TY - JOUR

T1 - Transport of beta-blockers and calcium antagonists by diffusion in cat myocardium

AU - Haunsø, Stig

AU - Sejrsen, Per

AU - Svendsen, Jesper Hastrup

PY - 1991/3/1

Y1 - 1991/3/1

N2 - Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion. In anesthetized cats the hearts were excised. Apparent diffusion coefficients in cat myocardium at 37 degrees C (D'37) for 14C-verapamil (protein bound), 3H-metoprolol (lipophilic), 3H-atenolol (hydrophilic), and 3H-propranolol (lipophilic and protein bound) were determined by means of a "true transient diffusion" method and compared with the free diffusion coefficients in water (D37). D'37 of 14C-verapamil, 3H-metoprolol, 3H-atenolol, and 3H-propranolol (in cm2 s-1 10(5)) were (mean +/- SEM) 0.025 +/- 0.002, 0.055 +/- 0.003, 0.041 +/- 0.007, and 0.025 +/- 0.002, respectively. The mean diffusive progression of the concentration profile of 3H-metoprolol and 3H-atenolol into the tissue during 20 min was calculated to be 0.36 and 0.31 mm, respectively. The protein binding of 14C-verapamil and 3H-propranolol caused a significant fall in the progression to 0.24 mm for both drugs. These results indicate that, by diffusion, these drugs traverse the tissue too slowly to reach a significant amount of myocardium before myocyte necrosis occurs during conditions of noflow. Cardioprotective drugs are probably most effective, provided sufficient amounts are present in the tissue prior to the ischemic episode or sufficient supply via collateral blood flow is achieved.

AB - Beta-blockers and calcium antagonists have been claimed to possess cardioprotective properties. This study addresses the question of whether a significant amount of these drugs will reach the cardiac myocytes during no-flow ischemia, where solute transport depends solely on diffusion. In anesthetized cats the hearts were excised. Apparent diffusion coefficients in cat myocardium at 37 degrees C (D'37) for 14C-verapamil (protein bound), 3H-metoprolol (lipophilic), 3H-atenolol (hydrophilic), and 3H-propranolol (lipophilic and protein bound) were determined by means of a "true transient diffusion" method and compared with the free diffusion coefficients in water (D37). D'37 of 14C-verapamil, 3H-metoprolol, 3H-atenolol, and 3H-propranolol (in cm2 s-1 10(5)) were (mean +/- SEM) 0.025 +/- 0.002, 0.055 +/- 0.003, 0.041 +/- 0.007, and 0.025 +/- 0.002, respectively. The mean diffusive progression of the concentration profile of 3H-metoprolol and 3H-atenolol into the tissue during 20 min was calculated to be 0.36 and 0.31 mm, respectively. The protein binding of 14C-verapamil and 3H-propranolol caused a significant fall in the progression to 0.24 mm for both drugs. These results indicate that, by diffusion, these drugs traverse the tissue too slowly to reach a significant amount of myocardium before myocyte necrosis occurs during conditions of noflow. Cardioprotective drugs are probably most effective, provided sufficient amounts are present in the tissue prior to the ischemic episode or sufficient supply via collateral blood flow is achieved.

KW - Adrenergic beta-Antagonists

KW - Animals

KW - Atenolol

KW - Biological Transport

KW - Calcium Channel Blockers

KW - Cats

KW - Diffusion

KW - Metoprolol

KW - Myocardium

KW - Propranolol

KW - Sucrose

KW - Verapamil

M3 - Journal article

C2 - 1711595

VL - 17

SP - 357

EP - 364

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 3

ER -