Exercise-induced mitral regurgitation is a predictor of morbid events in subjects with mitral valve prolapse.

OBJECTIVES: This study attempted to determine whether a subset of patients with mitral valve prolapse and no mitral regurgitation at rest will develop mitral regurgitation during exercise and have a higher than anticipated risk of morbid cardiovascular events. BACKGROUND: Mitral regurgitation in patients with mitral valve prolapse identifies a subset of patients at higher risk for morbid events. However, mitral regurgitation in patients with mitral valve prolapse may be intermittent and could go unrecognized. A provocative test to unmask mitral regurgitation in these patients would be useful. METHODS: Ninety-four adult patients with mitral valve prolapse and no mitral regurgitation at rest were studied during supine bicycle ergometry using color flow Doppler echocardiography in the apical four-chamber and long-axis views. Patients were prospectively followed up for morbid events. RESULTS: Thirty (32%) of 94 patients had exercise-induced mitral regurgitation. Prospective follow-up (mean 38 months) showed more morbid events in the group with than without mitral regurgitation and included, respectively, syncope (43% vs. 5%, p < 0.0001), congestive heart failure (17% vs. 0%, p < 0.005) and progressive mitral regurgitation requiring mitral valve replacement surgery (10% vs. 0%, p < 0.05). Cerebral embolic events, endocarditis or sudden death were rare and not different between groups. CONCLUSIONS: In patients with mitral valve prolapse without mitral regurgitation at rest, exercise provokes mitral regurgitation in 32% of patients and predicts a higher risk for morbid events.

Transesophageal echocardiography: normal variants and mimickers.

An accurate diagnosis of cardiac pathology using TEE is contingent upon the ability to recognize and differentiate normal cardiac structures and normal variants from pathologic conditions. We describe several normal cardiac structures commonly imaged using TEE of the atria, interatrial septum, aorta, valves, and extracardiac spaces that may mimic diverse pathologic states, such as intracardiac tumor and thrombus, valvular vegetations, mitral and tricuspid valve prolapse, atherosclerotic plaque, and aortic dissection. Methods to aid in the differentiation of normal cardiac structures from pathology are offered.

Comparison of cardiac dimensions by transesophageal and transthoracic echocardiography.

Transesophageal echocardiography (TEE) has advanced rapidly as a valuable cardiovascular diagnostic technique. As the use of TEE increases, so does the importance of well-defined normal cardiac measurements. Presently, few data exist on the accuracy of M-mode TEE-derived measurements. Therefore in 81 adult patients, TEE-derived M-mode measurements were compared with analogous measurements that were made by standard M-mode transthoracic echocardiography (TTE). The TTE and TEE measurements did not differ in aortic root diameter, end-diastolic left ventricular diameter, end-diastolic septal wall versus anterior wall thickness, or end-diastolic posterior wall versus inferior wall thickness. These TEE measurements were within 95% confidence limits of TTE measurements. TEE-derived left atrial diameter (3.5 +/- 0.8 cm) was less than that derived by TTE (3.8 +/- 0.8 cm; p less than 0.001) and fell outside of the 95% confidence interval. TTE left atrial size could be estimated as follows: TTE-derived left atrial diameter = TEE-derived left atrial diameter x 0.6 + 1.5 cm. In conclusion, M-mode measurements of aortic root diameter, left ventricular diameter, and wall thicknesses as derived by TTE and TEE are comparable. TEE-derived left atrial diameter may be used to estimate the left atrial TTE measurement. TEE-derived M-mode measurements are likely to be most useful when results of TTE are technically inadequate.

Restoration of orbicularis oculi function by contralateral orbicularis oculi innervated muscle flap vs neuromuscular pedicle technique.

In preliminary experiments with dogs and cats, unilateral paralysis of the orbicularis oculi muscle group was produced by a section of the seventh nerve that included the posterior auricular branch. Either one of two procedures was then employed in attempts to reinnervate the paralyzed eyelid. In one group of animals, a neuromuscular pedicle was employed and in another, a contralateral orbicularis innervated muscle flap was used. Both methods restored synchronous, reflex blinking to the denervated eyelid. Of the two procedures, neurotization appears to offer the greater promise because the use of a neuromuscular pedicle requires an expendable nerve that is functional, and no such suitable substitute is available in humans.

Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans.

A reasonably sensitive and specific noninvasive test for doxorubicin cardiotoxicity is needed. In addition, few data exist on the short- and long-term effects of doxorubicin on diastolic filling. To determine if pulsed Doppler indexes of diastolic filling could predict doxorubicin-induced systolic dysfunction, 26 patients (mean age 48 +/- 12 years) were prospectively studied before receiving chemotherapy (control) and 3 weeks after obtaining cumulative doses of doxorubicin. In nine patients developing doxorubicin-induced systolic dysfunction (that is, a decrease in ejection fraction by greater than or equal to 10 ejection fraction units to less than 55%), the isovolumetric relaxation time was prolonged (from 66 +/- 18 to 84 +/- 24 ms, p less than 0.05) after a cumulative doxorubicin dose of 100 to 120 mg/m2. This prolongation preceded a significant decrease in ejection fraction. Other Doppler indexes of filling were impaired after doxorubicin therapy but occurred simultaneously with the decrease in ejection fraction. A greater than 37% increase in isovolumetric relaxation time was 78% (7 of 9) sensitive and 88% (15 of 17) specific for predicting the ultimate development of doxorubicin-induced systolic dysfunction. In 15 patients studied 1 h after the first treatment, doxorubicin enhanced Doppler indexes of filling and shortened isovolumetric relaxation time. In 22 patients, indexes of filling remained impaired and isovolumetric relaxation time was prolonged 3 months after the last doxorubicin dose. In conclusion, doxorubicin-induced systolic dysfunction is reliably predicted by prolongation of Doppler-derived isovolumetric relaxation time. Early after administration, doxorubicin enhances filling and isovolumetric relaxation time. The adverse effects of doxorubicin on both variables persist at least 3 months after cessation of treatment.

The transesophageal echocardiographic diagnosis of left atrial myxoma simulating a left atrial thrombus in the setting of mitral stenosis.

We report a case of left atrial myxoma simulating a thrombus on transthoracic echocardiography, but correctly diagnosed using transesophageal echocardiography. As this tumor is usually fatal unless surgically resected, a correct diagnosis is essential. Myxomas which do not prolapse between the mitral valve leaflets and coexist with mitral stenosis may be difficult to diagnose accurately using transthoracic echocardiography. The advantages of transesophageal compared with transthoracic echocardiography in the diagnosis of nonclassical left atrial myxoma are discussed.

Two-dimensional transesophageal echocardiographic determination of aortic valve area in adults with aortic stenosis.

To determine if aortic stenosis severity could be accurately measured by two-dimensional transesophageal echocardiography (TEE), 62 adult subjects (mean age 66 +/- 12 years) with aortic stenosis had their aortic valve area (AVA) determined by direct planimetry using TEE, and with the continuity equation using combined transthoracic Doppler and two-dimensional echocardiography (TTE). Eighteen subjects had AVA calculated by the Gorlin method during catheterization. An excellent correlation (r = 0.93, SEE = 0.17 cm2) was found between AVA determined by TEE (mean 1.24 +/- 0.49 cm2; range 0.40 to 2.26 cm2) and TTE (mean 1.23 +/- 0.46 cm2; range 0.40 to 2.23 cm2). The absolute (0.13 +/- 0.12 cm2) and percent (10.8 +/- 8.9%) differences between AVA determined by TEE versus TTE were small. Excellent correlations between AVA by TEE and TTE were also found in subjects with normal systolic function (r = 0.95, SEE = 0.14 cm2; n = 38) and impaired function (r = 0.91, SEE = 0.21 cm2; n = 24). AVA determined by catheterization correlated better with AVA measured by TEE (r = 0.91, SEE = 0.15 cm2) than AVA measured with TTE (r = 0.84, SEE = 0.19 cm2). These data demonstrate that AVA can be accurately measured by direct planimetry using TEE in subjects with aortic stenosis. TEE may become an important adjunct to transthoracic echocardiography in the assessment of aortic stenosis severity.

Cytolysis of rat glioma cells in vitro by autonomic drugs.

The results of glioma chemotherapy obtained so far have been rather disappointing. New attempts have been made to kill glioma cells with autonomic drugs. Experiments were done with rat C-6 glioma cells in the cell culture. Among all cholinergic blockers tested, only the irreversible cholinergic blockers such as bromoacetylcholine (BrACh), iodoacetylcholine and alphabungarotoxin were effective to inhibit glioma cells (with 50% cytolytic doses of 6.7 x 10(-6)M, 3.0 x 10(-6)M and 7.4 x 10(-5)M respectively). It is interesting to note that the hydrolytic product of BrACh, bromoacetate, was as potent as BrACh to inhibit glioma cells. Most of the adrenergic blockers, both reversible and irreversible ones, showed no cytolytic activity on glioma cells with concentrations up to 1.0 x 10(-4)M except phentolamine and propranolol which showed weak cytolytic activities. It is interesting to note, on the other hand, that 6-hydroxydopamine (an adrenergic neuron degenerating agent) and 5,6-dihydroxytryptamine (a serotonergic neuron degenerating agent) also showed mild cytolytic effects on glioma cells with 50% cytolytic doses of 5.0 x 10(-5)M and 5.3 x 10(-5)M, respectively.

Inhibition by anions of human red cell carbonic anhydrase B: physiological and biochemical implications.

The hydration rate of CO2 catalyzed by human red cell carbonic anhydrase B is 92 percent reduced by the normal concentrations of chloride and bicarbonate in red cells. This reflects a general sensitivity of this reaction to halides and other anions, up to 87 times greater than the effect on red cell carbonic anhydrase C. The catalytic hydration of CO2 is generally more (up to 24 times) sensitive to inhibition by anions and sulfonamides than the dehydration of HCO3-, probably reflecting different mechanisms. The sensitivity of enzyme B to anion inhibition also depends upon the substrate, being much greater for CO2 than for certain esters. On the basis of the very low catalytic activity of B for CO2 in the presence of physiological concentration of chloride, and the fact that carbonic anhydrase C is effective for CO2 hydration (in the presence of chloride) at a rate 340 times greater than that of CO2 output from tissues, it appears that the biological role of enzyme B is not that of a carbonic anhydrase.

CO2 retention as a basis for increased toxicity of salicylate with acetazolamide: avoidance of increased toxicity with benzolamide.

Two carbonic anhydrase inhibitors, acetazolamide and benzolamide, are capable of increasing the toxicity of sodium salicylate in mice. Beginning at about 2 mg/kg, each of the inhibitors, in combination with a fixed (400 mg/kg) dose of salicylate, generates a dose-mortality curve that reaches a plateau at about 60% deaths at 6 to 8 mg/kg. This effect can be duplicated by 8 to 10% inspired CO2. It appears that the respiratory acidosis secondary to the inhibition of red cell carbonic anhydrase is responsible for the increased toxicity; earlier work by others shows that acidosis increases the concentration of salicylate in the brain. In the treatment of salicylate poisoning by carbonic anhydrase inhibitors, the goal is to alkalinize the urine and increase the excretion of salicylate. With the newer inhibitor, benzolamide, it is possible to dissociate the respiratory acidosis from the renal effect. Maximal alkalinization of the urine is possible with a dose (about 1 mg/kg) below that which generates a respiratory acidosis. With this dose, there is no increase in the early toxicity of salicylate.