Coronary vascular hemodynamic and permeability changes during reperfusion after no-flow ischemia in isolated, diltiazem-treated rabbit hearts.
Effects of diltiazem on coronary vascular functional integrity were assessed in isolated rabbit hearts during reperfusion after 30 min of global, no-flow ischemia. External detection of radiolabeled albumin, [125I]bovine serum albumin ([125I]BSA), and compartmental-model analysis were used to estimate the mean transit time of [125I]BSA (tBSA), vascular volume (V1), and vascular into extravascular space clearance (F21) for [125I]BSA. Perfusion pressure, left ventricular (LV) end-diastolic pressure, LV developed pressure, maximum +dP/dt, and V1 remained constant during 5 h of continuous perfusion, while tBSA and F21 gradually increased (1.5 and 2.4 times baseline, respectively). Diltiazem, 4 microM, increased total water content (8.5%) and decreased perfusion pressure (11%), LV developed pressure (22%), and +dP/dt (24%) in nonischemic control experiments, but did not significantly affect estimates of V1, extracellular space, tBSA, or albumin permeation. During reperfusion after 30 min of ischemia, V1 increased 40% and perfusion pressure increased 60%, while tBSA and F21 increased three and eight times baseline, respectively. LV developed pressure and +dP/dt returned to control levels, even though the water content and extracellular space of ischemic hearts were increased significantly. Diltiazem, 4 microM, blocked ischemia-reperfusion-induced increases in water content, extracellular space, vascular resistance, V1, and vascular permeability to [125I]BSA, without reducing LV developed pressure or +dP/dt relative to nonischemic diltiazem controls. These results suggest that protection of ischemic myocardium by diltiazem is mediated, at least in part, by preservation of vascular functional integrity.
R G
RG
Tilton
E K
EK
Williamson
P A
PA
Cole
K B
KB
Larson
C
C
Kilo
J R
JR
Williamson
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001834:Body Water / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002451:Cell Compartmentation; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology*; D004492:Edetic Acid / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008433:Mathematics; D008955:Models, Cardiovascular; D009929:Organ Size / Q000187:drug effects; D010477:Perfusion; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013997:Time Factors
D001552:Benzazepines; D012710:Serum Albumin, Bovine; D004492:Edetic Acid; D004110:Diltiazem