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Dae-Hyeong Kim,
Roozbeh Ghaffari,
Nanshu Lu,
Shuodao Wang,
Stephen P Lee,
Hohyun Keum,
Robert D'Angelo,
Lauren Klinker,
Yewang Su,
Chaofeng Lu, [......],
Yung-Yu Hsu,
Zhuangjian Liu,
Jeremy Ruskin,
Lizhi Xu,
Chi Lu,
Fiorenzo G Omenetto,
Yonggang Huang,
Moussa Mansour, Marvin J Slepian,
John A Rogers
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ABSTRACT: Curved surfaces, complex geometries, and time-dynamic deformations of the heart create challenges in establishing intimate, nonconstraining interfaces between cardiac structures and medical devices or surgical tools, particularly over large areas. We constructed large area designs for diagnostic and therapeutic stretchable sensor and actuator webs that conformally wrap the epicardium, establishing robust contact without sutures, mechanical fixtures, tapes, or surgical adhesives. These multifunctional web devices exploit open, mesh layouts and mount on thin, bio-resorbable sheets of silk to facilitate handling in a way that yields, after dissolution, exceptionally low mechanical moduli and thicknesses. In vivo studies in rabbit and pig animal models demonstrate the effectiveness of these device webs for measuring and spatially mapping temperature, electrophysiological signals, strain, and physical contact in sheet and balloon-based systems that also have the potential to deliver energy to perform localized tissue ablation.
Proceedings of the National Academy of Sciences 11/2012; · 9.68 Impact Factor
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Suk-Won Hwang,
Hu Tao,
Dae-Hyeong Kim,
Huanyu Cheng,
Jun-Kyul Song,
Elliott Rill,
Mark A Brenckle,
Bruce Panilaitis,
Sang Min Won,
Yun-Soung Kim, [......],
Abid Ameen,
Rui Li,
Yewang Su,
Miaomiao Yang,
David L Kaplan,
Mitchell R Zakin, Marvin J Slepian,
Yonggang Huang,
Fiorenzo G Omenetto,
John A Rogers
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ABSTRACT: A remarkable feature of modern silicon electronics is its ability to remain physically invariant, almost indefinitely for practical purposes. Although this characteristic is a hallmark of applications of integrated circuits that exist today, there might be opportunities for systems that offer the opposite behavior, such as implantable devices that function for medically useful time frames but then completely disappear via resorption by the body. We report a set of materials, manufacturing schemes, device components, and theoretical design tools for a silicon-based complementary metal oxide semiconductor (CMOS) technology that has this type of transient behavior, together with integrated sensors, actuators, power supply systems, and wireless control strategies. An implantable transient device that acts as a programmable nonantibiotic bacteriocide provides a system-level example.
Science 09/2012; 337(6102):1640-4. · 31.20 Impact Factor
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ABSTRACT: Obesity is a growing epidemic in the United States (US). Obesity has been recognized as a modifiable risk factor for many diverse diseases including diabetes, cardiovascular disease and cancer burden. Common contributors to obesity include a high fat diet, smoking and physical inactivity. Systemic effects of obesity include increased micro-inflammatory molecules such as nuclear factor kappa B (NF-κB) that influence the both endothelial and epithelial layers as well as the supportive stroma. An emerging risk factor for micro-inflammation also includes periodontal disease. These pro-inflammatory states are hypothesized to contribute to diabetes as well as cardiovascular disease and cancer through the direct activation of NF-κB. Therefore, a comprehensive health care strategy would include reduction of diabetes, cardiovascular and cancer risk through the decrease in micro-inflammation.
Medical Hypotheses 01/2012; 78(1):29-32. · 1.39 Impact Factor
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ABSTRACT: Periodontitis, one of the most common chronic inflammatory diseases afflicting man, is increasingly being recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD). Non-antimicrobial tetracyclines are known to have inhibitory effects on inflammatory mediators and effector molecules, including cytokines and matrix metalloproteinases (MMPs), associated with both diseases. In this paper, we discuss the evidence that doxycycline and related non-antibiotic chemically modified tetracyclines (e.g., CMT-3) can effectively reduce cytokine (TNF-α, IL-6, and MCP-1) production by human mononuclear inflammatory cells when stimulated either by endotoxin (LPS) or by a complex of C-reactive protein/oxidized LDL cholesterol relevant to the pathogenesis of periodontal disease and ASCVD, respectively. This inhibition by tetracycline compounds appears to be mediated at least in part by a suppression of the phosphorylation/activation of the NFκB cell signaling pathway. We are currently conducting clinical trials on patients who exhibit both diseases, and our preliminary data suggest that virtually all acute coronary syndrome (ACS) patients exhibit moderate-to-severe periodontitis, a higher incidence of this oral inflammatory disease than that seen in the population at large. In other studies, a non-antimicrobial formulation of doxycycline (SDD) has been found to dramatically reduce hsCRP, IL-6 and MMP-9 levels in plasma of ACS patients, and SDD has also been found to significantly increase serum levels of both cardio-protective HDL cholesterol and its core molecule apolipoprotein A-I in ASCVD-vulnerable patients with periodontitis. Our current research suggests that one mechanism involved may be the ability of SDD to inhibit MMP-mediated HDL loss by protecting apolipoprotein A-I from proteinase attack. These pleiotropic mechanisms of non-antimicrobial tetracyclines provide significant therapeutic potential to treat chronic inflammatory diseases including both periodontitis and ASCVD.
Pharmacological Research 07/2011; 64(6):573-9. · 4.44 Impact Factor
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Dae-Hyeong Kim,
Nanshu Lu,
Roozbeh Ghaffari,
Yun-Soung Kim,
Stephen P Lee,
Lizhi Xu,
Jian Wu,
Rak-Hwan Kim,
Jizhou Song,
Zhuangjian Liu, [......],
Bassel de Graff,
Brian Elolampi,
Moussa Mansour, Marvin J Slepian,
Sukwon Hwang,
Joshua D Moss,
Sang-Min Won,
Younggang Huang,
Brian Litt,
John A Rogers
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ABSTRACT: Developing advanced surgical tools for minimally invasive procedures represents an activity of central importance to improving human health. A key challenge is in establishing biocompatible interfaces between the classes of semiconductor device and sensor technologies that might be most useful in this context and the soft, curvilinear surfaces of the body. This paper describes a solution based on materials that integrate directly with the thin elastic membranes of otherwise conventional balloon catheters, to provide diverse, multimodal functionality suitable for clinical use. As examples, we present sensors for measuring temperature, flow, tactile, optical and electrophysiological data, together with radiofrequency electrodes for controlled, local ablation of tissue. Use of such 'instrumented' balloon catheters in live animal models illustrates their operation, as well as their specific utility in cardiac ablation therapy. The same concepts can be applied to other substrates of interest, such as surgical gloves.
Nature Material 03/2011; 10(4):316-23. · 32.84 Impact Factor
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ABSTRACT: Periodontitis has been reported to be associated with coronary artery disease (CAD). Research is needed to determine if therapies that improve periodontal health also reduce systemic measures of inflammation associated with both diseases.
The study registrar randomly assigned 128 eligible postmenopausal women with chronic periodontitis to a twice-daily regimen of subantimicrobial-dose-doxycycline (SDD) or placebo tablets for two years as an adjunct to periodontal maintenance therapy. Through a supplement to the main trial, in which they investigated alveolar bone and clinical attachment level changes, the authors assayed inflammatory mediators and lipid profiles in baseline, one-year and two-year serum samples. The authors analyzed the data by using generalized estimating equations.
In the intent-to-treat analysis across two years, SDD treatment reduced median high-sensitivity C-reactive protein (hs-CRP) by 18 percent (primary outcome; P = .02) and reduced serum matrix metalloproteinase (MMP)-9 (92 kilodalton gelatinase; difference in mean scanning units, -28.44; P < .001), with no significant effect on serum lipids. However, in women more than five years postmenopausal, SDD elevated the level of high-density lipoprotein (HDL) cholesterol (difference in means [milligrams per deciliter], 5.99; P = .01).
A two-year SDD regimen in postmenopausal women significantly reduced the serum inflammatory biomarkers hs-CRP and MMP-9 and, among women more than five years postmenopausal, increased the HDL cholesterol level.
SDD significantly reduced the systemic inflammatory biomarkers hs-CRP and MMP-9. More research is needed to determine whether SDD has a role in managing the care of patients at risk of developing CAD.
Journal of the American Dental Association (1939) 03/2011; 142(3):262-73. · 1.77 Impact Factor
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ABSTRACT: Safety and efficacy studies of various mechanical circulatory support devices are important, but may not be strictly comparable. Lacking prospective randomized studies for different devices, we believe that comparison of risk factor analyses may give the surgeon a tool more powerful than current studies for matching a patient with an appropriate device. In this paper, we report risk factor profiles for bridge to transplantation with the CardioWest total artificial heart and summarize reports for other devices.
A multiinstitutional risk factor analysis of the CardioWest total artificial heart, as a bridge to transplantation in 81 patients, was conducted. Univariate analyses were performed on 43 preimplantation prognostic factors. From this group, eight factors were chosen for multivariate analysis. Our results were compared with all recent risk factor analyses for other devices.
Independent predictors for death at three intervals by multivariate analysis were as follows: "implant to transplant": history of smoking (odds ratio, 34); "implant to 30 days after transplant": history of smoking (odds ratio, 10.00), prothrombin time greater than 16 seconds (odds ratio, 4.76); and "implant to 1 year after transplant": prothrombin time greater than 16 seconds (odds ratio, 3.85). The major difference between this experience and multiple reported experiences with left ventricular assist devices is that for left ventricular assist devices, but not for the temporary CardioWest total artificial heart, right heart failure, high central venous pressure, and being on a ventilator (with or without sepsis) were independent predictors of mortality.
Risk factors for bridge to transplantation with the CardioWest total artificial heart are different from those reported for left ventricular assist devices. Recognition of these risk factor differences may facilitate appropriate device selection.
The Annals of thoracic surgery 06/2008; 85(5):1639-44. · 3.74 Impact Factor
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Nature Clinical Practice Cardiovascular Medicine 03/2008; 5(2):64-5. · 7.04 Impact Factor
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ABSTRACT: Congenital quadricuspid aortic valves (QAVs) are rare phenomena. They are often associated with aortic insufficiency and significant morbidity. A QAV with an associated ascending aortic aneurysm is extremely rare, and these conditions might have a shared embryonic etiology. We describe the case of a patient with a QAV associated with aortic aneurysm. Pertinent literature on the QAV is reviewed, and embryological factors that may contribute to its pathogenesis are discussed.
Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology 11/2007; 18(1):49-52. · 1.63 Impact Factor
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ABSTRACT: The CardioWest Total Artificial Heart orthotopically replaces both native cardiac ventricles and all cardiac valves, thus eliminating problems commonly seen in the bridge to transplantation with left ventricular and biventricular assist devices, such as right heart failure, valvular regurgitation, cardiac arrhythmias, ventricular clots, intraventricular communications, and low blood flows.
We conducted a nonrandomized, prospective study in five centers with the use of historical controls. The purpose was to assess the safety and efficacy of the CardioWest Total Artificial Heart in transplant-eligible patients at risk for imminent death from irreversible biventricular cardiac failure. The primary end points included the rates of survival to heart transplantation and of survival after transplantation.
Eighty-one patients received the artificial-heart device. The rate of survival to transplantation was 79 percent (95 percent confidence interval, 68 to 87 percent). Of the 35 control patients who met the same entry criteria but did not receive the artificial heart, 46 percent survived to transplantation (P<0.001). Overall, the one-year survival rate among the patients who received the artificial heart was 70 percent, as compared with 31 percent among the controls (P<0.001). One-year and five-year survival rates after transplantation among patients who had received a total artificial heart as a bridge to transplantation were 86 and 64 percent.
Implantation of the total artificial heart improved the rate of survival to cardiac transplantation and survival after transplantation. This device prevents death in critically ill patients who have irreversible biventricular failure and are candidates for cardiac transplantation.
New England Journal of Medicine 08/2004; 351(9):859-67. · 53.30 Impact Factor
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Jack G Copeland,
Richard G Smith,
Francisco A Arabia,
Paul E Nolan,
Douglas McClellan,
Pei H Tsau,
Gulshan K Sethi,
Raj K Bose,
Mary E Banchy,
Diane L Covington, Marvin J Slepian
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ABSTRACT: The SynCardia CardioWest total artificial heart (CardioWest TAH) is a biventricular, orthotopic, pneumatic, pulsatile blood pump driven by an external console. For each ventricle, the length of the blood-flow path is shorter and the inflow and outflow valves are larger than in any other bridge-to-transplant device, resulting in greater blood flow at smaller pre-load. Such a device should be optimal for bridging transplant candidates who have biventricular failure and for whom all other therapies have failed.
From January 1, 1993, to April 1, 2002, we prospectively studied 62 consecutive CardioWest TAH implant recipients to document safety and efficacy in bridge to transplantation. We used multisystem monitoring and multidrug therapy for anti-coagulation in 58 patients starting September 1, 1994.
Before implantation, patients were critically ill with biventricular heart failure. Mortality in this group from the time of implantation until transplantation was 23%. Causes of death during device support included multi-organ failure (6), sepsis (3), and valve entrapment (2). Forty-eight patients underwent transplantation (77%). Forty-two survived to hospital discharge (68% of the total, 88% of those undergoing transplantation). Adverse events included bleeding (20%), device malfunction (5%), fit complications (3%), mediastinal infections (5%), visceral embolus (1.6%), and stroke during support (1.6%). The linearized stroke rate was 0.068 events per patient-year.
Sixty-eight percent of critically ill transplant candidates for whom medical therapy failed were bridged to transplantation with the CardioWest TAH and survived long-term. Most deaths that occurred during device support were related to pre-implant problems. Infection and stroke were rare events. Therefore, we recommend the CardioWest TAH as the biventricular bridge-to-transplant device of choice.
The Journal of Heart and Lung Transplantation 08/2004; 23(7):823-31. · 4.33 Impact Factor
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ABSTRACT: The objective of this study was to assess acute patency of a new myocardial revascularization device that connects the left ventricular cavity to a coronary artery (termed ventriculo-coronary artery bypass, VCAB) thereby providing proximal and distal blood flow from the site of the anastomosis.
A device made of expanded polytetrafluoroethylene and low density polyethylene was implanted from the base of the left ventricle to the mid left anterior descending coronary artery (LAD) in 11 juvenile domestic pigs using a beating heart approach. Flow rates were measured in the distal LAD before and after implant using ultrasonic flow techniques, and patency was assessed at explant at either 2 or 4 weeks post-implantation. Myocardial perfusion using positron emission tomography (PET) was assessed in a separate set of pigs (n=2) revascularized by VCAB 2 weeks post-implant.
Net forward flow distal to the implanted device was 73 +/- 15% of native LAD flow. PET demonstrated that the target myocardium was perfused at 85% of that seen in the remote, control myocardium. Device patency rate was 80% (4/5) at 2 weeks in one set of pigs and 83% (5/6) at 4 weeks in a second set of pigs. Histologic analysis showed formation of neointima along the extraventricular segment of the device.
This study demonstrates the promise of perfusing ischemic myocardium using a VCAB approach with a device that provides blood flow both proximal and distal to the anastomosis. Patency of the transmyocardial device was encouraging at 2 and 4 weeks and warrants further investigation.
European Journal of Cardio-Thoracic Surgery 02/2004; 25(1):43-50. · 2.55 Impact Factor
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ABSTRACT: The CardioWest TAH was created and initially tested at the same time as the Thoratec, Novacor, and HeartMate devices. It was designed as a permanent artificial heart and was the first-ever mechanical circulatory device to be used as destination therapy. Twenty years have passed since that early experience. Pneumatic technology is still current and being developed as in existing or new implantable Thoratec VADs the pneumatic HeartMate, and the Abiomed BVS 5000 pumps. Portable pneumatic drivers have been available since 1982, and in recent times have allowed discharge to home of substantial numbers of patients, thus reducing the length of hospital stays and making mechanical device support less expensive to society and more tolerable to patients. Within months, a portable driver for the CardioWest will be available. The documented benefits of the CardioWest TAH include rescue of: critically ill patients with advanced heart failure; patients with biventricular failure especially those with significant right heart failure, elevated pulmonary vascular resistance, or pulmonary edema; patients with renal or hepatic failure secondary to low cardiac output; patients with massive myocardial damage such as those with post-\infarction VSD or irreversible cardiac graft rejection; patients with mechanical valves or native valve disease; and patients with intractable arrhythmias and heart failure. High device outputs with restoration of normal filling pressures result in high perfusion pressures that have led to dramatic recoveries, convalescence, and return to levels of activity compatible with normal life. The average device output with the CardioWest TAH is higher than any other approved or investigational device. The reason for this resides in design simplicity this device has the shortest and largest inflow pathway. Stroke, in the authors' own series, is rare with a linearized rate of 0.068 events per patient year. If the experiences of La Pitie and the University of Arizona are combined, there has been one stroke in 25 patient years (0.04 events/patient year). Serious infections have been rare (12% of patients). No clinical mediastinitis has occurred. Drivelines have healed in tightly and never caused an "ascending" infection. There has not been a case of device endocarditis. Using a broad definition of bleeding, including takeback reoperation for bleeding, bleeding more than 8 units in the first postoperative 24 hours or 5 units over any other 48-hour period, a 25% to 36% incidence has been documented. No cases of fatal exsanguination have resulted, as there have been with the HeartMate. The incidence of bleeding as an adverse event is about 17% lower than the rate reported for the HeartMate VE LVAD, and it is about the same as that reported for Novacor and for Thoratec. Implantation of this device is relatively easy and often done (with attending help) by the authors' residents. If one follows the guidelines for fitting the device, and takes the recommended advice for implantation, hemostasis is excellent and restoration of immediate cardiac function with high flows is nearly automatic. Use of a neopericardium of 0.1 mm EPTFE at the time of implantation assures atraumatic and relatively quick re-entry for transplantation and prevents the normal inflammatory mediastinal reaction that might be desirable in a destination application. In selected patients the CardioWest TAH is the device of choice for bridge to transplantation. When a portable driver becomes available, out of hospital management of CardioWest TAH patients will be feasible and consideration of use of this device for longer term applications, (e.g., "destination therapy,") will be reasonable. A wearable driver, even smaller than a portable, will improve quality of life and expand the patient population that may be therapeutically served with this system. In short, the CardioWest TAH has come nearly full circle. It was first used as a destination device. It has since been used as a bridge to transplantation in nearly 200 patients as the Jarvik-7/Symbion TAH and, since 1993, in over 225 patients as CardioWest. The results have improved with time. Thromboembolism and infection rates have been competitive with currently available devices. Device reliability and durability have been excellent. Survival rates have been very high in a group of perhaps the sickest patients to be supported with any pulsatile device. Pneumatic technology has improved with portability and miniaturization, and there is reason to believe that it will become even better. Application of modern manufacturing techniques to this very simple device raises the possibility of significant manufacturing cost reduction, in an era of prohibitive cost for other devices. All of this establishes the CardioWest as a valuable device for any program that is seriously interested in end-stage heart disease and a likely device for permanent use in appropriately selected patients.
Cardiology Clinics 03/2003; 21(1):101-13. · 1.36 Impact Factor
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ABSTRACT: Despite the advance of laparoscopic partial nephrectomy, significant technical limitations remain with regard to control of bleeding and closure of the collecting system. An attractive approach on the horizon for local hemostatic and wound control is the use of local tissue sealants. To date, sealants remain largely derived from natural biologic products and are difficult to apply laparoscopically with precise local control. In this study, we examined the novel strategy of forming occlusive tissue-adherent hydrogels utilizing a synthetic biodegradable polyethylene glycol-lactide copolymer (PEG-lactide) as an in situ occlusive barrier for hemostasis and wound control. Specifically, the objects of this study were to determine if PEG-lactide hydrogels could be formed intraperitoneally on renal tissue, to test the adhesiveness of the hydrogels to injured renal parenchyma, and to evaluate the ability of adherent hydrogel barriers to limit renal parenchymal bleeding and collecting system leakage following renal pole amputation or wedge excision.
Five kidneys from three female pigs were used in a nonsurvival study. A standardized model for laparoscopic partial nephrectomy was created by performing wedge excision or polar amputation under vascular control using a laparoscopic Satinsky clamp. Bleeding briskness following injury was assessed utilizing a scoring system and free blood quantitated comparing a conventional "clamp and wait" strategy with an adherent hydrogel strategy. For the hydrogel group, PEG-lactide hydrogel primer and macromer were applied through laparoscopic ports. The hydrogel was polymerized using a xenon light source, and the pedicle clamp was released to observe for bleeding. A subsequent opposite polar injury was created to confirm renal perfusion and the sites were compared. The kidneys were removed, and the adhesion of the hydrogel to the renal parenchyma was examined.
The PEG-lactide macromer was effectively applied to five kidneys following partial nephrectomy. In all cases, successful intraperitoneal in situ polymerization was achieved, with resultant hydrogel formation. Polymeric hydrogel adhesion to the cut renal parenchyma was assessed semiquantitatively following vigorous cyclic washing. In all cases, polymer gels remained adherent without any evidence of peeling, delamination, or separation from the underlying tissue surface. In the control group, the mean bleeding score was 2.63 +/- 0.48 v 0.00 +/- 0.00 in the gel-treated group (P < 0.001). Blood loss in the control group was 56 +/- 5 ml v 0.00 +/- 0.00 in the gel-treated group (P < 0.001). In an ex vivo retrograde ureteral perfusion, no leakage was observed at pressure as high as 100 mm Hg.
In this feasibility study, a biodegradable PEG-lactide polymer system photopolymerized rapidly in situ on exposed renal parenchymal surfaces, forming adherent hydrogel barriers. When applied during vascular clamping, an adequate physical bond and patch-like cap was created to prevent bleeding at physiologic renal perfusion pressures. Use of locally applied occlusive hydrogels holds promise for hemostasis and local wound control during laparoscopic urologic procedures.
Journal of Endourology 09/2002; 16(7):489-94. · 1.85 Impact Factor
