Integrated bubble trap device and clamp for working heart apparatus

Abstract

An integrated bubble trap device for a working heart system includes a body having an internal cavity configured to be partially filled with a liquid, an inlet configured to be in fluid communication with a liquid reservoir, an outlet configured to connect to a left atrium of an excised heart of a test specimen, and a syringe port configured to connect the internal cavity of the body with a syringe. An aperture at the bottom of the body is configured to connect to a pressure sensor. The integrated bubble trap device may further include a catheter extension configured to connect the liquid reservoir to the inlet adapter of the integrated bubble trap device and an adjustable clamp to hold the liquid reservoir in a position. In a method of use, the integrated bubble trap device removes bubbles from a perfusion buffer.

Description

INTEGRATED BUBBLE TRAP DEVICE AND CLAMP FOR WORKING HEART APPARATUSCross-Reference to Related Applications

[0001] Priority is claimed to United States Provisional Patent Application No. 63 / 617,815, filed January 5, 2024, the entire contents of which are hereby incorporated by reference herein.Field of the Disclosure

[0002] The present disclosure relates to a three-dimensional clamp for a working heart apparatus to facilitate atrial cannulation and an integrated bubble trap device for a working heart apparatus to obtain stable measurements without interference from bubbles.Background

[0003] Working heart models are useful for investigating the physiology and pharmacology of the heart without interference from the rest of the body. Using a heart excised from a test specimen in a laboratory setting, researchers can run experiments on the excised heart that would not otherwise be possible. A working heart model is arranged so that flow of perfusate is via left atria to left ventricle to aorta, mimicking the flow of blood in situ, and thus the working heart model can perform a physiological pumping action that allows measurement of various cardiac functional parameters under the influence of tested agents.Summary

[0004] In accordance with an example, an integrated bubble trap device for a working heart system includes a body, an inlet, an outlet, and a syringe port. The body is arranged along a longitudinal axis and includes an internal cavity configured to be partially filled with a liquid. The inlet includes an inlet end configured to be in fluid communication with a liquid reservoir, and an inlet lumen extending from the inlet end to the internal cavity of the body. The outlet includes an outlet end configured to be an atrial cannula and directly connect to a left atrium of an excised heart of a test specimen and an outlet lumen extending from the internal cavity of the body to the outlet end. The syringe port is configured to connect a syringe to the internal cavity of the body. The syringe port is positioned above the inlet and the outlet when the longitudinal axis is arranged vertically. A catheter extension is configured to directly connect to the inlet end of the inlet of the body. The catheter extension includes an extension lumen in fluid communication with the inlet lumen when the catheter extension is connected to the inlet end of the inlet.

[0005] In some forms, the inlet may be positioned above the outlet when the longitudinal axis is arranged vertically.

[0006] In some forms, the internal cavity may be configured to be filled by the liquid to a level above the inlet and the outlet when the longitudinal axis is arranged vertically.

[0007] In some forms, an aperture may be provided at bottom of the body that is configured to connect to a pressure sensor.

[0008] In some forms, the integrated bubble trap device may include a flow sensor positioned at the inlet lumen or the outlet lumen for atrial flow rate or cardiac output measurement. .

[0009] In some forms, the syringe port may be configured to connect a headspace of the body to the syringe to at least one of hold extra air, to adjust the buffer height in the internal cavity of the body, and to adjust atrial filling compliance.

[0010] In some forms, the catheter extension may have a first portion arranged along a first axis and a second portion arranged along a second axis. The first axis may be disposed at an obtuse angle relative to the second axis.

[0011] In some forms, the integrated bubble trap device may include the liquid reservoir and a clamp configured to hold the liquid reservoir in a position. The clamp may be adjustable in three dimensions to adjust the position of the liquid reservoir and thereby the position of the outlet of the integrated bubble trap device.

[0012] In some forms, the position of the liquid reservoir may be at least one inch from the inlet of the body.

[0013] In accordance with an example, a working heart system includes a left atrial block, an integrated bubble trap device, a pulmonary artery cannula, and an aortic block. The left atrial block includes a liquid reservoir and a left atrial port. The left atrial port is in direct fluid communication with the liquid reservoir and configured for fluid communication with a left atrium of an excised heart of a test specimen. The integrated bubble trap device includes a body including an internal cavity configured to be partially filled with a liquid and a syringe port. The internal cavity includes a headspace configured to be filled by air. The internal cavity is in fluid communication with the liquid reservoir and is configured to be fluidly connected to a left atrium of an excised heart of a test specimen. The syringe port is configured to connect the headspace of the body to a syringe to at least one of hold extra air, adjust the buffer height in the internal cavity of the body, and to adjust atrial filling compliance. An aortic block includes an aortic cannula configured to connect to an aorta of the excised heart and a peristaltic pump to pump fluid into the excised heart, and a pressure-volume catheter port configured to enable insertion of a pressure-volume catheter into left ventricle of the excised heart. The pulmonary artery cannula includes a cannula inlet configured to connect to a pulmonary artery of the excised heart and a cannula outlet in fluid communication with a measuring container.

[0014] In some forms, the integrated bubble trap device may further include an inlet having an inlet end configured to be in fluid communication with a liquid reservoir, and an inlet lumen extending from the inlet end to the internal cavity of the body. The integrated bubble trap device may further include an outlet having an outlet end configured to connect to a left atrium of an excised heart of a test specimen and an outlet lumen extending from the internal cavity of the body to the outlet end.

[0015] In some forms, the headspace may be positioned above the inlet and the outlet when a longitudinal axis of the body is arranged vertically.

[0016] In some forms, the integrated bubble trap device may include an aperture in the body configured to connect to a pressure sensor.

[0017] In some forms, the working heart system may include a flow sensor.

[0018] In some forms, the syringe port may be positioned above the inlet and the outlet when a longitudinal axis of the body is arranged vertically.

[0019] In some forms, a catheter extension may be configured to connect to the inlet end of the inlet of the body. The catheter extension may include an extension lumen in fluid communication with the inlet lumen when the catheter extension is connected to the inlet end of the inlet.

[0020] In some forms, the working heart system may include a clamp configured to hold the liquid reservoir in a position. The clamp may be adjustable along in three dimensions to adjust the position of the liquid reservoir.

[0021] In some forms, the position of the liquid reservoir may be at least one inch from the inlet of the body.

[0022] In accordance with an example, a method of using a working heart system includes providing a left atrial block including a liquid reservoir containing a perfusion buffer, the left atrial block further including a left atrial port in fluid communication with the liquid reservoir. The method further includes fluidly connecting the left atrial port to an integrated bubble trap device, the integrated bubble trap device including an internal cavity partially filled with the perfusion buffer, a headspace, and a syringe port. The method further includes fluidly connecting the integrated bubble trap device to a left atrium of an excised heart of a test specimen. The method further includes flowing perfusion buffer from the liquid reservoir into the left atrium of the excised heart via the integrated bubble trap device. The method further includes removing bubbles from the flowing perfusion buffer in the integrated bubble trap device.

[0023] In some forms, the left atrial port may be secured to a catheter extension that is secured to the integrated bubble trap device, the catheter extension fluidly connecting the left atrial port and the integrated bubble trap device.

[0024] In some forms, the method may include securing the liquid reservoir in a clamp and adjusting the clamp to adjust a position of the liquid reservoir.

[0025] In some forms, the method may include measuring a pressure in the internal cavity of the integrated bubble trap device.Brief Description of the Drawings

[0026] The figures described herein depict various aspects of the system and methods disclosed herein. It should be understood that each figure depicts an example of aspects of the present systems and methods.

[0027] FIG. 1 illustrates a commercial isolated perfused working heart system for small rodents.

[0028] FIG. 2 illustrates a modified working heart system with a catheter extension between a liquid reservoir and an excised heart of a test specimen.

[0029] FIG. 3 illustrates schematically a modified working heart system including a schematic catheter extension and a schematic integrated bubble trap device.

[0030] FIG. 4 illustrates a portion of a modified working heart system, such as the modified working heart system shown schematically in FIG. 3, including a first exemplary catheter extension and a first exemplary integrated bubble trap device between a liquid reservoir and an excised heart of a test specimen.

[0031] FIG. 5A illustrates a second exemplary catheter extension and a second exemplary integrated bubble trap device.

[0032] FIG. 5B illustrates a top view of the exemplary integrated bubble trap device of FIG. 5A.

[0033] FIG. 5C illustrates a front view of the exemplary integrated bubble trap device of FIGS. 5A and5B.

[0034] FIG. 6 illustrates a third exemplary integrated bubble trap device.

[0035] FIG. 7 illustrates a fourth exemplary integrated bubble trap device.

[0036] FIG. 8 illustrates a plurality of exemplary catheter extensions.

[0037] FIG. 9 illustrates a plurality of exemplary integrated bubble trap devices.

[0038] FIG. 10 illustrates schematically a method for using a working heart system including an integrated bubble trap device.

[0039] FIG. 1 1 A illustrates use of a working heart system at box 802 of the method of FIG. 10.

[0040] FIG. 1 1 B illustrates use of the working heart system of FIG. 1 1 A at box 804 of the method of FIG. 10.

[0041] FIG. 1 1 C illustrates use of the working heart system of FIGS. 1 1 A and B at boxes 806 and 808 of the method of FIG. 10.

[0042] FIG. 1 1 D illustrates use of the working heart systems of FIGS. 1 1 A-C at box 810 of the method of FIG. 10.

[0043] FIG. 12A illustrates data collected from a working heart system in a first experiment without using an integrated bubble trap device.

[0044] FIG. 12B illustrates data collected from a working heart system in a second experiment without using an integrated bubble trap device.

[0045] FIG. 13A illustrates data collected from a working heart system in a third experiment with use of an integrated bubble trap device.

[0046] FIG. 13B illustrates data collected from a working heart system in a fourth experiment with use of an integrated bubble trap device.

[0047] Skilled artisans will appreciate that elements in the figures are illustrated for simplicity and clarity and have not necessarily been drawn to scale. For example, the dimensions and / or relative positioning of some of the elements in the figures may be exaggerated relative to other elements to help to improve understanding of various examples. Also, common but well-understood elements that are useful or necessary in a commercially feasible embodiment are often not depicted in order to facilitate a less obstructed view of these various embodiments. It will further be appreciated that certain actions and / or steps may be described or depicted in a particular order of occurrence while those skilled in the art will understand that such specificity with respect to sequence is not actually required. It will also be understood that the terms and expressions used herein have the ordinary technical meaning as is accorded to such terms and expressions by persons skilled in the technical field as set forth above except where different specific meanings have otherwise been set forth herein.Detailed Description

[0048] The working heart system of the present disclosure provides several notable benefits over known working heart systems. An integrated bubble trap device is added to the working heart system to eliminate bubbles created by, for example, degassing of the perfusion buffer. Because the bubbles negatively impact the ability to collect data from the working heart system, the integrated bubble trap device improves the accuracy of data collected using the system. In addition, the atrial cannula is integrated with integrated bubble trap device as an outlet. Thus, de-bubbled buffer immediately flows into the left atrium. Further, a catheter extension is added to the working heart system between a liquid reservoir of a left atrial block and the excised heart of the test specimen. The catheter extension increases the operating space available between the atrial cannula (e.g., outlet of the integrated bubble trap device) and the excised heart, thereby improving the ability to access the left atrium of the excisedheart. Additionally, a three-dimensional adjustable clamp is provided to optimally position the atrial cannula relative to the incision of the left atrium.

[0049] FIG. 1 illustrates a working heart system 100. The working heart system includes a left atrial block 102 having a liquid reservoir 104 and a left atrial port 106. The left atrial port 106 is configured to connect to a left atrium LA of an excised heart 108 of a test specimen as shown in FIG. 1 , and perfusion buffer contained in the liquid reservoir 104 can enter the excised heart 108 through the left atrial port 106. A pressure-volume catheter 1 12 is connected to the left ventricle LV of the excised heart 108 via the aorta A to measure select parameters and enable the collection data during operation of the working heart system 100. An aortic block 1 14 is connected to the aorta A of the excised heart by an aortic cannula 1 16.

[0050] The working heart system 100 can operate in at least two modes: Langendorff heart perfusion mode and working heart perfusion mode. In Langendorff perfusion mode, a perfusion buffer is pumped through the aorta toward the heart in a retrograde perfusion. In the working heart perfusion model, the flow of the perfusion buffer replicates the flow of blood in situ. The perfusion buffer enters the left atrium (typically via the pulmonary vein), is pumped into the left ventricle, and exits via the aorta. Each of the two modes is useful for collecting select data.

[0051] In the working heart model 100, the liquid reservoir 104 of the left atrial block 102 is connected to the excised heart 108 and the left atrial port 106 via a short left atrial cannula 105. The position of the liquid reservoir 104 is fixed in two dimensions, and the liquid reservoir 104 is adjustable only in one dimension (i.e., upward and downward). The limited adjustability prevents optimal positioning of the left atrial cannula relative to the left atrium of the excised heart 108. The proximity of the atrial block 102 to the excised heart 108 limits the working space around the excised heart 108, making the atrial cannula 105 difficult to connect to the left atrium LA of the excised heart 108.

[0052] FIG. 2 illustrates a working heart model 200 in accordance with the teachings of the present disclosure. The working heart model 200 is substantially similar to the working heart model 100. Elements of the working heart model 200 depicted in FIG. 2 are designated by similar reference numbers indicated on the arrangements illustrated in FIG. 1 increased by 100. Accordingly, these features will not be described in substantial detail. Further, it is appreciated that any combination or sub-combination of features described in regard to the working heart model 100 may be incorporated into the working heart model 200, and vice versa.

[0053] In the working heart model 200, a catheter extension 227 connects the left atrial port 206 to the excised heart 208. This allows the liquid reservoir 204 to be placed in a position a distance D1 from the excised heart 208 that is far greater than is possible without use of a catheter extension 227. The distance D1 provides more room (i.e., space) for a user of the working heart model 200 to manipulate and cannulate to the excised heart 208. Further, because the position of the liquid reservoir 204 is no longer fixed in two dimensions, the position of the liquid reservoir 204 can be adjusted, and the catheter extension 227 is positioned to span the resulting distance D1 between the liquid reservoir 204 and the excised heart 208. A clamp 230 holds the liquid reservoir 204 in position. The clamp 230 may be a two-prong clamp and may be fixed on a commercially available three-axis coarse positioning micromanipulator. The micromanipulator may be held by a rod holder clamp on a post. By operating the micromanipulator control knobs, the clamp 230 can be moved in three dimensions, namely, upwardand downward, backward and frontward, and leftward and rightward. In this way, the position of the liquid reservoir 204 can be adjusted in space along any of the three dimensions.

[0054] Because perfusion buffer degasses, bubbles can form in the perfusion buffer that can negatively impact the quality of data collected from the working heart system 100 or the working heart system 200. Accordingly, FIGS. 3-7 and 9 illustrate exemplary integrated bubble trap devices that can be added to the working heart system 100 or the working heart system 200 to reduce the number of bubbles entering the excised heart 108 or 208 and thereby improve the quality of data collected, as discussed in greater detail with respect to FIGS. 12A, 12B, 13A, and 13B below.

[0055] Specifically, FIG. 3 illustrates schematically how an integrated bubble trap device 300 can be added to the working heart system 200 discussed above. In addition to the features already discussed (identified by the same reference number in FIGS. 2 and 3), the aortic block 214 of the working heart system 200 may further include a pump 218 to pump fluid through the excised heart 208. A pulmonary artery cannula 220 includes an inlet 222 configured to connect to a pulmonary artery of the excised heart 208 and an outlet 224 in fluid communication with a measuring container 226, such as a graduated cylinder, that allows further data collection from the working heart system 200. As discussed above, the catheter extension 227 connects the left atrial port 206 to the excised heart 208. However, in the arrangement shown in FIG. 3, the integrated bubble trap device 300 is positioned between the catheter extension 227 and the excised heart 208. During use of the working heart system 200, the bubble trap device 300 is therefore able to remove bubbles from flowing perfusion buffer prior to the perfusion buffer entering the excised heart 208 as discussed further below.

[0056] FIG. 4 illustrates the structure of the integrated bubble trap device 300. The integrated bubble trap device 300 includes a body 336. The body 336 has an internal cavity 338 that is configured to be partially filled with a liquid (e.g., the perfusion buffer being used in the working heart system 100 or 200). The internal cavity 338 includes a headspace 340 filled with air, and a syringe port 341 is provided in the body 336 to connect headspace 340 with a syringe 343 (shown in FIG. 3). As shown in FIG. 4, the internal cavity 338 is in fluid communication with the liquid reservoir 204 and is configured to connect to the left atrium of the excised heart 208. During operation of the working heart system 200, perfusion buffer comes into and goes out of the internal cavity 338. Bubbles in the perfusion buffer pumped into the internal cavity 338 rise to the headspace 340 so that the perfusion buffer pumping out of the internal cavity 338 is substantially free from bubbles. As a result, bubbles are not flow into the excised heart 208 and measurements of the working heart system 200 are not negatively impacted by bubbles.

[0057] FIGS. 5A-C illustrate the integrated bubble trap device 300 disconnected from working heart system 200 or 300. The body 336 is arranged along a longitudinal axis L. The integrated bubble trap device 300 includes an inlet 342 having an inlet end 344 configured for fluid communication with the liquid reservoir 104 or 204 and an inlet lumen 346 extending from the inlet end 344 to the internal cavity 338 of the body 336. The integrated bubble trap integrated 300 further includes an outlet 348 including an outlet end 350 configured to connect to a left atrium of an excised heart 108 or 208 and an outlet lumen 352 extending from the internal cavity 338 of the body 336 to the outlet end 350. In FIG. 5A, a flow sensor 353 is positioned at the outlet lumen 353 for atrial flow rate or cardiac output measurement. In other arrangements, the flow sensor 353 may be positioned at the inlet lumen 346 for atrial flow rate or cardiac output measurement. The flow sensor 353 may be a micro flow sensor.

[0058] As shown in FIG. 4, when the longitudinal axis L is arranged vertically, the headspace 340 and the syringe port 341 is positioned above the inlet 342 and the outlet 348. The internal cavity 338 is configured to be filled by the liquid (e.g., perfusion buffer) to a level above the inlet 342 and the outlet 348 when the longitudinal axis L is arranged vertically. The inlet 342 and the outlet 348 may be positioned at any location along the longitudinal axis L relative to one another (e.g., with the inlet 342 above, equal to, or below the outlet 348 when the longitudinal axis L is arranged vertically). In the arrangement shown in FIGS. 4 and 5A-C, the inlet 342 is positioned above the outlet 348 when the longitudinal axis L is arranged vertically.

[0059] As shown in FIG. 5B, the inlet lumen 346 of the inlet 342 is horizontally offset from the outlet lumen 352 of the outlet 348 by an angle a (between axis A1 aligned with the inlet lumen 346 and axis A2 aligned with the outlet lumen 352) when the longitudinal axis L is arranged vertically. In some arrangements, the angle a is between 10 and 30 degrees. Further, as shown in FIG. 5C, the inlet lumen 346 of the inlet 342 is vertically offset from the outlet lumen 352 of the outlet 348 by an angle p (between axis A3 aligned with the inlet lumen 346 and axis A4 aligned with the outlet lumen 352) when the longitudinal axis L is arranged vertically. In some arrangements, the angle p is between 5 and 15 degrees. In the arrangement shown, the axis A3 is roughly horizontal and the axis A4 is downwardly disposed when the longitudinal axis L is arranged vertically. The angle a and the angle p align the outlet 348 with the atrial flow track, which reduces the risk of the outlet 348 getting stuck in the atrial wall. The angle a and the angle p also facilitate flow of the perfusion buffer into the atrium.

[0060] In the arrangement shown in FIG. 4, the inlet end 344 is connected indirectly to the liquid reservoir 204 by the catheter extension 227. As shown in FIG. 5A, the catheter extension 227 includes an extension lumen 454 in fluid communication with the inlet lumen 346 when the catheter extension 227 is connected to the inlet end 344 of the inlet 342. The catheter extension 227 provides fluid communication between the liquid reservoir 204 and the integrated bubble trap device 300. In other arrangements, the inlet end 344 of the integrated bubble trap device 300 may be directly connected to the liquid reservoir 104 or 204. In the arrangement shown in FIG. 4, the outlet end 350 of the integrated bubble trap device 300 is directly connected to the excised heart 208. In other arrangements, the outlet end 350 may be fluidly connected to the excised heart 208 indirectly (e.g., by an intermediate component allowing fluid flow).

[0061] The integrated bubble trap device 300 may optionally include an aperture 356 in the body 336 to connect to a pressure sensor. The pressure sensor allows measurements of pressure within the integrated bubble trap device 300, which are useful for measuring atrial perfusing pressure. Further, the body 336 may use the syringe port 341 to connect the internal cavity 338 with the syringe 343 to hold extra air, to adjust the buffer height in the internal cavity of the body, and to adjust atrial filling compliance.

[0062] As shown in FIG. 5A, the catheter extension 227 has a first portion 460 arranged along a first axis F and a second portion 462 arranged along a second axis S. The first axis F is disposed at an obtuse angle O relative to the second axis S. The catheter extension 427 has a catheter extension inlet 464, a catheter extension outlet 466, and the catheter extension lumen 454 extends between the catheter extension inlet 464 and the catheter extension outlet 466. The catheter extension inlet 464 connects directly to the liquid reservoir 104 or 204 and the catheter extension outlet 466 connectsdirectly to the integrated bubble trap device 300. The catheter extension 227 has a distance D2 between the catheter extension inlet 464 and the catheter extension outlet 466 that ensures adequate room for assembly and operation of the working heart system 100 or 200. For example, the distance D2 may be at least two inches.

[0063] FIGS. 6 and 7 illustrate integrated bubble trap device 500 and integrated bubble trap device 600, respectively. The integrated bubble trap devices 500 and 600 are substantially similar to the integrated bubble trap device 300 discussed above. Elements of the integrated bubble trap device 500 and the integrated bubble trap device 600 depicted in FIGS. 6 and 7 are designated by similar reference numbers indicated for integrated bubble trap device 300 illustrated in FIGS. 4 and 5, increased by a multiple of 100. Accordingly, these features will not be described in substantial detail. Further, it is appreciated that any combination or sub-combination of features described in regard to the integrated bubble trap devices 500 and 600 may be incorporated into the integrated bubble trap device 300, and vice versa.

[0064] In the arrangement shown in FIGS. 5A-C, the body 336 of the integrated bubble trap device 300 is substantially cylindrical. In FIG. 6, the body 536 of the integrated bubble trap device 500 is substantially rectangular. In FIG. 7, the body 636 of the integrated bubble trap device 600 is a hexahedron with two curved sides 668a and 668b and two flat sides 670a and 670b that are substantially oval-shaped. In other arrangements not herein depicted, the size, shape, and location of any of the inlets 342, 532, and 632, any of the outlets 348, 548, 648, any of the syringe ports 341 , 541 , and 641 , and any of the apertures 356, 556, and 656 may differ. The position and size of other components of working heart system 100 or working heart system 200 may influence these size, shape, and location choices. For example, the size, shape, and location of the inlets 342, 542, and 642 may depend on the size, shape, and location of the catheter extension 227.

[0065] FIG. 8 illustrates a plurality of exemplary catheter extensions 727a, 727b, 727c, 727d, and 727e (collectively 727a-e). The catheter extensions 727a-e are substantially similar to the catheter extension 227 discussed above. Elements of the catheter extensions 727a-e depicted in FIG. 8 are designated by similar reference numbers indicated for catheter extension 227 illustrated in FIGS. 4 and 5, increased by a multiple of 100. Accordingly, these features will not be described in substantial detail. Further, it is appreciated that any combination or sub-combination of features described in regard to the catheter extensions 727a-e may be incorporated into the catheter extension 227, and vice versa.

[0066] Each of the catheter extensions 727a-e are different because the combination of their respective catheter extension inlet 764a-e and respective catheter extension outlet 766a-e varies, each of which may have a male or a female lure syringe adapter / connector end. For example, catheter extension 727a has a catheter extension inlet 764a and a catheter extension outlet 766a that are similarly sized and shape, whereas catheter extension 727b has a catheter extension inlet 764b similarly sized to the catheter extension inlet 764a but a catheter extension outlet 766b that has a greater diameter that the catheter extension outlet 766a. The size and shape of each catheter extension inlet 764a-e may depend on the size and shape of the left atrial port 206 to which it is intended to connect, and the size and shape of each catheter extension outlet 766a-e may depend on the size and shape of the inlet end 344 of the integrated bubble trap device 300. While all of the catheter extensions 727a-e are depicted as being substantially rigid, a flexible tubing may be used as a catheter extension. Further, while all of thecatheter extensions 727a-e are depicted as including a respective first portion 760a-e and a respective second portion 762a-e, the catheter extensions 727a-e may instead have a single portion arranged in a straight configuration or may have more than two portions connected to form the respective catheter extension lumens 754a-e. Further, the angle O (shown in FIG. 4) may vary for each of the catheter extensions 727a-e.

[0067] FIG. 9 illustrates a plurality of exemplary integrated bubble trap devices 700a, 700b, 700c, 700d, 700e, 700f, 700g, and 700h illustrating the variety of sizes, shapes, and designs possible for respective syringe ports 741 a-h, outlets 748a-h, and inlets 732a-h, each of which may be female or male lure adaptors / connectors. The exemplary integrated bubble trap devices 700a-700d are configured for left atrial cannulation from the right side, and the exemplary integrated bubble trap devices 700e-700h are configured for left atrial cannulation from the left side.

[0068] FIG. 10 illustrates a method 800 of using a working heart system 200 in, for example, experiments in a laboratory setting using a heart excised from a test specimen. At box 802 of FIG. 10, as further illustrated in FIG. 1 1 A, the method 800 includes providing a left atrial block 202 including a liquid reservoir 204 containing a perfusion buffer, the left atrial block 202 further including a left atrial port 206 in fluid communication with the liquid reservoir 204. The left atrial port 206 may be secured to a catheter extension 227 that is secured to the integrated bubble trap device 300, the catheter extension 227 fluidly connecting the left atrial port 206 and the integrated bubble trap device 300. At box 804 of FIG. 10, as further illustrated in FIG. 1 1 B, the method 800 includes fluidly connecting the left atrial port 206 to an integrated bubble trap device 300, the integrated bubble trap device 300 including an internal cavity 338 partially filled with the perfusion buffer, a headspace 340, and a syringe port 341 . At box 806 of FIG. 10, as further illustrated in FIG. 1 1 C, the method 800 includes fluidly connecting the bubble trap 300 to a left atrium of an excised heart 208 of a test specimen. At box 808 of FIG. 10, as also illustrated in FIG. 1 1 C, the method 800 includes flowing perfusion buffer from the liquid reservoir 204 into the left atrium of the excised heart 208 via the bubble trap 300. At box 810 of FIG. 10, as further illustrated in FIG. 1 1 D, the method 800 includes removing bubbles from the flowing perfusion buffer in the integrated bubble trap device 300. The method 800 may further include securing the liquid reservoir 204 in a clamp 230 and adjusting the clamp 230 to adjust a position of the liquid reservoir 204.

[0069] FIGS. 12A - 13B illustrate the superior results obtained from a working heart system (such as working heart system 100 or working heart system 200) using an integrated bubble trap (such as integrated bubble trap device 300, 500, or 600). In FIGS. 12A-12B, 902 illustrates measurements of the left ventricular pressure, 904 illustrates measurements of the left ventricular volume, 906 illustrates measurements of coronary perfusion pressure, 908 illustrates measurements of atrial perfusion pressure, and 910 illustrates measurements of the rate of pressure changes in the ventricular cavity during the isovolumic contraction and relaxation period. FIGS. 12A and 12B illustrate measurements obtained from a system that does not include an integrated bubble trap device. As shown, all measurements 902, 904, 906, 908, and 910 include numerous fluctuations resulting from bubbles entering the excised heart and interfering with the collection of data. FIGS. 13A and 13B illustrate measurements obtained from a system that does include an integrated bubble trap device. In comparison to the measurements collected in FIGS. 12A and 12B, the measurements 902, 904, 906,908, and 910 are relatively stable within the experimental periods, illustrative of the improved data quality achieved by use of an integrated bubble trap device.

[0070] In the foregoing specification, specific embodiments have been described. However, one of ordinary skill in the art appreciates that various modifications and changes can be made without departing from the scope of the invention as set forth in the claims below. Accordingly, the specification and figures are to be regarded in an illustrative rather than a restrictive sense, and all such modifications are intended to be included within the scope of present teachings. Additionally, the described embodiments / examples / implementations should not be interpreted as mutually exclusive and should instead be understood as potentially combinable if such combinations are permissive in any way. In other words, any feature disclosed in any of the aforementioned embodiments / examples / implementations may be included in any of the other aforementioned embodiments / examples / implementations.

[0071] The benefits, advantages, solutions to problems, and any element(s) that may cause any benefit, advantage, or solution to occur or become more pronounced are not to be construed as a critical, required, or essential features or elements of any or all the claims. The claimed invention is defined solely by the appended claims including any amendments made during the pendency of this application and all equivalents of those claims as issued.

[0072] Moreover, in this document, relational terms such as first and second, top and bottom, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. The terms "comprises," "comprising," “has”, “having,” “includes”, “including,” “contains”, “containing” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises, has, includes, contains a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. An element proceeded by “comprises ...a”, “has ...a”, “includes ...a”, “contains ...a” does not, without more constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises, has, includes, contains the element. The terms “a” and “an” are defined as one or more unless explicitly stated otherwise herein. The terms “substantially”, “essentially”, “approximately”, “about” or any other version thereof, are defined as being close to as understood by one of ordinary skill in the art, and in one non-limiting embodiment the term is defined to be within 10%, in another embodiment within 5%, in another embodiment within 1 % and in another embodiment within 0.5%. The term “coupled” as used herein is defined as connected, although not necessarily directly and not necessarily mechanically. A device or structure that is “configured” in a certain way is configured in at least that way but may also be configured in ways that are not listed.

[0073] The patent claims at the end of this patent application are not intended to be construed under 35 U.S.C. § 1 12(f) unless traditional means-plus-function language is expressly recited, such as “means for” or “step for” language being explicitly recited in the claim(s).

Claims

What is Claimed is:1 . An integrated bubble trap device for a working heart system comprising:(a) a body arranged along a longitudinal axis, the body including an internal cavity configured to be partially filled with a liquid;(b) an inlet including:(i) an inlet end configured to be in fluid communication with a liquid reservoir, and(ii) an inlet lumen extending from the inlet end to the internal cavity of the body;(c) an outlet including:(i) an outlet end configured to be an atrial cannula and directly connect to a left atrium of an excised heart of a test specimen, and(ii) an outlet lumen extending from the internal cavity of the body to the outlet end;(d) a syringe port configured to connect a syringe to the internal cavity of the body, the syringe port positioned above the inlet and the outlet when the longitudinal axis is arranged vertically; and(e) a catheter extension configured to directly connect to the inlet end of the inlet of the body, the catheter extension including an extension lumen in fluid communication with the inlet lumen when the catheter extension is connected to the inlet end of the inlet.

2. The integrated bubble trap device of claim 1 , the inlet positioned above the outlet when the longitudinal axis is arranged vertically.

3. The integrated bubble trap device of claim 1 or claim 2, the internal cavity configured to be filled by the liquid to a level above the inlet and the outlet when the longitudinal axis is arranged vertically.

4. The integrated bubble trap device of any one of claims 1 to 3 further comprising an aperture at the bottom of the body configured to connect to a pressure sensor.

5. The integrated bubble trap device of claim 4 further comprising a flow sensor positioned at the inlet lumen or the outlet lumen for atrial flow rate or cardiac output measurement.

6. The integrated bubble trap device of any one of claims 1 to 5, the syringe port configured to connect a headspace of the body to the syringe to at least one of hold extra air, to adjust the buffer height in the internal cavity of the body, and to adjust atrial filling compliance.

7. The integrated bubble trap device of any one of claims 1 to 6, the catheter extension having a first portion arranged along a first axis and a second portion arranged along a second axis, the first axis disposed at an obtuse angle relative to the second axis.

8. The integrated bubble trap device of any one of claims 1 to 7, further comprising the liquid reservoir and a clamp configured to hold the liquid reservoir in a position, the clamp adjustable in three dimensions to adjust the position of the liquid reservoir.

9. The integrated bubble trap device of claim 8, the position of the liquid reservoir being at least one inch from the inlet of the body.

10. A working heart system comprising:(a) a left atrial block including:(i) a liquid reservoir, and(ii) a left atrial port in direct fluid communication with the liquid reservoir and configured for fluid communication with a left atrium of an excised heart of a test specimen;(b) an integrated bubble trap device comprising:(i) a body including an internal cavity configured to be partially filled with a liquid, the internal cavity including a headspace configured to be filled by air, the internal cavity in fluid communication with the liquid reservoir and configured to be fluidly connected to a left atrium of an excised heart of a test specimen, and(ii) a syringe port configured to connect the headspace of the body to a syringe to at least one of hold extra air, to adjust the buffer height in the internal cavity of the body, and to adjust atrial filling compliance;(c) an aortic block comprising:(i) an aortic cannula configured to connect to an aorta of the excised heart and a peristaltic pump to pump fluid into the excised heart.(ii) a pressure-volume catheter port configured to enable insertion of a pressurevolume catheter into a left ventricle of the excised heart;(d) a pulmonary artery cannula including:(i) a cannula inlet configured to connect to a pulmonary artery of the excised heart, and(ii) a cannula outlet in fluid communication with a measuring container;11 . The working heart system of claim 10, the integrated bubble trap device further comprising an inlet including an inlet end configured to be in fluid communication with a liquid reservoir, and an inlet lumen extending from the inlet end to the internal cavity of the body, and the integrated bubble trap device further comprising an outlet including an outlet end configured to connect to a left atrium of an excised heart of a test specimen and an outlet lumen extending from the internal cavity of the body to the outlet end.

12. The working heart system of claim 11 , the headspace positioned above the inlet and the outlet when a longitudinal axis of the body is arranged vertically.

13. The working heart system of any one of claims 10 to 12 further comprising an aperture in the body configured to connect to a pressure sensor.

14. The working heart system of claim 13 further comprising a flow sensor.

15. The working heart system of claim 11 , the syringe port positioned above the inlet and the outlet when a longitudinal axis of the body is arranged vertically.

16. The working heart system of any one of claims 11 to 15 further comprising a catheter extension configured to connect to the inlet end of the inlet of the body, the catheter extension including an extension lumen in fluid communication with the inlet lumen when the catheter extension is connected to the inlet end of the inlet.

17. The working heart system of any one of claims 10 to 16, further comprising a clamp configured to hold the liquid reservoir in a position, the clamp adjustable in three dimensions to adjust the position of the liquid reservoir.

18. The working heart system of claim 17, the position of the liquid reservoir being at least one inch from the inlet of the body.

19. A method of using a working heart system, the method comprising: providing a left atrial block including a liquid reservoir containing a perfusion buffer, the left atrial block further including a left atrial port in fluid communication with the liquid reservoir; fluidly connecting the left atrial port to an integrated bubble trap device, the integrated bubble trap device including an internal cavity partially filled with the perfusion buffer, a headspace, and a syringe port; fluidly connecting the integrated bubble trap device to a left atrium of an excised heart of a test specimen; flowing perfusion buffer from the liquid reservoir into the left atrium of the excised heart via the integrated bubble trap device; and removing bubbles from the flowing perfusion buffer in the integrated bubble trap device.

20. The method of claim 19, wherein the left atrial port is secured to a catheter extension that is secured to the integrated bubble trap device, the catheter extension fluidly connecting the left atrial port and the integrated bubble trap device.21 . The method of claim 20 further comprising securing the liquid reservoir in a clamp and adjusting the clamp to adjust a position of the liquid reservoir.

22. The method of claim 19 further comprising measuring a pressure in the internal cavity of the integrated bubble trap device.

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