Ventriculographic and hemodynamic features of mitral regurgitation of cardiomyopathic, rheumatic and nonrheumatic etiology.

Quantitative angiographic findings were reviewed in 40 patients with significant mitral regurgitation classified into three etiologic groups: group I, primary mitral regurgitation (prolapse, ruptured chordae); group II, mixed stenosis and regurgitation of rheumatic origin; and group III, cardiomyopathic mitral regurgitation. For patients in both groups I and II, left ventricular end-diastolic volume was directly related to regurgitant fraction, and ejection fraction was generally well maintained. In contrast, patients in group III had a depressed ejection fraction (less than 0.40) and end-diastolic volume that was disproportionately increased in relation to the degree of regurgitation. Left ventricular end-diastolic pressure was a poor indicator of severity of regurgitation in all patient groups. There was a significant negative correlation between forward cardiac index and regurgitant fraction. There was significant relation, although with considerable variation, between the normalized V wave and regurgitant fraction. The graphs of chamber size, ejection fraction and hemodynamic measures plotted against the severity of regurgitation in different patient groups provide a perspective for interpreting the findings in individual patients.

Provocation of coronary spasm with ergonovine maleate. New test with results in 57 patients undergoing coronary arteriography.

Ergonovine maleate (Ergotrate) was given to 57 patients undergoing coronary arteriography for investigation of angina occurring at rest or without provocation when routine study showed normal arteries or insufficient occlusive disease to explain their symptoms. This provocative test induced coronary arterial spasm in 13 patients, 10 of whom had definite Prinzmetal's angina. The spasm was easily reversed with sublingually administered nitroglycerin. The spasm was occlusive or nearly occlusive in nine patients, and there was associated reproduction of the chest pain and S-T elevation similar to the spontaneous episodes. One patient with Prinzmetal's angina had S-T depression rather than elevation in association with the chest pain. The other three patients without Prinzmetal's angina had focal narrowing without coronary occlusion, reproduction of the chest pain or electrocardiographic changes. Of the 44 patients who did not demonstrate coronary spasm in response to ergonovine, 29 had normal coronary arteries and 15 had various degrees of atherosclerotic occlusive disease. We conclude that cautious administration of ergonovine maleate during coronary arteriography can be safely used to elicit coronary spasm in some patients who have insufficient fixed occlusive disease to explain their symptoms.

Hemodynamic consequences of afterload reduction in patients with chronic aortic regurgitation.

Nitroprusside was used to reduce afterload in 13 patients with isolated, severe aortic regurgitation. The drug significantly lowered mean aortic pressure, pulse pressure, left ventricular end-diastolic pressure and left ventricular volume. Total ventricular, or angiographic, cardiac index was generally unaffected, but forward cardiac index was improved significantly in 8 of 13 patients. Augmentation of forward cardiac index was seen in patients with subnormal resting forward cardiac index, in patients with decidedly elevated end-diastolic pressure, and in those with depressed resting ejection fractions. Regurgitant fraction fell with nitroprusside in six patients and remained unchanged in seven. Total stroke work index was diminished in all patients. These data show that afterload reduction in patients with severe aortic regurgitation may improve hemodynamics by reducing aortic regurgitation or by improving ventricular pump function. The lowered total stroke work, reduced ventricular size and improved forward cardiac index imply that afterload reduction may benefit left ventricular failure and delay progressive ventricular dysfunction in patients with aortic regurgitation.

Echocardiographic features of supravalvular aortic stenosis.

A method for the echocardiographic detection of supravalvular aortic stenosis (SVAS) is described and the findings in a series of patients are presented. When compared to angiography, the echo tended to underestimate the severity of the supravalvular aortic obstruction. However, echocardiography appears to be a valuable, noninvasive method for detecting SVAS.

Comparison of dobutamine and dopamine in treatment of severe heart failure.

The haemodynamic effects of dobutamine, a new synthetic catecholamine, were studied in 12 patients with severe congestive heart failure and compared with those of dopamine in 10 clinically similar patients. Dobutamine produced a distinct increase in cardiac index, while lowering left ventricular end-diastolic pressure and leaving mean aortic pressure unchanged. Dopamine also significantly improved cardiac index, but at the expense of a greater increase in heart rate than occurred with dobutamine. Dopamine was ineffective in lowering left ventricular end-diastolic pressure, but increased mean aortic pressure. We conclude that dobutamine is an effective, positive inotropic agent in patients with severe congestive heart failure. Because it has comparatively little effect on heart rate and aortic pressure, both major determinants of myocardial oxygen consumption, it may be of special value in patients with the low output syndrome associated with coronary heart disease.

Analysis of left ventricular function in response to afterload changes in patients with mitral stenosis.

In order to assess left ventricular function in patients with rheumatic mitral stenosis, left ventricular function curves (plotting stroke work index vs left ventricular end-diastolic pressure) were constructed using angiotensin to augment, and nitroprusside to reduce, afterload. Hemodynamic responses to these alterations in afterload were measured. Resting ejection fractions and qualitative assessment of left ventricular angiographic contraction abnormalities were also determined. Changes in left ventricular end-diastolic pressure following afterload interventions could be linearly related to changes in mean aortic pressure, but mitral valve gradients were unaffected. Afterload reduction with nitroprusside did not augment cardiac output. Afterload elevation with angiotensin significantly depressed both cardiac output and calculated mitral valve areas. Patients with normal resting ejection fractions evidenced normal ventricular function curves and those with depressed ejection fractions showed flat or declining function curves. Contraction abnormalities, generally in the posterobasal area, correlated well with abnormal left ventricular function curves.

Isolation of viable mouse primordial germ cells by antibody-directed flow sorting.

The germ line represents a cell type of unique interest in mammals because it retains complete genotypic totipotency while undergoing significant phenotypic differentiation. Analysis of the mechanism that underlies the maintenance of this totipotency requires the ability to isolate and study all stages of the germ cell lineage. The primordial germ cells (PGC) are the earliest identifiable germ cells in the embryo. It has not previously been possible to isolate PGC in sufficient numbers and purity to facilitate biochemical and/or molecular analysis. We report here that the use of a monoclonal antibody in combination with flow cytometry does permit the isolation of reasonably large and pure yields of viable mouse PGC.

Evaluation of left ventricular function in patients with aortic regurgitation using afterload stress.

Left ventricular function was assessed in 14 patients with chronic aortic regurgitation by afterload elevation with angiotensin. Seven of 14 patients maintained their resting ejection fraction with angiotensin (group A), while the remaining seven experienced a decline of greater than 0.10 in ejection fraction (group B). Six of seven group A patients showed an appropriate rise in left ventricular stroke work index in response to the angiotensin-induced rise in left ventricular end-diastolic pressure. In contrast, six of seven group B patients showed abnormal, flat, or declining stroke work indices. Included in the seven group B patients were two patients with left ventricular dysfunction secondary to coronary artery disease. The five other group B patients, who did not have coronary diseases, exhibited similar stress-induced ventricular dysfunction, despite the absence of any significant resting hemodynamic differences from patients in group A. These five stress-induced dysfunction patients were distinctive from patients who maintained their ejection fraction level in that the former all had regurgitant fractions of greater than 0.50, whereasl all gruop A patients had regurgitant fractions of less than 0.50. Similarly, these five stress-induced dysfunction patients had significantly larger left ventricular end-diastolic volumes than did the group A patients. These data suggest that patients with pronounced aortic regurgitation measured in terms of regurgitant fraction greater than 0.50 and left ventricular end-diastolic volume of greater than 160 cm3/m2 exhibit impaired ventricular function if appropriately stressed. As most of the patients with stress-induced dysfunction had a normal ejection fraction at rest, it may be that stress-induced dysfunction represents a stage before overt resting dysfunction and cardiac failure.

Cell-cycle-dependent expression of human melanoma membrane antigen analyzed by flow cytometry.

Knowledge of tumor antigenic expression is crucial to the design of therapeutic strategy. A murine monoclonal antibody (BE4) against a human melanoma membrane antigen, was used to study the in vitro expression of this antigen. By membrane immunofluorescence, BE4 reacted against 5 of 8 melanoma lines as compared to zero of 13 other cell populations. Using flow cytometry, the antigenic M14 CEM melanoma cells consisted of 40% to 60% of the total cell population. Dual-parameter measurements of DNA content and membrane antigen demonstrated that the nonantigenic cells were predominantly in G0/G1 phase, whereas the antigenic cells were distributed throughout the cell cycle. Within one passage, the sorted and recultured nonantigenic population demonstrated a similar proportion of antigenic cells as the unsorted original population. It was concluded that the expression of human melanoma antigen was cell-cycle-dependent. Understanding factors that turn off the expression of antigen in G0/G1 phase may lead to better immunotherapeutic strategies.

Bispecific antibody mediated targeting of nido-carboranes to human colon carcinoma cells.

Boron neutron capture therapy, a binary form of cancer treatment, has the potential to deliver potent cytotoxic radiation to tumor cells with minimal collateral damage to normal tissues if methods for the selective accretion of elevated concentrations of boron-10 in tumor can be developed. In this regard, a monoclonal antibody with dual specificity, for both anionic boron cluster compounds (nido-carboranes) and a tumor-associated antigen (carcinoembryonic antigen, CEA), was produced. The specific binding of a nido-carborane to CEA-expressing tumor cells was achieved using this bispecific antibody. The ability of this bispecific antibody to concentrate selectively at tumor sites in vivo has also been demonstrated, thus suggesting its potential for sequestering boron-rich compounds in tumors.