Left ventricular surgical restoration for anteroseptal scars: Volume versus shape

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La insuficiencia mitral isquémica crónica: el dilema quirúrgico de esta década

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Defective One- or Two-electron Reduction of the Anticancer Anthracycline Epirubicin in Human Heart RELATIVE IMPORTANCE OF VESICULAR SEQUESTRATION AND IMPAIRED EFFICIENCY OF ELECTRON ADDITION

One-electron quinone reduction and two-electron carbonyl reduction convert the anticancer anthracycline doxorubicin to reactive oxygen species (ROS) or a secondary alcohol metabolite that contributes to inducing a severe form of cardiotoxicity. The closely related analogue epirubicin induces less cardiotoxicity, but the determinants of its different behavior have not been elucidated. We developed a translational model of the human heart and characterized whether epirubicin exhibited a defective conversion to ROS and secondary alcohol metabolites. Small myocardial samples from cardiac surgery patients were reconstituted in plasma that contained clinically relevant concentrations of doxorubicin or epirubicin. In this model only doxorubicin formed ROS, as detected by fluorescent probes or aconitase inactivation. Experiments with cell-free systems and confocal laser scanning microscopy studies of H9c2 cardiomyocytes suggested that epirubicin could not form ROS because of its protonation-dependent sequestration in cytoplasmic acidic organelles and the consequent limited localization to mitochondrial one-electron quinone reductases. Accordingly, blocking the protonation-sequestration mechanism with the vacuolar H+-ATPase inhibitor bafilomycin A1 relocalized epirubicin to mitochondria and increased its conversion to ROS in human myocardial samples. Epirubicin also formed ∼60% less alcohol metabolites than doxorubicin, but this was caused primarily by its higher Km and lower Vmax values for two-electron carbonyl reduction by aldo/keto-reductases of human cardiac cytosol. Thus, vesicular sequestration and impaired efficiency of electron addition have separate roles in determining a defective bioactivation of epirubicin to ROS or secondary alcohol metabolites in the human heart. These results uncover the molecular determinants of the reduced cardiotoxicity of epirubicin and serve mechanism-based guidelines to improving antitumor therapies

Intermittent antegrade warm cardioplegia reduces oxidative stress and improves metabolism of the ischemic-reperfused human myocardium

AbstractThe aim of this study was to compare the effect of intermittent antegrade warm blood cardioplegia and intermittent antegrade cold blood cardioplegia on myocardial metabolism and free radical generation of the ischemic-reperfused human myocardium. Thirty patients undergoing mitral valve procedures were randomly allocated to two groups: group 1 (15 patients) received warm blood cardioplegia and group 2 (15 patients), cold blood cardioplegia. Myocardial metabolism was assessed before aortic clamping, 1 minute after crossclamp removal, and after 20 minutes of reperfusion, by collecting blood simultaneously from the radial artery and coronary sinus. All samples were analyzed for lactate, creatine kinase, reduced and oxidized glutathione, ascorbic acid, fluorescent products of lipid peroxidation, and leukocyte activation (elastase). In all patients, early reperfusion was associated with significant coronary sinus lactate release. In group 2, but not in group 1, significant coronary sinus release of reduced and oxidized glutathione, fluorescent products of lipid peroxidation, and creatine kinase was also found; moreover, arterial-coronary sinus difference of ascorbic acid content was increased only in group 2, suggesting a transmyocardial consumption of this antioxidant vitamin. After 20 minutes of reperfusion, coronary sinus lactate release was no longer present in group 1, whereas significant production was still evident in group 2. In this group, significant coronary sinus release of fluorescent products of lipoperoxidation and reduced and oxidized glutathione was also observed at this time. No significant release of elastase from the coronary sinus was noted in the two groups throughout the study. The left ventricular stroke work index measured at the end of the study indicated a better functional recovery in group 1 than in group 2. In conclusion, intermittent antegrade warm blood cardioplegia protects the myocardium from ischemia-reperfusion injury better than intermittent antegrade cold blood cardioplegia; this phenomenon may be partly due to the decreased tissue oxidant burden mediated by intermittent warm blood cardioplegia. (J THORAC CARDIOVASC SURG 1995;109:787-95

Surgical bleeding after pre-operative unfractionated heparin and low molecular weight heparin for coronary bypass surgery

Background and Objectives Since the impairment of platelet function may cause excess peri-operative bleeding, pre-operative discontinuation of aspirin and heparin bridging are common for cardiac surgery. We evaluated the impact of pre-operative administration of enoxaparin and unfractionated heparin (UFH) on coagulation parameters and peri-operative bleeding in patients undergoing elective coronary artery bypass grafting (CABG) surgery after discontinuation of aspirin. Design and Methods Forty-three patients with three-vessel coronary artery disease undergoing elective CABG surgery discontinued aspirin and were randomized to receive either UFH 180 UI/Kg × 2/day s.c. or enoxaparin 100 UI/Kg × 2/day s.c. until 12 h before surgery (median pre-operative treatment 8 days, range 6–12 days). Surgery was performed as usual with UFH. Neither UFH nor any low molecular weight heparin was given in the immediate post-operative period. The effects of UFH and enoxaparin were monitored by the activated partial thromboplastin time (aPTT) and the Enox-test (sensitive to factor Xa inhibition) using a Rapidpoint® Coagulation Analyzer. aPTT and factor Xa activity were also measured by standard methods. Peri-operative bleeding and the nadirs of hemoglobin concentration, hematocrit and platelet count were monitored post-operatively. Results Patients in the two groups were similar for number of bypasses, on-pump time, total surgery time, and time from the last heparin administration. Coagulation parameters increased significantly and similarly at 30 min and 6 h with both treatments, but returned within the normal range at 12 h. Hemoglobin, hematocrit and platelet counts significantly decreased to the same extent after CABG and re-normalized at the same time. Transfusional requirements of blood and plasma units were similar in the two groups. Interpretation and Conclusions From the kinetics of coagulation parameters and the evaluation of bleeding, enoxaparin is a safe alternative to UFH as a bridging therapy to CABG after discontinuation of aspirin

Bilateral internal thoracic artery grafting with and without cardiopulmonary bypass: Six-year clinical outcome

ObjectivesWe sought to evaluate whether early and late results in patients who underwent off-pump or on-pump myocardial revascularization with bilateral internal thoracic artery grafting were similar.MethodsFrom November 1994 through December 2001, 1835 patients underwent isolated myocardial revascularization with bilateral internal thoracic artery grafting. By applying propensity score pairwise matching, 1194 patients were selected and operated on either off pump (n = 597) or on pump (n = 597).ResultsThe overall 30-day mortality was 1.5% (1.2% in the off-pump group and 1.8% in the on-pump group, P = .342). There was no difference for all the other complications between the 2 groups. Mean follow-up was 5.2 ± 1.8 years. Forty-two patients died over the follow-up period (22 in the off-pump group and 20 in the on-pump group), 15 of them of cardiac causes (7 in the off-pump group and 8 in the on-pump group). Six-year outcomes (freedom from death, cardiac death, acute myocardial infarction and reoperation in all or in the grafted area, target cardiac events, and any other event) were similar for both categories. After a mean of 30.7 ± 20.1 months, 202 patients had a postoperative angiography showing similar results.ConclusionsOur results with extensive arterial revascularization clearly show that with the technical improvements achieved in the most recent years, off-pump operations can be performed safely with the same quality of late results as those obtained with on-pump operations

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Right coronary occlusion during tricuspid band annuloplasty

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