Author + information
- Received September 19, 1988
- Revision received November 28, 1988
- Accepted January 4, 1989
- Published online July 1, 1989.
- Mark D. Jacobstein, MD FACC∗,
- Thomas A. Gerken, PHD,
- Abdul M. Bhat, MD and
- Pierre G. Carlier, MD PHD
- ↵∗Address for reprints: Mark D. Jacobstein, MD, Rainbow Babies and Children's Hospital, Room 793, 2101 Adelbert Road, Cleveland. Ohio 44106.
The ability of 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine), a synthetic creatine analog, to protect myocardium during global ischemia was assessed in isovolumic rat hearts using phosphorus-31 nuclear magnetic resonance spectroscopy. Wistar rats were fed a 1 % cyclocreatine diet. After 2 weeks, cyclocreatine-fed (n = 8) and control (n = 7) rats were anesthetized, the heart was excised and retrograde perfusion was begun at 10 ml/min per g with 37°C, phosphate-free buffer containing glucose and oxygen. Hemodynamic and spectroscopic data were obtained during baseline, ischemia and recovery periods (each 24 min). During ischemia, the heart of control rats developed a rigor-like increase in tonic pressure (ischemic contracture) not seen in the heart of cyclocreatine-fed rats (22 versus 1 mm Hg, p < 0.01). This change was associated with significantly more adenosine triphosphate (ATP) at endischemia in the cyclocreatine group (1.6 versus 0.6 μol/g, p < 0.01) and delayed development of acidosis (p < 0.001). With reperfusion, the heart of cyclocreatine-fed rats spontaneously defibrillated sooner than did the heart in control rats (178 versus 346 s, p < 0.03). Diastolic pressure remained significantly elevated throughout recovery in control hearts compared with treated hearts (p < 0.001).
Prior feeding with cyclocreatine preserves myocardial adenosine triphosphate during ischemia, delays the development of acidosis and ischemic contracture and improves recovery of mechanical function on reperfusion.
This study was supported by a grant from the American Heart Association, Northeast Ohio Affiliate, Cleveland, Ohio.
- Received September 19, 1988.
- Revision received November 28, 1988.
- Accepted January 4, 1989.