PubMed Health⌕ Search

Biomedical subjects

Sidney Levitsky

Publications and source records attributed to Sidney Levitsky.

17 recordsLinked to original sources
PubMed2006

Protecting the myocardial cell during coronary revascularization. The William W. L. Glenn Lecture.

BACKGROUND: Using the ischemic myocardial cell as a paradigm, competitive coronary revascularization technologies will be analyzed for their potential in causing additional myocardial cell damage during the course of therapeutic procedures. METHODS AND RESULTS: Percutaneous coronary intervention (PCI) using balloon and/or stent (bare metal or coated) approaches may be associated with myonecrosis related to atherosclerotic debris plugging the downstream coronary microcirculation as well as ischemia/reperfusion injury associated with revascularization of occluded coronary vessels. The placement of distal mechanical devices and filters during the course of PCI has not been successful in ameliorating this problem. Coronary revascularization using coronary artery bypass grafting (CABG) similarly may be associated with myocardial stunning and cell necrosis associated with ischemia/reperfusion injury. Surgically induced myocardial ischemia secondary to aortic cross clamping, results from the attenuation or cessation of coronary blood flow such that oxygen delivery to the myocardium is insufficient to meet basal myocardial requirements to preserve cellular membrane stability and viability. Recovery involves: (1) resumption of normal oxidative metabolism and the restoration of myocardial energy reserves; (2) reversal of ischemia induced cell swelling and loss of membrane ion gradients and the adenine nucleotide pool; (3) repair of damaged cell organelles such as the mitochondria and the sarcoplasmic reticulum. Despite meticulous adherence to presently known principles of surgical myocardial protection using advanced cardioplegic technologies, some patients require inotropic support and/or mechanical assist devices postoperatively, when none was required preoperatively. CONCLUSIONS: Which method of coronary revascularization causes the least amount of myocardial cell injury and is associated with superior long-term outcomes remains an area of increasing controversy.

Angioplasty, Balloon, Coronary↗
PubMed2006

Study of the Therapeutic Effects of Intercessory Prayer (STEP) in cardiac bypass patients: a multicenter randomized trial of uncertainty and certainty of receiving intercessory prayer.

BACKGROUND: Intercessory prayer is widely believed to influence recovery from illness, but claims of benefits are not supported by well-controlled clinical trials. Prior studies have not addressed whether prayer itself or knowledge/certainty that prayer is being provided may influence outcome. We evaluated whether (1) receiving intercessory prayer or (2) being certain of receiving intercessory prayer was associated with uncomplicated recovery after coronary artery bypass graft (CABG) surgery. METHODS: Patients at 6 US hospitals were randomly assigned to 1 of 3 groups: 604 received intercessory prayer after being informed that they may or may not receive prayer; 597 did not receive intercessory prayer also after being informed that they may or may not receive prayer; and 601 received intercessory prayer after being informed they would receive prayer. Intercessory prayer was provided for 14 days, starting the night before CABG. The primary outcome was presence of any complication within 30 days of CABG. Secondary outcomes were any major event and mortality. RESULTS: In the 2 groups uncertain about receiving intercessory prayer, complications occurred in 52% (315/604) of patients who received intercessory prayer versus 51% (304/597) of those who did not (relative risk 1.02, 95% CI 0.92-1.15). Complications occurred in 59% (352/601) of patients certain of receiving intercessory prayer compared with the 52% (315/604) of those uncertain of receiving intercessory prayer (relative risk 1.14, 95% CI 1.02-1.28). Major events and 30-day mortality were similar across the 3 groups. CONCLUSIONS: Intercessory prayer itself had no effect on complication-free recovery from CABG, but certainty of receiving intercessory prayer was associated with a higher incidence of complications.

Aged↗
PubMed2006

Initial impact of drug-eluting stents on coronary artery bypass graft surgery.

BACKGROUND: Drug-eluting stents (DES) reduce the incidence of restenosis after percutaneous coronary intervention and have been predicted to decrease the number of patients referred for coronary artery bypass grafting (CABG). The purpose of this study was to determine the impact of DES on the number and characteristics of patients referred for CABG. METHODS: Drug-eluting stents were introduced at our hospital in April 2003 and reached maturity by June 2003. We compared our isolated CABG patients from the 12 months before the introduction of DES (year 1) with those from the 12 months after full implementation of DES (year 2). RESULTS: In year 1, of 4,348 cardiac catheterization patients, 2,144 (49.3%) underwent percutaneous coronary intervention, and 432 (9.9%) had CABG. In year 2, of 3,986 cardiac catheterization patients, 2,027 (50.9%) had percutaneous coronary intervention, and 337 (8.5%) had CABG, representing a 14% reduction in proportion of cardiac catheterization patients referred for CABG (p = 0.021). Among CABG patients, there was no change in age, prevalence of diabetes, or prevalence of three-vessel disease; however, patients in year 2 were more likely to have left main coronary artery disease (year 1, 36% versus year 2, 44.5%; p < 0.02) and left ventricular ejection fraction greater than 0.50 (year 1, 45% versus year 2, 52%; p < 0.02). CONCLUSIONS: The clinical introduction of DES was associated with a modest decrease in the percentage of cardiac catheterization patients referred for CABG. Of those referred for surgery, an increasing proportion had left main coronary artery disease and preserved left ventricular systolic function. Defining the role of DES versus CABG for coronary revascularization will require elucidation of the long-term outcomes of DES compared with CABG.

Aged↗
PubMed2006

Age- and gender-related differences in ischemia/reperfusion injury and cardioprotection: effects of diazoxide.

BACKGROUND: Recent studies have demonstrated that aging is associated with reduced tolerance to ischemia and that the aged (not senescent) female heart has greater susceptibility to ischemia as compared with the aged male heart. Previously, we have shown that ischemia can be modulated with cardioplegia in the male heart; however, efficacy in the female heart was unknown. METHODS: In this study, male and female mature (15 to 20 weeks) aged (>32 months) rabbit hearts (n = 134) were subjected to Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia hearts received 30 minutes of equilibrium, 30 minutes of global ischemia, and 120 minutes of reperfusion. Cardioplegia +/- diazoxide was infused separately, 5 minutes before global ischemia. RESULTS: Global ischemia significantly decreased postischemic functional recovery and significantly increased infarct size in the mature and aged male and female heart (p < 0.05 versus control). The effects of global ischemia were significantly exacerbated (p < 0.05) in the aged heart as compared with the mature heart. Cardioplegia +/- diazoxide significantly increased postischemic functional recovery and significantly decreased infarct size in mature male and female hearts, but these effects were significantly decreased in the aged heart (p < 0.05) and in the aged female as compared with the aged male heart. CONCLUSIONS: Postischemic functional recovery and infarct size are affected by age but not by gender. The cardioprotection afforded by cardioplegia is affected by age and gender with a strong age-by-gender interaction for end-diastolic pressure and infarct size. Our results indicate that currently optimized cardioplegia protocols effective in the male heart are not as efficacious in the aged female heart.

Aging↗
PubMed2006

Reduction and redistribution of gap and adherens junction proteins after ischemia and reperfusion.

BACKGROUND: Previous studies have demonstrated that alterations in myocardial structure, consistent with tissue and sarcomere disruption as well as myofibril dissociation, occur after myocardial ischemia and reperfusion. In this study we determine the onset of these structural changes and their contribution to electrical conduction. METHODS: Langendorff perfused rabbit hearts (n = 47) were subjected to 0, 5, 10, 15, 20, 25, and 30 minutes global ischemia, followed by 120 minutes reperfusion. Hemodynamics were recorded and tissue samples were collected for histochemical and immunohistochemical studies. Orthogonal epicardial conduction velocities were measured, with temperature controlled, in a separate group of 10 hearts subjected to 0 or 30 minutes of global ischemia, followed by 120 minutes of reperfusion. RESULTS: Histochemical and quantitative light microscopy spatial analysis showed significantly increased longitudinal and transverse interfibrillar separation after 15 minutes or more of ischemia (p < 0.05 versus control). Confocal immunohistochemistry and Western blot analysis demonstrated significant reductions (p < .05 versus control) of the intercellular adherens junction protein, N-cadherin, and the active phosphorylated isoform of the principal gap junction protein, connexin 43 at more than 15 minutes of ischemia. Cellular redistribution of connexin 43 was also evidenced on immunohistochemistry. No change in integrin-beta1, an extracellular matrix attachment protein, or in epicardial conduction velocity anisotropy was observed. CONCLUSIONS: These data indicate that there are significant alterations in the structural integrity of the myocardium as well as gap and adherens junction protein expression with increasing global ischemia time. The changes occur coincident with previously observed significant decreases in postischemic functional recovery, but are not associated with altered expression of matrix binding proteins or electrical anisotropic conduction.

Adherens Junctions↗
PubMed2004

Opening of mitochondrial KATP channels enhances cardioprotection through the modulation of mitochondrial matrix volume, calcium accumulation, and respiration.

Previously, we have shown that the pharmacological opening of the mitochondrial ATP-sensitive K channels with diazoxide (DZX) enhances the cardioprotection afforded by magnesium-supplemented potassium (K/Mg) cardioplegia. To determine the mechanisms involved in the cardioprotection afforded by K/Mg + DZX cardioplegia, rabbit hearts (n=24) were subjected to isolated Langendorff perfusion. Control hearts were perfused for 75 min. Global ischemia (GI) hearts were subjected to 30 min of equilibrium, 30 min of GI, and 15 min of reperfusion. K/Mg and K/Mg + DZX cardioplegia hearts received either K/Mg or K/Mg + DZX for 5 min before GI and reperfusion. Tissue was harvested for mitochondrial isolation and transmission electron microscopy (TEM). Mitochondrial structure, area, matrix volume, free calcium, and oxygen consumption were determined. TEM demonstrated that GI mitochondria were damaged and that K/Mg and K/Mg + DZX preserved mitochondrial structure. TEM and light scattering demonstrated separately that mitochondrial matrix and cristae area and matrix volume were significantly increased after GI and reperfusion with GI > K/Mg + DZX > K/Mg hearts (P <0.05 vs. control). Mitochondrial free calcium was significantly increased in GI and K/Mg hearts. K/Mg + DZX significantly decreased mitochondrial free calcium accumulation (P <0.05 vs. GI and K/Mg). State 3 oxygen consumption and respiratory control index in malate (complex I substrate)- and succinate (complex II substrate)-energized mitochondria were significantly decreased (P <0.05 vs. control) in the GI and K/Mg + DZX groups. These data indicate that the enhanced cardioprotection afforded by K/Mg + DZX cardioplegia occurs through the preservation of mitochondrial structure and the significant decrease in mitochondrial free calcium accumulation and mitochondrial state 3 oxygen consumption.

Adenosine Triphosphate↗
PubMed2004

Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury.

Necrosis and apoptosis differentially contribute to myocardial injury. Determination of the contribution of these processes in ischemia-reperfusion injury would allow for the preservation of myocardial tissue. Necrosis and apoptosis were investigated in Langendorff-perfused rabbit hearts (n = 47) subjected to 0 (Control group), 5 (GI-5), 10 (GI-10), 15 (GI-15), 20 (GI-20), 25 (GI-25), and 30 min (GI-30) of global ischemia (GI) and 120 min of reperfusion. Myocardial injury was determined by triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), bax, bcl2, poly(ADP)ribose polymerase (PARP) cleavage, caspase-3, -8, and -9 cleavage and activity, Fas ligand (FasL), and Fas-activated death domain (FADD). The contribution of apoptosis was determined separately (n = 42) using irreversible caspase-3, -8, and -9 inhibitors. Left ventricular peak developed pressure (LVPDP) and systolic shortening (SS) were significantly decreased and infarct size and TUNEL-positive cells were significantly increased (P < 0.05 vs. Control group) at GI-20, GI-25, and GI-30. Proapoptotic bax, PARP cleavage, and caspase-3 and -9 cleavage and activity were apparent at GI-5 to GI-30. Fas, FADD, and caspase-8 cleavage and activity were unaltered. Irreversible inhibition of caspase-3 and -9 activity significantly decreased (P < 0.05) infarct size at GI-25 and GI-30 but had no effect on LVPDP or SS. Myocardial injury results from a significant increase in both necrosis and apoptosis (P < 0.05 vs. Control group) evident by TUNEL, TTC staining, and caspase activity at GI-20. Intrinsic proapoptotic activation is evident early during ischemia but does not significantly contribute to infarct size before GI-25. The contribution of necrosis to infarct size at GI-20, GI-25, and GI-30 is significantly greater than that of apoptosis. Apoptosis is significantly decreased by caspase inhibition during early reperfusion, but this protection does not improve immediate postischemic functional recovery.

Animals↗
PubMed2003

Mitochondrial ATP-sensitive potassium channels in surgical cardioprotection.

ATP-sensitive potassium channels allow for the coupling of membrane potential to cellular metabolic status. Two K(ATP) channel subtypes coexist in the myocardium with one subtype located in the sarcolemma membrane and the other in the inner membrane of the mitochondria. The ATP-sensitive potassium channels can be pharmacologically modulated by a family of structurally diverse agents of varied potency and selectivity, collectively known as potassium channel openers and blockers. Sufficient evidence exists to indicate that the ATP-sensitive potassium channels and in particular the mitochondrial ATP-sensitive potassium channels play an important role both as a trigger and an effector in surgical cardioprotection. In this review, the biochemistry and specificity of the ATP-sensitive potassium channels is examined in relation to surgical cardioprotection.

Adenosine↗
PubMed2003

The mitochondrial K(ATP) channel and cardioprotection.

Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels allow coupling of membrane potential to cellular metabolic status. Two K(ATP) channel subtypes coexist in the myocardium, with one subtype located in the sarcolemma (sarcK(ATP)) membrane and the other in the inner membrane of the mitochondria (mitoK(ATP)). The K(ATP) channels can be pharmacologically modulated by a family of structurally diverse agents of varied potency and selectivity, collectively known as potassium channel openers and blockers. Sufficient evidence exists to indicate that the K(ATP) channels and, in particular, the mitoK(ATP) channels play an important role both as a trigger and an effector in surgical cardioprotection. In this review, the biochemistry and surgical specificity of the K(ATP) channels are examined.

Adenosine Triphosphate↗
PubMed2003

Mitochondrial DNA deletions in coronary artery bypass grafting patients.

OBJECTIVE: Mitochondrial DNA (mitoDNA) deletions have been shown to increase with aging and ischemia and have been suggested to contribute to myocardial dysfunction. The purpose of this study was to determine the prevalence and specificity of mitoDNA deletions in coronary artery bypass patients. METHODS: Right atrial appendix tissue from 51 cardiac surgical patients (30-93 years; mean 64+/-14 years) was obtained during cardiopulmonary bypass cannulation (Control), just prior to the removal of the venous cannula (Ischemia, 169+/-38 min) and following removal of the cannula (Reperfusion) and used for polymerase chain reaction (PCR) and sequence analysis. RESULTS: A novel mitoDNA deletion (approximately 7.3 kb, mitoDNA(7.3)) was found in three unrelated, male patients (53, 67, 75 years old). All mitoDNA(7.3) deletion breakpoints were found downstream of the ATP synthase 8 genes and at the 3' end of the cytochrome b genes. The prevalence of the mitoDNA(7.3) deletion was significantly increased (P<0.05) following ischemia and reperfusion. Clinical data indicated that postoperative left ventricular ejection fraction was lower (38.3 vs. 46.4%), and the incidence of previous myocardial infarction higher (1.7 vs. 0.6) in patients exhibiting mitoDNA deletions. CONCLUSION: Our results reveal a novel mitochondrial DNA deletion occurring within the genome region coding for the mitochondrial genes of oxidative phosphorylation that is significantly increased during ischemia and reperfusion. The incidence and prevalence of mitoDNA(7.3) deletions in patients with clinical indications of poor recovery suggests that mitoDNA(7.3) deletions may provide an important indicator to surgical outcome in the cardiac surgical patient.

Adult↗
PubMed2002

Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor.

BACKGROUND: The activation of poly (ADP-ribose) synthetase plays an important role in the pathogenesis leading to myocardial ischemia-reperfusion injury. The aim of this study was to determine if a novel potent inhibitor of poly (ADP-ribose) synthetase, PJ34, provides myocardial protection. METHODS: Pigs were subjected to 60 minutes of regional ischemia followed by 180 minutes of reperfusion. Ten mg/kg of PJ34 (PJ34; n = 6) was administrated intravenously (treated group) from 15 to 5 minutes before reperfusion followed by 3 mg/kg/hour of PJ34 from 5 minutes before reperfusion to the end of 180 minutes reperfusion. Control pigs (n = 7) received vehicle only. Arterial and left ventricular pressure and coronary flow were monitored. RESULTS: The PJ34 showed significant reduction on infarct size (37.5%+/-4.5% and 50.5%+/-4.8% of the area at risk) for PJ34 and control pigs groups, respectively, (p < 0.05). Significant reduction in postsystolic shortening, as well as improvement on segment shortening, and positive first derivative of pressure over time (+dP/dt) maximum were also observed in PJ34 versus control pigs (p < 0.05). CONCLUSIONS: Our results suggest that PJ34 provides cardioprotection by decreasing myocardial infarct size and enhancing postischemic regional and global functional recovery.

Animals↗
PubMed2002

A novel peroxynitrite decomposer catalyst (FP-15) reduces myocardial infarct size in an in vivo peroxynitrite decomposer and acute ischemia-reperfusion in pigs.

BACKGROUND: Reactive oxygen and nitrogen species generated after reperfusion injury result in organ dysfunction. Peroxynitrite, a reactive nitrogen molecule produced from the reaction of superoxide anions and nitric oxide, is thought to be a causative agent in oxidative reperfusion injury. The aim of this study was to investigate the effects of a novel peroxynitrite decomposition catalyst (FP-15) in an acute myocardial ischemia/reperfusion model. METHODS: Pigs were subjected to 60 minutes of regional ischemia by reversibly ligating the left anterior descending coronary artery followed by 180 minutes of reperfusion. In the treatment group (n = 6), an FP-15 (1 mg/kg) bolus was infused through the jugular vein after 30 minutes of ischemia followed by a continuous infusion (1 mg x kg(-1) x h(-1)) during reperfusion. Vehicle was infused in the control group (n = 6). Coronary flow was recorded by an ultrasonic flow probe and infarct size determined by tetrazolium staining. Arterial and left ventricular pressures were monitored continuously and regional myocardial function determined by sonomicrometry. RESULTS: No significant differences were observed in either hemodynamics or ischemic area at risk. However, the infarct size was significantly reduced (35.3% +/- 3.5% versus 21.6% +/- 2.6% of the ischemic area, control versus FP-15-treated groups, respectively, p < 0.05). +dP/dt was transiently improved in the FP-15-treated groups while during most of the reperfusion period coronary flow, and was significantly lower in the FP-15-treated group as compared to the control group (p < 0.01). CONCLUSIONS: FP-15 administration reduces myocardial infarct size and reactive hyperemia. These data support the pathogenic role of endogenously produced peroxynitrite and that FP-15 is effective in preventing myocardial reperfusion injury.

Animals↗
PubMed2002

Diazoxide amelioration of myocardial injury and mitochondrial damage during cardiac surgery.

BACKGROUND: Recently, we have shown that the selective opening of mitochondrial ATP-sensitive potassium channels with diazoxide significantly decreases myocardial injury. The purpose of this study was to determine the effects of diazoxide on apoptosis and the mechanisms modulating apoptosis and myocardial injury in a blood-perfused model of acute myocardial infarction. METHODS: Pigs (32 to 42 kg) undergoing total cardiopulmonary bypass underwent left anterior descending coronary artery occlusion for 30 minutes. The aorta was cross-clamped and magnesium-supplemented potassium cold-blood cardioplegia (DSA; n = 6) or magnesium-supplemented potassium cardioplegia containing 50 micromol/L diazoxide (DZX; n = 6) was administered, followed by 30 minutes of global ischemia and 120 minutes of reperfusion. Left ventricular tissue samples from DSA and DZX hearts were obtained after reperfusion. Apoptosis was determined by TUNEL, caspase-3 and PARP cleavage, and caspase-3 activity. Bax and bcl-2 levels were determined and tissue morphology was examined by light and transmission electron microscopy. RESULTS: Apoptosis, as estimated by TUNEL-positive nuclei/3,000 myocardial cells, was 120.3 +/- 48.8 in DSA hearts and was significantly decreased to 21.4 +/- 5.3 in DZX hearts (p < 0.05 vs control). Caspase-3 and poly-ADP-ribose polymerase cleavage and pro-apoptotic bax protein levels were significantly decreased with diazoxide (p < 0.05 vs DSA). Light and transmission electron microscopy indicated severe disruption of tissue with capillary dilatation, mitochondrial cristae damage, and evidence of increased presence of mitochondrial granules in DSA as compared with DZX hearts. CONCLUSIONS: The addition of diazoxide (50 micromol/L) to cardioplegia significantly decreases regional myocardial apoptosis and mitochondrial damage, and provides an additional modality for achieving myocardial protection.

Animals↗
PubMed2002

Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis.

OBJECTIVE: Mitochondrial ATP-sensitive potassium channels have been proposed to be myoprotective. The relevance and specificity of this mechanism in cardiac surgery was unknown. The purpose of this study was to examine the effects of the mitochondrial potassium ATP-sensitive channel opener diazoxide on regional and global myocardial protection using a model of acute myocardial infarction. METHODS: Pigs (n=19) were placed on total cardiopulmonary bypass and then subjected to 30 min normothermic regional ischemia by snaring the left anterior descending coronary artery (LAD). The aorta was then crossclamped and cold blood Deaconess Surgical Associates cardioplegia (DSA; n=6) or DSA containing 50 microM diazoxide (DZX; n=6) was delivered via the aortic root and the hearts subjected to 30 min hypothermic global ischemia. The crossclamp and snare were removed and the hearts reperfused for 120 min. RESULTS: No significant differences in preload recruitable stroke work relationship, Tau, proximal, distal or proximal/distal coronary flow, regional or global segmental shortening, systolic bulging or post-systolic shortening were observed within or between DSA and DZX hearts during reperfusion. Infarct was present only in the region of LAD occlusion in both DSA and DZX hearts. Infarct size (% of area at risk) was 33.6+/-2.9% in DSA and was 16.8+/-2.4% in DZX hearts (P<0.01 versus DSA). Apoptosis as estimated by TUNEL positive nuclei was 120.3+/-48.8 in DSA and was significantly decreased to 21.4+/-5.3 in DZX hearts. Myocardial infarct was located centrally within the area at risk in both DSA and DZX hearts but was significantly increased at borderline zones within the area at risk in DSA hearts. CONCLUSIONS: The addition of diazoxide to cardioplegia significantly decreases regional myocardial cell necrosis and apoptosis in a model of acute myocardial infarction and represents an additional modality for achieving myocardial protection.

Animals↗
PubMed2002

Study of the Therapeutic Effects of Intercessory Prayer (STEP): study design and research methods.

BACKGROUND: The effect of intercessory prayer (IP) on outcome in cardiac cases has been evaluated previously, but results are controversial. The goals of the Study of the Therapeutic Effects of Intercessory Prayer (STEP) are to evaluate the effects of receipt of additional study IP and awareness of receipt of additional study IP on outcomes in patients undergoing coronary artery bypass graft surgery. STEP is not designed to determine whether God exists or whether God does or does not respond to IP. METHODS: STEP is a multicenter, controlled trial of 1802 patients in 6 US hospitals, randomized to 1 of 3 groups. Two groups were informed that they may or may not receive 14 consecutive days of additional IP starting the night before coronary artery bypass graft surgery; Group 1 received IP, Group 2 did not. A third group (Group 3) was informed that they would receive additional IP and did so. Three mainstream religious sites provided daily IP for patients assigned to receive IP. At each hospital, research nurses blinded to patient group assignment reviewed medical records to determine whether complications occurred, on the basis of the Society for Thoracic Surgeons definitions. A blinded nurse auditor from the Coordinating Center reviewed every study patient's data against the medical record before release of study forms. RESULTS: The STEP Data and Safety Monitoring Board reviewed patient safety and outcomes in the first 900 study patients. Patients were enrolled in STEP from January 1998 to November 2000.

Adult↗
PubMedDate not supplied

Interactive biomaterials: taking surgery to the next level.

Medicine has been advanced greatly by implantable biomaterials, but today's standard materials are not without problems. Infection, erosion, adhesions, persistent pain, and other complications suggest that something better is possible. Just as normal tissues self-renew, it is desirable to have an implant recapitulate original anatomy for both structure and function. Short of complete tissue regeneration, perhaps an implant material could transition from an inanimate bridge to a living tissue with strong similarity to the original host architecture-to optimize the biology and not simply the mechanics of tissue repair. Such remodelable or tissue-inductive materials exist today and are in use in a wide variety of surgical applications. Changing the idea that implants must be rigid, inert, and permanent to an understanding that implants can provide short-term mechanics and long-term repair by harnessing the host's healing abilities represents a paradigm shift that will ultimately benefit patients and the practice of surgery.

Animals↗