Hisao Oku

Circulating immunoreactive endothelin in ischemic heart disease

Circulating immunoreactive endothelin (ir-ET) was measured in nine patients with acute myocardial infarction (AMI), 10 patients with stable angina pectoris (SAP), and 25 normal control subjects. In patients with AMI, the plasma ir-ET level was elevated in the acute phase and was highest on the day of onset (AMI: 3.8 +/- 1.7 pg/ml, normal control value: 0.5 +/- 0.2 pg/ml). The plasma ir-ET level showed a positive correlation with the wall motion abnormality index (rs = 0.56, p less than 0.01), thrombin-antithrombin III complex (rs = 0.55, p less than 0.01), and beta thromboglobulin (rs = 0.39, p less than 0.05). An especially high plasma ir-ET level was detected in patients in whom the Killip subset was IV. The plasma ir-ET level was not increased in patients with SAP (0.8 +/- 0.3 pg/ml). The plasma ir-ET level is increased in the acute phase of AMI. A pathophysiologic state characterized by cardiac dysfunction, an activated coagulation system, and platelet hyperactivity may be associated with this increase in plasma ir-ET.

The complement system in ischemic heart disease.

The mechanisms by which tissue injury after acute myocardial infarction (AMI) occurs has not been fully elucidated. Recent evidence in experimental models has suggested involvement of the complement system in microvascular and macrovascular injury subsequent to AMI. With respect to angina pectoris, whether or not the complement system is activated is not clear. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation, including C3d, C4d, Bb, and SC5b-9 complexes, in 31 patients with AMI, 17 patients with unstable angina pectoris, 19 patients with stable angina pectoris, and 20 normal volunteers. The plasma C3d levels increased in patients with AMI and in those with unstable angina pectoris (p less than 0.01). The plasma levels of C4d, Bb, and SC5b-9 increased only in patients with AMI (p less than 0.01). The plasma SC5b-9 level was related to peak creatine phosphokinase (r = 0.71) and inversely related to the ejection fraction (r = -0.71). The plasma SC5b-9 level of patients with congestive heart failure was higher than that of patients without congestive heart failure in AMI. These results show that activation of complement system occurs after AMI and show an association of myocardial damage with complement activation. With respect to angina pectoris, the complement system is mildly activated in patients with unstable angina pectoris; however, the cardiac function of patients with unstable angina pectoris is not damaged. The complement system of patients with stable angina pectoris is not activated.

Effect of exercise on circulating atrial natriuretic polypeptide in valvular heart disease

Abstract The atrial peptides that have potent natriuretic, diuretic and vasodilatory effects have been purified from human tissues and their structures have been determined.1 Also, it has been shown that acute volume expansion causes an immediate increase in plasma concentration of immunoreactive atrial natriuretic polypeptide (ANP) in rats.2 These data imply that ANP is secreted from cardiac atria, presumably by the stimulation of atrial stretch receptor. We measured plasma ANP concentrations during 3 grades of exercise (25, 50 and 75 W) on a bicycle ergometer in 6 patients with valvular heart disease.

Influence of exercise on plasma atrial natriuretic favor 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.

Alterations in myocardial systolic and diastolic function in patients with active systemic lupus erythematosus

Echocardiographic studies were performed to evaluate myocardial function in active patients with systemic lupus erythematosus (SLE). Fourteen patients were studied in the active stage before corticosteroid therapy (active SLE); 10 of them were reexamined after therapy (inactive SLE). Computer-assisted analysis of digitized echoes of the left ventricular dimension was performed. The peak rate of change in dimension during systole (-dD/dt) was reduced in active SLE compared with normal control subjects (2.57 +/- 0.15 cm/sec vs 3.37 +/- 0.14 cm/sec, p less than 0.01). The peak rate of change in dimension during diastole (+dD/dt) was also reduced in active SLE compared with normal control subjects (3.16 +/- 0.19 cm/sec vs 4.41 +/- 0.20 cm/sec, p less than 0.01). After therapy, -dD/dt in inactive SLE was improved compared with active SLE (from 2.56 +/- 0.20 cm/sec to 3.13 +/- 0.19 cm/sec, p less than 0.001). Positive dD/dt in inactive SLE was also improved compared with active SLE (from 3.29 +/- 0.22 cm/sec to 4.23 +/- 0.23 cm/sec, p less than 0.01). No significant differences were found between inactive SLE and normal control subjects as to -dD/dt and +dD/dt. Significant correlations were found between anti-DNA antibody titers and both -dD/dt and +dD/dt (r = -0.97 p less than 0.0001, and r = -0.71 p less than 0.05, respectively). These results suggest that active SLE patients have left ventricular dysfunction that may be caused by an immunopathologic mechanism in SLE.

Case Report: Hereditary Hemorrhagic Telangiectasia with Growing Pulmonary Arteriovenous Fistulas Followed for 24 Years

A 47-year-old man was admitted for follow-up of an abnormal chest x-ray. He had a history of epistaxis and a brain abscess and a family history of pulmonary arteriovenous fistulas. Physical examination showed clubbed fingers and telangiectasia of the tongue. Laboratory data revealed evidence of polycythemia and hypoxia. Contrast echocardiography and pulmonary perfusion scintigraphy were suggestive of a right-to-left shunt. From the oxygen tension and content of blood taken at cardiac catheterization, the shunt ratio was calculated to be 57.8%. Multiple bilateral pulmonary arteriovenous fistulas were confirmed by angiography, and the patient was diagnosed as having hereditary hemorrhagic telangiectasia. A review of x-ray films taken over a 24-year period demonstrated that the fistulas in both lungs had been increasing gradually in size at different rates. A right lower lobectomy relieved the hypoxia, but the patient died unexpectedly on the twelfth postoperative day. There was no evidence of fistula rupture on chest film, but no autopsy was performed.

Plasma levels of platelet-derived growth factor in normal subjects and patients with ischemic heart disease

Plasma levels of platelet-derived growth factor (PDGF) were measured in 24 normal control subjects, 31 patients with stable angina pectoris, 25 patients with unstable angina pectoris, and 31 patients with acute myocardial infarction (AMI) by a sensitive direct radioimmunoassay. The plasma PDGF level in normal control subjects was 273 +/- 25 pg/ml; there was no significant correlation between the plasma PDGF level and age. Plasma PDGF levels in patients with unstable angina pectoris and acute myocardial infarction were significantly lower than those in normal control subjects and patients with stable angina pectoris (p less than 0.05). In patients with acute myocardial infarction the plasma PDGF level in the chronic phase was significantly higher than that in the acute phase (p less than 0.05). These observations raise the possibility that PDGF is involved in the pathophysiology of ischemic heart disease.

Pheochromocytoma with electrocardiographic change mimicking angina pectoris, and cyclic change in direct arterial pressure : a case report

A forty-two-year-old man was admitted because of chest pain. Electrocardio grams at admission showed horizontal ST depression in leads, II, III, aVF, V4, V5, and V 6. Direct blood pressure monitoring revealed cyclic change between 160/100 mmHg and 70/50 mmHg and heart rate between 80/sec and 120/sec at fifteen minute intervals. The plasma norepinephrine and epinephrine concentrations were elevated during the episodes of hypertension. Pheochromocytoma was found in the right adrenal gland. These cyclic changes in blood pressure and heart rate are an aid for diagnosis.

Influence of Nisoldipine on Hemodynamics and Atrial Natriuretic Polypeptides at Exercise Loading in Hypertensive Patients

The effect of a calcium antagonist, nisoldipine, on cardiac hemodynamics and the response of atrial natriuretic polypeptides (ANP) were investigated at exercise loading in hypertensive patients. A dose of 5 mg nisoldipine was administered to seven patients with untreated essential hypertension. Multistage exercise loading (25 W, 50 W, and 75 W) was performed before and after administration on a supine bicycle ergometer for 4 min at each exercise stage. Heart rate, blood pressure, pulmonary artery pressure (PAP), and pulmonary artery wedge pressure (PAWP) were measured at rest and at each exercise stage under catheterization using a Swan-Ganzcatheter. At the same time, blood samples were collected from the pulmonary artery for measurement of ANP. Radioimmunoassay, as we reported previously, was used in the measurement of ANP (1986), (Biochem Biophys Res Commun 134: 178–183).