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Treatment of Right Ventricular Failure through Partial Volume Exclusion: An Experimental Study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Implantation of a left ventricular assist device (LVAD) is a potential treatment in terminal heart failure. Right ventricular (RV) failure is a severe complication in these patients and sometimes requires additional placement of a right ventricular assist device (RVAD). RVAD implantation, however, is an invasive treatment associated with both increased mortality and morbidity. The aim of this thesis was to study whether partial volume exclusion of the RV through a modified Glenn shunt or cavoaortic shunt could treat severe RV failure. The ultimate goal would be to use it as an alternative to a RVAD in RV failure during LVAD therapy.

Swine were used as the model animal in all studies. In Study I, experimental RV failure was induced by ischemia, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis and improved hemodynamics in general. In Study II, experimental RV failure was induced by the same method as in Study I. Treatment with a cavoaortic shunt in addition to LVAD therapy proved to reduce venous stasis and improved hemodynamics in general, which was feasible with preserved oxygen delivery despite cyanotic shunting. In Study III, experimental RV failure was induced by pulmonary banding, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis but did not improve hemodynamics in general compared with a control group. In Study IV, the effects of LVAD therapy and subsequent treatment with a modified Glenn shunt on the normal RV function were studied. It demonstrated that LVAD therapy can put strain on the RV by increasing stroke work and end-diastolic volume, and that these effects can be reversed by treatment with a modified Glenn shunt during LVAD therapy.

In conclusion, partial volume exclusion through a modified Glenn shunt or cavoaortic shunt is a feasible treatment of experimental RV failure. Thus, it could potentially be used as an alternative treatment to a RVAD in severe RV failure during LVAD therapy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. , 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1096
Keyword [en]
Right Heart Failure, Left Ventricular Assist Device, Glenn shunt
National Category
Surgery
Research subject
Thorax Surgery
Identifiers
URN: urn:nbn:se:uu:diva-248164ISBN: 978-91-554-9228-1 (print)OAI: oai:DiVA.org:uu-248164DiVA: diva2:800503
Public defence
2015-05-27, Robergsalen, Akademiska Sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2015-05-05 Created: 2015-03-29 Last updated: 2015-07-07
List of papers
1. A modified Glenn shunt improves haemodynamics in acute right ventricular failure in an experimental model
Open this publication in new window or tab >>A modified Glenn shunt improves haemodynamics in acute right ventricular failure in an experimental model
2013 (English)In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 43, no 3, 612-618 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES:

Right heart failure is a major cause of morbidity and mortality after left ventricular assist device implantation and is still hard to predict. This study investigated the haemodynamic effect of a modified Glenn shunt on induced right ventricular (RV) failure.

METHODS:

Isolated RV failure was induced by coronary ligation in 11 pigs. A modified Glenn shunt was established by a superior vena cava to pulmonary artery connection. Haemodynamic data were obtained at baseline, RV failure, and RV failure and open shunt. Myocardial biopsies were taken to ascertain established heart failure.

RESULTS:

RV failure defined as right atrial pressure ≥20 mmHg was achieved in all 11 animals. A reduction in cardiac output (CO) from 3.7 (3.5-4.2) to 2.3 l/min (2.0-2.6) and mean arterial pressure (MAP) from median 72.7 (70.1-82.2) to 55.9 mmHg (52.6-59.8) was seen during heart failure. The median flow in the shunt was 681 ml. Right atrial pressures decreased from 20.3 (19.6-21.1) to 13.4 mmHg (12.7-14.0), and RV pressures decreased from 18.1 (16.4-20.1) to 13.6 mmHg (13.5-14.2) with open shunt (P = 0.001 for both). CO increased to 2.9 l/min (2.4-3.3) when the shunt was in use. Mixed venous oxygen saturation increased with the shunt from 32 (27-38) to 49% (45-56), P = 0.001. Genes associated with heart failure were upregulated during heart failure.

CONCLUSIONS:

A modified Glenn shunt improved haemodynamics by reduced right atrial pressure, increased CO, MAP and mixed venous oxygen saturation in an experimental model of induced RV failure.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-188728 (URN)10.1093/ejcts/ezs386 (DOI)000314852500038 ()22761503 (PubMedID)
Available from: 2012-12-19 Created: 2012-12-19 Last updated: 2017-12-06Bibliographically approved
2. Cavoaortic shunt improves hemodynamics with preserved oxygen delivery in experimental right ventricular failure during left ventricular assist device therapy
Open this publication in new window or tab >>Cavoaortic shunt improves hemodynamics with preserved oxygen delivery in experimental right ventricular failure during left ventricular assist device therapy
2014 (English)In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685X, Vol. 147, no 2, 625-631 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

Right heart failure is a major cause of morbidity and mortality after left ventricular assist device (LVAD) implantation. This study evaluated the approach of a cavoaortic shunt included in the LVAD circuit, which would aim to relieve venous congestion and improve hemodynamics with preserved oxygen delivery during induced right ventricular failure.

METHODS:

Right ventricular failure was induced by coronary ligation in 10 pigs. An LVAD was implanted and a cavoaortic shunt was created from the right atrium and included in the assist circuit. Hemodynamic measures and blood gas analyses were analyzed. Oxygen delivery and oxygen consumption were estimated.

RESULTS:

Right atrial pressure decreased from more than 20 mm Hg to 17.2 mm Hg (14.8-18.4) with the LVAD and to 14.1 mm Hg (11.2-15.5) (P < .01) with the LVAD and cavoaortic shunt. Mean arterial pressure increased from 70.9 mm Hg (67.6-79.8) to 81.5 mm Hg (70.8-92.6) (P = .02) with addition of the shunt into the assist circuit. Cardiac output increased from 3.5 L/min (2.6-4.2) to 4.9 L/min (3.5-5.6) (P < .01) with cavoaortic shunting. Oxygen delivery with the cavoaortic shunt was 337 mL/min (±70) as compared with left ventricular assist alone at 258 mL/min (±52) (P < .01). Oxygen consumption was restored during use of the cavoaortic shunt.

CONCLUSIONS:

A cavoaortic shunt combined with an LVAD during right ventricular failure reduces central venous pressures, increases systemic arterial pressure, and enables increased cardiac output compared with device therapy alone. This was feasible with preserved oxygen delivery.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-216406 (URN)10.1016/j.jtcvs.2013.02.010 (DOI)000329724700014 ()23477692 (PubMedID)
Available from: 2014-01-21 Created: 2014-01-21 Last updated: 2017-12-06Bibliographically approved
3. A modified Glenn shunt reduces venous congestion during acute right ventricular failure due to pulmonary banding: a randomized experimental study
Open this publication in new window or tab >>A modified Glenn shunt reduces venous congestion during acute right ventricular failure due to pulmonary banding: a randomized experimental study
2014 (English)In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 18, no 4, 418-425 p.Article in journal (Refereed) Published
Abstract [en]

Right ventricular failure after left ventricular assist device implantation is a serious complication with high rates of mortality and morbidity. It has been demonstrated in experimental settings that volume exclusion of the right ventricle with a modified Glenn shunt can improve haemodynamics during ischaemic right ventricular failure. However, the concept of a modified Glenn shunt is dependent on a normal pulmonary vascular resistance, which can limit its use in some patients. The aim of this study was to explore the effects of volume exclusion with a modified Glenn shunt during right ventricular failure due to pulmonary banding, and to study the alterations in genetic expression in the right ventricle due to pressure and volume overload. Experimental right ventricular failure was induced in pigs (n = 11) through 2 h of pulmonary banding. The pigs were randomized to either treatment with a modified Glenn shunt and pulmonary banding (n = 6) or solely pulmonary banding (n = 5) as a control group. Haemodynamic measurements, blood samples and right ventricular biopsies for genetic analysis were sampled at baseline, at right ventricular failure (i.e. 2 h of pulmonary banding) and 1 h post-right ventricular failure in both groups. Right atrial pressure increased from 10 mmHg (9.0-12) to 18 mmHg (16-22) (P < 0.01) and the right ventricular pressure from 31 mmHg (26-35) to 57 mmHg (49-61) (P < 0.01) after pulmonary banding. Subsequent treatment with the modified Glenn shunt resulted in a decrease in right atrial pressure to 13 mmHg (11-14) (P = 0.03). In the control group, right atrial pressure was unchanged at 19 mmHg (16-20) (P = 0.18). At right heart failure, there was an up-regulation of genes associated with heart failure, inflammation, angiogenesis, negative regulation of cell death and proliferation. Volume exclusion with a modified Glenn shunt during right ventricular failure reduced venous congestion compared with the control group. The state of right heart failure was verified through genetic expressional changes.

Keyword
Right-sided heart failure, Bidirectional Glenn shunt, Assisted circulation, Microarray analysis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-223874 (URN)10.1093/icvts/ivt547 (DOI)000333271300004 ()
Available from: 2014-05-09 Created: 2014-04-28 Last updated: 2017-12-05Bibliographically approved
4. A Modified Glenn Shunt Reduces Right Ventricular Stroke Work During Left Ventricular Assist Device Therapy
Open this publication in new window or tab >>A Modified Glenn Shunt Reduces Right Ventricular Stroke Work During Left Ventricular Assist Device Therapy
(English)Article in journal (Other academic) Submitted
Keyword
Glenn shunt, Left Ventricular Assit Device Therapy, Right Heart Failure
National Category
Surgery
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-248163 (URN)
Available from: 2015-03-29 Created: 2015-03-29 Last updated: 2015-07-07Bibliographically approved

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