Dichloroacetate Reduces Tissue Necrosis in a Rat Transverse Rectus Abdominis Musculocutaneous Flap Model

Tyner, Tim; Tong, Weiwei; Donovan, Kelli; Mcdonald, Travis; Sian, Kenty; Yamaguchi, Kent T.

doi:10.1097/01.sap.0000194549.39544.cd

Cited by 6 publications

(3 citation statements)

References 47 publications

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“…The urinary excretion of unchanged DCA in male rats increases with age, whereas oxalate and DCA end metabolites show the opposite trend [100]. It is notable that preclinical studies of DCA metabolism are conducted only in male rats [93,95,96,100,109,117,118,119,120,121], male mice [96,122] or male dogs [105], while some others do not indicate the gender of tested animals [99].…”

Section: Preclinical Research Of Dca Pharmacologymentioning

confidence: 99%

The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo

Stakišaitis

Juknevičienė

Damanskienė

et al. 2019

Cancers

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Sodium dichloroacetate (DCA) is an investigational medicinal product which has a potential anticancer preparation as a metabolic regulator in cancer cells’ mitochondria. Inhibition of pyruvate dehydrogenase kinases by DCA keeps the pyruvate dehydrogenase complex in the active form, resulting in decreased lactic acid in the tumor microenvironment. This literature review displays the preclinical research data on DCA’s effects on the cell pyruvate dehydrogenase deficiency, pyruvate mitochondrial oxidative phosphorylation, reactive oxygen species generation, and the Na+–K+–2Cl− cotransporter expression regulation in relation to gender. It presents DCA pharmacokinetics and the hepatocarcinogenic effect, and the safety data covers the DCA monotherapy efficacy for various human cancer xenografts in vivo in male and female animals. Preclinical cancer researchers report the synergistic effects of DCA combined with different drugs on cancer by reversing resistance to chemotherapy and promoting cell apoptosis. Researchers note that female and male animals differ in the mechanisms of cancerogenesis but often ignore studying DCA’s effects in relation to gender. Preclinical gender-related differences in DCA pharmacology, pharmacological mechanisms, and the elucidation of treatment efficacy in gonad hormone dependency could be relevant for individualized therapy approaches so that gender-related differences in treatment response and safety can be proposed.

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Section: Preclinical Research Of Dca Pharmacologymentioning

confidence: 99%

The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo

Stakišaitis

Juknevičienė

Damanskienė

et al. 2019

Cancers

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“…The lactate level is an indicator of tissue ischemia and hypoxia. 37,38 Lactate levels in experimental groups 2 and 1 returned to normal values, but remained high in the control group at 7 days after surgery (Fig. 7).…”

Section: Discussionmentioning

confidence: 84%

A Preliminary Study of the Effects of Venous Drainage Position on Arterial Blood Supply and Venous Return within the Conjoined Flap

Cheng

Lou

et al. 2019

Plastic &Amp; Reconstructive Surgery

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Background:Conjoined flap viability is associated with arterial blood supply and venous return. This study aimed to assess the effects of venous drainage position on arterial blood supply and venous return within the conjoined flap.Methods:Fifty-four rats were divided randomly into three groups (n = 18 per group). In experimental group 2, only the right intercostal posterior artery and the left iliolumbar vein were maintained; meanwhile, only the right intercostal posterior artery and the left intercostal posterior vein were preserved in experimental group 1. The control group had only the right intercostal posterior artery and vein preserved. The distances between angiosomes were measured. At 7 days after surgery, flap survival was evaluated, lead oxide–gelatin flap angiography was performed, and average microvessel density was assessed by hematoxylin and eosin staining, and lactate levels were assessed.Results:The distance between angiosomes I and II was the shortest, whereas angiosomes I and III were most distant (p < 0.05). At 7 days after surgery, survival rates in experimental group 2 and experimental group 1 were both 100 percent, whereas 86.5 ± 1.6 percent of controls survived. Furthermore, angiogenesis was more obvious in experimental group 2 than in experimental group 1 and controls. Moreover, lactate levels were lower in experimental group 2 (7.47 ± 0.17 mM) and experimental group 1 (8.03 ± 0.31 mM) compared with control values (9.98 ± 0.37 mM; p < 0.05).Conclusion:Changes in position of venous drainage might cause continuous arterial high-pressure perfusion and venous superdrainage, which improves flap survival.

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“…In each animal, a transverse TRAM flap was created based on a unilateral rectus abdominis muscle. 17,18 The skin paddle (7.0 3 3.5 cm) was designed on the upper abdomen extending between both anterior axillary lines from the costal margin to the mid-abdomen (0.5 cm above the umbilicus). The rectus abdominis muscle was divided cranially and caudally, and the superior epigastric vessel was divided so that the flap was based solely on the inferior epigastric vascular pedicle.…”

Section: Surgical Proceduresmentioning

confidence: 99%

Effects of various protocols of ischemic preconditioning on rat tram flaps

Wang

Liu

2007

Microsurgery

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We used rat transverse rectus abdominis musculocutaneous (TRAM) flaps to investigate whether the ischemic cycle duration and number of cycles influenced the effectiveness of ischemic preconditioning (IPC). First, the animals were divided into one control group and four treatment groups. Controls received no preconditioning; flaps with IPC were treated by two cycles of pedicel clamping and reperfusion for either 5 or 10 min. Then the best of IPC protocols in first part was selected, and flaps were subjected to one or three cycles of IPC before 4 h of normothermic ischemia. The preconditioned flap survival area had improved 2.5-3 times over that of the control area by postoperative day 7. Serum creatine phosphokinase (CPK), water content, and malondialdehyde (MDA) in muscle were significantly decreased in the preconditioned groups after 4 h of reperfusion. Especially, 2 and 3 cycles of the 10/5-min combination were more effective than other protocols of IPC.

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Dichloroacetate Reduces Tissue Necrosis in a Rat Transverse Rectus Abdominis Musculocutaneous Flap Model

Abstract: This study indicates that DCA may provide a useful pharmacologic tool for reducing ischemia-related necrosis in TRAM flaps.

Cited by 6 publications

References 47 publications

The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo

The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo

A Preliminary Study of the Effects of Venous Drainage Position on Arterial Blood Supply and Venous Return within the Conjoined Flap

Effects of various protocols of ischemic preconditioning on rat tram flaps

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