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Ann Thorac Surg 2005;79:168-177
© 2005 The Society of Thoracic Surgeons


Original article: Cardiovascular

In Vitro Studies of Human Hearts

Alexander J. Hill, PhDa,c,d, Timothy G. Laske, PhDa,d, James A. Coles, Jr, PhDd, Daniel C. Sigg, MD, PhDd, Nicholas D. Skadsberg, MSa,c, Sarah A. Vincent, MSa,c, Charles L. Soule, BSc, William J. Gallagher, BAc, Paul A. Iaizzo, PhDb,c,*

a Department of Biomedical Engineering
b Department of Physiology
c Department of Surgery, University of Minnesota
d Medtronic Inc, Minneapolis, Minnesota, USA

Accepted for publication June 16, 2004.

* Address reprint requests to Dr Iaizzo, Department of Surgery, MMC 107, 420 Delaware St SE, Minneapolis, MN 55455 (E-mail: iaizz001{at}umn.edu).


    Abstract
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Isolated mammalian hearts have been used in numerous studies that have led to many important discoveries in cardiac physiology, pharmacology, and surgery. Multiple methods of perfusion have been described including retrograde and/or antegrade flows and crystalloid or blood perfusates. Furthermore, multiple species have been utilized for such studies including the following: rat, rabbit, guinea pig, canine, and swine. The objective of this study was to describe a unique isolated heart preparation, utilizing human hearts not viable for transplant, which allows for physiologic perfusion and endocardial imaging.

METHODS: Utilizing standard cardiac transplantation procedures, 12 human hearts deemed not viable for transplant were explanted to an isolated heart apparatus. A clear, modified Krebs-Henseleit buffer was used as a blood substitute, which allowed for endocardial imaging utilizing 6.0 mm endoscopic video cameras inserted into the cardiac chambers. The hearts were perfused in Langendorff (retrograde) and/or working (physiologic) mode.

RESULTS: Eleven of 12 hearts achieved the following performance in working mode: peak left ventricular pressure of 21.5 to 75.8 mm Hg, with an average of 42.7 ± 19.9 mm Hg. Intracardiac anatomical imaging was possible in all hearts, providing unique views of normal and pathological endocardial anatomy as well as biomedical device-heart interactions.

CONCLUSIONS: We have described a unique isolated heart preparation with which we have successfully reanimated 11 human hearts deemed not viable for transplant, perfused them by working mode, and performed intracardiac anatomical imaging. This approach provides a novel means for obtaining images of functional human cardiac anatomy and various types of unique biomedical assessments.


    Introduction
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

Drs Hill, Laske, Coles, and Sigg disclose that they have a financial relationship with Medtronic, Inc.

 

Since Langendorff first described his perfusion procedure [1], isolated mammalian hearts have been used in numerous studies that have led to many important discoveries in the fields of cardiac physiology, pharmacology, and surgery. Isolated hearts are unique because they allow for the study of myocardial characteristics separate from the milieu of the intact animal and allow for increased control over experimental conditions. Multiple methods of perfusion are described including retrograde [1] and/or antegrade [2–4] flows and crystalloid or blood perfusates [4–8].

Primarily, isolated heart preparations are performed on small mammals such as the rat, rabbit, and guinea pig [2, 3, 5, 7, 9], although large mammalian preparations have been described [4, 7, 8, 10–13]. Selection of an experimental model depends on many factors including cost, ease of data collection, relevance to the human condition, and experimental questions to be answered [14]. Cost and ease of data collection are primary reasons for the widespread use of small mammalian hearts instead of large mammalian hearts. Nevertheless, there may be certain instances where large mammalian hearts, and even human hearts, would be better suited; ie, anatomical studies and biomedical device design and testing.

The specifics of the ex vivo swine heart preparation used in our laboratory have previously been described [4]. More specifically, this preparation simulates in situ physiology of swine and allows for specific anatomical characterization, pharmacologic studies, ischemia studies, and/or biomedical device testing. It was hypothesized that this model could be adapted to allow explanted human hearts to function in a four-chamber working mode in vitro, which would allow for similar studies as those conducted on the swine hearts. The specific aims of this publication are to present an in-depth description of our experiences with isolated human hearts, describe physiologic data obtained, provide examples of anatomic features, and make suggestions for future study.


    Material and Methods
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
These studies were approved by the Institutional Review Board: Human Subjects Committee at the University of Minnesota. Additionally, consent for use of the hearts for research purposes was received from the donor's closest relative(s) before explantation. Twelve donor human hearts, deemed not viable for transplant, were explanted using standard cardiac transplant procedures. The hearts were not transplanted due to viral infection, low ejection fraction, or lack of a suitable recipient. In each procedure, a median sternotomy was performed and a chest retractor was placed to expose contents of the thoracic cavity. The pericardial sac was opened with a midsagittal incision and the heart was reflected anteriorly. The inferior vena cava was located and umbilical tape ties were placed around it and tied off. The aortic root and a portion of the descending aorta were dissected clear of connective tissue. An aortic root cannula (11012; Medtronic, Inc, Minneapolis, MN) was secured into the ascending aorta for cardioplegia delivery (Plegisol, Abbott Laboratories, North Chicago, IL). Just before Plegisol delivery, the inferior vena cava was removed with the liver and the superior vena cava and aorta were cross-clamped (distal to the aortic root cannula). Plegisol was delivered under pressure (> 100 mm Hg) to the heart through the aortic cannula at the same time the abdominal organs were perfused, and the heart was surrounded by ice. After cardiac arrest, the rate of Plegisol delivery was slowed and maintained until all other organs were recovered. The heart-lung block was excised by transecting the major vessels as well as the trachea and esophagus. In some individual cases, the lungs were recovered for transplant or research by other investigators. If the lungs were used for transplant, they were recovered before removal of the heart. The heart or heart-lung block was placed in cold saline or University of Wisconsin solution and excess tissue was removed (including the lungs, if used for research). The heart was then placed in a sealed container and bathed in University of Wisconsin solution; this container was then placed on ice for transportation to our research laboratory. Unfortunately, four hearts (Nos. 9 to 12) were not arrested with cardioplegia as described above due to constraints in the operating room during organ harvest. These hearts were arrested by cross-clamp and topical cooling with ice; even so, cessation of cardiac electrical activity was seen within 3 to 5 minutes.

Upon arrival at our research laboratory (< 2 hours in all cases), the heart was placed in an ice slurry of modified Krebs-Henseleit buffer solution and the major vessels were cannulated with silicone tubing (50 to 75 minutes). See Table 1 for total ischemic times, including operating room time, transport time, and cannulation time. The following major vessels were cannulated: superior vena cava, pulmonary trunk, descending aorta, brachiocephalic artery, and the left superior pulmonary vein. In the last four hearts (Nos. 9 to 12), the right superior pulmonary vein was cannulated as well. The rest of the pulmonary veins were tied off with umbilical tape. The inferior vena cava was also cannulated. In some instances, due to the recovery of the liver, the inferior vena cava was dissected very close to the right atrium or completely removed. In these cases, the inferior vena cava ostia were either sutured closed or a flange adapter was sewn in. In several hearts, an additional cannula was sewn into the right atrial appendage to facilitate endoscopic imaging. The left common carotid and the left subclavian artery arising off the arch of the aorta were sealed with snares to allow access.


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Table 1. Preexplantation Demographic Data
 
After cannulation, the hearts were placed on an in vitro apparatus previously described by Chinchoy and colleagues [4] (Fig 1). The newer, modified apparatus in these experiments is suitable for all large mammalian hearts including human hearts, and is capable of supporting both Langendorff and four-chamber working modes. The hearts were oriented similar to a patient on the operating table with the heart exposed through a sternotomy, and the posterior surface resting on a foam pad when the bucket was empty of fluid (Fig 1). A clear, modified Krebs-Henseleit solution was used as a blood substitute to perfuse the hearts, as it allowed for endocardial imaging. Circulating volumes of perfusate were approximately 7 L throughout the entire circuit. Periodic buffer changes of 4 L were performed to maintain visual clarity, washout metabolic by-products, and maintain physiologic viability (approximately every 30 to 60 minutes). To maintain proper perfusate and myocardial temperature, water jackets surrounding the arterial compliance chamber and both preload chambers were maintained at 40°C (370 Bio-Cal, Medtronic, Inc), which resulted in perfusate temperatures of 38°C. Measured myocardial temperatures were maintained at 37°C ± 0.5°C. Two pumps (550 Bio-Console, Medtronic, Inc) pumped perfusate to the preload chambers; additionally, a central filter-reservoir with an attached oxygenator (Affinity NT 541, Medtronic, Inc) filtered large particulate matter from the perfusate, oxygenated the perfusate pumped to the left heart, and acted as a venous pool. In Langendorff perfusion mode, perfusate was pumped through the left-side pump in a retrograde direction down the aortic cannula and through the coronary system to empty into the right atrium. In four-chamber working mode, perfusate was circulated through the heart in a physiologic manner. The heights of the fluid column in the preload chambers above entry into the heart determined the amount of preload placed on the heart and were kept at near physiologic values (mean right atrial pressure: 9.1 ± 6.3 mm Hg; mean left atrial pressure: 14.4 ± 6 mm Hg) by adjusting the heights of the chamber and/or the speed of the pumps. In four-chamber working mode, perfusate was ejected from both ventricles during systole and returned to the central reservoir. Afterload was simulated by adjusting the heights of the tubing leading from the aortic and pulmonic cannulas to the reservoir, and arterial compliance was simulated by employing an air-filled closed chamber in line between the aortic cannula and the reservoir.



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Fig 1. Schematic diagram illustrating the isolated heart apparatus. Blue lines indicate deoxygenated fluid flow and red lines indicate oxygenated fluid flow. Arrows indicate direction of flow. Also shown is an external image of heart (No 12) in the bucket supported on the posterior aspect by a foam pad (upper left corner of the image). The foam pad has been carved out to mimic the contours of the heart and reduce pressure points on the organ. Additionally, holes have been cut through the foam to allow pass-through of the vessel cannulas. 1 = left side afterload; 2 = right side afterload; 3 = left side preload; 4 = right side preload; 5 = filtered venous reservoir; 6 = right and left side flow divider; 7 = right side variable speed pump; 8 = left side variable speed pump; 9 = right side holding chamber; 10 = hollow fiber oxygenator; 11 = Langendorff and working mode divider; 12 = left side holding chamber; 13 = Langendorff and aortic output union; 14 = arterial compliance chamber; 15 = aortic afterload chamber; 16 = pulmonary afterload chamber; 17 = prewarming chamber; 18 = inferior vena cava; 19 = pulmonary vein; 20 = superior vena cava; 21 = brachiocephalic artery; 22 = aorta; 23 = pulmonary artery.

 
As needed, defibrillation support was provided by an internal pacing-defibrillatory lead (6932; Medtronic, Inc) placed in the right ventricle, an external patch electrode (6721 M; Medtronic, Inc) placed on the epicardium of the left ventricle, and a programmer-analyzer unit (9790C, 8090, 5358; Medtronic, Inc). Pacing support was also provided by internal or external pacing electrodes (Medtronic, Inc).

Hemodynamic monitoring was accomplished by pressure-tip catheters (MPC-500, Millar Instruments, Houston, TX) inserted into the right and left ventricles and ultrasonic flow probes (16N; Transonic Systems, Inc, Ithaca, NY) placed in line with the aorta, pulmonary vein, and inferior vena cava. In addition, a bipolar configuration of surface electrodes was used to record electrocardiograms. Furthermore, noncontact mapping of the left ventricle was performed in two of the most recent hearts (EnSite 3000, Endocardial Solutions, Inc, St Paul, MN). Isochronal and isopotential maps were produced and visualized together with virtual electrograms from any site.

Due to the clear nature of the perfusate, real-time imaging was possible within these hearts. As described by Chinchoy and colleagues [4], real-time imaging was accomplished by 6 mm endoscopic cameras (ILV-C1, DSM-2, PF type 14, IV6C6–13; Olympus Optical, Tokyo, Japan) inserted into the chambers of the hearts. Insertion points were the superior vena cava, the right atrial appendage, the brachiocephalic artery, the pulmonary trunk, and/or the pulmonary veins. In addition, smaller diameter (1.8 mm) fiberscopes (Olympus) were used to image small areas of the hearts such as the lumens of coronary arteries. Fluoroscopy (DXR-5, OEC/Diasonics, Salt Lake City, UT) was also performed. All output from imaging techniques was time-synched and recorded to Beta format videotape (UVW-1800, Sony Inc, Tokyo, Japan). Imaging allowed visualization of functional anatomy and device interactions. All data are presented as means ± standard deviations.


    Results
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
To date, twelve human hearts have been explanted and reanimated using this procedure. All hearts fibrillated upon reperfusion; all were successfully defibrillated with varying numbers of shocks of no greater than 34 J each. Two hearts required inotropic support (epinephrine or dobutamine) before successful defibrillation. The average age of the donors before explantation was 55.2 ± 12.9 years; all but three donors were male. Donors' average height was 1.7 ± 0.09 m, and average weight was 91.1 ± 14.1 kg. The average heart weight for 9 of the 12 hearts with available data before reperfusion was 601.1 ± 117.2 g. All available preexplantation demographic data are presented in Tables 1 and 2. It should be noted that above-normal heart weights correlated with clinical diagnosis of left ventricular hypertrophy in hearts Nos. 2, 4, 5, 11, and 12. The resultant physiologic data obtained from the heart recovered from patient No. 1 was discarded because this heart was severely diseased and did not achieve satisfactory physiologic performance upon reperfusion on the isolated heart apparatus; in addition, it would not function even briefly in four-chamber working mode. Physiologic factors from the remaining eleven hearts obtained while functioning in four-chamber working mode are summarized in Table 3. For comparison, the physiologic performances of hearts Nos. 8 to 11 while functioning in Langendorff mode are also presented in Table 3. It should be noted that hemodynamic performance was better while in Langendorff mode for all but one heart. Performance could be augmented by inotropic agents and was typically done prior to imaging of anatomic features.


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Table 3. Summarized In Vitro Physiologic Parameters From Isolated Human Hearts
 
Selected functional anatomical images include: (1) the coronary sinus ostium (Fig 2); (2) serial images of the tricuspid, pulmonary, aortic, and mitral valves (Fig 3); (3) the apex of the right and left ventricle (Fig 4); (4) calcifications on the aortic valve and fatty depositions on endocardial surface (Fig 5); (5) an active fixation lead implanted in the right atrial appendage, a mapping catheter near the coronary sinus, and an EnSite 3000 (Endocardial Solutions, Inc) catheter in the left ventricle (Fig 6); and (6) a tined lead implant into the right ventricular apex (Fig 6).



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Fig 2. Images showing the coronary sinus ostium (CS) of heart No. 9 (A), heart No. 10 (B), heart No. 11 (C), and heart No. 12 (D). The images of the coronary sinus ostium of hearts Nos. 2 to 7 have previously been published [20]. Notice the variations in the thebesian valve covering the CS. Heart No. 9 has a large, fenestrated thebesian valve, while heart No. 12 has a more rudimentary thebesian valve with a few bands spanning the ostium, and hearts Nos. 10 and 11 have no appreciable thebesian valves.

 


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Fig 3. Serial images showing the movement of the tricuspid (A), mitral (B), aortic (C), and pulmonary (D) valves during the cardiac cycle. All images are sequential frames collected at 30 frames/s; the total time for each sequence is 0.267 seconds. The aortic valve shown in this figure is not opening fully; this is probably due to the calcium deposits and depressed left ventricular function. It should be noted that most of the hearts imaged had some form of aortic valve disease.

 


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Fig 4. Images showing the apices of the right (A) and left (B) ventricles. Notice the degree of trabeculations present in both, as well as the presence of fibrous bands (arrowheads) that are presumably conduction fibers.

 


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Fig 5. Images showing calcification of the aortic valve (A, arrows) and fatty deposits on the endocardium of the right ventricle (B).

 


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Fig 6. Images showing an active fixation lead implanted into the right atrial appendage (A), a mapping catheter in the right atrium (B), an EnSite 3000 (Endocardial Solutions, Inc) noncontact mapping catheter in the left ventricle (C), and three serial images (D–F) showing a tined lead during implantation into the right ventricular apex. In (A), the lead is wedged into the pectinate muscles. In (B), the mapping catheter is located on the interatrial septum, near the coronary sinus ostium (CS) that is covered by a large, fenestrated thebesian valve. In (C), the EnSite 3000 catheter is deployed in the left ventricle. Also shown is a mapping catheter touching the left ventricular endocardium. In images (D–F), the top image (D) shows the tines on the lead before embedding into the apex, and the middle (E) and bottom (F) images show the lead embedding into the trabeculations of the right ventricular apex. (TV = tricuspid valve.)

 

    Comment
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
We have described the methods by which we have successfully reanimated eleven donor human hearts deemed not suitable for transplant for the purpose of studying functional cardiac anatomy and biomedical device design. The physiologic factors obtained from these hearts while in physiologic perfusion mode (ie, four-chamber working) and Langendorff perfusion mode have been presented, as well as examples of functional cardiac anatomy and biomedical device-heart interactions.

The hearts described in this paper maintained relatively stable physiologic performance for variable time frames from less than an hour to up to 5 hours, which is similar to that reported by other authors [15, 16]. A number of factors may have influenced the viability of the heart preparations including the following: the method of cardiac arrest, the amount of ischemic time before reperfusion, inotropic support over hours to sustain blood pressure for successful organ recovery, the degree of prior pathophysiologic changes within the heart, experimental setup, perfusate concentrations, and possible air or dislodged plaque emboli in the coronary system (although utmost care was taken to remove air from the preparations before reperfusion). Importantly, useful experimental protocols were still considered possible after physiologic performance declined. It should be noted that most hearts required intermittent inotropic support throughout the experiments in order to maintain suitable performance; this support also served to extend the viability of the preparation. Dobutamine and epinephrine were used as inotropic agents at concentrations of 0.5 mg/mL and 0.1 mg/mL, respectively. Depending on the individual performance of the heart, boluses of 0.5 to 1 mL were injected into the circulating perfusate as often as necessary to maintain viability. Inotropic support was also required for the successful defibrillation of two hearts; it is speculated that, in these cases, the prior history of the patients with chronic stimulant abuse necessitated the high preload of catecholamines.

The factors affecting the viability of the preparations may have also influenced the subsequent physiological performance of these hearts, which was variable (Table 3). However, the range of peak left ventricular pressure generation in these hearts without inotropic support immediately before data collection (21.5 to 75.8 mm Hg) was similar to that reported in the literature; 15 to 70 mm Hg for a similar ex vivo human heart preparation using a blood perfusate [16]. Nevertheless, with inotropic support, we could achieve systolic pressures in the range of 70 to 90 mm Hg for extended periods of time, which allowed for assessment of the functional anatomy and/or device interactions.

Langendorff perfused isolated human hearts have previously been described [15–19]. However, we report successful reanimation of human hearts that are physiologically perfused (ie, in four-chamber working mode). Furthermore, we present functional anatomical images obtained from isolated human hearts. It should be noted that all of our hearts were from organ donors whose hearts were deemed not viable for transplant, mainly due to the presence of significant pathophysiology or viral infection. Hence, we were able to obtain these specimens with the great vessels intact (excluding the inferior vena cava). The studies by Burkhoff and colleagues [17], Slater and colleagues [16, 19], and Holubarsch and colleagues [18], primarily utilized cardiac transplant recipient hearts, although small numbers of "normal" donor hearts were utilized for comparison [18, 19]. The hearts employed by Durrer and colleagues [15] were from recently deceased patients and were recovered within thirty minutes of cessation of cardiac activity. Another notable difference was that the previously described perfusates included the addition of human or bovine red blood cells; this was attempted in swine hearts in our laboratory, but compromised the ability for intracardiac visualization. Similar to Durrer and colleagues [15], our preparations facilitate study of the cardiac conduction system. However, we are also able to examine the interaction of pacemakers, defibrillators, leads and electrophysiologic catheters with the cardiac conduction system and visualize the interaction of these devices with the endocardium. Furthermore, by utilizing the capabilities of intracardiac visualization and the EnSite 3000 noncontact mapping system, we were able to precisely relate cardiac electrophysiologic activation sequences and properties to accurately defined pacing locations observed in real-time (Fig 7).



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Fig 7. Geometry of the left ventricle in heart No. 9 reconstructed by the EnSite 3000 system (Endocardial Solutions, Inc) shown in anterior (left) and posterior (right) views. The location of the multielectrode array is represented by the yellow ellipsoid shown through the cutout. Color-coded activation times are shown on the left. (A) Baseline rhythm isochronal map. Left ventricular endocardial breakout occurs at the posteroinferior portion of the septal wall. Activation travels down the septum (at ~ 1m/s), activates the apex and then travels radially upwards (at ~ 1.5 m/s), terminating in the basal lateral region of the chamber. Baseline total activation duration was 79 ms. (B) Isochronal map during pacing from the base of the right ventricular anterior papillary muscle: endocardial breakout occurred more anteriorly on the midseptum and proceeded to activate the anterior regions of the heart in ~ 20 ms before activating the posterior regions of the heart (~ 50 ms) in a caudal-cranial direction, before terminating in the posterolateral region of the chamber (68 ms).

 
Our experimental approach is not without limitations, many of which are similar to those that were faced by the previous investigators. Ischemic time results in injury to the myocardium, even if optimal procedures for protection are used. The perfusion system and perfusate, while they simulate in situ conditions, are not exact and therefore have an impact on the performance of the heart in vitro. Furthermore, the orientation of the heart on the apparatus may have influenced the performance of the heart. The first few hearts were hung from the great vessels, but in an effort to improve device handling and imaging capabilities (fluoroscopy), they were rotated to a position similar to that seen on the operating table. Although soft foam was used to cushion the heart, it is possible that residual compression of the coronary vessels compromised perfusion to the posterior aspect of the hearts.

It would be ideal to study a heart free from pathology on this apparatus, as the physiologic factors could be more readily compared with those found in normal human hearts, and it would be a stringent test as to how well the apparatus stimulates in situ physiology. However, the likelihood of obtaining a normal human heart is small due to the great number of patients awaiting heart transplants and the small number of donors.

The ability to achieve satisfactory physiologic performance following reperfusion allowed for the collection of functional intracardiac anatomical images. These images are useful for education and training purposes as they present a unique perspective on cardiac anatomy. To that end, these images have been presented in a number of educational settings including the following: (1) an educational CD-ROM entitled The Visible Heart Viewer; (2) the Visible Heart website (http://www.visibleheart.com); (3) courses at the University of Minnesota; (4) the Science Museum of Minnesota; and (5) scientific conferences including North American Society of Pacing and Electrophysiology, Biomedical Engineering Society, and Cardiostim.

In conclusion, we have demonstrated the successful reanimation of isolated donor human hearts deemed not viable for transplant using physiologic perfusion. Specifically, this preparation allows for intracardiac visualization of anatomy and biomedical device-heart interactions. This is an ongoing study, which is dependent on the procurement of human hearts deemed not viable for transplant. We have no control over when hearts will be obtained, or what physiologic state the hearts will be in when we receive them. In spite of this, we still eagerly look forward to the next opportunity to study a human heart on our apparatus. The future goals include gathering improved images of functioning anatomy, improving physiologic performance on the apparatus, and performing noncontact mapping studies of the various chambers of the heart.


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Table 2. Preexplantation Cardiovascular Data
 

    Acknowledgments
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 
The authors thank the LifeSource staff for their assistance with this study, in addition to all the generous individuals and families who donated their hearts for research. This research was supported, in part, by Medtronic, Inc, and the Lillehei Heart Institute and Biomedical Engineering Institute of the University of Minnesota.


    References
 Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 Acknowledgments
 References
 

  1. Langendorff O. Untersuchungen am uberlebenden saugenthierherzen Pflugers Arch fur die Gesante Physiologie des Menschen und der Tiere 1895;61:291-332[Investigations on the surviving mammalian heart].
  2. Neely JR, Liebermeister H, Battersby EJ, Morgan HE. Effect of pressure development on oxygen consumption by isolated rat heart Am J Physiol 1967;212:804-814.[Free Full Text]
  3. Taegtmeyer H, Hems R, Krebs HA. Utilization of energy-providing substrates in the isolated working rat heart Biochem J 1980;186:701-711.[Medline]
  4. Chinchoy E, Soule CL, Houlton AJ, et al. Isolated four-chamber working swine heart model Ann Thorac Surg 2000;70:1607-1614.[Abstract/Free Full Text]
  5. Gamble WJ, Conn PA, Kumar AE, Plenge R, Monroe RG. Myocardial oxygen consumption of blood-perfused, isolated, supported, rat heart Am J Physiol 1970;219:604-612.[Free Full Text]
  6. Pasini E, Solfrini R, Bachetti T, et al. The blood perfused isolated heart: characterization of the model Basic Res Cardiol 1999;94:215-222.[Medline]
  7. Sutherland FJ, Hearse DJ. The isolated blood and perfusion fluid perfused heart Pharmacol Res 2000;41:613-627.[Medline]
  8. Modersohn D, Eddicks S, Grosse-Siestrup C, Ast I, Holinski S, Konertz W. Isolated hemoperfused heart model of slaughterhouse pigs Int J Artif Organs 2001;24:215-221.[Medline]
  9. Depre C. Isolated working heart: description of models relevant to radioisotopic and pharmacological assessments Nucl Med Biol 1998;25:711-713.[Medline]
  10. Vick JA, Herman EH. An isolated dog or monkey heart preparation for studying cardioactive compounds Pharmacology 1971;6:290-299.[Medline]
  11. Suga H, Sagawa K. Instantaneous pressure-volume relationships and their ratio in the excised, supported canine left ventricle Circ Res 1974;35:117-126.[Abstract/Free Full Text]
  12. Suga H, Sagawa K. End-diastolic and end-systolic ventricular volume clamper for isolated canine heart Am J Physiol 1977;233:H718-722.
  13. Casali C, Obadia JF, Canet E, et al. Design of an isolated pig heart preparation for positron emission tomography and magnetic resonance imaging Invest Radiol 1997;32:713-720.[Medline]
  14. Hearse DJ, Sutherland FJ. Experimental models for the study of cardiovascular function and disease Pharmacol Res 2000;41:597-603.[Medline]
  15. Durrer D, van Dam RT, Freud GE, Janse MJ, Meijler FL, Arzbaecher RC. Total excitation of the isolated human heart Circulation 1970;41:899-912.[Abstract/Free Full Text]
  16. Slater JP, Lipsitz EC, Chen JM, Levin HR, Oz MC, Burkhoff D. Use of explanted human hearts as a model for the study of cardiac pathophysiologic conditions J Thorac Cardiovasc Surg 1995;110:239-247.[Abstract/Free Full Text]
  17. Burkhoff D, Flaherty JT, Yue DT, et al. In vitro studies of isolated supported human hearts Heart Vessels 1988;4:185-196.[Medline]
  18. Holubarsch C, Ruf T, Goldstein DJ, et al. Existence of the Frank-Starling mechanism in the failing human heartInvestigations on the organ, tissue, and sarcomere levels. Circulation 1996;94:683-689.[Abstract/Free Full Text]
  19. Slater JP, Lipsitz EC, Chen JM, et al. Systolic ventricular interaction in normal and diseased explanted human hearts J Thorac Cardiovasc Surg 1997;113:1091-1099.[Abstract/Free Full Text]
  20. Hill AJ, Coles Jr JA, Sigg DC, Laske TG, Iaizzo PA. Images of the human coronary sinus ostium obtained from isolated working hearts Ann Thorac Surg 2003;76:2108.[Free Full Text]



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Eur. J. Cardiothorac. Surg.Home page
Y. Araki, A. Usui, O. Kawaguchi, S. Saito, M.-H. Song, T. Akita, and Y. Ueda
Pressure-volume relationship in isolated working heart with crystalloid perfusate in swine and imaging the valve motion
Eur. J. Cardiothorac. Surg., September 1, 2005; 28(3): 435 - 442.
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