The contribution of neutrophils to reperfusion arrhythmias and a possible role for antiadhesive pharmacological substances.
OBJECTIVE
It is known that neutrophilic leukocytes contribute to cellular damage in the course of cardiac ischemia/reperfusion. A role in arrhythmogenesis, although controversial, has been ascribed in some studies to the leukocytes, but investigations evaluating possible beneficial effects of inhibitors of neutrophil adhesion or transmigration are still missing.


METHODS
Isolated spontaneously beating rabbit hearts, perfused with saline solution at constant pressure according to the Langendorff technique, were treated with 15 min infusion of autologous neutrophils. 10 min after the start of this infusion the hearts were submitted to coronary occlusion (LAD) for 30 min followed by 30 min reperfusion. Four experimental groups were investigated: (1) saline-perfused control hearts, (2) leukocyte-perfused hearts, (3) leukocyte-perfused hearts treated with RGDS peptide, (4) leukocyte-perfused hearts treated with chondroitin sulfate C. In all experiments epicardial potential mapping was carried out (256 unipolar leads). At the end of each experiment the hearts were prepared for histology and after staining leukocyte accumulation in the ischemic zone, in the border zone and in the non-ischemic area was evaluated.


RESULTS
In leukocyte-perfused hearts submitted to ischemia/reperfusion we found a somewhat enhanced arrhythmogenesis, enhanced ST-segment deviation, and a 2-3-fold increase in leukocyte accumulation in the ischemic and border zone as compared to the non-ischemic tissue as well as increased dispersion of epicardial potential duration especially during reperfusion. These changes and the leukocyte accumulation could be suppressed by treatment with RGDS and to a somewhat lesser extent with chondroitin sulfate C. In addition, arrhythmogenesis could be reduced but not completely suppressed by that treatment.


CONCLUSIONS
From these results we conclude that: (a) leukocytes exert an aggravating effect in arrhythmogenesis during ischemia/reperfusion, (b) the arrhythmogenic substrate for this effect may consist of an enhanced dispersion of potential duration and (c) that inhibition of leukocyte accumulation can at least partially reduce arrhythmogenesis and may be of therapeutic interest as an additional treatment.
Dhein
S
S
Institute of Pharmacology, University of Cologne, Germany.
Schott
M
M
Gottwald
E
E
Müller
A
A
Klaus
W
W
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000517:prevention & control; D002448:Cell Adhesion / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000627:therapeutic use; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000517:prevention & control*; D009206:Myocardium / Q000276:immunology; D009504:Neutrophils / Q000473:pathology / Q000502:physiology*; D009842:Oligopeptides / Q000627:therapeutic use*; D010477:Perfusion; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011817:Rabbits
D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; D002809:Chondroitin Sulfates; C046617:arginyl-glycyl-aspartyl-serine