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1 An in vitro study, using helical preparations of human umbilical arteries and veins obtained from healthy women at term pregnancy, was designed to determine: (a) whether three local anaesthetics commonly utilized in obstetric anaesthesia (bupivacaine, 2-chloroprocaine, and lignocaine) can induce contraction or relaxation of resting umbilical vessels; (b) whether these agents can induce contraction or relaxation of umbilical vessels which have been previously induced to contract by a known activator, potassium chloride (KCI); and (c) the relative potency of these agents as compared to KC1. 2 The results indicate that: (a) these local anaesthetics are vasoactive on human umbilical vascular smooth muscle; (b) bupivacaine induces contraction in over 90% of the resting vessels examined, while 2-chloroprocaine consistently causes relaxation and lignocaine causes a small degree of contraction in 40% of vessels examined; (c) bupivacaine causes further contraction (or potentiation) of KC1-contracted muscle in 50% of the vessels studied, while 2-chloroprocaine and lignocaine both induce relaxation of these contracted vessels.Introducion

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This study explores the use of both histamine HI-and H2-receptor antagonists in two different forms of circulatory shock and suggests that histamine may be involved in more than one way in the pathophysiology of circulatory shock. Various single doses of diphenhydramine, chlorpheniramine, promethazine, and burimamide were administered intravenously to Wistar rats subjected to hemorrhagic or bowel ischemia shock. Cumulative survival and mortality, as well as arterial blood pressures and microhematocrits, were monitored. Pretreatment of the animals with the three different Hi-receptor antagonists exerted significant protection against both forms of shock. Rats pretreated with the H2-receptor antagonist, burimamide, demonstrated an exacerbated mortality after induction of shock. Animals pretreated with HI-receptor antagonists showed significantly higher mean arterial blood pressure, greater compensatory rebound of blood pressure after induction of shock, and greater responses to transfusion after hemorrhage than control, shocked animals. Similarly, rats pretreated with the Hi-receptor blockers demonstrated significantly greater compensatory hemodilution which continued late in shock. In marked contrast, rats pretreated with burimamide exhibited opposite effects after hemorrhage and bowel ischemia, i.e., significant falls in blood pressure, lack of compensatory rebound and response to transfusion of shed blood, and a progressive hemoconcentration. This report clearly demonstrates beneficial actions of histamine HI-receptor antagonists and detrimental effects of H2-receptor antagonists on survival and other parameters in these forms of circulatory shock.For more than 75 years, numerous investigators have suggested that various blood-borne substances are involved in the pathophysiology of circulatory shock syndromes. The release into the blood stream of several vasoactive agents has, from time to time, been implicated as both etiologic and sustaining factors in many shock syndromes (1-5). In order to gain insight into this area, specific pharmacologic antagonists to several of these vasoactive substances have been used by various workers over the past 40 years (6-9).Although histamine HI-receptor antagonists have been used previously to explore the possible contribution of histamine in some forms of circulatory shock (10-12), no previous study used several different antihistamines over a wide dose range in controlled sublethal shock models (see review, ref. 13). Nor have studies been done with histamine H2-receptor antagonists in hermorrhagic or intestinal ischemic shock. The studies presented herein explore the use of both H1-and H2-receptor blockers in rats and indicate that histamine may be involved in more than one way in the pathophysiology of different forms of circulatory shock. (1,10 or 25 mg/kg). Sixty minutes later, the animals were bled via femoral arteries over a 30-min period to a fixed 3% by body weight. The blood was withheld from the latter animals for 110 min. At the conclusion of this hypot...