Study of microcirculation by coloured microspheres and NMR-microscopy in isolated rat heart: Effect of ischaemia, endothelin-1 and endothelin-1 antagonist BQ 610

K.-H. HILLER, F. RODER, P. ADAMI, S. VOLL, P. KOWALLIK, A. HAASE, G. ERTL AND W. R. BAUER. Study of Microcirculation by Coloured Microspheres and NMR-microscopy in Isolated Rat Heart: Effect of Ischaemia, Endothelin-1 and Endothelin-1 Antagonist BQ 610. Journal of Molecular and Cellular Cardiology (1997) 29, 3115-3122. Although the investigation of coronary microcirculation is of great importance, available methods have severe restrictions. They do not allow the study of vasodynamics of resistance vessels and microscopic conductance vessels simultaneously in the isolated beating rat heart. We now demonstrate that the combined measurement of perfusion which reflects the state of resistance vessels and cross-sections of microscopic conductance vessels is feasible in the model of the isolated constant now perfused rat heart. Perfusion measurement was based on injection of coloured microspheres. Cross-sections of microscopic conductance vessels (diameter >140 mu m) were determined by NMR-microscopy by flow weighted imaging. Both methods were established recently by our group. The combined measurement was applied to hearts which were subjected to ischaemia and reperfusion (group 1: n=5, 15 min ischaemia/group 2: n=7, 30 min ischaemia/measurements before ischaemia and 15/30 min after reperfusion), 200 pmol endothelin-1 bolus application (group 3: n=6/measurements before and 5 min after drug application), continuous infusion of the endothelin-1 antagonist BQ 610 (group 4: n=6/measurements before and 20 min after onset of infusion), and 200 pmol endothelin-1 application superimposed on 20 min of continuous BQ 610 infusion (group 5: n=7/combined measurement before BQ 610 infusion and 5 min after endothelin-1 application). In group 1, 15 min reperfusion restored the pre-ischaemic perfusion state, whereas conductance vessels were dilated (80.8 +/- 2.6%), after 30 min reperfusion pre-ischaemic conditions were also restored for conductance vessels. In group 2, a redistribution of perfusion from left ventricular endocardium to the right ventricular wall was observed. Post-ischaemic rhythm disturbances made NMR-imaging in this group impossible. In group 3, a shift of perfusion from the left ventricular myocardium to the right ventricular wall was observed. Similarly, the cross-section of left ventricular conductance vessels decreased (-32.6 +/- 2.1%), whereas size of right ventricular vessels increased. In group 4, BQ 610 had no effect on perfusion nor on vessel size and antagonized the effect of endothelin-1 on perfusion and vessel size in group 5. (C) 1997 Academic Press Limited.