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Regen Med. Author manuscript; available in PMC Jul 19, 2013.
Published in final edited form as:
PMCID: PMC3715838
EMSID: EMS53379
Auto-bionics – a new paradigm in Regenerative Medicine and Surgery
Hutan Ashrafian,* Ara Darzi, and Thanos Athanasiou
Department of Biosurgery and Surgical Technology, Imperial College London
*Corresponding author: Hutan Ashrafian, Wellcome Trust Research Fellow and Surgical Registrar, The Department of Biosurgery and Surgical Technology, Imperial College London. 10th Floor, Queen Elizabeth the Queen Mother (QEQM) Building, Imperial College Healthcare NHS Trust at St Mary’s Hospital, Praed Street, London, W2 1NY, United Kingdom. h.ashrafian/at/imperial.ac.uk. Telephone: +44 (0)20 7886 7651, Fax: +44 (0)20 7886 6309.
The concept of bionics represents the development of engineering and technology based on natural biological systems. Traditional applications of bionics in healthcare include artificial bionic organs which can be used to replace, mimic and even enhance biological function when compared to native organic equivalents (so-called ‘Exo-bionics’). Recently there has been a new wave of bio-inspired treatments that act through the reorganisation of the existing biological organs in an individual to enhance physiology. Here the technology does not replace biological tissue, but augments function by tissue reorganization and modification – so-called ‘Auto-bionics’. Examples include the Ross (Pulmonary Autograft) Procedure, Cardiomyoplasty, Skeletal-Muscle-Ventricles, Graciloplasty and Metabolic Gastric-Bypass (gastrointestinal rearrangement to modulate hormone release and treat diabetes). These procedures will have an increased role in reconstructive strategies and the treatment of obesity, diabetes, cardiovascular disease and cancer. Auto-bionics can enhance physiological function beyond normality in some cases and represents a new era in bio-inspired versatility.
Keywords: Bionics, Biomimicry, Ross Procedure, Cardiomyoplasty, Skeletal Muscle Ventricle, Graciloplasty, Bariatric, Gastric Bypass, Metabolic Surgery
The development of tools to treat injury and disease has been one of mankind’s earliest legacies. Luminaries such as Leonardo da Vinci ignited the development of engineering concepts that could be applied to the human body.[1, 2] In 1958, the air force physician Jack Steele first proposed the term bionics (also termed biomimetics)[3, 4] to represent the application of biological processes for the design of synthetically engineered objects. Many of these proposed bionic objects were anticipated to be functional aids for injured humans.
Advances in materials sciences, electrical engineering, biochemistry, enhanced biomaterials, robotics, tissue engineering and computing power have led to significant developments in medical bionics. As a result, this field is now recognised as an important component of modern biotechnological healthcare treatments (Figure 1).
Figure 1
Figure 1
Regenerative medicine and surgery
Common examples of bionic therapies include mechanical limb prostheses, artificial muscles and hearts, retinal and cochlear implants.[4, 5] On occasion some of these bionic aids do not only act as ‘tissue replacements’, but rather out-perform their dynamic human equivalents. This includes the case of the athlete Oscar Pistorius who has no legs, yet can outperform other ‘normal bodied’ sprinters when utilising his carbon fibre leg prostheses.[6, 7]
The current lack of biological organs available for tranplantation,[8] and the continued difficulties of immunosuppresion[9] have led to our need for the increased development of bionic therapies. Many of these ‘conventional’ bionic therapies largely focus on electronic or artificially engineered treatment solutions. The use of these external synthetic therapies can therefore be considered as ‘Exo-bionic’ treatments (Greek exo - external). A converse paradigm however also exists. Here human treatment and enhancement can take place through the re-organisation and re-design of inherent organs and tissue within each individual – the process of Auto-bionics (Greek auto - self) (Table 1).
Table 1
Table 1
Definitions of Auto-bionic and Exo-bionic
The application of Auto-bionic treatments is relatively new, and medical technology has only recently realised the benefits of such a concept. Some uses are static and include skin grafting, arterial and vein grafts for coronary operations and the use of muscle flaps in reconstructive surgery. However some auto-bionic therapies are active and result in dynamic or metabolic changes (Figure 2). Examples include heart and sphincter enhancement through dynamic myoplasty and metabolic pancreatic augmentation through metabolic surgery. Furthermore, just as in exo-bionics where an artificial prosthetic can hyper-augment normal function, some auto-bionic treatments can also lead to a supra-physiological functioning of organs. We herein describe some relevant examples of dynamic and metabolic auto-bionics in modern healthcare.
Figure 2
Figure 2
Auto-bionics and Exo-bionics
Ross Procedure (replacing the aortic valve) - Synthetic exo-bionic cardiac valve replacement is fraught with long term anticoagulation problems, particularly in young patients. In order to overcome these difficulties, experimental models introduced the use of the pulmonary valve to replace the aortic valve.[10-12] Both valves were morphologically semilunar with three leaflets, and had similar function that permitted them to considered as substitutes for each other.[13] Donald Ross performed the first pulmonary valve autograft to replace an aortic valve in a human in 1967,[14] a procedure that has since been named after him as the ‘Ross Procedure’. Here the pulmonary valve is placed at the site of the aortic valve, and a homograft valve is placed at the pulmonary position (Figure 3a).
Figure 3
Figure 3
Cardiac Auto-bionics. (a) Ross Procedure, (b) Dynamic Cardiomyoplasty (c) Skeletal Muscle Ventricle
Despite the technical intricacy of this operation, it has gained increased favour worldwide in view of it’s long term durability,[15-17] excellent cardiac haemodynamics and ventricular remodelling.[18] The current indication for the Ross procedure includes the treatment of aortic valve disease not subject to repair in patients with a life expectancy of over twenty years. This is particularly useful for women who wish to childbear after this operation.[19, 20] The operation has gained particular favour for the paediatric population in cases of critical aortic stenosis, as artificial biological prostheses show accelerated calcification and degeneration.[21, 22] The auto-bionic nature of this procedure was confirmed by a study by Gorczynski that although the pulmonary valve has evolved in vertebrates to sit in the low pressure pulmonary system, its tensile strength within this procedure is superior to that of the aortic valve.[23] The success of this operation has led to the use of the pulmonary valve at other sites in the heart including the mitral position (Ross II procedure).[24]
Cardiomyoplasty and aortomyoplasty (improving cardiac function) – As early as the 1930’s, pectoral skeletal muscle was successfully applied to repair damaged and post-ischemic cardiac tissue.[25, 26] These skeletal muscle grafts had the advantage of developing collateral blood flow to the cardiac epicardium.[27, 28] This early success led to the mechanical application of diaphragmatic skeletal muscle to augment the pump function of failing hearts.[29-31] Just as in graciloplasty, the native skeletal muscle suffered from fatigue when used for continuous pump activity and was successfully overcome by transforming slow-twitch muscles by electrical stimulation.[32, 33] It was subsequently demonstrated that once the skeletal muscle was transformed, it could achieve ‘cardiac-like function’ continuously.[34]
Of the many skeletal muscles available for use in augmenting cardiac muscle, the latissimus dorsi was particularly applicable as an auto-bionic pump due to its proximity to the heart. This is because it could be harvested with its own native pedicle (blood supply), which would decrease any muscle ischaemia, and would naturally overcome any technical difficulties of finding alternative sources of oxygenated blood. In the mid 1980’s a latissimus dorsi wrap around the heart was introduced for the treatment of congestive cardiac failure – this was known as the Dynamic Cardiomyoplasty.[35] In this operation, the left latissimus muscle is typically harvested and detached from the humerus. The thoracodorsal artery, vein and nerve are kept intact. It is then wrapped around the cardiac ventricles and is stimulated by electrodes linked to an electrical pacemaking device. Both the geometry and the pacing device allow the muscle graft to contract with the ventricles in synchrony to the heart during cardiac systole (Figure 3b). The operation demonstrated early success by dramatically improving symptoms, typically reducing patients New York Heart Association (NYHA) functional class by 1.5. Dynamic cardiomyoplasty results in increased myocardial contractility, reduced left ventricular wall stress and less oxygen demand. It improves effective ventricular wall thickness, reduces left ventricular volumes and can induce beneficial reverse ventricular remodelling.[36-43]
The proposed mechanisms of cardiac benefit after these procedures include a passive “girdling” effect and a dynamic “systolic squeezing effect”,[42] where controversially some have reported the muscle graft to contract up to four times stronger than inherent cardiac mucle.[44] However many studies cannot consistently confirm treatment effectiveness in terms of cardiac output and ejection fraction. As the patient group for cardiomyoplasty have such significant heart failure their inherent perioperative mortality can be as high. Mortality rates are lower in experienced centres, and vary from 2.6%-31%.[45, 46] Some of the experimental studies of cardiomyoplasty revealed that the beneficial effects of the procedure were due to the wall stress relief of the skeletal muscle wrap as opposed to its contractile function. This had led to the development of the exo-bionic cardiac wrap treatments such as the CorCap™ CSD mesh (Acorn Cardiovascular)[47] or the Myosplint® device.[48] The current uses of cardiomyoplasty however still includes the treatment of patients with congestive heart failure, chronically depressed right ventricular function, some individuals with ventricular tumours and as a bridge to transplanation.[49]
In order to provide further skeletal muscle options to increase the inherent cardiac muscle pump function, other auto-bionic procedures have been developed to address congestive cardiac failure. Of these aortomyoplaty resembles cardiomyoplasty in that it involved the wrapping of skeletal muscle around the ascending or descending thoracic aorta.[50, 51] This procedure has the advantage of increased technical ease although it has the possible disadvantages of dislodging atherosclerotic plaques or constricting the pulmonary vessels. It is currently still considered an experimental procedure, although early studies in a canine model demonstrate that it can offer provide haemodynamic support equivalent to that of an Intra Aortic Balloon Pump.[50]
Skeletal Muscle Ventricles (improving cardiac function) are also still in their experimental phase as an auto-bionic therapy. In this procedure, the skeletal muscle from latissimus dorsi ventricles is applied to form an accessory cardiac pump (Figure 3c) as opposed to directly augmenting the contractility of the heart or vessels as in cardiomyolpasty or aortomyoplasty. The concept of an accessory heart is well known in other biological systems,[52] and an added pumping chamber in series with the native heart is common in current exo-bionic hearts.[53]
The procedure involves mobilising the latissimus dorsi muscle and wrapping it concentrically around a mandrel in the shape of a conical spiral that approximates to the size of a subjects ventricle. This is left in the chest cavity and is electrically conditioned in order to transform the muscular wrap into a fatigue-resistant muscular cavity. After approximately six weeks, the mandrel is removed at the ventricular cavity can therefore act as an accessory cardiac pumping chamber.[34, 54] It is most commonly placed in continuity with the descending thoracic aorta to act as an aortic diastolic counterpulsator.
In order to decrease the rates of thromboembolism from the neo-ventricle, autologous pericardium is used to line the muscular cavity. This not only reduces thrombotic risk, but also adds structural integrity to the artificial chamber. Skeletal muscle ventricles therefore have an advantage over synthetic exo-bionic organs as, they do not add the complications of sever anti-coagulation and furthermore do not suffer from subsequent rupture.[55, 56]
These auto-bionic skeletal muscle ventricles have been demonstrated to function well in an animal model for over 4 years,[57] and have an added ability to permit the successful seeding of autogenous endothelial cells.[58] Haemodynamically, they can pump 464mL/min against an afterload of 80mmHg and a preload of 40-50mmHg, generating 194% of the left ventricular stroke work.[59, 60] After four hours, they can generate 0.68 × 106 erg of stroke work, approximately half that of the left ventricle.[61] Skeletal muscle ventricles can provide a cardiac assist contribution that is at least equal to that of the well established intra-aortic balloon pump (IABP),[62] and at 836 days they can still produced 19% diastolic augmentation.[63]
Other configurations for the skeletal muscle ventricle also exist. These include the pump placed between the left atrium and aorta which can produce a power output that corresponds to 22% of left ventricular power.[64] A left ventricular apex to aorta model also exists where the pump can produced 40-47% of the systemic output and increase the mean diastolic pressure by as much as 73%.[65]
These auto-bionic procedures therefore demonstrate significant potential, and are constantly evolving towards ‘real-life’ applications. Current developments include muscle conditioning though improved pacing systems and the use of vascular delay[46] that prepares a mobilised muscle in-vivo before final use as a pump.
Graciloplasty (Creating a functional anal sphincter) - Gracilis is a muscle that lies medially in the adductor compartment of the thigh. Although it is large in all quadrupeds,[66] in hominids it is small and acts only as a weak adductor. It’s role in human locomotion is therefore negligible, and it has been termed light-heartedly by some anatomists as the ‘custodes virginitatis’.[67] As a result of this muscle’s functional redundancy it has therefore been applied for various uses in reconstructive surgery.[68, 69]
In 1952, Pickrell and colleagues first described the use of applying the gracilis muscle to form a rectal neo-sphincter in the treatment of anal incontincence.[70] Although this had some success, a need for improved continence in patients with congenital and acquired anorectal dysfunction who had sphincter function too poor for the consideration of sphincteroplasty resulted in the development of dynamic graciloplasty (DGP).
In dynamic graciloplasty, the gracilis muscle is explanted and then transposed to encircle the anal canal. The aim of this procedure is to bring about changes in the fast-twitch fatigable (Type II) muscle fibres of gracilis to transform them into slow-twitch, fatigue-resistant (Type I) muscle fibres that more closely resemble the histological characteristics of the internal anal sphincter. The gracilis in its normal state only has 43% type I fibres as opposed to the anal sphincter which has 80% type I fibres.[71] The muscle is ‘wrapped’ around the anal canal forming either alpha, gamma (most common) or epsilon loops to reflect the patient’s pelvic anatomy. An electric neurostimulator placed in the tissue of the lower abdominal wall, and communicates with the gracilis muscle via electrodes. The neurostimulator discharges a current that contracts the muscle (for the majority of the day), however when stimulation is turned off, the muscle relaxes and defecation occurs.
Indications for this operation include congenital anal atresia or spina bifida, whilst acquired conditions include severe neural damage, or some patients who have already undergone abdominoperinal resection or total anorectal reconstruction for anorectal neoplasms. The mechanism of this auto-bionic transformation is that type I and II muscle fibres can be transformed interchangeably depending on the motor neurone supply they receive. Thus transposing a nerve for a type I muscle onto a type II, it will induce changes to adopt type I morphology. Similarly, electrical stimulation of the muscle externally can produce similar effects.[33, 72]
Results for this operation are quoted to deliver continence rates between 35-85%, with a preponderance of higher success rates attributed to centres with higher procedural volumes. Although this procedure can dramatically improve the quality of life of patients when successful, it does carry mortality rates ranging from 0-13%. This auto-bionic procedure does demonstrate some considerable success in the face of significant disease and has demonstrated cost-effectiveness,[73] it’s direct competition is the exo-bionic procedure of implanting an artificial bowel sphincter (ABS). Both procedures have similar effectiveness in terms of continence, although the ABS demonstrates increased side effects in 82%-100% of patients compared to 74-82.8% for dynamic graciloplasty.[74, 75] It is clear that both procedures currently have unacceptably high complication rates, and the future of auto-bionic dynamic graciloplasty lies in further advances of muscle adaption (including the use of the Glutei and Sartorius). These auto-bionic neo-sphincters can then be applied in combination with other modalities such as biomaterials, gene therapy and stem cell therapy to augment treatment efficacy.
Roux-en-Y Gastric Bypass (improving insulin sensitivity and release) – The burgeoning pandemic of world obesity coupled with poor results of weight loss pharmacotherapy led to the development of ‘so-called’ weight loss or bariatric procedures to treat morbid obesity. It was soon realised however that these procedures did far more than simply weight loss. Pories and colleagues published on their series of gastric bypass in obese patients after a 14 year follow-up, reporting that in patients with type II diabetes mellitus, 83% achieved normal glucose level in the absence of medication.[76, 77] This was astounding at the time, as the improvement in glucose metabolism occurred within a few days of surgery before any noticeable weight loss. These findings were subsequently confirmed in numerous other studies. A large meta-analysis of 621 studies with 135,246 patients reported that in these bariatric operations, 78.1% of diabetic patients had complete resolution, and diabetes was improved or resolved in 86.6% of patients.[78] These operations have subsequently been termed as metabolic operations as they do not only deliver anatomical change but also induce metabolic benefits.[79]
The Roux-en-Y procedure (Figure 4) creates a small stomach pouch (<50ml) as a result of surgical partition of the upper part of the stomach. The remaining stomach accompanied by the duodenum and a segment of jejunum (‘biliopancreatic limb’) is then divided and anstomosed lower down the jejunum, with the segment distal to this forming a ‘common limb’. The free segment of jejunum is now anastomosed to the small stomach pouch(gastroenterostomy stoma) to complete the ‘Y’ shape of the Roux-en-Y thus becoming the ‘alimentary limb’. This rearrangement of alimentary organs allows processed food to ‘bypass’ the main portion of the stomach whilst maintaining the hormonal presence of the stomach within the alimentary tract and also preventing toxic biliary reflux.
Figure 4
Figure 4
Pancreatic Auto-bionics
These operations achieve weight loss by decreasing energy input (appetite and food intake) but also modulate energy expenditure (increasing metabolic rate) with only minimal impact calorie absorption.[79-81] Their dramatic effect on diabetes has been proposed to ensue from two main schools. One considers ingested nutrients bypassing the stomach which subsequently releases an altered ‘gut hormonal signal’ in the lower gut (hindgut hypothesis). Alternatively a lack of nutrients in the main body of stomach may result in ‘gut hormonal signals’ released from the upper gastrointestinal system (foregut hypothesis). Other factors may also come into play as each operation actually results in five biological changes.[79] These include (1) Bile Flow alteration, (2) Restriction of stomach size, (3) Altered flow of nutrients, (4) Vagal manipulation and (5) Enteric gut and adipose hormone modulation. The so called ‘BRAVE’ effects.
The gut hormones that are significantly increased by these operations include Glucagon-like peptide-1 (GLP-1) and Peptide YY (PYY). GLP-1 may have an important role in the resolution of diabetes as it protects against pancreatic Beta-Cells Against Apoptosis,[82] and also stimulates cAMP-dependent insulin exocytosis.[83, 84] Furthermore it acts on other systems such as the heart were it can act as an inotrope and may contribute to the beneficial reverse remodelling seen in the heart after these operations.[85] The auto-bionic nature of this metabolic procedure is further demonstrated in a rare group of patients who develop post-operative hyperinsulinaemic hypoglycaemia (nesidioblastosis).[86, 87] In the these patients, the pancreas has augmented supra-physiological insulin release, to the extent that some patients need to go on to undergo a partial pancreatectomy so as to maintain normal insulin levels.
The concept of auto-bionics – where the body is enhanced through the application of biological design in re-designing or rearranging inherent body tissue is expanding. Dynamic Graciloplasty, the Ross procedure, Dynamic Cardiomyoplasty, Skeletal Muscle Ventricles and Roux-en-Y gastric bypass are only some contemporaneous examples. These procedures can lead to novel treatments and physiological enhancements not only limiting our need for organ transplantation but also compete successfully against traditional exo-bionic therapies (such as artificial prostheses). The future of this field lies with continued research into inherent body physiology coupled with increased application of this novel area of bionics alongside other therapeutic modalities including genetic modification and stem cell therapy.
Auto-bionics will have an increased role in reconstructive strategies and the treatment of obesity, diabetes, cardiovascular disease and cancer. It has been known since the time of Hippocrates[88] that the nature of getting well is inherent within each individual. The concept of auto-bionics clarifies that the future of mankind’s healthcare is not only dependent on external technological advances, but also on how we can apply novel biological principles to transform our body systems using increasingly innovative methods.
Auto-bionic procedures are likely are increase in volume and variety. The lack of organs available for transplantation and the continuing improvements necessary for conventional exo-bionic procedures will lead to further requirements, adoption and development of auto-bionic concepts. These procedures can be augmented through the use of other regenerative medical technologies including developments in stem cell therapy. Ultimately this will allow the introduction of novel treatment strategies that can be purely auto-bionic or alternatively combination therapies. Specific uses will include the treatment of type II diabetes associated with the worldwide epidemic of obesity, but also for management of diabetic patients at lower weight categories. Auto-bionics will also play an increased role in cardiovascular treatments, cancer and reconstructive strategies.
Executive Summary
Concept
  • Auto-bionics is the application of biological principles to augment or replace physiological functions by manipulation of inherent body tissue/organs.
  • Conventional bionics or biomimicry represents Exo-bioncs: the application of biological principles to augment or replace physiological functions by electronic or electromechanical components.
  • Auto-bionic and exo-bionic therapies can be dynamic or static.
  • Auto-bionic therapies can include Tissue Replacement, System Reorganization and Tissue Redesignation.
Examples
  • The Ross procedure is auto-bionic as it applies a semi-lunar valve from one location in the heart to another, this offers improved haemodynamics and tensile strength.
  • Dynamic Cardiomyoplasty and skeletal muscle ventricles provide auto-bionic cardiac pumping using inherent skeletal muscles.
  • Dynamic Graciloplasty can use inherent skeletal muscles to transform their function to provide auto-bionic sphincter activity.
  • Metabolic Gastric Bypass offers the auto-bionic resolution of type II diabetes and may hyper-augment insulin release in some cases.
Future
  • Auto-bionic procedures can be augmented through the use of other regenerative medical technologies including developments in stem cell therapy.
  • Auto-bionics will have an increased role in reconstructive strategies and the treatment of obesity, diabetes, cardiovascular disease and cancer.
1. Monties Leonardo da vinci: Precursor member of the international society for rotary blood pumps? Artif Organs. 1999;23(6):477–479. [PubMed]
2. Robicsek F. Leonardo da vinci and the sinuses of valsalva. Ann Thorac Surg. 1991;52(2):328–335. [PubMed]
3. Vincent Jf, Bogatyreva Oa, Bogatyrev Nr, Bowyer A, Pahl Ak. Biomimetics: Its practice and theory. J R Soc Interface. 2006;3(9):471–482. [PMC free article] [PubMed]
4. Historical highlights in bionics and related medicine. Science. 2002;295(5557):995. [PubMed]
5. Craelius W. The bionic man: Restoring mobility. Science. 2002;295(5557):1018–1021. [PubMed]
6. Camporesi S. Oscar pistorius, enhancement and post-humans. J Med Ethics. 2008;34(9):639. [PubMed]
7. Miodownik M. The bionic future of sport. Mater Today. 2007;10(9):6.
8. Taylor Do, Edwards Lb, Aurora P, et al. Registry of the international society for heart and lung transplantation: Twenty-fifth official adult heart transplant report--2008. J Heart Lung Transplant. 2008;27(9):943–956. [PubMed]
9. Perl J, Bargman Jm, Davies Sj, Jassal Sv. Clinical outcomes after failed renal transplantation-does dialysis modality matter? Semin Dial. 2008;21(3):239–244. [PubMed]
10. Lower Rr, Stofer Rc, Shumway Ne. A study of pulmonary valve autotransplantation. Surgery. 1960;48:1090–1100. [PubMed]
11. Lower Rr, Stofer Rc, Shumway Ne. Autotransplantation of the pulmonic valve into the aorta. J Thorac Cardiovasc Surg. 1960;39:680–687. [PubMed]
12. Pillsbury Rc, Shumway Ne. Replacement of the aortic valve with the autologous pulmonic valve. Surg Forum. 1966;17:176–177. [PubMed]
13. Hochrein M. Der mechanismus der semilunarklappen des herzens. Dtsch Arch Klin Med. 1927;54:131–164.
14. Ross Dn. Replacement of aortic and mitral valves with a pulmonary autograft. Lancet. 1967;2(7523):956–958. [PubMed]
15. Ashrafian H, Griselli M, Rubens Mb, Mullen Mj, Sethia B. Pulmonary homograft endocarditis 19 years after a ross procedure. Thorac Cardiovasc Surg. 2007;55(1):55–56. [PubMed]
16. Hon Jk, Melina G, Wray J, Yacoub Mh. Insights from 36 years’ follow up of a patient with the ross operation. J Heart Valve Dis. 2003;12(5):561–565. [PubMed]
17. Gonzalez-Lavin L, Metras D, Ross Dn. Anatomic and physiologic bases for the ross procedure. J Heart Valve Dis. 1996;5(4):383–390. discussion 401-383. [PubMed]
18. Legarra Jj, Concha M, Casares J, Merino C, Munoz I, Alados P. Left ventricular remodeling after pulmonary autograft replacement of the aortic valve (ross operation) J Heart Valve Dis. 2001;10(1):43–48. [PubMed]
19. Yacoub Mh, Klieverik Lm, Melina G, et al. An evaluation of the ross operation in adults. J Heart Valve Dis. 2006;15(4):531–539. [PubMed]
20. Bonow Ro, Carabello Ba, Chatterjee K, et al. 2008 focused update incorporated into the acc/aha 2006 guidelines for the management of patients with valvular heart disease: A report of the american college of cardiology/american heart association task force on practice guidelines (writing committee to revise the 1998 guidelines for the management of patients with valvular heart disease): Endorsed by the society of cardiovascular anesthesiologists, society for cardiovascular angiography and interventions, and society of thoracic surgeons. Circulation. 2008;118(15):e523–661. [PubMed]
21. Yacoub Mh. The ross operation--an evolutionary tale. Asian Cardiovasc Thorac Ann. 2006;14(1):1–2. [PubMed]
22. Williams Db, Danielson Gk, Mcgoon Dc, Puga Fj, Mair Dd, Edwards Wd. Porcine heterograft valve replacement in children. J Thorac Cardiovasc Surg. 1982;84(3):446–450. [PubMed]
23. Gorczynski A, Trenkner M, Anisimowicz L, et al. Biomechanics of the pulmonary autograft valve in the aortic position. Thorax. 1982;37(7):535–539. [PMC free article] [PubMed]
24. Athanasiou T, Cherian A, Ross D. The ross ii procedure: Pulmonary autograft in the mitral position. Ann Thorac Surg. 2004;78(4):1489–1495. [PubMed]
25. Dejesus Fr. Breve consideraciones sobre un case de herida penetrante del corazon. Bol Asoc Med P R. 1931;23:380–382.
26. Leriche R, Fontaine R. Essai expérimental de traitement de certains infarctus du myocarde et de l’anéurysme du coeur par une graffe muscle strié Bull Soc Nat Chir. 1933;9:229–232.
27. Beck Cs. The development of a new blood supply to the heart by operation. Ann Surg. 1935;102:801–813. [PubMed]
28. Beck Cs. A new blood supply to the heart by operation. Surg Gynecol Obstet. 1935;61:407–410.
29. Kantrowitz A, Mc Kw. The experimental use of the diaphragm as an auxiliary myocardium. Surg Forum. 1958;9:266–268. [PubMed]
30. Kusaba E, Schraut W, Sawatani S, Jaron D, Freed P, Kantrowitz A. A diaphragmatic graft for augmenting left ventricular function: A feasibility study. Trans Am Soc Artif Intern Organs. 1973;19:251–257. [PubMed]
31. Dewar Ml, Drinkwater Dc, Wittnich C, Chiu Rc. Synchronously stimulated skeletal muscle graft for myocardial repair. An experimental study. J Thorac Cardiovasc Surg. 1984;87(3):325–331. [PubMed]
32. Salmons S, Sreter Fa. Significance of impulse activity in the transformation of skeletal muscle type. Nature. 1976;263(5572):30–34. [PubMed]
33. Salmons S, Vrbova G. The influence of activity on some contractile characteristics of mammalian fast and slow muscles. J Physiol. 1969;201(3):535–549. [PubMed]
34. Acker Ma, Hammond Rl, Mannion Jd, Salmons S, Stephenson Lw. Skeletal muscle as the potential power source for a cardiovascular pump: Assessment in vivo. Science. 1987;236(4799):324–327. [PubMed]
35. Carpentier A, Chachques Jc. Myocardial substitution with a stimulated skeletal muscle: First successful clinical case. Lancet. 1985;1(8440):1267. [PubMed]
36. Chachques Jc, Grandjean P, Schwartz K, et al. Effect of latissimus dorsi dynamic cardiomyoplasty on ventricular function. Circulation. 1988;78(Suppl):III, 203–216. [PubMed]
37. Lee Kf, Dignan Rj, Parmar Jm, et al. Effects of dynamic cardiomyoplasty on left ventricular performance and myocardial mechanics in dilated cardiomyopathy. J Thorac Cardiovasc Surg. 1991;102(1):124–131. [PubMed]
38. Bellotti G, Moraes A, Bocchi E, et al. Late effects of cardiomyoplasty on left ventricular mechanics and diastolic filling. Circulation. 1993;88(5 Pt 2):II304–308. [PubMed]
39. Nakajima H, Niinami H, Hooper Tl, et al. Cardiomyoplasty: Probable mechanism of effectiveness using the pressure-volume relationship. Ann Thorac Surg. 1994;57(2):407–415. [PubMed]
40. Bolotin G, Lorusso R, Schreuder Jj, Kaulbach Hg, Uretzky G, Van Der Veen Fh. Effects of acute dynamic cardiomyoplasty in a goat model of chronic ventricular dilatation: Part 1. Ann Thorac Surg. 2002;74(2):507–513. [PubMed]
41. Kaulbach Hg, Lorusso R, Bolotin G, Schreuder Jj, Van Der Veen Fh. Effects of chronic cardiomyoplasty on ventricular remodeling in a goat model of chronic cardiac dilatation: Part 2. Ann Thorac Surg. 2002;74(2):514–521. [PubMed]
42. Mott Bd, Oh Jh, Misawa Y, et al. Mechanisms of cardiomyoplasty: Comparative effects of adynamic versus dynamic cardiomyoplasty. Ann Thorac Surg. 1998;65(4):1039–1044. discussion 1044-1035. [PubMed]
43. Shirota K, Kawaguchi O, Huang Y, et al. Ventricular remodeling after cardiomyoplasty in heart failure sheep: Passive and dynamic effects. Ann Thorac Surg. 2000;70(6):2102–2106. [PubMed]
44. Silverman Na. Invited letter concerning: Clinical and left ventricular function outcomes up to five years after dynamic cardiomyoplasty. J Thorac Cardiovasc Surg. 1995;109(2):397–398. [PubMed]
45. Furnary Ap, Jessup Fm, Moreira Lp. Multicenter trial of dynamic cardiomyoplasty for chronic heart failure. The american cardiomyoplasty group. J Am Coll Cardiol. 1996;28(5):1175–1180. [PubMed]
46. Astra Li, Stephenson Lw. Skeletal muscle as a myocardial substitute. Proc Soc Exp Biol Med. 2000;224(3):133–140. [PubMed]
47. Starling Rc, Jessup M, Oh Jk, et al. Sustained benefits of the corcap cardiac support device on left ventricular remodeling: Three year follow-up results from the acorn clinical trial. Ann Thorac Surg. 2007;84(4):1236–1242. [PubMed]
48. Schenk S, Reichenspurner H, Groezner Jg, et al. Myosplint implantation and ventricular shape change in patients with dilative cardiomyopathy-first clinical experience. J Heart Lung Transplant. 2001;20217(2) [PubMed]
49. Chachques Jc. Cardiomyoplasty: Is it still a viable option in patients with end-stage heart failure? Eur J Cardiothorac Surg. 2009;35(2):201–203. [PubMed]
50. Sherwood Jt, Schomisch Sj, Thompson Dr, George Dt, Cmolik Bl. Aortomyoplasty: Hemodynamics and comparison to the intraaortic balloon pump. J Surg Res. 2003;110(2):315–321. [PubMed]
51. Trainini J, Cabrera Fischer Ei, Barisani J, et al. Dynamic aortomyoplasty in treating end-stage heart failure. J Heart Lung Transplant. 2002;21(10):1068–1073. [PubMed]
52. Choy Ds, Ellis R. Multiple hearts in animals other than barosaurus. Lancet. 1998;352(9129):744. [PubMed]
53. Gray Na, Jr., Selzman Ch. Current status of the total artificial heart. Am Heart J. 2006;152(1):4–10. [PubMed]
54. Acker Ma, Anderson Wa, Hammond Rl, et al. Skeletal muscle ventricles in circulation. One to eleven weeks’ experience. J Thorac Cardiovasc Surg. 1987;94(2):163–174. [PubMed]
55. Thomas Ga, Isoda S, Hammond Rl, et al. Pericardium-lined skeletal muscle ventricles: Up to two years’ in-circulation experience. Ann Thorac Surg. 1996;62(6):1698–1706. discussion 1706-1697. [PubMed]
56. Thomas Ga, Lu H, Isoda S, et al. Skeletal muscle ventricles in circulation: Decreased incidence of rupture. Ann Thorac Surg. 1996;61(1):430–436. [PubMed]
57. Thomas Ga, Hammond Rl, Greer K, et al. Functional assessment of skeletal muscle ventricles after pumping for up to four years in circulation. Ann Thorac Surg. 2000;70(4):1281–1289. discussion 1290. [PubMed]
58. Thomas Ga, Lelkes Pi, Chick Dm, et al. Endothelial lined skeletal muscle ventricles: Open and percutaneous seeding techniques. J Card Surg. 1995;10(3):245–256. [PubMed]
59. Mannion Jd, Hammond R, Stephenson Lw. Hydraulic pouches of canine latissimus dorsi. Potential for left ventricular assistance. J Thorac Cardiovasc Surg. 1986;91(4):534–544. [PubMed]
60. Pochettino A, Spanta Ad, Hammond Rl, et al. Skeletal muscle ventricles for total heart replacement. Ann Surg. 1990;212(3):345–352. [PubMed]
61. Mannion Jd, Acker Ma, Hammond Rl, Stephenson Lw. Four hour circulatory assistance with canine skeletal muscle ventricles. Surg Forum. 1986;37:211–213.
62. Ramnarine Ir, Capoccia M, Ashley Z, et al. Counterpulsation from the skeletal muscle ventricle and the intraaortic balloon pump in the normal and failing circulations. Circulation. 2006;114(1 Suppl):I10–15. [PubMed]
63. Mocek Fw, Anderson Dr, Pochettino A, et al. Skeletal muscle ventricles in circulation long-term: One hundred ninety-one to eight hundred thirty-six days. J Heart Lung Transplant. 1992;11(5):S334–340. [PubMed]
64. Hooper Tl, Niinami H, Hammond Rl, et al. Skeletal muscle ventricles as left atrial-aortic pumps: Short-term studies. Ann Thorac Surg. 1992;54(2):316–322. [PubMed]
65. Lu H, Fietsam R, Jr., Hammond Rl, et al. Skeletal muscle ventricles: Left ventricular apex to aorta configuration. Ann Thorac Surg. 1993;55(1):78–85. [PubMed]
66. Dabareiner Rm, Schmitz Dg, Honnas Cm, Carter Gk. Gracilis muscle injury as a cause of lameness in two horses. J Am Vet Med Assoc. 2004;224(10):1630–1633. 1605–1636. [PubMed]
67. Last Rj. Anatomy: Regional and applied. 7th Churchill Livingstone (Longman Group); Edinburgh: 1984.
68. Coquerel-Beghin D, Milliez Py, Auquit-Auckbur I, Lemierre G, Duparc F. The gracilis musculocutaneous flap: Vascular supply of the muscle and skin components. Surg Radiol Anat. 2006;28(6):588–595. [PubMed]
69. Macchi V, Vigato E, Porzionato A, et al. The gracilis muscle and its use in clinical reconstruction: An anatomical, embryological, and radiological study. Clin Anat. 2008;21(7):696–704. [PubMed]
70. Pickrell Kl, Broadbent Tr, Masters Fw, Metzger Jt. Construction of a rectal sphincter and restoration of anal continence by transplanting the gracilis muscle; a report of four cases in children. Ann Surg. 1952;135(6):853–862. [PubMed]
71. Konsten J, Baeten Cg, Havenith Mg, Soeters Pb. Morphology of dynamic graciloplasty compared with the anal sphincter. Dis Colon Rectum. 1993;36(6):559–563. [PubMed]
72. Buller Aj, Eccles Jc, Eccles Rm. Interactions between motoneurones and muscles in respect of the characteristic speeds of their responses. J Physiol. 1960;150:417–439. [PubMed]
73. Adang Em, Engel Gl, Rutten Ff, Geerdes Bp, Baeten Cg. Cost-effectiveness of dynamic graciloplasty in patients with fecal incontinence. Dis Colon Rectum. 1998;41(6):725–733. discussion 733-724. [PubMed]
74. Belyaev O, Muller C, Uhl W. Neosphincter surgery for fecal incontinence: A critical and unbiased review of the relevant literature. Surg Today. 2006;36(4):295–303. [PubMed]
75. Madoff Rd. Surgical treatment options for fecal incontinence. Gastroenterology. 2004;126(1 Suppl 1):S48–54. [PubMed]
76. Flickinger Eg, Pories Wj, Meelheim Hd, Sinar Dr, Blose Il, Thomas Ft. The greenville gastric bypass. Progress report at 3 years. Ann Surg. 1984;199(5):555–562. [PubMed]
77. Pories Wj, Swanson Ms, Macdonald Kg, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995;222(3):339–350. discussion 350-332. [PubMed]
78. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: Systematic review and meta-analysis. Am J Med. 2009;122(3):248–256 e245. [PubMed]
79. Ashrafian H, Le Roux Cw. Metabolic surgery and gut hormones - a review of bariatric entero-humoral modulation. Physiol Behav. 2009;97(5):620–631. [PubMed]
80. Celi Fs. Brown adipose tissue--when it pays to be inefficient. N Engl J Med. 2009;360(15):1553–1556. [PMC free article] [PubMed]
81. Carey Dg, Pliego Gj, Raymond Rl, Skau Kb. Body composition and metabolic changes following bariatric surgery: Effects on fat mass, lean mass and basal metabolic rate. Obes Surg. 2006;16(4):469–477. [PubMed]
82. Cornu M, Yang Jy, Jaccard E, Poussin C, Widmann C, Thorens B. Glp-1 protects beta-cells against apoptosis by increasing the activtiy of an igf-2/igf1-receptor autocrine loop. Diabetes. 2009 [PMC free article] [PubMed]
83. Holz Gg, Leech Ca, Heller Rs, Castonguay M, Habener Jf. Camp-dependent mobilization of intracellular ca2+ stores by activation of ryanodine receptors in pancreatic beta-cells. A ca2+ signaling system stimulated by the insulinotropic hormone glucagon-like peptide-1-(7-37) J Biol Chem. 1999;274(20):14147–14156. [PMC free article] [PubMed]
84. Holz Gg. Epac: A new camp-binding protein in support of glucagon-like peptide-1 receptor-mediated signal transduction in the pancreatic beta-cell. Diabetes. 2004;53(1):5–13. [PMC free article] [PubMed]
85. Ashrafian H, Le Roux Cw, Darzi A, Athanasiou T. Effects of bariatric surgery on cardiovascular function. Circulation. 2008;118(20):2091–2102. [PubMed]
86. Service Gj, Thompson Gb, Service Fj, Andrews Jc, Collazo-Clavell Ml, Lloyd Rv. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med. 2005;353(3):249–254. [PubMed]
87. Cummings De. Gastric bypass and nesidioblastosis--too much of a good thing for islets? N Engl J Med. 2005;353(3):300–302. [PubMed]
88. Grammaticos Pc, Diamantis A. Useful known and unknown views of the father of modern medicine, hippocrates and his teacher democritus. Hell J Nucl Med. 2008;11(1):2–4. [PubMed]