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    Nitroprusside increases gene transfer associated with intracoronary delivery of adenovirus.
    Hum Gene Ther 2004 Oct;15(10):989-94
    Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA.
    Efficient gene transfer by vectors that can be easily delivered to target organs is desirable in clinical gene therapy. We tested the hypothesis that intracoronary infusion of the nitric oxide donor nitroprusside would increase the efficiency of adenovirus vector-mediated gene transfer to the heart. Intracoronary delivery of an adenovirus encoding murine adenylyl cyclase type VI (Ad.AC(VI)) was performed in adult pigs with and without simultaneous intracoronary infusion of nitroprusside. Animals were killed 12-14 days after Ad.AC(VI) delivery and myocardial adenylyl cyclase activity was measured. Addition of nitroprusside during intracoronary infusion of Ad.AC(VI) was associated with a 4-fold increase in cAMP-generating capacity in the left ventricle. Transgene expression was confirmed by immunoblotting. Intracoronary nitroprusside produced mild dose-dependent changes in blood pressure and heart rate during infusion. Intracoronary nitroprusside infusion is a safe and effective means to increase the extent of cardiac gene transfer with intracoronary delivery of adenovirus vectors.

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    Indirect intracoronary delivery of adenovirus encoding adenylyl cyclase increases left ventricular contractile function in mice.
    Am J Physiol Heart Circ Physiol 2004 Jul 4;287(1):H172-7. Epub 2004 Mar 4.
    Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161, USA.
    We performed indirect intracoronary delivery of adenovirus vectors in mice and explored techniques including hypothermia and pharmacological means to increase cardiac gene transfer. Mice were maintained in a normothermic state or cooled to 25 degrees C. The aorta or both the pulmonary artery and aorta were clamped while a needle was advanced into the left ventricular cavity to deliver adenovirus vectors encoding enhanced green fluorescent protein (EGFP) or murine adenylyl cyclase type VI (AC(VI)) with saline, sodium nitroprusside, acetylcholine, or serotonin. Read More
    Intracoronary adenovirus encoding adenylyl cyclase VI increases left ventricular function in heart failure.
    Circulation 2004 Jul 12;110(3):330-6. Epub 2004 Jul 12.
    Department of Medicine, University of California, San Diego, USA.
    Background: 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.

    Methods And Results: Pigs (52+/-6 kg; n=16) underwent placement of pacemakers, LV pressure transducers, and left atrial and aortic catheters. Read More
    Intracoronary delivery of adenovirus encoding adenylyl cyclase VI increases left ventricular function and cAMP-generating capacity.
    Circulation 2000 Nov;102(19):2396-401
    San Diego VA Healthcare System, Department of Medicine, San Diego, CA, USA.
    Background: We tested the hypothesis that intracoronary injection of a recombinant adenovirus encoding adenylyl cyclase type VI (AC(VI)) would increase cardiac function in pigs.

    Methods And Results: Left ventricular (LV) dP/dt and cardiac output in response to isoproterenol and NKH477 stimulation were assessed in normal pigs before and 12 days after intracoronary delivery of histamine followed by intracoronary delivery of an adenovirus encoding lacZ (control) or AC(VI) (1.4x10(12) vp). Read More
    Adenylylcyclase gene transfer increases function of the failing heart.
    Hum Gene Ther 2006 Oct;17(10):1043-8
    San Diego Veterans Healthcare System, and Department of Medicine, University of California, San Diego 92093, USA.
    A persistent question in cardiovascular gene transfer concerns whether an exogenously delivered gene can increase function of the failing heart. Here we test the hypothesis that intracoronary delivery of adenovirus encoding adenylylcyclase type VI (Ad.ACVI) in the setting of active heart failure will increase function of the failing heart. Read More