The Journal of Thoracic and Cardiovascular Surgery, Vol 70, 955-965, Copyright © 1975 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
Protective effect of methylprednisolone on the heart during ischemic arrest
RW Busuttil, WJ George and RL Hewitt
Although corticosteroids have been shown to stabilize lysosomal membranes
and prevent release of hydrolytic enzymes, the mechanism of membrane
stabilization remains obscure. The few reports regarding the use of
steroids in myocardial ischemia have been conflicting. This study was
undertaken to determine if a pharmacologic dose of the glucocorticoid
methylprednisolone would protect the heart during ischemic cardiac arrest.
A randomized double-blind study was performed in 25 dogs. Biochemical and
hemodynamic parameters were assessed during and after cardiopulmonary
bypass and after 30 minutes of ischemic cardiac arrest. Animals were
divided into two groups. Group I served as controls and consisted of dogs
injected intravenously with the vehicle of methylprednisolone 18 hours and
1 hour prior to experiment. Group II comprised dogs injected with
methylprednisolone, 30 mg. per kilogram, IV, at the same time periods.
Blood pH, gases, and electrolytes were measured; aortic, left atrial, and
left ventricular pressures were monitored; the first derivative of the left
ventricular pressure (dp/dt max.) was also determined. Arterial and
coronary sinus blood samples were assayed for lactate levels and activity
of the lysosomal enzyme, beta-glucuronidase. Left ventricular muscle was
assayed for the nucleotides cyclic adenosine 3',5' monophosphate (AMP) and
cyclic guanosine 3',5' monophosphate (GMP). Following restoration of
coronary flow, mean aortic and left ventricular systolic pressures and left
ventricular contractility as determined by dp/dt max. and dp/dt max./IP
were depressed in both groups as expected but were significantly higher in
Group II than in Group I (p less than 0.05). An increase in levels of both
cyclic nucleotides occurred in each group during ischemia, but this
increase in cyclic GMP was significantly greater in Group I (p less than
0.05). beta-glucuronidase activity and myocardial potassium loss as
determined in coronary sinus blood were both significantly greater in Group
I than in Group II (p less than 0.05). Results of this study demonstrate
that pretreatment with a pharmacologic dose of methylprednisolone
significantly enhances cardiac recovery after ischemia. Lysosomal membrane
stability and modulation of cyclic GMP levels may be critical determinants
in the mechanism of cardiac ischemia.
