The use of "2-octyl cyanoacrylate" as skin adhesive in pediatric and congenital cardiac surgery.

AIM: The aim of this paper was to evaluate the safety and cost-effectiveness of "2-octyl-cyanoacrylate" as skin adhesive in congenital heart surgery. METHODS: From April 2010 to December 2011, we collected data from 300 patients who underwent cardiac surgery for congenital heart disease. We divided our population into 3 groups: group-1 (N.=100):"2-octyl-cyanoacrylate" has been used to replace the intra-dermal suture line; group-2 (N.=100):"2-octyl-cyanoacrylate" has been utilized as a barrier ("add-on measure") in addition to the intra-dermal suture line, group-3 (N.=100) with a standard intra-dermal suture line. RESULTS: Median age of patients was 1.36 years. One-hundred and thirty-nine patients were younger than 12 months and 56 older than 16 years. There were 11 wound dehiscence (3.6%) (2 in group-1 and 9 in group-3, P=0.001) and 1 superficial wound infection (group-1). Six patients (2%) required surgical wound revision (2 in group-1 and 4 in group-3, P=NS). Wound complication was significantly associated to delayed sternal closure (3/12 patients, 25% versus 13/288 patients, 4.5%) (P=0.04). Median cost (intra-/postoperative) for wound treatment was lower in group-1 and 2 (19±5.5 and 23.9±7.4 € respectively) when compared to Group-3 (26.7±3.2) (P<0.0001). CONCLUSION: The use of "2-octyl-cyanoacrylate" proved to be safe and effective; the "add-on measure" strategy provided the best cost-effective solution.

The use fibrinogen/thrombin-coated equine collagen patch in children requiring reoperations for congenital heart disease. A single center clinical experience.

AIM: The aim of this study was to evaluate the efficacy and cost-effectiveness of fibrinogen/thrombin-coated collagen patch (FTCCP)(TachoSil®) during intraoperative hemostasis in patients with congenital heart disease, who required a reoperation during childhood. METHODS: We reviewed data on the intraoperative blood product requirements and hospital costs of children (age <16 years) who underwent a reoperation for treating their congenital heart disease between January 2009 and December 2011. RESULTS: One-hundred and seventeen patients were included. Median age at surgery was 2.1 years (range 3 days-14.1 years). Main causes of intraoperative bleeding were: 1) reinforcement of suture lines (106 patients, 90.6%); 2) lung lesions (5 patients, 4.2%); 3) epicardial lesions (3 patients, 2.6%); and 4) chest wall lesions (3 patients, 2.6%). At logistic regression the amount of packed red blood cells (PRBC) requirement was significantly higher in patients with preoperative cyanosis (P=0.008, OR=3.85) and in patients who required the use of cardiopulmonary bypass (P=0.005, OR=21.19). The use of FTCCP (N.=90 patients) as first line treatment was significantly associated with a lower PRBC requirement (P=0.0003, OR=0.1) which in addition to the avoidance of other hemostatic/sealant agents, leads to lower hospital cost. CONCLUSION: FTCCP is an effective hemostatic agent which can be safely used during the hemostasis of children requiring reoperations for their congenital heart malformations. When used as first line treatment, with specific indications, FTCCP limited the intraoperative PRBC requirement and the use of other hemostatic/sealant agents thus reducing hospital costs.

Mitochondrial permeability transition and release of cytochrome c induced by retinoic acids.

Retinoic acids, structurally related to vitamin A, inhibit the in vitro proliferation of different types of normal and neoplastic cells. The effects of all-trans, 9-cis, and 13-cis retinoic acids were tested on mitochondria isolated from rat liver. All the compounds were able to induce the membrane permeability transition observed as swelling and decrease in membrane potential, but 13-cis retinoic acid appeared to be the most effective. The latter was also shown to stimulate the release of cytochrome c from mitochondria, suggesting a potential target of retinoids in the induction of cell apoptosis. Interestingly, EGTA and cyclosporin A, which strongly inhibit the permeability transition induced by 13-cis retinoic acid, were without effect on the release of cytochrome c from the mitochondrial intermembrane space.

Purification of mitochondrial thioredoxin reductase and its involvement in the redox regulation of membrane permeability.

The isolation to purity of a rat liver mitochondrial thioredoxin reductase is reported. The mitochondrial enzyme shows a chromatographic behavior different from that of the cytosolic enzyme. The purified enzyme, after sodium dodecylsulfate-polyacrylamide gel electrophoresis, yields a single band with a molecular weight of approximately 54 kDa. The apparent Km for E. coli thioredoxin is about 13 microM, while the apparent Km for 5,5'-dithiobis (2-nitrobenzoic acid) is 530 microM, values comparable to those reported for the cytosolic enzyme. Mitochondrial thioredoxin reductase, in addition to its natural substrate thioredoxin, is also able to reduce chemically unrelated compounds such as 5,5 '-dithiobis (2-nitrobenzoic acid), selenite, and alloxan; the enzyme is inhibited by classical inhibitors of the cytosolic enzyme such as 1-chloro-2,4-dinitrobenzene and 13-cis-retinoic acid. A strong inhibitory action is also elicited by Mn2+ and Zn2+ ions. Thiol status appears critically involved in the control of membrane permeability and, therefore, a thiol/disulfide transition involving reduced pyridine nucleotides, matrix soluble thiols, and inner membrane thiols appears to play a fundamental role. The potential role of thioredoxin/thioredoxin reductase system in the control and redox regulation of the mitochondrial membrane permeability, is discussed.

Influence of the redox state of pyridine nucleotides on mitochondrial sulfhydryl groups and permeability transition.

This work addresses a correlation between the redox state of pyridine nucleotides and that of sulfhydryl groups of the mitochondrial membranes. Several major observations emerge: (1) Conditions leading to an oxidation of the pyridine nucleotides such as incubation with tert-butyl hydroperoxide or acetoacetate determine a decrease of total mitochondrial sulfhydryl groups. Glutathione does not follow the same pattern since it decreases in the presence of tert-butyl hydroperoxide but not in the presence of acetoacetate. In addition, only in the presence of tert-butyl hydroperoxide is the decrease of sulfhydryl groups concomitant with a membrane protein polymerization, observed by polyacrylamide gel electrophoresis. (2) Under all conditions tested, the oxidation of sulfhydryl groups is further stimulated by the presence of calcium and phosphate ions. (3) Respiratory substrates, which prevent the swelling of mitochondria, also partially prevent the decrease of sulfhydryl groups.

Effect of polycation peptides on mitochondrial permeability transition.

Synthetic polycation peptides obtained with the basic aminoacids lysine, arginine and ornithine are able to inhibit the permeability transition induced in mitochondria by calcium ions and inorganic phosphate. At least three basic aminoacid residues must be present in the peptide in order to elicit the inhibitory effect. In the presence of synthetic polycations and similarly to spermine, a lack of correlation between inhibition of swelling and glutathione release is apparent, since glutathione release occurs before the onset of a large amplitude swelling. The same lack of correlation is observed in the presence of cyclosporin. From the results obtained with the above reported polycations, different in both aminoacid composition and length, it appears that the effect is not to be referred to the individual properties of the molecules examined but rather to their cationic character; in addition, a critical number of positive charges is necessary to elicit the effect.

Inhibitory effect of pyruvate on release of glutathione and swelling of rat heart mitochondria.

Pyruvate prevents the permeability transition of rat heart mitochondria induced by the system calcium ions + phosphate or by the dithiol reagent phenylarsenoxide and measured as swelling. Since swelling induced by the latter is relieved by the dithiol 2,3-dimercaptopropanol (BAL), it is inferred that the effect of pyruvate might be mediated by the reduction of lipoic acid. In isolated mitochondria, pyruvate also exerts a protective effect when calcium + phosphate-induced swelling is exacerbated by hypoxic conditions. These results agree with our previous observations that pyruvate markedly prevents the loss of cytosolic and mitochondrial glutathione after ischemia or ischemia followed by reperfusion.