Effects of local anesthetics on wound healing / Efeitos dos anestésicos locais na cicatrização de feridas

Abstract Introduction Local anesthetic infiltration is used widely for post-operative analgesia in many situations. However the effects of local anesthetics on wound healing are not demonstrated clearly. This study planned to evaluate the effects of lidocaine, prilocaine, bupivacaine and levobupivacaine on wound healing, primarily on wound tensile strength and on collagen ultrastructure. Methods This study was conducted on male Sprague Dawley rats. On days 0, 8th, 15th, and 21st, all animals were weighed and received a preincisional subcutaneous infiltration of 3 mL of a solution according the group. Control saline (C), lidocaine (L) 7 mg.kg-1, prilocaine (P) 2 mg.kg-1, bupivacaine (B) 2 mg.kg-1 and levobupivacaine (LVB) 2.5 mg.kg-1. The infiltrations were done at the back region 1.5 cm where incision would be performed at the upper, middle and lower part along the midline, under general anesthesia. Wound tensile strengths were measured after 0.7 cm × 2 cm of cutaneous and subcutaneous tissue samples were obtained vertical to incision from infiltrated regions. Tissue samples were also obtained for electron microscopic examination. Evaluations were on the 8th, 15th and 21st days after infiltration. Results There was no difference between groups in the weights of the rats at the 0th, 8th, 15th and 21st days. The collagen maturation was no statistically different between groups at the 8th and 15th days. The maturation scores of the B and L groups at the 21st day was significantly lower than the Group C (1.40, 1.64 and 3.56; respectively). The wound tensile strength was no statistically different between groups at the 8th and 15th days but at the 21st day the Groups B and LVB had significantly lower value than Group C (5.42, 5.54 and 6.75; respectively). Conclusion Lidocaine and prilocaine do not affect wound healing and, bupivacaine and levobupivacaine affect negatively especially at the late period.

Resumo Introdução A infiltração de anestésico local é amplamente usada para analgesia pós-operatória em muitas situações. No entanto, os efeitos dos anestésicos locais na cicatrização de feridas não foram demonstrados claramente. Neste estudo planejamos avaliar os efeitos de lidocaína, prilocaína, bupivacaína e levobupivacaína sobre a cicatrização de feridas, principalmente sobre a força tênsil da ferida e a ultraestrutura do colágeno. Métodos Este estudo foi feito em ratos machos da linhagem Sprague Dawley. Nos dias 0, 8, 15 e 21, todos os animais foram pesados e receberam uma infiltração subcutânea pré-incisional de 3 mL de uma solução, de acordo com a designação dos grupos: Grupo C recebeu salina (controle); Grupo L recebeu lidocaína (7 mg.kg-1); Grupo P recebeu prilocaína (2 mg.kg-1); Grupo B recebeu bupivacaína (2 mg.kg-1); Grupo LVB recebeu levobupivacaína (2,5 mg.kg-1). As infiltrações foram feitas na região posterior a 1,5 cm de onde a incisão seria feita na parte superior, média e inferior ao longo da linha média, sob anestesia geral. A força tênsil da ferida foi medida após amostras de 0,7 × 2 cm de tecido cutâneo e subcutâneo serem obtidas das regiões infiltradas, verticalmente à incisão. Amostras de tecido também foram obtidas para exame microscópico eletrônico. As avaliações foram feitas nos dias 8, 15 e 21 após a infiltração. Resultados Não houve diferença entre os grupos em relação ao peso dos ratos nos dias 0, 8, 15 e 21. A maturação do colágeno não foi estatisticamente diferente entre os grupos nos dias 8 e 15. Os escores de maturação dos grupos B e L no dia 21 foram significativamente inferiores aos do Grupo C (1,40, 1,64 e 3,56, respectivamente). A força tênsil da ferida não foi estatisticamente diferente entre os grupos nos dias 8 e 15, mas no dia 21 os grupos B e LVB apresentaram valores significativamente menores que o Grupo C (5,42, 5,54 e 6,75, respectivamente). Conclusão Lidocaína e prilocaína não afetam a cicatrização de feridas, enquanto bupivacaína e levobupivacaína afetam negativamente, especialmente no período tardio.

[Effects of local anesthetics on wound healing]. / Efeitos dos anestésicos locais na cicatrização de feridas.

INTRODUCTION: Local anesthetic infiltration is used widely for post-operative analgesia in many situations. However the effects of local anesthetics on wound healing are not demonstrated clearly. This study planned to evaluate the effects of lidocaine, prilocaine, bupivacaine and levobupivacaine on wound healing, primarily on wound tensile strength and on collagen ultrastructure. METHODS: This study was conducted on male Sprague Dawley rats. On days 0, 8th, 15th, and 21st, all animals were weighed and received a preincisional subcutaneous infiltration of 3mL of a solution according the group. Control saline (C), lidocaine (L) 7mg.kg-1, prilocaine (P) 2mg.kg-1, bupivacaine (B) 2mg.kg-1 and levobupivacaine (LVB) 2.5mg.kg-1. The infiltrations were done at the back region 1.5cm where incision would be performed at the upper, middle and lower part along the midline, under general anesthesia. Wound tensile strengths were measured after 0.7cm×2cm of cutaneous and subcutaneous tissue samples were obtained vertical to incision from infiltrated regions. Tissue samples were also obtained for electron microscopic examination. Evaluations were on the 8th, 15th and 21st days after infiltration. RESULTS: There was no difference between groups in the weights of the rats at the 0th, 8th, 15th and 21st days. The collagen maturation was no statistically different between groups at the 8th and 15th days. The maturation scores of the B and L groups at the 21st day was significantly lower than the Group C (1.40, 1.64 and 3.56; respectively). The wound tensile strength was no statistically different between groups at the 8th and 15th days but at the 21st day the Groups B and LVB had significantly lower value than Group C (5.42, 5.54 and 6.75; respectively). CONCLUSION: Lidocaine and prilocaine do not affect wound healing and, bupivacaine and levobupivacaine affect negatively especially at the late period.

Electron Microscopic Comparison of Radial Artery Grafts in Non-Diabetic and Diabetic Coronary Bypass Patients.

OBJECTIVE: We compared electron microscopic histologic changes of the radial artery grafts in non-diabetic and diabetic patients. METHODS: Thirty-six patients were divided into three groups according to their diabetic status (Group I had no diabetes mellitus [DM], Group II had type two DM and HbA1c levels were <7.5%, and Group III had type 2 DM but HbA1c levels were >7.5%). Distal parts of radial artery grafts were evaluated with scanning electron microscopy in a blind fashion by two histologists. Electron microscopic scores were compared among the groups. RESULTS: Radial artery electron microscopic scores were significantly different between group 1, 2 and 1, 3 and 2, 3 (p = 0.028, p < 0.001, and p < 0.001). In linear regression analysis, duration of DM (p = 0.027) and fasting plasma glucose (p = 0.001) were found as independent risk factors for histologic changes of radial artery grafts. CONCLUSION: Duration of DM and poor glycemic control were found to be associated with radial artery electron microscopic changes. doi: 10.1111/jocs.12761 (J Card Surg 2016;31:410-415).

Electron microscopic analysis of an angiosarcoma of the thyroid from a non-Alpine endemic goiter region: A case report and brief review of the literature.

Angiomatoid tumors of the thyroid gland are rare endocrine neoplasms, which exhibit an aggressive behavior. Angiosarcomas of the thyroid are generally reported from the European Alpine region and have a histogenesis that has been under debate for a number of years. The current study presents a rare case of angiosarcoma of the thyroid in a 62-year-old Turkish female. The patient had a 10-year history of goiter and was from the Black Sea region, an endemic goiter region of Turkey. The patient was not taking any medication at the time of admission and swelling had been observed on the right side of the neck throughout the previous few months. Thyroid function tests, which analyzed the levels of thyroid-stimulating hormone, thyroxine and triiodothyronine, were within the normal limits, however, the histopathological findings were consistent with an angiosarcoma of the thyroid. The patient rejected the complementary surgery and chemotherapy options, and is currently disease-free (as per the 15-month follow-up). The current study describes a case of angiosarcoma that was characterized by Weibel-Palade bodies, and light microscopy and immunohistochemical findings, as well as an endothelial origin, which was demonstrated via electron microscopy. To the best of our knowledge, this is the first reported case of angiosarcoma of the thyroid in a patient from Turkey to be validated by electron microscopy. Furthermore, this case is one of the few reported thyroid angiosarcoma cases in a non-Alpine region.

Effects of the recreational use of PDE5 inhibitors on the corpus cavernosum of young, healthy rats.

PURPOSE: PDE5 inhibitors are widely used for the treatment of erectile dysfunction. However, these drugs have recently become popular among men without erectile dysfunction as a means of enhancing sexual performance and improving sexual desire. The aim of this study was to investigate the histopathological and ultrastructural effects of PDE5 inhibitors on the corpus cavernosum in young, healthy male rats. METHODS: Twenty-four 4-month-old male rats were divided into four groups: group 1 was the control group, group 2 rats received sildenafil citrate, group 3 rats received vardenafil hydrochloride, and group 4 rats received tadalafil. All drugs were administered for 4 weeks. Penile tissue was collected for electron microscopy and tissue collagen measurements. Electron microscopic analysis indicated that the number of active fibroblasts and macrophages and the synthesis of new collagen fibers increased in treated rats. RESULTS: Cavernous tissue collagen levels were significantly higher in the sildenafil-, vardenafil-, and tadalafil-treated groups than in controls (46.16 ± 4.9, 42.06 ± 2.4, 41.07 ± 2.4, and 29.20 ± 3.3, respectively) (p < 0.001). CONCLUSIONS: Young men who use these drugs to enhance performance in the absence of erectile dysfunction may experience irreversible damage to the cavernosal tissue. However, more studies are needed to evaluate the molecular mechanisms by which PDE5 inhibitors affect the corpus cavernosum.

Protective effect of a potent antioxidant, pomegranate juice, in the kidney of rats with nephrolithiasis induced by ethylene glycol.

PURPOSE: We aimed to study the protective effects of pomegranate juice (PJ) on ethylene glycol (EG)-induced crystal deposition in renal tubules, renal toxicity, and inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB activities in rat kidneys. MATERIALS AND METHODS: Fifty-six rats were divided into four equal groups: Control, EG, EG + 50 microL PJ/d (PJ50), and EG + 100 microL PJ/d (PJ100). Rats were sacrified on days 10 and 45. Tissue sections were evaluated under light and polarized microscopy for the presence and degree of crystal deposition and toxicity in the kidneys. Crude extracts of the cortex were used to determine reduced gluthatione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels. RESULTS: In the EG group, crystal depositions were more evident and mild crystalization was observed in proximal tubules on day 10; severe crystalization and granulovacuolar epithelial cell degeneration were observed on day 45. There was limited or no crystal formation in the EG + PJ-given groups. There were completely normal renal and tubular structures in the control group. There was no significant difference between the four groups in serum levels of sodium, potassium, blood urea nitrogen, and creatinine in any sampling time. Hyperoxaluria, a marked increase in MDA and NO levels, and decrease of GSH were observed in the EG-given groups compared with the others. There were marked iNOS and p65 expressions in only the EG-given rats compared with control and PJ groups, immunohistochemically. CONCLUSION: This experiment shows the protective effect of PJ in the EG-induced crystal depositions in renal tubules.

Rapid communication: protective effect of a nuclear factor kappaB inhibitor, pyrolidium dithiocarbamate, in the kidney of rats with nephrolithiasis induced by ethylene glycol.

PURPOSE: To study the protective effects of a selective nuclear factor kappa B (NF-kappaB) inhibitor, pyrolidium dithiocarbamate (PDTC), on ethylene glycol-induced crystal deposition in the renal tubules, renal toxicity, as well as inducible nitric oxide synthase (iNOS) and NF-kappaB activities in rat kidneys. MATERIALS AND METHODS: Rats were divided into three equal groups: control, ethylene glycol-treated (EG), and ethylene glycol + PDTC treated (EG+PDTC). Rats were sacrificed on day 7, 15, or 45, and tissue sections were evaluated under light and transmission electron microscopy for the presence and degree of crystal deposition and toxicity in the kidneys. The iNOS and NF-kappaB activity were evaluated immunohistochemically, with p65 being stained to define NF-kappaB activity. Crude extracts of the cortex were used to determine reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) concentrations. RESULTS: Crystal depositions were more evident in the proximal tubules on day 7 in the EG than in the other groups. Mild crystallization was observed on day 15, and severe crystallization and granulovacuolar epithelial-cell degeneration were observed on day 45. There was limited or no crystal formation in the EG+PDTC group and completely normal renal and tubular structures in the control group. Whereas ethylene glycol administration stimulated iNOS and NF-kappaB/p65 activity in renal tubules, PDTC inhibited it. Rats given only vehicle demonstrated no significant alterations. Hyperoxaluria, a marked increase in MDA and NO concentrations, and a decrease in GSH were observed in the EG group. CONCLUSION: This experiment has shown the role of transcription factors, NF-kappaB, and iNOS in ethylene glycol-induced crystal depositions in renal tubules.