Effects of nylidrin, isoproterenol and phenoxybenzamine on dogs subjected to hemorrhagic shock.

The effects of beta-adrenergic receptor stimulants (nylidrin and isoprotere-nol) on the hemorrhagic shock state of anesthetized dogs were measured and compared to those of phenoxybenzamine to determine the therapeutic effectiveness of the combined cardiac stimulatory and peripheral vasodilatory actions of the former drugs. Anesthetized dogs were subjected to 3 hours of hypo-volemia followed by the return of the shed blood. Nylidrin, isoproterenol (continuous infusion), and phenoxybenzamine were administered 1 hour after bleeding the animals and heart rate, arterial blood pressure, venous hemato-crit, coronary blood flow, cardiac output, ventricular contractility, and survival rates were measured. Nylidrin and isoproterenol afforded significant protection against shock deaths, whereas phenoxybenzamine did not increase survival over control values. Mild to moderate intestinal hemorrhage and distention were noted in the isoproterenol-and phenoxybenzamine-treated animals, but not in the nylidrin-treated animals. Phenoxybenzamine gradually decreased the arterial blood pressure and additional quantities of blood had to be infused to maintain cardiac output and blood pressure. Ventricular contractile force progressively decreased in the phenoxybenzamine-treated animals, whereas iso-proterenol and nylidrin enhanced the force of ventricular contractions. In the presence of existing hypotension, isoproterenol and nylidrin maintained cardiac output. These agents deserve further consideration as potentially useful dierapeutic agents in the management of shock states. ADDITIONAL KEY WORDS ventricular contractility hypovolemic shock survival rates intestinal necrosis beta-adrenergic receptor stimulants arterial blood pressure alpha-adrenergic receptor blocker bleeding volumes cardiac output • Alpha-adrenergic (1) and ganglionic (2) blocking agents and certain vasodilators (3) are known to increase survival rates in animals subjected to standard shock procedures. These agents reduce vascular resistance and favorably redistribute blood flow to the vas-cular beds of certain critical tissues during hypovolemia. These vascular effects retard the development of the irreversible shock state and improve cardiac function during shock, presumably by decreasing systemic vascular resistance and the work of the heart. Although most investigators conclude that peripheral vascular factors, rather than cardiac failure, usually cause irreversible shock, evidence that has been accumulated indicates that, at least in certain circumstances, decline in myocardial contractility may contribute significantly to the development of irreversible shock (4, 5). Drugs that stimulate beta-adrenergic receptors , such as isoproterenol and nylidrin, exert