Direct visualization of the coronary microcirculation for pharmacologic and physiologic studies.
An isolated, arrested rat heart preparation which has coronary tone similar to that found in vivo and allows direct visualization of the coronary microcirculation is described. The rat hearts are perfused in situ prior to isolation. This procedure obviates any ischemic ischemic damage to the heart. The perfusate used is a modified Krebs solution with 40 mM potassium, 2 g% albumin, and washed red cells (20% HCT). To directly view the coronary microcirculation, a fluorescent albumin conjugate is added to the cell-rich perfusate. The epicardial microvessels are illuminated and observed with a fluorescence microscope. It was found that the control intercapillary distance in this model (33 microns) was almost twice that reported by other investigators for working hearts and suggested a 60-70% coronary capillary reserve in the arrested heart. The calcium blocker nisoldipine (Miles Laboratories) caused a dose-dependent coronary vasodilation using either a constant-flow or constant-pressure protocol. The coronary reactivity of this preparation to nisoldipine was 50 times greater than reported for isolated hearts perfused with cell-free Krebs solution. Further, the preparation vasodilated in a dose-dependent manner to histamine, but histamine did not cause a significant increase in coronary permeability to macromolecules. This model is appropriate for both physiologic and pharmacologic studies. It is particularly well suited for determining the direct effects of an intervention on coronary tone and the coronary microcirculation.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D002200:Capillary Resistance / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins / Q000378:metabolism; D006324:Heart Arrest, Induced / Q000379:methods*; D006632:Histamine / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D015737:Nisoldipine; D010477:Perfusion / Q000295:instrumentation; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000378:metabolism
D002121:Calcium Channel Blockers; D005452:Fluoresceins; C039217:fluorescein isothiocyanate bovine serum albumin; D012710:Serum Albumin, Bovine; D015737:Nisoldipine; D006632:Histamine; D016650:Fluorescein-5-isothiocyanate; D009543:Nifedipine