Papers - KAIKITA Koichi
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Increased plasma tissue factor levels in acute myocardial infarction Reviewed
Suefuji H., Ogawa H., Yasue H., Kaikita K., Soejima H., Motoyama T., Mizuno Y., Oshima S., Saito T., Tsuji I., Kumeda K., Kamikubo Y., Nakamura S.
American Heart Journal 134 ( 2 I ) 253 - 259 1997
Language：English Publishing type：Research paper (scientific journal) Publisher：American Heart Journal
Background: Tissue factor (TF) is a low molecular weight glycoprotein that initiates the clotting cascade and is considered to be a major regulator of coagulation, hemostasis and thrombosis Methods and Results: We examined plasma TF levels in 31 consecutive patients with acute myocardial infarction (AMI) (within 6 hours after the onset of symptoms), 27 patients with stable exertional angina, and 27 control subjects. Ten patients with AMI had a history of unstable angina before infarction, and 21 had a sudden onset of infarction. The plasma TF level was higher in the AMI group than in the stable exertional angina and control groups (240 ± 112 vs 184 ± 46 pg/ml [p < 0.05] vs 177 ± 37 pg/ml, p < 0.01, respectively). TF levels were decreased in the chronic phase (2 weeks after admission) compared with the acute phase of infarction (from 240 ± 112 pg/ml to 222 ± 97 pg/ml, p < 0.05). In addition, plasma TF levels were higher in patients with AMI with prodromal unstable angina than in patients with a sudden onset of infarction (300 ± 169 pg/ml vs 212 ± 57 pg/ml, p < 0.05). TF levels were similar in the acute and chronic phases in the patients with AMI with prodromal unstable angina (300 ± 169 pg/ml vs 290 ± 136 pg/ml, p = not significant) but were decreased in the chronic phase in the patients with AMI with sudden onset (from 212 ± 57 pg/ml to 190 ± 49 pg/ml, p < 0.05). Conclusion: Increased plasma TF levels in patients with AMI may reflect enhanced intravascular procoagulant activity. The higher TF levels in patients with AMI with prodromal unstable angina may be associated with repeated episodes of myocardial ischemia and reperfusion.
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Oshima S., Ogawa H., Mizuno Y., Yamashita S., Noda K., Saito T., Sumida H., Suefuji H., Kaikita K., Soejima H., Yasue H.
American Heart Journal 134 ( 5 I ) 961 - 966 1997
Language：English Publishing type：Research paper (scientific journal) Publisher：American Heart Journal
This study sought to determine whether early treatment with angiotensin- converting enzyme (ACE) inhibitors in patients with acute myocardial infarction (AMI) is useful for the improvement of fibrinolytic function, as well as left ventricular function. This study was designed to examine the levers of plasma plasminogen activator inhibitor (PAI) activity and serum ACE activity during the course of 2 weeks in 40 patients with AMI within 12 hours after the onset of the symptom and who randomly received early treatment with either the ACE inhibitor imidapril or a placebo (20 patients in the imidapril group and 20 in me placebo group). The levels of serum ACE activity in the imidapril group decreased significantly (p < 0.01) 8 hours after the administration of imidapril, and the levels 24 hours after administration were significantly lower than those in the placebo group (3.6 ± 0.6 IU/L vs 7.4 ± 0.8 IU/L; p < 0.001). The plasma PAI activity increased gradually to peak levels 16 hours after the administration of imidapril and placebo. The levels in the placebo group decreased gradually but remained high during the study period. On the other hand, the levels of PAI activity in the imidapril group decreased rapidly and those 48 hours after administration were significantly lower than those in the placebo group (7.9 ± 1.9 IU/ml vs 18.4 ± 3.5 IU/ml; p < 0.01). The levels of left ventricular election fraction about 2 weeks after admission were significantly higher in the imidapril group than in the placebo group (65.9% ± 2.5% vs 49.1% ± 4.4%; p < 0.01). This study showed that imidapril, an ACE inhibitor, might be useful for the improvement of fibrinolytic function and left ventricular function in the acute phase of myocardial infarction.
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Tissue factor expression on macrophages in coronary plaques in patients with unstable angina Reviewed
Kaikita K., Ogawa H., Yasue H., Takeya M., Takahashi K., Saito T., Hayasaki K., Horiuchi K., Takizawa A., Kamikubo Y., Nakamura S.
Arteriosclerosis, Thrombosis, and Vascular Biology 17 ( 10 ) 2232 - 2237 1997
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Arteriosclerosis, Thrombosis, and Vascular Biology
Tissue factor is a membrane-bound glycoprotein that functions in the oxtrinsic pathway of blood coagulation by acting as a cofactor for factor VII, and the resulting complex leads to thrombin production in vivo. The purpose of the present study is to determine whether macrophages express tissue factor in human coronary atherosclerotic plaques. We examined directional coronary atherectomy specimens from 24 patients with unstable angina and 23 with stable exertional angina. In these specimens, macrophages were detected in 22 (92%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P=.003). The percentage of macrophage infiltration area was significantly larger in patients with unstable angina than in those with stable exertional angina (17±3% versus 6±2%, P=.008). The immunohistochemical double staining revealed the expression of tissue factor on macrophages in 18 (75%) of 24 patients with unstable angina versus 3 (13%) of 23 with stable exertional angina (P<.0001). Thrombus was identified in 20 (83%) of 24 patients with unstable angina versus 12 (52%) of 23 with stable exertional angina (P=.02). Fibrin deposition was mainly observed around macrophages expressing tissue factor in the patients with unstable angina. We have shown that tissue factor expression on macrophages was more frequent in coronary atherosclerotic plaques in patients with unstable angina. Tissue factor expressed on macrophages may play an important role in the thrombogenicity in coronary atherosclerotic plaques of these patients.
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Effects of enalapril on tissue factor in patients with uncomplicated acute myocardial infarction Reviewed
Soejima H., Ogawa H., Yasue H., Suefuji H., Kaikita K., Tsuji I., Kumeda K., Aoyama N.
American Journal of Cardiology 78 ( 3 ) 336 - 340 1996.8
Language：English Publishing type：Research paper (scientific journal) Publisher：American Journal of Cardiology
In a randomized, double-blind, placebo-controlled study beginning 4 weeks after uncomplicated acute myocardial infarction, it was established that the baseline plasma tissue factor antigen level was significantly higher in patients with myocardial infarction than in control subjects, and enalapril therapy significantly reduced the elevated plasma tissue factor antigen level. This may be associated with the reduction in the risk of coronary thrombosis seen with the use of angiotensin-converting enzyme inhibitors.
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Suefuji H., Ogawa H., Yasue H., Imoto N., Sakamoto T., Miyao Y., Kaikita K., Soejima H., Nishiyama K.
Coronary Artery Disease 7 ( 2 ) 167 - 172 1996
Language：English Publishing type：Research paper (scientific journal) Publisher：Coronary Artery Disease
Background: Lipoprotein (a) [Lp(a)] is an independent risk factor for coronary artery disease and niceritrol (a prodrug of nicotinic acid) is known to reduce Lp(a) levels. Patients with coronary artery disease often have impairment of the fibrinolytic system. Methods: To elucidate the effect of niceritrol on fibrinolysis and Lp(a) levels, we examined plasminogen activator inhibitor (PAI) activity, tissue-type plasminogen activator (t-PA) antigen, and serum Lp(a) levels before and after administration of niceritrol to coronary artery disease patients with high baseline Lp(a) levels (≤ 20 mg/dl). Niceritrol was administered to 26 patients for 12 weeks at 750 mg/day. Fasting blood samples were obtained at 0800 h from each patient before treatment, after administration of niceritrol for 12 weeks and 4 weeks after the discontinuation of therapy. Results: There were significant reductions in PAI activity (9.9 ± 1.8 compared with 5.4 ± 1.6 IU/ml, P < 0.01), t-PA antigen levels (10.0 ± 0.5 compared with 8.8 ± 0.6 ng/ml, P < 0.05), and Lp(a) levels (49.3 ± 5.9 compared with 42.5 ± 5.4 mg/dl, P < 0.01) after 12 weeks of niceritrol administration. Four weeks after the discontinuation of niceritrol treatment, all these parameters returned to baseline. Conclusions: This study demonstrated that niceritrol administration decreases PAI activity and t-PA antigen levels together with Lp(a) levels in patients with coronary artery disease. These observations suggest that niceritrol administration may tend to normalize fibrinolysis in such patients.
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Hokimoto S., Yasue H., Fujimoto K., Yamamoto H., Nakao K., Kaikita K., Sakata R., Miyanioto E.
Circulation 94 ( 7 ) 1513 - 1518 1996
Language：English Publishing type：Research paper (scientific journal) Publisher：Circulation
Background: Local ACE in the heart may be important in the pathophysiological state after myocardial infarction (MI). It is unknown, however, whether ACE is expressed in myocytes of the human heart. Methods and Results: Using a newly generated polyclonal antibody to a synthetic peptide corresponding to part of the human endothelial ACE sequence, we examined the localization of ACE in left ventricles of patients (n=10) with MI obtained at left ventricular aneurysmectomy or autopsy and in the hearts of control subjects at autopsy (n=10). The avidin-biotinylated peroxidase complex method was used for the immunohistochemical staining for ACE. In the left ventricles, positively stained myocytes for ACE were found in 8 of the 10 patients with MI. ACE immunoreactivity was seen in the remaining viable myocytes located near the infarct scar of the aneurysmal left ventricle and in nonmyocytes such as fibroblasts, macrophages, vascular smooth muscle cells, and endothelial cells within the scarred tissue. On the other hand, no immunoreactivity for ACE was detected in the ventricular myocytes of all control hearts obtained at autopsy. Conclusions: We observe immunohistochemical staining for ACE in the left ventricular myocytes of the region adjacent to the infarct scar and in nonmyocytes. These results indicate that ACE is markedly increased on the edge of the infarct scar and suggest that local ACE may be important in the ventricular remodeling after MI.
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Soluble P-selectin is released into the coronary circulation after coronary spasm Reviewed
Kaikita K., Ogawa H., Yasue H., Sakamoto T., Suefuji H., Sumida H., Okumura K.
Circulation 92 ( 7 ) 1726 - 1730 1995.10
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Circulation
Background: The glycoprotein P-selectin is an adhesion molecule involved in the property change of leukocytes at the initiation of the inflammatory process. The purpose of the present study was to determine whether acute myocardial ischemia induced by coronary spasm causes an acute inflammatory response in the coronary circulation. Methods and Results: We examined plasma soluble P-selectin levels in the coronary sinus and the aortic root simultaneously in 16 patients with coronary spastic angina before and after left coronary artery spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Ten control patients with chest pain but normal coronary arteries and no coronary spasm also received intracoronary acetylcholine. Plasma soluble P-selectin levers were increased significantly in the coronary sinus (32.8 ± 3.6 to 52.8 ± 5.9 ng/mL, P<.001) and in the aortic root (34.6±3.7 to 41.9±4.4 ng/mL, P<.05) after the attacks in the coronary spastic angina group but remained unchanged in the stable exertional angina group after the attacks and in the control group after the administration of acetylcholine. Furthermore, the coronary sinus-arterial difference of soluble P-selectin increased significantly after the attacks in the coronary spastic angina group (1.8 ± 2.2 to 10.9 ± 2.7 ng/mL, P<.001). Conclusions: Our data indicate that soluble P-selectin is released into the coronary circulation after coronary artery spasm. We conclude that coronary artery spasm may induce the leukocyte adhesion in the coronary circulation and may lead to myocardial damage.
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A Case of 5-Fluorouracil Cardiotoxicity Simulating Acute Myocardial Infarction Reviewed
Mizuno Y., Hokamura Y., Kimura T., Kimura Y., Kaikita K., Yasue H.
Japanese Circulation Journal 59 ( 5 ) 303 - 307 1995
Language：English Publishing type：Research paper (scientific journal) Publisher：Japanese Circulation Journal
5-Fluorouracil (5-FU) is widely used in the treatment of various solid tumors. However, 5-FU cardiotoxicity is being reported with increasing frequency. The main symptom of cardiotoxicity is chest pain at rest with ischemic electrocardiographic changes. Up until now, the underlying mechanism has been suspected to be coronary artery spasm. However, this chest pain associated with 5-FU has several characteristics that are incompatible with coronary artery spasm; eg, inefficacy of calcium-channel blocker and a slow increase in cardiac enzyme levels. We experienced a case of 5-FU-induced cardiotoxicity which showed clinical findings consistent with acute myocardial infarction. Based on the clinical findings, coronary angiography, and left ventricular angiography in a prolonged attack, we concluded that the cardiotoxicity in this case was not due to ischemia caused by coronary artery spasm. © 1995, The Japanese Circulation Society. All rights reserved.
DOI： 10.1253/jcj.59.303