Shuji Kondo

Myocardial contrast echocardiography: a reproducible technique of myocardial opacification for identifying regional perfusion deficits.

The effects and reliability of a simple method of contrast two-dimensional echocardiographic delineation of myocardium after intracoronary injections were evaluated in closed-chest dogs. Multiple injections of an agitated saline-Renografin (meglumine diatrizoate) mixture (3:2 ratio, 2-ml bolus) into the left main coronary artery as well as at different sites of the left anterior descending and circumflex coronary arteries were studied in several short-axis and long-axis cross sections of the left ventricle. These contrast injections opacified specific regions of left ventricular myocardium depending on the site of injection. Contrast injection into the left main coronary artery provided a clear, echo-free outline (negative contrast) of underperfused myocardium distal to the coronary occlusion. Reproducibility studies of the extent of involved zones measured in echocardiographic cross sections indicated high intra- and interobserver correlation coefficients (r = 0.97 and 0.97). The effects of the intracoronary injection of contrast material appeared minor and brief. ECG ST-T changes lasted 49.4 ± 36.7 seconds, aortic systolic pressure was reduced by 7.6 ± 4.4% for 18.9 ± 4.8 seconds, and the peak rate of left ventricular pressure rise decreased by 14.3 ± 2.6%, but returned to control levels within 19.4 ± 6.1 seconds. The zone of left ventricular asynergy after coronary occlusions was also delineated by cross-sectional echocardiography and corresponded to the contrast-outlined underperfused zone (negative contrast). This new intracoronary echocardiographic technique has only minor hemodynamic consequences and provides reliable quantitation of underperfused and dysfunctioning zones after experimental coronary occlusions. Further investigation and validation of this method may provide useful characterization of the extent and severity of myocardial ischemia and infarction.

Hyperemic response of intracoronary contrast agents during two-dimensional echographic delineation of regional myocardium

Several intracoronary echo contrast agents that provided satisfactory regional myocardial delineation with two-dimensional echocardiography were compared in 15 dogs and their effects on coronary blood flow were examined. Reproducible delineation of myocardium subserved from the intracoronary echo contrast injection site was achieved with hand-agitated agents containing greater than or equal to 30% Renografin, greater than or equal to 30% glucose, greater than or equal to 30% sucrose or 6% dextran. After a 2 cc injection of the echo contrast agent, peak hyperemic augmentation of coronary flow was 56.7 +/- 54.4% for 6% dextran, 116.0 +/- 71.1% for 30% Renografin, 119.3 +/- 47.8% for 30% sucrose, 173.8 +/- 38.3% for 30% glucose. Although, 6% dextran resulted in the lowest and shortest hyperemic response of the four agents, computer-derived echo contrast appearance-disappearance analysis indicated a prolonged myocardial contrast decay half-life (21.0 seconds). On the other hand, 30% Renografin had a more rapid myocardial echo contrast washout (T 1/2 = 15.5 seconds), but a significantly greater hyperemic effect was observed. It is concluded that development of echo contrast agents for myocardial contrast two-dimensional echocardiographic assessment of myocardial perfusion will require consideration of alterations in coronary flow due to contrast-induced hyperemia.

Hangover Susceptibility in Relation to Aldehyde Dehydrogenase-2 Genotype, Alcohol Flushing, and Mean Corpuscular Volume in Japanese Workers

BACKGROUND A study of Asian-American students suggested a positive association between inactive ALDH2*2 and susceptibility to hangover. A biomarker for moderate-to-heavy drinking in persons with inactive aldehyde dehydrogenase-2 (ALDH2) is increased mean corpuscular volume (MCV). METHODS Associations between hangover and ALDH2 genotype, alcohol flushing, and MCV were examined for 251 Japanese workers (139 men, 112 women). RESULTS Inactive ALDH2*1/2*2 heterozygotes drank less alcohol than active ALDH2*1/2*1 homozygotes (p < 0.0001), but the frequency of hangover did not significantly differ between the two groups for either gender. The amount of drinking reported to lead to hangover was significantly less for male and female ALDH2*1/2*2 heterozygotes than for their ALDH2*1/2*1 homozygous counterparts (p < 0.005). The proportion of men who had hangover three times or more during the past year increased significantly with increased daily alcohol consumption in men with the ALDH2*1/2*2 genotype (p = 0.0002) but not in those with the ALDH2*1/2*1 genotype. For men who usually consumed <44 g of ethanol/day, the median amount of drinking before hangover was significantly lower for ALDH2*1/2*2 men than for ALDH2*1/2*1 men reporting the same level of consumption. Hangover occurred with consistently high frequency among ALDH2*1/2*1 men, regardless of their daily consumption. Similar findings were observed in a comparison of men who never flushed and those who reported current or former flushing, a surrogate marker of inactive ALDH2. Assessment of hangover risk by quartiles of MCV showed that men with MCV of > or =96 had a significantly higher risk of hangover than did men with MCV of <91 (odds ratio = 5.56; 95% confidence interval = 1.69-18.25). CONCLUSIONS Inactive heterozygous ALDH2, alcohol flushing, and increased MCV were positively associated with hangover susceptibility in Japanese workers, suggesting that acetaldehyde is etiologically linked to the development of hangover.

Mitral valve prolapse in short-term experimental coronary occlusion: a possible mechanism of ischemic mitral regurgitation.

Experimental coronary occlusions were carried out in 12 closed-chest dogs to investigate the functional anatomic characteristics of the mitral valve complex during acute myocardial ischemia. Two-dimensional echocardiography was used to assess left ventricular function, the mitral valve complex, and left atrial size. Presence of mitral regurgitation was assessed by left ventricular contrast echocardiography. Thirty-seven coronary occlusions of up to 10 min in duration were carried out in proximal or distal locations in the left anterior descending and the left circumflex coronary arteries. Mitral regurgitation, which was mild in severity as judged by a small rise in pulmonary artery wedge pressures, was observed in 15 of 37 brief coronary occlusion experiments. Mitral valve prolapse was noted in all 15 experiments, as well as in four additional studies in which mitral regurgitation was not seen. The development of experimental mitral valve prolapse was explained by measurements that demonstrated a relative displacement of the papillary muscle tips toward the mitral orifice. We conclude that mitral valve prolapse is a common sequela of short-term coronary occlusion and is often associated with mild mitral regurgitation. Relative displacement of ischemic papillary muscles toward the mitral orifice appears to be a likely mechanism of acute ischemic mitral valve prolapse.

Mean Corpuscular Volume and the Aldehyde Dehydrogenase‐2 Genotype in Male Japanese Workers

BACKGROUND Increased mean corpuscular volume (MCV) is common in alcohol abusers and alcoholics. MCV is higher in Japanese heavy drinkers with inactive aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/2*2 than among those with active ALDH2 encoded by ALDH2*1/2*1. Inactive ALDH2 dramatically increases blood acetaldehyde levels after alcohol intake. Because moderate and heavy drinkers with ALDH2*1/2*2 have very high risks for esophageal cancer, MCV might serve as an indicator of these high-risk drinkers. METHODS In this investigation of the association of red cell values with the ALDH2 genotype and possible confounding factors, the drinking, smoking, and dietary habits reported on a structured questionnaire by 163 Japanese working men were subjected to multivariate analyses. RESULTS Aging, lower body mass index (BMI), more alcohol consumption, and more smoking were positively associated with increased MCV. Among moderate to heavy drinkers (>or=9 units/week; 1 unit = 22 g of ethanol), both MCV and mean corpuscular hemoglobin were higher and the red cell count was lower in those with ADLH2*1/2*2 than in those with ALDH2*1/2*1. Multiple linear regression analysis after adjustment for age, BMI, and smoking revealed that a positive relationship between the amount of drinking and MCV but inverse relationships for drinking and red cell count, as well as hemoglobin and hematocrit values, were significantly stronger for men with ALDH2*1/2*2 than for those with ALDH2*1/2*1, demonstrating a gene-environment interaction. Drinking accounted for 19.9% of interindividual MCV variance among men with ALDH2*1/*2*2 but for only 1.3% of variance among those with ALDH2*1/2*1. Age, BMI, drinking, and smoking accounted for 52.1 and 34.7% of the variation among those with ALDH2*1/2*2 and ALDH2*1/2*1, respectively. Macrocytosis (MCV >or=100.0 fl) was observed in 18 subjects (11.0%), and use of macrocytosis as a biomarker of moderate to heavy drinkers with ALDH2*1/2*2 had a sensitivity of 54.5% (6 of 11) and a specificity of 92.1% (140 of 152). CONCLUSIONS Alcohol-related red cell value changes associated with inactive ALDH2 in Japanese men suggest the importance of acetaldehydes role in increasing MCV and the potential for using MCV as a marker for high-risk drinkers for esophageal cancer.

Diagnosis of Coronary Stenosis by Two-Dimensional Echographic Study of Dysfunction of Ventricular Segments During and Immediately After Pacing

The adequacy of two-dimensional echocardiography during right atrial pacing for the detection and characterization of coronary artery stenosis was examined in 10 closed chest dogs. Pacing at successively higher rates up to 210 beats/min was carried out in the control state and again during a 70% left anterior descending coronary artery stenosis-induced with intracoronary plugs. Left ventricular short-axis echographic cross sections were obtained at several levels of the left ventricle. After computer-aided standardized subdivision, contractile function of the global section and its subsegments was characterized by computed systolic fractional area change percent and wall thickening percent. Ventricular segments supplied from the site of the 70% coronary stenosis were delineated in a low papillary level cross section by a myocardial contrast echographic technique, and these segments demonstrated significant dysfunction during pacing at 150 to 210 beats/min. Echographic observation of the involved segments immediately after pacing revealed a maximal depression of function 5 seconds after pacing, equivalent to dysfunction at peak pacing, with function returning to control levels within about 2 minutes. Both maximal pacing and early postpacing studies facilitated satisfactory discrimination of ischemic from normally perfused myocardial segments. These experiments show that right atrial pacing study with quantitative two-dimensional echocardiography may serve to detect and assess a coronary stenosis associated with minor or no cardiac dysfunction in the rest state.