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EXPERIMENTAL STUDIES

Coronary collateral development during chronic ischemia: serial assessment using harmonic myocardial contrast echocardiography

^a Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Manuscript received August 10, 1999; revised manuscript received December 3, 1999, accepted March 29, 2000.

Reprint requests and correspondence: Dr. Flordeliza S. Villanueva, Division of Cardiology, University of Pittsburgh, S568 Scaife Hall, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213
villanuevafs{at}msx.upmc.edu

OBJECTIVES

We sought to characterize collateral development in an experimental model of chronic myocardial ischemia by using myocardial contrast echocardiography (MCE).

BACKGROUND

Coronary collaterals maintain myocyte viability during myocardial ischemia. The natural history and determinants of collateral development are difficult to study serially in vivo.

METHODS

The left anterior descending coronary artery (LAD) in nine dogs was encircled (day 0) with a hydraulic occluder and ameroid constrictor to enable reversible and gradual total LAD occlusion, respectively. Myocardial contrast echocardiography was performed using intravenous injection of perfluorocarbon gas-containing microbubbles during two-dimensional harmonic echocardiographic imaging. Myocardial contrast echocardiography images and radiolabeled microsphere flow measurements were obtained during transient LAD occlusion on day 0. Over the ensuing six weeks, MCE imaging was performed during LAD occlusion at 10-day intervals.

RESULTS

Myocardial contrast echocardiography risk area size (expressed as a percent of the left ventricular short axis slice) decreased over the course of six weeks (32% ± 3% on day 0, 21% ± 3% at day 10, 5 ± 3% at day 20, 1% ± 1% at day 30 and 1% ± 1% at day 42, p 0.001 vs. day 0). Radiolabeled microsphere-derived LAD flow, normalized to left circumflex flow, correspondingly increased between day 0 and day 42 (0.14 ± 0.02 to 0.90 ± 0.07, p < 0.02).

CONCLUSIONS

Collateral development occurs relatively early and rapidly in this chronic canine model. Myocardial contrast echocardiography using harmonic imaging and intravenous injection of microbubbles can uniquely track the spatial and temporal course of collateral growth, and may be a powerful tool for noninvasively mapping the efficacy of therapeutic angiogenic strategies in vivo.

Abbreviations and Acronyms   LAD = left anterior descending coronary artery   LCX = left circumflex coronary artery   MCE = myocardial contrast echocardiography   TTC = triphenyl tetrazolium chloride

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