Ella U. Choe

A novel model to study the effects of burn lymph on pulmonary vascular hemodynamic variables.

OBJECTIVE To determine the effects of burn lymph on pulmonary hemodynamic variables. METHODS A balloon-tipped catheter was fluoroscopically passed from a jugular vein into the right lower lobe (RLL) pulmonary artery of rats, its distal lumen used to measure pulmonary artery pressure. Inflation allowed measurement of RLL wedge pressure, which represents pulmonary venous pressure. After inflation, the RLL underwent constant flow pump-perfusion with carotid artery blood. Preburn (n = 5) or post-burn (n = 6) dog lymph was infused into the RLL for 50 minutes. MEASUREMENTS Because perfusion flow rate was constant throughout the experiment, RLL changes in pulmonary artery pressure reflect changes in pulmonary vascular resistance. RESULTS Animals given preburn lymph had no alterations in RLL pulmonary hemodynamics. The immediate, significant (p < 0.005, analysis of variance) increases in RLL pulmonary artery pressure (16.2 +/- 2.3 mm Hg at baseline vs. 35.4 +/- 2.1 mm Hg at 30 minutes) and pulmonary vascular resistance (0.0 at baseline vs 1.37 +/- 0.24 at 30 minutes) after burn lymph injection persisted beyond infusion interruption. CONCLUSION The persistent pulmonary hypertensive response to postburn lymph warrants further investigation.

Organ Blood Flow Redistribution in Response to Hypoxemia in Neonatal Piglets

This study was designed to determine the effects of severe hypoxemia on newborn piglet visceral blood flow. While the hemodynamic effects of a severe hypoxemic insult are well characterized in newborn animals, its impact on organ perfusion in premature infants is not well characterized. Cannulas were placed in the femoral vessels and left atrium of term (1-14 days old) and prematurely delivered (cesarean section at 90% of term gestation) piglets. After stabilization, some animals were subjected to 1 h of ventilator-controlled hypoxia (yielding PaO2 approximately = 30-40 torr) followed by 30 min of reoxygenation; the remaining animals served as unchallenged controls. Radiolabeled microspheres were injected in all animals at times 0 min (baseline), 5 and 60 min (hypoxia), and 90 min (reoxygenation). Blood flows (mL/min/g tissue) to organs were determined using reference organ techniques. Control animals displayed no alterations in any of the variables monitored. Throughout the experimental period, organ blood flows were almost uniformly lower (p<.05, ANOVA) in premature versus term animals. The trend toward increased cerebral and cardiac blood flows during hypoxia observed in the premature piglets was similar to that of term animals, but of lower magnitude. In term piglets, hypoxia produced an immediate and significant (*p<.05) decline in small-intestinal blood flow followed by autoregulatory escape (2.02+/-0.17 mL/min/g at time 0, 1.56+/-0.15 mL/min/g at 5 min hypoxia, 1.88+/-0.18 mL/min/g at 60 min hypoxia, 2.26+/-0.19 mL/min/g at 30 min reoxygenation), an effect not readily observed in the premature piglets (0.48+/-0.10 mL/min/g at time 0, 0.44+/-0.07 mL/min/g at 5 min hypoxia, 0.46+/-0.10 mL/min/g at 60 min hypoxia, 0.42+/-0.08 mL/min/g at 30 min reoxygenation). However, mucosal blood flows measured in these younger animals declined throughout the experimental period to almost 50% of baseline, compared to a complete restoration to baseline blood flow observed following reoxygenation of term piglets. Intestinal blood flow in premature infants is small when compared to term animals, and alterations in small intestinal blood mucosal flow induced by hypoxia appear less well tolerated by the premature animals. Taken together, this may in part account for the increased risk of developing intestinal ischemic diseases in premature infants who are even temporarily exposed to a severe hypoxic challenge.

Alpha-trinositol reduces edema formation at the site of scald injury

BACKGROUND The effects of alpha-trinositol (1D-myo-inositol-1,2,6-triphosphate, IP3) on burn-induced edema formation were investigated. METHODS Lymph flow (QL; microliter/min) and lymph-to-plasma protein ratio (CL/CP) were monitored in groups of five to six dogs before and 4 hours after (1) a 5-second 100 degrees C or 90 degrees C foot paw scald; (2) IP3 (45 mg/kg intravenous bolus, then a 20 mg/kg/hr infusion) 30 minutes before or after 100 degrees C scald, or 30 minutes after 90 degrees C scald. Hind paw venous pressure was elevated and maintained by outflow restriction until reaching steady state QL and (CL/CP)min. Macromolecular reflection coefficient (1-CL/CP) was measured. Fluid filtration coefficient (Kf; ml/min/mm Hg/100 gm) was calculated. Relative paw weight gain (%) was measured. RESULTS Compared with preburn values, scald uniformly produced significant increases in QL, CL/CP, and Kf, IP3 significantly (p < 0.02, ANOVA) reduced paw weight gain when given before, but not after, 100 degrees C burn (41% +/- 5% versus 18% +/- 7% preburn IP3 and 31% +/- 3% postburn IP3). Compared with 90 degrees C burn animals, postburn treatment significantly (p < 0.017) attenuated 4-hour increases in QL (550 +/- 87 versus 252 +/- 29 microliters/min), Kf (0.016 +/- 00 versus 0.007 +/- 00 microliter/min/mm/Hg/100 gm), and relative paw weight gain (28% +/- 3% versus 12% +/- 5%). CONCLUSIONS alpha-Trinositol given after a 90 degrees C scald blunted edema formation at the site of scald, likely through reduced transmembrane fluid flux.

Dopexamine maintains mesenteric blood flow during systemic hypoxemia in the neonatal piglet

In adults, dopexamine is a specific dopaminergic and β2-adrenergic agonist; its effects in neonates are unknown. Ultrasonic flow probes were placed around the ascending and descending aorta and cranial mesenteric artery of 0- to 2-day-old and 2-week-old piglets. Animals of each age group (9 to 14 per group) were subjected to (1) dopexamine infusion (5 μg/kg/min); (2) 30 minutes of hypoxia (inspired oxygen content 0.12) followed by 30 minutes of reoxygenation; and (3) dopexamine infusion during hypoxia and reoxygenation. In both age groups dopexamine alone increased ascending aorta blood flow (cardiac output minus coronary artery blood flow), mildly decreased mean arterial pressure, and increased cranial mesenteric artery blood flow. Compared to baseline values, 30 minutes of hypoxia produced significant (P<0.05, analysis of variance) decreases in cranial mesenteric artery blood flow in 0- to 2-day-old (58±13 ml/min vs. 30±8 ml/min) and 2-week-old (125±18 ml/min vs. 60±11 ml/min) piglets. In all cases blood flow returned to baseline values after reoxygenation. In both animal groups treated with dopexamine before hypoxia, the decreases in cranial mesenteric artery blood flow were eliminated (47±5 ml/min vs. 44±6 ml/min in 0-to 2-day-old piglets; 140±27 ml/min vs. 117±18 ml/min in 2-week-old piglets). Dopexamine may prove to be of clinical benefit when neonates are threatened by hypoxemia-induced decreases in intestinal blood flow.

Effects of Anti-inflammatory Agents on Hydrochloric Acid-Induced Pulmonary Injury

To determine the effects of anti-inflammatory agents on hydrochloric acid lung injury, the heart and lungs were harvested from rats, placed in a lung chamber, constant flow perfused with whole blood, and ventilated. The following experiments were conducted: observation alone; intratracheal injection of normal saline; intratracheal hydrochloric acid; and intravenous meclofenamate or indomethacin before intratracheal hydrochloric acid. Wet-to-dry lung weights were measured. Peak airway pressures increased immediately (p < .001 vs. baseline; ANOVA) in all intratracheal groups, hydrochloric acid producing even greater (p < .05) increases than saline-effects unaltered by meclofenamate or indomethacin. The increased (p < .001 vs. baseline) 2-h pulmonary artery pressures in hydrochloric acid-treated groups were unaltered by meclofenamate or indomethacin. All hydrochloric acid-treated groups demonstrated increases (p < .05) in weight that were unchanged by meclofenamate or indomethacin. These data suggest that the beneficial effects of these medications described elsewhere, using a variety of in vivo lung injury experimental models, may be attributed to their experimental design, or to contributions from organs/systems outside the pulmonary circuit.

Serotonin receptors regulate canine regional vasodilator responses to burn.

OBJECTIVE To determine which serotoninergic receptor subtype(s) mediates the regional vasodilator response to scald injury. DESIGN Prospective, randomized trial. SETTING Microcirculation research laboratory. SUBJECTS Anesthetized dogs. INTERVENTIONS Mechanically ventilated dogs underwent cannulation of a brachial artery and placement of an ultrasonic flow probe around one femoral artery. All animals received a 2% to 3% body surface area partial thickness scald injury by immersing the paw ipsilateral to the instrumented femoral artery into 100 degrees C water for 5 secs. In one group of dogs, BMY 7378 (a serotoninergic1A receptor antagonist) was given by the peripheral intravenous route before burn. These results were compared with those findings obtained from a group of animals that received a burn only, and groups of animals given a peripheral intravenous injection of methysergide (a serotoninergic receptor antagonist) or ritanserin (a serotoninergic2 receptor blocking agent) before burn. Experiments were conducted for two postburn hours. MEASUREMENTS AND MAIN RESULTS Burn injury caused a marked and persistent increase in regional (e.g., femoral artery) blood flow, an effect that was significantly blunted by preburn administration of the serotoninergic receptor antagonist, methysergide. Preburn administration of BMY 7378 increased baseline femoral blood flow by 13%, reflecting its known serotonin agonist properties. However, when compared with the mean postscald increases in femoral blood flow over baseline seen in scald only dogs and in animals given the serotoninergic2 receptor blocking agent, ritanserin (before scald), the BMY 7378-treated group demonstrated a significant (p < .001 by analysis of variance) 2-hr-postscald blunting of this femoral vasodilator response. CONCLUSION These data suggest that serotoninergic1A-like receptors play an integral, albeit not an exclusive, role in blood flow regulation to the site of burn injury.

Indomethacin-induced reduction in neonatal piglet mesenteric blood flow is blunted by dopexamine

BACKGROUND Dopexamine is a specific dopaminergic and beta2-adrenergic agonist. Using newborn piglets, we have previously shown that (1) dopexamine increases cardiac output and mesenteric blood flow; (2) indomethacin reduces mesenteric blood flow. METHODS Ultrasonic blood flow probes were placed around the ascending aorta, cranial mesenteric artery, and a renal artery of 0 to 2-day-old and 2-week-old piglets. Animals of each age were grouped (5 to 8 animals per group) and subjected to one of three experimental protocols: (1) 0.4 mg/kg indomethacin infusion, (2) 10 microg/kg/min dopexamine infusion begun 10 minutes before indomethacin, or (3) no treatment. RESULTS Control animals demonstrated no significant alterations in mesenteric blood flow. Compared with baseline, indomethacin produced significant (P< .05, analysis of variance) declines in cranial mesenteric artery blood flow in 0 to 2-day old (37.2+/-5.7 mL/min v 17.9+/-3.7 mL/min at 90 min), and 2-week-old (80.2+/-12.5 mL/min v 29.7+/-5.7 mL/min at 90 minutes) piglets. In both animal groups treated with dopexamine before indomethacin, the decreases in cranial mesenteric artery blood flow were eliminated (38.4+/-7.6 mL/min at baseline v 36.5+/-6.8 mL/min at 90 minutes in 0 to 2 day olds; 79.9+/-10.0 mL/min at baseline v 77.5+/-14.7 mL/min in 2 week olds). Indomethacin-induced declines in renal blood flow were similarly abrogated by dopexamine. CONCLUSION Dopexamine may prove of clinical benefit when a neonate is considered a candidate for indomethacin therapy.

Characterization of α‐Adrenoceptor Activity in Term‐newborn Piglet Mesentery

For further characterization of neonatal mesenteric α1‐adrenoceptor populations, an extracorporeal perfusion circuit was established to control intestinal blood flow in 0‐2 day old piglets.

Characterization of α-adrenoceptor activity in the preterm piglet mesentery☆

Abstract To characterize neonatal mesenteric α-adrenoceptor populations, an extracorporeal perfusion circuit was established to control intestinal blood flow in prematurely delivered (by cesarean section at 90% of gestational age) piglets. Activation of α 1 -adrenoceptors was documented by observing dose-dependent increases in mesenteric perfusion pressure after intramesenteric arterial injection of methoxamine; α 2 -adrenoceptor activity was confirmed by finding similar increases in mesenteric perfusion pressure after intramesenteric arterial injections of BHT 933. Peripheral intravenous injections of WB 4101 (a competitive α 1A -adrenoceptor antagonist), but not clorethylclonidine (CEC, an α 1B -adrenoceptor antagonist), significantly blunted ( P 2 -adrenoceptor agonist) also was blunted by WB 4101, but not by CEC. These data suggest that α 1A - and α 2 -adrenoceptors can be activated in the small intestinal mesentery of piglets well before they reach full-term maturation, although receptor specificity has not been fully established.