Biomedical subjects

R J Connolly

Publications and source records attributed to R J Connolly.

At least 19 recordsLinked to original sources

PubMed2000

Comparison of poly-N-acetyl glucosamine (P-GlcNAc) with absorbable collagen (Actifoam), and fibrin sealant (Bolheal) for achieving hemostasis in a swine model of splenic hemorrhage.

OBJECTIVE: To compare the hemostatic capabilities of poly-Nacetylglucosamine (p-GlcNAc) with three currently available products: Actifoam, Surgicel, and Bolheal fibrin glue. This study was conducted in a controlled animal model, with monitoring of hematologic parameters over the course of the study. Two series were conducted, one in unheparinized animals comparing Bolheal fibrin sealant, Actifoam (absorbable collagen, AC), and Surgicel (ORC) with p-GlcNAc, and the second in systemically heparinized animals comparing p-GlcNAc with AC. METHODS: This study was performed in immature female Yorkshire White swine. Splenic lacerations controlled for length and depth of wound were used as sources of bleeding, with one material used per wound to assess hemostatic effectiveness. A total of 97 wounds in 12 animals were created for the study, 74 wounds in unheparinized animals, and 23 wounds in the heparinized animals. In the heparinized animals, hemostatic efficacy was judged by number of applications needed to achieve complete hemostasis. In the unheparinized animals, hemostatic efficacy was judged by length of time required to achieve complete hemostasis (p-GlcNAc vs. fibrin sealant) or the number of applications needed to achieve complete hemostasis (p-GlcNAc vs. AC or ORC). RESULTS: In systemically heparinized animals, p-GlcNAc demonstrated greater hemostatic efficacy (72.7 %) in one application than did the control material (0%), p < 0.01. In the unheparinized animals, p-GlcNAc took less time to achieve hemostasis (mean, 22.9 seconds) than fibrin sealant (mean, 172.9 seconds), p < 0.01. p-GlcNAc achieved hemostasis with a greater efficacy (79.2%) in one application than did the AC or ORC (16.7%), p < 0.01, whereas there was no difference in the efficacy of the control materials. CONCLUSION: The results of the previous series in unheparinized animals demonstrated that p-GlcNAc in the form of a membrane is a more effective topical hemostatic agent than Bolheal fibrin glue, AC or ORC. The results in the anticoagulated animals similarly demonstrate that p-GlcNAc is a more effective topical hemostatic agent than the control material AC. These data indicate that p-GlcNAc is a promising hemostatic agent as evaluated in this model.

Acetylglucosamine↗

PubMed1999

A pilot study evaluating the efficacy of a fully acetylated poly-N-acetyl glucosamine membrane formulation as a topical hemostatic agent.

BACKGROUND: Topical hemostatic agents are frequently needed for control of intraoperative bleeding. Currently available topical products each have potential drawbacks, making a more effective topical hemostatic agent desirable. This study was performed to evaluate the effectiveness of a particular formulation of a newly available polysaccharide polymer, poly-N-acetyl glucosamine (p-GlcNAc), as a topical hemostatic agent for use in the operating room. Swine splenic incision and splenic capsular stripping hemorrhage models were initially used, with a subsequent pilot human study then performed. METHODS: For the swine splenic incision model, anesthetized immature female Yorkshire white swine had a 3 x 8 mm incision created on the spleen. One of 3 agents (p-GlcNAc membrane, oxidized cellulose, or absorbable collagen) was sequentially applied to individual wounds and digitally compressed for 20 seconds. The wound was observed without pressure for 2 minutes. Up to 8 wounds per animal were created in 7 animals. For the swine splenic capsular stripping model a 2 x 2 cm area of capsular stripping on the surface of the spleen to a depth of 3 mm was created. Either p-GlcNAc membrane or oxidized cellulose was applied and digitally compressed for 60 seconds, followed by observation without pressure for 2 minutes. Six wounds per animal were created in 2 animals. If bleeding persisted in either model, a new cycle of compression was applied. These steps were repeated until hemostasis was achieved. No change in hemodynamics or coagulation factors was observed in either model. Subsequently, 10 consecutive patients undergoing elective small-bowel surgery were enrolled on pilot study. A 5 x 3 x 3 mm cruciate incision was created midway between the mesenteric and antimesenteric borders of the small bowel. Either p-GlcNAc membrane formulation or oxidized cellulose was applied (the sequence alternated per patient) with a 400-mg weight used for even, direct pressure. A second cruciate incision was then created on the contralateral side of the bowel to evaluate the second material. The number of applications required for hemostasis was assessed. Hemodynamics, small-bowel pathologic condition, and hematologic parameters were evaluated. RESULTS: The p-GlcNAc membrane required fewer cycles of compression in the swine splenic incision model to achieve hemostasis than either absorbable collagen or oxidized cellulose (1.25 vs 2.58 and 3.41, respectively; P < .01) and caused more effective immediate cessation of bleeding (79% for p-GlcNAc vs 17% for both absorbable collagen and oxidized cellulose). With the more traumatic splenic capsular stripping model, p-GlcNAc required fewer cycles of compression to achieve hemostasis than oxidized cellulose (average, 2.5 versus 6.8 respectively; P < .01) and was able to achieve hemostasis with greater efficacy (50%) in 2 applications than did oxidized cellulose (0%; P < .01). When used in the human pilot study, p-GlcNAc membranes required fewer cycles of compression than oxidized cellulose (2.5 vs 5.4, respectively; P < .002), was able to stop bleeding with greater efficacy in 1 cycle of compression (50% vs 0%, respectively; P < .01), and ultimately accomplished hemostasis in 80% of the cases as opposed to 20%. CONCLUSIONS: On the basis of its greater hemostatic efficacy as compared with collagen or oxidized cellulose-based products, p-GlcNAc holds promise as an effective topical hemostatic agent and deserves further evaluation.

Acetylation↗

PubMed1998

Microwave applications in clinical medicine.

Over the last fifty years, energy has been applied to various human tissues for both the diagnosis and therapy of numerous diseases. However, in general, the medical community remains uninformed about the many potential applications of this energy source. We review the many areas in which microwave energy has shown clinical utility.

Adult↗

PubMed1997

Use of an adjustable tourniquet to reverse cyanosis in the newborn pig.

BACKGROUND: Previous surgical models of cyanosis have been permanent. Because normal oxygenation was not restored in these models, it is unclear whether the metabolic changes produced by prolonged exposure to hypoxemia are irreversible. We therefore designed an experimental model of cyanosis that is reversible. METHODS: The left atrial appendage was anastomosed directly to the main pulmonary artery in 8 piglets, aged 2 to 4 weeks. RESULTS: The oxygen saturation fell from 95.3% +/- 0.8% to 72.4% +/- 3.9% (p < 0.001). A tourniquet was placed around the anastomosis to produce incremental changes in the level of cyanosis. Complete tourniquet occlusion resulted in obliteration of the right to left shunt, with return of systemic oxygen saturation to baseline levels. Systemic, left atrial, and pulmonary pressures did not change during the study. CONCLUSIONS: In this acute preparation, stable hemodynamic conditions were maintained despite substantial variations in systemic levels of oxygenation. Most important, this model allows reversal of cyanosis with the return of normal oxygenation. Application of this experimental design in a chronic model may help to determine whether the metabolic effects of prolonged hypoxemia are potentially reversible.

Anastomosis, Surgical↗

PubMed1996

In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function.

To examine the hypothesis that surface P-selectin-positive (degranulated) platelets are rapidly cleared from the circulation, we developed novel methods for tracking of platelets and measurement of platelet function in vivo. Washed platelets prepared from nonhuman primates (baboons) were labeled with PKH2 (a lipophilic fluorescent dye), thrombin-activated, washed, and reinfused into the same baboons. Three-color whole blood flow cytometry was used to simultaneously (i) identify platelets with a mAb directed against glycoprotein (GP)IIb-IIIa (integrin alpha 11b beta 3), (ii) distinguish infused platelets by their PKH2 fluorescence, and (iii) analyze platelet function with mAbs. Two hours after infusion of autologous thrombin-activated platelets (P-selectin-positive, PKH2-labeled), 95 +/- 1% (mean +/- SEM, n = 5) of the circulating PKH2-labeled platelets had become P-selectin-negative. Compared with platelets not activated with thrombin preinfusion, the recovery of these circulating PKH2-labeled, P-selectin-negative platelets was similar 24 h after infusion and only slightly less 48 h after infusion. The loss of platelet surface P-selectin was fully accounted for by a 67.1 +/- 16.7 ng/ml increase in the plasma concentration of soluble P-selectin. The circulating PKH2-labeled, P-selectin-negative platelets were still able to function in vivo, as determined by their (i) participation in platelet aggregates emerging from a bleeding time wound, (ii) binding to Dacron in an arteriovenous shunt, (iii) binding of mAb PAC1 (directed against the fibrinogen binding site on GPIIb-IIIa), and (iv) generation of procoagulant platelet-derived microparticles. In summary, (i) circulating degranulated platelets rapidly lose surface P-selectin to the plasma pool, but continue to circulate and function; and (ii) we have developed novel three-color whole blood flow cytometric methods for tracking of platelets and measurement of platelet function in vivo.

Animals↗

PubMed1996

Planning, development, and execution of an international training program in laparoscopic surgery.

In the late 1980s, minimally invasive surgery experienced unprecedented growth. Centers appeared worldwide, providing a variety of training opportunities and laboratory experiences. Because standard surgical training varies greatly from country to country, it became apparent that this variety was even more pronounced in the area of minimally invasive and laparoscopic surgery, posing significant credentialling difficulties for professional standards committees wishing to certify surgical staff who submit unevaluable credentials from all over the world. In January 1993, the Center for Minimally Invasive Surgery at New England Medical Center and Tufts University School of Medicine was asked to plan and execute a program of education, training, and credentialling for a multispecialty surgical staff in the Eastern province of Saudi Arabia. A four-stage program was designed and developed to provide credentialling from the technician level through the instructor surgeon level. A multidisciplinary course was developed and a team placed on site for 1 month to execute the program. This program began with an 8-h didactic/video session in basic laparoscopy, covering areas common to the involved subspecialties: surgery, urology, and gynecology. This session was followed by hands-on training sessions in general surgery and urology and credentialling in gynecology. Physicians who successfully completed the examination in basic laparoscopy were later eligible for credentialling at one of three clinical specialty levels: basic clinical laparoscopy, advanced clinical laparoscopy, or instructor in clinical laparoscopy. Education and credentialling in minimally invasive surgery can be accomplished by executing a program of basic science and clinical training for physicians, technicians, and nurses that accommodates a wide range of experience of participants, from novice to master surgeon. Support from the hospital administrators and department chairs was instrumental in the program's success. Among the goals we accomplished was identification of persons in an institution who could serve as future instructors and certifiers for the hospital's self-sustaining program as well as providing a relationship in which international institutions can serve as a resource for further continuing medical education and clinical and laboratory training. This program may well serve as the model template for international credential standards of the future.

Education, Medical, Continuing↗

PubMed1995

Comparison of Eurocollins and University of Wisconsin solution in single flush preservation of the ischemic reperfused lung: an in vivo rabbit model.

The standard preservation technique in lung transplantation is cold single pulmonary artery flush (PAF) with Eurocollins solution (ECS). We compared ECS with University of Wisconsin (UW) solution, with and without added indomethacin, in single PAF preservation in an in vivo rabbit model of warm ischemia-reperfusion lung injury. Six groups of four New Zealand white rabbits each underwent isolation and hilar stripping of the left lung. In the four experimental groups, the left lung was flushed with (15 ml/kg) of cold ECS or UW solution, with or without added indomethacin, before warm ischemia for 120 minutes and before reperfusion for 60 minutes. The remaining two groups were the nonischemic and the ischemic "no flush" controls. Transcapillary flux of 99mTechnitium-labeled albumin and electron microscopy were used to demonstrate lung injury. Pulmonary vascular resistance (PVR) and thromboxane B2 (TXB2) concentrations were measured. There was a significant rise in PVR after ischemia/reperfusion in the ischemic control group (54.7 +/- 13.9 to 117.8 +/- 20.7 mm Hg/L.min-1, P < 0.05). The net rise in PVR after ischemia-reperfusion was significantly smaller in the two groups in which indomethacin was added (16.8 +/- 17.5 and 4.5 +/- 10.6 mm Hg/L.min-1 for UW and ECS, respectively) compared with the ischemic control (63.1 +/- 24.6 mm Hg/L.min-1, P < 0.05). Post-reperfusion TXB2 levels tended to be lower in the nonischemic control group and in the indomethacin-flush groups. We conclude that the increase in PVR produced by unilateral ischemia-reperfusion lung injury in this model was improved by single PAF perfusion. There was no significant difference between UW solution and ECS in this regard. The addition of indomethacin to the flush solution was associated with lower PVRs as well as morphologic improvement by electron microscopy. These findings may indicate a prominent role for the provision of PG synthesis inhibition during preservation for lung transplantation.

Adenosine↗

PubMed1995

Impedance cardiography in the measurement of cardiac output: studies in rabbits.

A thoracic electric bioimpedance device with improved signal processing was used to noninvasively measure cardiac output in eight New Zealand White rabbits (average wt = 4.7 kg). Prospective correlation was performed between aortic thermodilution and impedance cardiography in a closed chest model. Aortic thermodilution was compared to the electromagnetic flowmeter in an open chest model. In four rabbits, the change in the impedance signal (dZ/dt) was quantified after repeated mechanical occlusion of the aorta and pulmonary artery. The mean cardiac output as measured by the impedance device was 0.56 +/- 0.01 liter/min (range 0.29-1.16 liter/min) compared to 0.53 +/- 0.01 liter/min (range 0.25-0.83 liter/min) by aortic thermodilution. For the 116 data pairs, regression analysis revealed a statistically significant agreement (r = 0.82, P < 0.001) between the two techniques. The mean difference between the techniques (bias) was -0.03 liter/min and 81% of the impedance values were within 0.1 liter/min of the individual thermodilution measurements. A statistically significant decline in the mean magnitude of the dZ/dt signal tracing (1.6 +/- 0.10 V-pre, 0.31 +/- 0.4 V-post, P < 0.005, n = 21) was observed upon aortic arch occlusion. conversely, pulmonary artery occlusion did not have a statistical effect on the impedance signal (1.07 +/- 0.09-pre, 0.95 +/- 0.08-post, P > 0.05, n = 20). In conclusion, a significant correlation was observed between impedance cardiography and aortic thermodilution in measurement of cardiac output in sedated, anesthetized rabbits. This simple technique which involves application of skin electrodes may prove useful in measurement of cardiac output in surgical experimental small animal models.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Glycosylated recombinant human tumor necrosis factor binding protein-1 reduces mortality, shock, and production of tumor necrosis factor in rabbit Escherichia coli sepsis.

OBJECTIVE: To examine the effect of glycosylated recombinant human tumor necrosis factor binding protein-1 (r-hTNF binding protein-1), the extracellular domain of the tumor necrosis factor receptor p55 produced in mammalian cells, in a rabbit model of circulatory shock due to Escherichia coli. DESIGN: Prospective, randomized, controlled trial. SETTING: University hospital research laboratory. SUBJECTS: Eighteen female, New Zealand white rabbits. INTERVENTIONS: Anesthetized rabbits, infused with E. coli (10(9) organisms/kg), were pretreated with either r-hTNF binding protein-1 or saline. Mean arterial pressure, central venous pressure, cardiac output, and heart rate were recorded every 20 mins for 1 hr before, and for 4 hrs after, the infusion of E. coli. Blood samples were obtained at 1-hr intervals for platelet count and white blood cell count, r-hTNF binding protein-1, and tumor necrosis factor (TNF) measurements. MEASUREMENTS AND MAIN RESULTS: Administration of r-hTNF binding protein-1 resulted in improvement of mean arterial pressure, cardiac output, and systemic vascular resistance, as compared with the vehicle-treated group (p < .05). Treatment with r-hTNF binding protein-1 was associated with 100% survival, as compared with 55.6% of the saline-treated rabbits (p < .05). Approximately 85% of r-hTNF binding protein-1 was cleared from the circulation 1 hr after the bolus injection (from 171 +/- 27 micrograms/mL at time = 0, to 27 +/- 4 micrograms/mL at 60 mins, decreasing to 6 +/- 2 micrograms/mL for the next 3 hrs). The r-hTNF binding protein-1-treated rabbits had lower serum TNF bioactivity during the first 2 hrs (p < .01). The decreased bioactivity of TNF was confirmed by a specific radioimmunoassay for rabbit TNF. However, at 4 hrs, the vehicle-treated rabbits had lower serum bioactive TNF concentrations (p < .05). The decrease in TNF concentrations in the r-hTNF binding protein-1-treated rabbits resulted from decreased production and, in part, from carry-over of r-hTNF binding protein-1 into the bioassay. CONCLUSIONS: Treatment with r-hTNF binding protein-1 improved hemodynamic variables and survival of E. coli-challenged rabbits. Administration of r-hTNF binding protein-1 suppressed bioactivity of TNF in the circulation of these rabbits, and the production of TNF as well.

Animals↗

PubMed1995

In-line microwave blood warming of in-date human packed red blood cells.

OBJECTIVE: To verify two hypotheses: a) In-line microwave warming of cold in-date packed red blood cells (RBCs) does not produce significant hemolysis; and b) in-line microwave warming achieves higher outlet temperatures as compared with current blood warming technology at high flow rates (> 250 mL/min). DESIGN: Multiple part, randomized, controlled study. SETTING: Surgical research laboratory of a large university medical center. SUBJECTS: Twenty-four units of cold, ready for transfusion in-date packed RBCs ranging in storage age from 6 to 16 days. INTERVENTIONS: Part I: Microwave apparatus outlet, warmed vs. unwarmed. Six units of cold packed RBCs was split into paired samples and infused at 13 mL/min through a 700-watt in-line microwave test apparatus. One paired specimen was warmed to 37 degrees C; the other was infused without warming (control). Blood was analyzed at the outlet. Part II: Microwave and countercurrent warming, inlet vs. outlet. Twelve units of cold packed RBCs was analyzed biochemically both before (inlet) and after (outlet) simulated transfusions. Six units was infused through a 900-watt in-line microwave test apparatus at > 500 mL/min. Six separate cold units were warmed at this rate using single channel countercurrent water bath warming. Part III: Microwave and countercurrent technology, inlet vs. outlet, warmed vs. unwarmed. a) Six units of cold packed RBCs was also analyzed biochemically and infused at 5 mL/min through either a microwave or countercurrent water bath warmer. b) Packed RBCs from the units used in part a) were allowed to remain stationary in the microwave heating cartridge for 15 mins with an activated heating element. Parallel stationary flow studies were done using the countercurrent blood warmer. Control unwarmed samples were also tested. MEASUREMENTS AND MAIN RESULTS: Part I: No statistical differences in hemolysis parameters were observed between microwave warmed and unwarmed packed RBCs. Part II: At high-flow rates, no statistical increases in hemolysis parameters were seen after in-line microwave or countercurrent water bath warming as compared with prewarmed cold controls. Part III: At slow-flow rates, nonstatistically significant increases were seen by passing the packed RBCs through either test apparatus unwarmed. Packed RBCs remaining stationary within microwave and countercurrent heating cartridges for 15 mins did show biochemical evidence of hemolysis. Mean plasma hemoglobin increased from 14 +/- 1.7 mg/dL in cold prewarmed units to 57.7 +/- 5.8 mg/dL (p < .05), when warmed in the microwave heating cartridge, and to 55.2 +/- 25 mg/dL (p < .05), when warmed in the countercurrent heat exchanger. Outlet Temperature Studies. Part II: The in-line 900-watt microwave device warmed cold units from a mean inlet temperature of 8.3 +/- 0.3 degrees C to a mean outlet temperature of 31.8 +/- 0.5 degrees C within 5 secs at a mean flow rate of 556 mL/min. At 30 secs, the mean outlet temperature was 33.9 +/- 0.4 degrees C (mean inlet temperature = 9.6 +/- 0.2 degrees C) for microwave warmed packed RBCs as compared with 32.1 +/- 0.5 degrees C (mean inlet temperature = 9.6 +/- 0.3 degrees C) in countercurrent water bath warmed blood (p < .05). From 20 to 30 secs, the packed RBCs warmed by microwave were statistically warmer than the countercurrent water bath warmed packed RBCs. CONCLUSIONS: a) Both in-line countercurrent warming and in-line microwave warming were associated with small increases in parameters of red cell damage representing statistically and clinically insignificant hemolysis. b) Blood sitting in any blood warming device is subject to statistically significant but clinically irrelevant increases in those parameters. c) At high-flow rates, the in-line microwave device warmed blood to higher outlet temperatures than the single channel countercurrent water bath warmer. This method may represent a clinical blood warming modality of the near future.

Blood Preservation↗

PubMed1994

Comparison of titanium and absorbable polymeric surgical clips for use in laparoscopic cholecystectomy.

The use of hemostatic surgical clips is crucial in laparoscopic surgery. Metal clips can cause significant interference with computerized tomography, may have poor holding power, and may erode into important anatomic structures. Polymeric absorbable clips, which have advantages over metallic clips, are evaluated in this study. In vitro and in vivo studies were undertaken to evaluate the hold force, rate of degradation, tissue reactivity and safety of absorbable polymeric clips. Absorbable and titanium clips were applied across excised canine cystic ducts and both axial and transverse pull-off forces were measured. In the second phase, absorbable clips were implanted subcutaneously into male rats and the strength remaining within the clips was measured after 7, 10, 14, or 21 days. In phase 3, 30 pigs were randomized into six groups and each animal underwent a laparoscopic cholecystectomy. The cystic duct and artery were ligated with absorbable polymeric clips (experimental group) or titanium clips (control group). Animals were sacrificed at 7, 14, or 28 days and a celiotomy was performed. Intraabdominal adhesions were assessed and scored. The force required to dislodge the absorbable clip was significantly greater than for metallic clips for both axial and transverse forces. Absorbable clip strength retention decreased over time as expected with a retention of 11% original strength by the 21st day. Adhesions were highest when bile spillage occurred, but did not differ significantly between either clip type. Absorbable polymeric clips were hemostatically effective in this laparoscopic model and may offer advantages over metallic clips.

Animals↗

PubMed1994

Platelet activating factor-antagonist improves survival in experimental staphylococcal septicemia.

Platelet activating factor (PAF) amplifies the cytokine cascade in experimental models. This study was designed to investigate the role of PAF blockade during experimental Gram-positive shock by pretreatment with platelet activating factor-antagonist (PAF-A). Three groups of anesthetized rabbits were studied. Control animals received either saline or PAF-A only, and all survived, without hemodynamic changes. Animals in the second group received an infusion of Staphylococcus epidermidis, and all died in septic shock. Animals in the third group were pretreated with PAF-A and given the staphylococcal infusion; five of the six were alive at 200 minutes, with near-normal hemodynamics. The survival rate for animals pretreated with PAF-A was significantly higher than that for animals receiving staphylococci alone (P < .02). These results suggest that PAF is an important mediator of Gram-positive sepsis. Antagonism of PAF may be an effective potential therapy for sepsis.

Animals↗

PubMed1994

Selective alpha IIb beta 3 receptor blockage with peptide TP9201 prevents platelet uptake on Dacron vascular grafts without significant effect on bleeding time.

Synthetic vascular prostheses lack the uniquely low thrombogenicity provided by the endothelial cell lining of autogenous saphenous vein or artery grafts. The thrombogenic nature of the synthetic graft surface becomes a major determinant of early prosthetic graft patency. We demonstrate in a baboon ex vivo synthetic graft model that modification of the host's platelet interaction with the graft surface results in inhibition of platelet thrombus formation and thereby, a possible enhancement of early prosthetic graft patency. This was achieved by selective blockage of the platelet alpha IIb beta 3 receptor by the arginine-glycine-aspartic acid-containing synthetic peptide TP9201. Platelet thrombus formation on a Dacron graft indicated by accumulation of indium III-oxine-labeled autologous platelets was measured by gamma camera imaging. After 60 minutes of circulation, TP9201 at a bolus of 125 micrograms/kg; infusion of 3 micrograms/kg/min, bolus of 190 micrograms/kg; infusion of 5 micrograms/kg/min, bolus of 250 micrograms/kg; infusion of 6 micrograms/kg/min, and bolus of 500 micrograms/kg; infusion of 12 micrograms/kg/min decreased platelet uptake on the graft to 50%, 40%, 30%, and 10% of control uptake, respectively. Forelimb template bleeding times were not found to be significantly prolonged at doses that effectively inhibit ex vivo platelet aggregation. As a result of drug treatment, no changes in hemodynamic parameters or hematologic profile, including platelet number and clotting time, were observed. We demonstrate here that the arginine-glycine-aspartic acid-containing peptide TP9201, which competitively inhibits the alpha IIb beta 3 integrin-fibrinogen interaction, significantly decreased the accumulation of platelets on a Dacron vascular graft. Molecules like peptide TP9201, because of its unique activity profile, may represent a superior approach to the control of platelet accumulation on thrombogenic surfaces.

Animals↗

PubMed1992

PEO enhancement of platelet deposition, fibrinogen deposition, and complement C3 activation.

Whereas it has been commonly thought that adding polyethylene oxide PEO to a surface would diminish the capacity of the surface to cause deposition of platelets and of fibrinogen, and to activate complement C3, we present data showing exactly the opposite. These unexpected results are obtained with low molecular weight (2000) PEO, and are not found with higher molecular weight (20,000) PEO.

Animals↗

PubMed1992

Granulocyte sequestration and early failure in the autoperfused heart-lung preparation.

We investigated the role of pulmonary granulocyte sequestration in the development of early failure of the autoperfused working heart-lung preparation. A significant decline in the total circulating leukocyte count in 21 preparations at 60 minutes of perfusion (5.0 to 1.4 x 10(3)/microL; 28% of baseline; p less than 0.001) was observed. Differential cell counts in 14 of these preparations revealed a predominant decrease in granulocyte count (8.7% of baseline) and a moderate decline in lymphocyte count (46% of baseline). In study I, indium 111-labeled autologous granulocytes were injected intravenously into 10 adult New Zealand White rabbits. In group I (n = 5), an autoperfused working heart-lung preparation was harvested and perfused for 60 minutes. In group II (controls, n = 5), the heart-lung block was harvested following 60 minutes of in situ perfusion. Organ blocks were imaged before and after saline flush. There was a significant decline in granulocyte counts at 60 minutes of perfusion in group I versus no change in group II (I, 2.3 +/- 0.4 to 0.3 +/- 0.1; p less than 0.01; II, 1.7 +/- 0.2 to 2.3 +/- 0.5; not significant; x 10(3)/microL +/- standard error of the mean). Postflush lung activity was significantly increased in group I versus group II (I, 3,751 +/- 566; II, 1,867 +/- 532; p less than 0.05; counts +/- standard error of the mean). In study II, 15 autoperfused preparations were divided into two groups. Group I (n = 10) preparations were controls. Group II (n = 5) animals were depleted of leukocytes by pretreating with nitrogen mustard. Group I (controls) produced a bimodal survival distribution (Ia, 8.2 +/- 1.0; Ib, 26.4 +/- 2.0; hours +/- standard error of the mean). Group II survival was significantly longer than that of group Ia and similar to that of group Ib (II, 25.3 +/- 2.2; p less than 0.01 versus group Ia, not significant versus group Ib; hours +/- standard error of the mean). Hemodynamic profiles for group II closely paralleled those of group Ib. In conclusion, pulmonary sequestration of granulocytes occurs early in the autoperfused working heart-lung preparation (within 60 minutes of autoperfusion), and preoperative leukocyte depletion prolongs survival of the autoperfused working heart-lung preparation by eliminating the subset group Ia (short survivors) seen in untreated preparations.

Animals↗

PubMed1992

The effect of in-line microwave energy on blood: a potential modality for blood warming.

The treatment of hypothermia associated with hemorrhage, exposure, or intraoperative intervention continues to represent a challenge for trauma care teams. An innovative technique for combining microwave heating with continuous temperature monitoring into a feedback-controlled system for blood warming has been developed. The effect of microwave warming on the structure and function of blood was compared with that in nonheated controls. Erythrocyte structural integrity (hemolysis) was evaluated by comparing levels of lactate dehydrogenase (LDH), potassium (K+), and plasma hemoglobin (PHGB), and hematocrit (HCT) in heated and nonheated (control) samples of banked red blood cells. Hemoglobin function was evaluated in fresh blood by comparing the P50 and hemoglobin electrophoresis of experimental and control samples. Prewarming temperatures were 3 degrees or 23 degrees C; temperatures after warming were 35 degrees, 37 degrees, or 39 degrees C. The results reflect the percentage of changes for 84 heated and 24 unheated blood samples. There were no statistical differences in any of the biochemical variables measured. The P50 for three heated and three unheated samples was 30.7 +/- 1.2 and 30.5 +/- 0.9 mm Hg (p greater than 0.05). There were no changes in the hemoglobin electrophoretic patterns in experimental or control samples. This system is designed to deliver microwave energy in a uniform and controlled manner, overcoming the limitations of conventional microwave ovens that in the past caused local overheating and subsequent hemolysis when used for blood warming. The structural and functional integrity of erythrocytes after microwave warming indicate the safety and effectiveness of this technique.

Blood↗

PubMed1991

Spinal cord protection during aortic occlusion: efficacy of intrathecal tetracaine.

Spinal cord ischemia and resultant paraplegia are devastating sequelae in up to 40% of patients undergoing repair of thoracoabdominal aneurysms. We investigated the effect of intrathecal tetracaine on the neurological sequelae of spinal cord ischemia and reperfusion with aortic occlusion. Cocaine-derived anesthetics (lidocaine and its analogues) have been shown to decrease neuronal cell metabolism and also have specific neuronal membrane stabilizing effects. New Zealand white rabbits were anesthetized and spinal cord ischemia was then induced by infrarenal aortic occlusion. Animals were divided into six treatment groups. Tetracaine (groups 2 and 4) or normal saline solution (group 5) was administered intrathecally before aortic cross-clamping. Groups 1 and 3 functioned as controls. Group 6 animals received intravenous thiopental. Rabbits were classified as either neurologically normal or injured (paralyzed or paretic). Among controls, 25 minutes of aortic occlusion produced varied neurological sequelae (group 1, 3/6 injured, 50%) whereas 30 minutes resulted in more consistent injury (group 3, 5/6 injured, 83%). All rabbits that received intrathecal saline solution were paralyzed (group 5, 4/4 injured, 100%). Animals treated with intrathecal tetracaine and aortic occlusion of 30 minutes (group 4) showed significantly better preservation of neurological function (6/7 normal, 86%) than controls and saline-treated animals (groups 3 and 5). All animals treated with intrathecal tetracaine and aortic occlusion for 25 minutes (group 2) showed no signs of injury (5/5 normal, 100%), but this was not significant versus controls (group 1). Intravenous thiopental (group 6, 5/5 injured, 100%) had no beneficial effect. Intrathecal tetracaine significantly and dramatically abrogated the neurological injury secondary to spinal cord ischemia and reperfusion after aortic occlusion at 30 minutes in the rabbit model.

Animals↗

PubMed1991

Complement activation by vascular sutures both alone and in combination with synthetic vascular prostheses.

Polymer surfaces activate complement pathways resulting in platelet and leucocyte deposition as well as possible release of growth factors. A consequence of these interactions may be early graft failure or intimal hyperplasia leading to late graft failure. C5a generation in human plasma by vascular sutures, both alone and in combination with synthetic vascular prostheses was measured by radioimmunoassay to determine the influence of suture materials on C5a activation. Prolene and ePTFE suture material caused significant activation of C5a (p less than 0.01), while Novafil did not. Both Dacron and ePTFE graft material caused significant activation (p less than 0.01) of C5a. The addition of the suture materials to the ePTFE did not increase the C5a levels above the ePTFE material alone. In contrast, the addition of either Prolene or Novafil suture to Dacron material elevated C5a levels significantly over Dacron alone (p less than 0.01). The combination of Dacron material with ePTFE suture did not increase C5a levels over Dacron alone. The pattern of C5a activation by Prolene, ePTFE and Novafil sutures parallels the relative degree of in-vivo platelet accumulation on these suture materials as previously reported by our group. Since these experiments demonstrate that vascular suture material influences human complement activation, it may be that this interaction contributes to either early or late graft failure by enhancing platelet reactivity or neointimal proliferation, respectively.

Blood Vessel Prosthesis↗