Noninvasive assessment of pharmaceutical intervention during myocardial ischemia-reperfusion in a canine model using two-dimensional ³¹P chemical shift imaging

Abstract

The metabolic effects during myocardial ischemia and sustained reperfusion of the antianginal agents diltiazem (n = 10) and propranolol (n = 10) were monitored with noninvasive phosphorus nuclear magnetic resonance spectroscopy to establish any correlation between metabolic changes and infarct size. Spectroscopy followed changes in high-energy phosphate concentrations and myocardial intracellular pH during 2 h of left anterior descending coronary artery occlusion and 3 subsequent weeks of reperfusion, in a closed chest canine infarct model. Gadolinium-DTPA enhanced magnetic resonance imaging was used to assess the extent of myocardial injury (infarct size). Microspheres were used to document the zone at risk and the success of reperfusion. Whereas diltiazem appeared to reduce the derangement in high-energy phosphates during coronary occlusion, there was no significant change in infarct size when compared with a previously studied control group. Propranolol, which produced a lesser decline in pH during occlusion and smaller pH changes during early reperfusion, was associated with a significant reduction in the degree of tissue necrosis (compared with controls). There was an inverse correlation (r = -0.51) between the change in myocardial pH (occlusion end to immediate reperfusion) and the recovery index (an index of myocardial salvage). By 1 h into reperfusion, there was a stronger inverse correlation between pH and infarct size (r = -0.75), implying a protective effect of delaying pH recovery during early reperfusion and indicating the potential use of this parameter as a predictor of tissue viability.

MRI/MRS evaluation of cariporide in a canine long‐term model of reperfused ischemic insults

“…The animal was sacrificed with an intravenous bolus of 10 mL of KCl (149 mg/mL; Abbott Laboratories, Montreal, PQ), and the heart was excised and then imaged using a T 1 ‐weighted 3D FLASH sequence (TR/TE = 22/10 msec, FOV = 80–120 mm, thickness = 1 mm). Previous experiments in our laboratory and others have validated this technique of contrast‐enhanced MRI with triphenyltetrazolium chloride histochemical staining to demarcate myocardial necrosis (13, 14, 19, 20).…”

“…Two‐dimensional 31 P CSI was performed with a Siemens 1 H‐ 31 P radiofrequency surface coil, as previously described (13–15). The coil includes a transmit/receive 1 H loop as well as a single‐loop transmit 31 P coil and a “pseudoquadrature” 31 P receive coil.…”

“…All spectra were then fitted to a sum of damped sinusoids using a software package designed in our laboratory. The software uses an iterative, nonlinear Marquardt/Levenberg fitting algorithm in the time domain, incorporating prior knowledge of the spectrum as determined from the literature and our previous results (13–15, 17, 18).…”

“…1). Blood flow determination (F, expressed in mL/minute/g) has been previously described in detail (13, 14, 17, 19, 21).…”

“…The combination of MRI and MRS employed in this protocol is a clinically useful technique that has been used to study a variety of cardiac disease states (12). We have previously reported the long‐term benefits of propranolol, nitroglycerin, and superoxide dismutase with this canine model (13, 14). However, testing a lower dose of cariporide with this model of ischemia/reperfusion, we found no long‐term cardioprotection (15).…”