Hisayoshi Nakajima

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.

Relative Attenuation of Sympathetic Drive During Exercise in Patients With Congestive Heart Failure

Patients with congestive heart failure have been considered to have augmented sympathetic drive both at rest and during dynamic exercise. The augmentation observed during exercise may be related to the state of near exhaustion experienced by patients with heart failure at relatively low work loads. To compare the response of the sympathetic nervous system to exercise in normal subjects and patients with heart failure when they are working in a comparable physiologic frame of reference, the data for both groups can be expressed as percent peak oxygen consumption achieved (percent peak VO2) rather than as a function of absolute oxygen consumption (VO2). Ten healthy control subjects and 31 patients with chronic clinical class II and III heart failure were studied during upright maximal bicycle exercise. Eighteen of the 31 patients had primary cardiomyopathy and 13 had ischemic cardiomyopathy. The average ejection fraction at rest was 24 +/- 10% (+/- SD) in the group with heart failure. Heart rate, systolic blood pressure, VO2 and plasma norepinephrine levels were measured at rest and throughout exercise. When the data were expressed as a function of percent peak VO2 achieved, patients with heart failure demonstrated a flatter slope (p = 0.004) than normal in the response of plasma norepinephrine to exercise, indicating a relative blunting of sympathetic drive. This was accompanied by attenuated heart rate (p = 0.001) and blood pressure (p less than 0.001) responses. These differences were not apparent when the data are expressed as a function of absolute VO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostacyclin therapy in patients with congestive heart failure

The acute hemodynamic effects of intravenous prostacyclin (PGI2), in doses of 22 +/- 11 ng/kg per min were studied in nine patients with severe congestive heart failure refractory to digitalis and diuretic drugs. After prostacyclin infusion, mean (+/- standard deviation) pulmonary capillary wedge pressure decreased from 21.0 +/- 7.9 to 15.0 +/- 6.6 mm Hg (p less than 0.001), mean arterial pressure from 98.9 +/- 12.8 to 76.2 +/- 7.0 mm Hg (p less than 0.001), systemic vascular resistance from 2,574 +/- 384 to 1,368 +/- 283 dynes s cm-5 (p less than 0.001), pulmonary vascular resistance from 1,008 +/- 451 to 443 +/- 135 dynes s cm-5 (p less than 0.001) and pulmonary arteriolar resistance from 330 +/- 111 to 189 +/- 73 dynes s cm-5 (p less than 0.001). Heart rate increased from 78 +/- 21 to 82 +/- 24 beats/min (p = not significant [NS]), cardiac index from 2.0 +/- 0.37 to 3.2 +/- 0.59 liters/min per m2 (p less than 0.001) and stroke index from 27.6 +/- 8.69 to 42.0 +/- 0.62 cc/m2 (p less than 0.001). With prostacyclin, moreover, coldness of the limbs and face disappeared, and patients felt warmth and mild flushing of the face. After prostacyclin, plasma norepinephrine levels, renin activity and aldosterone concentrations rose from 824 +/- 375 to 880 +/- 468 pg/ml (NS), 0.68 +/- 1.36 to 0.95 +/- 1.21 ng/ml per h (NS), and 6.64 +/- 2.50 to 6.38 +/- 2.88 ng/dl (NS), respectively, while plasma epinephrine increased from 140 +/- 80 to 250 +/- 154 pg/ml (p less than 0.025).

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.

Effects of coronary artery reperfusion on relation between creatine kinase-MB release and infarct size estimated by myocardial emission tomography with thallium-201 in man.

The quantitative relations between serum creatine kinase-MB isoenzyme (CK-MB) release and the final infarct size estimated by myocardial emission computed tomography with thallium-201 was assessed in 37 patients with a first acute transmural myocardial infarction who underwent intracoronary thrombolysis using urokinase 4.6 +/- 1.9 hours after the onset of symptoms. Serial CK-MB determinations were used to calculate the accumulated release of CK-MB (sigma CK-MB). Myocardial emission tomography with thallium-201 was performed 4 weeks after the onset, and infarct volume was measured from reconstructed tomographic images by computerized planimetry. The results are presented for two groups of patients: 11 patients with unsuccessful thrombolysis (group A) and 26 patients with successful thrombolysis (group B). An excellent linear relation was found for group A (sigma CK-MB = 6.4 X infarct volume + 47.7, r = 0.91), whereas a different linear relation was observed for group B (sigma CK-MB = 10.5 X infarct volume + 89.1, r = 0.80). Moreover, serum CK-MB activity reached a peak at 21.1 +/- 2.2 hours after the onset in group A and reached an earlier peak at 12.5 +/- 2.9 hours in group B (p less than 0.001). These data suggest that acute coronary recanalization alters the kinetics of CK-MB release, resulting in greater CK-MB release into the serum for equivalent infarct volume estimated by myocardial emission tomography with thallium-201. Thus, serum CK-MB time-activity curves after acute myocardial infarction may be influenced considerably by acute reperfusion, which is an important factor that should be incorporated in the interpretation of enzymatic estimates of infarct size in human patients.

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.

Circadian variation in the success rate of intracoronary thrombolysis for acute myocardial infarction

Abstract Intracoronary thrombolytic therapy for acute myocardial infarction (AMI) has been demonstrated to be effective in terms of the limitation of myocardial necrosis, the preservation of left ventricular function and the improvement of survival. 1–3 The recanalization rate by intracoronary thrombolysis has been reported to be affected by various factors, such as the type and dose of thrombolytic agents, 4,5 and the extent of underlying stenosis severity of the infarct-related coronary artery. 6,7 It is postulated that the recanalization rate is influenced by the level of plasminogen activator inhibitor which is one of the major components of the fibrinolytic system. In the present study we measured a circadian variation in the success rate of intracoronary thrombolysis, as there is a report that plasminogen activator inhibitor activity is markedly increased during the early morning hours. 8

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.

Comparative Hemodynamic Effects of Intravenous Dobutamine and Dibutyryl Cyclic AMP, a New Inotropic Agent, in Severe Congestive Heart Failure

In nine patients with chronic congestive heart failure, the acute hemodynamic response to intravenous (i.v.) dibutyryl cyclic AMP (DBcyclicAMP) administration was compared with i.v. dobutamine administration. Both agents led to a significant and similar increase in cardiac index. Dobutamine caused a significant increase in mean arterial pressure but did not produce a significant change in pulmonary capillary wedge, mean pulmonary artery, or mean right atrial pressures. In contrast, DBcyclicAMP caused a significant decrease in mean arterial, mean pulmonary capillary wedge, mean pulmonary artery, and mean right atrial pressures, reflecting vasodilator activity. The fall in systemic vascular resistance was larger after DBcyclicAMP than after dobutamine. DBcyclicAMP achieves an optimal improvement in cardiovascular hemodynamics in concert with substantial vasodilating effect. This pharmacologic action constitutes the mainstay of i.v. therapy for severe congestive heart failure (CHF).

Functional characteristics of nonischemic region during pacing-induced myocardial ischemia in angina pectoris

To investigate the details of the hyperfunction of nonischemic area during acute ischemia, the regional myocardial function at rest and immediately after rapid cardiac pacing was compared using cineventriculography in 12 patients with stable effort angina. Three left ventricular boundaries at the time of end-diastole, aortic valve opening and end-systole were superimposed, and 128 radial grids were drawn from the center of gravity of end-diastolic frame to the endocardial margin. The changes in the length of each radial grid provided quantitative description of segmental systolic function. In the ischemic area, the percent of total segment shortening decreased from 36 +/- 6% (mean +/- standard error of the mean) to 24 +/- 8% (p less than 0.05) in patients with a significant narrowing of left anterior descending coronary artery (LAD), and from 42 +/- 6% to 20 +/- 4% (p less than 0.05) in those with right coronary artery (RCA) involvement. In the nonischemic area, the percent of total segment shortening increased from 33 +/- 7% to 44 +/- 7% (p less than 0.05) in LAD disease, while it was unchanged in RCA involvement (40 +/- 5% vs 41 +/- 7%). The percentage of isovolumic segment shortening increased from 1 +/- 4% to 7 +/- 3% (p less than 0.05) and from 1 +/- 1% to 5 +/- 2% (p less than 0.05) in LAD and RCA involvement, respectively. Meanwhile, ejection phase shortening did not change significantly (33 +/- 6% vs 40 +/- 7% in LAD involvement, and 39 +/- 6% vs 38 +/- 7% in RCA involvement).(ABSTRACT TRUNCATED AT 250 WORDS)