Masaru Miyataka

Basic fibroblast growth factor increased regional myocardial blood flow and limited infarct size of acutely infarcted myocardium in dogs

Basic fibroblast growth factor (bFGF), a growth factor potent in promoting angiogen esis, has been shown to reduce infarct size in experimentally induced acute myocardial infarction. However, the effect of bFGF on regional myocardial blood flow (Qm) in the acutely infarcted myocardium has not been well clarified. In 20 open-chest dogs, the left anterior descending (LAD) coronary artery was occluded and animals were maintained in this condition for 4 weeks. In eight of these dogs, bFGF (300 μg) was injected into the myocardium supplied by the LAD and the artery was ligated (bFGF group), and in the other 12 dogs, saline was injected (control group). Nonradioactive colored microspheres were used to measure Qm. The amount of viable myocardium as percent of visual field in the microscope and the extent of fibrosis scored histologically from 0 to 5 in the infarcted area 4 weeks after occlusion were measured. In the outer layer, the Qm values immediately after and 4 weeks after occlusion were 26 ± 2% and 70 ± 6%, respectively, in the control group, and 46 ± 5% and 121 ± 13%, respectively, in the bFGF group. The Qm at both times in the bFGF group was significantly higher than the corresponding control group values (p < 0.01). The Qm at 4 weeks in the inner and the middle layers also significantly increased in the bFGF group. There was more viable myocardium (control vs bFGF group; 41 ± 5 vs 61 ± 7%, p<0.05) and less fibrosis (3.1 ± 0.2 vs 2.0 ± 0.4, p < 0.01) at the outer layer in the bFGF group. It was found that bFGF caused a marked increase in Qm, an increase of viable myocardium, and a decrease of fibrosis in the infarcted myocardium in dogs.

Basic fibroblast growth factor increases regional myocardial blood flow and salvages myocardium in the infarct border zone in a rabbit model of acute myocardial infarction.

Basic fibroblast growth factor (bFGF) has been shown by some to promote angiogenesis and myocardial salvage in experimentally induced acute myocardial infarction. Although these findings have spurred much clinical interest, they are not universally observed, and the true efficacy of bFGF remains unclear. The authors used a rabbit model of acute myocardial infarction to further elucidate the effects of bFGF on acutely infarcted myocardium containing few collaterals. Myocardial infarction was evoked by ligation of the left coronary artery. Prior to ligation, either 100 μg of bFGF (bFGF group; n = 15) or physiological saline (control group; n = 22) was injected into the myocardium supplied by the ligated artery. With use of nonradioactive colored microspheres, regional blood flow (Qm) was measured before, immediately after, and 4 weeks after coronary artery ligation. Infarct and border zone sizes were measured in cross-sectional slices of the resected hearts, and the amount of viable myocardium (myocardium score) and the extent of fibrosis were histologically determined in each area. Four weeks after ligation, Qm values in the infarcted area did not significantly differ between the bFGF and control groups (0.54 ± 0.36 vs 0.48 ± 0.30 mL/min/g); in the border zone, Qm tended to be higher in the bFGF group (3.39 ± 2.68 vs 1.47 ± 0.80 mL/min/g), but the difference was not significant; finally in the noninfarcted area, Qm was significantly (p < 0.05) higher in the bFGF group (6.06 ± 3.85 vs 2.09 ± 0.82 mL/min/g). There was no significant differ ence in the amount of viable myocardium or the extent of fibrosis in the infarcted areas of the two groups. In the border zone, however, the amount of viable myocardium was significantly (p < 0.005) larger in the bFGF group (61.8 ±8.5% vs 35.8 ±20.3% of the visual field). Likewise, as graded on a scale from 0 to 5, the extent of fibrosis was signif icantly (p < 0.005) less in the bFGF group (2.1 ±0.5 vs 3.3 ±0.8). In conclusion, injection of bFGF into acutely infarcted myocardium increased blood flow to the noninfarcted area and salvaged the myocardium in the border zone.

Incidence of cancer in postmyocardial infarction patients treated with short‐acting nifedipine and diltiazem

Recent reports suggest a possible link between nifedipine (but not diltiazem) and an increased risk of cancer in patients being treated with calcium antagonists.

Efficacy of Coronary Angioplasty Following Conventional Coronary Thrombolysis in Patients with Acute Myocardial Infarction

The efficacy of combined thrombolysis and angioplasty for the purpose of coronary reperfusion after acute myocardial infarction has been controversial. The present study was conducted, therefore, to evaluate the effects of angioplasty following administration of conventional thrombolytic agents on the long-term prognosis of acute myocardial infarction patients. A total of 409 patients admitted to the hospital within 12 hours of the onset of infarction between January 1990 and May 2001 were studied retrospectively. These included 151 patients treated with thrombolysis alone (group T), 73 patients treated with angioplasty alone (group A), and 35 patients treated with angioplasty after thrombolysis (group T&A). Group T&A had shorter intervals from onset to initial treatment than group A (3.0 hours vs 6.3 hours, p<0.01), a higher reperfusion success rate than group T (91.4% vs 74.8%, p<0.01), and more improved left ventricular wall motion than group A. One-year cardiac mortality rates tended to be higher in group T, which had a higher rate of unsuccessful reperfusion than groups T&A or A (8.1% vs 3.4% vs 3.5%). The frequencies of hemorrhagic complications were similar among the 3 groups. From these findings, we conclude that thrombolytic therapy with subsequent angioplasty is an effective strategy for achieving cardiac reperfusion following acute myocardial infarction.

Intramyocardial Ejection of Basic Fibroblast Growth Factor Increased Regional Myocardial Blood Flow Andsalvaged Infarcted Myocardium in Dogs

We studied whether basic fibroblast growth factor (bFGF) might increase regional Myocardial blood flow (Qm) at the infarcted myocardium. In eight dogs, bFGF 300 μg was injected into the myocardium supplied by the left anterior descending coronary artery (LAD), and the artery was ligated. In 12 dogs, saline was injected (control group). Nonradioactive colored microspheres were used to determine Qm. The amount of viable myocardium and the extent of fibrosis in the infarcted area four weeks after occlusion were measured histologically. In the outer layer, the Qm values immediately after and four weeks after occlusion were 26 ± 2% and 70 ± 6%, respectively, in the control group, and 46 ± 5% and 121 ± 13%, respectively, in the bFGF group. The Qm at both times in the bFGF group was significantly higher than the corresponding control group values (p < 0.01). The Qm at four weeks in the inner and middle layers also significantly increased in the bFGF group. There was more viable myocardium (control vs. bFGF group: 41 ± 5% vs. 61 ± 7%, p < 0.05) and less fibrosis (3.1 ± 0.2 vs. 2.0 ± 0.4, p < 0.01) at the outer layer in the bFGF group. bFGF caused a marked increase of the Qm, an increase of viable myocardium, and a decrease of fibrosis at the infarcted myocardium. We conclude bFGF was effective in limiting infarct size in acute myocardial infarction.

Reperfusion 12 Hours after Coronary Occlusion Salvages Myocardium in Dogs: Studies in a Single-Heart Model

In our single-heart model, half permanently occluded and half reperfused, reperfusion 12 hours after coronary artery occlusion salvaged myocardium in dogs. This finding may be one of the reasons why late reperfusion is beneficial in patients with acute myocardial infaction.