Intracellular accumulation of
calcium is thought to play an integral role in the progression of ischemic injury and cell death. We infused the
calcium entry blocker,
nitrendipine (1.5 micrograms/kg per min), into cats in order to investigate the importance of extracellular Ca2+ influx during
hemorrhagic shock.
Nitrendipine proved to be a potent hypotensive agent in
sham shock cats when infused over a 4 h period (156 +/- 9 to 90 +/- 5 mm Hg) (P less than 0.01). However, in hemorrhaged animals,
nitrendipine treatment maintained the post-reinfusion MABP at a significantly higher (P less than 0.01) value than untreated controls (79 +/- 5 vs. 51 +/- 4 mm Hg, respectively). Superior mesenteric artery flow (SMAF) for hemorrhaged animals treated with
nitrendipine was significantly higher (9.8 +/- 1.4 ml/min per kg) (P less than 0.01) than that for untreated cats (4.2 +/- 0.4 ml/min per kg), at 2 h post reinfusion. There was no significant increase in SMAF during oligemia in the
nitrendipine-treated animals.
Nitrendipine was also found to significantly retard the appearance of
cathepsin D in the plasma of hemorrhaged cats as well as reduce plasma proteolysis to values not significantly different from
sham shock animals. Furthermore,
myocardial depressant factor (
MDF) activity in the plasma of
nitrendipine-treated
shock cats was not significantly different from
sham shock animals, while the plasma
MDF activity for
shock cats receiving vehicle increased 3-fold (P less than 0.001). The beneficial effects for
nitrendipine in
hemorrhagic shock are likely due to both its
vasodilator function and its ability to reduce intracellular Ca2+ accumulation during
ischemia, thereby reducing disruption of cell membrane systems.