Outcomes of surgical management of total colonic aganglionosis.

PURPOSE: The purpose of this study was to assess the long-term clinical outcomes and bowel function of patients with total colonic aganglionosis (TCA) after surgery. METHODS: The hospital records of 17 TCA patients treated surgically during 1985 to 2004 were reviewed. Long-term follow-up was done by telephone interviews with the parents. RESULTS: Primary enterostomy was performed in 13 (76%) patients. In three (17%) patients, TCA was not suspected initially. They underwent conservative surgery primarily, which required a second operation soon after. One had transverse colectomy with ileostomy. By pathologic review, nine (53%) patients had small bowel involvement of aganglionosis. Six (35%) patients died before corrective surgery. They all had extensive small bowel involvement. Among 11 patients who had a corrective operation, 10 were treated with Martin's procedure. Long-term (mean 74 months) follow-up was available in seven patients, and the mean weight-for-age percentiles was 27.1% (range 5-50%), the frequency of defecation was three to five times a day in four patients (57%), one or two times a day in two patients (28%), and more than five times a day in one patient (15%). CONCLUSIONS: TCA is difficult to diagnose; but once it is diagnosed correctly and treated by corrective surgery, outcomes seem promising. Martin's operation brought about a good outcome and enabled patients to have acceptable bowel habits. The prognosis is highly dependent on the extent of aganglionosis.

Singlet oxygen quenching effects of phosphatidylcholine in emulsion containing sunflower oil.

Effects of phosphatidylcholine (PC) on the oxidation of oil by singlet oxygen in a W/O microemulsion and an emulsion food model containing tocopherol-stripped sunflower oil (TSSO) have been studied. The W/O microemulsion consisted of methylene chloride, butanol, and sodium dodecyl sulfate with PC (0, 250, 1000 ppm) and TSSO (0, 3.3, 16.5, 33 mg/mL). Production of singlet oxygen in the microemulsion was done chemically with hydrogen peroxide in the presence of sodium molybdate, and indirectly evaluated by rubrene oxidation at A529. The emulsion food model consisted of TSSO, distilled water, and xanthan gum with addition of 250 ppm PC and 4 ppm chlorophyll b, and was placed at 25 degrees C under fluorescent lights (1700 lux) for 24 h. The oxidation of TSSO was determined by thin-layer chromatography and values of conjugated dienoic acid (CDA) and peroxides (POV). PC significantly decreased the oxidation of rubrene and TSSO in the W/O microemulsion, but its content was decreased to approximately one-half by a 20-min reaction, indicating its degradation. This clearly shows that PC acted as an antioxidant via chemical quenching of singlet oxygen in the W/O microemulsion. A possible synergism between PC and TSSO was observed in singlet oxygen quenching in the microemulsion. PC also significantly decreased the chlorophyll-photosensitized oxidation of TSSO in the emulsion food model, possibly by singlet oxygen quenching. This study clearly suggested that PC be used as an antioxidant to improve the lipid oxidative stability of an emulsion food containing chlorophyll under light.

Oxidation of corn oil during frying of soy-flour-added flour dough.

Oxidation of corn oil during frying of soy-flour-added dough was studied. Flour dough containing soy flour at 0%, 10%, 20%, and 30% was fried in corn oil at 180 degrees C for 2.5 min, and a total of 60 fryings were performed every 30 min. The oxidation of oil was determined by contents of free fatty acids (FFA), conjugated dienoic acids (CDA), polar compounds, and p-anisidine values (PAV). Tocopherols and phospholipids (PLs) in the oil were determined by HPLC. Tocopherols were present in corn oil at 1000 ppm before frying and increased after the first frying of dough containing soy flour due to tocopherol transfer from soy-flour-added dough to the oil during frying. However, as the oil repeated frying, tocopherol contents decreased and its degradation rate was higher in the oil that fried soy-flour-added dough than in the oil that fried the dough without soy flour. PL was not detected in corn oil before and after frying. As the oil repeated frying, FFA, CDA, and polar compounds contents, and PAV of frying oil increased due to the oil oxidation. The values were higher in the oil which fried soy-flour-added dough than in the oil fried the dough without soy flour, indicating the acceleration of oil oxidation by soy flour added to dough. Increase in the oil oxidation by soy flour added to the dough was highly correlated with fast decomposition of tocopherol in the oil.

Group I metabotropic glutamate receptor activation increases phosphorylation of cAMP response element-binding protein, Elk-1, and extracellular signal-regulated kinases in rat dorsal striatum.

Cyclic AMP response element-binding protein (CREB) is a major transcriptional activator at the calcium and cAMP response-element (CaCRE). Phosphorylated (p)CREB facilitates gene expression in striatal neurons. Elk-1 is another transcriptional regulator at the serum response element in the upstream promoter region of the CaCRE. Elk-1 is phosphorylated by extracellular signal-regulated kinases (ERK) and may also contribute to the regulation of gene expression. To evaluate putative roles of group I metabotropic glutamate receptors (mGluRs) in CREB, Elk-1, and ERK phosphorylation, the group I selective agonist, 3,5-dihydroxyphenylglycine (DHPG), was infused into the dorsal striatum at doses of 125, 250, or 500 nmol in freely moving rats. Semi-quantitative immunohistochemistry demonstrated that DHPG significantly increased levels of pCREB, pElk-1, and pERK immunoreactivity of ipsilateral dorsal striatum in a dose dependent manner. The increased immunoreactivity by 500 nmol DHPG was significantly blocked by intrastriatal infusion of the group I selective antagonist, n-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC, 25 nmol), but not by the group II/III antagonist, (RS)-alpha-methylserine-o-phosphate monophenyl ester (MSOPPE, 25 nmol). These data suggest that group I mGluR activation is positively linked to signaling cascades resulting in CREB, Elk-1, and ERK phosphorylation in the striatum in vivo.

Group I metabotropic glutamate receptors control phosphorylation of CREB, Elk-1 and ERK via a CaMKII-dependent pathway in rat striatum.

In vivo activation of group I metabotropic glutamate receptors (mGluRs) upregulates phosphorylation of cyclic AMP response element-binding protein (CREB), Elk-1 and extracellular signal-regulated kinases (ERK) in striatal neurons. To evaluate putative roles of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in CREB, Elk-1 and ERK phosphorylation, the CaMKII inhibitor, KN62, was infused simultaneously with the group I mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG), into the rat dorsal striatum. The results showed that DHPG (125, 250, and 500 nmol) increased phosphorylated (p) CaMKII immunoreactivity (IR) in a dose-dependent manner. KN62 (50 nmol) significantly attenuated 500 nmol DHPG-induced pERK, pElk-1 and pCREB IR in the ipsilateral dorsal striatum. These data indicate that pCaMKII is a possible upstream effector that is responsible for the regulation of CREB, Elk-1 and ERK phosphoproteins in response to group I mGluR stimulation in striatal neurons.

Cyclic AMP and mitogen-activated protein kinases are required for glutamate-dependent cyclic AMP response element binding protein and Elk-1 phosphorylation in the dorsal striatum in vivo.

Dopaminergic and glutamatergic signalling cascades are integrated in striatal medium spiny neurones by cyclic AMP response-element binding protein and Elk-1 phosphorylation. Phosphorylated cyclic AMP response-element binding protein and phosphorylated Elk-1 contribute to c-fos expression by binding to the calcium and cyclic AMP response-element and the serum response element, respectively, in the c-fos promoter. The role of cyclic AMP and mitogen-activated protein kinase signalling cascades in glutamate-induced cyclic AMP response-element binding protein and Elk-1 phosphorylation and Fos expression was investigated using semiquantitative immunocytochemistry in vivo. Intracerebroventricular infusion of the sodium channel blocker, tetrodotoxin, decreased the glutamate-induced increase in phosphorylated cyclic AMP response-element binding protein, phosphorylated Elk-1, and Fos immunoreactivity. Intracerebroventricular infusion of the mitogen-activated and extracellular signal-regulated kinase inhibitor, PD98059, the p38 mitogen-activated protein kinase inhibitor, SB203580, or the cyclic AMP inhibitor, Rp-8-Br-cAMPS, decreased glutamate-induced phosphorylated cyclic AMP response-element binding protein, phosphorylated Elk-1, and Fos immunoreactivity. Simultaneous infusion of glutamate and Sp-8-Br-cAMPS, a cyclic AMP analogue, augmented induction of Fos immunoreactivity but not phosphorylated cyclic AMP response-element binding protein or phosphorylated Elk-1 immunoreactivity. These data indicate that cyclic AMP and mitogen-activated protein kinase signalling cascades are necessary for glutamate to induce cyclic AMP response-element binding protein and Elk-1 phosphorylation and Fos expression in the striatum. Furthermore, neuronal activity plays an important role in glutamate-induced signalling cascades in vivo.

N-Methyl-D-aspartate receptors and p38 mitogen-activated protein kinase are required for cAMP-dependent cyclase response element binding protein and Elk-1 phosphorylation in the striatum.

In vivo cyclic adenosine monophosphate (cAMP)-induced N-methyl-D-aspartate receptor and mitogen-activated protein kinase activation was investigated in the dorsal striatum by semiquantitative immunocytochemistry. Intracerebroventricular infusion of 8-bromo-adenosine 3',5'-cyclic monophosphorothioate, Sp isomer (Sp-8-Br-cAMPS), increased phosphorylated cAMP-responsive element binding protein, phosphorylated Elk-1 and Fos immunoreactivity in a dose-dependent manner. Intracerebroventricular infusion of the N-methyl-D-aspartate antagonist, MK801, decreased, but tetrodotoxin or the mitogen-activated extracellular-regulated kinase inhibitor, PD98059, did not affect Sp-8-Br-cAMPS-induced phosphorylated c-AMP-responsive element binding protein, phosphorylated Elk-1, phosphorylated extracellular-signal-regulated kinase and Fos immunoreactivity. The p38 mitogen-activated protein kinase inhibitor, SB203580, decreased the Sp-8-Br-cAMPS-induced increase in all markers, except phosphorylated extracellular-signal-regulated kinase, in a dose-dependent manner. We suggest that N-methyl-D-aspartate receptors couple c-AMP to phosphorylation events and immediate early gene induction in the nucleus of striatal medium spiny neurons. These events are mediated by crosstalk between protein kinase A and mitogen-activated protein kinase cascades in vivo.

Training in clinical breast examination as part of a general surgery core curriculum.

BACKGROUND: Early detection of breast cancer relies on a multidisciplinary approach that includes patient breast self-examination, radiographic studies, and clinical breast examination (CBE). This study was undertaken to assess the value of formal CBE instruction by the surgery department using solicone breast models. METHODS: Thirty students were randomized in their first week of junior surgical clerkship to undergo or forgo a one-hour CBE retraining session. They were subsequently evaluated on technical competence and the ability to detect masses in an opaque silicone breast model. These skills were reassessed one month later. RESULTS: The students who underwent the teaching session performed significantly better than the control group in both the early (scores 1.23 vs 2.67, p < 0.05) and the late (scores 0.15 vs 2.14, p < 0.05) testing sessions. CONCLUSIONS: These data suggest significant improvement in CBE in students receiving formalized instruction. Further evaluation is needed prior to incorporation of this technique into the surgery core curriculum.

Bax, but not Bcl-xL, decreases the lifetime of planar phospholipid bilayer membranes at subnanomolar concentrations.

Release of proteins through the outer mitochondrial membrane can be a critical step in apoptosis, and the localization of apoptosis-regulating Bcl-2 family members there suggests they control this process. We used planar phospholipid membranes to test the effect of full-length Bax and Bcl-xL synthesized in vitro and native Bax purified from bovine thymocytes. Instead of forming pores with reproducible conductance levels expected for ionic channels, Bax, but not Bcl-xL, created arbitrary and continuously variable changes in membrane permeability and decreased the stability of the membrane, regardless of whether the source of the protein was synthetic or native. This breakdown of the membrane permeability barrier and destabilization of the bilayer was quantified by using membrane lifetime measurements. Bax decreased membrane lifetime in a voltage- and concentration-dependent manner. Bcl-xL did not protect against Bax-induced membrane destabilization, supporting the idea that these two proteins function independently. Corresponding to a physical theory for lipidic pore formation, Bax potently diminished the linear tension of the membrane (i.e., the energy required to form the edge of a new pore). We suggest that Bax acts directly by destabilizing the lipid bilayer structure of the outer mitochondrial membrane, promoting the formation of a pore-the apoptotic pore-large enough to allow mitochondrial proteins such as cytochrome c to be released into the cytosol. Bax could then enter and permeabilize the inner mitochondrial membrane through the same hole.

Efficacy of a novel synthetic material to close exposed fascial defects.

BACKGROUND: After developing a synthetic composite material (TMS-1) made from a porous polypropylene mesh (placed in apposition to fascia) coated on the "visceral" side with solid polyurethane, we compared its efficacy with that of porous polytetrafluoroethylene, polypropylene, and primary fascial closure when the repairs were left exposed to the environment. METHODS: We created 1 cm2 abdominal wall defects in each of the four abdominal quadrants of rats (n = 12). We used porous polytetrafluoroethylene, polypropylene, and TMS-1 to repair three defects; the fourth we primarily closed. The skin was left open in all cases, leaving the fascial closures exposed. A second group of rats (n = 24) had the same operation, except that peritonitis was induced using a standard fecal inoculation technique. When the rats were killed 2 weeks later, a "blinded" observer using a standard scale assessed the surface area and severity of adhesions formed. RESULTS: When compared with the other synthetic materials, the surface area of adhesions formed was significantly less after primary closure in clean conditions; in contaminated conditions, it was less than porous polytetrafluoroethylene, polypropylene, and the same as TMS-1. Furthermore, in contaminated conditions, the severity of adhesions beneath TMS-1 was the same as primary closure and significantly less than those beneath the polypropylene. CONCLUSION: The overall superiority of TMS-1 over porous polytetrafluoroethylene and polypropylene in septic conditions justifies further experiments to define its long-term efficacy in the repair of large defects.

Comparison of novel synthetic materials with traditional methods to repair exposed abdominal wall fascial defects.

Repair of large abdominal wall defects is a challenge, particularly when full-thickness tissue loss prohibits coverage of the fascial repair. Two novel synthetic materials (TMS-1 and TMS-2) have been shown to be better accepted than expanded polytetrafluoroethylene (Gore-Tex), and polypropylene (Marlex) in the closure of clean and contaminated fascial wounds that are immediately covered by skin/soft tissue. Therefore, 1-cm2 abdominal wall defects were created in each of the four quadrants of rat groups. Gore-Tex, Marlex, and TMS-1 or TMS-2 were used to repair three defects, the fourth being primarily closed. To ensure that each repair remained exposed, skin edges were sutured to underlying muscle. Additional animal groups underwent the same protocol; however, peritonitis was induced at surgery using a fecal inoculum technique. Animals were sacrificed 2 weeks later, at which time a blinded observer assessed the surface area and severity of adhesions. In clean wounds, the surface area of formed adhesions was less (p < .004) after primary closure than each synthetic material; among the synthetics, TMS-2 caused significantly (p < .01) less extensive adhesions than Marlex. In addition, the severity of adhesions to TMS-2 was comparable to that of defects closed primarily, and less severe (p < .02) than those formed to Gore-Tex and Marlex. In animals with peritonitis, primary closure caused less extensive (p < .03) adhesions than Marlex and Gore-Tex and significantly (p < .002) less severe adhesions than Marlex, Gore-Tex, and TMS-2. However, the severity of adhesions formed to TMS-1 repairs proved comparable to primarily closed wounds. These experiments reaffirm the tenet that, whenever possible, abdominal wounds should undergo primary fascial closure. When soft tissue coverage over the repair cannot be achieved, TMS-2 is well tolerated in clean wounds. However, the superiority of TMS-1 over the other synthetic materials in contaminated wounds suggests it may also ultimately prove to be of clinical utility.

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.

Development of a novel synthetic material to close abdominal wall defects.

To compare the efficacy of a novel synthetic material (TMS-2) with polytetrafluoroethylene, polypropylene (Marlex), and primary closure of experimentally fashioned clean and contaminated abdominal wounds, 1-cm2 abdominal wall defects were created in each of the four abdominal quadrants of rats (n = 10). Patches of each material were used to repair three of these defects, the fourth being primarily closed. A second group of rats (n = 7) underwent the same operative protocol; however, peritonitis was induced at the time of surgery using a fecal inoculation technique. Animals were killed 2 weeks later, and surface area and severity of formed adhesions were assessed by a "blinded" observer. All closure techniques were successful insofar as none demonstrated fascial dehiscence. Compared with each synthetic material, the surface area of formed adhesions was smaller after primary closure in clean and in contaminated conditions; however, the three synthetic materials were equally matched regarding surface area of adhesions under both conditions. In the face of fecal contamination, TMS-2 proved identical to primary closure, each generating significantly (P < 0.02) milder adhesions than the other prosthetic materials. It is concluded that the TMS-2 may prove of clinical benefit to repair abdominal wall defects.

The incidence of secondary hernias diagnosed during laparoscopic total extraperitoneal inguinal herniorrhaphy.

During a 24-month period beginning in July of 1995, laparoscopic total extraperitoneal inguinal herniorrhaphy was attempted in 53 patients. All procedures were performed at a single institution, by senior-level general surgery residents, with the same attending surgeon functioning as first assistant. Three patients required conversion to an "open" procedure (all had a prior history of herniorrhaphy or lower abdominal surgery), leaving 50 patients for analysis. Preoperatively, a unilateral hernia was evident on clinical grounds in 29 patients, the remaining 21 presenting with signs of a bilateral hernia; of the total, 11 had a history of prior hernia repair on the presently affected side. At surgery, a total of 115 hernia defects (indirect, direct, femoral) were identified, 38% of which were discovered only at the time of surgery. Sixty-four percent of patients were found to have at least one of these "secondary" hernias. After reduction of the hernia(s), all defects were covered with polypropylene mesh secured with spiral tacks. There were 10 perioperative complications, one of which required corrective surgical intervention. Over 70% of patients were discharged on the day of surgery; 92% returned home within 23 h of their operation. The most common reason for delay of hospital discharge was urinary retention. There have been no recurrences in short-term follow-up. Most patients were pleased with the recovery time from and the cosmetic results of their surgery. These results suggest that laparoscopic total extraperitoneal herniorrhaphy represents a safe, effective, cosmetically appealing alternative to open hernia repair. Moreover, this approach may provide an added advantage insofar as identifying additional hernia defects that, when repaired, may ultimately yield a lower recurrence rate than might otherwise have been expected.

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 Beta2-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 microg/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.

Adrenomedullin mediates coronary vasodilation through adenosine receptors and KATP channels.

The following experiments were conducted to determine whether, and the mechanisms through which, endogenous peptides alter coronary artery blood flow. Ultrasonic transit time probes were placed around the ascending aorta and left anterior descending coronary artery in groups of anesthetized, open-chest dogs. A Millar pressure catheter monitored left ventricular developed pressure. Intracoronary artery bolus injections of adenosine (a purinergic receptor activator), pinacidil (a KATP channel activator), calcitonin gene-related peptide (CGRP; which causes vascular smooth muscle relaxation by intracellular increases in cyclic-AMP), and adrenomedullin (mechanism unknown) each significantly (P < 0.05, Student's t test) increased coronary blood flow in a dose-dependent fashion, without altering systemic hemodynamic measurements. Intracoronary artery injection of U37883A (a KATP channel antagonist) significantly (P < 0.05) blocked the coronary vasodilator responses to adenosine, adrenomedullin, and pinacidil. Intracoronary xanthine amine congener (an adenosine receptor antagonist) blocked only the responses to adenosine and adrenomedullin, not pinacidil. Intracoronary CGRP8-37 (CGRP receptor antagonist) blocked only the vasodilator response to CGRP. These data suggest that the coronary vasodilator effect of adrenomedullin is initiated first by activation of adenosine receptors, and subsequently through KATP channels-not by activation of CGRP receptors. That there were no changes in left ventricular developed pressure or in systemic hemodynamics after intracoronary artery infusions of adrenomedullin indicates that this endogenous peptide may have clinical utility in facilitating myocardial protection or preconditioning.

Characterization of alpha-adrenoceptor activity in the preterm piglet mesentery.

To characterize neonatal mesenteric alpha-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 alpha 1-adrenoceptors was documented by observing dose-dependent increases in mesenteric perfusion pressure after intramesenteric arterial injection of methoxamine; alpha 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 alpha 1A-adrenoceptor antagonist), but not clorethylclonidine (CEC, an alpha 1B-adrenoceptor antagonist), significantly blunted (P < .05, ANOVA) the mesenteric vasoconstrictor responses to methoxamine. The mesenteric vasoconstrictor response to BHT 933 (an alpha 2-adrenoceptor agonist) also was blunted by WB 4101, but not by CEC. These data suggest that alpha 1A- and alpha 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.

Dopexamine prevents depression of mesenteric blood flow caused by positive end-expiratory pressure in rats.

BACKGROUND: The purpose of this study was to investigate the effects of two vasoactive agents, dopamine and dopexamine, on the depression of mesenteric blood flow caused by positive end-expiratory pressure (PEEP) during mechanical ventilation. METHODS: Sprague-Dawley rats were mechanically ventilated with either no PEEP (control group) or increasing levels of PEEP (PEEP group) up to 20 cm H2O pressure. We evaluated PEEP's effect on blood pressure, cardiac output (CO), and the mesenteric microcirculation with a continuous infusion of 2.5 or 12.5 micrograms/kg/min dopamine or 1, 3, or 5 micrograms/kg/min dopexamine. RESULTS: PEEP caused a 20% to 25% decrease in mean arterial pressure and a 30% decrease in CO at both 15 and 20 cm H2O of PEEP (all p < 0.05 versus baseline). Low dose dopamine partially corrected the decrease in CO to 16% and 21% below baseline at 15 and 20 cm H2O of PEEP, respectively (both p < 0.05 versus PEEP group) and partially ameliorated the depression of mesenteric blood flow associated with the application of PEEP. High dose dopamine did not positively affect either CO or mesenteric blood flow. Dopexamine had little effect on CO compared with dopamine. All three doses of dopexamine blocked the effect of PEEP on mesenteric blood flow (p < 0.05 compared with the PEEP group at all levels of PEEP, p < 0.05 compared with the low dose dopamine group at 15 and 20 cm H2O of PEEP). CONCLUSIONS: Dopexamine is superior to dopamine in protecting mesenteric blood flow in the face of increasing levels of PEEP.

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.