Author + information
- Received August 20, 1988
- Revision received November 3, 1988
- Accepted December 7, 1988
- Published online May 1, 1989.
- Hermann H. Klein, MD∗,
- Sibylle Pich, PhD,
- Stefanie Lindert,
- Klaus Nebendahl, MD,
- Gerhard Warneke, MD and
- Heinrich Kreuzer, MD
- ↵∗Address for reprints: Priv. Doz. Dr. H. H. Klein, Med. Klinik der Universität. Robert-Koch-Str. 40, 3400 Göttingen, West Germany.
The effect of intracoronary diltiazem, EGTA (ethylenebis-(β-aminomethylether)-N,N′-tetraacetic acid), nifedipine, verapamil and isotonic saline solution as placebo on reperfusion injury was investigated in regionally ischemic, reperfused porcine hearts. The left anterior descending coronary artery was distally occluded for 45 min and was reperfused for 3 days. Intracoronary infusion was started immediately before reperfusion and continued during 45 min of reperfusion. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was assessed by sonomicrometry.
Apart from left ventricular end-diastolic pressure before ischemia and during 45 min of reperfusion, global hemodynamic values in the five treatment groups did not differ; in particular, calculated left ventricular oxygen consumption before and during ischemia was equally low. Intracoronary EGTA decreased coronary venous free calcium concentration to about 70% of baseline value. Infarct size was reduced from 76 ± 10% (control group, n = 8) to 60 ± 10% (p < 0.01) by intracoronary diltiazem (n = 8) and to 55 ± 15% (p < 0.01) by intracoronary EGTA (n = 8). Insignificant reductions in infarct size were found after treatment with intracoronary verapamil (63 ± 18%, n = 8) and intracoronary nifedipine (68 ± 9%, n = 7). Regional systolic shortening of the risk region, which did not differ among the groups before occlusion and during ischemia, recovered to the greatest extent in the EGTA-treated pigs (p < 0.01 compared with values in the control group). Treatment with intracoronary calcium antagonists resulted in only marginal improvement of systolic shortening. Reperfusion-induced rhythm disturbances were not beneficially affected by either treatment.
It is concluded that reperfusion injury exists in regionally ischemic, reperfused porcine hearts, which can be attenuated by intracoronary EGTA and intracoronary diltiazem administered during the first 45 min of reperfusion. The favorable action of EGTA is ascribed to a reduced ionized extracellular calcium concentration, whereas the beneficial mechanism of diltiazem is unknown.
☆ This study was supported by a grant from the Deutsche Forschungsgemeinschaft, SFB 330-Organprotektion, Gottingen.
- Received August 20, 1988.
- Revision received November 3, 1988.
- Accepted December 7, 1988.