Akira Ohno

Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction.

The effect of preexistent coronary collateral perfusion on the prevention of left ventricular aneurysm formation was examined in 47 patients undergoing an intracoronary thrombolysis within 6 hours after the onset of a first acute anterior myocardial infarction. Left ventricular aneurysm formation and wall motion were analyzed with cineventriculography. A left ventricular aneurysm was determined as well-defined demarcation of the infarcted segment from normally contracting myocardium. In 25 patients with successful thrombolysis (group A), a left ventricular aneurysm was observed in one patient (4%) during the chronic stage of infarction. In 10 patients who had a significant collateral circulation to the infarct-related coronary artery and unsuccessful reperfusion (group B), the left ventricular aneurysm was observed in only one patient (10%). In the remaining 12 patients with unsuccessful recanalization in the absence of a significant collateral perfusion (group C), there was a higher incidence (seven of 12, 58%) of left ventricular aneurysm formation than in groups A and B (p less than 0.05). In group A, both the global ejection fraction and regional wall motion in the infarct areas improved significantly (p less than 0.05) between the acute and chronic stages of infarction. By contrast, in groups B and C, these indexes on the ventricular function did not change significantly during the convalescent period. Thus, although the collateral perfusion existing at the onset of acute myocardial infarction may not improve ventricular function, it exerts a beneficial effect on the prevention of left ventricular aneurysm formation.

Improvement of treadmill capacity and collateral circulation as a result of exercise with heparin pretreatment in patients with effort angina.

It has been demonstrated in animal experiments that heparin accelerates the coronary collateral development induced by repeated coronary occlusion. We used this effect of heparin for the treatment of patients with stable effort angina. In 10 patients, treadmill exercise was performed according to standard Bruce protocol twice a day for 10 days. A single intravenous dose of heparin (5000 IU) was given 10 to 20 min before each exercise period. Exercise with heparin pretreatment increased the total exercise duration from 6.3 +/- 1.9 (SD) to 9.1 +/- 2.2 min (p less than .001) and the maximal double product (DP) from 18,900 +/- 5100 to 25,500 +/- 6800 mm Hg.beats/min (p less than .001). The DP at the onset of angina was also increased by 35% (p less than .01) and the DP at which ST depression (0.1 mV) first appeared was 19% (p less than .05) greater after treatment. Repeat coronary cineangiography revealed an increase in the extent of opacification of collaterals to the jeopardized myocardium. In an additional six patients, treadmill exercise was performed with no medication twice a day for 10 days. All of the above-mentioned variables of treadmill capacity remained unchanged, despite 20 exercise periods without heparin pretreatment. Thus, heparin accelerates exercise-induced coronary collateral development by promoting angiogenesis. The development of such a therapeutic modality will open a new field for the treatment of patients with ischemia.

Significance of preinfarction angina for preservation of left ventricular function in acute myocardial infarction.

The effect of preinfarction angina on the preservation of left ventricular function was evaluated with the use of cineventriculography in 37 patients who had either total or subtotal occlusion of the proximal left anterior descending coronary artery during the convalescent period of myocardial infarction. In 15 patients who had preinfarction angina more than 1 week before the onset of acute myocardial infarction (group A), the global left ventricular ejection fraction was 54 +/- 3% (SEM) and regional wall motion in the infarct area was 10 +/- 3%. In 10 patients who had preinfarction angina occurred within 1 week before the onset of acute myocardial infarction (group B), the left ventricular ejection fraction and regional wall motion in the infarct area were 42 +/- 3% and 1 +/- 2%, respectively. In 12 patients without preinfarction angina (group C), the left ventricular ejection fraction and regional wall motion in the infarct area were 38 +/- 3% and -1 +/- 2%, respectively. In groups B and C, both the left ventricular ejection fraction and regional wall motion in the infarct area were lower than those in group A (p less than 0.05). The collateral circulation at the onset of acute myocardial infarction was better in group A compared with groups B and C (p less than 0.05). Thus the collateral circulation, promoted by repetitive anginal episodes indicative of myocardial ischemia, causes the preservation of myocardial function.

Importance of coronary collateral circulation for kinetics of serum creatine kinase in acute myocardial infarction

The effect of coronary collateral perfusion on the kinetics of creatine kinase (CK) was examined in 32 patients undergoing intracoronary thrombolysis within 6 hours after the onset of a first acute myocardial infarction (AMI). Blood sampling for CK was performed every 2 to 4 hours for a period of 72 hours after AMI. The cumulative CK release was determined using the integrated appearance function curve with the individual disappearance rate. In 19 patients in whom thrombolysis was successful (group A), time to peak CK level was 11 +/- 1 (standard error of the mean) hours after AMI and cumulative CK release was 2,599 +/- 424 U/liter. In 6 patients who had a significant collateral circulation to the infarct-related coronary artery and unsuccessful reperfusion (group B), the time to peak CK was 16 +/- 1 hours (p less than 0.05 compared with group A) and cumulative CK release was 1,897 +/- 478 U/liter (difference not significant compared with group A). In the remaining 7 patients, with neither recanalization nor significant collateral perfusion group C, time to peak CK was 21 +/- 1 hours and significantly (p less than 0.05) longer than groups A and B. Cumulative CK release (2,707 +/- 776 U/liter) was not significantly different from groups A and B. Thus, collateral perfusion is an important determinant of the CK time-activity curve during AMI. Early peaking of CK levels does not reliably identify spontaneous or drug-induced recanalization of the infarct-related coronary artery.

Comparative effect of heparin treatment with and without strenuous exercise on treadmill capacity in patients with stable effort angina

It has recently been demonstrated that treadmill capacity and collateral circulation improve as a result of exercise with heparin pretreatment in patients with effort angina. In the present study, we assessed whether heparin alone is effective in increasing treadmill capacity in 14 patients with effort angina. Patients were randomly assigned to one of two treatment arms: (1) group A--20 treadmill exercise periods with standard Bruce protocol twice a day for 10 days with heparin (5000 IU intravenously) pretreatment (seven patients) or (2) group B--10 injections of heparin calcium (10,000 IU subcutaneously) once a day for 10 days (seven patients). In group A, total exercise time was increased from 6.9 +/- 1.2 (SD) to 9.9 +/- 1.9 minutes (p less than 0.0005), as was the maximal double product, from 21,700 +/- 3,500 to 27,000 +/- 4,800 mm Hg/min (p less than 0.05). The double product at the onset of angina was also increased by 34% (p less than 0.05), and the double product at which ST depression (0.1 mV) first appeared was 22% (p less than 0.05) greater after treatment. In contrast, in group B, all of the above-mentioned parameters of treadmill capacity remained unchanged. These data indicate that heparin does not serve as an angiogenic factor by itself, but that it potentiates the ischemia-derived angiogenic factor.

Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction

The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 +/- 0.5 (SD), which was significantly higher than the 0.7 +/- 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area.

A new method for assessment of collateral development after acute myocardial infarction

OBJECTIVES The purpose of this study was to test the hypothesis that the diameter of the recipient coronary artery of the well developed collateral circulation in patients with acute myocardial infarction increases because of the augmented intravascular pressure caused by subsequent collateral development. BACKGROUND It is well known that collateral circulation develops after acute myocardial infarction. However, some patients have a well developed collateral circulation at the onset of infarction, which may limit the angiographic evaluation of further development of collateral circulation. METHODS We measured the diameter of the donor and recipient arteries of the collateral circulation by means of a computer-assisted analysis system in seven patients with acute myocardial infarction who had a totally occluded infarct-related coronary artery during the acute and chronic stages of infarction. All coronary angiograms were obtained after the administration of sublingual nitroglycerin. The measurement was repeated immediately after (within 6 h) and late after (42 +/- 11 days) the onset of acute myocardial infarction. RESULTS The diameter of the donor artery remained unchanged (1.32 +/- 0.98 vs. 1.42 +/- 1.12 mm). In contrast, the diameter of the recipient artery increased from 1.25 +/- 0.63 to 1.55 +/- 0.61 mm (p < 0.01). These changes in coronary artery diameter were associated with an improvement in regional myocardial wall motion at rest in infarct areas (6.7 +/- 7.0% vs. 13.6 +/- 10.7%, p < 0.05). CONCLUSIONS These findings indicate that serial measurement of coronary artery diameter is useful for the evaluation of collateral development after acute myocardial infarction.

Importance of coronary collateral circulation for increased treadmill exercise capacity by nitrates in patients with stable effort angina pectoris

The purpose of this study was to elucidate the mechanism that induces an improvement in exercise capacity by nitrates in patients with stable effort angina pectoris. The study population was composed of 19 patients: group A, 10 patients with chronic stable effort angina who had a well-developed coronary collateral circulation to the potentially ischemic region; group B, 9 patients with chronic stable effort angina who had no collateral circulation to the jeopardized myocardium. Treadmill exercise was performed according to the standard Bruce protocol with and without pretreatment with orally administered 10 mg isosorbide dinitrate. Percent increases (mean +/- SE) in exercise duration were not significantly different between groups A and B (25 +/- 6 vs. 14 +/- 6%). Percent increases in the maximal rate-pressure product tended to be greater in group A than in group B (27 +/- 6 vs. 10 +/- 6%). Percent increases in the rate-pressure product at the onset of angina pectoris were significantly greater in group A than in group B (37 +/- 7 vs. 7 +/- 6%; p less than 0.01). Percent increases in the rate-pressure product at 0.1 mV S-T segment depression were also significantly greater in group A than in group B (26 +/- 6 vs. 1 +/- 5%; p less than 0.01). These results suggest that isosorbide dinitrate dilates epicardial collateral vessels with smooth muscle layers, but fails to dilate the coronary arteries with significant organic stenoses.

Importance of myocardial ischemia for coronary collateral development in conscious dogs

The purpose of this study was to evaluate the effects of myocardial ischemia on the development of collateral circulation. Thirteen conscious dogs were instrumented for serial measurements of subendocardial segment length in the area perfused by the left circumflex coronary artery, left circumflex coronary artery flow and left ventricular pressure. In 6 dogs (group A), 1 min left circumflex coronary artery occlusions were carried out at 30 min intervals. When the 442nd 1 min left circumflex coronary artery occlusion produced a reduction in segment shortening and a significant reactive hyperemia, the occlusion time was increased to 2 min. In the remaining 7 dogs (group B), 2 min left circumflex coronary artery occlusions were conducted hourly. In group A, following 451 +/- 201 (SD) min of total occlusion time with the mixture of 1 and 2 min left circumflex coronary artery occlusions (43 +/- 18 days) a left circumflex coronary artery occlusion produced no reduction in segment shortening and negligible reactive hyperemia. By contrast, in group B, 218 +/- 99 min of total occlusion time (18 +/- 8 days) was required to develop adequate collateral circulation. The relative contribution of the first and second 1 min of left circumflex coronary artery occlusion to the collateral development was mathematically evaluated. This analysis indicated that the second 1 min of left circumflex coronary artery occlusion is 4.43-fold more effective than the first 1 min of occlusion in terms of the collateral induction. We concluded that severe myocardial ischemia plays an important role in the development of collateral circulation.

Relationship between the preexistent coronary collateral circulation and successful intracoronary thrombolysis for acute myocardial infarction

The purpose of this study was to evaluate whether the existence of coronary collateral circulation influences recanalization rates of intracoronary thrombolysis. The study population consisted of 85 consecutive patients undergoing intracoronary thrombolysis within 6 hours after the onset of the first acute myocardial infarction, all of whom had a complete occlusion of the infarct-related coronary artery. Intracoronary thrombolysis with high-dose urokinase (960,000 IU) was attempted at a rate of 24,000 IU/min. Of 18 patients (group A) who had good angiographic collateral circulation to the area perfused by the infarct-related coronary artery, the obstructed artery was recanalized to a residual luminal diameter stenosis of less than or equal to 90% (successful recanalization) in only five (28%). In contrast, of 67 patients (group B) with poor or no collateral circulation, recanalization was successful in 40 (60%) (p less than 0.05). Antegrade flow of infarct-related arteries was observed following thrombolysis in 12 (67%) of 18 group A patients and in 56 (84%) of 67 group B patients (p = NS). It was concluded that (1) the presence of collaterals correlates with the presence of high-grade stenosis; (2) the presence of collaterals correlates with the presence of high-grade stenosis; (2) the presence of collaterals is inversely related to the efficacy of thrombolytic therapy; and (3) the difference in successful recanalization rates observed between the two groups probably reflects the impact of underlying stenosis severity on the effectiveness of lytic therapy.