Ikuo Misumi

Elevated plasma interleukin-6 levels in patients with acute myocardial infarction

Interleukin-6 (IL-6) plays a key role in the synthesis of human acute-phase protein and several acute-phase responses occur in patients with acute myocardial infarction (AMI). We examined the plasma levels of IL-6 in 23 consecutive patients with AMI over the course of 4 weeks and in 30 control subjects. In patients with AMI, the plasma IL-6 levels (in picograms per milliliter) were increased at all sampling points from admission to discharge (ranging from 28.5 +/- 6.6 to 46.5 +/- 7.8) compared with levels in control subjects (11.4 +/- 2.9; p < 0.01). Cardiac catheterization did not influence plasma IL-6 levels. The plasma IL-6 level reached its peak approximately 3 days (46.5 +/- 7.8) and approximately 1 week after admission in patients with AMI. There was a significant positive linear correlation between the peak level of plasma IL-6 minus the level on admission and the peak level of plasma C-reactive protein in patients with AMI. The peak IL-6 level did not correlate with the peak levels of creatine kinase, pulmonary capillary wedge pressure, or left ventricular ejection fraction at 4 weeks. We conclude that the plasma IL-6 level is increased over a time course of 4 weeks in patients with AMI.

Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells.

Decreased fibrinolytic activity has been reported in atherosclerotic cardiovascular diseases. To determine whether oxidized low-density lipoprotein (Ox-LDL), which accumulates in atherosclerotic arteries, modulates the endothelial fibrinolytic system, cultures of human umbilical vein endothelial cells were incubated with low-density lipoproteins or lipids, and levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) antigens in the conditioned medium were measured by enzyme-linked immunosorbent assay. Ox-LDL (30 micrograms protein/mL) and its extracted lipid (50 micrograms cholesterol/mL) stimulated PAI-1 release by 42 +/- 3% and 29 +/- 3% of control cultures, respectively, whereas Ox-LDL and its lipid inhibited t-PA release by 42 +/- 4% and 53 +/- 3% of control cultures, respectively. Native LDL and its lipid were inactive on their release. Ox-LDL depleted of hydrophilic lipids, which was prepared by the incubation with defatted albumin (an acceptor for hydrophilic lipids), lost both the stimulatory action on PAI-1 and the inhibitory action on t-PA. The extracted lipid from the incubated albumin, which has been found to accept the hydrophilic lipids from Ox-LDL, gained the stimulatory action on PAI-1 and the inhibitory action on t-PA. Ox-LDL depleted of lysophosphatidylcholine (LPC), which was prepared by the incubation with phospholipase B, lost the stimulatory effect on PAI-1, whereas the inhibitory effect on t-PA remained present in the Ox-LDL depleted of LPC. The incubation with synthetic palmitoyl LPC (10 microM) stimulated PAI-1 release by 85 +/- 7% of control.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian variation in fibrinolytic activity in patients with variant angina.

BACKGROUND--Coronary artery spasm induces activation of the coagulation system. Turnover and maintenance of thrombus depend not only on formation but also on lysis. The relation between coronary spasm and fibrinolytic system has not been elucidated. OBJECTIVE--To examine whether there is impairment of or a circadian variation in fibrinolytic activity in patients with variant angina. METHODS--Plasminogen activator inhibitor (PAI) activity and concentrations of tissue plasminogen activator (t-PA) antigen were measured in venous plasma samples taken at 2200, 0600, and 1400 and 24 h Holter tapes were recorded in 15 patients with variant angina, 12 patients with stable exertional angina, and 12 controls. RESULTS--There were significant circadian variations in PAI activity and t-PA antigen with peak values at 0600 in all three groups. Mean (SEM) PAI activity (IU/ml) at 2200, 0600, and 1400 was 6.1 (1.1), 11.0 (1.3), and 4.4 (0.6) in the variant angina group; 1.8 (0.7), 5.6 (1.1), and 1.2 (0.3) in the stable exertional angina group; and 1.1 (0.5), 4.5 (0.8), and 0.7 (0.3) in the control group. Furthermore, both plasma PAI activity and t-PA antigen concentrations were significantly higher in the variant angina group than in the stable exertional angina group and the control group at each sampling time. CONCLUSIONS--In patients with variant angina there was a circadian variation in fibrinolytic activity, which was lowest in the early morning, and impaired fibrinolytic activity particularly in the early morning, when attacks of angina occur most frequently.

Association of patency of the infarct-related coronary artery with plasma levels of plasminogen activator inhibitor activity in acute myocardial infarction

To examine the fibrinolytic capacity in patients with acute myocardial infarction (AMI), baseline levels of plasma plasminogen activator inhibitor (PAI) activity and tissue-type plasminogen activator (t-PA) antigen were measured in 47 patients with Q-wave AMI who underwent emergent coronary angiography 3.0 +/- 0.2 hours after the symptom onset. They received intracoronary injection of urokinase if their infarct-related arteries were occluded. They were classified into 3 groups according to the patency of the infarct-related artery before and after thrombolytic therapy: the patent group (13 patients), the recanalized group (23 patients) and the occluded group (11 patients). The mean level of plasma PAI activity (IU/ml) was higher in patients with AMI as a whole than in the control group (12.8 +/- 1.6 vs 5.4 +/- 0.5, p less than 0.01). The level was lower in the patent group (3.0 +/- 1.1) and higher in the recanalized (18.6 +/- 2.2) and occluded (10.8 +/- 2.5) groups than in the control group (each p less than 0.01). The level was lower in the occluded than in the recanalized group (p less than 0.01) and 62% of the patients in the occluded group had levels within range of the control group. The mean level of plasma t-PA antigen (ng/ml) was higher in patients with AMI as a whole than in the control group (10.3 +/- 0.8 vs 5.8 +/- 0.3, p less than 0.01). There was no difference in the level among the 3 groups with AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma plasminogen activator inhibitor activity and tissue plasminogen activator levels in patients with unstable angina and those with coronary spastic angina

Plasminogen activator inhibitor (PAI) activity and tissue plasminogen activator (TPA) antigen were measured in venous samples in 14 patients with unstable angina consisting of eight patients with organic stenosed coronary arteries and six patients with coronary spastic angina (unstable angina group); in 14 patients with stable exertional angina (stable exertional angina group); and in 14 patients with chest pain syndrome (chest pain syndrome group). The plasma levels of PAI activity were higher (p less than 0.01) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (12.3 +/- 1.0 versus 5.1 +/- 0.7 and 4.8 +/- 0.6 IU/ml). The plasma levels of TPA antigen were also higher (p less than 0.05) in the unstable angina group than in the stable exertional angina group and the chest pain syndrome group (10.2 +/- 1.3 versus 6.5 +/- 0.8 and 6.0 +/- 0.7 ng/ml). There were no significant differences in PAI activity and TPA antigen levels between the stable exertional angina group and the chest pain syndrome group. Furthermore, both PAI activity and TPA antigen levels in the unstable angina group decreased to the levels in the stable exertional angina group and the chest pain syndrome group after treatment (p less than 0.01). In conclusion, the increased plasma PAI activity in patients with unstable angina and in those with coronary spastic angina indicates that the fibrinolytic system is impaired in these patients.

Electrophysiological Delineation of the Tachycardia Circuit in Atrioventricular Nodal Reentrant Tachycardia

BACKGROUND The exact boundaries of the reentry circuit in atrioventricular nodal reentrant tachycardia (AVNRT) have not been convincingly defined. METHODS AND RESULTS To define the tachycardia circuit, single extrastimuli were delivered during AVNRT to 8 sites of the right intra-atrial septum: 3 arbitrarily divided sites of the AV junction extending from the His bundle (HB) site to the coronary sinus ostium (CSOS) (sites S, M, and I) and the superior (S-CSOS), inferior (I-CSOS), posterior (P-CSOS), and posteroinferior (PI-CSOS) portions of the CSOS and the CSOS in 18 patients. The mean tachycardia cycle length (TCL) was 368+/-52 ms. Retrograde earliest atrial activation was observed at the HB site in all patients. The longest coupling intervals of single extrastimuli that reset AVNRT at sites S, M, I, I-CSOS, CSOS, S-CSOS, P-CSOS, and PI-CSOS were 356+/-51, 356+/-51, 355+/-52, 357+/-51, 318+/-47, 305+/-53, 311+/-56, and 312+/-56 ms, respectively, and the following return cycles at these sites were 368+/-52, 368+/-53, 367+/-53, 367+/-53, 407+/-66, 431+/-73, 415+/-55, and 412+/-56 ms, respectively. The longest coupling intervals at sites S, M, I, and I-CSOS did not differ from each other and were longer than those at CSOS and S-, P-, and PI-CSOS (P<0.0001). The return cycles at sites S, M, I, and I-CSOS did not differ from the TCL, whereas those at CSOS and S-, P-, and PI-CSOS were longer than the TCL (P<0.0001). CONCLUSIONS The perinodal atrium extending from the HB site to I-CSOS was involved in the tachycardia circuit. I-CSOS was thought to be the entrance of the slow pathway.

Conduction Properties of the Crista Terminalis and Its Influence on the Right Atrial Activation Sequence in Patients with Typical Atrial Flutter

YAMABE, H., et al.: Conduction Properties of the Crista Terminalis and Its Influence on the Right Atrial Activation Sequence in Patients with Typical Atrial Flutter. The conduction properties of the crista terminalis (CT) and its influence on the right atrial activation sequence were analyzed in 14 patients with typical atrial flutter (AF). Atrial mapping was performed with 35 points of the right atrium during typical AF and during atrial pacing performed after linear ablation of inferior vena cava‐tricuspid annulus (IVCTA) isthmus. Atrial pacing was delivered from the septal isthmus at cycle lengths of 600 ms and the tachycardia cycle length (TCL). The right atrial activation sequence and the conduction interval (CI) from the septal to lateral portion of the IVC‐TA isthmus were analyzed. During AF, the conduction block line (CBL) (detected by the appearance of double potentials along the CT and craniocaudal activation on the side anterior to CT) was observed along the CT in all patients. The TCL and CI during AF were 254 ± 19 and 207 ± 14 ms, respectively. During pacing at a cycle length of 600 ms, the CBL was observed along the CT in four patients, however, a short‐circuiting activation across the CT was observed in the remaining ten patients. The CI during pacing at 600 ms was 134 ± 38 ms, shorter than that during AF (P < .0001). During pacing at the TCL, the CBL was observed along the CT in all patients. The presence of the CBL along the CT prevented a short‐circuiting activation across the CT and resulted in the same right atrial activation as observed during AF. With the formation of the CBL, the CI significantly increased to 206 ± 17 ms and was not different from that during AF. These data suggest that the conduction block along the CT is functional. It was presumed that presence of conduction block at the CT has some relevance to the initiation of typical AF though it was not confirmed.

Plasma platelet-derived growth factor levels in coronary circulation in unstable angina pectoris

To examine whether plasma platelet-derived growth factor (PDGF) levels are elevated in the coronary circulation of patients with unstable angina, the plasma PDGF levels in the coronary sinus and aortic root were simultaneously examined in 14 patients with unstable angina, 15 with stable exertional angina, and 15 control subjects. The mean plasma PDGF level (pg/ml) in the coronary sinus was significantly higher (p less than 0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (502.1 +/- 98.7 vs 301.3 +/- 62.5, and 312.7 +/- 62.6). However, there were no significant differences in mean plasma PDGF levels in the aortic root among the 3 groups. It is concluded that PDGF release is increased in the coronary circulation in patients with unstable angina.

Role of bipolar electrogram polarity mapping in localizing recurrent conduction in the isthmus early and late after ablation of atrial flutter

OBJECTIVES Bipolar electrogram polarity was analyzed to localize the recurrent conduction site in the isthmus between the tricuspid annulus (TA) and inferior vena cava (IVC) in recurrent atrial flutter (AF). BACKGROUND Despite the initial successful linear isthmus ablation, recurrence of transisthmus conduction and AF is not uncommon. It is unclear how the recurrent conduction site can be identified. METHODS Fourteen patients with recurrent AF were studied: four with late recurrence remote from the first ablation and 10 with early recurrence within 60 minutes after the initial successful ablation. Bipolar electrogram polarity mapping was performed during low lateral right atrium (LLRA) pacing during sinus rhythm while recording bipolar electrograms from the septal portion of the isthmus along the previously ablated line. The septal side of the isthmus from TA to IVC was arbitrarily divided into five sites, and the bipolar electrodes with cathode at the tip and anode at the second was placed at each site. The recurrent conduction site was localized by analyzing the polarity of the bipolar electrogram recorded at each site. RESULTS All recurrent AF was due to reentry around TA. During pacing from LLRA, as the mapping electrode was moved from TA to IVC side, the major polarity of the electrogram changed from negative to positive in all patients. A transitional electrogram with the equal amplitudes in positive and negative components was recorded between the sites showing mainly negative and positive electrograms, indicating electrogram polarity reversal at this site. Application of radiofrequency energy to this single site resulted in the elimination of transisthmus conduction in all patients with a single application in 11 patients and 2 or 3 in the remaining 3. CONCLUSIONS Bipolar electrogram polarity mapping with attention to the polarity reversal point is useful for identifying and ablating the recurrent conduction site.

Congenitally Corrected Transposition of the Great Arteries with a Patent Foramen Ovale in an 81-Year-Old Man A Case Report

Congenitally corrected transposition of the great arteries is a rare cardiac anomaly with a poor prognosis. In this report, the authors describe an 81-year-old man admitted to the hospital with generalized fatigue, chest pain, and cyanosis. Computed tomography and cardiac catheterization revealed corrected transposition of the great arteries. Transesophageal echocardiography disclosed moderate right atrioventricular regurgita tion and a right-to-left shunt across a patent foramen ovale during systole. Because this patient had no other congenital cardiac anomalies, the right-to-left shunt through the patent foramen ovale was thought to be the major cause of cyanosis.