Susumu Imai

Interleukin-6 and cardiac myxoma

Abstract We conclude that IL-6 should be considered a marker of myxoma. The frequent immunologic abnormalities in patients with cardiac myxoma may be related to the IL-6 secreted from the myxoma itself.

Cardiac Myxoma Metastasized to the Brain: Potential Role of Endogenous lnterleukin-6

Metastasis of a cardiac myxoma to the brain is extremely rare. We present the case of a 70-year-old man who had an atrial myxoma and two metastatic myxomas in the brain. The intracranial lesions were in fact diagnosed before the cardiac myxoma, since the patient developed hemiparesis before his cardiac symptoms occurred. Computerized tomography of the brain showed two high-density lesions, the larger of which was removed surgically. Follow-up computerized tomography revealed a progressive enlargement of the second lesion which was then resected. Histopathological examination showed all lesions to the benign myxomas. Interestingly, high concentrations of interleukin-6 were present in the patients serum and cardiac myxoma. Interleukin-6 may possibly potentiate metastasis of cardiac myxoma.

Effects of Na(+)-H+ exchange blocker amiloride on left ventricular remodeling after anterior myocardial infarction in rats.

SummaryWe investigated the effects of amiloride, a Na+-H+ exchange blocker, on ventricular remodeling in an infarcted rat model. In the amiloride group, the left descending coronary artery was ligated and rats were given amiloride (1 mg/kg/day, n=11) in their drinking water for 4 weeks. In the control group, rats were given water for 4 weeks (n=8) after myocardial infarction. The rats were killed on day 28. Both the ratio of heart weight to body weight and that of left ventricular weight to body weight were significantly less in the amiloride group (p<0.05). The diameter of a myocardial fiber in the region adjacent to the operated area was significantly reduced in the amiloride group compared with the control group (p<0.05). Left ventricular cavity dimension was significantly smaller in the amiloride group than that in control group (p<0.05). Our findings suggest that amiloride prevents ventricular remodeling after myocardial infarction.

A Na+–H+ exchange inhibitor (SM-20550) protects from microvascular deterioration and myocardial injury after reperfusion

Na+-H+ exchange inhibitors may reduce myocardial damage after reperfusion. However, their effects on microvascular deterioration are not known. We examined the potency of a novel Na+-H+ exchange inhibitor, SM-20550 [ N-(Aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonate], and its effects on microvascular damage after reperfusion. In an in vitro study, the Na+-H+ exchange inhibiting activity of SM-20550 was about 10 times greater than that of ethylisopropyl amiloride. In in vivo experiments, we occluded the left circumflex coronary artery in 29 dogs for 2 h and then reperfused for 5 h. SM-20550 was administered either before ischemia (n = 11) or before reperfusion (n = 7). Another 11 dogs served as controls. We found that SM-20550 not only improved coronary vasodilator responses to acetylcholine and adenosine after reperfusion, but also reduced infarct size (P < 0.01). Intramyocardial bleeding, which should reflect microvascular damage, was not found in dogs with SM-20550 treatment. Infarct size was correlated inversely with collateral blood flow in control (both, P < 0.01) but not in SM-20550-treated animals. Furthermore, SM-20550 significantly suppressed ventricular fibrillation during both ischemia and reperfusion. These results suggest that protective effects of Na+-H+ exchange inhibitors on reperfused myocardium are due at least in part to microvascular protection.

Comparative effects of losartan, captopril, and enalapril on murine acute myocarditis due to encephalomyocarditis virus.

Summary: Losartan, a recently developed nonpeptide angiotensin II (AII) receptor antagonist, was orally administered for 14 days to mice with viral myocarditis, beginning 7 days after encephalomyocarditis virus inoculation. The angiotensin-converting enzyme inhibitors (ACEI) captopril and enalapril were also administered in the same manner to compare the therapeutic effects of these three drugs on the degree of myocarditis, acute heart failure, and left ventricular (LV) hypertrophy. Heart weight and the heart weight/body weight ratio were reduced by losartan (60 mg/kg/day) and captopril (7.5 mg/ kg/day), but not by enalapril (1 mg/kg/day). LV wall thickness and cavity dimension were decreased in the losartan and captopril groups. Captopril reduced both myocardial necrosis and inflammation, whereas enalapril reduced myocardial necrosis but not inflammation. However, none of the studied losartan doses (1.2, 12, 60 mg/ kg/day) influenced myocardial necrosis and inflammation resulting from viral infection. Thus, specific blockade of AII is beneficial in congestive heart failure (CHF) and LV hypertrophy but is not effective in viral-evoked inflammation and injury.

Semotiadil improves survival of rats with monocrotaline-induced pulmonary hypertension: comparison with diltiazem

We compared the effects of semotiadil, a novel Ca2+ channel blocker, with those of diltiazem on survival and regression of right ventricular hypertrophy and media thickening of pulmonary arteries in a rat model of pulmonary hypertension. Pulmonary hypertension was induced by a single injection of monocrotaline (80 mg/kg). Four weeks later, after pulmonary hypertension was confirmed, oral administration of semotiadil (10, 30, or 100 mg/kg/day) or diltiazem (100 or 300 mg/kg/day) was initiated. The rats were observed for 3 weeks. Survival was significantly longer in the group that received semotiadil 100 mg/kg/day than in the groups treated with diltiazem 100 or 300 mg/kg/day. Media thickness and smooth muscle area in pulmonary arteries were significantly less in rats treated with semotiadil 100 mg/kg/day than in animals treated with diltiazem 100 mg/kg/day. The right ventricle to left ventricle mass ratio, right ventricular wall thickness, and right ventricular myocardial fiber diameter were equal in these two groups. Semotiadil 100 mg/kg/day improved the survival of rats, which responded with a significant regression of right ventricular hypertrophy and media thickening of pulmonary arteries in comparison with rats treated with diltiazem 100 or 300 mg/kg/day.

Comparison of adenosine, dobutamine, and exercise radionuclide ventriculography in the detection of coronary artery disease.

The diagnostic values of adenosine, dobutamine, and exercise radionuclide ventriculography (RNVG) in the detection of coronary artery disease (CAD), and the characteristics of those patients who showed myocardial ischemia during the infusion of adenosine or dobutamine were assessed in 41 patients with suspected CAD. Sensitivity, specificity, and accuracy, respectively, for detecting patients with CAD were 35 (p < 0.01 vs. exercise RNVG), 100 and 46% (p < 0.01 vs. exercise RNVG) with adenosine RNVG, 74, 100 and 78% with dobutamine RNVG and 88, 71 and 85% with exercise RNVG. There was a significant difference in physiologic parameters during the provocation of ischemia by adenosine versus exercise RNVG, although these parameters were similar by dobutamine and exercise RNVG. Stepwise discriminant analysis revealed that the number of stenotic vessels was an important and independent predictor for the myocardial ischemia induced by each stress; the peak filling rate was the only predictor for adenosine-induced ischemia. Dobutamine induced myocardial ischemia in a way similar to that of exercise, and was more useful than adenosine for pharmacologic stress RNVG. The mechanism of the adenosine-induced ischemia seemed to differ from that of the ischemia induced by dobutamine or exercise, and to be closely associated with left ventricular diastolic function.

Semotiadil inhibits the development of right ventricular hypertrophy and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension

SummaryThis study was designed to compare the effects of semotiadil, a novel calcium antagonist, with those of diltiazem on the development of right ventricular hypertrophy and medial thickening of pulmonary arteries in a rat model of pulmonary hypertension. Pulmonary hypertension was induced by a single injection of monocrotaline (80 mg/kg). Twenty-four hours later (day 1), oral administration of semotiadil (10, 30, or 100 mg/kg per day) or diltiazem (100 or 300 mg/kg per day) was initiated. The wall thickness of the right ventricle (RV), the RV myocardial fiber diameter, the percent medial pulmonary artery thickness, and the percent area of smooth muscle in pulmonary arteries were determined on day 28. The magnitude of all parameters was significantly less in the group of seven rats that received semotiadil at 100 mg/kg per day than in the group of seven rats treated with diltiazem at 300 mg/kg per day. Semotiadil at 100 mg/kg per day inhibits the development of RV hypertrophy and medial thickening of pulmonary arteries significantly more effectively than diltiazem at 300 mg/kg per day.

Sandostatin inhibits development of medial proliferation of pulmonary arteries in a rat model of pulmonary hypertension.

We investigated the effects of subcutaneous administration of 50 and 100 micrograms/kg/day of sandostatin on monocrotaline-induced medial proliferation of pulmonary arteries and right ventricular overload in rats. In a dosage of 100 micrograms/kg/day, sandostatin significantly reduced right ventricular systolic pressure, the mass ratio of the right ventricular free wall to the left ventricle, the right ventricular wall thickness, the right ventricular myofiber diameter, the percent medial pulmonary artery thickness, the percent area of smooth muscle cell, and proliferating cell nuclear antigen activity. Our results suggest that sandostatin inhibits development of medial proliferation of pulmonary arteries and right ventricular overload in a dosage of 100 micrograms/kg/day.

Myocardial Uptake of an lodinated Branched Fatty Acid Analog, Assessed by SPECT, May Detect Metabolic Derangement of the Myocardium in Diabetic Patients with Coronary Heart Disease

The clinical implications of single-photon emission computed tomography using both a beta-methyl-branched fatty acid analog, 123I-15-(p-iodophenyl)-3-methyl-pentadecanoic acid (BMIPP), and thallium-201 (201Tl) were assessed in 30 patients with myocardial infarction (MI), 8 diabetics, 4 patients with impaired glucose tolerance, and 18 nondiabetic patients. Discordant decreases in BMIPP uptake, as compared with 201Tl uptake, in diabetic patients were significantly (p < 0.01) more frequent than in nondiabetic patients. The left ventricular (LV) ejection fraction in diabetics was significantly (p < 0.05) reduced and the LV diastolic dimension was significantly increased (p < 0.01), as compared with those in nondiabetic subjects. Analysis of peripheral blood showed no significant differences among the three test groups in metabolic abnormality. A discordant decrease in BMIPP uptake, as compared with Tl uptake, in cardiac tomography may indicate a metabolic derangement of the myocardium in diabetic patients with MI.