Effect of Isoproterenol on Survival in Canine Endotoxin Shock

Abstract

ATIEMPTS to evaluate therapy in patients having shock due to gram-negative microorganisms (endotoxin shock) are obscured by the lack of quantitative data on the natural course of human shock. The canine experimental model for studying endotoxin shock has provided basic information on the pathophysiology of this disorder.6 11,22,23 Agents that have altered the progress of canine endotoxin shock favorably have at timnes been beneficial in human subjects.17' 23 However, the management of human endotoxin shock still constitutes a major therapeutic problem.Isoproterenol, a synthetic catecholamine, structurally similar to the endogenous catecholamines norepinephrine and epinephrine appears to be a promising adjunct in the management of patients with endotoxin shock. 3' 4, 13, 16 Studies have indicated that isoproterenol can partially reverse the undesirable hemodynamic effects of endotoxin shock in sheep and in dogs.4 10,26 But, because of experimental design, lack of proper controls, or insufficient numbers, proper assessment of isoproterenol in survival is lacking.Extensive observations on canine endotoxin shock in our laboratory have demonstrated that significant survival or mor-

Hemodynamic effects of isoproterenol in canine endotoxin shock

“…Experiments were conducted on a pair of dogs simultaneously. At 60 min after endotoxin, infusions of 5 ml/kg per hr with constant infusion pumps were started; one dog (group I) receiving 5%o dextrose and another (group II), dextrose and isoproterenol 7 (0.25 ,Ag/kg per min). In the first five pairs, infusion was given for 4 hr and in the remaining 13 pairs, for 12 hr.…”

“…This drug has reversed the severe hemodynamic and pulmonary alterations in sheep (4) and has been confirmed in dogs (5,6). Isoproterenol has significantly reduced the mortality in canine endotoxin shock (7). Various studies have shown that it increases cardiac output (8), dilates lower respiratory airways, relaxes arterioles, constricts veins, increases ventilation (9) and improves function of the failing heart (10,11).…”

Effects of Alpha and Beta Receptor Stimulating and Blocking Agents on Experimental Disseminated Intravascular Coagulation

“…According to some authors, the sympathetic denervation (Palmiero et al 1962) or the preventive administration of alpha receptor blocking agents (Mc Kay 1969;Muller Berghaus et al 1967;Muller Berghaus 1969;Whitaker et al 1969) or beta receptor blocking agents (Berk et al 1967(Berk et al , 1969 should reduce the biological and clinical disorders of endotoxin shock (generalized Shwartzman reaction). According to others, the preventive administration of alpha receptor blocking agents (Kardos 1966;Mc Lean et al 1965) or beta receptor blocking agents (Halmagyi et al 1963;Vick et al 1965) should enhance consumptive coagulopathy whereas the alpha or beta stimulating agents (Starzecki et al 1968;Vick et al 1965) should have an opposite effect.…”

Κυκλοφορικαι Και Μεταβολικαι Μεταβολαι Προκαλουμεναι Υπο Συνεχους Ενδοφλεβιου Εγχυσεως Ισοπρεναλινης

“…Αί καταστάσεις αύται εϊναι λίαν συχναί καί απαντούν επί μορφών τίνων πυελονεφρίτιδος καί περιτονίτιδος, επί των πλείστων περιπτώσεων shock εξ ήπατίτιδος ή κιρρώσεως 46 , πολλών καταστά σεων σηπτικού shock 20 • ένδοτοξικοΰ shock 25 . 64 καί σχεδόν άπασών των περιπτώσεων shock οφειλομένου εις σηψαιμίαν εκ θετικών κατά Gram μικροοργανισμών. Ή χορήγησις Ίσοπρεναλίνης υπό τάς υποτασικός ταύτας συνθήκας, μή επηρεάσασα σημαντικως την Μ.Α.Π., απέτυχε του να αύξηση το Π.Π.Α.…”