Effect of cardiopulmonary bypass on pulmonary gas exchange: a prospective randomized study

BACKGROUND: Conventional coronary artery bypass surgery is associated with postoperative pulmonary dysfunction. Inflammation due to cardiopulmonary bypass has been regarded as one of the main causes. In this study, we investigated the effect of coronary revascularization with or without cardiopulmonary bypass on pulmonary function. METHODS: Fifty-two patients (40 male, mean age 60.1 years) were prospectively randomized to undergo coronary revascularization via median sternotomy, with or without normothermic cardiopulmonary bypass. Alveolar-arterial oxygen gradients were measured before and after induction of anesthesia, postoperatively in the intensive care unit during mechanical ventilation and 6 hours after tracheal extubation. The techniques of anesthesia and mechanical ventilation were standardized throughout. RESULTS: Patient characteristics were similar in the two groups. The alveolar-arterial oxygen gradients increased progressively throughout the perioperative period, with no significant differences in the two groups at any time during the study. CONCLUSIONS: Myocardial revascularization with or without cardiopulmonary bypass caused a similar degree of pulmonary dysfunction, as assessed by alveolar-arterial oxygen gradient. Our study suggests that the deterioration in pulmonary gas exchange associated with cardiac surgery is due to factors other than the use of cardiopulmonary bypass.     

Inflammatory response after coronary revascularization with or without cardiopulmonary bypass

BACKGROUND: We sought to investigate the effect of multiple coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass (CPB) on the perioperative inflammatory response. METHODS: Sixty patients undergoing CABG were randomly assigned to one of two groups: (A) on pump with conventional CPB and cardioplegic arrest, and (B) off pump on the beating heart. Serum samples were collected for estimation of neutrophil elastase, interleukin 8 (IL-8), C3a, and C5a preoperatively and at 1, 4, 12, and 24 hours postoperatively. Furthermore, white blood cell (WBC), neutrophil, and monocyte counts were carried out preoperatively and at 1, 12, 36 and 60 hours postoperatively. Overall incidence of infection and perioperative clinical outcome were also recorded. RESULTS: The groups were similar in terms of age, weight, gender ratio, extent of coronary disease, left ventricular function, and number of grafts per patient. Neutrophil elastase concentration peaked early after CPB in the on-pump group, with a decline with time. Repeated-measures analysis of variance between groups and comparisons at each time point (modified Bonferroni) showed elastase concentrations were significantly higher in the on-pump than the off-pump group (both p < 0.0001). IL-8 increased significantly after surgery in the on-pump group, with no decline during the observation period (p = 0.01 vs off pump). C3a and C5a rose early after surgery in both groups when compared with baseline values. Postoperative WBC, neutrophil, and monocyte counts were significantly higher in the on-pump than the off-pump group (p < 0.01). Finally, the incidence of postoperative overall infections was significantly higher in the on-pump group (p < 0.0001 vs off pump). CONCLUSIONS: CABG on the beating heart is associated with a significant reduction in inflammatory response and postoperative infection when compared with conventional revascularization with CPB and cardioplegic arrest.     

Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.

PURPOSE: The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments. PATIENTS AND METHODS: Overall, 1,638 patients from 12 countries were enrolled onto a large, prospective multicenter project aimed at describing the clinical history of polycythemia vera for the following outcomes: survival, the cumulative rate of cardiovascular death and thrombosis, the cumulative rate of leukemia, myelodysplasia, and myelofibrosis. The mean duration of the disease at entry and the duration of the follow-up were 4.9 and 2.7 years, respectively. RESULTS: The overall mortality rate of 3.7 deaths per 100 persons per year resulted from a moderate risk of cardiovascular death and a high risk of death from noncardiovascular causes (mainly hematologic transformations). Age older than 65 years and a positive history of thrombosis were the most important predictors of cardiovascular events. Antiplatelet therapy, but not cytoreductive treatment, was significantly associated with a lower risk of cardiovascular events. We found a consistent association between age and risk of leukemia, and between duration of the disease with risk of myelofibrosis. CONCLUSION: The European Collaboration on Low-Dose Aspirin in Polycythemia Vera study documents that large international collaborative studies are feasible in this field, in which few epidemiologic data are available. The persistently high mortality rate from hematologic malignancies characterizes the unmet therapeutic need of polycythemic patients and suggests a priority for future studies in this disease.     

Synthesis and Antimuscarinic Activity of Derivatives of 2-Substituted-1,3-Dioxolanes

Geometric cis, trans isomers, derivatives of 2-substituted-1,3-dioxanes were designed and studied as antimuscarinic agents. The synthesized compounds were evaluated as perchlorides and methiodides by functional tests with rabbit vas deferens (putative M₁), guinea-pig heart (M₂) and guinea-pig ileum (M₃). The effect of the replacement of a trimethylammonium group with a dimethysulfonium in the two rings was also evaluated. Pharmacological results indicate that the 1,3-dioxane nucleus shows the highest stereoselective values on the studied receptors.     

Proline-rich tyrosine kinase Pyk2 regulates deep vein thrombosis

Deep vein thrombosis results from the cooperative action of leukocytes, platelets, and endothelial cells. The proline-rich tyrosine kinase Pyk2 regulates platelet activation and supports arterial thrombosis. In this study, we combined pharmacological and genetic approaches to unravel the role of Pyk2 in venous thrombosis. We found that mice lacking Pyk2 almost completely failed to develop deep venous thrombi upon partial ligation of the inferior vena cava. Pyk2-deficient platelets displayed impaired exposure of phosphatidylserine and tissue factor expression by endothelial cells and monocytes was completely prevented by inhibition of Pyk2. In human umbilical vein endothelial cells (HUVEC), inhibition of Pyk2 hampered IL-1β-induced expression of VCAM and P-selectin, and von Willebrand factor release. Pyk2-deficient platelets showed defective adhesion on von Willebrand factor and reduced ability to bind activated HUVEC under flow. Moreover, inhibition of Pyk2 in HUVEC strongly reduced platelet adhesion. Similarly, Pyk2-deficient neutrophils were unable to efficiently roll and adhere to immobilized endothelial cells under venous flow conditions. Moreover, platelets and neutrophils from Pyk2-knockout mice showed defective ability to form heterogeneous aggregates upon stimulation, while platelet monocyte interaction occurred normally. Consequently, platelet neutrophil aggregates, abundant in blood of wild-type mice upon inferior vena cava ligation, were virtually undetectable in Pyk2-knockout mice. Finally, we found that expression of Pyk2 was required for NETosis induced by activated platelets. Altogether our results demonstrate a critical role of Pyk2 in the regulation of the coordinated thromboinflammatory responses of endothelial cells, leukocytes and platelets leading to venous thrombosis. Pyk2 may represent a novel promising target in the treatment of deep vein thrombosis.