Propranolol preserves ultrastructure in adult cardiocytes exposed to anoxia/reoxygenation: a morphometric analysis.
The protective effect of d,l-propranolol was studied using freshly isolated canine ventricular cardiocytes (1.5 x 10(6)/mL) exposed to 30 min anoxia (95% N2/5% CO2) and 0, 3, 20, and 45 min of reoxygenation (95% O2/5% CO2). In addition to preventing lipid peroxide formation, propranolol maintained cellular viability, and minimized ultrastructural alterations. In the absence of propranolol, the outer mitochondria become swollen and rounded up within the first few minutes of reoxygenation. The perinuclear mitochondrial area increased only slightly. We observed that the cellular injury process proceeded differentially from the exterior to the interior, with a mitochondrial area increase and outer membrane rupture. Sarcolemmal damage was also observed with prevalent blebbing and membrane loss. The Z-lines became wider and more diffuse with reoxygenation. Injury to the nuclear double membrane was observed. Incubation with propranolol showed significant protection during postanoxia reoxygenation. In contrast, the more water soluble beta-blocker atenolol only exhibited slight protection. In addition, d-propranolol (the non beta-blocking isomer) and the antioxidant enzymes, SOD and catalase, showed significant protection. These data support previous findings concerning the antioxidant properties of propranolol which appear to be independent of beta-receptor blockade.
Department of Medicine, George Washington University Medical Center, Washington, DC 20037.
A M
AM
Freedman
J H
JH
Kramer
I T
IT
Mak
M M
MM
Cassidy
W B
WB
Weglicki
D000818:Animals; D000975:Antioxidants; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure*; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010100:Oxygen / Q000494:pharmacology*; D011433:Propranolol
D000975:Antioxidants; D011433:Propranolol; D010100:Oxygen