Effect of Alpha and Beta Adrenergic Blockade on Epinephrine Induced Pulmonary Insufficiency

Abstract

Recent studies demonstrated that epinephrine causes significant pulmonary A-V shunting. This study reports the effect of alpha and beta adrenergic blockade on this shunting. Sixty-three anesthetized mongrel dogs were ventilated with a mechanical respirator. Measurements of (1) the pulmonary shunt, (2) cardiac output, (3) mean pulmonary artery, pulmonary capillary wedge and systemic pressures, and (4) pulmonary and systemic vascular resistances were obtained at 5, 15 and 30 minute intervals during the first hour and hourly for 5 hours. Fifteen dogs received no treatment. All others received epinephrine hydrochloride, 2 mug/kg/min for 5 hours. Ten received epinephrine only. Ten were pretreated with propranolol hydrochloride, 250 mug/kg, 12 with phenoxybenzamine, 1 mg/kg, and 16 with phenoxybenzamine and propranolol. Propranolol significantly decreased the epinephrine induced pulmonary shunt at all times and was the most effective drug. Phenoxybenzamine decreased the early shunting, but less than propranolol, and did not decrease the late shunting. Blockade with propranolol and phenoxybenzamine was less effective than propranolol alone. Based on the observed hemodynamic changes it was suggested that beta blockade is effective in reducing epinephrine induced pulmonary insufficiency by favorably altering the flow and distribution of pulmonary blood flow which in turn decreases epinephrine induced ventilation-perfusion inequalities and capillary hypertension both of which result in shunting. Conversely phenoxybenzamine has an unfavorable effect on the pulmonary flow. These studies support previous work in animals and man which showed that beta adrenergic stimulation is important in the pathogenesis of pulmonary insufficiency. Because the amounts of epinephrine used produce blood levels observed in critical illness, these studies add support to a relationship between the increased catecholamine stimulation of critical illness and the associated and often unexplained pulmonary insufficiency.

Epinephrine Induces Rapid Deterioration in Pulmonary Oxygen Exchange in Intact, Anesthetized Rats

“…Berk et al 15 and others 16,17 theorized that shunt during prolonged epinephrine infusion was initially due to pulmonary arterial flow redistribution with secondary ventilation-perfusion inequalities and that only after several hours was it caused by interstitial and alveolar edema. They ascribed these effects to β -adrenergic stimulation as they were reversed by propranolol whereas phenoxybenzamine pretreatment had only minor protective effects.…”

Catecholamine-induced opening of intrapulmonary arteriovenous anastomoses in healthy humans at rest

“…Indeed, using 15-to 30-m radioactive albumin microspheres, Nomoto et al (40) demonstrated that IPAVA open in dogs infused with EPI. Additionally, Berk and colleagues also suggested a direct effect of EPI increasing venous admixture in anesthetized dogs based on an immediate fall in arterial partial pressure of oxygen (PO 2 ) during EPI infusion (2)(3)(4), while Huckauf et al (22) suggested a similar effect in patients with left heart failure receiving DA infusion. Thus these catecholamines could potentially be opening IPAVA; however, their role and mechanism of action in opening IPAVA in healthy humans is unknown.…”

A Novel and Effective Balanced Intravenous-Inhalant Anaesthetic Protocol in Swine by Using Unrestricted Drugs

“…the spo 2 enhanced of about 2% along the anaesthesia session and this effect might be referred to the potent peripheral alpha receptor antagonism induced by the tranquilizer aCe. in effect aCe, a central dopaminergic receptor blocker at level of basal ganglia, forebrain, chemoreceptor trigger zone and hypothalamus, could improve the arterial oxygenation by inducing vasorelaxation in the pulmonary vascular bed and by reducing the pulmonary arteriovenous shunt in swine as previously suggested for different species [5,9,45]. in fact, it was demonstrated that during anaesthesia, the impaired arterial oxygenation can be attributed to an increased shunt and ventilation-perfusion ratio mismatch [45].…”