Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study.

OBJECTIVE: In addition to lowering lipid levels, statins might reduce leukocyte-endothelial cell interactions. Therefore, we assessed whether this effect could limit the inflammatory response to cardiopulmonary bypass (CPB) in cardiac surgical patients. METHODS: Twenty patients undergoing valve or coronary operations with tepid (34 degrees C) CPB were randomized to receive an oral dose of atorvastatin (40 mg the evening before and 40 mg the morning of surgery) or to serve as controls. Pre- and post-CPB blood samples were assayed for neutrophil CD11b surface adhesion molecule and oxidative burst. Plasma levels of interleukins 6 and 8, P-selectin, soluble intercellular adhesion molecule-1, and lactoferrin were measured by enzyme-linked immunosorbent assay (ELISA). In addition, right atrial biopsies were taken before and at the end of CPB, and processed for the expression of the transcription nuclear factor-kappa B (NF-kappaB). RESULTS: The two groups did not differ with regard to pre- and intraoperative data. Except for P-selectin, postbypass values of all markers significantly increased over baseline values, but atorvastatin therapy failed to attenuate the magnitude of this increase. In the two groups, the expression of NF-kappaB significantly (p = 0.004) increased over baseline without group effect. Postoperative clinical outcomes did not differ either between the two groups. CONCLUSION: These data show that acute preoperative statin therapy fails to limit the inflammatory response to CPB; however, the data also document a major upregulation of NF-kappaB during cardiac operations, thereby providing a sound rationale for interventions targeted at inactivating this key component of the inflammatory cascade.

Is adenosine preconditioning truly cardioprotective in coronary artery bypass surgery?

BACKGROUND: The large number of experimental studies showing that adenosine "turns on" the protein kinase C (PKC)-mediated pathway that accounts for the cardioprotection conferred by ischemic preconditioning contrasts with the scarcity of clinical data documenting the preconditioning-like protective effect of adenosine during cardiac operations on humans. METHODS: Forty-five patients undergoing coronary artery bypass were randomized to receive, after the onset of cardiopulmonary bypass, a 5-minute infusion of adenosine (140 microg x kg(-1) x min(-1)) followed by 10 minutes of washout before cardioplegic arrest (n = 23) or an equivalent period (15 minutes) of prearrest drug-free bypass (controls, n = 22). Outcome measurements included troponin I release over the first 48 postoperative hours and activity of ecto-5'-nucleotidase, an admitted reporter of PKC activation, as assessed on right atrial biopsies taken before bypass and at the end of the preconditioning protocol (or after 15 minutes of bypass in control patients). RESULTS: Aortic cross-clamping times were not different between the two groups. Likewise, prebypass values of ecto-5'-nucleotidase (nanomoles/mg protein per minute) were similar in control (3.14+/-1.02) and adenosine-treated (2.66+/-1.08) patients. They subsequently remained unchanged in control patients (3.87+/-1.65) whereas they significantly increased after adenosine preconditioning (4.47+/-1.96, p<0.001 versus base line values). However, peak postoperative values of troponin I (microg/L) were not significantly different between control (4.8+/-2.8) and adenosine-preconditioned patients (5.9+/-6.6) nor were the areas under the curve. There were no adverse effects related to adenosine. CONCLUSIONS: Adenosine, given at a clinically safe dose, can turn on the PKC-mediated signaling pathway involved in preconditioning but this biochemical event does not translate into reduced cell necrosis after coronary artery surgery, suggesting that a preconditioning-like protocol may not be the best suited for exploiting the otherwise well-documented cardioprotective effetcs of adenosine.

[Echocardiographic diagnosis of left intraventricular thrombi: contribution of high frequency probes]. / Diagnostic échocardiographique des thrombi intraventriculaires gauches : apport des sondes de hautes fréquences.

Two-dimensional echocardiography is the reference technique for the diagnosis of left ventricular thrombi. However, it has some limitations due to poor imaging of the apex; location of many thrombi. Apical resolution improvement is possible using a 5 MHz ultrasonic transducer, which may identify 3.5MHz ultrasonic transducer false positive results. In a series of 53 patients with left ventricular dysfunction, we detected 11 thrombi. Using the 5MHz ultrasonic transducer as a reference the sensitivity of the 3.5MHz ultrasonic transducer was 100%, and much greater than that of the 2.5MHz ultrasonic transducer (55%), which was associated with 4 false positive results. The increased sensitivity associated with transducers of higher frequency was however limited by the echogenicity of patients, all the more since we used a medium instead of a short focalisation. Due to its therapeutic consequences, the detection of left ventricular thrombi must be enhanced using 5 MHz ultrasonic transducer, all the more in echogenic patients.

[Echocardiographic diagnosis of left intraventricular thrombus. A comparative study of 2.5, 3.5 and 5 MHz transducers]. / Diagnostic échographique des thrombus intraventriculaires gauches. Etude comparative des sondes de 2,5, 3,5 et 5 MHz.

The authors undertook a prospective and comparative echocardiographic study of 2.5, 3.5 and 5 MHz ultrasonic transducers for the detection of left ventricular mural thrombosis in 53 patients with left ventricular dysfunction. Thirty-three patients had advanced ischaemic heart disease following anterior myocardial infarction and 20 had dilated cardiomyopathy with a left ventricular ejection fraction of < or = 40%. Eighty-two per cent of patients had anticoagulant therapy. The diagnosis of thrombosis was based on Asinger's classification. Eleven thrombi were detected, an incidence of 21%. Using the 5 MHz transducer as a reference, the sensitivity of the 3.5 MHz transducer was 100% and much greater than that of the 2.5 MHz transducer (55%) which was associated with 4 false positive results. The specificities were respectively 97 and 86% for the 3.5 and 2.5 MHz transducers. There was no correlation between the apical Doppler flow velocities and the presence of mural thrombosis. Atrial fibrillation was significantly associated with mural thrombosis (p = 0.04). The increased sensitivity associated with transducers of higher frequency is, however, limited by the echogenicity of patients. The introduction of transducers of variable frequencies should facilitate the diagnosis and improve the sensitivity of echocardiography in detecting left ventricular mural thrombosis.