Intracoronary adenovirus encoding adenylyl cyclase VI increases left ventricular function in heart failure

Circulation
N Chin LaiH Kirk Hammond

Abstract

We tested the hypothesis that intracoronary delivery of an adenovirus encoding adenylyl cyclase type VI (Ad.AC(VI)) would be associated with increased left ventricular (LV) function in pigs with congestive heart failure. Pigs (52+/-6 kg; n=16) underwent placement of pacemakers, LV pressure transducers, and left atrial and aortic catheters. Physiological and echocardiographic studies were obtained from conscious animals 13 days later, and pacing was initiated (220 bpm). Seven days later, measures of LV function were reduced, documenting severe LV dysfunction and dilation. Pigs then received intracoronary Ad.AC(VI) (1.4x10(12) vp; n=7) or saline (PBS; n=9) (randomized, blinded), with concomitant infusion of nitroprusside (50 microg/min, 6.4 minutes) to increase gene transfer. Pacing was continued for 14 days, and final studies were obtained. The a priori key end point was change in LV dP/dt during isoproterenol infusion (pre-Ad.AC(VI) value minus value after 21 days of pacing). Pigs receiving Ad.AC(VI) showed a smaller decrease in both LV +dP/dt (P=0.0014) and LV -dP/dt (P=0.0008). Serial echocardiography showed that Ad.AC(VI) treatment was associated with increased LV function and reduced LV dilation and that end-systolic wall s...Continue Reading

References

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Citations

Jan 12, 2013·Current Cardiology Reports·Charbel NaimRoger J Hajjar
Mar 16, 2012·Gene Therapy·M G KatzC R Bridges
Feb 4, 2012·Gene Therapy·K IshikawaY Kawase
Apr 27, 2012·Gene Therapy·T TangH Kirk Hammond
May 17, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tuomas T Rissanen, Seppo Ylä-Herttuala
Feb 11, 2009·Antioxidants & Redox Signaling·Mohammad N Jameel, Jianyi Zhang
May 7, 2009·Antioxidants & Redox Signaling·Ebo D de Muinck
Sep 13, 2012·Human Gene Therapy Methods·Hongfei FangH Kirk Hammond
Sep 30, 2006·Human Gene Therapy·Brian RebolledoH Kirk Hammond
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Jun 21, 2008·Circulation Research·Leif Erik VingeWalter J Koch
Mar 3, 2012·Circulation Research·Lisa TilemannRoger J Hajjar
Jan 3, 2013·The Journal of Clinical Investigation·Roger J Hajjar
Oct 23, 2013·PloS One·Mei Hua GaoH Kirk Hammond
Jul 1, 2007·Future Cardiology·Larissa LipskaiaAnne-Marie Lompre
Aug 8, 2013·Journal of Cardiovascular Pharmacology·Armen YerevanianRoger J Hajjar
Apr 24, 2014·Pflügers Archiv : European journal of physiology·Aziz GuellichRodolphe Fischmeister
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Dec 25, 2012·Translational Research : the Journal of Laboratory and Clinical Medicine·Tong Tang, H Kirk Hammond
Mar 1, 2011·Journal of Molecular and Cellular Cardiology·Mei Hua Gao, H Kirk Hammond
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May 9, 2007·Journal of Molecular and Cellular Cardiology·Tetsuo SasanoJ Kevin Donahue
Oct 30, 2004·The Journal of Gene Medicine·Brian K KasparH Kirk Hammond
Nov 30, 2006·Annals of the New York Academy of Sciences·H Kirk Hammond
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Aug 10, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Daniel MasonShilpa Sant
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Nov 16, 2010·Archives of Cardiovascular Diseases·Jerome RoncalliDouglas W Losordo
Nov 16, 2010·Archives of Cardiovascular Diseases·Mario T Njeim, Roger J Hajjar

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