From mitochondria to disease: role of the renin-angiotensin system.

Mitochondria are energy-producing organelles that conduct other key cellular tasks. Thus, mitochondrial damage may impair various aspects of tissue functioning. Mitochondria generate oxygen- and nitrogen-derived oxidants, being themselves major oxidation targets. Dysfunctional mitochondria seem to contribute to the pathophysiology of hypertension, cardiac failure, the metabolic syndrome, obesity, diabetes mellitus, renal disease, atherosclerosis, and aging. Mitochondrial proteins and metabolic intermediates participate in various cellular processes, apart from their well-known roles in energy metabolism. This emphasizes the participation of dysfunctional mitochondria in disease, notwithstanding that most evidences supporting this concept come from animal and cultured-cell studies. Mitochondrial oxidant production is altered by several factors related to vascular pathophysiology. Among these, angiotensin-II stimulates mitochondrial oxidant release leading to energy metabolism depression. By lowering mitochondrial oxidant production, angiotensin-II inhibition enhances energy production and protects mitochondrial structure. This seems to be one of the mechanisms underlying the benefits of angiotensin-II inhibition in hypertension, diabetes, and aging rodent models. If some of these findings can be reproduced in humans, they would provide a new perspective on the implications that RAS-blockade can offer as a therapeutic strategy. This review intends to present available information pointing to mitochondria as targets for therapeutic Ang-II blockade in human renal and CV disease.

Effects of pulsed magnetic energy on a microsurgically transferred vessel.

This article reports the findings of a study that attempted to elucidate whether pulsed magnetic energy stimulates neovascularization in vivo, using a microsurgically created arterial loop model in a prospective randomized trial of 108 rats (n = 12/group). Pulsed magnetic energies of 0.1 and 2.0 gauss were applied immediately postoperatively and for 4, 8, and 12 weeks, respectively, with a statistically significant increase in neovascularization among the treated animals compared with control rats. The study provides a starting point for future study and evaluation of the stimulation of angiogenesis with the use of pulsed magnetic energy and suggests a possible use of this modality to increase the quality of revascularized tissue.

1457 years of microsurgical experience.

Microsurgery is a relatively new field of surgery involving various methods and practices that are currently evolving. Our goal was to register the current practices employed by the members of the American Society for Reconstructive Microsurgery. A survey was mailed to the 319 members of the society, resulting in a response rate of 33 percent (106 of 319). The data reflect the combined experience of 10,839 free-tissue transfers and 3487 digital and upper and lower extremity replants over a 4-year period between 1990 and 1994. Practices employed, such as pharmacologic adjuvant therapy, monitoring techniques, flap types, and success rates reported by the members of the American Society for Reconstructive Microsurgery, were analyzed.

The ten test.

The authors describe a new test for clinical sensibility, initiated in response to the need of the senior author for a rapid, reliable method to evaluate sensibility. Using this test, the patient develops a ratio between normal light moving touch and diminished moving touch. Subsequent determinations can detect serial changes. The ratios obtained can be compared with a standard scale of sensibility with a high degree of validity and reliability. The interexaminer and intraexaminer results obtained are reliable and repeatable. Statistical evaluations substantiating the validity of the test are presented. Simplicity and depend-ability recommend this test for use in a busy clinical setting.

Determining the maximal length of a vein conduit used as an interposition graft for nerve regeneration.

Although autogenous veins have been used as nerve conduits (AVNCs) both experimentally and clinically for short nerve gaps up to 3 cm, investigators have not as yet determined the maximal effective length for functional nerve regeneration. In addition, the role of the distal nerve stump on subsequent nerve growth remains unclear. A rabbit peroneal nerve AVNC model was used to study axonal regeneration through nerve gaps of 1 to 6 cm. After allowing ample time for nerve regeneration, clinical, electophysiologic and neurohistologic studies were performed to evaluate nerve growth and functional muscle reinnervation. Comparisons were made with 6-cm conventional nerve grafts. Excellent growth and function were found with AVNCs up to 3 cm in length, with increasing incapacity for regeneration at lengths greater than 3 cm. The distal nerve stump is believed to play a vital role in nerve regrowth.

The effect of epigastric vessel ligation on the vascular territories of the pig rectus muscle.

In a pig model, unilateral ligation of the inferior epigastric vessels caused an initial decrease in normal vascularity, followed by an increase toward normal vascularity, in the inferior portion of the rectus muscle over 42 days. Ligation appeared to dilate the choke vessels between the superior and inferior arterial territories. The results indicate that by ligation of the inferior epigastric vessels, the vascular territory, which is normally tenuous, can undergo a transposition without vascular compromise.

Anatomy of the chicken foot for the experimental investigation in flexor tendon surgery.

A chicken model for research in flexor tendon surgery is used despite the considerable differences between avian foot and human hand anatomy. In order to properly correlate and interpret the data collected from such experiments, a reexamination of chicken anatomy and terminology was undertaken. Thirty chicken feet were studied anatomically for tendon-tendon sheath structures including vascularization, flexor systems, and histologic specimens. The data collected show, besides striking similarities between human and avian anatomy, differences critical enough to warrant a reevaluation of previous descriptions of the avian structure.

The use of pentoxifylline in microvascular surgery.

The authors studied the effect of pentoxifylline (Trental), a hemorrheologic agent that increases erythrocyte flexibility and augments microcirculatory blood flow, on the patency of a known thrombosis model. In Sprague-Dawley rats, a double-blind study was performed, with animals receiving either intraperitoneal injections of pentoxifylline (20 mg/kg/day) or saline in an equivalent volume, 4 weeks prior to surgery and continued for 1 week postoperatively. In all animals, the left femoral artery was used for a 2-mm arterial inversion graft (AIG), and the contralateral femoral artery for a 2-mm crush injury model. In the control group, patency of the AIG was 0 percent (0/19) and that of the crush model 31 percent (6/19). The pentoxifylline-treated group showed an AIG patency of 37 percent (7/19) and a crush model patency of 84 percent (16/19). p values were .004 and .005, respectively. Furthermore, hematoma formation was associated with none of the control sides (0/38) and only with 5 percent (2/38) of the pentoxifylline-treated animals. This study demonstrated statistically significant improvement on microvascular patency in animals treated with pentoxifylline, whether they were in the crush or the arterial inversion graft groups. The clinical ramifications of using a hemorrheologic agent that improves microvascular circulation, without effecting changes in coagulation, are apparent.

Distraction of the frontal bone outside the cranial plane: a rabbit model.

Distraction of the frontal bone outside the cranial plane using the Ilizarov principle was performed in 17 22-week-old New Zealand white rabbits. Five rabbits had frontal bone osteotomy only and were in the control group; 5 rabbits were placed in the sham control group and had frontal bone osteotomy plus application of a customized headgear appliance; and 7 rabbits were placed in the experimental group, which underwent frontal bone osteotomy application of the headgear and distraction. The frontal bone was elevated 1 mm every other day for a period of 8 weeks, and the animals were then killed. Cephalometry was performed both preoperatively and at the end of the 8-week period. Histological examination of the skulls was also performed. The experimental group showed a significantly elevated frontal bone compared to the sham control group (p < 0.05). Callous bone filled the distracted segment, which united the frontal bone with the cranial plane. Therefore, frontal bone advancement by distraction osteogenesis is possible using this rabbit model.

pH-balanced solutions with superoxide dismutase (SOD): an attempt to increase island groin flap survival in rats.

Balanced salt solution (BSS) and balanced salt solution plus (BSS+), alone and in combination with heparin or superoxide dismutase (SOD), were used as irrigation solutions for rat groin flaps after prolonged ischemia. SOD always improved flap survival when it was present in solution, although when combined with BSS and BSS+, it was less effective than when combined with Ringer's lactate. The physiological pH solutions BSS and BSS+ had no advantages over Ringer's lactate in any of the tested combinations.

A simple device to control the amount of vasoactive drugs topically applied to blood vessels during experimental studies.

A simple, readily available, inexpensive device is presented that makes research of topically applied vasoactive drugs more accurate and reproducible. It is possible to recollect the drug or wash it away from the vessel. Reversal drugs can also be used in the immediate vicinity of the vessel wall.

"No suture" microanastomosis using Vicryl rings and fibrin adhesive system: an unsuccessful attempt.

Vascular repairs using a combination of Vicryl rings to evert vessel edges and the Tisseel two-component fibrin adhesive system failed to achieve patent microanastomosis without using stay sutures. The bonding force of Tisseel alone was not sufficient to hold the cut ends of rat femoral arteries and veins together. All 10 arterial and 8 venous end-to-end anastomoses separated under normal intraluminal pressure immediately after the removal of microclamps. This method was found to be an unacceptable alternative to the conventional suturing method.

Autocannibalization of sensate and denervated rat groin flaps.

The extent to which rats self-mutilate was studied in 30 Sprague-Dawley rats. The experiment tested unilateral and bilateral sensate and denervated groin flaps, with statistically significant results obtained between the bilateral groups.

Prevention of flap necrosis by chlorpromazine.

Chlorpromazine administered to Sprague-Dawley rats 30 minutes prior to elevation of McFarlane back flaps and continued 14 days thereafter resulted in near complete flap survival, compared with 48 percent necrosis in control animals. Chlorpromazine demonstrates a wide variety of actions that appear to meet all presently known requirements for flap preservation.

A simplified technique for end-to-end microanastomosis.

A simplified technique for end-to-end microanastomosis is presented. It combines the advantages of the anterior and posterior wall techniques; it is especially suitable when only short vessel segments are available; it eliminates severe torsion of the vessels; and it is relatively easy to perform.

The rat groin flap: can it survive on the epigastric nerve blood supply alone?

Rat groin flaps were divided from their blood supply with and without cutting the epigastric nerve. Only small areas of the flaps were infrequently able to survive, probably as skin grafts. The intrinsic blood supply of the nerve did not contribute to the survival of these flaps.

Improved survival of island flaps after prolonged ischemia by perfusion with superoxide dismutase.

Perfusion of rat groin flaps after 10 and 11 hours of complete ischemia with superoxide dismutase, an oxygen free-radical scavenger, significantly improved the survival of these flaps. This finding provides further evidence for the important role that oxygen-derived free radicals play in ischemic injury. The study also demonstrates that while restoration of blood supply alone is not enough to ensure tissue survival after prolonged ischemia, chemical agents can be utilized to achieve viable flaps beyond what was believed to be "a point of no return".

A new experimental model for myocutaneous flaps: latissimus dorsi of the rabbit--an anatomic study.

A new experimental model, the latissimus dorsi flap of the rabbit, was studied. This was found to be a relatively inexpensive research model. Its use is advocated for composite tissue transfer as transposition, island, or free myocutaneous flaps.

The fate of tendon healing after restoration of the integrity of the tendon sheath with autogenous vein grafts.

This experimental study in the chicken model compares the results of sheath closure during primary tendon surgery. Sheath closure after tendon grafting was accomplished by trapdoor of the original sheath, vein patch, and vein conduit. After casting in flexion for 14 days, the operated foot and digits were taken through a full passive range of motion every 3 days. At the 28th postoperative day, all immobilization was removed and free active range of motion and daily perching began. Active flexion was measured after death by continuous traction on the proximal profundus tendon: simulated active flexion. The unoperated contralateral foot served as the control. All operated middle toes achieved significantly greater functional return when the sheath was restored either with trap-door closure, vein conduit, or vein patch compared with simple excision of the sheath. The results indicate the efficacy of sheath closure as well as the possibility of utilizing vein patches or conduits during primary tendon repair.