Measurement of plasma brain natriuretic peptide level as a guide for cardiac overload.

OBJECTIVES: We examined whether measurement of the plasma BNP concentrations might be useful for the early diagnosis of the existence and severity of disease in patients with heart disease in daily clinical practice. METHODS AND RESULTS: The plasma BNP and ANP concentrations in 415 patients with heart disease and hypertension and 65 control subjects were measured. Patients with heart disease had higher plasma BNP and ANP concentrations than did those with hypertension or control subjects. Among the etiology of cardiac diseases, specifically dilated cardiomyopathy and hypertrophic cardiomyopathy, was associated with the highest plasma BNP concentrations, whereas dilated cardiomyopathy was associated with the highest plasma ANP concentrations. Plasma BNP concentrations showed an increase as the severity of the heart disease, as graded according to the NYHA classification of cardiac function, increased. In both patients with heart disease and hypertension, the plasma BNP values were higher in those who had abnormalities in their echocardiogram and electrocardiogram as compared to those without any abnormalities. The plasma BNP levels also showed a significant correlation with left ventricular wall thickness and left ventricular mass. On the other hand, the plasma ANP levels showed significant correlations with left ventricular dimension. Receiver operative characteristic analysis revealed that plasma BNP levels showed substantially high sensitivity and specificity to detect the existence of heart diseases. CONCLUSION: Measurements of the plasma BNP concentrations is useful to detect the existence of the diseases, and abnormalities of left ventricular function and hypertrophy in patients with heart disease in daily clinical practice.

Evaluation of regurgitant fraction of the left ventricle by gated cardiac blood-pool scanning using SPECT.

Regurgitant fraction (RF) of patients with and without mitral regurgitation (MR) and/or aortic regurgitation (AR) was evaluated by gated cardiac blood-pool scanning using single photon emission computed tomography (SPECT). Using the stroke count image of a short-axis tomogram to separate the right atrium and ventricle, the left ventricular stroke count (LVSC) and right ventricular stroke count (RVSC) were determined. The RF equaled (LVSC - RVSC)/LVSC. Calculated RF in 14 subjects without significant regurgitation by contrast angiography was 5.8 +/- 5.9% (mean +/- s.d.), RF of 17 cases with angiographic regurgitation was 42.5 +/- 16.8% (p less than 0.001). The sensitivity of the radionuclide method compared to angiography was 94% (16/17 cases), and specificity was 100% (14/14 cases). RF of mild Re (1+ or 2+) was 26.0 +/- 8.9% (n = 6) and RF of severe Re (3+ or 4+) was 51.5 +/- 12.7% (n = 11) (p less than 0.001). Correlation between the RF determined with the radionuclide method and with cardiac catheterization was good (y = 5.85 + 0.700 x, r = 0.821, n = 17). We conclude that RF of MR and/or AR can be accurately evaluated by gated cardiac blood-pool scanning using SPECT.

Effects of steroid treatment on release of cardiac myosin light chain II in acute myocardial infarction in dogs.

The effect of methylprednisolone sodium succinate (MP) on release of myosin light chain II (LCII) from the myocardium was studied in experimental myocardial infarction (MI). Acute MI was produced in conscious, closed-chest dogs by ligating the left anterior descending coronary artery beyond the first diagonal branch. MP, 30 mg/kg, was administered intravenously just before and 24 hours after MI. After MI, LCII levels in the serum were determined serially up to 240 hours. MI size was determined histologically 10 days after MI. In the MP group, LCII levels in the serum within 72 hours were lower than in the control, and cumulative LCII release for 3 days decreased from 530 +/- 159 to 310 +/- 101 ng/ml (mean +/- standard deviation) (p less than 0.001). However, the peak LCII level appeared later (control vs MP, 63 +/- 27 vs 122 +/- 25 hours, p less than 0.001), and the peak LCII level and cumulative LCII release for 10 days were not decreased by MP treatment. MI size also was not reduced by MP (11.0 +/- 4.4% vs 11.8% +/- 4.5% of the left ventricle, difference not significant). Since the rate of disappearance of LCII is rapid and was not affected by MP, these results suggest that MP treatment early after acute MI delays breakdown of myosin filaments, but cannot prevent it.

Endothelin: a potent vasoconstrictor associated with coronary vasospasm.

Endothelin, administered into the coronary arteries of anesthetized dogs, produced a profound and long-lasting reduction in coronary blood flow with electrocardiographical evidence of myocardial ischemia. Coronary angiography revealed delayed filling of the distal branches and, in some cases, cessation of the blood flow distal to the epicardial portions of coronary arteries. The coronary vasoconstriction induced by endothelin subsided after intracoronary administration of nitroglycerin. Pretreatment with the Ca2+-channel antagonist, nitrendipine, suppressed endothelin-induced vasoconstriction. These findings suggest that endothelin, produced by vascular endothelial cells, may contribute to the pathogenesis of coronary vasospasm.

Angiotensin converting enzyme polymorphism is associated with severity of coronary heart disease and serum lipids (total cholesterol and triglycerides levels) in Japanese patients.

BACKGROUND: Much past research has concerned the relationship between coronary heart disease and the angiotensin converting enzyme (ACE) genotype, with many lines of evidence demonstrating polymorphism to be an independent risk factor for myocardial infarction. Interestingly, however, association of ACE polymorphism and severity of coronary artery stenosis according to racial background has recently been proposed. OBJECTIVE: To clarify the relationship between the ACE genotype and severity of coronary artery stenosis in Japanese patients. METHODS: In 36 consecutive patients undergoing coronary catheterization, comparative examination of coronary angiography findings with the ACE genotype was conducted. RESULTS: The severity of coronary artery stenosis indeed showed a relationship with the ACE genotype, with more severe coronary artery stenosis associated with the deletion (D) allele (P < 0.05). The serum lipids, total cholesterol and triglycerides levels, were also elevated in patients with the D allele (P < 0.05). CONCLUSION: We have provided further evidence that ACE polymorphism is associated with severity of coronary heart disease in a Japanese population. A possible relationship between serum lipids and the ACE genotype is also suggested.

Right ventricular inflow obstruction due to giant hematoma formed by chronic constrictive pericarditis.

A 26-year-old man having chronic constrictive pericarditis with rare complications is described. Right ventricular inflow obstruction was caused by an intracavity giant mass which was surrounded by thick calcified pericardium. The mass consisted of old bloody fluid with some calcified tissue. The findings of auscultation closely mimicked those of tricuspid valvular stenosis.

[Aortic pulse wave velocity in patients with coronary atherosclerosis--a comparison with coronary angiographic findings].

This study was conducted to investigate the relationship between aortic pulse wave velocity (PWV) and coronary atherosclerosis. We measured PWV in 105 subjects (84 males and 21 females; age 59 +/- 0.5) who received coronary angiographic examination (CAG). PWV was measured by simultaneous recording of pulse waves from the left carotid and the left femoral arteries, electrocardiogram and phonocardiogram. The subjects were classified into 4 groups according to the number of major coronary arteries having stenosis, that is, N group with normal CAG, 1 vessel disease (VD) group, 2VD group and 3VD group. The PWV value was significantly greater only in 3VD group (n = 10, age 63 +/- 3.6, PWV 10.0 +/- 0.88 m/sec) than that in N group (n = 18, age 53 +/- 2.0, PWV 8.0 +/- 0.34 m/sec). No significant difference was observed between PWV value in N group and that in all patients with coronary artery stenosis (n = 87, age 60 +/- 2.0, PWV 8.9 +/- 0.2 m/sec). To further investigate the relationship between PWV values and CAG findings, we used a CAG score which means the sum of the points assigned to each coronary artery segment (American Heart Association) according to the severity of stenosis (0, 1, 2, 3, and 4 for normal, less than 49% stenosis, 50 to 74% stenosis, 75 to 99% stenosis, and complete occlusion, respectively). The PWV values significantly correlated with the CAG score and also with age by a simple regression analysis. Multivariate analysis, however, revealed that PWV values did no longer correlate with CAG score. PWV values still significantly correlated with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Reconstitution of heavy chain and light chain 1 in cardiac subfragment-1 from hyperthyroid and euthyroid rabbit hearts.

It is now established that cardiac myosin from hyperthyroid rabbit hearts (TXM) exhibits high Ca2+ ATPase activity. The high Ca2+ ATPase activity of TXM was completely retained in cardiac myosin subfragment-1 (S-1) (1.33 +/- 0.04 mumol Pi/mg per min; euthyroid, 0.51 +/- 0.04). Cardiac S-1 from hyperthyroid and euthyroid rabbits (TXS-1 and NS-1) had the same pattern in SDS-polyacrylamide gel electrophoresis. The possible influence of heavy and light chains of TXM on increasing the ATPase activity was examined by reconstitution in the S-1 preparation. Crosswise reconstitution was performed using cardiac S-1 heavy chain (90,000 daltons) and light chain 1 (LC1) (27,000 daltons) from hyperthyroid and euthyroid hearts. Reconstitution was verified by using radiolabeled LC1. More than 95% of S-1 was recovered with full ATPase activity. When TXS-1 was reconstituted with LC1 from euthyroid hearts, the reconstituted molecule retained high ATPase activity. On the other hand, NS-1 reconstituted with LC1 from hyperthyroid hearts failed to increase the ATPase activity. The ATPase activity of S-1 was determined by the source of the heavy chain. These results suggest that the high Ca2+ ATPase activity of cardiac myosin and S-1 from hyperthyroid animals arises from the molecular alteration of the heavy chain induced by thyroxine administration.

[Hemodynamic responses to supine bicycle exercise in juvenile hypertensive subjects: an echocardiographic assessment (author's transl)].

Six juvenile hypertensive patients were studied by supine bicycle ergometer exercise during continuous echocardiographic recording. Thirteen normotensive young men were also studied for the control. Left ventricular end-diastolic dimensions (Dd) during exercise was significantly increased from 28.8 +/- 0.5 mm/m2 to 29.7 +/- 0.6 mm/m2 in normotensives, but the increase in Dd was not observed in hypertensives. Effects of propranolol on changes in Dd during exercise were almost equal in two groups. Left ventricular end-systolic dimensions (Ds) were decreased during exercise in both groups. After propranolol administration, Ds in hypertensives was significantly increased from 18.8 +/- 1.0 mm/m2 to 19.4 +/- 1.1 mm/m2 at rest, and during the following exercise it reached to 19.7 +/- 1.1 mm/m2, whereas Ds in normotensives was decreased during exercise even after propranolol. Peripheral vascular resistance at rest was almost equal between the two groups, but in hypertensives the reduction during exercise was restricted. These results suggest that sympathetic activities of cardiovascular system are accentuated in juvenile hypertensive subjects.

Myocardial infarct size from serum cardiac myosin light chain. Clinical and experimental studies.

The relationship between myocardial infarct size and serum cardiac light chain (LC) levels was studied in experimental and clinical myocardial infarction. In dogs with left anterior descending coronary artery occlusion, regression analysis showed good correlation between infarct size and LC II release, but CPK-MB release failed to correlate with infarct size because of a decreasing value of cumulative CPK with larger sized infarctions. In patients with acute myocardial infarction, Peak LC I levels correlated well with CPK release, since the phenomenon of the decreased CPK release in larger sized infarction was not so distinctive in human cases. Thus, LC determination may better quantitate the extent of myocardial damage as well as provide a specific and sensitive method for diagnosis of acute myocardial infarction.

Quantification of myocardial infarct size after coronary reperfusion by serum cardiac myosin light chain II in conscious dogs.

The effects of early coronary artery reperfusion on the relation between the extent of myocardial infarction and serum levels of cardiac myosin light chain II or plasma creatine kinase levels were evaluated in the conscious dog. Hydraulic occluders were placed on the left anterior descending arteries of 38 dogs. Seven to 10 days later, myocardial infarction was produced. Coronary reperfusion was performed 3 hours (group A1, n = 13) and 6 hours (group A2, n = 12) after the occlusion. In the other 13 dogs, coronary occlusion was sustained throughout the course of the experiment (group B). Seven days after the occlusion, the heart was cut from the apex to the base into 4-mm slices, and infarct size was determined macroscopically. Rapid appearance and early peaking of creatine kinase were observed in group A. Cumulative release of creatine kinase significantly correlated with infarct size in group A (infarct size ranged from 0.1 to 20.1 g, r = 0.90) and group B (from 0.6 to 26.8 g, r = 0.91). However, since creatine kinase release in group A was greater in comparison with that from infarcts of the same size in group B, the slope of the regression line for group A was significantly steeper (p less than 0.05). Cardiac myosin light chain II appeared as early as creatine kinase did and continued to be elevated for 7 days. A very close relation was observed between infarct size and total cardiac myosin light chain II release (r = 0.87 for group A, and r = 0.88 for group B) or peak level of light chain II (r = 0.85 for group A, and r = 0.81 for group B). In addition, the slopes of the regression lines for infarct size and both peak and total release of light chain II did not differ between group A and group B. On histological examination, viable myocardium was frequently observed in the epicardium of the ischemic area in group A1; therefore, infarct size was greater in group B than in group A1 (p less than 0.05). Also, myocardial creatine kinase content in the epicardium of the center of the ischemic area in group A1 was greater than that in group B. Cardiac myosin light chain II release in group A1 was less than that in group B, whereas no difference was found in plasma creatine kinase release among groups A1, A2, and B.(ABSTRACT TRUNCATED AT 250 WORDS)

High renin hypertension in the elderly.

This paper describes clinical features of high renin hypertension in the elderly. Peripheral plasma renin activity ranged from 0 to 20.1 ng/ml/hr in 59 hypertensive in-patients aged 70 to 86. The patients were divided into 2 groups: 9 cases with plasma renin activity greater than or equal to 3.0 ng/ml/hr (high renin group) and the remaining 50 with plasma renin activity less than 3.0 ng/ml/hr (control group). The development of hypertension differed between the 2 groups. Six of the high renin group (66.7%) had a history of acceleration of previously mild hypertension, while only 3 of the control group (6.0%) had this history (p less than 0.01). The frequencies of high diastolic blood pressure (greater than or equal to 120 mmHg), massive proteinuria (at least 3.0 g/day), hypokalemia (serum potassium less than or equal to 3.0 mEq/L) and high serum cholesterol (greater than or equal to 250 mg/100 ml) were significantly greater in the high renin group than in the control group (p less than 0.01, respectively). Renovascular hypertension was suspected in 6 patients from the high renin group (66.7%), as compared with 1 of the control group (2.0%) (p less than 0.001). There was massive proteinuria in 3 of 6 patients with renovascular hypertension in the high renin group and 2 showed nephrotic syndrome. Thus, two-thirds of the elderly patients with high renin hypertension had probable renovascular hypertension with a history of rapid progression of hypertension.