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.

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.

No abstract

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.