricles, respectively (p less than 0.01, between ventricles, n = 31), which coincided well with subendocardial-to-subepicardial-flow ratios at 24 hours, ie, 0.86 +/- 0.04 in the right ventricle and 0.32 +/- 0.06 in the left ventricle (p less than 0.01). The regional distribution of myocardial infarction correlated well with flow distribution inside the risk area; the slope of these relations was similar between the subendocardium and subepicardium in the right ventricle, whereas in the left ventricle it was larger in the subendocardium than in the subepicardium. Thus, in the dog, the inherent change in the regional distribution of coronary collateral blood flow is an important modifier in the evolution of myocardial infarction, especially in the left ventricle.     

Coronary artery aneurysms and myocardial infarction: adult sequelae of Kawasaki disease?

Coronary artery aneurysms developed in a 43 year old man who had suffered an acute myocardial infarction at the age of 30. In childhood he had had an illness that was consistent with Kawasaki disease, and it is suggested that the proximal discrete aneurysms and myocardial infarction may be the adult sequelae of this.     

Coronary artery aneurysms and myocardial infarction: adult sequelae of Kawasaki disease?

Coronary artery aneurysms developed in a 43 year old man who had suffered an acute myocardial infarction at the age of 30. In childhood he had had an illness that was consistent with Kawasaki disease, and it is suggested that the proximal discrete aneurysms and myocardial infarction may be the adult sequelae of this.     

Estimation of myocardial hemodynamics before and after intervention in children with Kawasaki disease

OBJECTIVES: We used myocardial fractional flow reserve (FFR(myo)) and coronary flow reserve (CFR) to estimate cut-off values for assessment of the functional severity of coronary stenosis and myocardial ischemia, and we tested the usefulness of coronary blood hemodynamic measurements before and after plain old balloon angioplasty (POBA) and coronary artery bypass graft surgery (CABG). BACKGROUND: Fractional flow reserve and CFR are useful for assessing the functional severity of coronary artery stenosis, coronary microvascular dysfunction, and myocardial ischemia during cardiac catheterization in adults. However, there have been no reports on the use of these measurements in children with Kawasaki disease (KD). METHODS: The study group included 128 patients with 314 coronary branches. The subjects were classified into three groups: normal coronary group, with 206 branches; abnormal coronary artery without ischemia group, with 58 branches; and ischemia group, with 50 branches. RESULTS: In each branch, CFR and FFR(myo) were significantly lower in the ischemia group than in the other groups. Cut-off values for assessing the functional severity of coronary stenosis and CFR were approximately equal to those obtained for adults (CFR: <2.0; FFR(myo): <0.75). We obtained very high sensitivity and specificity for estimating myocardial ischemia using CFR and FFR(myo) (CFR: 94.0% and 98.5%, respectively; FFR(myo): 95.7% and 99.1%, respectively). Both CFR and FFR(myo) were reliable indicators of coronary hemodynamics before and after POBA and CABG. CONCLUSIONS: Together, CFR and FFR(myo) provide a useful index for assessing the functional severity of coronary artery stenosis and myocardial ischemia and estimating the effectiveness of POBA and CABG in children with KD, the same as they do for adults.     

Coronary stent deployment in a young adult with Kawasaki disease and recurrent myocardial infarction

A 19-year-old man developed a huge coronary aneurysm and stenosis in the right coronary artery as a sequela of Kawasaki disease (KD) that resulted in recurrent episodes of myocardial infarction. Coronary ischemic events were successfully prevented after balloon angioplasty followed by coronary stent implantation into the stenotic lesion. The stent deployment may have an advantage compared with balloon angioplasty and other new devices for the treatment for patients with KD showing stenotic lesions without dense calcification.     

不同期血吸虫病患者血浆心钠素变化的临床研究

目的观察急性、慢性和晚期血吸虫病患者血浆中心钠素(ANP)的浓度。方法对在湘岳医院2002～2003年间住院的急性、慢性和晚期血吸虫病患者取静脉血2ml,采用放射免疫技术非平衡法,在γ计数器上直接测定血浆ANP的浓度。同时与健康者作对照。结果急性、慢性、巨脾型晚期和腹水型晚期血吸虫病等患者均高于对照组,急性(P<0.01);慢性(P<0.01);巨脾型晚期(P<0.05);腹水型晚期血吸虫病(P<0.01)。而急性血吸虫病患者与慢性、巨脾型晚期血吸虫病患者比较差异无统计学意义(P>0.05);巨脾型晚期与慢性血吸虫病患者比较差异无统计学意义(P>0.05)。腹水型晚期血吸虫病患者与急性、慢性与巨脾型晚期血吸虫病患者相比,差异有统计学意义(P<0.01)。结论人体感染血吸虫后,血浆中ANP的含量升高,其机理仍需进一步研究。