Epicardial coronary artery Doppler: validation in the animal model.

The aim of the study was to validate a newly-designed epicardial coronary artery Doppler probe and test its detection of changes in coronary blood flow velocity. Left anterior descending (LAD) coronary blood flow and flow velocity were evaluated in four pigs with a pericoronary transit time flow (TTF) probe and a newly-designed epicardial Doppler micro-probe. Four consecutive measurements were taken for each of the following conditions: basal, partial stenosis, occlusion, and reperfusion of the LAD. Mean TTF value (ml/min) was 23.2+/-6.6 in basal condition, 16.2+/-5.7 after partial LAD stenosis, 0.1+/-0.3 during LAD occlusion, and 67.4+/-23.3 at reperfusion (P<0.001). Similar patterns were recorded in terms of Doppler velocity (cm/s) with values of 4.0+/-1.9 in basal condition, 3.5+/-2.3 after partial LAD stenosis, 0.5+/-1.4 during LAD occlusion, and 11.1+/-5.5 at reperfusion (P<0.001). No significant differences in both TTF and Doppler velocity were detected between basal condition and partial LAD stenosis (P=ns). Epicardial coronary arterial Doppler represents a valuable tool to detect coronary arterial flow velocity in basal condition. Although changes in flow velocity are easily recorded after coronary occlusion and reperfusion, modifications after partial coronary stenosis are not clearly defined.

Reperfusion injury in humans: a review of clinical trials on reperfusion injury inhibitory strategies.

The principal therapy in patients with myocardial infarction to limit infarct size is myocardial reperfusion by mechanical or pharmacological intervention. Reperfusion has been proposed to cause myocardial injury beyond that caused by the preceding ischaemia, termed "reperfusion injury" (RI). While the precise mechanism of RI is still incompletely understood, a large number of clinical studies have been performed over the past decade targeting some of the postulated mechanisms of RI. These clinical studies were based on experimental data demonstrating significant myocardial salvage. Nevertheless, clinical benefits were absent or very limited. The purpose of this review is to provide an overview of the various strategies that inhibit RI and to discuss potential mechanisms that may contribute to the discrepancy between the promising pre-clinical data and the rather disappointing results obtained from prospective clinical trials. There are numerous differences between the experimental models and clinical studies, including the fact that experimental studies typically use abrupt occlusion and reperfusion protocols in animals with previously healthy myocardium that apparently do not predict the therapeutic efficacy of novel cardioprotective agents in a clinical setting with pre-existing progressive coronary disease, intermittent coronary occlusion, and relatively late reperfusion. However, discrepancies also exist between experimental studies. Future experimental studies of reperfusion injury should use models that mimic the clinical situation more closely. Furthermore, future large clinical trials should only be performed in cases where the drug under investigation proved to reduce RI in a series of well-designed (possibly multicenter) experimental studies and in clinical trials with predefined subgroups.

The effect of ITF-1697 on reperfusion in patients undergoing primary angioplasty. Safety and efficacy of a novel tetrapeptide, ITF-1697.

AIM: ITF-1697 is a C-reactive protein-derived tetrapeptide that, based on pre-clinical studies, is thought to reduce reperfusion injury. We performed a dose-finding study to assess safety, preliminary efficacy and clinical outcome of prolonged i.v. infusion of ITF-1697 in patients with an acute myocardial infarction (AMI) who were eligible for percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a multicentre dose-finding study that was randomised, double blind, and placebo-controlled. Four hundred and two patients were enrolled. Intravenous infusion of four dosages of ITF-1697 (0.1, 0.5, 1.0 or 2.0 microg/kg/min) or placebo was started before PCI and continued for 24 h. After interim analysis of data from 242 patients the study continued with the 0.1 and 1.0 microg/kg/min ITF-1697 regimes. Analysis did not raise any safety concerns. Post-procedure perfusion, assessed by TIMI flow, corrected TIMI frame count, blushgrade and ST-segment resolution, was similar for the placebo, 0.1 and 1.0 microg/kg/min regimes. Furthermore, the results showed no differences between the treatment regimes in enzymatic infarct size or clinical outcome up to 30 days. CONCLUSION: ITF-1697 was well tolerated. However, neither a dose-relation nor improvement of perfusion, clinical outcome or reduction of myocardial damage could be demonstrated with ITF-1697 during and after primary PCI for AMI.