Anesthetic-induced alteration in expression of myocardial calcium cycling proteins

OBJECTIVE: The purpose of this study was to test the hypothesis that anesthesia alone or in combination with high F(I)(O)2 alters expression of the myocardial calcium cycling proteins, sarcoplasmic endoreticular calcium adenosine triphosphatase subtype 2a (SERCA2a), and the sarcolemmal sodium-calcium exchanger (NCX). DESIGN: Multigroup comparison of protein expression using analysis of variance. SETTING: University research laboratory. SUBJECTS: Twenty-seven New Zealand white rabbits. INTERVENTIONS: After sedation and the induction of anesthesia, animals underwent either tracheal intubation and ventilation for 5 hours with 1.0% end-tidal halothane in oxygen (HAL-O(2) , n = 5) or air (HAL-air, n = 5) or time-control recovery while spontaneously breathing oxygen (TC-O(2) , n = 5) or air (TC-air, n = 5) for 5 hours. Halothane dose was based on pilot data from 2 rabbits. Animals were then sacrificed, and the hearts were removed for Western blot analysis. Data were normalized to those from a group of rabbits immediately sacrificed (n = 5) without any prior treatment. MEASUREMENTS AND MAIN RESULTS: In comparison to their respective time controls, SERCA2a was decreased 23 % in both HAL-air and HAL-O(2) groups, whereas NCX was increased 34% and 122%, respectively. Expression was distinctly different between HAL-air and HAL-O(2) for both SERCA2a (p = 0.009) and NCX (p < 0.001), indicating an influence of high F(I)O(2). Similarly, SERCA2a in the TC-O(2) group was reduced 25% relative to the TC-air group. CONCLUSION: Halothane alters the expression of myocardial calcium cycling proteins, and this effect is potentiated by high F(I)O(2) . These data offer the broad conclusion that perioperative interventions may influence the study of myocardial molecular remodeling and suggest the possibility of anesthetic-induced myocardial molecular remodeling.     

A Prospective Analysis of the Effect of Blue-Dye Volume on Sentinel Lymph Node Mapping Success and Incidence of Allergic Reaction in Patients With Breast Cancer

Background This study examined whether the volume of isosulfan blue dye used in sentinel lymph node (SLN) mapping in breast cancer is related to the SLN identification rate or to the incidence of allergic reactions.Methods From January 2001 to November 2002, 1728 breast cancer patients underwent 1832 SLN mapping procedures with the combined technique of intraparenchymal blue dye and intradermal radioisotope. Details of each procedure and all allergic reactions were prospectively recorded. Bilateral synchronous SLN procedures were considered as one dye exposure but as two distinct procedures for determining mapping success. Dye-only success was defined as the proportion of cases in which the SLN was identified by blue dye alone. Overall dye success was defined as the proportion of cases in which the SLN was identified by blue dye with or without isotope.Results When stratified by volume of blue dye, there were no significant differences in dye-only successes, overall dye successes, or mapping failures. Allergic reactions were documented in 31 (1.8%) of 1728 patients. Hypotensive reactions occurred in 3 (.2%) of 1728 patients; 2 (.1%) required pressor support. There was a nonsignificant trend toward fewer allergic reactions with smaller volumes of blue dye.Conclusions In combined-technique SLN mapping protocols for breast cancer, using smaller volumes of blue dye may represent a means of optimizing the safety of the procedure without compromising its success.     

The intrinsic mitochondrial membrane potential (Deltapsim) is associated with steady-state mitochondrial activity and the extent to which colonic epithelial cells undergo butyrate-mediated growth arrest and apoptosis

Transformation of colonic epithelial cells is characterized by decreased mitochondrial activity, increased mitochondrial membrane potential (Deltapsi(m)), and disruptions in the equilibrium between cell proliferation and death by apoptosis. We have previously shown that an intact Deltapsi(m) is essential for growth arrest and apoptosis induced by butyrate, a physiological regulator of maturation in these cells, suggesting a role for the Deltapsi(m) in the initiation and integration of proliferation and apoptotic pathways. To extend this work, we have generated isogenic cell lines, from SW620 human colonic carcinoma cells, which exhibit significant differences in intrinsic Deltapsi(m). These differences in Deltapsi(m) are not linked to alterations in viability, Bcl-2 levels, or the differentiation status of the cells. However, compared with parental cells and those with increased Deltapsi(m), cells with decreased intrinsic Deltapsi(m) exhibit significantly higher levels of steady-state mitochondrial mRNA and butyrate-induced p21(WAF1/Cip1) and G(0)-G(1) arrest. Moreover, despite butyrate-mediated translocation of proapoptotic Bax and Bak to the mitochondria, fewer cells with elevated intrinsic Deltapsi(m) exhibit concomitant cytochrome c release, and cells with elevated Deltapsi(m) undergo significantly lower levels of Deltapsi(m) dissipation and apoptosis than parental cells, or cells with decreased Deltapsi(m). Homeostasis of the colonic mucosa depends on balancing cell proliferation with apoptosis, and mitochondrial abnormalities are associated with disruptions in this balance. Thus, by affecting steady-state mitochondrial activity and the extent to which cells enter growth arrest and apoptotic cascades, these data establish a role for the intrinsic Deltapsi(m) in contributing to the probability of colonic tumorigenesis and progression.     

Patient reluctance toward tamoxifen use for breast cancer primary prevention

Background: The National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial demonstrated that tamoxifen reduces the incidence of new breast cancers by 49% in women at increased risk for breast cancer development. Tamoxifen does have side effects, however, including marginally increased risks of endometrial cancer and thromboembolic events. In this study, women at increased risk for breast cancer development were offered tamoxifen. Their knowledge of tamoxifen as a chemopreventive agent was assessed, and factors influencing their acceptance of tamoxifen and willingness to take it were determined.Methods: Forty-three patients were identified who qualified to take tamoxifen for primary prevention. Patients qualified by having at least a 1.7% 5-year risk of developing breast cancer, the criteria for entry into the NSABP P-1 trial. Patients initially completed questionnaires designed to assess their knowledge of tamoxifen and its associated risks and benefits. Patients were then provided neutral educational sessions and literature delineating the actual risks and benefits of tamoxifen. Subsequently, patients decisions regarding taking tamoxifen were reassessed.Results: Mean patient age was 52.8 years, with a range of 39 to 74 years. Ten patients (23.2%) qualified based on the presence of lobular carcinoma in situ (LCIS), seven patients (16.3%) qualified based on increased risk secondary to age >60 years, and 26 patients (60.5%) age range 35 to 59 qualified based on risk profiles demonstrating significantly increased risk. Of the total 43 patients, two (4.7%) elected to start taking tamoxifen. Fifteen patients (34.8%) declined immediately, and 26 patients (60.5%) were undecided initially but ultimately declined. Educational sessions did not influence patients decisions. Fear of side effects, including endometrial cancer, thromboembolic events, and menopausal symptoms, was the most commonly cited reason for declining to take tamoxifen.Conclusions: In this study, the vast majority of patients at increased risk for breast cancer perceived that the risks of taking tamoxifen outweighed the benefits and declined to take it.Presented at 53rd Annual Meeting of the Society of Surgical Oncology, New Orleans, Louisiana, March 16–19, 2010434_2001_Article_580.     

Case report: paradoxical ventricular septal motion in the setting of primary right ventricular myocardial failure

Purpose

In this report, a case of right ventricular (RV) failure, hemodynamic instability, and systemic organ failure is described to highlight how paradoxical ventricular systolic septal motion (PVSM), or a rightward systolic displacement of the interventricular septum, may contribute to RV ejection.

Clinical features

Multiple inotropic medications and vasopressors were administered to treat right heart failure and systemic hypotension in a patient following combined aortic and mitral valve replacement. In the early postoperative period, echocardiographic evaluation revealed adequate left ventricular systolic function, akinesis of the RV myocardial tissues, and PVSM. In the presence of PVSM, RV fractional area of contraction was ≥35% despite akinesis of the primary RV myocardial walls. The PVSM appeared to contribute toward RV ejection. As a result, the need for multiple inotropes was re-evaluated, in considering that end-organ dysfunction was the result of systemic hypotension and prolonged vasopressor administration. After discontinuation of phosphodiesterase inhibitors, native vascular tone returned and the need for vasopressors declined. This was followed by recovery of systemic organ function. Echocardiographic re-evaluation two years later, revealed persistent akinesis of the RV myocardial tissues and PVSM, the latter appearing to contribute toward RV ejection.

Conclusions

This case highlights the importance of left to RV interactions, and how PVSM may mediate these hemodynamic interactions.     

The emerging role of minimally invasive surgical techniques for the treatment of lung malignancy in the elderly

As a consequence of the general aging of the population, improved diagnostic techniques, and preoperative interventions to enhance the efficacy of surgical therapy, increasing numbers of elderly patients are presenting for pulmonary resection. Clear association between advanced age and the perioperative morbidity and mortality associated with lung cancer surgery has generated considerable interest in applying minimally invasive operative techniques in the geriatric population under the belief that this approach will improve outcome. This review examines the available data regarding video-assisted thoracoscopic lobectomy and concludes that this technique for the surgical treatment of early-stage lung cancer may parallel conventional thoracotomy in terms of oncologic efficacy while decreasing perioperative morbidity in the elderly.