Effect of skeletonizationof the internal thoracic artery on vessel wall integrity

Background. This study was conceived to evaluate the effect of internal thoracic artery (ITA) skeletonization on vessel wall integrity. Methods. Forty consecutive patients undergoing coronary artery bypass were randomized to receive a skeletonized (n = 22) or a pedicled (n = 18) ITA graft. ITA harvesting was performed by 2 experienced surgeons using the same instrumentation and technique. Specimens were examined by light and electron microscope in order to assess vascular wall integrity. A specific immunohistochemical staining and a computerized method were used to quantify the degree of endothelial integrity after surgical preparation. Results. Morphologic analysis revealed 2 cases of limited subadventitial hemorrhage tone for each group) and no case of major arterial damage. Immunohistochemical staining demonstrated an extremely high degree of maintenance of the endothelial integrity in both groups (97.2% +/- 1.9% in the skeletonized and 96.8% +/- 2.1% in the pedicled one; p = 0.53). Conclusions. Skeletonization does not affect ITA wall integrity in humans submitted to coronary artery bypass procedures. (C) 1999 by The Society of Thoracic Surgeons

Secondary alcohol metabolites mediate iron delocalization in cytosolic fractions of myocardial biopsies exposed to anticancer anthracyclines. Novel linkage between anthracycline metabolism and iron-induced cardiotoxicity.

The cardiotoxicity of doxorubicin (DOX) and other quinone-containing antitumor anthracyclines has been tentatively attributed to the formation of drug semiquinones which generate superoxide anion and reduce ferritin-bound Fe(III), favoring the release of Fe(II) and its subsequent involvement in free radical reactions. In the present study NADPH- and DOX-supplemented cytosolic fractions from human myocardial biopsies are shown to support a two-step reaction favoring an alternative mechanism of Fe(II) mobilization. The first step is an enzymatic two-electron reduction of the C-13 carbonyl group in the side chain of DOX, yielding a secondary alcohol metabolite which is called doxorubicinol (3.9 +/- 0.4 nmoles/mg protein per 4 h, mean +/- SEM). The second step is a nonenzymatic and superoxide anion-independent redox coupling of a large fraction of doxorubicinol (3.2 +/- 0.4 nmol/mg protein per 4 h) with Fe(III)-binding proteins distinct from ferritin, regenerating stoichiometric amounts of DOX, and mobilizing a twofold excess of Fe(II) ions (6.1 +/- 0.7 nmol/mg protein per 4 h). The formation of secondary alcohol metabolites decreases significantly (Pi < 0.01) when DOX is replaced by less cardiotoxic anthracyclines such as daunorubicin, 4'-epi DOX, and 4-demethoxy daunorubicin (2.1 +/- 0.1, 1.2 +/- 0.2, and 0.6 +/- 0.2 nmol/mg protein per 4 h, respectively). Therefore, daunorubicin, 4'-epi DOX, and 4-demethoxy daunorubicin are significantly (P < 0.01) less effective than DOX in mobilizing Fe(II) (3.5 +/- 0.1, 1.8 +/- 0.2, and 0.9 +/- 0.3 nmol/mg protein per 4 h, respectively). These results highlight the formation of secondary alcohol metabolites and the availability of nonferritin sources of Fe(III) as novel and critical determinants of Fe(II) delocalization and cardiac damage by structurally distinct anthracyclines, thus providing alternative routes to the design of cardioprotectants for anthracycline-treated patients

Normothermia does not improve postoperative hemostasis nor does it reduce inflammatory activation in patients undergoing primary isolated coronary artery bypass.

Background: Despite its common acceptance in clinical practice, the effective benefits of normothermic systemic perfusion during coronary artery bypass operations are far from established. Methods: A total of 113 patients undergoing primary isolated coronary artery bypass were randomly assigned to normothermic (37\ub0C) or hypothermic (26\ub0C) systemic perfusion. The clinical course of the patients was prospectively recorded, and several inflammatory and fibrinolytic markers (C-reactive protein, fibrinogen, interleukin 6, plasminogen activator inhibitor 1, prothrombin time, activated partial thromboplastin time, platelets, and white blood cell counts) were determined before surgical intervention; 24, 48, and 72 hours thereafter; and at hospital discharge. Results: Postoperatively, 2 in-hospital deaths occurred in the normothermic series and none in the hypothermic series. Four patients had a myocardial infarction, 1 had respiratory insufficiency, 1 had to be reoperated on for graft malfunction, and none had renal insufficiency in the hypothermic group versus 1 patient with each of these complications in the normothermic series. Mean blood loss in the first 24 hours was 766 \ub1 223 mL in the normothermic group and 740 \ub1 220 mL in the hypothermic group. None of these differences was statistically significant. Similarly, no significant difference in the postoperative level of any of the measured variables at any time point was evident between the patients in the normothermic and hypothermic groups. Conclusion: Normothermic systemic perfusion does not influence the clinical course or the extent of inflammatory and hemostatic activation in patients undergoing primary isolated coronary artery bypass

Myocardial apoptosis predicts postoperative course after aortic valve replacement in patients with severe left ventricular hypertrophy

BACKGROUND AND AIM OF THE STUDY: Myocardial apoptosis has been implicated in heart failure and post-infarct remodeling. In some patients with severe aortic stenosis, delayed valvular replacement is associated with a poor in-hospital outcome. The study aim was to evaluate the impact of cardiomyocyte apoptosis on the postoperative course after aortic valve replacement (AVR) for severe aortic stenosis. METHODS: During elective AVR, myocardial biopsies were obtained from the left ventricle of 11 patients with severe left ventricular hypertrophy (LVH), and the samples analyzed for apoptosis. RESULTS: The mean apoptotic rate was 10.4 +/- 3.7 per thousand. (range: 5-16 per thousand). The apoptotic rate correlated directly with preoperative NYHA functional class, duration of intensive care unit (ICU) stay, number of days of postoperative acute renal insufficiency, and serum level of troponin T at 24 h; the apoptotic rate correlated inversely with cardiac index at 24 h postoperatively. At multivariate analysis, the apoptotic rate and left ventricular mass index were independent predictors of prolonged ICU stay. The apoptotic rate and duration of cardiopulmonary bypass were predictive of the duration of postoperative acute renal insufficiency. CONCLUSION: The study results showed an association between myocardial apoptosis and postoperative outcome in patients with severe LVH submitted for AVR. Non-invasive correlates of apoptosis may be introduced as a means of identifying patients at a higher operative risk, and may help in the evaluation of asymptomatic patients with severe aortic stenosis. Anti-apoptotic strategies before and during surgery would possibly ameliorate the surgical result

Myocardial ischemia, stunning, inflammation, and apoptosis during cardiac surgery: a review of evidence

Cardiac surgery (CS), in particular cardiopulmonary bypass and cardioplegia, have been reported to trigger myocardial inflammation and apoptosis. This surgery-related inflammatory reaction appears to be of extreme complexity with regard to its molecular, cellular and tissue mechanisms. Both experimental and clinical studies have ascertained the role of several hormonal mediators, mitochondria, cardioplegia and extracorporeal circulation temperature, apoptosis and even genetic modulators of damage. However, the correlations between these factors in vivo and post-surgery outcome and prognosis have not yet been systematically investigated. In animal models of myocardial cardioplegia and/or ischemia-reperfusion, experimental drugs such as antioxidants have been documented to provide amelioration of post-intervention cardiac performance and reduction of apoptosis suggesting the possibility of new therapeutic strategies. However, these findings have been only partially confirmed in humans. Moreover, markers for the differential detection of early and late phases of apoptosis are subjects of intense investigations. This review will provide an overview of the major studies about the link between ischemia, myocardial inflammation and apoptosis during and after CS, with particular regard to the markers and methods for apoptosis detection. (C) 2003 Elsevier B.V. All rights reserved