Hironari Koka

New collateral flow increasing early after coronary occlusion prevented myocardial necrosis in dogs

SummaryIncreases in regional myocardial blood flow (Qm) developing soon after myocardial infarction may minimize myocardial necrosis. To test this hypothesis, Qm in the area surrounding an acutely occluded coronary artery was determined successively over 4 weeks in 11 dogs. Non-radioactive colored microspheres were injected into the left atrium 5s (Qm at this time is referred to as Q1), 3h (Q2), 12h (Q3), and 4 weeks (Q4) after occlusion of the coronary artery. After termination of the experiment, the heart was removed, and Qm and three indices of myocardial necrosis i.e., myocardial creatine kinase activity (CK), infarct size determined by triphenyl tetrazolium chloride stain (TTC), and myocardial fibrosis visualized by Azan-Mallory stain, were determined. Each Qm was expressed as a percentage of normal: Qm (% of normal) = [Q/Qc] ischemic area/[Q′/Qc′]non-ischemic area × 100, where Qc indicates Qm determined before coronary occlusion. In the ischemic area of the left ventricle, Q1, Q2, Q3, and Q4 were 25 ± 3%, 30 ± 3%, 31 ± 3%, and 42 ± 3% of normal, respectively, in the inner layer, and 31 ± 3%, 52 ± 4%, 52 ± 4%, and 77 ± 6% of normal, respectively, in the outer layer. During the 4-week period, the increase of Qm in the outer layer was greater than that in the inner layer. The inner layer showed a small increase of flow from Q3 to Q4 (9 ± 2%), but in the outer layer there were greater flow increases from Q1 to Q2 (21 ± 3%) and from Q3 to Q4 (24 ± 6%). No consistent flow change from Q2 to Q3 was seen in the inner, middle, or outer layers. Q1 showed good correlation with the three indices of myocardial necrosis, indicating that abundant pre-existing collaterals are important in minimizing myocardial necrosis. The Qm increase within 3h after occlusion (Q2 − Q1) also showed a good correlation with the three indices while that after 12h (Q4 − Q3) showed a variable relationship with these indices. Myocardial necrosis was mild provided that Q2 − Q1 was high. This study demonstrated that there is a considerable flow increase until 3 h after coronary occlusion and that this flow increase may contribute to the reduction of myocardial necrosis.

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.