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Gregory Supple

Publications and source records attributed to Gregory Supple.

2 recordsLinked to original sources

Reverse ventricular remodeling reduces ischemic mitral regurgitation: echo-guided device application in the beating heart.

BACKGROUND: In ischemic mitral regurgitation (MR), mitral leaflet closure is restricted by ventricular remodeling with displacement of the papillary muscles (PMs). Therapy is uncertain because ring annuloplasty does not alleviate PM displacement. We tested the hypothesis that echo-guided PM repositioning using an external device can reduce MR without compromising left ventricular (LV) function. METHODS AND RESULTS: We studied 10 sheep with ischemic MR produced by circumflex ligation with inferior infarction, 6 acutely and 4 eight weeks after myocardial infarction (MI). A Dacron patch containing an inflatable balloon was placed over the PMs and adjusted under echo guidance to reverse LV remodeling and reposition the infarcted PM. 3D echo assessed mitral valve geometric changes. In 7 sheep, sonomicrometry and Millar catheters assessed changes in end-systolic and end-diastolic pressure-volume relationships, and microspheres were injected to assess coronary flow. Moderate MR after MI resolved with patch application alone (n=3) or echo-guided balloon inflation, which repositioned the infarcted PM, decreasing the PM tethering distance from 31.1+/-2.5 mm after MI to 26.8+/-1.8 with patch (P<0.01; baseline=25.5+/-1.5). LV contractility was unchanged (end-systolic slope=3.4+/-1.6 mm Hg/mL with patch versus 2.8+/-1.6 after MI). Although there was a nonsignificant trend for a mild increase in stiffness constant (0.07+/-0.05 mL(-1) versus 0.05+/-0.03 after MI, P=0.06), LV end-diastolic pressure was unchanged as MR resolved. Coronary flow to noninfarcted regions was not reduced. CONCLUSIONS: An external device that repositions the PMs can reduce ischemic MR without compromising LV function. This relatively simple technique can be applied under echo guidance in the beating heart.

Angioplasty, Balloon↗

New efficient catheter-based system for myocardial gene delivery.

BACKGROUND: Manipulating gene expression in the failing heart has therapeutic promise, but until now efficient and homogeneous cardiac gene delivery has required an open-chest approach. This study examines the hypothesis that vector delivery promoted by echo contrast microbubbles will be maximized by injection of the vectors into the aortic root with brief balloon occlusion above the sinuses, while at the same time prolonging diastole and vasodilating with acetylcholine (ACh) to maximize coronary exposure. METHODS AND RESULTS: After incubation with albumin-coated perfluorocarbon microbubbles, an adenovirus encoding a reporter gene was infused into the aortic root of rats. To maximize delivery, the aortic root was transiently occluded with a balloon catheter during a brief ACh-induced asystole. Ultrasound was used to image the delivery and disrupt the microbubbles. Aortic occlusion with concomitant ACh increased myocardial gene expression for virus + microbubbles by >2.5-fold, from 925+/-165 to 2358+/-376 relative units (RU; P<0.01). This delivery system also produced substantial expression with vector alone (1473+/-549 RU). All uptakes were significant compared with 433+/-332 RU without virus. CONCLUSIONS: An adenoviral delivery system combining echo contrast with a catheter-based technique to maximize coronary perfusion increases gene delivery compared with echo contrast alone. This novel method permits efficient percutaneous gene delivery in closed-chest animals.

Acetylcholine↗