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Journal of Rehab R&D
Vol. 39 No. 4 July/August 2002
Pages 497-504

Development of a mechanical device to replace medicinal leech (Hirudo medicinalis) for treatment of venous congestion


Michael L. Conforti, DVM, MS; Nadine P. Connor, PhD; Dennis M. Heisey, PhD; Ray Vanderby, PhD; David Kunz, PhD; Gregory K. Hartig, MD
Department of Research, William S. Middleton VA Hospital, Madison, WI; Department of Surgery, University of Wisconsin Medical School, Madison, WI

Abstract: Medicinal leeches are used to treat venous congestion, a complication of reconstructive surgery. Despite substantial drawbacks of leeching, little progress has been made to develop a device that would replace the leech for this purpose. The goal of this study was to develop and test mechanical prototypes for the treatment of venous congestion. We tested four prototypes (1, 2, 3a, and 3b) using congested fasciocutaneous flaps in swine. Blood removed by each prototype was measured for up to 4 hours. On average, the four prototypes removed 609%, 644%, 853%, and 811% more blood, respectively, from congested flaps versus a leech. Prototypes 3a and 3b, which allowed for innovative subcutaneous chemical (3a and 3b) and mechanical (3b) anticoagulation at the bleeding wound, sustained high levels of blood removal for up to 4 hours. Thus, a mechanical device can potentially replace the use of leeches for treating venous congestion.

Key words: Hirudo medicinalis, mechanical device, medicinal leech, reconstruction, replantation, venous congestion.


This material was based on work supported by a Rehabilitation Research and Development grant from the Department of Veterans Affairs.
Address all correspondence and requests for reprints to Michael L. Conforti, DVM, MS, William S. Middleton VA Hospital, Department of Research, 2500 Overlook Terrace, Madison, WI 53705.

INTRODUCTION

Reconstructive surgical procedures, such as free flaps, pedicle flaps, and replantation of amputated tissues, often include an anastomosis between either surgically ligated or traumatically severed blood vessels. Venous congestion is a serious complication of these types of procedures and occurs when the venous outflow from a tissue is reduced relative to arterial input. Kinking or impingement on the veins and/or thrombus formation within the veins can cause this reduction [1-4]. If venous congestion is not corrected (either surgically or via some other means), the developed stasis within the vasculature of the tissue will cause the replanted region to necrose.

Although medicinal leeches (Hirudo medicinalis) have been a part of medical practice for thousands of years, not until the advent of reconstructive microsurgery in the 1960s did bloodletting by the leech have a legitimate medical purpose. Specifically, medicinal leeches are placed upon the congested tissue to facilitate removal of excess blood until microvenous circulation can be effectively reestablished approximately 4 to 10 days after surgery [5-11]. Unfortunately, leeches only remove small quantities of blood from the congested tissue and cannot be relied upon to effectively decongest large regions of tissue. In addition, the use of leeches is suboptimal because of other drawbacks [12]. These drawbacks are substantial and include negative patient and family perception, unreliability of leech attachment (i.e., the leeches may not attach to, or may migrate from, the impaired tissue and may feed on healthy adjacent skin), excessive cost because of constant staff monitoring, and the possibility of infection [13-16].

There have been several attempts in the last 10 years to develop a mechanical and/or chemical leech that would replace the medicinal leech [17-20]. Although these attempts showed some success, a clinically applicable product has not been developed to date, which would replace the use of medicinal leeches for the successful treatment of venous congestion.

The specific goal of this study was to begin prototype development and testing of a mechanical device to replace the medicinal leech. Ultimately, the mechanical device will be optimized for minimum skin surface (cosmetic) and underlying tissue damage, maximum therapeutic bleeding time, and maximum therapeutic blood removal. Our first generation prototypes described in this study begin the testing and manipulation of functional concepts for device optimization. A swine model was chosen over a small animal model to maximize the clinical relevance of this study. Swine have cutaneous morphology similar to humans and a large blood supply, preventing the possibility of fatal exsanguination during treatment [21-22].

METHODS

Eleven mixed-breed pigs, weighing 20.5 kg to 24.2 kg were preanesthetized with intramuscular xylazine (2 mg/kg), Telazol (6 mg/kg), and atropine (1 mL). The animals were mechanically ventilated with 100 percent 02 and isoflurane (1.5 to 2.5 percent). Isotonic fluids were administered intravenously (IV) throughout the experiment (10 mL/kg/h). Blood pressure and rectal temperature were monitored.

Model of Venous Congestion

A 9- ∞ 9-cm cutaneous pedicle flap based on the superficial circumflex iliac artery and venae comitantes (VCs) was elevated, one per animal, as described previously [12,23]. The right or left flank was used based on a predetermined random schedule. The VCS were completely occluded with the use of vascular clamps; after which, the artery was treated with 0.1 mL of topical lidocaine (4 percent) to prevent and/or treat vascular spasm. A thin cloth was placed under the flap to isolate it from the surrounding tissue. Before any surgical manipulation and after the VCs were clamped, laser Doppler images were taken to verify venous stasis.

Mechanical Device Prototypes

All prototypes consisted of a hand-blown glass shell (approximately 1.5 cm in diameter) that was adhered to the skin over a bleeding wound with veterinary-grade adhesive (Nexaband). Each shell had inflow and outflow ports that allowed suction, anticoagulation, and air intake into the glass shell. Full schematics of prototypes 1 to 3 are shown in Figure 1. Prototype 3 had two slightly different variants, denoted as 3a and 3b. In total, six functional concepts were integrated into the design of these prototypes, as described in the following paragraphs. Parameters of concepts 1, 5, and 6 were varied across prototypes. A summary of the variations among the prototypes is found in the Table.


Figure 1. Schematics of prototypes.

Table Summary of prototype variations. Surgically created bleeding wound, subcutaneous chemical anticoagulation, and subcutaneous mechanical anticoagulation (concepts 1, 5, and 6, respectively) were varied among mechanical prototypes. Suction, surface chemical anticoagulation, and surface mechanical anticoagulation (concepts 2 to 4) were constant among four prototypes. N/A = not applicable for that particular prototype.


     

Concept 1

Concept 5

Concept 6


Prototype

Trials
(n)

Test
Duration
(h)

Wound

SubQ Chemical (Heparin) Anticoagulation

SubQ Mechanical Anticoagulation


1

2

3

Punch biopsy

Bolus injections

N/A

2

2

3

Crossed stab incisions

Bolus injections plus continuous infusion at injection sites

N/A

3a

4

4

Crossed stab incisions

Bolus injections plus continuous infusion into wound via hydrogel disk

N/A

3b

5

4

Crossed stab incisions

Bolus injections plus continuous infusion into wound via hydrogel disk

Manual disk rotation



Prototype 1

Prototype 2

Prototypes 3a and 3b

The hydrogel that impregnated the microporous disk consisted of 10 percent polyvinyl alcohol (hot soluble), 5 percent MgCl2, 0.5 percent glutaraldehyde (50 percent), 3 percent formaldehyde (37 percent), 4 percent glycerol, and 2 percent sodium heparin mixed in sterile water (adapted from Goosen, 1983) [24]. The microporous disk was impregnated with 0.5 mL of hydrogel under negative pressure. Sigma Aldrich manufactured all chemicals.

Experiment Protocol

The flap was allowed to congest for 15 minutes after clamping the veins. One mechanical prototype was then adhered to the skin flap over the prototype-specific bleeding wound. The mechanical prototypes were developed and tested sequentially. When testing prototype 3b, we placed two prototypes on the congested flap of two of the animals, bringing the overall sample size to 13 prototype trials.

For each experiment, the blood-irrigant mixture removed by the prototype was collected in 1-hour aliquots over a period of at least 3 hours. We measured the blood volume in each aliquot using methods described in detail in a prior report [25]. Briefly, the red blood cell count (RBCC) per milliliter in a 1-hour blood-irrigant aliquot was multiplied by the number of milliliters in the aliquot. This product equaled the total number of RBCCs in the aliquot, which was divided by the RBCC per milliliter in an IV blood sample to give the blood volume in each hourly aliquot in milliliters. Blood volumes removed by the mechanical devices were compared to medicinal leech standards previously documented under identical conditions (i.e., 4.7 mL over 3 hours) [12]. Percent increase in blood removed over a 3-hour period using the mechanical prototypes was calculated relative to the values of blood loss during leech therapy. We performed statistical analysis using independent t-tests ( α = 0.05).

In two separate representative experiments (one treatment and one control), similar but smaller 6-cm ∞ 7-cm flaps were congested as previously described in this paper. One flap was left untreated and one flap was treated with prototype 3b. The treatment and control periods of complete venous obstruction were 4 hours. The amount of decongestion or congestion that developed over the 4-hour experimentation period was documented via digital photography.

RESULTS

The combined mean increase in blood removed for all prototypes (n = 13 trials) as compared to blood removed by medicinal leeches over a 3-hour period was 759 percent. As shown in Figure 2, prototypes 3a and 3b removed significantly more blood over a 3-hour period than the average medicinal leech under identical conditions [12]. Blood volumes removed by prototypes 1 and 2 dropped substantially after the first hour. In contrast, blood removal by prototypes 3a and 3b was relatively stable across time (Figure 3).


Figure 2. Mean blood volume removed over a 3 hour period.


Figure 3. Blood volume removed v. treatment method after 4 hours.

Figure 4 contains images of an untreated control flap and a treated flap using prototype 3b after 4 hours of complete venous obstruction. As suggested by these images, prototype 3b allowed stable decongestion of the entire flap across time, evidenced by the minimal color difference between the flap and surrounding normal skin. Without treatment, the color of the control flap progressively darkened, as observed by the very dusky, deep purple when compared to the surrounding normal skin.


Figure 4. Representative images of a) untreated and b) treated flaps

DISCUSSION

Venous congestion is a serious complication of reconstructive surgery. Given the many drawbacks of medicinal leech therapy, the use of leeches to alleviate venous congestion only compounds an extremely difficult clinical situation. The four prototypes developed and tested in our laboratory exceeded the capability of the medicinal leech (Hirudo medicinalis) in removing blood from a clinically relevant congested flap model. The most effective prototypes (3a and 3b) sustained relatively stable bleeding rates for at least 4 hours. Furthermore, these prototypes do not possess the negative characteristics of live leech use.

In this study, the device concepts and concept manipulations were used to advance the long-term goals of minimizing skin surface (cosmetic) and underlying subcutaneous tissue destruction, maximizing therapeutic bleeding time, and maximizing therapeutic blood removal. The crossed stab incisions (concept 1, prototypes 2, 3a, and 3b) were less destructive and more easily repaired with respect to the skin surface versus the excisional punch biopsy used in prototype 1. By undermining between the dermal and hypodermal layers (8-mm to 10-mm diameter area), we presumably were able to tap into a greater number of large cutaneous vessels located between these layers. Thus, undermining created increased bleeding surface area without the excision of overlying skin.

Suction strength (concept 2, all prototypes) was chosen based on the prior observation that increased suction caused increased tissue damage (visible bruising) of the skin surface under the device. Blood vessel rupture and destruction (bruising) within the dermal and epidermal layers could possibly decrease bleeding time and volume. The use of chemical and mechanical anticoagulation of the skin surface via irrigation and turbulence (concepts 3 and 4, all prototypes) prevented obstructive clot formation on the skin surface that would impede the exit of blood from the wound.

Heparinization of the flap via six bolus injections of heparin (concept 5, all prototypes) most likely minimized thrombosis formation within the flap. The extent of this minimization needs to be studied further to determine the optimal use of heparin in areas distant to the actual device application site. The hydrogel and microporous polyethylene disk (concept 5, prototypes 3a and 3b) allowed for innovative subcutaneous anticoagulation (chemical and mechanical). The slow release of heparin at the bleeding edge of the wound via the disk presumably created a heparinized subcutaneous microenvironment. This microenvironment was more effective at sustaining bleeding than continuously injecting heparin at three sites 5 mm to 8 mm from the wound center (prototype 2). Furthermore, the combination of heparin infusion into the disk and disk rotation (concept 6, prototype 3b) was the best modality for sustaining bleeding past 3 hours, most likely because of the added disruption of subcutaneous clot formation. Optimization of heparin concentration for disk infusion and optimization of disk rotation timing will be studied in future studies.

The amount of decongestion obtained by treating a congested flap with prototype 3b was encouraging, in that an entire 6-cm ∞ 7-cm (42-cm2) flap was visually decongested after 4 hours of complete venous obstruction. In comparison, the maximum skin surface area decongested by a medicinal leech was a 1.6-cm diameter area (4-cm2) under identical conditions, when evaluated via laser Doppler imaging and visual assessment of improvements in skin color [12]. Furthermore, maximal decongestion by a medicinal leech was short-lived, occurring during the latter half of active feeding (~30 to 40 minutes) and the first hour of passive bleeding after the leech detached.*1

In summary, prototype 3b demonstrated excellent potential to replace the use of medicinal leeches for the treatment of surgically uncorrectable venous congestion. Extended protocols to study the efficacy of prototype 3b for the successful treatment of congested fasciocutaneous flaps in swine will be the next stage in developing a medicinal leech replacement. Through further concept optimization, testing, and clinical trials, we are confident that a commercially viable medical device can be produced in approximately 2 to 3 years.

The development of a mechanical device for the treatment of venous congestion appears critical, especially considering the many drawbacks of medicinal leech therapy and the recent advancements in microsurgery that involve replantation and transplantation of large regions of tissues, including entire hands [26,27]. The development of such a medical device would have significant societal benefits. Namely, the psychological trauma and limited effectiveness of medicinal leech use would be overcome in modern medicine.

CONCLUSION

Four mechanical device prototypes were developed and tested for the removal of excess blood from congested fasciocutaneous flaps. The two prototypes that used an innovative subcutaneous anticoagulation technique removed significantly larger blood volumes, relative to the medicinal leech. Furthermore, we were able successfully to decongest a 6- ∞ 7-cm fasciocutaneous flap using the most effective prototype over a 4-hour period of complete venous obstruction. These findings are encouraging with respect to the development of a mechanical device to replace the medicinal leech for the treatment of venous congestion.

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1. *Unpublished observations, Conforti ML, 2000.

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