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Effect of Potassium-Channel Opener Therapy on Reperfused Infarction in Hypertrophied Hearts: Demonstration of Preconditioning by Using Functional and Contrast-Enhanced Magnetic Resonance Imaging

Department of Radiology, University of California San Francisco, San Francisco, California

Charles B. Higgins, MD

Department of Radiology, University of California San Francisco, San Francisco, California

Mitsuaki Chujo, PhD

Chugai Pharmaceutical Co., Ltd, Tokyo, Japan

Maythem Saeed, DVM, PhD

Department of Radiology, University of California San Francisco, San Francisco, California

Effects of therapy with the potassium-channel opener and vasodilator nicorandil were studied in reperfused infarction of hypertrophied hearts by using magnetic resonance imaging (MRI), hemodynamic measurements, and histochemical staining. Aortic banding was performed on 22 Sprague-Dawley rats to induce left ventricular (LV) hypertrophy; 11 were the controls. Eight weeks later, the left coronary artery was occluded for 25 minutes in all 33 animals, followed by 3 hours of reperfusion. During occlusion, 11 rats with LV hypertrophy received nicorandil (0.1 mg/kg bolus and 1.5 mg/kg/h for 3 hours). The new necrosis-specific contrast agent Gadophrin-3 was administered to all animals to delineate infarction on multislice T1-weighted spin-echo MRI. Nicorandil increased ischemic tolerance of LV hypertrophy as shown by the reduction of infarction size from 19.3% ± 1.3% to 10.0% ± 2.5% LV (P= .005). Infarction size in treated animals was identical to control (9.3% ± 1.6%). Close correlation was found between MRI and postmortem findings. Functional MRI revealed an improvement in ejection fraction in nicorandil-treated hearts (48.5% ± 3.4% vs 38.1% ± 3.2%, P = .04). LV end-diastolic volume and pressure, aortic pressure, and peripheral vascular resistance were highest in untreated hypertrophied hearts. Brief ischemia caused severe injury in hypertrophied hearts. Infusing nicorandil increased the tolerance of hypertrophied hearts to ischemia. MRI is a suitable technique for the evaluation of new therapies in LV hypertrophy.

Key Words: potassium channel opener • myocardial infarction • preconditioning • hypertrophy • nicorandil • hemodynamics • Gadophrin-3

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 9, No. 3, 193-202 (2004)
DOI: 10.1177/107424840400900307


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