Reperfusion injury in ischemic myocardium: effects of nifedipine and verapamil.
Coronary reperfusion following myocardial ischemia may result in further damage to injured myocytes, as judged by their ultrastructural appearance. Calcium entry into myocytes has been implicated in this effect, and calcium channel-blocking agents have been used in attempts to prevent or limit such damage. In this study, we produced myocardial ischemia in pigs by means of reversible coronary artery occlusion. The pigs were infused with either nifedipine or verapamil (both clinically employed calcium channel-blocking agents) prior to and during coronary reperfusion. During reperfusion, nifedipine produced a lowering of mean arterial pressure, while mean arterial pressure was constant in verapamil-treated pigs and rose in pigs not receiving drugs. Myocardial samples from the ischemic, reperfused region were examined by electron microscopy. Ischemic damage to nuclei, mitochondria, and myofibrils and glycogen depletion were independently graded on a three-point scale by two investigators. For each of the organelles studied, ischemic damage was significantly less for nifedipine-treated animals than for controls. Ischemic damage in verapamil-treated pigs was not different from that seen in control animals, except for a slight improvement in myofibrillar appearance. We conclude that nifedipine, administered prior to and during reperfusion of myocardium, protects against reperfusion injury. The mechanism of this protective effect may be attributable, in part, to afterload reduction and, in part, to inhibition of transmembrane calcium flux in cardiac fibers.
Mrak
R E
RE
Division of Pathology, John L. McClellan Memorial Veterans Hospital, Little Rock, AR.
Carry
M M
MM
Murphy
M L
ML
Peng
C F
CF
Straub
K D
KD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000648:ultrastructure; D006003:Glycogen / Q000378:metabolism; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000648:ultrastructure; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D009210:Myofibrils / Q000648:ultrastructure; D009543:Nifedipine / Q000627:therapeutic use*; D013552:Swine; D014700:Verapamil / Q000627:therapeutic use*
D006003:Glycogen; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium