Calcium-activated neutral protease (CANP), also known as calpain, has been implicated in the development of cell death in ischemic hearts. CANP is thought to be activated by the calcium overload that develops during ischemia. We studied the involvement of CANP in cell death in cultured neonatal rat cardiomyocytes during metabolic inhibition (5 mmol/L NaCN + 10 mmol/L 2-deoxyglucose). First, we isolated CANP using ion exchange and affinity chromatography. Then the efficacy of the CANP inhibitors calpain I inhibitor, leupeptin, and E64 to inhibit isolated CANP activity was tested with the use of fluorescently labeled beta-casein as a substrate. The IC50 for the inhibitors was between 2.1 and 56 mumol/L. Uptake of the inhibitors by intact cells was assessed with the use of 99mTc-radiolabeled inhibitors. The calculated intracellular inhibitor concentrations were sufficiently high to yield substantial inhibition of intracellular CANP activity. Intracellular CANP activity was measured directly with the use of the cell-permeant fluorogenic CANP-specific substrate N-succinyl-Leu-Leu-Val-Tyr-7-amido-4-methyl-coumarin. During metabolic inhibition, intracellular CANP activity was increased compared with control incubation. The time course of CANP activation was compatible with that of the rise in [Ca2+]i, as measured by fura 2 and digital imaging fluorescence microscopy. Calpain I inhibitor and leupeptin inhibited intracellular CANP activity both during metabolic inhibition and control incubation, whereas E64 did not. Despite their substantial inhibition of intracellular CANP activity, calpain I inhibitor and leupeptin did not attenuate cell death during metabolic inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

LAD embolisation not only results in a significantly diminished LV systolic function but also causes RV systolic function to decline significantly. Regional dysfunction by necessity entails global dysfunction as well. Analysis of ventricular geometry reveals that both the septum and the RV free wall increase their length, which plays an important role in the pathophysiology of diminished RV systolic function concomitant with reduced LV function.

This study shows the usefulness of echo planar MRI to assess myocardial contractility of both ventricles simultaneously. Furthermore, the study shows that beta-adrenergic stimulation has a significantly greater positive inotropic effect on LV contractility than on RV contractility.

An MRI-compatible catheter was developed for pacing the heart during MRI imaging. The device was tested in vitro and in vivo in 10 animal experiments, using spin-echo, gradient-echo, and echo-planar MRI sequences. Images were of good quality in all sequences. Pacing was effective without induced arrhythmias. Therefore, pacing the heart during MRI is feasible and seems to be safe when using dedicated hardware.