Atrial muscle isolated from guinea pigs subjected to
Escherichia coli endotoxin shock was used to study the myocardial changes associated with this experimental disease state. Isometric contractile tension and its first derivative (dT/dt) consistently were depressed by about 45% in muscle from the
shock group (P less than 0.001), but contraction time intervals of the
shock tissues were not significantly altered. The inotropic deficit of
shock was completely antagonized by high concentrations of Ca2+ (greater than 4.5 mM). However, the maximal positive inotropic response to increased frequency of stimulation (0.1-2.2 Hz) only partially antagonized
shock-induced cardiac depression. Heart muscle from shocked animals exhibited increased sensitivity to the negative inotropic effects of Mn2+, low Ca2+, and
gentamicin; recovery from the depressant actions of these agents was prolonged 3.6- to 4.8-fold in
shock. However, the negative inotropic potency of slow Ca2+ channel blockers,
D 600 and
nifedipine, was unaffected by
shock. Similarly, studies with an
isoproterenol-activated slow Ca2+ channel technique demonstrated equivalent inotropic responses of
shock and control heart muscle. Present data provide evidence for a disruption of myocardial Ca2+ metabolism associated with
endotoxin-induced inotropic depression of the heart but suggest that slow Ca2+ channels of the sarcolemma remain functional in this disease state.