Search PubMed⌕ Search

Biomedical subjects

L M Flint

Publications and source records attributed to L M Flint.

At least 37 records · Page 2Linked to original sources
PubMed1997

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.

Adamantane↗
PubMed1997

Mild preischemia hypothermia adversely affects postischemic myocardial function in the neonatal piglet heart.

BACKGROUND: During cardiac surgery, operative hypothermia has been shown to be beneficial in certain situations, although in children perioperative hypothermia has been associated with several physiologic alterations that have proven detrimental to their postoperative function. Little attention has been given to the effects of mild (34.5 degrees C) perioperative hypothermia on postischemic myocardial function in the pediatric population. It was hypothesized that mild hypothermia would be detrimental to postischemic ventricular function in the neonatal heart. METHODS: Neonatal (0-2 days old) piglets were subjected to mild perioperative hypothermia without rewarming (HT-only, n = 6), hypothermia followed by rewarming (HT-RW, n = 6), or continuous normothermia (NT, n = 8). The hearts were rapidly excised, suspended on an isolated perfusion apparatus, and allowed to spontaneously beat while being perfused with an asanguinous solution. All hearts were subjected to 20 min global, normothermic, zero-flow ischemia followed by 45 min oxygenated crystallite buffer reperfusion (I-R). RESULTS: Compared to that of NT piglets, there were significant (P < 0.05) reductions in recovery of left ventricular (LV) diastolic and systolic function following ischemia and reperfusion in HT-RW animals. When the hearts were rendered ischemic without first rewarming, the degree of myocardial dysfunction was not as severe. In contrast to the NT piglets, HT-RW animals demonstrated significant (P < 0.05) reductions in the final recovery of LV developed pressure (71 +/- 6 vs 105 +/- 6 in NT), LV rate pressure product (52 +/- 4 vs 102 +/- 9 NT), and LV end diastolic pressure (32 +/- 7 vs 3 +/- 1 in NT) following I-R. When compared to the HT-RW group, HT-only piglets did not exhibit significant differences in systolic function, although diastolic function was minimally altered initially as evidenced by the slight elevation of LV end diastolic pressure at 5 min, with reperfusion in the HT-only group (P < 0.05). CONCLUSIONS: In this newborn piglet model, mild hypothermia significantly reduces recovery of systolic and diastolic left ventricular function when followed by an episode of global myocardial ischemia-reperfusion only when the animals are returned to normothermia prior to the ischemic insult. When hypothermia is immediately followed by the ischemic event, left ventricular function is unaffected.

Animals↗
PubMed1997

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.

Animals↗
PubMed1996

Burn edema reduction by methysergide is not due to control of regional vasodilation.

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.

Animals↗
PubMed1996

Effect of maturation on alpha-adrenoceptor activity in newborn piglet mesentery.

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.

Age Factors↗
PubMed1996

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.

Adrenergic alpha-Agonists↗
PubMed1996

Evaluation of a novel synthetic material for closure of large abdominal wall defects.

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.

Abdominal Muscles↗
PubMed1996

Characterization of alpha-adrenoceptor activity in term-newborn piglet mesentery.

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.

Animals↗
PubMed1996

Iatrogenic esophageal pseudodiverticulum: a case report.

Iatrogenic injury of the esophagus is not an uncommon complication of diagnostic endoscopy and dilation. Herein is described what is felt to be the first reported case of a traumatic pseudodiverticulum after dilation of an esophageal stricture. The management of what was preoperatively felt to be an esophageal perforation is discussed.

Aged↗
PubMed1996

Small bowel necrosis in association with jejunostomy tube feedings.

Nutritional support is thought to be an important adjunct for minimizing perioperative morbidity. For a variety of reasons, it is now felt that nutrition delivered by the enteral route is preferred over that given parenterally. Although delivery of nutrients into the small intestine, either via a nasoduodenal tube or a surgically placed jejunostomy, is effectively tolerated by most patients, morbid complications are being described with increased frequency. Herein, we describe two patients who underwent major intra-abdominal surgery, one for a malignancy, the other for trauma management. Immediate postoperative feedings were instituted through a surgically placed jejunostomy tube. Several days later, each patient underwent emergency reoperation for clinical findings of an intra-abdominal catastrophe. In both patients, small intestinal infarction in juxtaposition to the site of the tube feedings was found. This experience suggests that the enteral feedings were causally related to this morbid complication, which proved fatal in one patient.

Adult↗
PubMed1995

Polypropylene mesh closure of the complicated abdominal wound.

BACKGROUND: Closure of the abdominal wall in the face of fascial necrosis or massive intestinal edema remains a difficult problem with frequent complications. Prior studies have addressed both the utility and the pitfalls of placing polypropylene mesh in this setting. METHODS: We performed a retrospective evaluation of our experience with polypropylene mesh in traumatic and nontraumatic difficult abdominal closures. Timing of mesh placement and removal relative to the initial operation were recorded, as were abdominal complications, number of operative procedures, and type of ultimate abdominal closure. RESULTS: Between 1988 and 1993, polypropylene mesh was placed in 26 critically ill or injured patients requiring celiotomy, of whom 23 survived more than 3 weeks. Ultimate wound management was delayed mesh removal and primary closure (17%), myocutaneous flap coverage over mesh (4%), split-thickness skin grafting to the granulating wound (35%), or closure by secondary intention over mesh (43%). Split-thickness skin grafting and closure by secondary intention resulted in enterocutaneous fistulas in 50% and 40% of cases, respectively. Full-thickness closure with or without mesh removal resulted in no fistulas. CONCLUSION: Mesh provided adequate fascial closure, even with gross wound contamination. Coverage of polypropylene mesh by secondary intention or split-thickness skin grafting resulted in unacceptably high rates of fistulous complications, and this procedure should be replaced by either mesh removal or full-thickness coverage.

Abdominal Injuries↗
PubMed1995

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.

Animals↗
PubMed1995

Prospective assessment of the value of computed tomography for trauma.

UNLABELLED: The use of computed tomography (CT) has helped revolutionize the process and accuracy of diagnosis of the trauma patient. We have noted a striking increase in the use of CT scanning early in the management of trauma patients at our trauma center and sought to assess our experience. METHODS: All trauma patients admitted to our trauma center from February 1991 to February 1992 who received any CT scan within the first 12 hours after arrival were enrolled in the study. A positive (+) CT scan was defined as a scan that demonstrated a significant finding consistent with the injury and a negative (-) CT scan was one in which there were either no abnormalities or only incidental findings unrelated to the injury. Each patient was followed daily by one of the authors (A.G.R.). Patient records were reviewed and treating surgeons were interviewed to determine whether the CT scan improved the process of therapy. Morbidity incident to the performance of the CT scans was assessed. RESULTS: 1609 trauma patients underwent 2047 CT scans (1.3 CT scans per patient). Sixteen percent (n = 260) had scans of more than one part of the body. Thirty-eight percent (n = 770) of scans were positive but 29% (n = 225) of these were not helpful to the patient care process. Overall, 29% of scans, either because they were positive or negative, assisted in the clinical care of the patient. Six percent (n = 45) of CT scans were falsely positive. Sixty-five percent of scans were true negatives. Two patients died in the CT suite, 6 died shortly after completion of the scan, and 12 required emergency trips to the operating room from the CT suite. CONCLUSIONS: A large number of CT scans are being performed in our trauma patient population. Less than 30% contributed to patient management. Because of morbidity and cost, strict surgeon and radiologist oversight of CT for trauma is essential.

Extremities↗
PubMed1995

Effects of methysergide administration on edema formation at the site of scald.

Femoral blood flow (Qa), hind paw lymph flow (Qlym), and lymph-to-plasma protein concentration ratio (Clym/Cp) were monitored before and 4 h after 1) 5-s 100 degrees C paw scald, 2) methysergide (1 mg/kg iv) 20 min before scald, 3) methysergide 30 min after scald, and 4) methysergide only. Before experimentation, hind paw venous pressure was elevated and maintained until steady-state Qa, Qlym, and minimal Clym/Cp levels were reached. The reflection coefficient (sigma d) was determined as 1 - minimal Clym/Cp; the filtration coefficient (Kf) was calculated. Methysergide alone caused no changes. Increases in Qa, Qlym, Clym/Cp, and Kf were identified in all scald groups. Compared with scald only animals, pre- and postscald methysergide blunted the increases in Qa, Qlym, Kf, and paw weight gain without an effect on sigma d. These data demonstrate that methysergide reduces edema formation at the site of scald, perhaps by modulating the burn-induced vasodilator response and/or by limiting the burn-induced increase in microvascular surface area.

Animals↗
PubMed1994

Effects of graded thermal injury on microvascular permeability at the site of injury.

To define whether capillary permeability traits at the site of a burn differ according to injury severity, a canine hind leg lymphatic was cannulated to measure macromolecular permeability in response to three different scalding solutions. Leg venous pressure was raised to approximately 40 mm Hg and maintained until a minimal lymph-to-plasma total protein ratio (CL/CP)min and steady-state lymph flow (QL; microliter/min/100 g) was attained. The protein reflection coefficient (1-CL/CP), fluid filtration coefficient (Kf; microliter/min/mm Hg/100 g), and QL were determined before and for 6 hr after a 5-sec hind paw immersion in either 100 degrees C (n = 7), 80 degrees C (n = 7), or 70 degrees C (n = 7) water. A group of five animals served as controls. In the absence of any systemic hemodynamic alterations, the 100 and 80 degrees C scald groups experienced significant (P < 0.05, ANOVA) increases in QL, CL/CP, and Kf as compared to respective preburn values and time-matched unburned control values. Most monitored parameters were significantly higher following 100 degrees C injury vs 80 degrees C injury. Parameters in the 70 degrees C group did change after scald, but were not significantly different from preburn values or from the control group. Alterations in capillary permeability to protein and fluid flux measured at the burn site are graded, not all or none phenomena, being dependent upon the severity of injury.

Analysis of Variance↗
PubMed1994

Laparoscopic cholecystectomy: what's so special?

One hundred seventy-one laparoscopic cholecystectomies were done by senior surgery residents who received only traditional "hands-on" training. Eight patients (5%) required conversion to open cholecystectomy, and two had complications requiring immediate celiotomy (one common bile duct injury, one "dropped" gallbladder). The average operative time was 91 minutes (range, 30 to 245 minutes). There were no deaths and only five postoperative complications related to the procedure (retained common bile duct stone in four cases, intra-abdominal hemorrhage in one). There were three complications unrelated to the procedure. Data acquired from recent resident training program graduates show that these practicing surgeons are doing laparoscopic cholecystectomy with a 95% success rate and have yet to encounter appreciable complications. We concluded that a large-volume general surgery resident training program provides adequate opportunity for training surgeons in the techniques of laparoscopic cholecystectomy; there is no need to attend an expensive and time-consuming classroom and animal laboratory course.

Adolescent↗
PubMed1994

Analysis of regional hemodynamic regulation in response to scald injury.

Ultrasonic probes were placed around dog femoral arteries to record blood flow. Hind paw scalding with boiling water (5 s) caused a marked increase in ipsilateral femoral blood flow that persisted for the 2-h observation period. Contralateral femoral blood flow and systemic and pulmonary vascular resistances were unchanged. Compared to scald only animals, methysergide pretreatment diminished and shortened the femoral vasodilator response to scald (109 +/- 14 vs 243 +/- 27 ml/min at 5 min; 59 +/- 14 vs 191 +/- 31 ml/min at 2 h). Pretreatment with ritanserin, BW A1433U83, atropine, ICI 118551, diphenhydramine, ranitidine, meclofenamate, L-nitro-arginine methyl ester, 3-amino-1,2,4-triazine, and U 37883A had no effect on the increased femoral blood flow response to scald, suggesting this vasodilator response is not dependent upon activation of serotonergic2, adenosineA1, muscarinic, beta 2-adrenergic, histaminergic1 or histaminergic2 receptors, on cyclooxygenase products, endothelium-derived relaxing factor derived from nitric oxide (NO) synthase III, NO derived from NO synthase II, or KATP channels, respectively. Methysergide given after burn immediately reduced the augmented femoral blood flow to preburn levels, suggesting the vasodilator response to scald is mediated through continual activation of local serotonergic1-like receptors, which may be target site(s) for therapeutic interventions to influence burn-induced hemodynamic alterations.

Adamantane↗