Increased susceptibility of the left compared to the right ventricle to remote ischemia/reperfusion injury in human C1-inhibitor-overexpressing transgene mice.

Acute myocardial injury has been demonstrated as a remote sequela of severe lower torso ischemia-reperfusion (I/R) due to proinflammatory events. In a model of I/R injury, administration of C1 esterase inhibitor (C1-Inh) reduces myocardial necrosis. We investigated the susceptibility of the left (LV) versus right ventricle (RV) and the protective effect of transgenic C1-Inh-overexpressing mice. Two groups of mice (n = 6) underwent a 2-h lower torso ischemia followed by 3 h of reperfusion: transgenic and wild type with sham-operated controls. Animals were then injected with (125)I bovine albumin. Heart was removed and samples from right and left ventricular free wall were harvested, weighted, and radioactivity was determined. Permeability index for wild-type animals in the RV was 0.22 +/- 0.04, compared to 0.17 +/- 0.07 in controls (NS), and in the LV 0.36 +/- 0.08, compared to 0.21 +/- 0.05 in controls (p <.01). The LV showed a significantly higher value compared to the right (0.22 +/- 0.04 vs. 0.36 +/- 0.08, p <.01). No difference was seen in the RV between transgenic and wild-type mice; however, in the LV the values decreased significantly in transgenic animals (p <.015). Thus, remote myocardial injury after lower torso I/R is present in both ventricles; however, the LV seems to be more susceptible as assessed by albumin permeability. Inhibition of the classic complement cascade may be a promising therapeutic approach for myocardial protection in reperfusion injury.     

Less Invasive Surgical Treatment of Renal Cell Carcinomas Extending into the Right Heart and Pulmonary Arteries: Surgery for Renal Cell Carcinoma

Abstract Background: Radical resection using deep hypothermic circulatory arrest improves the survival of patients with transvenous intracardiac tumor extension of renal cell carcinomas. A less invasive surgical approach avoiding deep hypothermia, circulatory arrest, and cross-clamping of the aorta is presented. Methods: Between 1987 and 1999, 12 patients (mean age 57 ± 8 years) underwent resection of a renal cell carcinoma extending into the right atrium, right ventricle, or pulmonary arteries. After median sterno-laparotomy, nor-mothermic cardiopulmonary bypass is used cannulating the ascending aorta, superior caval vein, and inferior caval vein below the renal veins. The tumor and the corresponding kidney are radically excised, including the renal vein. Tumor fragments from the inferior caval vein, the right heart, and pulmonary arteries are removed either on the fibrillating or beating heart . Results: Operative mortality was 0%. Mean cardiopulmonary bypass time was 53 ± 27 minutes (median 36; range 32–110 minutes). Mean blood loss per patient was 1200 mL. Mean duration of postoperative mechanical ventilation was 36 ± 12 hours (median 36; range 30–77 hours), mean intensive care stay 5·5 ± 5 days (median 3; range 1–48 days), and mean duration of hospitalization 22 ±; 12 days (median 21; range 10–58 days). All patients were discharged home. Patients with multiple tumor manifestations outside the cardiovascular systems died within 9 months after the operation. Conclusions: The use of normothermic cardiopulmonary bypass is a less invasive method for radical resection of renal cell carcinoma with intracardiac tumor extension. Radical resection does not improve survival in patients with multiple distant metastases.     

Preconditioning by Sevoflurane Decreases Biochemical Markers for Myocardial and Renal Dysfunction in Coronary Artery Bypass Graft Surgery: A Double-blinded, Placebo-controlled, Multicenter Study

Background: Preconditioning by volatile anesthetics is a promising therapeutic strategy to render myocardial tissue resistant to perioperative ischemia. It was hypothesized that sevoflurane preconditioning would decrease postoperative release of brain natriuretic peptide, a biochemical marker for myocardial dysfunction. In addition, several variables associated with the protective effects of preconditioning were evaluated.

Methods: Seventy-two patients scheduled for coronary artery bypass graft surgery under cardioplegic arrest were randomly assigned to preconditioning during the first 10 min of complete cardiopulmonary bypass with either placebo (oxygen-air mixture only) or sevoflurane 4 vol% (2 minimum alveolar concentration). No other volatile anesthetics were administered at any time during the study. Treatment was strictly blinded to anesthesiologists, perfusionists, and surgeons. Biochemical markers of myocardial dysfunction and injury (brain natriuretic peptide, creatine kinase-MB activity, and cardiac troponin T), and renal dysfunction (cystatin C) were determined. Results of Holter electrocardiography were recorded perioperatively. Translocation of protein kinase C was assessed by immunohistochemical analysis of atrial samples.

Results: Sevoflurane preconditioning significantly decreased postoperative release of brain natriuretic peptide, a sensitive biochemical marker of myocardial contractile dysfunction. Pronounced protein kinase C [delta] and [epsilon] translocation was observed in sevoflurane-preconditioned myocardium. In addition, postoperative plasma cystatin C concentrations increased significantly less in sevoflurane-preconditioned patients. No differences between groups were found for perioperative ST-segment changes, arrhythmias, or creatine kinase-MB and cardiac troponin T release.     

Living patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells.

OBJECTIVE: A major shortcoming in contemporary congenital heart surgery is the lack of viable replacement materials with the capacity of growth and regeneration. Here we focused on living autologous patches engineered from human umbilical cord derived fibroblasts and endothelial progenitor cells (EPCs) as a ready-to-use cell source for paediatric cardiovascular tissue engineering. METHODS: EPCs were isolated from 20 ml fresh umbilical cord blood by density gradient centrifugation and myofibroblasts were harvested from umbilical cord tissue. Cells were differentiated and expanded in vitro using nutrient media containing growth factors. Before seeding, cell-phenotypes were assessed by immuno-histochemistry. Biodegradable patches fabricated from synthetic polymers (PGA/P4HB) were seeded with myofibroblasts followed by endothelialization with EPCs. All patches were cultured in a perfusion bioreactor. A subgroup of patches was additionally stimulated by cyclic strain. Analysis of the neo-tissues comprised histology, immuno-histochemistry, extracellular matrix (ECM) analysis and biomechanical testing. RESULTS: Endothelial phenotypes of EPCs before seeding were confirmed by Ac-Dil-LDL, CD 31, von-Willebrand-Factor and eNOS staining. Histology of the seeded patches demonstrated layered viable tissue formation in all samples. The cells in the newly formed tissues expressed myofibroblast markers, such as desmin and alpha-SMA. The EPCs derived neo-endothelia showed constant endothelial phenotypes (CD 31, vWF). major constituents of ECM such as collagen and proteoglycans were biochemically detected. Stress-strain properties of the patches showed features of native-analogous tissues. CONCLUSIONS: Living tissue engineered patches can be successfully generated from human umbilical cord derived myofibroblasts and EPCs. This new cell source may enable the tissue engineering of versatile, living, autologous replacement materials for congenital cardiac interventions.     

Treatment outcome after radical prostatectomy is not adversely affected by a pre-existing penile prosthesis

Objectives. To report on the safety of radical retropubic prostatectomy (RRP) in patients with a penile prosthesis presenting with clinically localized prostate cancer.Methods. From January 1990 to December 1997, 8 consecutive men with a penile prosthesis underwent RRP for clinically localized prostate cancer. Retrospective data regarding patient population, operating time, estimated blood loss, length of hospital stay, and clinical outcome were evaluated.Results. Mean patient age was 65.4 years (range 57 to 70) at the time of RRP, with a mean preoperative serum prostate-specific antigen level of 11.5 ng/mL. Mean duration of RRP surgery was 183.9 minutes, and the mean estimated blood loss was 1281.8 mL. No complication requiring penile prosthesis removal occurred. In 1 case, the reservoir tubing was punctured during closure of the abdominal fascia wall. This was immediately recognized and fixed. All patients had a functioning penile prosthesis after RRP.Conclusions. RRP can be safely and expeditiously performed in patients with a pre-existing penile prosthesis. The risk of prosthesis malfunction after RRP is very low. Patients with a penile prosthesis and prostate cancer should not be denied the option of undergoing RRP.     

Selective proliferation of normal human melanocytes in vitro in the presence of phorbol ester and cholera toxin.

Cultures consisting almost entirely of human melanocytes were obtained from epidermal single-cell suspensions by using phorbol 12-myristate 13-acetate (10 ng/ml) in the culture medium. At this concentration, phorbol ester is toxic to human keratinocytes but not to melanocytes. When the seeding density was optimal (0.8-2 x 10(4)/cm2) and the medium contained both phorbol ester and cholera toxin, melanocytes proliferated extensively. Under these conditions, human melanocytes could be passaged serially in vitro and grown in quantity. This cell culture system can thus be used to answer basic questions related to pigment cell biology and may serve as a control for studies of malignant melanocytes.