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Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk

Published: July 27, 2022 doi: 10.3791/64073


The present protocol describes methods for transgene expression in rat and mouse hearts by direct intramyocardial injection of the virus under echocardiography guidance. Methods for the assessment of the susceptibility of hearts to ventricular arrhythmias by the programmed electrical stimulation of isolated, Langendorff-perfused hearts are also explained here.


Heart disease is the leading cause of morbidity and mortality worldwide. Due to the ease of handling and abundance of transgenic strains, rodents have become essential models for cardiovascular research. However, spontaneous lethal cardiac arrhythmias that often cause mortality in heart disease patients are rare in rodent models of heart disease. This is primarily due to the species differences in cardiac electrical properties between human and rodents and poses a challenge to the study of cardiac arrhythmias using rodents. This protocol describes an approach to enable efficient transgene expression in mouse and rat ventricular myocardium using echocardiography-guided intramuscular injections of recombinant virus (adenovirus and adeno-associated virus). This work also outlines a method to enable reliable assessment of cardiac susceptibility to arrhythmias using isolated, Langendorff-perfused mouse and rat hearts with both adrenergic and programmed electrical stimulations. These techniques are critical for studying heart rhythm disorders associated with adverse cardiac remodeling after injuries, such as myocardial infarction.


Cardiovascular disease is the leading cause of death worldwide, claiming the lives of 18 million people in 2017 alone1. Rodents, especially mice and rats, have become the most commonly used model in cardiovascular research due to the ease of handling and the availability of various transgenic overexpression or knockout lines. Rodent models have been fundamental for understanding the disease mechanisms and for identifying potential new therapeutic targets in myocardial infarction2, hypertension3, heart failure4, and atherosclerosis5. However, the use of rodents in studies of cardiac arrhythmias is limited by their small heart size and faster heart rate compared to human or large animal models. Therefore, spontaneous lethal arrhythmias in mice or rats after myocardial infarction are rare2. Investigators are forced to focus on indirect secondary changes that might reflect a pro-arrhythmic substrate, such as fibrosis or gene expression, without showing meaningful changes in arrhythmia burden or pro-arrhythmic tendencies. To overcome this limitation, a method that allows a reliable assessment of the susceptibility of mouse and rat hearts to ventricular tachyarrhythmias after genetic modification6,7 or myocardial infarction2 is described in the present protocol. This method combines adrenergic receptor stimulation with programmed electrical stimulation to induce ventricular tachyarrhythmias in isolated, Langendorff-perfused8 mouse and rat hearts.

Standard approaches for viral gene transfer in rodent myocardial tissue often involve the exposure of the heart by thoracotomy9,10,11, which is an invasive procedure and is associated with delayed recovery of the animals after the procedure. This article describes a method of direct intramyocardial injection of virus under ultrasound imaging guidance for the overexpression of transgenes. This less invasive procedure allows for faster animal recovery after viral injection and less tissue injury, as compared to thoracotomy, reduces post-operative pain and inflammation in the animal, and, thus, allows better assessment of the effects of transgenic genes on heart function.

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All the methods and procedures described were approved by the animal research ethical review board at the University of Ottawa and the biosafety review committee at the University of Ottawa Heart Institute. The developed safety protocols include that all the procedures dealing with recombinant adenovirus or adeno-associated virus (AAV) were performed in a level II biosafety cabinet. All the items in contact with the virus were thoroughly decontaminated after the experiment. Ctnnb1flox/flox and αMHC-MerCreMer mice (8-12 weeks old, of either sex) and Sprague-Dawley rats (200-250g, male) were used for the present study. The animals were obtained from commercial sources (see Table of Materials). All the procedures dealing with animals were performed by staff who have been trained and approved by institutional regulatory committees. Appropriate personal protective equipment was used during all procedures.

1. Viral transgene expression in rodent ventricular tissues

NOTE: Store recombinant adenovirus or AAV that expresses the target gene and the corresponding control virus, such as Ad-GFP (titer of 1 x 1010 PFU/mL) or AAV9-GFP (titer of 1 x 1013 GC/mL) (see Table of Materials), in a −80 °C freezer.

  1. On the day of virus injection, thaw the virus on ice. Aspirate the virus expressing the target gene and the control virus into two separate syringes (volume = 50 µL) with 30 G 1/2 needles and keep on ice until use.
    NOTE: Any bubbles in the syringe and needle must be carefully removed.
  2. Administer buprenorphine to rats or mice (0.05 mg/kg for rats, 0.1 mg/kg for mice, subcutaneous), 1 h later induce anesthesia using 3% isoflurane, and maintain isoflurane at 2% (in 100% oxygen at a flow rate of 0.5-1.0 L/min) for the subsequent procedure.
  3. Gently pinch the animal's body (e.g., the tail) with a pair of forceps, and if the animal does not respond to the pinch with any body movements, proper anesthetization is confirmed.
  4. Maintain body temperature at 37 °C using an electric heating pad. Shave the hair in the chest region using a hair clipper.
    NOTE: Care should be taken while using an electric heating pad due to potential uneven heat distribution.
  5. Apply ophthalmic ointment to both eyes to prevent the drying of the cornea.
  6. Keep the animal in a supine position and use a preclinical imaging system (see Table of Materials) for ultrasound imaging of the animal's heart in the short-axis orientation.
    NOTE: The following steps are performed in a level II biosafety cabinet which provides a sterile environment. Standard safety procedures, including those with safe needle handling, are employed.
  7. Sterilize the left lower chest region of the animal with alternating rounds of an iodine-based or chlorhexidine-based scrub and alcohol three times in a circular motion.
  8. Under ultrasound imaging guidance, insert the 30 G 1/2 needle of the syringe containing the virus as prepared in step 1.1. into the animal's chest via the left lower chest side of the body.
  9. Approach the needle tip into the left ventricular front free wall and slowly inject 10-15 μL of the virus. Verify successful injection in ultrasound images by the enhanced brightness near the tip of the needle.
    NOTE: The amount of virus injected at each site is no more than 15 μL to prevent physical damage to the myocardial tissues.
  10. Withdraw the needle from the heart and insert it into other regions of the left ventricle for a second and third injection of the same amount of virus.
    NOTE: The total number of injection sites is determined by the experimental design. If focal transgene expression is required, only one injection is needed; if more diffusive transgene expression is required, multiple injection sites (three to five) are usually needed.
  11. After the completion of the injections, return the animal to its cage.
  12. Carefully monitor the animal until it has regained sufficient consciousness to maintain sternal recumbency and return it to its housing room.
  13. Administer buprenorphine HCl (0.1 mg/kg, twice a day for mice, 0.05 mg/kg, twice a day for rats, subcutaneous) to the animal for the following 2 days. Return animals to the vivarium and monitor daily for any unusual signs of pain or distress, and if found, treat animals per the Institutional animal care committee protocols.

2. Assessment of cardiac arrhythmia susceptibility

NOTE: At 4-6 days after adenovirus injection and 1-2 weeks after AAV injection, assess the susceptibility of the animal hearts to cardiac arrhythmias following steps 2.1.-2.2.

  1. Perform Langendorff perfusion of the rat or mouse heart.
    1. Prepare Tyrode solution by adding the following to 1 L of water: NaCl, 7.9 g (final = 135 mM); KCl, 0.37 g (5.0 mM); CaCl2, 0.27 g (1.8 mM); MgCl2, 0.24 g (1.2 mM); HEPES, 2.38 g (10 mM); and glucose, 1.8 g (10 mM). Adjust the pH to 7.40 with NaOH (see Table of Materials).
    2. Filter the solution with a 0.2 μm filter and bubble with 100% O2 continuously during steps 2.1.6.-2.2.8.
    3. Administer heparin to the rat or mouse (500 U/kg, intraperitoneal injection) and 10 min later anesthetize the animal with 3% isoflurane. Ensure adequate anesthetization with a gentle pinch on the body.
    4. Use a scalpel to make a 1-1.5 cm vertical incision in the mid-clavicular line for a left thoracotomy and expose the heart.
    5. Collect the heart by cutting with a pair of scissors at the aortic arch level and immediately put the heart into ice-cold Tyrode solution.
      ​NOTE: Caution is exercised not to damage the heart during heart collection.
    6. Cannulate the aorta of the heart with a blunt needle (18 G for rats; 23 G for mice) connected to a modified Langendorff perfusion system (see Table of Materials) in the constant flow rate mode. Adjust the flow rate to keep the perfusion pressure at 70-80 mmHg.
      NOTE: Any bubbles in the perfusion needle must be removed before aortic cannulation. Using a dissecting microscope facilitates the cannulation.
    7. Place the cannulated heart in a silicone elastomer-coated9, 10 cm plastic dish with the left ventricle facing up and perfuse the heart9,12 with O2-bubbled Tyrode solution at 37 °C.
    8. Verify the correct aortic cannulation at the beginning of perfusion by observing the washout of blood from the heart during the first two to three heartbeats and the changing of the heart color from red to pale.
    9. Place the electrodes of a small animal ECG system (see Table of Materials) around the heart by inserting them into the silicone elastomer coating in the dish (Figure 1). Record ECG using compatible software.
  2. Perform adrenergic receptor stimulation and programmed electrical stimulation to induce ventricular tachyarrhythmias.
    1. After successful aortic cannulation, continue to perfuse the heart with Tyrode solution for 20 min to stabilize the heart preparation.
    2. Add 1 μM isoproterenol (see Table of Materials) to the Tyrode solution used for heart perfusion in steps 2.2.3.-2.2.8.
    3. After 10 min of isoproterenol perfusion, stimulate the heart at the apex with two platinum electrodes connected to an electrical stimulator (see Table of Materials).
    4. Start with the stimulation procedure (Figure 2), which includes 10 consecutive stimuli (S1, 5 V, 100 ms intervals) that are followed by an extra stimulus (S2) with an initial interval of 80 ms. Repeatedly reduce the S2 interval by 2 ms each time until the heartbeat can no longer be captured (i.e., reaching the heart's effective refractory period, ERP)13.
    5. Monitor any induced ventricular tachyarrhythmias (including ventricular tachycardia and fibrillation) by ECG.
    6. If no arrhythmias are induced by the above procedure, add another extra stimulus (S3) after S2 with the same initial (80 ms) and decrement (by 2 ms) intervals until the ERP is reached.
    7. If ventricular tachyarrhythmias are still not induced, add one more extra stimulus (S4) after S3 with the same initial and decrement intervals until the ERP is reached.
    8. If ventricular tachyarrhythmias are still not induced (as expected in control healthy hearts), stop the electrical stimulation protocol and consider the heart to be non-inducible.

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Representative Results

When perfused following the protocol described here (Figure 1), an isolated rat or mouse heart beats rhythmically and stably for at least 4 h. If the experimental design requires a longer period of heart perfusion, it is helpful to add albumin into the perfusion solution to reduce the occurrence of myocardial edema after long-time perfusion14. The inclusion of isoproterenol in the perfusion solution mimics the activation of the sympathetic nervous system which occurs in many arrhythmogenic conditions such as myocardial infarction and heart failure. During the programmed electrical stimulation, the successful pacing of the heart is verified by (1) the 1:1 capture of the heartbeat during the consecutive S1 stimuli and (2) the prolonged (or wider) QRS complex during S1 pacing (Figure 3 and Figure 4). The latter is because the heart is being paced at the apex and the slower conduction of the activation in the ventricular tissues increases the QRS complex duration.

As demonstrated in the published data2,7 (Figure 3 and Figure 4), these combined adrenergic and electrical stimulations induced no ventricular tachyarrhythmias (defined as at least three consecutive premature ventricular complexes, PVCs) in healthy mouse hearts (sham-operated wild-type hearts in Figure 3) or in control rat hearts (control Ad-GFP-injected rat hearts in Figure 4). By contrast, the same protocol induced ventricular tachyarrhythmias in 77% of wild-type mouse hearts after myocardial infarction (Figure 3B) and in three out of four rat hearts after intramyocardial injection of Ad-Wnt3a (Figure 4). This demonstrates the high fidelity of this ventricular arrhythmia-inducing approach.

Successful intramyocardial transgene expression after virus injection can be verified by upregulated mRNA and protein levels of the transgene in the myocardial tissues identified by real-time quantitative RT-PCR, western blot, or immunohistochemistry. If the virus expresses a fluorescent reporter gene, such as GFP, successful viral transduction can also be verified in isolated, live, single cardiomyocytes by their expression of GFP9.

Figure 1
Figure 1: Langendorff perfusion of an isolated rat heart. The heart is collected from the animal, and the aorta is cannulated with a blunt 18 G needle. The needle is connected to a 10 mL syringe filled with 37 °C Tyrode solution at a pressure of 70-80 mmHg. The heart is placed in a silicone elastomer-coated, 10 cm plastic dish with the left ventricle facing up. Electrodes (red, green, and black colors) of a small animal ECG system are placed around the heart by inserting them into the silicone elastomer coating in the dish. Please click here to view a larger version of this figure.

Figure 2
Figure 2: Adrenergic and electrical stimulations of the Langendorff-perfused heart. (A) Rat or mouse heart is perfused on a Langendorff system as shown in Figure 1, and 1 µM isoproterenol is added to the perfusing Tyrode solution to stimulate the β1 adrenergic receptors of the heart. The heart is then stimulated at the apex by two platinum electrodes connected to a stimulator. (B) Representation of the programmed electrical stimulation. For details, see step 2.2. The figure is modified with permission from Wang et al.2. Please click here to view a larger version of this figure.

Figure 3
Figure 3: Ventricular tachyarrhythmias induced in mouse hearts after myocardial infarction. (A) Representative ex vivo ECG (Lead II) showing programmed electrical stimulation (PES)-induced ventricular tachycardia (VT, defined as three or more consecutive premature ventricular complexes, PVCs) in a wild-type (WT) mouse heart (at 8 weeks after myocardial infarction, MI) when stimulated with one extra stimulus (S2) but only one single PVC in a cardiac-specific β-catenin knockout (KO) mouse heart (at 8 weeks after MI) when stimulated with three extra stimuli (S4). Isoproterenol (1 µM) was included in the perfusing Tyrode solution during the PES stimulation. Cardiac-specific β-catenin (Ctnnb1) knockout mice were generated by cross-breeding Ctnnb1flox/flox mice (with exons 2 to 6 floxed) with αMHC-MerCreMer mice. At the age of 8-12 weeks, Ctnnb1flox/flox;αMHC-MerCreMer+/− mice (KO) and littermate Ctnnb1flox/flox;αMHC-MerCreMer−/− mice (used as control wild-type mice) received daily subcutaneous injections of tamoxifen (20 mg/kg/day) for 5 consecutive days before they were assigned to either the MI or sham group. (B) Summary of PES-induced PVCs and VTs in WT and KO hearts at 1 week or 8 weeks after MI. An arrhythmia score was assigned to each heart according to the criteria in the left table. At 8 weeks after MI, VT was successfully induced in 77% of WT hearts but only in 18% of KO hearts. Data were analyzed by two-way ANOVA and a Bonferroni post-hoc comparison. The error bars indicate standard error (SE). The figure is reproduced with permission from Wang et al.2. Please click here to view a larger version of this figure.

Figure 4
Figure 4: Ventricular tachyarrhythmias induced in rat hearts after intramyocardial injection of a virus expressing Wnt3a. (A) PES induced ventricular arrhythmias in hearts of rats (200-250 g, male, Sprague-Dawley) at day 4-6 after intramyocardial injection of an adenovirus expressing Wnt3a (Ad-Wnt3a, bottom) but not in hearts injected with control adenovirus expressing GFP (Ad-GFP, top). Hearts were isolated and perfused on a Langendorff system. Isoproterenol (1 µM) was included in the perfusing Tyrode solution during the PES stimulation. Ex vivo ECG was continuously recorded during PES stimulation. Note that 11 consecutive S1 stimuli (blue color) were used in this experiment. (B) Summary of studies in Panel (A): Ventricular tachycardia (VT) was induced by PES in three out of four hearts with Ad-Wnt3a injection but in none of the four hearts with control Ad-GFP. The figure is reproduced with permission from Lu et al.7. Please click here to view a larger version of this figure.

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Several steps are critical for the success of the Langendorff-perfused, isolated heart preparation. Firstly, it is important to avoid any damage to the heart during heart collection (e.g., due to accidental squeezing or cutting with the scissors). Secondly, it is critical to put the collected heart into cold Tyrode solution as soon as possible because this will stop the heartbeat and reduce the oxygen consumption of the heart. Thirdly, the needle insertion into the aorta must not be too deep—ideally, the tip of the needle is close to the aortic valve level so that the heart is well-perfused through the coronary arteries. Lastly, bubbles in the perfusion needle need to be removed prior to aortic cannulation—it is usually helpful to turn on the pump for a few seconds right before cannulation to remove the bubble at the tip of the needle.

The Langendorff-perfused heart preparation has several advantages over the in vivo studies in animals. Firstly, it is possible to accurately control the concentration and duration of drugs applied to the heart (e.g., isoproterenol, as used in this study). Secondly, it allows easy access to the different regions of the heart for either stimulation (e.g., electrical pacing at the apex in this manuscript) or physiological signal recording (e.g., optical mapping of the ventricular tissues after loading with a Ca2+-sensitive or voltage-sensitive dye, which is not described here). In addition, cardiac function, such as ventricular contractility, can be readily measured by inserting a balloon into the left ventricle and connecting the balloon to a pressure transducer8. Thirdly, the intrinsic properties of the heart, such as heart rate and ventricular contractility, can be investigated without the complicating factors in in vivo studies, such as the autonomic nervous system and circulating hormones. However, the limitation of the Langendorff-perfused heart is that it lacks the cross-talk among different organs or tissues in vivo15,16,17 via either circulating factors or the autonomic nervous system, which may be critical players in some studies.

The ex vivo ECG recording of the Langendorff-perfused heart, as described here and in the previous publications2,6,7,9, has the advantage of contactless recording and poses no disturbance to the function of the heart as compared to other approaches such as optical mapping, which requires the loading of Ca2+-sensitive or voltage-sensitive dyes and the use of an excitation-contraction uncoupler to reduce mechanical heart movement (such as blebbistatin)12,18. However, the optical mapping has the advantage of providing more detailed information on the electrical activities of the heart, such as the origin of the heartbeat, the pattern of myocardial activation, and the myocardial conduction velocity.

The method of direct intramyocardial injection of a virus, as described here, can also be used for the delivery of other therapeutic materials19,20,21,22,23,24, such as biomaterials, exons, modified mRNA, and stem cell-derived cardiomyocytes. The ultrasound imaging-guided intramyocardial injection has several advantages over the traditional thoracotomy-based injection approach. Firstly, it is less invasive and allows for faster recovery of the animals after the injection procedure. This reduces procedure-associated effects on the animals (e.g., those caused by post-operative pain and chest tissue inflammation when an invasive thoracotomy is used). Secondly, ultrasound imaging verifies successful virus injection in the heart, which increases the consistency and reproducibility of the results. However, the limitation of the ultrasound-guided virus injection approach is that the locations of the virus injection sites cannot be controlled as precisely as in the thoracotomy-based approach, which allows visual localization of the different heart regions.

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The authors have no competing financial interests.


This work was supported by the Canadian Institutes of Health Research (CIHR) Project Grants (PJT-148918 and PJT-180533, to WL), the CIHR Early Career Investigator Award (AR8-162705, to WL), the Heart and Stroke Foundation of Canada (HSFC) McDonald Scholarship and New Investigator Award (S-17-LI-0866, to WL), Student Scholarships (to JW and YX), and a Postdoctoral Fellowship (to AL) from the University of Ottawa Cardiac Endowment Funds at the Heart Institute. The authors thank Mr. Richard Seymour for his technical support. Figure 2 was created with Biorender.com with approved licenses.


Name Company Catalog Number Comments
30 G 1/2 PrecisionGlide Needle Becton Dickinson (BD) 305106
adeno-associated virus (AAV9-GFP) Vector Biolabs 7007
adenovirus (Ad-GFP) Vector Biolabs 1060
adenovirus (Ad-Wnt3a) Vector Biolabs ADV-276318
Biosafety cabinet (Level II) Microzone Corporation N/A Model #: BK-2-4
Buprenorphine Vetergesic DIN 02342510
Calcium Chloride Sigma-Aldrich 102378
D-Glucose Fisher Chemical D16-1
Hair clipper WAHL Clipper Corporation 78001
Hamilton syringe Sigma-Aldrich 20701 705 LT, volume 50 μL
Heating pad Life Brand E12107
Heparin Fresenius Kabi DIN 02264315
HEPES Sigma-Aldrich H4034
Isoflurane Fresenius Kabi Ltd. M60303
Isoproterenol hydrochloride Sigma-Aldrich 1351005
LabChart 8 software ADInstruments Inc. Version 8.1.5 for ECG recording
Magnesium chloride hexahydrate Sigma-Aldrich M2393
Mice (Ctnnb1flox/flox) Jackson Labs 4152
Mice (αMHC-MerCreMer) Jackson Labs 5650
Microscope Leica S9i for Langendorff system
MS400 transducer VisualSonic Inc. N/A
Ophthalmic ointment Systane DIN 02444062
Potassium Chloride (KCl) Sigma-Aldrich P9541
Pressure meter NETECH DigiMano 1000 for Langendorff system
Pump Cole-Parmer UZ-77924-65 for Langendorff system
Rat (Sprague-Dawley, male) Charles River 400
Scalpel blades Fine Science Tools 10010-00
Scalpel handle Fine Science Tools 10007-12
Silicone elastomer Down Inc. Sylgard 184 for Langendorff system
Small animal ECG system ADInstruments Inc. N/A Powerlab 8/35 and Animal Bio Amp
Sodium Chloride Sigma-Aldrich S7653
Sodium Hydroxide Sigma-Aldrich 567530
Stimulator IonOptix MyoPacer EP
VEVO3100 Preclinical Imaging System VisualSonic Inc. N/A



  1. Virani, S. S., et al. Heart disease and stroke statistics-2020 update: A report from the American Heart Association. Circulation. 141 (9), 139 (2020).
  2. Wang, J., et al. Cardiomyocyte-specific deletion of β-catenin protects mouse hearts from ventricular arrhythmias after myocardial infarction. Scientific Reports. 11 (1), 17722 (2021).
  3. Wang, T., et al. Effect of exercise training on the FNDC5/BDNF pathway in spontaneously hypertensive rats. Physiological Reports. 7 (24), 14323 (2019).
  4. Lin, H. B., et al. Innate immune Nod1/RIP2 signaling is essential for cardiac hypertrophy but requires mitochondrial antiviral signaling protein for signal transductions and energy balance. Circulation. 142 (23), 2240-2258 (2020).
  5. Karunakaran, D., et al. RIPK1 expression associates with inflammation in early atherosclerosis in humans and can be therapeutically silenced to reduce NF-κB activation and atherogenesis in mice. Circulation. 143 (2), 163-177 (2021).
  6. Gharibeh, L., et al. GATA6 is a regulator of sinus node development and heart rhythm. Proceedings of the National Academy of Sciences of the United States of America. 118 (1), 2007322118 (2021).
  7. Lu, A., et al. Direct and indirect suppression of Scn5a gene expression mediates cardiac Na+ channel inhibition by Wnt signalling. Canadian Journal of Cardiology. 36 (4), 564-576 (2020).
  8. Liang, W., et al. Role of phosphoinositide 3-kinase {alpha}, protein kinase C, and L-type Ca2+ channels in mediating the complex actions of angiotensin II on mouse cardiac contractility. Hypertension. 56 (3), 422-429 (2010).
  9. Kapoor, N., Liang, W., Marban, E., Cho, H. C. Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18. Nature Biotechnology. 31 (1), 54-62 (2013).
  10. Kim, N. K., Wolfson, D., Fernandez, N., Shin, M., Cho, H. C. A rat model of complete atrioventricular block recapitulates clinical indices of bradycardia and provides a platform to test disease-modifying therapies. Scientific Reports. 9 (1), 6930 (2019).
  11. Cingolani, E., et al. Gene therapy to inhibit the calcium channel beta subunit: Physiological consequences and pathophysiological effects in models of cardiac hypertrophy. Circulation Research. 101 (2), 166-175 (2007).
  12. Ionta, V., et al. SHOX2 overexpression favors differentiation of embryonic stem cells into cardiac pacemaker cells, improving biological pacing ability. Stem Cell Reports. 4 (1), 129-142 (2015).
  13. Guss, S. B., Kastor, J. A., Josephson, M. E., Schare, D. L. Human ventricular refractoriness. Effects of cycle length, pacing site and atropine. Circulation. 53 (3), 450-455 (1976).
  14. Segel, L. D., Ensunsa, J. L. Albumin improves stability and longevity of perfluorochemical-perfused hearts. The American Journal of Physiology. 254, 1105-1112 (1988).
  15. Hong, P., et al. NLRP3 inflammasome as a potential treatment in ischemic stroke concomitant with diabetes. Journal of Neuroinflammation. 16 (1), 121 (2019).
  16. Lin, H. B., et al. Macrophage-NLRP3 inflammasome activation exacerbates cardiac dysfunction after ischemic stroke in a mouse model of diabetes. Neuroscience Bulletin. 36 (9), 1035-1045 (2020).
  17. Lin, H. B., et al. Cerebral-cardiac syndrome and diabetes: Cardiac damage after ischemic stroke in diabetic state. Frontiers in Immunology. 12, 737170 (2021).
  18. Brack, K. E., Narang, R., Winter, J., Ng, G. A. The mechanical uncoupler blebbistatin is associated with significant electrophysiological effects in the isolated rabbit heart. Experimental Physiology. 98 (5), 1009-1027 (2013).
  19. Allison, S., et al. Electroconductive nanoengineered biomimetic hybrid fibers for cardiac tissue engineering. Journal of Materials Chemistry. B. 5 (13), 2402-2406 (2017).
  20. Hamel, V., et al. De novo human cardiac myocytes for medical research: Promises and challenges. Stem Cells International. 2017, 4528941 (2017).
  21. Liang, W., Lu, A., Davis, D. R. Induced pluripotent stem cell-based treatment of acquired heart block: The battle for tomorrow has begun. Circulation. Arrhythmia and Electrophysiology. 10 (5), 005331 (2017).
  22. McLaughlin, S., et al. Injectable human recombinant collagen matrices limit adverse remodeling and improve cardiac function after myocardial infarction. Nature Communications. 10 (1), 4866 (2019).
  23. Villanueva, M., et al. Glyoxalase 1 prevents chronic hyperglycemia induced heart-explant derived cell dysfunction. Theranostics. 9 (19), 5720-5730 (2019).
  24. Kanda, P., et al. Deterministic paracrine repair of injured myocardium using microfluidic-based cocooning of heart explant-derived cells. Biomaterials. 247, 120010 (2020).
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Cite this Article

Lu, A., Wang, J., Xia, Y., Gu, R., Kim, K. H., Mulvihill, E. E., Davis, D. R., Beanlands, R. S., Liang, W. Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk. J. Vis. Exp. (185), e64073, doi:10.3791/64073 (2022).More

Lu, A., Wang, J., Xia, Y., Gu, R., Kim, K. H., Mulvihill, E. E., Davis, D. R., Beanlands, R. S., Liang, W. Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk. J. Vis. Exp. (185), e64073, doi:10.3791/64073 (2022).

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