Skip to main content
SpringerLink
Log in

Acute effects of inhaled iloprost on intracardiac conduction in patients with pulmonary arterial hypertension

Akute Wirkung von inhalativem Iloprost auf die intrakardiale Erregungsleitung bei Patienten mit pulmonalarterieller Hypertonie

  • Original articles
  • Published:
Herz Aims and scope Submit manuscript

Abstract

Background

Pulmonary arterial hypertension (PAH) is a severe, life-threatening disorder despite the availability of specific drug therapy. A lack of endogenous prostacyclin secondary to downregulation of prostacyclin synthase in PAH may contribute to vascular pathologies. Therefore, prostacyclin and its analogs including inhaled iloprost may decrease pulmonary arterial pressure and ventricular pressure.

Methods

Here, we studied that acute effects of iloprost used in pulmonary vasoreactivity testing on the intracardiac conduction system in patients with PAH. A total of 35 (15 idiopathic PAH, 20 congenital heart disease) patients with PAH were included in this prospective study. Patients were divided into two groups: 22 patients with negative pulmonary vasoreactivity in group 1 and 13 with positive pulmonary vasoreactivity in group 2. Electrophysiological parameters including basic cycle length, atrium-His (AH) interval, His-ventricle (HV) interval, PR interval, QT interval, QRS duration, Wenckebach period, and sinus node recovery time (SNRT) were evaluated before and after pulmonary vasoreactivity testing in both groups.

Results

The AH interval (81 [74–93]; 80 [65.5–88], p = 0.019) and SNRT (907.7 ± 263.4; 854.0 ± 288.04, p = 0.027) was significantly decreased after pulmonary vasoreactivity testing. Mean right atrium pressure was found to be correlated with baseline AH (r = 0.371, p = 0.031) and SNRT (r = 0.353, p = 0.037).

Conclusion

Inhaled iloprost can improve cardiovascular performance in the presence of PAH, primarily through a reduction in right ventricular afterload and interventricular pressure. Decreased pressure on the interventricular septum and ventricles leads to conduction system normalization including of the AH interval and SNRT due to resolution of inflammation and edema.

Zusammenfassung

Hintergrund

Die pulmonalarterielle Hypertonie (PAH) ist eine schwere, lebensbedrohliche Erkrankung trotz spezifischer medikamentöser Behandlung. Ein Mangel an endogenem Prostazyklin infolge einer Herabregulierung der Prostazyklinsynthase bei PAH kann zu Gefäßerkrankungen beitragen. Daher können Prostazyklin und seine Analoga einschließlich des inhalativen Iloprost den pulmonalarteriellen Druck und den Ventrikeldruck senken.

Methoden

In der vorliegenden Studie wurden die akuten Wirkungen von dem zur Prüfung der pulmonalen Vasoreaktivität eingesetzten Iloprost auf das intrakardiale Erregungsleitungssystem bei Patienten mit PAH untersucht. In die prospektive Studie wurden 35 Patienten mit PAH (15 mit idiopathischer PAH, 20 mit kongenitaler Herzerkrankung) eingeschlossen. Die Patienten wurden in 2 Gruppen eingeteilt: 22 Patienten mit negativer pulmonaler Vasoreaktivität in Gruppe 1 und 13 mit positiver pulmonaler Vasoreaktivität in Gruppe 2. Vor und nach der Prüfung der pulmonalen Vasoreaktivität wurden elektrophysiologische Parameter einschließlich grundlegender Zyklusdauer, Atrium-His(AH)-Intervall, His-Ventrikel(HV)-Intervall, PR-Intervall, QT-Intervall, QRS-Dauer, Wenckebach-Periode und Sinusknotenerholungszeit (SKEZ) in beiden Gruppen gemessen.

Ergebnisse

Das AH-Intervall (81 [74–93]; 80 [65,5–88], p = 0,019) und die SKEZ (907,7 ± 263,4; 854,0 ± 288,04; p = 0,027) waren nach Prüfung der pulmonalen Vasoreaktivität signifikant erniedrigt. Der mittlere Druck im rechten Vorhof erwies sich als mit dem Ausgangs-AH-Intervall korreliert (r = 0,371; p = 0,031) und SKEZ (r = 0,353; p = 0,037).

Schlussfolgerung

Inhalatives Iloprost kann die kardiovaskuläre Leistung bei Vorliegen einer PAH verbessern, in erster Linie durch eine Reduktion der rechtsventrikulären Nachlast und des interventrikulären Drucks. Ein verminderter Druck auf das Interventrikularseptum und die Ventrikel führt zur Normalisierung des Erregungsleitungssystems einschließlich des AH-Intervalls und der SKEZ aufgrund der Rückbildung von entzündlichen Veränderungen und Ödemen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A et al (2016) 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 37:67–119

    Article  PubMed  Google Scholar 

  2. Hill NS, Preston IR, Roberts KE (2015) Inhaled therapies for pulmonary hypertension. Respir Care 60:794–802

    Article  PubMed  Google Scholar 

  3. Tongers J, Schwerdtfeger B, Klein G, Kempf T, Schaefer A, Knapp JM et al (2007) Incidence and clinical relevance of spuraventricular tachyarrhythmias in pulmonary hypertension. Am Heart J 153:127–132

    Article  PubMed  Google Scholar 

  4. Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL et al (2006) Association of nocturnal arrhythmias with sleep-disordered breathing: The sleep heart health study. Am J Respir Crit Care Med 173:910–916

    Article  PubMed  PubMed Central  Google Scholar 

  5. Medi C, Kalman JM, Ling LH, Teh AW, Lee G, Lee G et al (2012) Atrial electrical and structural remodeling associated with longstanding pulmonary hypertension and right ventricular hypertrophy in humans. J Cardiovasc Electrophysiol 23:614–620

    Article  PubMed  Google Scholar 

  6. Yildiz M, Aykan AC, Kahveci G, Demir S, Ozkan M (2011) Transvenous radiofrequency ablation theraphy as an effective and safe method for the treatment of the slow pathway of atrioventricular nodal re-entrant tachycardia. Koşuyolu Kalp Derg 14:51–55

    Google Scholar 

  7. Gessler T, Seeger W, Schmehl T (2011) Gessler T, Seeger W, Schmehl T. The potential for inhaled treprostinil in the treatment of pulmonary arterial hypertension. Ther Adv Respir Dis 5:195–206

    Article  CAS  PubMed  Google Scholar 

  8. Lajoie AC, Bonnet S, Provencher S (2017) Combination therapy in pulmonary arterial hypertension: recent accomplishments and future challenges. Pulm Circ 7:312–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rabinovitch M, Guignabert C, Humbert M, Nicolls MR (2014) Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension. Circ Res 115:165–175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gomberg-Maitland M, Olschewski H (2008) Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur Respir J 31:891–901

    Article  CAS  PubMed  Google Scholar 

  11. Walmrath D, Schneider T, Pilch J, Grimminger F, Seeger W (1993) Aerosolised prostacyclin in adult respiratory distress syndrome. Lancet 342:961–962

    Article  CAS  PubMed  Google Scholar 

  12. Walmrath D, Schneider T, Schermuly R, Olschewski H, Grimminger F, Seeger W (1996) Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. Am J Respir Crit Care Med 153:991–996

    Article  CAS  PubMed  Google Scholar 

  13. Li D, Fareh S, Leung TK, Nattel S (1999) Promotion of atrial fibrillation by heart failure in dogs: Atrial remodeling of a different sort. Circulation 100:87–95

    Article  CAS  PubMed  Google Scholar 

  14. Shinagawa K, Shi YF, Tardif JC, Leung TK, Nattel S (2002) Dynamic nature of atrial fibrillation substrate during development and reversal of heart failure in dogs. Circulation 105(8):2672–2678

    Article  PubMed  Google Scholar 

  15. Rex S, Missant C, Claus P, Buhre W, Wouters PF (2008) Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension. Crit Care 12:R113

    Article  PubMed  PubMed Central  Google Scholar 

  16. Suga H (2003) Global cardiac function: mechano-energetico-informatics. J Biomech 36:713–720

    Article  PubMed  Google Scholar 

  17. Martinez RR, Setty S, Zong P, Tune JD, Downey HF (2005) Nitric oxide contributes to right coronary vasodilation during systemic hypoxia. Am J Physiol Heart Circ Physiol 288:1139–1146

    Article  Google Scholar 

  18. Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin LJ et al (2002) Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 347:322–329

    Article  CAS  PubMed  Google Scholar 

  19. Santamore WP, Gray L Jr. (1995) Significant left ventricular contributions to right ventricular systolic function. Mechanism and clinical implications. Chest 107:1134–1145

    Article  CAS  PubMed  Google Scholar 

  20. Ama R, Leather HA, Segers P, Vandermeersch E, Wouters PF (2006) Acute pulmonary hypertension causes depression of left ventricular contractility and relaxation. Eur J Anaesthesiol 23:824–831

    Article  CAS  PubMed  Google Scholar 

  21. Piazza N, Onuma Y, Jesserun E, Kint PP, Maugenest AM, Anderson RH et al (2008) Early and persistent intraventricular conduction abnormalities and requirements for pacemaking after percutaneous replacement of the aortic valve. JACC Cardiovasc Interv 1:310–316

    Article  PubMed  Google Scholar 

  22. Piazza N, Nuis RJ, Tzikas A, Otten A, Onuma Y, García-García H et al (2010) Persistent conduction abnormalities and requirements for pacemaking six months after transcatheter aortic valve implantation. EuroIntervention 6:475–484

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank Engin Baysal and Enver Karakaruk from Medtronic Turkey; Mustafa Bassorkun, Tugce Özcan and Serkan Ustakurt from St. Jude Medical Turkey for their support.

Author information

Authors and Affiliations

  1. Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Center, Training and Research Hospital, University of Health Sciences, İstasyon Mah. Turgut Özal Bulvarı No:11 Küçükçekmece, Istanbul, Turkey

    Mustafa Yildiz MD, PhD, Serkan Kahraman MD, Ozgur Surgit MD, Hicaz Zencirkiran Agus MD, Begum Uygur MD, Ali R. Demir MD, Mehmet E. Kalkan MD, Kadriye Memic Sancar MD, Ender Oner MD, İsmail Gurbak MD & Ali K. Kalkan MD

Authors
  1. Mustafa Yildiz MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serkan Kahraman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ozgur Surgit MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hicaz Zencirkiran Agus MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Begum Uygur MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ali R. Demir MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mehmet E. Kalkan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kadriye Memic Sancar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ender Oner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. İsmail Gurbak MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ali K. Kalkan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hicaz Zencirkiran Agus MD.

Ethics declarations

Conflict of interest

M. Yildiz, S. Kahraman, O. Surgit, H. Zencirkiran Agus, B. Uygur, A.R. Demir, M. E. Kalkan, K. Memic Sancar, E. Oner, İ. Gurbak and A. K. Kalkan declare that they have no competing interests.

All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional (Ethic Committee of Kartal Kosuyolu Yüksek Ihtisas Training and Research Hospital with a number of 2018/6/64 and date of 15/11/2018) and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yildiz, M., Kahraman, S., Surgit, O. et al. Acute effects of inhaled iloprost on intracardiac conduction in patients with pulmonary arterial hypertension. Herz 47, 158–165 (2022). https://doi.org/10.1007/s00059-021-05044-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00059-021-05044-z

Keywords

Schlüsselwörter

Search

Navigation