In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis.

Contrast-induced nephropathy accounts for >10% of all causes of hospital-acquired renal failure, causes a prolonged in-hospital stay and represents a powerful predictor of poor early and late outcome. Mechanisms of contrast-induced nephropathy are not completely understood. In vitro data suggests that contrast media (CM) induces a direct toxic effect on renal tubular cells through the activation of the intrinsic apoptotic pathway. It is unclear whether this effect has a role in the clinical setting. In this work, we evaluated the effects of CM both in vivo and in vitro. By analyzing urine samples obtained from patients who experienced contrast-induced acute kidney injury (CI-AKI), we verified, by western blot and immunohistochemistry, that CM induces tubular renal cells apoptosis. Furthermore, in cultured cells, CM caused a dose-response increase in reactive oxygen species (ROS) production, which triggered Jun N-terminal kinases (JNK1/2) and p38 stress kinases marked activation and thus apoptosis. Inhibition of JNK1/2 and p38 by different approaches (i.e. pharmacological antagonists and transfection of kinase-death mutants of the upstream p38 and JNK kinases) prevented CM-induced apoptosis. Interestingly, N-acetylcysteine inhibited ROS production, and thus stress kinases and apoptosis activation. Therefore, we conclude that CM-induced tubular renal cells apoptosis represents a key mechanism of CI-AKI.

Simultaneous dobutamine stress echocardiography and dobutamine scintigraphy (99mTc-MIBI-SPET) for assessment of coronary artery disease.

BACKGROUND: Simultaneous dobutamine stress echocardiography (DSE) and 99Tc-MIBI-SPET (DMS) for the evaluation of the presence and the extent of coronary artery disease (CAD) were assessed for a head to head comparison regarding the diagnostic acuracy of the two rests. METHODS AND RESULTS: Forty-five consecutive patients (33 males and 12 females: 53 +/- 6.8 yr.) underwent exercise electrocardiography and simultaneous dobutamine stress echocardiography and MIBI-SPET imaging. Coronary angiography was performed in all patients (significant coronary stenosis > 50%). On the basis of the results of exercise electrocardiogram the pre-test probability for coronary artery disease (Diamond's algorithm) was low (45.6 +/- 12.7%). The overall specificity, sensitivity and predictive accuracy of Echo-dobutamine stress test for diagnosis of the presence or absence of CAD were: specificity 82%, sensitivity 76%, diagnostic accuracy 80%, positive predictive value 90%, negative predictive value 40%. The overall specificity, sensitivity and predictive accuracy of MIBI-SPET-dobutamine test for diagnosis of the presence or absence of CAD were: specificity 86%, sensitivity 87%, diagnostic accuracy 84%, positive predictive value 97%, negative predictive value 54%. MIBI-SPET-dobutamine test showed a significantly higher sensitivity in comparison with ECHO-dobutamine test (P < 0.05). CONCLUSION: Both noninvasive methods for the detection of CAD showed a good diagnostic accuracy. Nevertheless the SPET model showed a higher sensitivity in comparison with DSE model, essentially in the presence of a lower extent of CAD and during submaximal test.

Incremental diagnostic value of dobutamine stress echocardiography and dobutamine scintigraphy (technetium 99m-labeled sestamibi single-photon emission computed tomography) for assessment of presence and extent of coronary artery disease.

BACKGROUND: The incremental diagnostic value of dobutamine stress echocardiography (DSE) and 99mTc-labeled sestamibi single-photon emission computed tomography for the evaluation of the presence and extent of coronary artery disease (CAD) was assessed with ordered logistic regression and receiver-operating characteristic curves. METHODS AND RESULTS: Forty-five consecutive patients (33 men and 12 women; 53 +/- 6.8 years) underwent exercise electrocardiography and simultaneous DSE and sestamibi single-photon emission computed tomographic imaging. Coronary angiography was performed in all patients (significant coronary stenosis > 50%). On the basis of the results of exercise electrocardiography, the pretest probability for CAD (Diamond's algorithm) was low (45.6% +/- 12.7%). According to ordered logistic regression analysis, some models were estimated that performed a diagnostic accuracy level for CAD. In particular, we evaluated a clinical model (model 1) determined by the following parameters: sex, age, presence of chest pain, and positivity of electrocardiogram during dobutamine stress test. This model was 64.3% +/- 10.7% accurate for the prediction of CAD. The addition to model 1 of DSE parameters (wall motion stress and rest score index and relative difference) (model 2) yielded a diagnostic accuracy of 81.4% +/- 4.3% (p < 0.045), whereas the addition to model 1 of single-photon emission computed tomographic parameters (the difference between perfusional stress and rest score index) (model 3) improved diagnostic accuracy to 92.3% +/- 5.5% (p < 0.003), a level that appeared significantly higher than that of model 2 (p < 0.016). CONCLUSION: Both noninvasive methods for the detection of CAD showed a good diagnostic accuracy, especially when test-derived parameters were combined with clinical data. Nevertheless, the single-photon emission computed tomographic model showed a higher sensitivity compared with the DSE model.