Masaru Yamazoe

Negative NO3− difference in human coronary circulation with severe atherosclerotic stenosis

To examine whether or not the levels of NOx (nitrite; NO2- and nitrate; NO3-) in coronary circulating blood reflect endothelial dysfunction due to coronary atherosclerosis, NOx levels in plasma obtained from ostium of left coronary artery and coronary sinus of patients who complained of chest pain were evaluated in relation to their coronary angiographic findings. Prior to the study, a HPLC-Griess system for NOx measurement was critically evaluated. This system has a detection limit of 0.1 microM of NO2- and NO3- by 10 microl of loading and was able to distinguish a difference of 0.1-0.2 microM of these substances. Heparin (1 U/10 microl) did not affect the detective and discriminative abilities. NO3- difference, calculated from sino-arterial difference of NO3-, was almost zero (-0.2 +/- 0.2 microM) in patients with either normal coronary arteries or mild organic coronary stenosis (< or = 20% narrowing), while a significant negative value (-5.9 +/- 1.7 microM) was obtained from patients with significant stenosis (> or = 70% narrowing) in the left coronary arteries. These results demonstrate reliable ability on the HPLC-Griess system in evaluating NO2- and NO3- in biological samples, and that the negative NO3- difference through coronary circulation may reflect endothelial dysfunction in the patients with coronary atherosclerosis with severe organic stenosis.

Coronary artery spasm is a major cause of sudden cardiac arrest in survivors without underlying heart disease.

BackgroundThe role of coronary spasm in underlying disease-free patients who were resuscitated from sudden cardiac arrest remained uncertain. This study investigated the cause of cardiac arrest, and the etiologic and prognostic differences were compared between patients with underlying heart disease (group I) and those patients without underlying heart disease (group II). MethodsTwenty-five survivors of sudden cardiac arrest were classified into two groups according to the presence or absence of underlying heart disease. To investigate the cause of cardiac arrest, we performed ergonovine testing and electrophysiologic study. Fifteen of the patients had underlying heart disease, while 10 did not. ResultsElectrophysiologic abnormalities were found in 13 of the 15 patients in group I. In group II, spontaneous attack of coronary spasm occurred in four patients during the observation period, and coronary spasm was induced in three of the remaining six patients. Four patients in group I had a cardiac event during a mean follow-up period of 32 ±23 months, whereas no patients in group II had recurrence of sudden cardiac arrest at a median follow-up of 32 months (range, 10 to 72 months). ConclusionsElectrophysiologic study identified a potential cause in 13 of 15 patients with underlying heart disease. Coronary spasm was involved in the pathogenesis of sudden cardiac arrest in survivors without identifiable underlying heart disease.

Balloon catheter with check valves for experimental relief of acute aortic regurgitation

To evaluate the ability of a newly designed balloon catheter with check valves to temporarily relieve hemodynamic deterioration in acute aortic regurgitation, we produced an experimental model of acute aortic regurgitation in closed-chest dogs using endomyocardial biopsy forceps. Aortic regurgitation was produced until an increase in aortic pulse pressure of over 50% was achieved. Left ventricular end-diastolic pressure rapidly increased after the production of aortic regurgitation. Immediately after the catheter began functioning, pulse pressure decreased from 133 +/- 1 to 78 +/- 5 mm Hg (mean +/- SEM) and left ventricular end-diastolic pressure also decreased from 26 +/- 1 to 13 +/- 1 mm Hg. These effects lasted as long as the catheter functioned. Although a mild (21 +/- 8 mm Hg) pressure gradient between the left ventricular peak systolic pressure and the aortic peak systolic pressure was observed when this catheter was used, forward stroke volume was no less than in the group in which the catheter had not been used. These findings suggest that the balloon catheter with check valves may effectively reduce aortic regurgitation.

Acute effect of percutaneous transvenous mitral commissurotomy on ventilatory and hemodynamic responses to exercise. Pathophysiological basis for early symptomatic improvement.

BackgroundImprovement of exertional dyspnea occurs immediately after percutaneous transvenous mitral commissurotomy (PTMC), but the pathophysiological basis for this early symptomatic improvement has not been elucidated. Methods and ResultsExercise hemodynamic measurement and exercise ventilatory measurement with arterial blood gas analysis were performed in 21 patients aged 50.4+9.5 years (mean±SD) with symptomatic mitral stenosis before and a few days after PTMC. Exercise ventilatory measurement were also performed in 14 normal control subjects aged 48.9±4.9 years. After PTMC, mitral valve area increased (from 1.0±03 to 1.7±03 cm2, p<.001), mean mitral gradient (from 12.2±5.2 to 5.2±2.2 mm Hg, p<.001), and mean left atrial pressure (from 18.7±6.1 to 12.1±4.0 mm Hg, p<.001) decreased. All patients experienced significant symptomatic improvement soon after PTMC. Comparison of hemodynamic parameters at the same ergometer work rate showed a significant decrease in pulmonary artery systolic pressure (from 77±_18 to 67±+14 mm Hg, p<.001) and diastolic pressure (from 36±10 to 28±7 mm Hg, p<.001) and a significant increase in cardiac output (from 6.4±1.4 to 8.1 ± 1.9 L/min, p<.001). Despite the improvement in exercise hemodynamics and symptoms, exercise capacity determined by peak oxygen uptake (from 18.0+2.9 to 18.6+3.1 mL- kg-1 min-1) and anaerobic threshold (from 11.7±2.4 to 12.0±2.4 mL* kg-1 min-1) remained unchanged. Excessive exercise ventilation, as assessed by the slope of the regression line between expired minute ventilation and carbon dioxide output, decreased significantly from 37.2±6.7 to 33.9±5.8 (P<.001), but remained significantly higher than that in the normal subjects (27.9±3.6, p<.01). The ratio of total dead space to tidal volume and total dead space per breath during exercise decreased significantly after PTMC (P<.05). The change in excessive exercise ventilation after PTMC was correlated with the change in dead space to tidal volume ratio (r=.59) ConclusionsSignificant relief of exertional dyspnea immediately after PTMC is not accompanied by an improvement in exercise capacity. A decrease in excessive exercise ventilation due to a decrease in physiological dead space resulting from hemodynamic improvement partly contributes to the early relief of symptoms after PTMC. However, lung compliance, which was not measured in the present study, may have changed after PTMC. This change may also contribute to the symptomatic improvement.

Possible role of coronary artery spasm in unexplained syncope

Coronary spasm provocation by intracoronary methylergonovine was performed in 14 patients (8 men and 6 women, mean age 56 +/- 6 years) with syncope that remained unexplained despite neurologic and noninvasive cardiac evaluations. Electrophysiologic testing was also performed in 6 of 14 patients. No patient had structural heart disease or significant fixed stenosis of greater than or equal to 75% in the coronary arteries. Six patients had no history of chest pain even when they developed syncope. Serious arrhythmia was documented in 2 patients, cardiac standstill in 1 and complete atrioventricular block in the other. Coronary spasm was induced in 9 patients using the methylergonovine provocation test. Multivessel spasms were found in 3 patients. Coronary spasm was induced in the artery supplying the inferior wall in 7 of 9 patients with positive results. In 4 of 9 patients who had a positive result, there was no prior history of chest pain. In 1 patient, whose electrocardiogram was recorded during syncope, cardiac standstill was documented and cardiac standstill and syncope also occurred during the provocation test. Monomorphic ventricular tachycardia was not induced by the electrophysiologic study. These results suggest that coronary spasm is involved in unexplained syncope.

Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina

The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.

Coronary artery perforation with subepicardial hematoma.

Coronary artery perforation is a relatively rare complication in coronary angioplasty. We report the case of a 71-year-old male, who was salvaged by emergency surgery, for cardiogenic shock due to subepicardial hematoma associated with balloon angioplasty. Such a case has not yet previously been reported.

Immediate effects of percutaneous transvenous mitral commissurotomy on pulmonary hemodynamics at rest and during exercise in mitral stenosis

Hemodynamics were evaluated during exercise in 33 patients with mitral stenosis who underwent percutaneous transvenous mitral commissurotomy (PTMC). PTMC was performed using an Inoue balloon. Each patient underwent a supine ergometer exercise test before and on the day after PTMC. Ergometer work load was started at 20 W and increased in increments of 20 W at 3-minute intervals until terminated by the patients fatigue or shortness of breath. Mitral valve area increased by 0.8 +/- 0.4 cm2 (1.1 +/- 0.3 to 1.9 +/- 0.4 cm2, p less than 0.001). Mean mitral pressure gradient decreased (12 +/- 5 to 6 +/- 2 mm Hg, p less than 0.001). Pulmonary arterial pressure significantly decreased and the cardiac index significantly increased both at rest and during exercise after PTMC. Before PTMC, the increases in pulmonary arterial pressure, total pulmonary resistance and pulmonary arteriolar resistance during exercise were greater in patients with a mitral valve area less than 1.0 cm2 than in patients with an area greater than or equal to 1.0 cm2. After PTMC, total pulmonary resistance still increased during exercise. However, pulmonary arteriolar resistance did not change during exercise in patients with a mitral valve area greater than or equal to 1.5 cm2, whereas it increased in patients with an area less than 1.5 cm2. An enlarged mitral valve area greater than or equal to 1.5 cm2, which may prevent pulmonary vasoconstriction and permits a greater increase in pulmonary blood flow during exercise, is considered a good result immediately after PTMC.

Three-dimensional characteristics of the intramyocardial microvasculature of hypertrophied human hearts

The three-dimensional architecture of the intramyocardial microvasculature was demonstrated in hypertrophied human hearts using Evans method: scanning electron microscopic observation of the cardiac muscle chemically digested by hydrochloric acid and collagenase. Twenty autopsied hearts, which had already been fixed in 10% formalin, were investigated, including 17 hypertrophied hearts (mean cardiac weight, 587 g) and three control hearts (mean cardiac weight, 238 g). The luminal surfaces of the arterioles were characterized by the coiled arrangement of their smooth muscle cells. The structure of these vessels was not significantly different in hypertrophied and normal hearts. The capillaries showed great changes in the hypertrophied muscle: capillaries running on the body of the myofibres, in loop form on disorganized myofibres, and protruding into myofibres and/or probably penetrating through them. These features indicated an increase in the ratio of capillary/myofibre in hypertrophied human hearts. In hypertrophied hearts the venules had a more developed system than normal hearts, but without change in their basic architecture.

Decrease in plasma NOx concentration by isosorbide dinitrate, an organic nitrate ester.

It has been suggested that isosorbide dinitrate (ISDN)–induced venodilation could be ascribed to preferential accumulation of the agent in venous tissues, resulting in higher concentrations of nitric oxide (NO). Here, the authors investigated whether the venodilating effect of ISDN is associated with a preferential increase in plasma concentrations of NOx (NO2− and NO3−, stable end-products of NO) in venous blood than arterial blood. Plasma NOx was measured by high-performance liquid chromatography–Griess system with a sensitivity of 0.01 &mgr;M for NO2− and 0.1 &mgr;M for NO3−. Arterial and venous blood samples were obtained after coronary angiography from the aorta and right atrium of patients with or without ischemic heart disease. Nicardipine, a calcium channel blocker, was used as a non–NO-related arteriovasodilator. At 1 mg i.v., it did not cause any changes in NOx concentration in arterial and venous blood irrespective of hemodynamic changes. However, ISDN (3 mg i.v.) increased NO2− and decreased NO3− in both arterial and venous blood, with concomitant venodilation. Further analysis revealed that plasma NO2− increased in the pulmonary circulation and this increase was preserved after nicardipine and ISDN, and that ISDN, but not nicardipine, increased plasma NO3− in the pulmonary circulation. The authors did not detect higher concentrations of NOx in venous blood relative to their level in arterial blood. Further studies are necessary to clarify the kinetics of NO and NO-related compounds in the whole body.