The Effects of Sodium Nitroprusside on Blood Flow and Oxygen Delivery to the Organs of the Hypoxemic Newborn Lamb

Abstract

ABSTRACT. Vasodilators are used in newborns underconditions where hypoxia may be prominent. To study the effects of vasodilator therapy on organ oxygen delivery we measured blood flow (using radioactive microspheres) and arterial oxygen content in six chronically catheterized newborn lambs. Cardiac output and its distribution were measured during normoxia, hypoxia (10% O2 and 5% C02), and hypoxia with a nitroprusside infusion. Hypoxia decreased oxygen content but did not change heart rate, mean blood pressure, or cardiac output. When nitroprusside was infused during hypoxemia, oxygen content and heart rate were not affected, but mean arterial blood pressure fell (39% decrease). During hypoxemia, blood flow increased to the heart, brain, and carcass but decreased to the gastrointestinal tract. When nitroprusside was infused during hypoxemia, blood flow decreased to the heart, brain, kidneys, and carcass. Oxygen delivery (arterial Oz content x blood flow) decreased to the brain as well as to kidneys, stomach, and carcass when nitroprusside was given to the hypoxemic lamb. (Pediatr Res 19: 15-18, 1985)Hypoxemia often accompanies neonatal cardiopulmonary disease. Such common problems as hyaline membrane disease, pneumonia, aspiration syndromes, cyanotic congenital heart disease, and persistent fetal circulation may present with hypoxemia as a prominent finding (8,14,20). When conventional therapy (high inspired oxygen concentration and mechanical ventilation) fails to increase arterial Po2, phannacologic agents have been used. In general, drug therapy is aimed at increasing arterial oxygen content by increasing pulmonary blood flow and thus is employed primarily when pulmonary blood flow is thought to be reduced as a result of pulmonary arterial vasoconstriction.Sodium nitroprusside is a potent, direct-acting vasodilator which has been used for systemic hypertension (16), pulmonary hypertension (7), and congestive heart failure (6, 17). Although experience with nitroprusside in the neonate is limited, two case reports (1, 4) have suggested that nitroprusside may have a therapeutic role in decreasing the high pulmonary vascular resistance of hyaline membrane disease.Nitroprusside is an iron-coordinated complex surrounded by cyanide groups with a single nitroso group (16). The drug is metabolized in the liver to cyanide which is then quickly con- This research was supported by a Grant-in-Aid from the Western Pennsylvania Heart Association, Inc.verted to thiocyanate. Cyanide and thiocyanate may have toxic effects which result in tissue hypoxia and resultant metabolic acidosis. Thiocyanate levels of 10-20 mg/100 m1 (16) result in adverse clinical symptoms. As toxic products accumulate during infusion, hazard increases when the infusion is prolonged.Further information about the response of the newborn's systemic circulation to vasodilator therapy, especially under hypoxemic conditions, would help to show when their use is appropriate. The purpose of this experiment is to examine the effect of nitroprusside on the distri...

The Newborn Rabbit: A Model for Studying Hypoxemia-Induced Renal Changes

“…RBF, renal vascular resistance and urine flow rate did not change significantly. In comparison with other immature animal species the newborn rabbit appears a valuable and inexpensive model for the study of acute hypoxemiainduced renal changes.Respiratory distress syndrome and birth asphyxia, hypoxemic conditions frequently encountered in newborn infants, can be asso ciated with an impairment in renal functions and renal failure [6,9,12,19,20], The pre cise role of hypoxemia in the absence of aci dosis and hypercarbia cannot be fully estab lished in human neonates [12] and has been assessed in neonatal animal models such as lambs [16,21,22,23], piglets [17] and pup pies [15]. However, the hypocarbia reported in some studies [15,17], as well as interspe cies variations and different experimental conditions could account for the discrepan cies reported in the literature.…”

Comparative Circulatory Effects of Isoproterenol and Dopamine in Lambs with Experimental Cyanotic Heart Disease

“…In addition, we found no reported data on the effects of nitroprus-side on lambs as young as our newborn group of 0-3 d. However, several studies describe the cardiovascular effects in slightly older lambs. Mirro et al (17) studied the effects of nitroprusside on systemic blood flow and oxyen delivery in hypoxemic conscious lambs at age 5-7 d. They found, as we did in our newborn lambs, that cardiac output and systemic arterial pressure decreased in each of the lambs; however, the decrease in cardiac output was not statistically significant, possibly because of large variability and slightly older age. They noted that the combination of nitroprusside and hypoxia caused decreased oxygen delivery to the brain, kidney, and carcass.…”

“…Agents with predominantly P-adrenergic effects may increase right to left shunting by decreasing peripheral vascular resistance, whereas agents with predominantly a-adrenergic effects may decrease myocardial performance by increasing systemic vascular resistance (17). Whereas the general hemodynamic effects of these agents have been previously studied in both normoxic (18, 19) and acutely hypoxemic newborns (20), it is not known whether chronic hypoxemia alters the hemodynamic responses to those agents.…”

Effect of Acidosis and Hypoxia on Intestinal Blood Flow of Sheep Fetus

“…The findings of the present study that hyp oxemia (Pa02, 15mmHg) did not signifi cantly alter small intestinal blood flow except in the jejunal mucosa (table III) is consistent with those of Edelslone and Holzman [ 1982], who found that moderate hypoxia (Pa02, 16 Torr) did not significantly change fetal intes tinal blood flow, however, a more severe degree of hypoxia (Pa02, 12 Torr) drastically reduced blood flow. In newborn lambs Nowicki et al [1984] and Mirro et al [1985] found no decline in intestinal blood flow dur ing hypoxemia. In contrast to the perinatal lamb, in adult animals arterial hypoxia in creased blood flow to the small intestine [Svanvik et al, 1968;Shepherd, 1978].…”