Discordant effects of nisoldipine on coronary vascular resistance and permeability changes during reflow after ischemia in isolated rabbit hearts.
Effects of a low dose (5 nM) of nisoldipine on vascular and ventricular function were assessed in isolated rabbit hearts during 2 h of reperfusion after 40 min of global, zero-flow ischemia. External detection of bolus injections of 125I-BSA and pressure data generated during the experiment provided repeated estimates of albumin permeation and vascular hemodynamics (resistance, vascular volume, and fractional rate of intravascular washout of 125I-BSA (k01]. In control hearts perfused continuously for 3.5 h, vascular resistance, vascular volume, LVEDP, and k01 remained constant, while maximum +dP/dt and -dP/dt increased 25% above baseline values, and estimates of albumin permeation increased 1.7 x baseline. Addition of 5 nM nisoldipine to the perfusate after the baseline period produced sustained decreases in vascular resistance (16% vs mean baseline value) without significantly affecting any other parameter. Postischemic perfusion of hearts increased vascular resistance and vascular volume approximately 50% above baseline, decreased k01 by 25% (intravascular washout of 125I-BSA was prolonged), and increased albumin permeation approximately 5 x baseline. While LVEDP remained elevated 3 x baseline, maximum +dP/dt and -dP/dt recovered 100% of baseline values (75-80% of untreated control values at comparable time points). Addition of 5 nM nisoldipine to the perfusate prior to ischemia prevented the increased vascular resistance during reflow, prevented the decrease in k01 and the increase in vascular volume, but did not affect the increased albumin permeation and, in general, did not affect the rate of recovery of left ventricle function. These results indicate that a low dose of nisoldipine preserves postischemic coronary vascular hemodynamics, but has little or no effect on the increased vascular leakage of albumin.
Tilton
R G
RG
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Watts
J A
JA
Land
M P
MP
Larson
K B
KB
Sutera
S P
SP
Williamson
J R
JR
D000818:Animals; D001783:Blood Flow Velocity; D002306:Cardiac Volume / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008954:Models, Biological; D015737:Nisoldipine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D007457:Iodine Radioisotopes; D012710:Serum Albumin, Bovine; D015737:Nisoldipine; D010100:Oxygen