Protection of myocardial function during endotoxin shock by ibuprofen.

We have concluded that Ibuprofen, a cyclooxygenase inhibitor with high specificity for the preferential blockage of thromboxane synthetase, significantly improves arterial blood pressure, cardiac index, and arterial pH during endotoxin shock in dogs (J. Clin. Invest. 70:536, 1982). This study was undertaken to determine whether Ibuprofen (25 mg/kg i.v.) administered 20 min prior to endotoxin (2 mg/kg i.v.) is able to overcome the depressed ability of cardiac microsomes to actively sequester calcium after 2 hrs of endotoxin shock. Results indicate that microsomes isolated from hearts of animals pretreated with Ibuprofen and then given endotoxin are able to sequester calcium at rates similar to microsomes isolated from control hearts. Microsomes isolated from hearts of animals in endotoxin shock without Ibuprofen show the anticipated depression of calcium sequestering ability. The improved ability of microsomes from the hearts of animals pretreated with Ibuprofen to sequester calcium is the result of normal Ca+2-Mg+2 ATPase activity in the microsomal membrane. We conclude that Ibuprofen protects against the detrimental hemodynamic derangements of endotoxin induced shock in the dog, and thereby also improves cardiac subcellular calcium transport; the factor regulating contractility. Ibuprofen may warrant evaluation as a protective agent to be used prophylactically in high risk cases of endotoxemia.

The role of prostaglandins E2 and F2 alpha on canine arterial in vitro lipid biosynthesis from 14C-acetate.

This study was designed to investigate the influence of prostaglandin on in vitro incorporation of 14C acetate into canine aortic lipid. Aortae were excised from pentobarbital-anesthetized dogs, stripped of their adventitial layer and incubated four hours in the presence of labeled substrate alone or labeled substrate plus prostaglandin. The tissue was subsequently homogenized and the lipid phase extracted. Thin layer chromatography was used to separate lipid subfractions. Incorporated 14C was measured by liquid scintillation. PGE2 (0.05-0.10 microgram/ml) significantly decreased (p less than 0.01) incorporation of 14C acetate into phospholipid. Other lipid subfractions were not affected. PGF2 alpha (0.01-0.05 microgram/ml) significantly increased (p less than 0.01) incorporation of 14C acetate into phospholipid, triglyceride and FFA. Other subfractions were not affected. Studies conducted on intimal and medial layers separately failed to alter the extent to which 14C was incorporated into these tissue layers. Tissue "blanks" performed following destruction of enzymatic activity failed to demonstrate any significant background uptake of 14C. Therefore, in vitro effect of PGE2 is to decrease aortic wall lipid synthesis from acetate, while the effect of PGF2 alpha is to increase aortic lipid synthesis from acetate.