Effects of a new cardiomyoplasty technique on cardiac function

OBJECTIVE: The current cardiomyoplasty technique was modified to maintain the resting tension of the latissimus dorsi muscle and to prevent lateral movement of the heart during muscle stimulation. The aim of this study is to compare the short term hemodynamic effects of the new cardiomyoplasty wrap (W1) with those of the clinically applied cardiomyoplasty wrap (W2). Preliminary indications of the long-term hemodynamic effects of W1 are presented. METHODS: In three acute experiments in sheep mean central venous pressure (MCVP), mean arterial pressure (MAP), mean cardiac output (MCOP), mean left ventricular systolic pressure (MLVSP), and mean left ventricular diastolic pressure (MLVDP) were measured for 30s before and five minutes after applying each procedure with and without stimulation of the muscle graft. The same parameters were also recorded 5min after removing each muscle wrap. Hemodynamic changes associated with unstimulated muscle wraps were compared to the baseline data. Hemodynamic effects of muscle stimulation were determined by comparing the assisted to the preceding unassisted cardiac cycle. The long-term effects of W1 on the hemodynamics of another three sheep were studied at 6-12months after the operation. The viability of the muscles used in the chronic experiments were evaluated by morphometric analysis. RESULTS: Unstimulated W2 significantly increased mean central venous pressure and reduced mean cardiac output. It also increased mean left ventricular diastolic pressure and reduced peak negative dP/dt. Unstimulated W1 had no deleterious effect on mean central venous pressure, mean left ventricular diastolic pressure or peak -dP/dt, but it also reduced mean cardiac output and increased mean left atrial pressure (MLAP). Synchronised muscle stimulation, in both techniques, augmented the mean arterial pressure, mean cardiac output and mean left ventricular systolic pressure. In W2, however, myostimulation was also associated with a significant increase of the mean left ventricular diastolic pressure. In two long-term experiments significant hemodynamic assistance was observed at 6months and at 1yr after W1. In those sheep 68% of the cross-sectional area of the muscle was well preserved. CONCLUSIONS: Unstimulated cardiomyoplasty wraps acutely impair left ventricular function in sheep. The new technique, however, may offer significant long-term hemodynamic assistance and adequate preservation of the structural and functional integrity of the muscle flap for up to 1yr.     

Fibrinogen biosynthesis in isolated guinea pig megakaryocytes

Fibrinogen synthesis was investigated in guinea pig megakaryocytes. Purified megakaryocytes were incubated with 35S-methionine in methionine-free incubation medium for 18 hours. Newly synthesized fibrinogen in megakaryocyte lysates enriched with purified carrier guinea pig fibrinogen was immunoprecipitated with a specific anti- guinea pig fibrinogen antiserum produced in rabbits. Proteins in the immunoprecipitates were analyzed with a 3.5% to 10.0% gradient polyacrylamide slab gel electrophoresis and auto-radiography. Radioactivity was detected in a protein band of 340,000 daltons. In order to verify fibrinogen synthesis, immunoprecipitate was analyzed by two-dimensional slab gel electrophoresis: (1) the first dimension separated unreduced fibrinogen using a 3.5% to 10.0% gradient gel; (2) following reduction by 2-beta-mercaptoethanol, fibrinogen chains were separated in the second dimension using a 10% gel. Alpha, beta, and gamma fibrinogen chains, which represented carrier guinea pig plasma fibrinogen, were visualized by Coomassie brilliant blue. Autoradiography identified the incorporation of radioactivity into the three fibrinogen chains. In control experiments, immunoprecipitates, produced by exposing megakaryocyte lysates to preimmune rabbit serum and goat anti-rabbit IgG, were also analyzed by the two-dimensional gel system. Radioactivity was not detected in sites corresponding to the migration of fibrinogen subunits. The study demonstrates that isolated guinea pig megakaryocytes can synthesize fibrinogen. The electrophoretic mobility of newly synthesized fibrinogen and subunits is similar to that of guinea pig plasma fibrinogen.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Flolan国际随机存活试验(FIRST)

标题　Ｆｌｏｌａｎ国际随机存活试验（ＦＩＲＳＴ）;最后的结果作者　ＣａｌｉｆｆＲＭ,ｅｔａｌ．ＪＡｍＣｏｌｌＣａｒｄｉｏｌ,１９９６,２７：１４１Ａ（英文）　　研究疾病：末期心力衰竭。目的：评估ｅｐｏｐｒｏｓｔｅｎｏｌ（前列环素）对末期心衰患者之病死率和发病率的影响。　　设计：随机对照式。病人资料：４７１例（预定８７５例）,平均年龄为（６５±１０）岁,左心室射血分数＜２５％,充血性心衰,ＮＹＨＡⅢ或Ⅳ级,肺毛细血管楔压＞１５ｍｍＨｇ,心功能指数＜２－５Ｌ／ｍｉｎ·ｍ２。随访：１２个月;６个月评估…     

Natural bioburden levels detected on rigid lumened medical devices before and after cleaning

Controversy exists concerning the degree of microbial contamination associated with the us of rigid lumened medical devices, the efficacy of standard cleaning techniques used to remove pathogenic microorganisms from lumen channels, and whether patients are placed at risk of cross infection because of microbial contamination. In this study the level and types of microorganisms found on rigid lumened medical devices before and after cleaning in a hospital environment were investigated. The bioburden level after clinical use was found to be relatively low, ranging from 10¹ to 10⁴ colony forming units (CFU) per device. After the instruments were cleaned, none of the devices studied contained bioburden levels greater than 10⁴ CFU and 83% had bioburden levels less than or equal to 10² CFU. The bioburden present before cleaning was comprised of organisms derived from the handling of the device, from the hospital environment, and from the patient. The bioburden present after cleaning was comprised of organisms typically derived from the handling of the device and from the hospital environment. The level of bioburden per device was also related to the anatomic site where the device was used, with lower numbers of organisms found on devices exposed to sterile body sites and the respiratory tract.     

Stratification of complexity in congenital heart surgery: comparative study of the Risk Adjustment for Congenital Heart Surgery (RACHS-1) method, Aristotle basic score and Society of Thoracic Surgeons-European Association for Cardio- Thoracic Surgery (STS-EACTS) mortality score

Objective

To determine whether stratification of complexity models in congenital heart surgery (RACHS-1, Aristotle basic score and STS-EACTS mortality score) fit to our center and determine the best method of discriminating hospital mortality.

Methods

Surgical procedures in congenital heart diseases in patients under 18 years of age were allocated to the categories proposed by the stratification of complexity methods currently available. The outcome hospital mortality was calculated for each category from the three models. Statistical analysis was performed to verify whether the categories presented different mortalities. The discriminatory ability of the models was determined by calculating the area under the ROC curve and a comparison between the curves of the three models was performed.

Results

360 patients were allocated according to the three methods. There was a statistically significant difference between the mortality categories: RACHS-1 (1) - 1.3%, (2) - 11.4%, (3)-27.3%, (4) - 50 %, (P<0.001); Aristotle basic score (1) - 1.1%, (2) - 12.2%, (3) - 34%, (4) - 64.7%, (P<0.001); and STS-EACTS mortality score (1) - 5.5 %, (2) - 13.6%, (3) - 18.7%, (4) - 35.8%, (P<0.001). The three models had similar accuracy by calculating the area under the ROC curve: RACHS-1- 0.738; STS-EACTS-0.739; Aristotle- 0.766.

Conclusion

The three models of stratification of complexity currently available in the literature are useful with different mortalities between the proposed categories with similar discriminatory capacity for hospital mortality.     

Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.