ABSTRACT
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.
Subject(s)
Breast Neoplasms/diagnosis , Breast Self-Examination , Curriculum , Education, Medical, Undergraduate/methods , General Surgery/education , Clinical Competence , Educational Measurement , Female , Humans , Louisiana , Male , Reference ValuesABSTRACT
A severe hypoxic insult is known to induce dramatic reductions in newborn intestinal blood flow and is, thus, considered a vector for the development of neonatal intestinal ischemic diseases. Dopexamine (DPX) is a novel synthetic agent that has potent B2-adrenoceptor and dopaminergic activity, the clinical effects of which include an increase in cardiac output and in mesenteric blood flow. Having previously shown that infusion of DPX before hypoxia (HYP) mitigated the reduction in newborn mesenteric blood flow, we sought to define its efficacy when given after an established hypoxic insult. Ultrasonic transit time blood flow probes were placed around the ascending aorta and cranial mesenteric artery of anesthetized, mechanically ventilated 0 to 2-day-old piglets. Small bowel mucosal oxygenation was observed with a tissue oxygen monitoring system. After stabilization, animals were subjected to one of the following: HYP (FIO2 = 0.12) for 60 minutes (n = 12); DPX (5 microg/kg/min) infusion begun 10 minutes after induction of HYP/DPX (n = 11). Almost no alterations in any of the monitored variables were shown in a group (n = 5) of similarly instrumented, untreated animals. In contrast, although both hypoxic piglet groups experienced significant (P < 0.05, analysis of variance) declines from baseline cardiac output, mesenteric blood flow, and mucosal oxygenation, each of these deleterious effects was significantly (P < 0.05) blunted in the DPX-treated animals. During periods of systemic hypoxemia, the reductions in neonatal mesenteric blood flow and oxygenation can be somewhat blunted by DPX. As such, this agent may prove of clinical benefit when an infant is threatened by a hypoxic episode.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Dopamine Agonists/pharmacology , Dopamine/analogs & derivatives , Hypoxia/physiopathology , Intestinal Mucosa/physiopathology , Animals , Animals, Newborn , Disease Models, Animal , Dopamine/pharmacology , Intestinal Mucosa/drug effects , Mesentery/blood supply , Regional Blood Flow/drug effects , SwineABSTRACT
To determine whether vitamin C would alter burn induced edema accumulation, hind paw venous pressure, lymph flow (QL), and lymph-to-plasma protein ratio (CL/CP) were monitored in groups of 5 dogs before and 4 hours after 1) a 5 sec 100 degrees C or 90 degrees C foot paw scald; 2) intravenous vitamin C given 30 min before or after a 100 degrees C scald; and 3) vitamin C given 30 min after a 90 degrees C scald. Throughout the experiments, hind paw venous pressure was elevated and maintained by outflow restriction until steady state QL and (CL/CP)min were reached. Changes in protein permeability (CL/CP), fluid conductance properties (Kf) of the capillary membrane, and paw weight gain were determined. Compared with preburn values, scald uniformly produced significant (P < .05, ANOVA) increases in QL, CL/CP and Kf. Although preburn infusion of vitamin C significantly (P < .01) attenuated burn-induced increases in paw weight gain (36 +/- 3% vs 19 +/- 4%), neither of the groups that received vitamin C postburn experienced significant modulations in paw weight gain (28 +/- 4% vs 36 +/- 3% in 100 degrees C burn only; 23 +/- 4% vs 28 +/- 3% in 90 degrees C burn only) or in any of the variables used to monitor capillary membrane integrity. Vitamin C infusions initiated after graded scald produced no changes in the burn-induced increases in microvascular permeability or in edema formation measured at the injury site.
Subject(s)
Ascorbic Acid/therapeutic use , Burns/complications , Edema/prevention & control , Animals , Ascorbic Acid/administration & dosage , Capillary Permeability , Dogs , Hindlimb , Infusions, Intravenous , Time FactorsABSTRACT
Large surface-area burns in patients have been associated with a severe impairment in cardiac performance, as evidenced by a decline in cardiac output. The mechanisms responsible for this profound myocardial dysfunction are largely unknown. We investigated the effects of lymph isolated from the scalded hind limb of dogs on regional myocardial blood flow, coronary vascular reactivity, and contractile performance. Dogs were instrumented with ultrasonic dimension crystals in the myocardium supplied by the left anterior descending (LAD) and by the left circumflex (LCx) coronary arteries. After cannulating a hind limb lymphatic, lymph was infused directly into the LAD before and after a 10-second 100 degrees C hind limb scald. Scalding alone did not alter myocardial contractile performance in the LAD or LCx regions, coronary artery blood flow, or systemic hemodynamics. Interestingly, postburn lymph infused into the LAD resulted in a 38% decline in LAD zone segment shortening (p < 0.01 vs baseline) that lasted throughout the 5-hour observation period. In contrast, segment shortening in the (control) LCx region was unaffected by postburn lymph injections into the LAD. Regional myocardial blood flow (radiolabeled microspheres) in the LAD and LCx regions was unchanged after scald injury or intracoronary injection of postburn lymph. In addition, LAD coronary artery vascular reactivity to acetylcholine and nitroglycerin was also unaffected by the regional thermal injury or by injection of lymph into the LAD. These data suggest that a regional scald injury results in the production and release of a potent myocardial depressant factor(s) that produces a direct negative inotropic effect on the canine myocardium.
Subject(s)
Burns/metabolism , Coronary Vessels/drug effects , Lymph/chemistry , Myocardial Contraction/drug effects , Animals , Dogs , Hemodynamics/drug effects , Time Factors , Vasomotor System/drug effectsABSTRACT
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.
Subject(s)
Abdomen/surgery , Biocompatible Materials , Fasciotomy , Polypropylenes , Polyurethanes , Animals , Immunohistochemistry , Male , Peritonitis/etiology , Polytetrafluoroethylene , Rats , Rats, Sprague-Dawley , Tissue AdhesionsABSTRACT
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.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/antagonists & inhibitors , Dopamine/analogs & derivatives , Indomethacin/antagonists & inhibitors , Splanchnic Circulation/drug effects , Analysis of Variance , Animals , Animals, Newborn , Disease Models, Animal , Dopamine/pharmacology , Drug Interactions , Injections, Intravenous , Random Allocation , Reference Values , SwineABSTRACT
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.
Subject(s)
Abdominal Muscles/surgery , Biocompatible Materials , Hernia, Ventral/surgery , Polycarboxylate Cement , Prosthesis Implantation , Silicone Elastomers , Surgical Wound Infection/surgery , Suture Techniques , Urethane , Abdominal Muscles/pathology , Animals , Hernia, Ventral/pathology , Male , Polyethylenes , Polypropylenes , Polytetrafluoroethylene , Rats , Rats, Sprague-Dawley , Surgical Wound Infection/pathology , Wound Healing/physiologyABSTRACT
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.
Subject(s)
Hernia/diagnosis , Herniorrhaphy , Laparoscopy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Hernia, Inguinal/diagnosis , Hernia, Inguinal/surgery , Humans , Length of Stay , Male , Middle Aged , Pain, Postoperative/prevention & control , Postoperative Complications , Treatment OutcomeABSTRACT
Diagnostic peritoneal lavage (DPL) is often used to determine whether a blunt trauma victim has significant intra-abdominal hemorrhage. One bedside test (BT) historically recommended to evaluate DPL fluid is the ability to read newsprint through the fluid contained within intravenous (i.v.) tubing. Few experimental data support this practice. Two hundred eighteen traumatologists were queried regarding their use of BTs. In a related clinical study, blinded volunteers were asked to read print through various unmarked containers filled with simulated DPL fluid, created by adding aliquots of whole human blood to liter bags of lactated Ringer's solution. Of the 97 traumatologists who completed our preliminary survey, 60 per cent reported using a visual BT to assess DPL fluid. Of these surgeons, 44 per cent attempted to read newsprint through i.v. tubing. Our clinical study showed that more volunteers could read print through a red top tube (95%) when it contained a red cell concentration of 827 +/- 41/mm3 than the i.v. bag (4%). Nearly 70 per cent of volunteers were able to read print through the tubing containing 41,429 +/- 2,967 red blood cells (RBCs)/mm3. Regardless of the receptacle, readability was lost at RBC counts far below 100,000/mm3. Many traumatologists utilize BTs as an adjunct to clinical decision making. We conclude that, if the clinician can read print through lavage fluid within an i.v. bag, Vacutainer tube, or i.v. tubing, the DPL will be negative at cell count. However, inability to read print through i.v. tubing requires laboratory confirmation to document an RBC count > 100,000/mm3.
Subject(s)
Erythrocyte Count , Hemoperitoneum/diagnosis , Peritoneal Lavage , Point-of-Care Systems , Abdominal Injuries/complications , Analysis of Variance , Hemoperitoneum/etiology , Humans , Point-of-Care Systems/statistics & numerical data , Surveys and Questionnaires , Time FactorsABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Burns/drug therapy , Edema/prevention & control , Inositol Phosphates/therapeutic use , Analysis of Variance , Animals , Anti-Inflammatory Agents, Non-Steroidal/blood , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Blood Pressure , Burns/physiopathology , Capillaries/drug effects , Capillaries/physiopathology , Dogs , Edema/etiology , Hindlimb/blood supply , Inositol Phosphates/blood , Inositol Phosphates/pharmacokinetics , Lymph/drug effects , Lymph/physiology , Time FactorsABSTRACT
BACKGROUND: The purpose of this work was to determine the effects of hypoxemia on systemic hemodynamic variables and regional conduit arterial blood flows in neonatal piglets. MATERIALS AND METHODS: Using transit time blood flow probes, cardiac output and cranial mesenteric artery blood flow were monitored in groups of prematurely delivered (90% of term gestational age) and 2-week-old piglets prior to, during, and after exposure to a 30-min hypoxic (FIO2 = 0.12) challenge. RESULTS: The documented alterations in systemic mean arterial pressure and cardiac output pressure during hypoxia and reoxygenation were consistent with the maturational age of the animals. In response to hypoxia, all animals demonstrated significant reductions in mesenteric blood flow, with returns to baseline levels during the 30-min reoxygenation phase. In still other prematurely delivered piglets, nutrient mesenteric arterial blood flows were measured using in vivo videomicroscopy. The marked hypoxemia-induced decline in mucosal blood flow was reversed by reoxygenation. CONCLUSIONS: The physiologic mechanisms responsible for neonatal mesenteric vasoactive responsiveness are present in conduit and in nutrient vessels well prior to birth and can be activated by a significant perturbation. These observations are germane insofar as they provide a stable, age-matched acute animal model to study neonatal intestinal ischemic diseases, including necrotizing enterocolitis.
Subject(s)
Hypoxia/physiopathology , Splanchnic Circulation/physiology , Animals , Animals, Newborn , Blood Pressure , Cardiac Output , Disease Models, Animal , Enterocolitis, Necrotizing/physiopathology , Female , Humans , Infant, Newborn , Intestines/blood supply , Mesenteric Arteries/physiopathology , Microscopy, Video , Pregnancy , SwineABSTRACT
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.
Subject(s)
Burns/physiopathology , Hemodynamics , Lung/physiopathology , Lymph/physiology , Animals , Disease Models, Animal , Dogs , Male , Pulmonary Artery/physiopathology , Rats , Rats, Sprague-DawleyABSTRACT
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.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Dopamine Agonists/pharmacology , Dopamine/analogs & derivatives , Hypoxia/physiopathology , Splanchnic Circulation/drug effects , Adrenergic beta-2 Receptor Agonists , Animals , Animals, Newborn , Aorta , Blood Flow Velocity/drug effects , Blood Pressure/drug effects , Cardiac Output/drug effects , Dopamine/pharmacology , Dose-Response Relationship, Drug , Heart Rate/drug effects , Sus scrofaABSTRACT
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.
Subject(s)
Coronary Vessels/physiology , Peptides/physiology , Potassium Channels/physiology , Receptors, Purinergic P1/physiology , Vasodilation/physiology , Adamantane/analogs & derivatives , Adamantane/pharmacology , Adenosine Triphosphate/metabolism , Adrenomedullin , Animals , Calcitonin Gene-Related Peptide/pharmacology , Calcitonin Gene-Related Peptide Receptor Antagonists , Coronary Circulation/drug effects , Coronary Circulation/physiology , Coronary Vessels/drug effects , Dogs , Morpholines/pharmacology , Peptide Fragments/pharmacology , Peptides/administration & dosage , Peptides/pharmacology , Potassium Channels/drug effects , Receptors, Purinergic P1/drug effects , Vascular Resistance/drug effects , Vascular Resistance/physiology , Vasodilation/drug effects , Xanthines/pharmacologyABSTRACT
For further characterization of neonatal mesenteric alpha 1-adrenoceptor populations, an extracorporeal perfusion circuit was established to control intestinal blood flow in 0-2 day old piglets. Activation of alpha 1-adrenoceptors was first documented by observing dose-dependent increases in mesenteric perfusion pressure after intra-mesenteric arterial injection of methoxamine and noradrenaline. Peripheral intravenous injections of WB 4101 (a competitive alpha 1A-adrenoceptor antagonist), but not clorethylclonidine (CEC, an alpha 1B-adrenoceptor antagonist), significantly (P < 0.05, analysis of variance) blunted mesenteric vasoconstrictor responses to those agonists. That the mesenteric vasoconstrictor response to mesenteric plexus stimulation was unaltered by CEC, but was muted by both WB 4101 and SK&F 104856 (a post-junctional alpha 1- and alpha 2-adrenoceptor antagonist) suggests that pre- and post-junctional alpha 1A-adrenoceptors are present and functional at birth.
Subject(s)
Animals, Newborn/physiology , Mesenteric Arteries/physiology , Receptors, Adrenergic, alpha/physiology , Animals , Benzazepines/pharmacology , Clonidine/analogs & derivatives , Clonidine/pharmacology , Dioxanes/pharmacology , Female , Male , Mesenteric Arteries/drug effects , Swine , Vasoconstriction/drug effectsABSTRACT
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.
Subject(s)
Mesenteric Arteries/metabolism , Receptors, Adrenergic, alpha/metabolism , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Animals , Animals, Newborn , Azepines/pharmacology , Dioxanes/pharmacology , Female , Fetal Organ Maturity/physiology , Mesenteric Arteries/drug effects , Mesenteric Arteries/embryology , Methoxamine/pharmacology , Perfusion , Pregnancy , Pressure , Receptors, Adrenergic, alpha/physiology , Swine , Vasoconstriction/drug effectsABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Hydrochloric Acid/adverse effects , Indomethacin/pharmacology , Meclofenamic Acid/pharmacology , Pneumonia, Aspiration/chemically induced , Acute Disease , Animals , Cardiac Output , In Vitro Techniques , Male , Perfusion , Pulmonary Wedge Pressure , Rats , Rats, Sprague-Dawley , Respiration , Respiratory Mechanics/physiology , Time FactorsABSTRACT
To characterize the mesenteric alpha1- and alpha2-adrenoceptor populations in newborn piglets, an extracorporeal circuit was established to control intestinal blood flow in 0- to 2-day old and 10- to 14-day old animals. In both groups, alpha-adrenoceptor activation was first documented by observing dose-dependent increases in mesenteric perfusion pressure after intramesenteric arterial injection of alpha-adrenoceptor agonists. In the 10- to 14-day old piglets, mesenteric vasoconstrictor responses to alpha1-adrenoceptor agonists (methoxamine and norepinephrine) and an alpha2-adrenoceptor agonist (BHT-933) were each blunted (P < 0.05, analysis of variance) by peripheral intravenous injections of prazosin (an alpha1-adrenoceptor antagonist) and yohimbine (an alpha2-adrenoceptor antagonist), respectively. The mesenteric vasoconstrictor responses to those agonists were not significantly attenuated by prazosin or yohimbine in 0- to 2-day old animals, nor were they blunted by YM-12617 (alpha1-adrenoceptor antagonist) or idazoxan (alpha2-adrenoceptor antagonist)--compounds that are structurally unrelated to prazosin and yohimbine, respectively. In addition, mesenteric vasoconstrictor responses to other known vasoconstrictor agents--angiotensin II, neuropeptide Y, and a thromboxane A2 mimic (U-46619)--were not effected in either age group by prazosin or yohimbine, implying these agents act independently of alpha-adrenoceptor mechanisms. These data suggest that (1) there exists functional mesenteric alpha1- and alpha2-adrenoceptor-like activity in 10- to 14-day old piglets that, in 0- to 2-day old animals, is not specifically expressed; and (2) mesenteric alpha-adrenoceptor function becomes more selective as newborn piglets mature.
Subject(s)
Animals, Newborn/physiology , Mesenteric Arteries/physiology , Receptors, Adrenergic, alpha/physiology , Age Factors , Animals , Female , Male , Prazosin/pharmacology , Swine , Vasoconstriction/drug effects , Yohimbine/pharmacologyABSTRACT
To determine the extent to which edema modulation by methysergide is due to a blunting of the regional vasodilator response to scald and/or local reduction of transvascular fluid flux, a canine hind limb lymphatic was cannulated. Femoral blood flow (Qa; ml/min), lymph flow (QL; microliter/min/100 g), and lymph-to-plasma protein ratios (CL/CP) were monitored in groups of five dogs before and 4 hr after 5-sec, 100 degrees C foot paw scald; high (1.0 mg/kg) or low (.5 mg/kg) dose of methysergide 30 min before scald. The compression on a clamp placed around the femoral artery in other dogs was adjusted after scald to simulate the blunting effect on Qa observed in methysergide treated dogs. Hind leg venous pressure was elevated to approximately = 40 mm Hg before experimentation until steady state QL and (CL/CP)min were reached. Protein reflection coefficient (sigma d; 1-C1/ CP) and fluid filtration coefficient (Kf) were calculated. Compared to preburn values, all groups showed significant (P < 0.002, analysis of variance) increases in CL/CP and Kf. Contrasted with the burn only group, methysergide blunted increases in Qa, Kf and paw weight gain in a dose-dependent fashion, with no effect on the reflection coefficient. Compression clamp control of femoral Qa caused no effects on permeability. Methysergide limits burn edema in a dose-related fashion, though not due to a blunting of the regional vasodilator response. Local, not regional, mechanism(s) likely mediate this response.
Subject(s)
Burns/complications , Edema/drug therapy , Edema/etiology , Methysergide/therapeutic use , Vasodilation/drug effects , Animals , Body Fluids/metabolism , Burns/physiopathology , Capillary Permeability , Constriction , Dogs , Dose-Response Relationship, Drug , Hemodynamics , Lymph/physiologyABSTRACT
BACKGROUND: This study was undertaken to compare the efficacy of a novel synthetic material (TMS-1) with polytetrafluoroethylene, polypropylene, and primary closure of experimentally fashioned clean and contaminated abdominal wounds. METHODS: One square centimeter full-thickness abdominal wall defects were created in each of the four abdominal quadrants of anesthetized rats (n = 6). Patches of polytetrafluoroethylene, polypropylene, and a polyurethane-polypropylene composite material (TMS-1) were used to repair three of these defects; the fourth was primarily closed. A second group of rats (n = 9) underwent the same operative protocol; however, peritonitis was induced at the time of operation by using the fecal inoculation technique. Animals were killed 2 to 3 weeks later, and surface area and severity of formed adhesions were assessed. RESULTS: By all methods of assessment, primary closure proved significantly superior to all other methods of closure in clean and contaminated conditions. The three synthetic materials were equally matched for surface area involved in adhesion formation. When compared with the other synthetic materials, TMS-1 was associated with significantly milder adhesions in uninfected (p < 0.002) and in infected (p < 0.002) conditions. CONCLUSIONS: The clear superiority of TMS-1 over other nonabsorbable synthetic materials shown in this pilot study warrants further investigation relative to its use to close large abdominal wall defects.