Blood flow improved by CR?

[Guest guest]

Hi All,

Evidence has apparently been found that CR is great

for regrowth of new tissues. Lipoic acid apparently not

only is beneficial, but is so in combination with CR, but

is more effective than CR alone.

First, here is some introduction.

Ischemia = " A low oxygen state usually

due to obstruction of the arterial blood supply or inadequate

blood flow leading to hypoxia in the tissue. " ,

and is improved by CR, which is considerably more effective

than other therapies, such as, from the bottom paper pdf:

" angiogenic factors,1 immunosuppressants,2 antioxidants,

and hyperbaric oxygen,3 on skin flap survival " ,

and, as I understand it, is used in reconstructive surgery.

Ischemia is maybe the greatest source of pathology for

us, since it is involved in the common diseases, heart

disease and stroke.

For an introduction to the system used in the CR study,

see:

" Tissue ischemia remains a common problem in plastic surgery and

one for which

proangiogenic approaches have been investigated. Given the recent

discovery of

circulating endothelial stem or progenitor cells that are able to

form new blood

vessels "

http://tinyurl.com/5mfsb

For a look at the data, here are the results from the table and

figure:

FIG. 1. Surviving flap length: Test groups 1 through 9 had

eight animals each. Group 1: control group (no lipoic acid),

groups 2 and 3: oral lipoic acid; groups 4 and 5:

intraperitoneal lipoic acid, group 6: restricted diet (no

lipoic acid), group 7: restricted diet plus lipoic acid (pre-

operatively

and postoperatively), group 8: restricted diet

plus lipoic acid (preoperatively only), group 9: restricted

diet plus lipoic acid (postoperatively only). Standard devia-tions

for each group are shown.

Table 1. Flap survival length (cm) for successive groups were:

5.4+/- 0.7, 5.7+/-0.4, 7.4+/-0.8, 7.2+/-0.5, 7.5+/-0.9,

7.7+/-1.1, 8.9+/-0.9, 10.3+/-0.3, 5.6+/-0.4.

And, here is the report that is available as a pdf:

Tyner TR, D, Yamaguchi KT.

Effects of lipoic acid and a reduced-calorie diet on skin flap

survival in a

rat model.

Plast Reconstr Surg. 2004 Dec;114(7):1980-2. No abstract available.

PMID: 15577391 [PubMed - in process]

Sir:

Random-pattern skin flaps are commonly used in reconstructive

surgery. Experimental skin flap models in rats have been widely used

to study the effects of potential therapies, such as angiogenic

factors,1 immunosuppressants,2 antioxidants, and hyperbaric oxygen,3

on skin flap survival. We conducted an experimental study to

investigate whether flap survival could be improved by lipoic acid, a

biological antioxidant capable of scavenging free radicals,4

inhibiting lipid peroxidation,5 and recycling endogenous antioxidant

systems.6 During our investigation of lipoic acid, we also, though

inadvertently, discovered a correlation between preoperative daily

caloric intake and flap survival.

Seventy-two male Sprague-Dawley rats weighing approximately 250 g

were used. Rats were separated into nine test groups of eight animals

each (Table I). Animals were placed on preoperative and/or

postoperative feeding regimens (Table I, row C). At the end of the

preoperative feeding period, rats were anesthetized intramuscularly

with ketamine and xylazine at 75 mg/kg and 7.5 mg/kg, respectively,

following which a 3 × 12-cm dorsal, cranial-based, full-thickness,

random-pattern skin flap was elevated and reapproximated with

surgical staples. At 10 days after elevation, the flaps were

evaluated for viability. One-way analysis of variance was applied to

flap survival data. Bonferroni and Dunnett post hoc tests were used

to determine significant differences among test groups. A p value of

<=0.05 was considered statistically significant.

In our initial study (groups 1 through 5), rats were fed 30 g of

standard rat chow (LabDiet no. 5001; PMI Nutrition International, St.

Louis, Mo.) daily supplemented with lipoic acid (Table I, row A).

Groups 2 and 3 received lipoic acid as an oral dietary supplement,

while groups 4 and 5 had lipoic acid injected intraperitoneally

(Table I, row . Group 1 received no lipoic acid supplementation

(control). In group 3, which was fed the highest dietary content of

lipoic acid (200 mg/kg per day), we determined that two of eight rats

had consumed only 50 percent of their daily allotted diet. These

animals had a body mass reduction of approximately 15 percent by the

end of the 1-week preoperative feeding period (Table I, row E, group

7). Surprisingly, these animals demonstrated the most dramatic

improvement in flap survival. Follow-up studies were undertaken to

confirm these findings. As shown in Table I, rows C and D, groups 6

through 9 were placed on a restricted diet of 15 g of chow per day

for 7 days preoperatively and/or postoperatively. Groups 7 through 9

also received lipoic acid supplementation (Table I, row A). The two

group 3 animals, which consumed only 50 percent of their diet in the

initial experiment, were included in the group 7 data. All animals

had access to water ad libitum.

The results of our studies are shown in Table I, row F, and Figure

1. Lipoic acid supplementation, both dietary and injected, produced a

significant increase in flap survival rates (groups 3 through 5).

Animals on a reduced-calorie diet without lipoic acid (group 6)

similarly displayed increased flap survival. The most significant

flap improvement, however, was seen with the combination of lipoic

acid and a reduced-calorie diet (groups 7 and 8). The data further

suggest that improved flap survival rates resulting from preoperative

treatments are not enhanced by continued postoperative treatment

(group 8 versus group 7; group 4 versus group 5). Postoperative

treatment alone did not appear to enhance flap viability (group 9).

On the basis of our findings, preconditioning with lipoic acid may

provide some benefit in procedures with potentially compromised

flaps. While less likely to be clinically applicable, a significant

reduction in caloric intake before surgery appears to greatly improve

flap survival rates. We hypothesize that this diet-associated flap

enhancement may be attributable to an elevation in glucocorticoid

levels in response to the physical stress of the restricted diet.

Previous studies have shown a correlation between restricted-calorie

diets and glucocorticoid elevation 7 and also between glucocorticoid

levels and flap survival.8

REFERENCES

1. Kryger, Z., Zhang, F., Dogan, T., Cheng, C., Lineaweaver, W., and

Buncke, H. J. The effects of VEGF on survival of a random flap in the

rat: Examination of various routes of administration. Br. J. Plast.

Surg. 53: 234, 2000. Bibliographic Links [Context Link]

2. Cetinkale, O., Sengul, R., Bilgic, L., Bolayirli, M., Senel, O.,

and Burcak, G. Involvement of neutrophils in ischemic injury: I.

Biochemical and histopathological investigation of the effect of

FK506 on dorsal skin flaps in rats. Ann. Plast. Surg. 39: 505, 1997.

Bibliographic Links [Context Link]

3. , R., , T., , B., Easton, M., Newton, G., and

Yamaguchi, K. Effect of free-radical scavengers and hyperbaric oxygen

on random-pattern skin flaps. Arch. Surg. 129: 982, 1994.

Bibliographic Links [Context Link]

4. Packer, L., Witt, E., and Tritschler, H. Alpha-lipoic acid as a

biological antioxidant. Free Radic. Biol. Med. 19: 227, 1995.

Bibliographic Links [Context Link]

5. Lapenna, D., Ciofani, G., Pierdomenico, S., Giamberardino, M., and

Cuccurullo, F. Dihydrolipoic acid inhibits 15-lipoxygenase-dependent

lipid peroxidation. Free Radic. Biol. Med. 35: 1203, 2003. [Context

Link]

6. , W., Li, X., Qu, Z., Perriott, L., Whitesell, R., and May,

J. Uptake, recycling, and antioxidant actions of alpha-lipoic acid in

endothelial cells. Free Radic. Biol. Med. 33: 83, 2002. [Context Link]

7. Yaktine, A., Vaughn, R., Blackwood, D., Duysen, E., and Birt, D.

Dietary energy restriction in the SENCAR mouse: Elevation of

glucocorticoid hormone concentrations but no change in distribution

of glucocorticoid receptor in epidermal cells. Mol. Carcinog. 21: 62,

1998. Bibliographic Links [Context Link]

8. Torkvist, L., Lundeberg, T., Thorlacius, H., et al. Effects of

environmental stress on tissue survival and neutrophil recruitment in

surgical skin flaps in relation to plasma corticosterone levels in

the rat. Inflamm. Res. 46: 199, 1997.

Cheers, Alan Pater