Publications by authors named "John P Carney"

9 Publications

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Establishing Background Pathologic Changes of Valve Replacement Surgery in Sheep.

Cardiovasc Eng Technol 2021 Jul 14. Epub 2021 Jul 14.

Experimental Surgical Services Laboratory, Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA.

Purpose: Sheep are the standard preclinical model for assessing safety of novel replacement heart valves, yet the anatomic and pathologic effects of invasive surgery, including those involving cardiopulmonary bypass (CPB), are unknown. Thus, we aimed to determine the gross, hematologic and biochemical effects of sham mitral and aortic replacement valve procedures in sheep to establish a useful control for evaluation of novel replacement valves.

Methods: Six control sheep were examined without any surgical intervention. Six sham mitral valve replacements (MVR) and six sham aortic valve replacements (AVR) were performed on 12 sheep. Complete blood counts and serum biochemistry were performed throughout the study. Sheep were sacrificed with a necropsy performed at 90 days.

Results: Renal infarcts (RIs) were the most frequently observed lesion, averaging 4.7 in control sheep, 2.5 with MVR and 5.8 with AVR. The number of infarcts strongly correlated with total estimated area of infarcted kidney (r = .84, p < .01). Additional cardiac interventions were significantly correlated with increased numbers of RIs (r = .85, p < .01). There was no correlation between number of RIs and time on CPB, or between AVR and MVR procedures.

Conclusion: The sheep model for AVR and MVR requires invasive surgery and CPB, which are associated with background anatomic and pathologic changes, especially in cases with additional surgical cardiac interventions. These findings serve as a critical control for future evaluation and development of novel replacement valves in order to distinguish device-related safety issues from expected outcomes of the surgical procedure and normal background changes in sheep.
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http://dx.doi.org/10.1007/s13239-021-00563-6DOI Listing
July 2021

Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs.

Sci Transl Med 2021 03;13(585)

Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.

There is a need for replacement heart valves that can grow with children. We fabricated tubes of fibroblast-derived collagenous matrix that have been shown to regenerate and grow as a pulmonary artery replacement in lambs and implemented a design for a valved conduit consisting of three tubes sewn together. Seven lambs were implanted with tri-tube valved conduits in sequential cohorts and compared to bioprosthetic conduits. Valves implanted into the pulmonary artery of two lambs of the first cohort of four animals functioned with mild regurgitation and systolic pressure drops <10 mmHg up to 52 weeks after implantation, during which the valve diameter increased from 19 mm to a physiologically normal ~25 mm. In a second cohort, the valve design was modified to include an additional tube, creating a sleeve around the tri-tube valve to counteract faster root growth relative to the leaflets. Two valves exhibited trivial-to-mild regurgitation at 52 weeks with similar diameter increases to ~25 mm and systolic pressure drops of <5 mmHg, whereas the third valve showed similar findings until moderate regurgitation was observed at 52 weeks, correlating to hyperincrease in the valve diameter. In all explanted valves, the leaflets contained interstitial cells and an endothelium progressing from the base of the leaflets and remained thin and pliable with sparse, punctate microcalcifications. The tri-tube valves demonstrated reduced calcification and improved hemodynamic function compared to clinically used pediatric bioprosthetic valves tested in the same model. This tri-tube valved conduit has potential for long-term valve growth in children.
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http://dx.doi.org/10.1126/scitranslmed.abb7225DOI Listing
March 2021

New Model for the Assessment of Transcatheter Aortic Valve Replacement Devices in Sheep.

J Invest Surg 2020 Dec 28:1-10. Epub 2020 Dec 28.

Experimental Surgical Services Laboratory, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.

Background: Transcatheter aortic valve replacement (TAVR) is an effective therapy in treating high-risk patients suffering from aortic stenosis. Animal models used to evaluate safety and efficacy of TAVR devices prior to clinical use lack a stenotic aortic annulus, a critical impediment to long-term TAVR device evaluation. We sought to create a reproducible model of aortic stenosis using a modified aortic annuloplasty (MAA) procedure in sheep, followed by deployment and long-term evaluation of TAVR devices using this model.

Methods: Twelve sheep underwent the MAA procedure and were recovered. Transthoracic echocardiography (TTE) was used to monitor changes in the aortic annulus in the postoperative period. At 60 days post-MAA, Test group animals were anesthetized for TAVR insertion and Control animals underwent a necropsy. Test animals were recovered following TAVR insertion and observed for a postoperative period of 140 days.

Results: Twelve sheep survived the annuloplasty procedure and the 60-day recovery period. Gross examination of seven Control group animals revealed the implanted annuloplasty ring segments formed hard protrusions into the aortic annulus. Five sheep in the Test group underwent successful deployment of Abbott's experimental TAVR device without evidence of migration. Examination at 140 days post-TAVR insertion showed all devices tightly anchored within the modified aortic annulus.

Conclusions: The MAA procedure creates stenotic segments in the aortic annulus with adequate rigidity for anchorage and long-term evaluation of TAVR devices. This represents the first model that successfully mimics human aortic stenosis and provides a clinically relevant TAVR deployment platform for long-term evaluation in sheep.
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http://dx.doi.org/10.1080/08941939.2020.1864796DOI Listing
December 2020

Porcine Model of the Arterial Switch Operation: Implications for Unique Strategies in the Management of Hypoplastic Left Ventricles.

Pediatr Cardiol 2021 Mar 30;42(3):501-509. Epub 2020 Nov 30.

Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.

There are no reports on the performance of the arterial switch operation (ASO) in a normal heart with normally related great vessels. The objective of this study was to determine whether the ASO could be performed in a healthy animal model. Cardiopulmonary bypass (CPB) and coronary translocation techniques were used to perform ASO in neonatal piglets or a staged ASO with prior main pulmonary artery (PA) banding. Primary ASO was performed in four neonatal piglets. Coronary translocation was effective with angiograms confirming patency. Piglets could not be weaned from CPB due to right ventricle (RV) dysfunction. To improve RV function for the ASO, nine piglets had PA banding. All survived the procedure. Post-banding RV pressure increased from a mean of 20.3 ± 2.2 mmHg to 36.5 ± 7.3 mmHg (p = 0.007). At 58 ± 1 days post-banding, piglets underwent cardiac MRIs revealing RV hypertrophy, and RV pressure overload with mildly reduced RV function. Catheterization confirmed RV systolic pressures of 84.0 ± 6.7 mmHg with LV systolic pressure 83.3 ± 6.7 mmHg (p = 0.43). The remaining five PA banded piglets underwent ASO at 51 ± 0 days post-banding. Three of five were weaned from bypass with patent coronary arteries and adequate RV function. We were able to successfully perform an arterial switch with documented patent coronary arteries on standard anatomy great vessels in a healthy animal model. To our knowledge this is the first time this procedure has been successfully performed. The model may have implications for studying the failing systemic RV, and may support a novel approach for management of borderline, pulsatile left ventricles.
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http://dx.doi.org/10.1007/s00246-020-02507-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990748PMC
March 2021

Anisotropic Polytetrafluoroethylene Cardiovascular Conduits Spontaneously Expand in a Growing Lamb Model.

J Invest Surg 2020 Aug 14:1-7. Epub 2020 Aug 14.

Experimental Surgical Services Laboratory, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.

Background: Insertion of conduits from the right ventricle (RV) to the pulmonary artery (PA) is a commonly used technique for repair of congenital heart defects. The vast majority of infants and children will require reoperation and/or re-intervention to replace the conduit. Some children may require multiple reoperations, with the risk of death and morbidity increasing significantly with each subsequent operation. We evaluated the feasibility and performance of a relatively novel anisotropic conduit for cardiovascular repair in the growing lamb model.

Materials And Methods: Lambs were allocated into a control ( = 3) or test ( = 4, anisotropic) conduit group. Control conventional polytetrafluoroethylene (PTFE) conduits or test anisotropic expanded PTFE (ePTFE) based test conduits measuring 10-11 mm in diameter were sewn as interpositional grafts in the main pulmonary artery (MPA) and followed up to 6 months. Clinical and echocardiographic evaluations were performed monthly with hemodynamic and angiographic assessment at 3 and 6 months.

Results: Control conduits did not expand, all 3 animals developed one or more adverse events including tachypnea, ascites, inappetence, lethargy, and mortality due to severe right heart failure and significantly higher peak trans-conduit gradients (48.5 ± 5.1 p = 0.02). The test conduits spontaneously expanded up to 14.8 ± 0.8 mm in diameter, no adverse events were observed in any animals and trans-conduit gradients were significantly lower (27.0 ± 8.3, p = 0.02).

Conclusions: Anisotropic ePTFE conduits can be safely implanted in growing lambs with stable hemodynamics. This spontaneously expanding anisotropic conduit may represent a novel approach to congenital heart repairs that would avoid the need for reoperation or multiple operations.
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http://dx.doi.org/10.1080/08941939.2020.1805056DOI Listing
August 2020

Feasibility Study of Catheter-Based Interventions for Anisotropic Expanded Polytetrafluoroethylene Cardiovascular Conduits in a Growing Lamb Model.

J Invest Surg 2020 Jul 20:1-7. Epub 2020 Jul 20.

Experimental Surgical Services Laboratory, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.

Background: Cardiovascular repair in children often requires implant of conduits which do not have growth potential and will require reoperation. In the current study we sought to determine the feasibility of catheter-based interventions of anisotropic conduits inserted as interposition grafts in the main pulmonary artery (MPA) of growing lambs.

Methods: Lambs underwent interpositional implant of either an anisotropic expanded polytetrafluoroethylene (ePTFE) (Test) conduit or conventional PTFE (Control) conduit. In the postoperative period, lambs were anesthetized and underwent catheter-based interventions consisting of hemodynamic and angiographic data collection, balloon dilation and/or stenting of the conduit at 3, 6 or 9 month postoperative time point.

Results: At 3 months, control lambs showed significant increases in right ventricular pressures and trans-conduit gradients in comparison to test lambs. Test conduit diameters were significantly larger compared to controls due to spontaneous radial expansion of the anisotropic conduit. Balloon dilation of test conduits at 3 and 6 months showed a reduction in RV pressure and statistically significant improvement in the RV outflow tract gradient as well as significant increase in graft diameter, compared to both control and pre-dilation conditions. Furthermore, the test conduit diameter increased significantly compared to the pre-balloon and control conditions at each time point. Necropsy of test conduits showed no evidence of tears, perforations, or clot and smooth interiors with well-healed anastomoses.

Conclusions: Anisotropic conduits implanted as interposition grafts in the MPA show spontaneous expansion, and can safely and effectively undergo catheter-based interventions, with significant increases in graft diameter occurring after balloon dilation.
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http://dx.doi.org/10.1080/08941939.2020.1795324DOI Listing
July 2020

Pilot study investigating the feasibility of mitral valve repair without aortic cross-clamping and cardioplegia.

Can J Vet Res 2020 Apr;84(2):159-162

Veterinary Medical Center North, University of Minnesota, 1365 Gortner Avenue, St. Paul, Minnesota 55108, USA (Gordon-Evans); University of Minnesota Medical School, 420 Delaware Street SE, Mayo Mail Code 195, Minneapolis, Minnesota 55455, USA (Carney, Lahti, Bianco).

There is evidence that perfusing the heart with a heart and lung machine is less injurious than cross-clamping the aorta and administering cardioplegia during cardiac surgery. Although mitral valve replacement has been carried out without aortic cross-clamping and cardioplegia, it has been stated that cross-clamping is necessary in order to maintain visualization and a motionless surgical field for mitral valve repair. The purpose of this study was to determine the surgical feasibility of mitral valve repair without cross-clamping the aorta and using cardioplegia. Our hypothesis was that a completely bloodless and motion-free field would not be necessary to carry out mitral valve repair with annuloplasty and synthetic chordae tendineae sutures. Papillary muscles, chordae tendineae, annulus, and mitral valve leaflets were all readily visualized. Chordae tendineae sutures were used and annuloplasty was conducted without visual obstruction or motion interference. Our results show that mitral valve repair is feasible without cross-clamping the aorta and using cardioplegia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088510PMC
April 2020

The Hancock® Valved Conduit for Right Ventricular Outflow Tract Reconstruction in Sheep for Assessing New Devices.

J Heart Valve Dis 2017 07;26(4):472-480

Division of Experimental Surgery, Department of Surgery, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA. Electronic correspondence:

Background And Aim Of The Study: Xenograft conduits have been used successfully to repair congenital heart defects, but are prone to failure over time. Hence, in order to improve patient outcomes, better xenografts are being developed. When evaluating a conduit's performance and safety it must first be compared against a clinically available control in a large animal model. The study aim was to evaluate a clinically available xenograft conduit used in right ventricular outflow tract (RVOT) reconstruction in a sheep model.

Methods: RVOT reconstruction was performed in 13 adult and juvenile sheep, using the Medtronic Hancock® Bioprosthetic Valved Conduit (Hancock conduit). The method had previously been used on patients, and a newly modified variant termed 'RVOT Extraction' was employed to facilitate the surgical procedure. Animals were monitored over predetermined terms of 70 to 140 days. Serial transthoracic echocardiography, intracardiac pressure measurements and angiography were performed. On study completion the animals were euthanized and necropsies performed.

Results: Two animals died prior to their designated study term due to severe valvular stenosis and distal conduit narrowing, respectively. Thus, 11 animals survived the study term, with few or no complications. Generally, maximal and mean transvalvular pressure gradients across the implanted conduits were increased throughout the postoperative course. Among 11 full-term animals, seven conduits were patent with mild or no pseudointimal proliferation and with flexible leaflets maintaining the hemodynamic integrity of the valve.

Conclusions: RVOT reconstruction using the Hancock conduit was shown to be successful in sheep, with durable and efficient performances. With its extensive clinical use in patients, and ability for long-term use in sheep (as described in the present study) it can be concluded that the Hancock conduit is an excellent control device for the evaluation of new xenografts in future preclinical studies.
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July 2017

Out-of-hospital cardiac arrest and airborne fine particulate matter: a case-crossover analysis of emergency medical services data in Indianapolis, Indiana.

Environ Health Perspect 2008 May;116(5):631-6

School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.

Background: Previous studies have found particulate matter (PM) < 2.5 microm in aerodynamic diameter (PM2.5) associated with heart disease mortality. Although rapid effects of PM2.5 exposure on the cardiovascular system have been proposed, few studies have investigated the effect of short-term exposures on out-of-hospital cardiac arrest (OHCA).

Objectives: We aimed to determine whether short-term PM2.5 exposures increased the risk of OHCA and whether risk depended on subject characteristics or presenting heart rhythm.

Methods: A case-crossover analysis determined hazard ratios (HRs) for OHCAs logged by emergency medical systems (EMS) versus hourly and daily PM2.5 exposures at the time of the OHCA and for daily and hourly periods before it.

Results: For all OHCAs (n = 1,374), exposures on the day of the arrest or 1-3 days before arrest had no significant effect on the incidence of OHCA. For cardiac arrests witnessed by bystanders (n = 511), OHCA risk significantly increased with PM2.5 exposure during the hour of the arrest (HR for a 10-microg/m3 increase in PM2.5 exposure = 1.12; 95% confidence interval, 1.01-1.25). For the subsets of subjects who were white, 60-75 years of age, or presented with asystole, OHCA risk significantly increased with PM2.5 during the hour of the arrest (HRs for a 10-microg/m3 increase in PM2.5 = 1.18, 1.25, or 1.22, respectively; p < 0.05). HR generally decreased as the time lag between PM2.5 exposure and OHCA increased.

Conclusion: The results suggest an acute effect of short-term PM2.5 exposure in precipitating OHCAs, and a need to investigate further the role of subject factors in the effects of PM on the risk of OHCA.
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http://dx.doi.org/10.1289/ehp.10757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367645PMC
May 2008
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