Murine tissue inhibitor of metalloproteinases-4 (Timp-4): cDNA isolation and expression in adult mouse tissues.

We have isolated cDNA clones corresponding to a new member of the murine tissue inhibitor of metalloproteinase (TIMP) family, designated Timp-4. The nucleotide sequence predicts a protein of 22,609 Da that contains the characteristic 12 cysteine TIMP signature. TIMP-4 is more closely related to TIMP-2 and TIMP-3 than to TIMP-1 (48%, 45% and 38% identity, respectively). Analysis of Timp-4 mRNA expression in adult mouse tissues indicated a 1.2 kb transcript in brain, heart, ovary and skeletal muscle. This pattern of expression distinguishes Timp-4 from other Timps, suggesting that the TIMP-4 protein may be an important tissue-specific regulator of extracellular matrix remodelling.

[Preventive effect of pravastatin on restenosis following coronary angioplasty: prospective randomized trial].

This study investigated the preventive effect of pravastatin on restenosis following successful transluminal coronary angiography (PTCA) in 109 consecutive patients. Patients were randomly and prospectively assigned to the pravastatin group (group P, n = 57) or the control group (group C, n = 52). The former received 10 mg/day pravastatin from the day of PTCA for 3 months. Restenosis was defined as a > or = 50% diameter stenosis at follow-up angiography with a > or = 15% reduction in luminal diameter compared to post-PTCA. The effect of pravastatin was analyzed in association with 7 clinical and 15 angiographic factors. Follow-up rate, serum lipid levels (total cholesterol, triglyceride, and HDL-cholesterol), and clinical and angiographic backgrounds except age and angularity of the lesions were not significantly different between the two groups at PTCA. Three months later, total cholesterol decreased from 222.3 +/- 35.1 to 179.2 +/- 31.2 mg/dl in group P, but was unchanged in group C (from 226.0 +/- 33.7 to 211.7 +/- 30.9 mg/dl). The restenosis rate was not different between the two groups (35.6 vs 35.7% per patient, 32.0 vs 33.3% per lesion). Moreover, no relationship between restenosis rate and serum total cholesterol level at follow-up angiography was observed. Multivariate analysis, including 7 clinical and 15 angiographic factors, found neither pravastatin administration nor serum lipid levels were significantly correlated with decreased luminal diameter. Pravastatin (10 mg/day) did not reduce the incidence of restenosis after PTCA when administered from the day of PTCA for 3 months.

[Surgical repair of valvular diseases in patients over 75 years of age].

From January 1985 through August 1993, 41 patients older than 70 years underwent valvular surgery. In them, 10 patients were older than 75 years old. We evaluated those operative results. First, we classified them into 3 groups; Group A: over 75 y.o. (10 cases), Group B: 70-74 y.o. (31 cases) and Group C: 60-69 y.o. (39 cases, from January 1992 through August 1993). Surgical deaths were 1 case in Group A, and 1 in Group B. Distant deaths were 1 case in Group B, and 2 in Group C. Preoperative cardiac catheterization data showed the progression of cardiac failure in proportion to aging. But postoperative data showed no difference among 3 groups, and the condition was reversible. NYHA classification and cardiothoracic ratio (CTR) showed the same results. In summary, in valvular diseases in patients over 75 years of age, the progression of the condition was recognized but it was reversible. So we conclude that the surgical repair of no influence of age is necessary.

[Reoperations for valvular heart disease through repeated median sternotomy incision].

One thousand and three hundred patients underwent open heart surgery for acquired valvular diseases in our hospital from 1952 through December 1993. There were 105 reoperative cases through repeated median sternotomy incision and 52 cases of prosthetic valve replacement by the same operator in the last 5 years. We studied technical procedures by these reoperative experience. There was only one case (1.9%) of hospital death in replacement cases. We believe that repeated open heart surgery for acquired valvular diseases should be done prior to deterioration of patient's clinical condition. We had to pay attention to facilitate mobilization of right atrium and aortic root in the aortic and mitral valvular reoperations. To decrease operative mortality of prosthetic valve replacement, each operative techniques were necessary by the reasons for reoperation.

Prediction of isolated first diagonal branch occlusion by 12-lead electrocardiography: ST segment shift in leads I and aVL.

OBJECTIVES: This study was performed to determine electrocardiographic (ECG) features that could distinguish first diagonal branch occlusion from left anterior descending coronary artery occlusion. BACKGROUND: The ECG findings associated with first diagonal branch obstruction have not previously been compared with those of left anterior descending coronary artery obstruction. METHODS: The ECG findings in 34 patients with isolated diagonal branch occlusion (group 9) were compared with those in 20 patients with occlusion at site 6 (group 6) and 20 with occlusion at site 7 (group 7), according to American Heart Association classification. This study had a power > 80% to detect a 50% difference between groups at a probability value of 0.05. RESULTS: ST segment elevation was observed in leads I and aVL for all group 9 patients, in 80% (p < 0.05) of group 6 patients for lead I and 90% for lead aVL and in 50% (p < 0.01) of group 7 patients for lead I and 55% (p < 0.01) for lead aVL. Similarly, there was a higher incidence of abnormal Q waves and inverted T waves in leads I and aVL in group 9 than in groups 6 and 7. In contrast, group 9 showed a significantly lower incidence of ST segment elevation (3.4%), abnormal Q waves (3.0%) and inverted T waves (0%) in lead V1 than group 6 (80%, 40% and 90%, respectively) and group 7 (75%, 60% and 70%, respectively) (p < 0.01 for each). Multivariate analysis revealed that abnormalities in leads I and aVL, combined with a normal lead V1 (and V6), provided good criteria for distinguishing isolated diagonal branch occlusion from left anterior descending coronary artery occlusion. CONCLUSIONS: Isolated diagonal branch occlusion more frequently caused ECG abnormalities in leads I and aVL and less frequently caused changes in the precordial leads compared with left anterior descending coronary artery obstruction, indicating that leads I and aVL represent myocardium perfused by the diagonal branch.

Histological abnormalities in a biopsy specimen obtained from the left ventricle without reduced function in a patient with right ventricular dysplasia.

Left ventricular histological examination was performed in a patient with right ventricular (RV) dysplasia. Although the left ventricle (LV) appeared to have a normal shape and function, the LV biopsy specimen revealed apparent myocyte hypertrophy and substantial fibrotic changes without fatty infiltration. It was not clear whether these considerable histological changes were part of right ventricular dysplasia or not. The present case indicates that even with normal LV shape and function in patients with right ventricular dysplasia, histological examination of LV may provide additional information on its pathogenesis and prognosis.

Acute left main coronary artery obstruction with myocardial infarction--reperfusion strategies, and the clinical and angiographic outcome.

We studied the clinical and angiographic outcomes in 8 patients with acute left main coronary artery obstruction. Intracoronary thrombolysis with 1.2 x 10(5) units of urokinase was performed in 3 patients during preparation for percutaneous transluminal coronary angioplasty (PTCA), and failed in all 3 cases. In 2 patients, the left main coronary artery was recanalized by intracoronary thrombolysis with 3.6 and 4.8 x 10(5) units of urokinase, respectively. PTCA was attempted either before or after intracoronary thrombolysis in 5 patients and achieved reperfusion in all 5 cases. However, 2 of the 8 patients had persistent high-grade residual stenosis 69% and 89% luminal reduction, respectively. Emergency coronary artery bypass grafting was successfully performed in these 2 patients, and both are currently alive. Although intraaortic balloon counterpulsation was performed in all 8 patients, 2 died acutely from pump failure in the catheterization laboratory. One patient died later due to congestive heart failure. The factors favoring survival were right coronary artery dominance and a well-developed collateral circulation. Our findings suggest that PTCA is a useful strategy for reperfusion following acute left main coronary artery occlusion. When PTCA cannot achieve sufficient revascularization, emergency coronary artery bypass grafting should be performed. To control pump failure, intraaortic balloon counterpulsation is insufficient in some cases and more aggressive measures may be required.

Progression of left ventricular enlargement in patients with hypertrophic cardiomyopathy: incidence and prognostic value.

A total of 51 patients with hypertrophic cardiomyopathy (HCM) were followed for at least 3 years (mean follow-up period 6.5 years) by serial M-mode and two-dimensional echocardiography. An increase of the left ventricular diastolic dimension (LVDd) to > or = 55 mm with a decrease in the left ventricular ejection fraction (LVEF) to < 55% was observed in eight (15.7%) patients (progressive disease group). In five of these eight patients, the LVDd was > or = 60 mm and the LVEF was < 40%. Ventricular enlargement was closely related to mortality and death due to congestive heart failure occurred in three of these patients. No deaths occurred among the 37 patients without significant progression of ventricular enlargement (nonprogressive group). The annual changes of LVEF and LVDd in the progressive disease group were larger than in the nonprogressive group (LVEF -0.18 +/- 1.45 vs. -2.46 +/- 1.47 %/year; LVDd 0.22 +/- 0.81 vs. 1.43 +/- 0.77 mm/year). An increment in LVDs occurred earlier than the enlargement of the LVDd. Therefore, close attention to the LVDs seems to be important to detect early left ventricular morphological changes in HCM. In summary, this study indicates that HCM patients include a subgroup with symptoms resembling dilated cardiomyopathy, in whom the left ventricle enlarges with hypofunction and in whom there is high mortality due to congestive heart failure.

[A surgical case report of severe valvular aortic stenosis with atrial septal defect in a 78-year-old female].

We have experienced open heart surgery of severe valvular aortic stenosis associated with atrial septal defect in a 78-year-old female patient. This is the oldest case in Japanese literature. Because balloon valvuloplasty can not produce improvement in hemodynamic and clinical status, open heart surgery was performed as the final decision. The operative procedure consisted of aortic valve replacement with a 19 mm St. Jude Medical valve and direct closure of atrial septal defect. Postoperative course was excellent. The patient is doing well at the two years and three months of follow-up period.

Emergency coronary angioplasty for acute myocardial infarction--factors affecting acute restenosis in catheterization laboratory and reocclusion during hospitalization.

A total of 107 consecutive patients with acute myocardial infarction underwent emergency coronary angioplasty (PTCA). Restoration of blood flow with TIMI grade III was established by emergency PTCA in 101 patients (94.4%). "Acute restenosis" was defined as a lesion that, when dilated to less than 50%, narrowed again to more than 75% luminar reduction 5 min after the balloon inflation. Acute restenosis occurred in 39 patients (39%). Multivariate analysis selected 3 factors associated significantly with an increased rate of acute restenosis: (1) dissection, (2) small balloon/artery diameter ratio and (3) low systolic blood pressure during PTCA. Reocclusion, which was defined as a total reobstruction of the lesion during hospitalization following emergency PTCA, was examined by predischarge coronary angiography. Acute restenosis correlated significantly with an increase in reocclusion rate. The incidence of documented reocclusion was 12%. Residual stenosis, multivessel disease and irregular dilation correlated significantly with an increased rate of reocclusion. The in-hospital and postdischarge mortalities were 5.6% and 2.1%, respectively. In summary, emergency PTCA produced a high angiographic success rate. Use of adequate balloon size and sufficient dilation correlated significantly with angiographic outcome in emergency PTCA. Patients with acute restenosis, high residual stenosis, irregular dilation, and multivessel disease would have a relatively high risk of reocclusion.

Effects of reperfusion on left ventricular ejection fraction and volume after acute myocardial infarction.

The effects of reperfusion on left ventricular (LV) function and volume were studied in patients with evolving acute myocardial infarction (AMI). We analyzed the LV ejection fraction and volume in patients who had been admitted within 24 h of the onset of their first AMI with culprit lesion of #6, #7 and #1 (American Heart Association classification). Sixty-five patients (Re group) received successful reperfusion therapy within 6 h after the AMI. The other 60 patients (Oc group), who were admitted from 6 to 24 h after the AMI, received conservative therapy. Patients with re-obstruction of the culprit lesion after reperfusion therapy were excluded from the Re group. Patients with spontaneous recanalization following conservative therapy were excluded from the Oc group. The LV ejection fraction (LVEF), LV end-systolic volume index (LVESVI), and LV end-diastolic volume index (LVEDVI) were measured using a modified Dodge's formula by left ventriculography performed 4 weeks after the AMI. LVEF in the Re group was significantly greater than in the Oc group (57 +/- 12 vs 49 +/- 11%) (mean +/- SD, p less than 0.01). LVESVI in the Re group was significantly smaller than in the Oc group (30 +/- 13 vs 38 +/- 16 ml/m2, p less than 0.01). Although LVEDVI was not significantly different between the 2 groups, in patients with a responsible coronary lesion of segment #6, LVEDVI in the Re group was significantly smaller than in the Oc group (67 +/- 14 vs 77 +/- 18 ml/m2, p less than 0.05). Although LVEF and LV volume correlated in both groups, the correlation was weak (r = 0.40-0.42), suggesting that LV volume was not dependent solely on LV functional recovery. The incidence of ventricular aneurysm in the Re group was significantly lower than in the Oc group (15.4 vs 45.0%, p less than 0.01). Multivariate analysis selected reperfusion of the responsible coronary artery as one of the factors significantly associated with a reduction of LVEDVI, LVESVI, an improvement of LVEF, and a decrease in the rate of aneurysm formation. In summary, our results indicated that reperfusion improved EF, reduced LV volume, and decreased the rate of aneurysm formation as compared to non-reperfusion, which suggests that reperfusion therapy is beneficial for both functional recovery and ventricular remodeling.