Masayoshi Mishima

NONINVASIVE EVALUATION OF PULMONARY HYPERTENSION BY A PULSED DOPPLER TECHNIQUE

We used a pulsed Doppler technique to examine the flow velocity pattern in the right ventricular outflow tract in 33 adults. In the patients with normal pulmonary artery pressure (mean pressure less than 20 mm Hg, 16 patients), ejection flow reached a peak level at midsystole (137 +/- 24 msec, mean +/- SD), producing a domelike contour of the flow velocity pattern during systole. In contrast, the flow velocity pattern in patients with pulmonary hypertension (mean pressure greater than or equal to 20 mm Hg, 17 patients) was demonstrated to accelerate rapidly and to reach a peak level sooner (97 +/- 20 msec, p less than .01); in 10 of the pulmonary hypertensive patients a secondary slower rise in flow velocity was observed during a deceleration, resulting in the midsystolic notching. The time to peak flow (acceleration time, AcT) and right ventricular ejection time (RVET) were measured from the flow velocity pattern. Either AcT or AcT/RVET decreased with increase in mean pulmonary artery pressure, and a very high correlation (r = -.90) was found between AcT/RVET and log10 (mean pulmonary artery pressure). The use of this technique permitted the noninvasive estimation of the pulmonary artery pressure.

Elevation of thromboxane B2 levels in patients with classic and variant angina Pectoris.

Thromboxane A2 (TXA2), a vasoconstrictive prostanoid, causes intense spasm of isolated coronary vessels and increases platelet aggregability. To define the role of TXA2, in the pathogenesis of angina pectoris, plasma levels of thromboxane B2 (TXB2), a biologically inactive product of TXAs, were determined in the coronary sinus (CS), aorta (AO) and peripheral vein of 30 patients with angina pectoris. Determinations were made by radioimmunoassay using anti-TXB2 antisera and [3HJTXB2. Acidic lipids were extracted from plasma after treatment of samples with ethylenediamine tetraacetic acid (EDTA) and indomethacin. The 18 patients with effort angina and angiographically documented coronary stenosis (> = 75%) showed a marked increase in peripheral TXB, (mean ± SD 505 ± 178 pg/mI plasma) compared with 24 normal subjects (254 ± 89 pg/ml plasma; p < 0.01). When AO and CS TXB2 levels were determined in 10 cases with simultaneous measurements of CS blood flow during atrial pacing, calculated TXB% release in coronary circulation at rest (-2.3 ± 14.8 ng/min) markedly rose during pacing-induced myocardial ischemia (34.7 ± 50.6 ng/min; p < 0.01), while in four control subjects with normal coronary arteries the values at rest (-1.0 ± 5.0 ng/min) did not change significantly at peak pacing (-1.5 ± 10.9 ng/min). All 12 patients with variant angina had a marked increase in peripheral TXB2 (802 ± 249 pg/ml plasma;p < 0.01); two of five cases who were subjected to coronary sampling showed increased TXB2 levels both in CS and AO during a spontaneous attack or attacks induced by ergonovine or by atrial pacing, which were accompanied by coronary vasospasm and fluctuation of CS blood flow. These results indicate that increased TXA2 production in the coronary circulation may be at least partly responsible for coronary vasospasm and angina.

The role of intracoronary thrombus in unstable angina: angiographic assessment and thrombolytic therapy during ongoing anginal attacks.

Intracoronary thrombus is regarded as a potentially important factor in the etiology of unstable angina, but the incidence of intracoronary thrombus in unstable angina has not been clearly defined. To determine the occurrence of intracoronary thrombus during ongoing angina pectoris, coronary angiography was performed during spontaneous ischemic attacks in 37 patients with prolonged rest angina. All patients exhibited significant (greater than 50%) stenoses of at least one major coronary artery. Of the 37 patients, 21 (57%) had intracoronary thrombus in major coronary arteries, whereas 14 (38%) had fixed narrowings without evidence of intracoronary thrombus and two exhibited coronary spasm. ST segment elevation was observed in 16 of 21 patients with thrombus and in all of the patients with coronary spasm, but all the patients with organic stable obstruction showed ST segment depression. Twenty of the 21 patients with thrombus improved after thrombolytic therapy with intracoronary injection of urokinase; obstructed arteries were reopened, or narrowings were attenuated, with relief of ischemic symptoms. In patients with fixed obstructions, the rate-pressure product during active symptoms was significantly higher than during an asymptomatic period, indicating that a transient increase in myocardial oxygen demand may contribute to the ischemic attack in these patients. A high incidence (71%) of recurrent symptoms was observed in patients with intracoronary thrombus even after successful thrombolysis, in contrast to a much lower incidence (36%) in those without intracoronary thrombus. Myocardial infarction within 4 weeks after catheterization was observed more frequently in patients with intracoronary thrombus (24%) than in those without thrombus (7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuation of increased regional myocardial oxygen consumption during exercise as a major cause of warm-up phenomenon

OBJECTIVES The aim of this study was to test the hypothesis that the warm-up phenomenon is attributable to a reduction of increased myocardial oxygen consumption rather than to increased coronary blood flow during exercise. BACKGROUND The underlying mechanism of the warm-up phenomenon is not elucidated. METHODS Thirteen patients with effort angina were subjected to two consecutive supine ergometer exercise tests performed 15 min apart. All patients had severe proximal stenosis (> 90%) in the left anterior descending coronary artery. Great cardiac vein flow was measured before and during exercise. Both regional myocardial oxygen consumption and adenosine release were determined. RESULTS Exercise was continued for significantly longer before angina onset in the second than in the first exercise test (507 +/- 44 vs. 410 +/- 42 s, p < 0.01). The extent of ST segment depression in lead V5 of the electrocardiogram (ECG) was larger at the time of angina onset in the first (1.7 +/- 0.2 mm) than in the second (1.1 +/- 0.2 mm, p < 0.01) exercise test. Neither systemic hemodynamic variables nor great cardiac vein flow differed between the first and second exercise tests. In contrast, regional myocardial oxygen consumption assessed at 3 min of exercise was significantly (p < 0.01) less in the second than in the first test (8.0 +/- 0.8 vs. 8.7 +/- 0.9 ml/min). Adenosine release during the second test was higher (p < 0.05) than in the first test (2.5 +/- 0.5 vs. 3.9 +/- 0.5 nmol/min at 3 min of the first and second tests, p < 0.01). CONCLUSIONS These results indicate that the warm-up phenomenon is not attributable to increased coronary flow but to attenuation of increased regional myocardial oxygen consumption, which may be mediated by adenosine A1 receptor activation.

Collateral channels that develop after an acute myocardial infarction prevent subsequent left ventricular dilation

OBJECTIVES We sought to evaluate the effect of collateral channels that develop late after a first anterior myocardial infarction on left ventricular dilation and function. BACKGROUND Collateral channels in an infarct-related artery may develop long after occlusion of the artery. Well visualized collateral channels that appear immediately after a myocardial infarction reduce infarct size and preserve left ventricular function. However, the functional significance of collateral channels that develop late after myocardial infarction has not been evaluated in terms of left ventricular function. METHODS We studied 21 patients with a first anterior myocardial infarction and an infarct-related artery that remained totally occluded after reperfusion therapy and did not reopen within 1 month of infarction. No collateral channels were observed during the acute period. Patients were classified into two groups according to the extend of collateral formation 1 month after infarction: group C, patients with well developed collateral channels (n = 11), and group NC, patients with absent or poorly developed collateral channels (n = 10). Infarct size was determined by peak creatine kinase activity and thallium-201 single-photon emission computed tomography. Global and regional left ventricular function and left ventricular volumes were assessed by left ventriculography. These measurements were identical in both groups 1 month after infarction. Left ventricular function was reevaluated after 2.12 +/- 0.79 years (mean +/- SD). RESULTS There were no significant changes in global and regional left ventricular function between the two groups during the long-term follow-up period. However, the end-diastolic volume index of group NC increased from 71 +/- 14 to 85 +/- 19 ml/m2, whereas that of group C decreased from 64 +/- 18 to 59 +/- 12 ml/m2. This important change during the long-term follow-up period resulted in a significant difference (p = 0.0006) in the end-diastolic volume index between the groups 2 years after onset (p = 0.002), whereas 1 month after infarction the difference was not significant (p = 0.36). A similar pattern was observed for the end-systolic volume index (group C: 38 +/- 16 to 35 +/- 14 ml/m2; group NC: 45 +/- 12 to 58 +/- 18 ml/m2, p = 0.018). The power of the tests to detect the observed differences showing nonsignificant results ranged from 0.05 to 0.38, whereas the power of the tests indicating a significant difference in end-diastolic and end-systolic volume indexes was >0.88. CONCLUSIONS Collateral channels that develop after a myocardial infarction do not reduce the infarct size or prevent left ventricular dilation within 1 month of infarction. In contrast, such collateral channels prevent subsequent ventricular dilation and the deterioration of left ventricular function over 2 years. However, our results may have been biased because of the small number of patients.

Temporal increase in resting coronary blood flow causes an impairment of coronary flow reserve after coronary angioplasty

Impaired coronary flow reserve immediately after coronary angioplasty may be attributed to an increase in resting coronary blood flow. To test this hypothesis we measured great cardiac venous flow (GCVF) at rest and during rapid atrial pacing before and immediately after angioplasty in 22 patients with significant narrowing of the left anterior descending artery and 12 patients (control group) with minimal narrowing. A follow-up (6 months) study was also done in seven patients. Immediately after angioplasty the coronary flow reserve (peak GCVF during pacing/resting GCVF) was not fully restored (1.5 +/- 0.36 before angioplasty, 1.76 +/- 0.42 after angioplasty, and 2.13 +/- 0.33 in the control group). Resting coronary vascular resistance (2.4 +/- 0.9 mm Hg/ml/min) was significantly decreased after angioplasty (2.0 +/- 0.8 mm Hg/ml/min), whereas coronary vascular resistance during rapid pacing was fully restored to normal. Resting hyperemia was restored 6 months later, whereas coronary vascular resistance during pacing was unaltered. In five patients, however, slight ischemic ST-T changes were observed during rapid pacing, even after successful angioplasty associated with a decrease in the lactate extraction ratio. These results indicate that the impaired coronary flow reserve immediately after angioplasty may be attributed mainly to the temporal but significant increase in resting coronary flow, although impaired coronary vascular response to augmented myocardial oxygen demand may also be partially involved.

Anomalous coronary arteries in adults detected by multislice computed tomography: presentation of cases from multicenter registry and review of the literature

Anomalous coronary arteries are a rare condition, but they may cause myocardial ischemia, heart failure, and sudden death. We evaluated the prevalence and multislice computed tomographic (MSCT) findings of anomalous coronary arteries in a large number of patients from the multicenter registry. At four institutes, 29 (0.74%) out of 3910 patients were found to have anomalous coronary arteries by MSCT. They consisted of 15 patients with anomalous origins of the right coronary artery, 1 with right-sided origin of the left circumflex artery, 1 with right-sided origin of the left main coronary artery, 2 with double right coronary arteries, 2 with the absence of the left circumflex artery, 1 with absence of the right coronary artery, 6 with coronary artery fistulas, and 1 with Bland-White-Garland syndrome. Multislice computed tomography findings were consistent with those obtained by conventional coronary angiography in all 14 patients undergoing both diagnostic procedures. Multislice computed tomography permits three-dimensional comprehension of coronary arteries, which is suitable for the diagnosis of anomalous coronary arteries.

Effect of successful late reperfusion by primary coronary angioplasty on mechanical complications of acute myocardial infarction.

It has been suggested that early treatment decreases, but late treatment increases, the risk of mechanical complications for a thrombolytic strategy. However, few studies have evaluated whether late reperfusion (LR) by primary coronary angioplasty decreases the risk of mechanical complications. A total of 2,209 patients with acute myocardial infarction treated with primary coronary angioplasty within 24 hours after the onset of symptoms were divided into 3 groups: early reperfusion (ER; < or =12 hours, n = 1,647), LR (>12 hours, n = 219), and failed reperfusion (FR; n = 343). We evaluated the incidence, risk ratio, and predictors of mechanical complications. The overall incidence of mechanical complications was 2.0%. The incidence of mechanical complications was highest in the FR group (ER 1.4%, LR 1.8%, FR 5.0%; p <0.01). After adjusting for clinical variables, the risk ratio for mechanical complications increased in the FR group compared with the LR group (risk ratio 7.34, 95% confidence interval [CI] 1.02 to 52.80; p = 0.04). Predictors of an increased risk of mechanical complications by multivariate analysis were age > or =70 years (odds ratio [OR] 3.68, 95% CI 1.56 to 8.64; p <0.01), Killip class > or =II (OR 3.73, 95% CI 1.53 to 9.12; p <0.01), absence of collateral vessels (OR 4.09, 95% CI 1.17 to 14.26; p = 0.03), and FR (OR 2.68, 95% CI 1.09 to 6.61; p = 0.03). In conclusion, successful LR by primary coronary angioplasty is associated with the reduced risk of mechanical complications in patients with acute myocardial infarction.

Clinical assessment of elastic properties of large coronary arteries : pressure-diameter relationship and dynamic incremental elastic modulus

Vascular elastic properties in vivo (dynamic incremental elastic modulus [Ep(dyn)]) of large coronary arteries were assessed from the pressure-diameter relationships of the large coronary arteries in 46 patients with suspected ischemic heart disease. Ep(dyn) represents the vascular stiffness primarily determined by the organic sclerotic changes of the vascular wall and the vascular smooth muscle tone. Coronary arterial diameter was obtained from the magnified cine coronary arteriograms by using a computerized caliber measurement technique. The mean Ep(dyn) of the left main coronary artery and the proximal portions of the left anterior descending and circumflex coronary arteries with apparently normal angiograms were significantly (P less than 0.01) increased as the number of involved coronary vessels was increased. Mean Ep(dyn) values in multi-vessel disease were comparable with those of dilated segment by the percutaneous transluminal coronary angioplasty, indicating that the vascular sclerotic changes are not localized to the narrowed segments but diffusely distributed to the angiographically normal vascular wall. In 4 patients who had successful percutaneous transluminal coronary angioplasty, Ep(dyn) of the dilated coronary segment showed markedly higher values (0.21-0.30 X 10(6) Nm-2) than the normal values (0.16 +/- 0.06 X 10(6) Nm-2 in left anterior descending coronary artery). In contrast, there was no significant difference in Ep(dyn) values of the angiographically normal left main coronary trunk, proximal portions of left anterior descending and circumflex arteries between patients with and without vasospastic angina. During myocardial ischemia induced by ergonovine maleate, vasospastic response of the non-diseased segment was comparable with that in patients who did not have an anginal attack during the ergonovine test. Thus, in contrast to the sclerotic change, abnormal vasoconstrictive property of the coronary artery may be localized to the diseased segment.

Myocardial hibernation in the infarcted region cannot be assessed from the presence of stress-induced ischemia: Usefulness of delayed image of exercise thallium-201 scintigraphy

To examine the relationship between the improvement of wall motion in infarcted regions after percutaneous transluminal coronary angioplasty (PTCA) and thallium-201 uptake in the delayed image of exercise thallium-201 scintigraphy before PTCA, 14 patients with anterior old myocardial infarction were studied. Exercise thallium-201 scintigraphy was performed before PTCA of left anterior descending artery, and mean percent thallium-201 uptake of abnormal segments was calculated in the initial and 4-hour delayed images. Left ventricular angiography was performed during catheterization, before, and 4 to 13 months after PTCA; and regional ejection fraction of anterior wall was calculated. Atrial pacing stress test with the measurement of lactate concentration of aorta and great cardiac vein was performed during catheterization before PTCA. In five patients with mean percent thallium-201 uptake in the delayed image < or = 50% (group I), regional ejection fraction did not increase after PTCA (23% +/- 9% to 24% +/- 12%). In the other nine patients with mean percent thallium-201 uptake > 50% (group II), regional ejection fraction increased significantly after PTCA (39% +/- 18% to 47% +/- 14%; p < 0.05). There was no significant difference in regional ejection fraction, lactate extraction ratio during maximal pacing, and the redistribution of exercise thallium-201 scintigraphy between the two groups before PTCA. Thus the delayed image before PTCA is useful to detect reversible nonfunctioning viable myocardium (hibernating myocardium) in the infarcted region. However, the wall-motion abnormality and the degree of stress-induced ischemia in the infarcted region before PTCA may not be necessarily useful for the detection of hibernating myocardium.