title: Delayed recovery of homogeneous perfusion distribution in isolated rat heart after vasodilatation induced by alpha 1 adrenoceptor blockade during postischaemic reperfusion.
abstract: The purpose of this study was to investigate whether vasodilatation induced by doxazosin, an alpha 1 adrenoceptor blocker, during postischaemic reperfusion was able to accelerate reflow in unperfused myocardium. Isolated isovolumetrically beating rat hearts were exposed to global ischaemia by perfusion at 15 mm Hg for 2 h, resulting in an end ischaemic coronary flow rate of 2.3 (SD 1.7)% of preischaemic value, and an unperfused myocardial volume of 71.8(4.3)% of total myocardial volume. Subsequent reperfusion at 80 mm Hg for 2 h produced a partial recovery of coronary flow rate of 41(6)% in the absence of doxazosin and a complete recovery [97(28)%] in the presence of doxazosin 2 mumol.litre-1. Surprisingly, doxazosin induced vasodilatation retarded the disappearance of "no reflow" during reperfusion: after 3 h of reperfusion the volume of unperfused myocardium was 14.3(5.5)% v 1.5(1.7)% in the control group (p less than 0.005). Assessed histologically the regions of "no-reflow" were localised predominantly in the subendocardium. In the presence of doxazosin, left ventricular end diastolic pressure during reperfusion was twice as high as in the control group, indicating pronounced subendocardial compression. The mechanism underlying prolonged subendocardial "no-reflow" in the presence of doxazosin during postischaemic reperfusion is a compressive action of dilated (sub)epicardial vessels on the vasculature in the unperfused subendocardial regions ("hydraulic" or "erectile" effect of increased vascular volume). Thus coronary vasodilatation induced by alpha 1 adrenergic receptor blockade during postischaemic reperfusion delays the recovery of homogeneous transmural perfusion distribution.
authors.affiliation: Department of Cardiology, University Hospital, Leiden, The Netherlands.
authors.forename: R W
authors.initials: RW
authors.lastname: Mohanlal
authors.forename: I
authors.initials: I
authors.lastname: Mauve
authors.forename: L
authors.initials: L
authors.lastname: van der Valk
authors.forename: A V
authors.initials: AV
authors.lastname: Bruschke
authors.forename: A
authors.initials: A
authors.lastname: van der Laarse
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017292:Doxazosin; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000032:analysis; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013318:Stroke Volume / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014665:Vasodilator Agents; D007770:L-Lactate Dehydrogenase; D017292:Doxazosin; D011224:Prazosin