Hypoxic reperfusion limits functional impairment following cardioplegic arrest in isolated rat heart.

BACKGROUND: Reperfusion injury decreases both systolic contractility and diastolic compliance. Several studies indicate that the sustained decrease in diastolic compliance is mainly due to reactive oxygen intermediates (ROI) generation and calcium overload. METHODS: Male Wistar isolated rat hearts were divided into 2 groups (n=10 each), perfused according to Langendorff technique and exposed to 45 min of ischemia. Hearts belonging to the first group were reperfused with Krebs-Henseleit solution at 600 mmHg pO2; a 150 mmHg pO2 perfusate was utilized in the second group during the first minute and switched to 600 mmHg pO2 thereafter. Modifications in diastolic compliance and systolic contractility were assessed by changes in left ventricular end-diastolic (LVEDP) and developed pressure (LVDP), and first derivative of the pressure curve (dP/dt). RESULTS: Increase in LVEDP values, with respect to pre-ischemic data, were detected at 1, 5, 10, 20 min following reperfusion at 600 mmHg pO2, and were respectively: +40.17+/-18.61, +57.5+/-28.8, +59.8+/-30.5 and +63.2+/-34.1 mmHg. At 150 mmHg pO2 they were: +15.69+/-13.13, +22.4+/-14.1, +26.2+/-13.7 and +28.9+/-15.8, with a significant difference within the first 20 min (p<0.05). At high pO2 levels, LVDP decreased of 53.0+/-27.35, 60.5+/-22.6, 59.8+/-23.3 and 50.7+/-25.0 mmHg, versus 42.7+/-25.7, 38.0+/-29.5, 39.2+/-30.9 and 38.7+/-32.7 mmHg at lower pO2 (p=NS). The correspondent values of the dP/dt were 37.8+/-27.7, 30.1+/-17.2, 32.2+/-13.6 and 35.4+/-14.0% of pre-ischemic values at high pO2, versus 43.3+/-27.09, 51.9+/-25.1, 50.1+/-24.6 and 53.1+/-29.9% at lower pO2. Statistical significance was lower for LVDP and dP/dt than LVEDP. CONCLUSIONS: Diastolic functional impairment was partially reduced within the first 20 min following low pO2 reperfusion, but without any significant improvement of contractility.

Relationship between cathepsin D and other pathological and biological parameters in 1752 patients with primary breast cancer.

The relationship between cathepsin D and other pathological or biological prognostic parameters has not yet been defined through systematic studies in breast cancer. The aim of the present investigation was to define the relationship between cathepsin D and nodal status, tumour size, steroid receptors and tumour grade in a wide patient series. Cytosol cathepsin D was assayed with an immunoradiometric assay in tumour samples from 1752 patients. A statistically significant, but not biologically meaningful association was found between cathepsin D and both tumour size and grade. Cathepsin D was significantly higher in node-positive than in node-negative tumours. However, cathepsin D is not of great use in order to predict the risk of axillary metastases in individual patients, due to overlapping of cathepsin D values between node-positive and node-negative cases. A significant, direct association was found between cathepsin D and both oestrogen receptor and progesterone receptor cytosol levels. Nevertheless, preliminary data indicate that cathepsin D and steroid receptors provide independent prognostic information.