Endothelin ETA receptor blockade reduces pulmonary vascular resistance following cardiopulmonary bypass

Endothelin ETA receptor blockade reduces pulmonary vascular resistance following cardiopulmonary bypass

S10 Surgical Forum Abstracts connected to a pacemaker and bipolar EKG recorders. Additional recording plaques were sewn onto the right atrium (RAR) ...

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S10

Surgical Forum Abstracts

connected to a pacemaker and bipolar EKG recorders. Additional recording plaques were sewn onto the right atrium (RAR) and left atrium (LAR). Three RF ablation protocols were used to create RAA and PV lesions with a specialized segmented RF catheter. In ablation Protocol I, RF was applied to the epicardium at 70°C for 30 sec, 80°C for 30 sec, and 85°C for 60 sec, in Protocol II: 70°C for 30 sec, 80°C for 30 sec, an 85°C for 120 sec, and in Protocol III: 70°C for 30 sec, 80°C for 30 sec, and 85°C for 240 sec. Post-ablation EKG’s were compared to pre-ablation EKG’s by pacing the quadrapolar plaques at 130 beats per minute. Following euthanasia and cardiectomy, 1% Tetrazolium Red (TTC) was used to stain the lesions to evaluate the burn and tissue depth. Results: RAA isolation was successfully performed in all 5 animals using Protocol I which was associated with transmural lesions by TTC staining. Protocol I and II ablations did not successfully isolate the PV and were not associated with transmural lesions. Only Protocol III ablations produced successful PV isolation. Mean tissue widths for ablated RAA and PV tissue was 2.8 ⫾ 0.2 mm and 5.5 ⫾ 0.4 mm, respectively. Conclusions: This pilot study demonstrated epicardial RF ablation can electrophysiologically isolate the RAA and PV. Longer burn durations were necessary to ablate thicker tissue surrounding the PV.

Endothelin ETA receptor blockade reduces pulmonary vascular resistance following cardiopulmonary bypass Cassandra Joffs MD, C Allyson Walker BA, Jennifer W Hendrick BS, David J Fary, Daniel K Almany, Jennifer Davis DVM, Aron T Goldberg MD, Fred A Crawford MD, Francis G Spinale PhD, MD. Medical University of South Carolina Contact: Francis G Spinale, Division of Cardiothoracic Surgery 114 Doughty Street, Suite 625 Charleston, SC, 29412, USA (843) 953-3498 Introduction: Endothelin-1 (ET-1) is elevated following cardiopulmonary bypass (CPB) and can increase pulmonary vascular resistance (PVR) via the ETA receptor. This study tested the hypothesis that ETA blockade following CPB would selectively decrease PVR without adversely affecting systemic hemodynamics. Methods: Adult pigs (45kg) underwent crystalloid cardioplegic arrest and CPB (90 minutes) and were randomized at 30 minutes post CPB to receive selective ETA antagonist (TBC 11251, 10mg/kg, n ⫽ 13) or saline vehicle (n ⫽ 10). No inotropic or vasoactive drugs were used at any time. LV function and hemodynamics at baseline, 30, 60, and 90 minutes post CPB were compared by ANOVA followed by a Bonferroni corrected t-test. Results: LV stroke volume fell from baseline. at 30 minutes post CPB (37.5 ⫾ 2.1 vs 18.8 ⫾ 1.9 ml/beat, p ⬍ 0.05) but was not different between groups at 90 minutes (20.4 ⫾ 2.8 vs 18.2 ⫾ 2.5 ml/beat, p ⫽ 0.56). PVR increased at 30 minutes post CPB and continued to rise in the vehicle group. However, PVR was significantly reduced in the ETA blockade group (Figure). Conclusions: The novel findings of this study were 2-fold. First, ETA receptor stimulation contributes to elevated PVR post CPB. Second, ETA blockade may provide a means to selectively modulate PVR without significantly altering LV performance, thus offering a potentially unique treatment option for pulmonary hypertension post CPB.

J Am Coll Surg

Francisco, CA 505 Parnassus Avenue Room S-549 Box 0118 San Francisco, CA 94143-0118, USA Daytime phone: (415) 476-3437 Introduction: The superior cavopulmonary anastomosis (SCPA), or classic Glenn shunt, has been used for palliation of various forms of congenital heart defects resulting in inadequate pulmonary blood flow. However, clinically significant pulmonary arteriovenous malformations (PAVMs) develop in 10 –25% of patients following this surgery. This study was designed to examine the role of the angiotensin AT2 receptor (AT2-R) in PAVM formation in this setting. The AT2 receptor is abundantly expressed in the fetal vasculature during periods of active vascular development. After birth, however, expression of this receptor rapidly diminishes. Methods: Lambs, aged 35– 45 days, underwent an end-to-end anastomosis of the superior vena cava to the right pulmonary artery. In age-matched controls, a sham operation was performed. PAVMs developed in all SCPA lambs by 6 weeks after surgery, as demonstrated by contrast echocardiography. Animals (n ⫽ 16) were then sacrificed and right lung tissue was harvested at various time points following surgery. Expression of RNA was measured by RT-PCR and quantified using densitometry. Protein levels of AT2-R were obtained by Western blot analysis. Localization of AT2-R in pulmonary tissue was accomplished using immunohistochemistry. Results: Superior cavopulmonary anastomosis resulted in upregulation of AT2-R. Compared to sham controls, both RT-PCR and Western blot analysis revealed a marked increase in AT2-R expression at 1–5 weeks following surgery. Similarly, pulmonary endothelium from lambs two weeks following SCPA distinctly stained positive for AT2-R, while specimens from sham controls lacked staining. Conclusions: The angiotensin AT2 receptor, whose expression is normally limited to fetal vascular development, is upregulated in the pulmonary vascular bed soon after cavopulmonary anastomosis in the lamb. The reexpression of a fetal gene involved in vascular remodeling during AVM formation may provide valuable information regarding the etiology of this disordered pulmonary angiogenesis that continues to be a significant source of morbidity of cavopulmonary anastomosis.

A canine model of single ventricle physiology with an adjustable systemic-pulmonary artery shunt: the relationship of arterial oxygen saturation to the pulmonary:systemic blood flow ratio William I Douglas, MD, Michael G Ehring, MD, Stephen G Pophal, MD, Joseph J Amato, MD, Michael Djuric, MA, CCP, Russell Brown, CCP, Christine Vassos, CCP, Robert J McCarthy, PhD. RushPresbyterian-St. Luke’s Medical Center 1653 W Congress Parkway Chicago, IL 60612, USA Phone: 312-942-5448 FAX: 312-942-5342 e-mail: [email protected] Introduction: The purpose of the study is to create an acute animal model of single ventricle physiology (SVP) with an adjustable systemicpulmonary artery (SPA) shunt. The study will define the relationship between SPA shunt flow (Qp), the pulmonary:systemic blood flow ratio (Qp:Qs), and arterial oxygen saturation (AO2). Methods: Five 10 kg immature dogs were converted to SVP by ligation of the proximal main pulmonary artery (MPA). A functional right atrial (RA) to left atrial (LA) connection was created by placing cannulae in both atria connected with polyvinyl chloride (PVC) tubing. RA-LA flow was assisted with a centrifugal pump; a Doppler flow probe was placed in the circuit to quantify the systemic venous return (systemic blood flow, Qs). An adjustable SPA shunt was created by placing cannulae in the innominate artery (IA) and MPA connected with PVC tubing. A roller pump in the IA-MPA circuit allowed precise control of SPA shunt flow. Oxygen saturation monitors were placed in the IAMPA and RA-LA circuits to measure continuous arterial and mixed venous saturations. Cardiopulmonary bypass (CPB) was not utilized.

Reexpression of the angiotensin AT2 receptor during pulmonary AVM formation following superior cavopulmonary anastomosis

Results: A relationship between AO2 and Qp:Qs was established: AO2 ⫽ 95 ⫺ 19.4/Qp:Qs (R2 ⫽ .90, p ⬍ .01). The relationship between AO2 and SPA shunt flow was less consistent.

Sunil Malhotra, MD, R. Kirk Riemer, PhD, You-Ping He, PhD, Stephan Thelitz, MD, Frank L Hanley, MD, V. Mohan Reddy, MD. Division of Cardiothoracic Surgery, University of California, San

Conclusions: This study demonstrates the feasibility creating an acute model of SVP with an adjustable SPA shunt, created without the use of CPB. A consistent relationship exists between AO2 and Qp:Qs.