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A previous study of endotoxemia in dogs demonstrated that exogenous prostacyclin (PGI2), normally a product of vascular endothelium, restored the cardiac index to normal and improved survival. To account for these results, a study was undertaken to test whether PGI2 would alter isolated rat or dog cardiac mitochondrial function following incubation with plasma from endotoxemic animals. A group of five animals served as anesthetized controls. A second group of seven mongrel dogs was given 1.75 mg Escherichia coli endotoxin/kg and was observed for 5 hours without treatment. Anesthesia did not alter cardiopulmonary function; however, 30 minutes after endotoxin administration, the cardiac index decreased from 148 ± 25 ( ± SD) to 111 ± 12 ml/kg · min (P < 0.05) and further decreased to 89 ± 20 ml/kg · min after 4 hours. Dog plasma obtained 2 to 5 hours after endotoxin infusion, incubated with rat or dog myocardial mitochondria, decreased succinate dehydrogenase (SDH) activity (P < 0.05) and depressed mitochondrial respiration in the presence of the substrate succinate and adenosine diphosphate (ADP) from 180 to 87 Natoms oxygen/mg protein · min (P < 0.05). There was no change in oxygen consumption when substrate alone was present, nor did plasma alter the amount of ADP phosphorylation as a function of oxygen consumption. A third group of seven animals, 30 minutes after administration of 7.75 mg endotoxin/kg, was treated with 100 ng/kg · min PGI2 for 3 hours. PGI2 infusion in this group prevented the decrease in cardiac index. Plasma obtained during and after PGI2 infusion did not decrease mitochondrial SDH activity, which remained higher than that in controls (P < 0.001); mitochondrial respiration was also not altered. A correlation was observed between cardiac index and SDH activity (r = 0.58, P < 0.001) and between cardiac index and mitochondrial respiration (r = 0.67, P < 0.001). In PGI2-treated dogs cardiac mitochondria were functionally and structurally normal in contrast to the depression and disruption produced by endotoxemia, as observed by enzymatic assay as well as electron microscopy. These results suggest that endotoxemia depresses cardiac mitochondrial respiration, an event related to the decrease in cardiac index. In contrast, cardiac function and mitochondrial respiration are maintained with PGI2 treatment.
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- Mechanisms of the hemodynamic effects of endotoxin.Physiol Rev. 1960; 40: 245-279
- Presence of negative inotropic agents in canine plasma during positive end-expiratory pressure.Circ Res. 1979; 45: 460-467
- A miniaturized chamber for the measure of oxygen consumption.J Appl Physiol. 1982; 52: 488-490
- Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, PGI2.J Appl Physiol. 1978; 45: 408-413
- Physiology of the heart.Raven Press, New York1977
- Reconstitution ot respiratory chain enzyme systems. XI. Use of artificial electron acceptors in the assay of succinate dehydrogenating enzymes.J Biol Chem. 1963; 238: 4032-4036
- Prostacyclin (PGI2) reversal of lethal endotoxemia in dogs.J Clin Invest. 1981; 67: 1118-1125
- Beneficial actions of prostacyclin in traumatic shock.Prostaglandins. 1970; 17: 761-767
- Salutary effects of prostacyclin in endotoxin shock.Pharmacology. 1980; 21: 206-212
- Protein measurement with the folin phenol reagent.J Biol Chem. 1951; 193: 265-275
- Action of bacterial endotoxin and lipid A on mitochondrial enzyme activities of cells in cultures and subcellular fraction.Infect Immunol. 1979; 25: 664-671
- Effects of bacterial endotoxin on lysosomal and mitochondrial enzyme activities of established cell cultures.J Reticuloendothel Soc. 1979; 26: 307-316
- A study of microcirculation in endotoxin shock.Surg Gynecol Obstet. 1974; 139: 11-16
- Physiologic and metabolic correlations in human sepsis.Surgery. 1979; 86: 163-193
- The mitochondria.Methods Pharmacol. 1971; 1: 247-286
- Studies on pulmonary complications due to cardiopulmonary bypass. II. Pulmonary changes after cardiopulmonary bypass in dogs.Kumamoto Med J. 1976; 29: 161-171
Accepted: March 19, 1982
☆Supported in part by The National Institute of Health grants GM24891-04, HL16714-06, and CA-EY-03171, The U.S. Army Medical Research and Development Command contract DAMD17-78-C-8026, The Brigham Surgical Group, Inc., and The Trauma Research Foundation.
© 1982 Published by Elsevier Inc.