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Functional evidence of low-pressure cardiopulmonary baroreceptor reinnervation 1 year after heart transplantation

  • Original Article
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European Journal of Applied Physiology Aims and scope Submit manuscript

Abstract

Purpose

Heart transplantation (HTx) implies denervation of afferent neural connections. Reinnervation of low-pressure cardiopulmonary baroreceptors might impact the development and treatment of hypertension, but little is known of its occurrence. The present prospective study investigated possible afferent reinnervation of low-pressure cardiopulmonary baroreceptors during the first year after heart transplantation.

Methods

A total of 50 heart transplant recipients (HTxRs) were included and were evaluated 7–12 weeks after transplant surgery, with follow-up 6 and 12 months later. In addition, a reference group of 50 healthy control subjects was examined once. Continuous, non-invasive recordings of cardiovascular variables were carried out at supine rest, during 15 min of 20° head-up tilt, during Valsalva maneuver and during 1 min of 30% maximal voluntary handgrip. In addition, routine clinical data including invasive measurements were used in the analyses.

Results

During the first year after HTx, the heart rate (HR) response to 20° head-up tilt partly normalized, a negative relationship between resting mean right atrial pressure and HR tilt response developed, low-frequency variability of the RR interval and systolic blood pressure at supine rest increased, and the total peripheral resistance response to Valsalva maneuver became stronger.

Conclusion

Functional assessments suggest that afferent reinnervation of low-pressure cardiopulmonary receptors occurs during the first year after heart transplantation, partially restoring reflex-mediated responses to altered cardiac filling.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AccHEART:

Autonomic cardiovascular control after heart transplantation

CI:

Cardiac index

DBP:

Diastolic blood pressure

EDVI:

End-diastolic volume index

HR:

Heart rate

HTx:

Heart transplantation

HTxRs:

Heart transplant recipients

LF:

Low-frequency power (of cardiovascular variability)

MAP:

Mean arterial blood pressure

RAP:

Right atrial pressure

RRI:

RR interval

SBP:

Systolic blood pressure

TPRI:

Total peripheral resistance index

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Acknowledgements

We thank the HTx nurses Anne Relbo Authen and Ingelin Grov for help in patient coordination; Hamsana Chaudrakumar and the bioengineers for blood sampling and laboratory assistance; Steinar Kumarasamy Aune, Knut Andresen and Elisabeth Bjørkelund for practical support; Henrik Brun and Arne Kristian Andreassen for discussion on study design and results; Terje Rootwelt for institutional support; and finally all the enthusiastic participants. This study was funded by the Health South–East Hospital Trust, Norway (2012044).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Akershus University Hospital, 1478, Lørenskog, Norway

    Vegard Bruun Bratholm Wyller

  2. Faculty of Medicine, University of Oslo, Oslo, Norway

    Vegard Bruun Bratholm Wyller, Sissel Nygaard, Anders Haugom Christensen, Katrine Rolid, Kari Nytrøen & Lars Gullestad

  3. Department of Pediatric Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway

    Sissel Nygaard, Anders Haugom Christensen, Erik Thaulow & Gaute Døhlen

  4. Department of Cardiology, Rikshospitalet, Oslo University Hospital, Oslo, Norway

    Katrine Rolid, Kari Nytrøen & Lars Gullestad

  5. KG Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway

    Lars Gullestad

  6. Department of Cardiothoracic Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway

    Arnt Fiane

  7. Department of Pediatrics, West Virginia University, Morgantown, WV, USA

    J. Philip Saul

  8. Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway

    Lars Gullestad

Authors
  1. Vegard Bruun Bratholm Wyller
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  2. Sissel Nygaard
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  3. Anders Haugom Christensen
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  4. Katrine Rolid
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  7. Arnt Fiane
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  8. Erik Thaulow
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  9. Gaute Døhlen
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Contributions

SN and AHC collected clinical data, contributed to study design and participated in data analyses. KR, KN, LG, AF, ET, GD and JPS supervised data analyses and contributed to study design. VBBW conceived of the study, contributed to study design and participated in data analyses. JPS is funded by the IDeA States Pediatric Clinical Trials Network (ISPCTN) of the National Institutes of Health, Grant #UG1OD024949. All authors contributed to data interpretation and drafting of the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Vegard Bruun Bratholm Wyller.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in the present study were in accordance with the ethical standards of the Norwegian National Committee for Ethics in Medical research and with the 1964 Helsinki declaration and its later amendments. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Communicated by Ellen Adele Dawson.

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Wyller, V.B.B., Nygaard, S., Christensen, A.H. et al. Functional evidence of low-pressure cardiopulmonary baroreceptor reinnervation 1 year after heart transplantation. Eur J Appl Physiol 121, 915–927 (2021). https://doi.org/10.1007/s00421-020-04586-0

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