Sino-Atrial Node Transplantation in the Dog

Morishita, Yasuo; Poirier, Robert A.; Rohner, Robert F.

doi:10.1177/153857448101500603

Cited by 5 publications

(6 citation statements)

References 5 publications

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“…Biological pacing has been explored in an effort to further optimize pacemaker therapy (21). One approach, autologous transplantation to the ventricle of the sinoatrial node (SAN) or intact nodal tissue, was reported over 30 years ago, but with poor success [summarized in (16)]. In the late 1990s gene delivery of the β 2 -adrenergic receptor was noted to augment the function of endogenous pacemaker tissues (8).…”

Section: Introductionmentioning

confidence: 99%

Implantation of Sinoatrial Node Cells Into Canine Right Ventricle: Biological Pacing Appears Limited by the Substrate

Zhang¹,

Lau²,

Shlapakova³

et al. 2011

cell transplant

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Biological pacing has been proposed as a physiologic counterpart to electronic pacing, and the sinoatrial node (SAN) is the general standard for biological pacemakers. We tested the expression of SAN pacemaker cell activity when implanted autologously in the right ventricle (RV). We induced complete heart block and implanted electronic pacemakers in the RV of adult mongrel dogs. Autologous SAN cells isolated enzymatically were studied by patch clamp to confirm SAN identity. SAN cells (400,000) were injected into the RV subepicardial free wall and dogs were monitored for 2 weeks. Pacemaker function was assessed by overdrive pacing and IV epinephrine challenge. SAN cells expressed a time-dependent inward current (If) activating on hyperpolarization: density = 4.3 ± 0.6 pA/pF at −105 mV. Four of the six dogs demonstrated >50% of beats originating from the implant site at 24 h. Biological pacemaker rates on days 7–14 = 45–55 bpm and post-overdrive escape times = 1.5–2.5 s. Brisk catecholamine responsiveness occurred. Dogs implanted with autologous SAN cells manifest biological pacing properties dissimilar from those of the anatomic SAN. This highlights the importance of cell and substrate interaction in generating biological pacemaker function.

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Section: Introductionmentioning

confidence: 99%

Implantation of Sinoatrial Node Cells Into Canine Right Ventricle: Biological Pacing Appears Limited by the Substrate

Zhang¹,

Lau²,

Shlapakova³

et al. 2011

cell transplant

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“…After a stable, complete heart block, the implanted autologous SANs established no influence on the recipient's preexistent idioventricular rhythm (Starzl et al, 1963 ). Uncertainties on the validity of the surgical technique applied and other technological difficulties related to the implantation and monitoring of the conduction tissue (e.g., pacemaker malfunctions) were also evident with further investigation (Morishita et al, 1981 ). Although not completely clear in the eyes of the scientists who tried it first, this initial approach could not be successful for many reasons, starting with a possible immune response to the allogeneic/xenogeneic tissue (foreign body reaction) up to the difficulties to achieve electrical integration and coupling with recipient's myocardium.…”

Section: Approaches For the Engineering Of Biological Pacemakersmentioning

confidence: 99%

“…After the initial unsuccessful, autologous, allogeneic, and xenogeneic transplantation trials of the SAN tissue (Rylant, 1927 ; Ernst and Paulson, 1962 ; Starzl et al, 1963 ; Morishita et al, 1981 ), subsequent attempts were realized using the methodologies characterized by an inferior technical demand.…”

Section: Approaches For the Engineering Of Biological Pacemakersmentioning

confidence: 99%

“…Due to the architectural and functional complexity of nodal tissues, such a strategy might fully regenerate cardiac conduction by combining scaffolds and cells opportunely in biomimetic, bioequivalent tissue constructs. However, the drawbacks of the first SAN tissue transplantation experiments (Starzl et al, 1963 ; Morishita et al, 1981 ) as core necrosis, immune response, and non-integration might hamper the success of tissue engineering approaches and have to be excluded to prevent any condition leading to graft failure.…”

Section: Approaches For the Engineering Of Biological Pacemakersmentioning

confidence: 99%

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Bioengineering the Cardiac Conduction System: Advances in Cellular, Gene, and Tissue Engineering for Heart Rhythm Regeneration

Naumova

Iop

2021

Front. Bioeng. Biotechnol.

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Heart rhythm disturbances caused by different etiologies may affect pediatric and adult patients with life-threatening consequences. When pharmacological therapy is ineffective in treating the disturbances, the implantation of electronic devices to control and/or restore normal heart pacing is a unique clinical management option. Although these artificial devices are life-saving, they display many limitations; not least, they do not have any capability to adapt to somatic growth or respond to neuroautonomic physiological changes. A biological pacemaker could offer a new clinical solution for restoring heart rhythms in the conditions of disorder in the cardiac conduction system. Several experimental approaches, such as cell-based, gene-based approaches, and the combination of both, for the generation of biological pacemakers are currently established and widely studied. Pacemaker bioengineering is also emerging as a technology to regenerate nodal tissues. This review analyzes and summarizes the strategies applied so far for the development of biological pacemakers, and discusses current translational challenges toward the first-in-human clinical application.

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“…Due to the heterogeneous nature of the Ebs (41), some groups have focused their effort on specifically isolating sino-atrial nodal type cells (52). But attempts to autologuously graft the SAN or inject SAN myocytes failed to provide sustained biological pacemaker activity, highlighting the critical role of the substrate (53,54). …”

Section: Recreating a San Function With Pluripotent Cellsmentioning

confidence: 99%

Stem cell–based biological pacemakers from proof of principle to therapy: a review

2014

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Electronic pacemakers are the standard therapy for bradycardia related symptoms but have shortcomings. Over the past 15 years experimental evidence has demonstrated that gene and cell-based therapies can create a biological pacemaker. Recently, physiologically acceptable rates have been reported with an adenovirus-based approach. But adenovirus-based protein expression does not last more than 4 weeks, which limits its clinical applicability. Cell-based platforms are potential candidates for longer expression. Currently there are two cell based approaches being tested: 1) Mesenchymal stem cells used as a suitcase for delivering pacemaker genes and 2) Pluripotent stem cells differentiated down a cardiac lineage with endogenous pacemaker activity. This review examines the current achievements in engineering a biological pacemaker, defines the patient population for whom this device would be useful and identifies the challenges still ahead before cell therapy can replace current electronic devices.

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Sino-Atrial Node Transplantation in the Dog

Cited by 5 publications

References 5 publications

Implantation of Sinoatrial Node Cells Into Canine Right Ventricle: Biological Pacing Appears Limited by the Substrate

Implantation of Sinoatrial Node Cells Into Canine Right Ventricle: Biological Pacing Appears Limited by the Substrate

Bioengineering the Cardiac Conduction System: Advances in Cellular, Gene, and Tissue Engineering for Heart Rhythm Regeneration

Stem cell–based biological pacemakers from proof of principle to therapy: a review

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