Angularis oris axial pattern buccal flap for reconstruction of recurrent fistulae of the palate

OBJECTIVE: To describe the use of an axial pattern flap based on the angularis oris artery and vein for reconstruction of palate defects. STUDY DESIGN: Clinical case report ANIMALS: Two dogs with recurrent oronasal fistulae. METHODS: Oronasal fistulae previously treated by buccal mucosal random pattern flaps that subsequently dehisced were repaired using an angularis oris-based buccal tissue axial pattern flap. This flap was developed by full thickness incision of the cheek tissue, excluding the skin, about the angularis oris vascular pedicle resulting in a vascularized flap covered by oral mucosa on one side. RESULTS: In one dog, the repair was intact and healed 6 months after surgery. In the second dog with a fistula that resulted because of radiation necrosis, approximately 95% of the defect healed with a small (<1.0 cm(2)) area of dehiscence. Repair of this persistent fistula with a random pattern buccal flap failed and this small fistula remained with minimal clinical signs. CONCLUSION: An axial pattern flap based on the angularis oris artery and vein can be used to repair difficult or recurrent palate defects. CLINICAL RELEVANCE: Angularis oris axial pattern flaps provide an additional effective option for repair of defects in the hard and soft palate to the distal gingival margin of the canine tooth or beyond, depending on skull conformation. Advantages of this flap include its highly vascular and robust character, high degree of mobility and a surface of tough buccal mucosa.     

The Isolated Perfused Equine Skin Flap Preparation and Metabolic Parameters

A model for the study of equine cutaneous physiology, pharmacology, and toxicology was developed. Four 4 x 12 cm and twenty-one 6 x 12 cm single-pedicle axial pattern skin flaps based on the caudal superficial epigastric artery, and eight 6 x 12 cm flaps based on the saphenous artery and medial saphenous vein, were raised and sutured in a tubed configuration. On day 2, each flap was removed, the artery was cannulated, and the flap was perfused with a modified Krebs-Ringer's albumin-based medium for at least 6 hours. Flap viability was assessed by glucose use, lactate production, and histologic examination at the end of the perfusion period. The 4 x 12 cm flaps had evidence of skin necrosis, but the 6 x 12 cm flaps remained histologically viable. Results were compared to those previously reported from perfusion of porcine skin flaps based on the caudal superficial epigastric artery. While the ratios of glucose use to lactate production were similar, equine flaps used less glucose and produced less lactate per gram of tissue than similar pig flaps. Equine skin flaps perfused by saphenous vessels used more glucose and produced more lactate than flaps perfused by caudal superficial epigastric vessels. These results indicate that conclusions drawn from cutaneous physiology studies should not be extrapolated across species lines and that site-specific skin should be used for cutaneous physiology, pharmacology, and toxicology studies. The identified skin flaps may have applications in equine reconstructive surgery.     

Axial pattern flap based on the lateral caudal arteries of the tail in the dog: an experimental study

OBJECTIVE: To determine applicability and size limits of an axial pattern flap based on the lateral caudal arteries in dogs to reconstruct caudodorsal trunk skin defects. STUDY DESIGN: Experimental study. ANIMALS: Ten mature, mixed breed dogs. METHODS: The lateral caudal vessels of the tail were incorporated in the flaps of the treatment group (n=5) and were ligated in the control group (n=5). Flaps were rotated and placed into experimentally created caudodorsal skin defects on the trunk. The length and area of tissue that remained viable in each flap were determined. RESULTS: Mean (+/-SD) survival area (222.8+/-32.9 cm2) and length (25.1+/-4.5 cm) of vascularized flaps were significantly greater (P<.05) compared with control flaps (94.9+/-13.4 cm2 and 14.61+/-4.7 cm). Necrosis occurred in all control flaps, resulting in lower percentage flap area (48.8%) and length (47.1%) survival compared with vascularized flaps (78.1%, 77.5%). CONCLUSIONS: Axial pattern flap based on lateral caudal arteries of the tail was successfully elevated and transferred in a single procedure, with 78% survival for closure of large experimentally created caudodorsal trunk defects in dogs. CLINICAL RELEVANCE: Large cutaneous defects of the caudodorsal trunk area in dog could be reconstructed with tail axial pattern flap. Limitations in terms of size and changes in animal appearance have to be considered before flap elevation.     

Axial Pattern Flap Based on the Superficial Temporal Artery in Cats: An Experimental Study

Objective — The purpose of this study was to determine the surgical guidelines for and the survivability of an axial pattern flap based on the superficial temporal artery in cats.
Study Design — The mean survival length and mean percentage area of survival of flaps after 7 days in control and experimental groups, are assessed and compared.
Animals — Ten mature, domestic shorthair cats.
Methods — The superficial temporal artery and vein were incorporated in the flaps of the experimental group (n = 5) and were ligated in the control group (n = 5). Seven days postoperatively, the length of tissue that remained viable in each flap was determined by measurement of the length of the grossly devitalized tissue and subtracting this from total flap length. Results — Mean width and length of all flaps was 2.0 ± 7.0 cm, respectively. Mean survival length (±SD) of experimental and control flaps was 6.9 (0.2) cm and 4.4 (2.2) cm, respectively. Necrosis occurred in all control flaps, resulting in a mean percentage area of survival of 62.8 (11.7)%, compared with 98.6 (3.2)% for experimental flaps. Results were significantly different (P <.05) between the experimental and control groups.
Conclusions — A flap based on the superficial temporal artery may be a source of skin for reconstructive procedures of the maxillofacial region in cats.
Clinical Relevance — Knowledge of the anatomic landmarks and survivability of an axial pattern flap are essential considerations when planning a reconstructive technique.     

Axial pattern flap based on the caudal auricular artery in dogs

An axial pattern flap that was based on the sternocleidomastoideus branches of the caudal auricular artery and vein was developed. Control flaps, which included ligation and division of the caudal auricular artery and vein, were similarly developed on the contralateral aspect of the neck. Mean survival of caudal auricular artery axial pattern flaps (85.2%), compared with control flaps (63.9%), was significantly different (P less than 0.05). On the basis of results of this study, an axial pattern flap based on the sternocleidomastoideus branches of the caudal auricular artery and vein may be a source of skin for reconstructive procedures of the head and neck.     

Development of surgical techniques for preparation of in vitro-isolated perfused porcine skin flaps for percutaneous absorption studies

We developed a single-pedicle, axial pattern tubed skin flap that could be transferred to an in vitro perfusion apparatus. On the basis of results of prosections, angiography, contact radiography, and surviving-length studies, it was concluded that a single-pedicle, axial pattern skin flap measuring 4 cm x 12 cm incorporating the caudal superficial epigastric artery would survive to its entire length. Subsequently, a surgical (stage 1) procedure was developed for the routine preparation of single-pedicle, axial pattern tubed skin flaps. Healing after the stage-1 procedure was evaluated by visual inspection and fluorescein angiography. Stage-1 procedures were performed successfully 149 of 160 (93%) times. A second surgical (stage 2) procedure was developed for routine cannulation of the caudal superficial epigastric artery and harvest of the tubed skin flap. Stage-2 procedures were performed successfully 136 of 144 (94%) times.     

Clinical evaluation of random skin flaps based on the subdermal plexus secured with sutures or sutures and cyanoacrylate adhesive for reconstructive surgery in dogs

OBJECTIVE: To evaluate the use of subdermal plexus skin flaps for closing defects after excision of cutaneous and subcutaneous tumors in dogs and to compare outcome of flaps secured with sutures and those secured with butyl-cyanoacrylate and intermittent sutures. STUDY DESIGN: Clinical study. ANIMALS: Fifteen dogs. METHODS: After excision of cutaneous or subcutaneous tumors the skin defect was reconstructed by random flaps based on the subdermal plexus. Flap skin edges were apposed with simple interrupted 4-0 monofilament nylon sutures (group 1; 5 dogs) or nylon sutures alternated with butyl-cyanoacrylate adhesive (group 2; 10 dogs). Flaps were evaluated every 48 hours when bandages were changed, until complete healing. RESULTS: Random flaps based on the subdermal plexus were effectively used to close wound defects; mean flap survival was 89%. Partial flap necrosis occurred in 4 dogs. Wound margins apposed with butyl-cyanoacrylate had thinner and more esthetic scars than sutured margins. CONCLUSION: Random flaps based on the subdermal plexus proved to be versatile for covering limb wounds after excision of cutaneous or subcutaneous tumors. Mean survival rate was comparable to that reported for axial pattern flaps. Butyl-cyanoacrylate adhesive was easy to apply, allowed accurate margin apposition with good cosmetic outcome and reduced sutures needed. CLINICAL RELEVANCE: Cyanoacrylate adhesive should be considered in lieu of suture closure to secure random skin flaps based on the subdermal plexus in dogs.     

Axial Pattern Flap Based on the Cutaneous Branch of the Superficial Temporal Artery in Dogs: An Experimental Study and Case Report

OBJECTIVE: To determine the anatomic guidelines and viability of an axial pattern flap based on the cutaneous branch of the superficial temporal artery (STA) in dogs. Application of the flap in a clinical patient is reported. STUDY DESIGN: Flap viability in control and experimental groups was determined 7 days postoperatively. ANIMALS: A total of 14 mature, mesaticephalic dogs; 1 clinical patient. METHODS: The cutaneous branch of the STA and vein were incorporated in the flaps of the experimental groups (group A, n = 5; group B, n = 4) and were ligated in the control group (n = 5). Flap length was extended in experimental group B. Seven days postoperatively, the length and area of tissue that remained viable in each flap was determined and compared with similar measurements performed intraoperatively. Cutaneous fluorescence was also used postoperatively to assess flap perfusion. The flap used in the clinical patient had the same dimensions as flaps developed in group A. RESULTS: Mean survival length (+/- SD) of STA flaps [group A, 9.1 (0.8) cm], was significantly increased (P < .05) compared with control flaps [7.0 (0.6) cm]. Percentage flap length survival (+/- SD) of STA flaps [group A, 91.8 (8.9)%], was significantly increased (P < .05) compared with control flaps [71.6 (7.0)%]. Mean percentage area of survival (+/- SD) of STA flaps [group A, 93.1 (7.5)%], was significantly increased (P < .05) compared with control flaps [73.5 (7.4)%]. Group B flaps had a mean survival length of 10.4 (1.1) cm, percentage flap length survival of 69.5 (4.8)%, and mean percentage area of survival of 69.1 (6.5)%. There was no positive correlation between the area of flap fluorescence at days 0, 1, and 3, and the area of flap survival. Application of the flap in a clinical patient allowed primary wound reconstruction with 100% survival. CONCLUSION: A flap based on the cutaneous branch of the STA may be a source of skin for reconstructive procedures of the maxillofacial region in dogs. CLINICAL RELEVANCE: Knowledge of the anatomic landmarks and expected viability of a STA axial pattern flap is essential before consideration of its use as a reconstructive surgical technique.     

Assessment of a caudal external thoracic artery axial pattern flap for treatment of sternal cutaneous wounds in birds

OBJECTIVE: To assess the use of a caudal external thoracic artery axial pattern flap to treat sternal cutaneous wounds in birds. ANIMALS: 16 adult Japanese quail. PROCEDURE: A cutaneous defect in the region of the mid-sternum was surgically created in all quail. In 6 quail (group I), an axial pattern flap was created from the skin of the lateral aspect of the thorax and advanced over the sternal defect. In 8 quail (group II), a flap was similarly created and advanced but the flap vasculature was ligated. All quail were euthanatized at 14 days after surgery and had necropsies performed. Sections of the flap and the surrounding tissue were examined histologically to assess flap viability. RESULTS: All axial pattern flaps in group-I quail had 100% survival. In group II, mean percentage area of flap survival was 62.5%; mean area of necrosis and dermal fibrosis of flaps were significantly greater than that detected in group I. In flaps of group-II quail, neovascularization in the deep dermis and profound necrosis of the vascular plexus in the superficial dermis were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the caudal external thoracic artery axial pattern flap could be used successfully in the treatment of surgically created sternal cutaneous defects in quail with no signs of tissue necrosis or adverse effects overall. Use of this technique to treat self-mutilation syndromes or application after surgical debulking of tumors or other masses might be beneficial in many avian species.     

Pedicle skin flaps in ponies: viable length is related to flap width.

The relationship between pedicle flap width and viable length was characterised for skin flaps of the flank in ponies. Four dorsally based, pedicle type skin flaps of 20 cm in length and 3, 6, 9 or 12 cm in width were created in a random sequence on one flank in each of 10 ponies. Flap survival length was assessed by skin texture and appearance, depilation of hair and wound healing at 14 days after surgery. There was considerable variation between animals in the viable length of flaps of the same width; however, a significant difference in the viable length of flaps of different widths was detected (P = 0.002). The viable length of the 3 cm flaps was significantly different from that of the 12 cm flaps (9.69 +/- 1.1 cm vs 12.97 +/- 1.0 cm, mean +/- se P less than 0.05). There was a positive correlation between flap width and viable length (r2 = 0.141, P = 0.017). There was no effect of flap order (cranial to caudal positioning relative to the other flaps) on viable length (P = 0.286). The results of this study demonstrate a significant relationship between flap width and viable length, confirming a previously unsupported assumption that flap width and viable length are related. These findings suggest that the clinician should employ broad pedicles when using local flaps to reconstruct skin defects on the flank of the horse.     

Effects of ring diameter and wire tension on the axial biomechanics of four-ring circular external skeletal fixator constructs.

OBJECTIVE: To determine relative effects of ring diameter and wire tension on axial biomechanical properties of 4-ring circular external skeletal fixator constructs. SAMPLE POPULATION: 4-ring circular external skeletal fixator constructs and artificial bone models. PROCEDURE: 4-ring constructs were assembled, using 50-, 66-, 84-, or 118-mm-diameter rings. Two 1.6-mm-diameter fixation wires were attached to opposing surfaces of each ring at intersection angles of 90 degrees and placed through a gap-fracture bone model. Three examples of each construct were loaded in axial compression at 7 N/s to a maximum load of 400 N at each of 4 wire tensions (0, 30, 60, and 90 kg). Response variables were determined from resulting load-displacement curves (construct stiffness, load at 1 mm of displacement, displacement at 400 N). RESULTS: Ring diameter and wire tension had a significant effect on all response variables and had a significant interaction for construct stiffness and displacement at 400 N. Significant differences within all response variables were seen among all 4 ring diameters and all 4 wire tensions. As ring diameter increased, effect of increasing wire tension on gap stiffness and gap displacement at 400 N decreased. Ring diameter had a greater effect than wire tension on all response variables. CONCLUSIONS AND CLINICAL RELEVANCE: Although effects of wire tension decrease as ring diameter increases, placing tension on wires in larger ring constructs is important because these constructs are inherently less stiff. The differential contribution of ring diameter, wire tension, and their interactions must be considered when using circular external skeletal fixators.     

Clinical evaluation of axial pattern skin flaps in dogs and cats: 19 cases (1981-1990).

Nineteen axial pattern skin flaps were used in 16 dogs and cats to provide skin for repair of extensive cutaneous defects. Retrospective evaluation of medical records was used to determine percentage flap survival, postoperative complications, and long-term outcome of axial pattern skin flaps. The most common indication for use of axial pattern flaps was to augment wound closure following tumor resection (n = 7). Other indications included trauma (n = 5), chronic nonhealing wounds (n = 4), urine-induced cellulitis (n = 1), idiopathic dermal necrosis (n = 1), and chronic lymphoplasmocytic dermatitis (n = 1). Mean flap survival (+/- SD) was 96% (+/- 8). Postoperative complications included wound drainage (n = 15), partial dehiscence of the sutured flap (n = 7), distal flap necrosis (n = 6), infection (n = 3), edema (n = 3), and seroma formation (n = 2). After a median follow-up time of 5 months, evaluation of animals indicated that surgery provided successful wound reconstruction with good cosmetic results. Reconstruction of large cutaneous defects is facilitated by axial pattern flap application regardless of cause of wound. Postoperative complications are common but amenable to standard wound management techniques such as drain placement and surgical debridement of devitalized distal flap skin.     

Tensions used on girths on thoroughbred racehorses

OBJECTIVE: To determine commonly used girth tensions in Thoroughbred racehorses in the Melbourne metropolitan area. DESIGN: A prospective industry survey. METHODS: Strappers were instructed to tension girths, using the same saddle, under-saddle packing and girth, sufficiently to hold the saddle for racing. These tensions were continuously recorded by an in-line load cell in the girth. Seventeen strappers from five stables participated in the study, which was conducted on 91 horses. RESULTS: Resting girth tensions varied considerably. The mean tension on inhalation was 13 +/- 0.4 kg. Male strappers recorded higher tensions than females for all indices measured. Age and girth size of the horse did not significantly influence results. CONCLUSION: This study confirms that there is no standard for application of a girth and saddle in the Thoroughbred racing industry and the range of tensions applied was large. Strappers were unable to reliably apply the same tensions between horses. Values recorded at the extremes of the range seem inappropriate for racing conditions as low values would result in slippage of the saddle and higher values may result in girth galls and possible reduction in athletic performance. Further work is necessary to determine the point at which girth tension affects performance.     

Use of local and axial pattern flaps for reconstruction of the hard and soft palate

There are numerous conditions that may result in defects of the hard and soft palate. Reconstruction of these defects may be difficult due to anatomical limitations and limited tissue availability. The majority of palate defects, even when large, may be closed using local and/or axial pattern flaps, while other more advanced techniques such as free tissue transfer and prosthetic implants are required in a smaller number of cases. This article describes the use of local and axial pattern flaps in the reconstruction of the hard and soft palate.     

Use of laser Doppler flowmetry to determine blood flow in and viability of island axial pattern skin flaps in rabbits

Perfusion and viability of island axial pattern skin flaps were tested in 37 healthy New Zealand white rabbits, using laser Doppler monitoring of blood flow in the capillary loops and the subpapillary plexus of the dermis. Skin flaps, selected on the basis of the caudal superficial epigastric vein and artery, were lifted and replaced in their original locus after selective occlusion of their vascular pedicles. Subjects were allotted into groups: control group (n = 10); arterial occlusion (n = 7); venous occlusion (n = 10); and arterial and venous occlusion (n = 10). The rabbits were monitored from 48 hours before surgery until euthanasia 48 to 72 hours after replacement of the flap. Flap viability was assessed on a clinical basis, using a comparative scoring method based on a numeric scale. The degree of necrosis in histologic sections was evaluated, using a scoring system. Laser Doppler measurements were obtained on 3 consecutive days before surgery, to establish the normal basal blood flow in the skin. Postsurgical measurements were obtained at 2-hour intervals for the first 8 hours and at 24, 48, and 72 hours after surgery. Measurements of basal blood flow varied significantly (P less than 0.05) from site to site on the surface of individual flaps and over time. When laser Doppler flowmetric (LDF) measurements from 6 sites on a flap were used as a measure of laser Doppler flow for the total flap, there was no significant difference between contralateral flap areas outlined on the abdomen of the rabbits. Temporal variations over 3 days for each rabbit or among rabbits were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

基于机器学习的阿勒泰地区草地地下生物量估测与数字制图

为精准估算草地地下生物量,分析其水平及垂直空间格局,实现草地地下生物量(BGB)的数字制图。调查了2015年阿勒泰地区草地生长季节(6-8月)的生态要素和地下生物量。以地理位置、地形、气候、土壤和植被中的代表性信息为基础,基于机器学习算法估测研究区0～30 cm的草地地下生物量,并根据估测结果利用空间插值法得到地下生物量的空间分布格局,最终实现草地地下生物量的数字制图。结果表明:1)相比偏最小二乘回归(PLS)和随机森林模型(RF),支持向量机模型(SVM)在0～10 cm、10～20 cm和20～30 cm土层地下生物量的估测中表现出最高的精度,验证集数据的精度(R²)依次为0.77、0.67和0.69,相应的RMSE为245.56、98.81和63.58 g·m^-2。从空间插值的效果看,反距离权重插值(IDW)优于径向基函数插值(RBF)和张力样条插值(SPL)。2)进一步比较了不同估测模型与空间插值方法间的组合能力,结果显示,在阿勒泰地区的草地地下生物量研究中,SVM+IDW是可靠的估测模型和空间化方法的组合。在0～10 cm、10～2...     

Use of skin stretchers to elongate a peninsular thoracodorsal axial pattern flap for antebrachial wound closure in a dog

Objective: To describe preoperative use of skin stretchers to elongate a peninsular thoracodorsal axial pattern flap to close a large antebrachial wound on a dog. Study Design: Case report. Animals: A 21 kg, 7‐year‐old, male intact mixed breed dog. Methods: Two skin stretchers were applied to the site of the thoracodorsal axial pattern flap 4 days before surgery. The elastic cables connecting the adhesive pads were tightened daily to increase the skin available for a peninsular thoracodorsal axial pattern flap, which was created and rotated 180° to cover an antebrachial defect to a level 2 cm proximal to the carpus. Results: The entire flap survived; there was a small amount of incisional separation at the distal margin of the flap that healed without further treatment. Conclusion: Preoperative skin stretching provided additional skin for the axial pattern flap used.     

Effects of Epidural Anesthesia on Microcirculatory Blood Flow in Free Medial Saphenous Fasciocutaneous Flaps in Dogs

OBJECTIVE: To assess the effects of epidural anesthesia using lidocaine on microcirculatory blood flow, volume, and velocity in free fasciocutaneous flaps in dogs. Study Design-In vivo experimental investigation. Animal Population-Ten adult dogs weighing 20 to 25 kg. METHODS: A medial saphenous fasciocutaneous free flap was removed and an orthotopic transfer was performed by anastomosing the primary flap vessels back to the medial saphenous vessels. Blood flow (mL(LD)/min/100 g), volume (%volume or tissue hematocrit) and velocity (mm/s) in the flap were recorded throughout the procedure. After epidural anesthesia, blood flow, volume, and velocity values were again recorded. RESULTS: Microcirculatory blood flow, volume, and velocity, as measured by a laser-Doppler flowmeter, failed to reveal any significant changes over time. Immediately after epidural anesthesia, mean arterial pressure was significantly reduced and remained depressed throughout the experimental procedure. CONCLUSIONS: Epidural anesthesia combined with general anesthesia does not improve microcirculatory flow in free flaps in the pelvic limbs of dogs. No significant change in blood flow to the medial saphenous fasciocutaneous free flap occurred after division and anastomosis of the vascular pedicle. CLINICAL RELEVANCE: We recommend that epidural anesthesia with 2% lidocaine be used with caution in dogs undergoing microvascular free-flap transfer.     

Contractile activity of cultured adult Dirofilaria immitis

A method for long-term maintenance of adult heartworms (HW) in culture for use in contractile activity studies was developed. Culture conditions included Eagle's minimum essential medium (MEM) containing Earle's balanced salt solution and MEM vitamins and supplemented with 10% horse serum, pH 7.6, 37 degrees C, and humidified 5% CO2:95% room air atmosphere. Motility was observed for up to 91 days. Reducing the culture atmosphere from 20% oxygen to 5% oxygen reduced acid production and survival to 28 days or less. Spontaneous contractile activity of adult HW coils (1 cm diameter) was measured using an isometric force displacement transducer system. Activity had an arrhythmic pattern of good magnitude that could be recorded after up to 50 days in culture for male HW and after up to 40 days in culture for female HW. Analyses of contractile activity included determination of its amplitude, frequency, contraction index, and basal tension. Amplitude for males (3.4 +/- 1.2 g) (mean +/- S.D.) was significantly greater (P < 0.02) than that for females (3.0 +/- 1.1 g), whereas frequency for females (8.2 +/- 2.3 min) was significantly greater (P < 0.03) than that for males (7.5 +/- 2.3 min). The contraction index for females was 16.7 +/- 13.7 mm/min and for males, 14.4 +/- 9.0 mm/min. The difference was not significant. The contraction index was based on line integration of the record of contractile activity. Amplitude and frequency of contractile activity for anterior segments (2.5 cm), suspended lengthwise, from cultured adult female HW, were not significantly different from results for coils, but the contraction index (34.5 +/- 33.8) was significantly higher (P < 0.01) indicating that the pattern of activity was more uniform in the segments. An applied basal tension of about 4 g was suitable for the coils, while a suitable basal tension for segments was about 1.5 g. For coils, amplitude, frequency, and contraction index increased significantly (P < 0.02) with increase in basal tension. Coils were not sensitive to changes in ionic, glucose, oxygen, and osmol concentrations, and pH (6.8-7.6) of the bathing solution. A pH of 8.0 markedly increased basal tension and contractile activity. At 20 degrees C contractile activity stopped. These effects of pH and temperature were reversible. The HW appeared resistant to changes in their environment. This is probably related to an efficient cuticular barrier. The culture and recording methods used in this study open improved opportunities for quantitative evaluation of responsiveness of HW to a variety of physiological and pharmacological factors.