PubMed Health⌕ Search

Biomedical subjects

T W Wakefield

Publications and source records attributed to T W Wakefield.

108 records · Page 6Linked to original sources
PubMed1986

Attenuation of hemodynamic and hematologic effects of heparin-protamine sulfate interaction after aortic reconstruction in a canine model.

This investigation documented the effect of protamine sulfate pretreatment on the adverse hemodynamic and hematologic sequela of rapid intravenous protamine administration in heparinized dogs having undergone prior implantation of aortic prostheses. Fourteen dogs underwent infrarenal aortic replacement with 6 mm inner diameter by 7 cm knitted Dacron double-velour grafts. Carotid arterial, central venous, and pulmonary arterial catheters were placed for continuous hemodynamic monitoring. All dogs were adequately anticoagulated with heparin (150 IU/kg) and reversed with protamine (1.5 mg/kg/10 sec) after graft insertion. Pretreatment regimens studied included normal saline (n4), protamine 0.75 mg/kg (n5), and protamine 2.25 mg/kg in three divided doses of 0.75 mg/kg each (n5). All pretreatment agents were administered 3 minutes before heparinization. Blood pressure (BP), heart rate (HR), pulmonary artery pressure (PAP) and cardiac output (CO) were measured. Hematologic assessments included platelet count (PC), leukocyte count, thrombin clotting time, and total hemolytic complement. Significant salutory effects were associated with protamine pretreatment regarding BP, HR, PAP, CO, and PC. It is concluded that adverse hemodynamic effects of protamine reversal are blocked and certain hematologic effects are reduced with protamine pretreatment before heparinization and its reversal in this canine experimental model.

Animals↗
PubMed1985

Nonpenetrating subclavian artery injuries.

Nonpenetrating subclavian artery trauma, a potentially catastrophic injury, has been recognized more frequently with the liberal use of angiography in evaluating blunt cervicothoracic trauma. Six patients, five men and one woman, recently underwent surgical treatment at the University of Michigan Hospital for blunt injury of the subclavian artery. The diagnoses were established by arteriography. Physical findings, chest roentgenograms, and results of noninvasive vascular evaluation were found to be nonspecific or unreliable. Operative treatment with resection of the injured arterial segments and either primary anastomosis or bypass grafting resulted in restoration of distal, upper extremity blood flow in all of the cases. One patient died 20 days after trauma from a severe associated cerebral injury. Among the five survivors, residual soft tissue and neurologic injury compromised full recovery in three. Thus, only two of the six patients survived without sequelae, a fact that underscores the seriousness of this type of subclavian artery injury.

Accidents, Traffic↗
PubMed1985

Celiac artery aneurysms: historic (1745-1949) versus contemporary (1950-1984) differences in etiology and clinical importance.

Celiac artery aneurysms were encountered in nine patients, ranging in age from 39 to 76 years, at the University of Michigan Medical Center between 1961 and 1983. Developmental defects and atherosclerosis were etiologic factors in six cases. Four patients were without symptoms, whereas five experienced abdominal pain, including one with a ruptured aneurysm. Eight patients were subjected to surgical treatment; no deaths occurred and symptoms were resolved in all patients. A literature review of 108 celiac artery aneurysms revealed two distinct subgroups. Among 60 celiac artery aneurysms encountered before 1950, representing the historic era, 40% were infectious (usually luetic), 7% were traumatic, and 52% were of undetermined cause. Most were symptomatic, 87% ruptured, and 95% were diagnosed at postmortem examination. The contemporary era since 1950 consisted of 48 cases, including nine in the Michigan experience. Congenital or developmental medial defects of the arterial wall and atherosclerosis were the most common causes of aneurysms. Most aneurysms in the contemporary period were either asymptomatic or accompanied by vague abdominal discomfort. Rupture affected 13% of those aneurysms. Operative therapy was successfully undertaken in 91% of 43 patients during the contemporary era, including eight in the present series.

Adult↗
PubMed1984

Depressed cardiovascular function and altered platelet kinetics following protamine sulfate reversal of heparin activity.

This investigation documented the hemodynamic effects of rapid intravenous and intra-arterial administration of protamine sulfate, altered platelet kinetics associated with intravenous protamine sulfate administration, and a possible method of reducing protamine sulfate-induced hypotension. Thirty-six anesthetized dogs underwent continuous hemodynamic monitoring prior to heparinization (150 U/kg) and for 30 minutes after rapid reversal with protamine sulfate (1.5 mg/kg over 10 seconds). Platelet counts, platelet aggregation, and serum thromboxane B2 levels were also assessed. Intra-arterial protamine sulfate administration caused fewer adverse hemodynamic changes than intravenous administration, including significantly (p less than 0.05) reduced falls in mean arterial pressure (-10 vs. -35 mm Hg), cardiac output (-0.2 vs. -0.6 L/min), femoral artery blood flow (+ 34 vs. -16 ml/min), and superior mesenteric artery flow (+ 107 vs. -48 ml/min). Thrombocytopenia following protamine sulfate administration was the same in the two groups. Marked hypotension accompanying intravenous protamine sulfate administration was completely attenuated by a small dose of protamine sulfate (0.75 mg/kg) administered prior to heparinization. Similarly, the thrombocytopenia caused by intravenous administration was significantly lessened by protamine sulfate pretreatment (74% vs. 23% reduction; p less than 0.01). These observations have important implications for both experimental and clinical use of heparin and protamine sulfate.

Animals↗
PubMed1983

Limb-threatening potential of arteriosclerotic popliteal artery aneurysms.

Eighty-eight popliteal artery aneurysms were diagnosed in 59 men and two women (mean age 67 +/- 10 years). Bilateral aneurysms affected 27 patients (44%). Aneurysm diameter ranged from 1.3 to 12 cm (mean 4 +/- 2.6 cm). Most aneurysms were symptomatic (55%). Dominant symptoms included rest pain (19%), claudication (14%), local pain (13%), and gangrene (9%). The remainder of the aneurysms were asymptomatic (45%). Aneurysm thrombosis occurred in 24% of extremities. Associated aneurysms involved the abdominal aorta (62%), iliac artery (36%), and femoral artery (38%). Aneurysms that caused local pain were larger (6.2 +/- 1.9 cm) than asymptomatic aneurysms (2.9 +/- 2.1 cm, P less than 0.01). Aneurysms smaller than 2 cm were more likely to be asymptomatic than larger aneurysms (P less than 0.05). Operative intervention was undertaken for 56 aneurysms, with aneurysmal exclusion or excision with arterial reconstruction performed most often. Four primary and five secondary major amputations were associated with thrombosed aneurysms, compared to no amputations with asymptomatic aneurysms (P less than 0.01). Thirty-two aneurysms were not treated surgically. Limb loss resulted from ischemic complications which developed in 18% of aneurysms treated without operation. The duration of follow-up for patients who had operation and those who did not averaged 62 months and 25 months, respectively. Operative treatment for all bland popliteal artery aneurysms appears justified if complications leading to major amputation are to be avoided.

Adult↗
PubMed1982

Abdominal aortic aneurysm rupture: statistical analysis of factors affecting outcome of surgical treatment.

One hundred sixteen patients underwent surgery for ruptured abdominal aortic aneurysms with intraoperative and overall mortality rates of 20.7% and 51.7%, respectively. The correlation of multiple factors to morbidity and mortality was assessed with detailed statistical analysis. Eight preoperative factors were identified as predictors of mortality. Increased intraoperative mortality rates were associated with heart disease (29%), hypertension (30%), flank ecchymoses (57%), and pulsatile abdominal mass (24%). Increased intraoperative and overall mortality rates were associated with preoperative hypotension (39%, 78%) and BUN levels higher than 30 mg/dl (47%, 82%). Increased overall mortality rates were associated with creatinine levels higher than 3 mg/dl (71%) and a hematocrit of 30.0 to 32.5 vol% (75%) (P less than 0.05). Seven intraoperative factors were identified as predictors of mortality. Increased postoperative mortality rates were associated with a duration of operation of more than 400 minutes (100%), hypotension lasting longer than 110 minutes (88%), estimated blood loss more than 11,000 ml (75%), blood transfusion more than 17 U (68%), fluid administration in excess of 7000 ml (70%), and a blood pressure lower than 100 mm Hg at the conclusion of the operation (88%). Cardiac arrest was associated with increased intraoperative and overall mortality rates (77%, 82%) (P less than 0.05). In general these factors cannot be controlled by the surgeon, and future significant reduction in the operative mortality rate may be possible. These findings support the general concept of aggressive elective resection of abdominal aortic aneurysms.

Aged↗
PubMed1975

Coronary arterial predominance or balance on the surface of the human cardiac ventricles.

Normal hearts obtained from suicide victims were studied after injection of gelatin containing red or blue pigment and a radiopaque substance into each coronary artery. Schlesinger's types of coronary artery unilateral predominance or bilateral balance were identified and their incidence determined. The relation to general factors of anatomical variation was also pointed out. Physiologic and clinical features were discussed on the basis of the morphologic pattern, diverse results recorded in the literature were pointed out, and some discrepancies explained. Hearts with right coronary artery predominance (73.5%) prevailed over left predominance (19.4%) and over the balanced hearts (7.1%). An evaluation of both the blood supply and drainage of the heart as a whole, not restricted to the superficial parietal arteries of the ventricles, would better meet the requirements of clinical cardiology.

Adolescent↗
PubMedDate not supplied

Detection of perivenous inflammation in a rat model of venous thrombosis using MRV.

Venous thrombosis is associated with a significant inflammatory response in the vein wall, which can be imaged noninvasively with gadolinium (Gd)-enhanced magnetic resonance venography (MRV). Interleukin-10 (IL-10), a naturally occurring anti-inflammatory cytokine, has been found to decrease the inflammatory response at the proper dosage and timing of administration. The present study determines if MRV with Gd is useful in a rat model of stasis-induced venous thrombosis to document the anti-inflammatory effects of rIL-10. Rats underwent laparotomy and ligation of the inferior vena cava (IVC). Animals were infused with rIL-10 at 2.5 microg (n = 6), rIL-10 at 10 microg (n = 6), or rIL-10 at 40 microg (n = 6). Six animals without IVC ligation or drug infusion served as controls. Two days after thrombosis induction, the rats underwent MRV with both time-of-flight imaging and pre/post-Gd T1-weighted imaging. Inflammation was analyzed by measuring the area of Gd enhancement at the point of IVC thrombosis. Enhancement area was also measured in the distal IVC where flow persisted. All animals with IVC ligation developed thrombosis, and all control rats were free of thrombus. In areas where flow remained, the area of enhancement was 1.8 +/- 0.4 mm2, while controls demonstrated 3.8 +/- 1.0 mm2 enhancement. Enhancement was significantly greater in all groups at the level of thrombus compared to the area of distal IVC flow and control IVCs (p < .001). Animals receiving rIL-10 at 40 microg revealed the most enhancement, 32.7 +/- 6.2 mm2, while the least enhancement was noted with 2.5 microg, 14.7 +/- 1.5 mm2 (p < .05). In conclusion, Gd-enhanced MRV was found useful in this rat model of stasis-induced venous thrombosis to document inflammation noninvasively and to evaluate the effects of anti-inflammatory interventions during stasis-induced IVC venous thrombosis.

Animals↗
PubMedDate not supplied

A novel approach to anticoagulation control.

Heparin used in extracorporeal therapy often leads to bleeding complications. Protamine used for heparin reversal can cause adverse hemodynamic responses. To control both types of complications, a cellulosic hollow-fiber filter device containing immobilized protamine (defined as a protamine filter) was developed. In vivo experiments with dogs showed that the filter not only removed more than 80% of the anticoagulant activity of heparin, but also caused no clinically significant hemodynamic response. In addition, the protamine filter also significantly attenuated both the thrombocytopenic and granulocytopenic responses associated with the use of protamine. Moreover, the use of immobilized protamine considerably reduced activation of the blood complement system by free protamine.

Animals↗
PubMedDate not supplied

Neutrophils are the initial cell type identified in deep venous thrombosis induced vein wall inflammation.

Venous thrombosis and inflammation are interrelated. The authors hypothesized that inferior vena cava thrombosis results in a predictable vein wall inflammatory response, characterized by early neutrophil infiltration. Thrombosis was induced in rats by placement of an inferior vena cava ligature with branch ligation. Animals were killed at baseline, 6 hrs, day 2, and day 6. Analysis included vein wall morphometrics, myeloperoxidase activity, and fluorescence activated cell sorting. At 6 hrs, there was an increase in neutrophils and lymphocytes as compared to sham animals (p < 0.0001 for neutrophils, p < 0.05 for lymphocytes). By day 2, only neutrophils were elevated in the experimental groups (experimental = 75.5 cells/5 high power fields vs. 9.6 cells/ 5 high power fields in shams, p < 0.0001). Myeloperoxidase activity in the experimental group was greater than shams on day 2(34.7 delta optical density/min vs. 5.9 delta optical density/ min, p < 0.0001). Fluorescence activated cell sorting of the neutrophil marker at 6 hrs confirmed the increase in neutrophils (experimental = 63.1%, shams = 39.1%, p < 0.0001), and peaked on day 2 (71.9%). This study suggests that 1) neutrophils are elevated early during the inflammatory response due to thrombus initiation, and 2) neutrophils, because of their early predominance, likely contributed to vein wall injury during venous thrombosis.

Animals↗
PubMedDate not supplied

Venous thrombosis incidence in burn patients: preliminary results of a prospective study.

There are few prospective data on the incidence of deep venous thrombosis (DVT) in burn patients. In an on-going prospective study, hospitalized burn patients 18 years or older with an expected hospital length of stay more than 72 hours were imaged with baseline venous duplex ultrasound of all extremities within the first 48 hours after admission and weekly until discharge. Patient demographics and clinical risk factors for DVT were assessed. At the time of submission, 40 patients met screening criteria, and 30 were enrolled. Ultrasound diagnosed seven patients with 11 acute DVT for an incidence of 23%. One pulmonary embolism was documented. DVT patients had a mean age of 49 +/- 23 years with an average TBSA burn of 15 +/- 4% compared with those without thrombosis with a mean age of 44 +/- 17 years (P = NS) and TBSA burn of 18 +/- 25% (P = NS). There were no statistically significant differences for DVT patients in terms of age, number of central line days, hospital length of stay, or TBSA burned. Given the preliminary findings of this small study, we believe that all hospitalized burn patients are at risk for DVT. On-going investigation will be helpful in defining level of risk and improved prevention strategies for thromboembolic complications in burn patients.

Adult↗
PubMedDate not supplied

Coagulation status during aortic aneurysm surgery: comparison of thrombelastography with standard tests.

A prospective comparison of thrombelastography to standard coagulation tests was undertaken in ten patients undergoing routine, uncomplicated abdominal aortic aneurysm surgery in order to explore potential clinical utility and establish normal patterns of change. Thrombelastograph k values increased (7.1 vs 5.4 min baseline, P < or = .01), and alpha angle (43 vs 52 degrees baseline, P < or = .001) and ma (39 vs 52 mm baseline, P < or = .01) values decreased following graft placement, while r values remained unaffected (6.4 vs 7.5 min baseline, P > .05). Weak correlations were observed between alpha angle and fibrinogen, prothrombin time, and partial thromboplastin time (aPTT), as well as between k and aPTT (0.70 < r < 0.79 for all). Systemic fibrinolysis was suggested by thrombelastography in 25% of samples, although euglobulin lysis times were abnormal in only 5% (chi 2 = 4.80, P < or = .05). Fibrin degradation product detection increased through the fifth postoperative day in all patients. Variations in thrombelastographic parameters and their correlation to standard coagulation tests in patients undergoing uncomplicated abdominal aortic aneurysm repair were documented. In such a setting, no clear advantages to thrombelastography were defined. Further observations will be necessary to establish the role for thrombelastography in the management of patients experiencing clinically significant perioperative coagulation disorders.

Aged↗
PubMedDate not supplied

A protamine filter for extracorporeal blood heparin removal.

Heparin employed in extracorporeal circuits often leads to hemorrhagic complications. Protamine employed for heparin neutralization can cause adverse hemodynamic responses. To control both types of complications, the authors propose an approach that consists of placing a filter device containing immobilized protamine (defined as a protamine filter) at the termination of the extracorporeal blood circulation (ECBC) procedure. This protamine filter would remove heparin from the extracorporeal circuit before heparin is returned to the patient. Meanwhile, the filter would also permit external protamine treatment. Since protamine toxicity generally results from the interaction of protamine with certain cells present in the liver, lungs, and tissues, the use of external protamine would minimize its potential adverse effects. Protamine was immobilized on a hollow fiber bundle obtained from a conventional hemodialyzer. Preliminary studies show that the protamine bound bundle is capable of neutralizing the anticoagulant activity of heparin both in vitro and in vivo. In addition, the protamine filter has abolished the hypotensive response normally associated with protamine reversal of heparin, as indicated by the insignificant changes in blood pressure, pulse rate, pulmonary artery systolic/diastolic pressures, and cardiac output. Further in vivo studies involving the use of dogs, as well as investigation of the activation of the complement system by the protamine filter, are currently being conducted.

Animals↗
PubMedDate not supplied

Karyotype analysis of cell sex to determine the source of vascular graft luminal linings following autologous and nonautologous endothelial cell seeding.

Endothelial cell-seeded bilateral carotid ePTFE grafts were studied in 11 dogs to determine the source of their eventual luminal linings. One graft was prepared with autologous cells and the other with nonautologous cells. Immunosuppression was accomplished with cyclosporin and prednisolone. At 2 and 3 weeks post implantation, grafts were removed, revealing 9 of 11 autologous and 8 of 11 nonautologous seeded conduits to be patent. Linings were harvested enzymatically and grown in tissue culture, with karyotype analysis limited to cultures that exhibited greater than or equal to 50% endothelium (n5 autologous, n7 nonautologous). Sex type was classified in 20 cells from each graft. All five autologous cell-seeded grafts revealed host cells. Among the seven nonautologous cell-seeded grafts, one harbored only non-autologous cells, three revealed only autologous cells, and three exhibited a predominance of autologous cells with lesser numbers of nonautologous endothelium. All 100 cells from the autologous-seeded grafts were the same sex as seeded cells, while only 28 of the 140 cells from the nonautologous seeded grafts were the same sex as seeded cells (P less than 0.001). Thus, nonautologous endothelial cell seeding with immunosuppression did not uniformly produce nonautologous cell linings, but was more often associated with autologous endothelial cell linings that may have been promoted by the nonautologous cell seeding.

Animals↗
PubMedDate not supplied

Tissue distribution, circulating half-life, and excretion of intravenously administered protamine sulfate.

Intravenous protamine reversal of heparin anticoagulation may cause adverse hemodynamic side effects, but little is known about protamine's tissue distribution, circulating half-life (t/2), and excretion. The latter were assessed by examining 125I Bolton-Hunter (125I BH) radiolabeled protamine kinetics in a rat model. Three groups were studied: Group I controls (n = 5) received intravenous 125I BH label alone; Group II (n = 10) received intravenous 125I BH radiolabeled protamine (0.15 mg/100 g); and Group III (n = 10) received intravenous heparin (15 IU/100 g) followed by intravenous 125I BH radiolabeled protamine (0.15 mg/100 g). Five animals in each group were killed at 3 min, and tissue radioactivity was quantitated. An additional five animals each in Groups II and III were followed up for 60 min to determine protamine's circulating t/2 and its renal excretion. The lungs, heart, and kidneys, compared with other organs, retained the most 125I BH radiolabeled protamine per gram tissue at 3 min. Retention of 125I BH radiolabeled protamine (Groups II & III) was greater (p < 0.05, Kruskal-Wallis) than control 125I BH label alone (Group I). Higher tissue 125I activity was observed in Group II than in Group III rats, suggesting that tissue retention of protamine was greater in the absence of prior heparin administration. Circulating t/2 was shorter (18 vs. 24 min) and urinary protamine 125I excretion was higher (34 vs. 24%) in Group III than in Group II, respectively, suggesting more rapid renal clearance of protamine in the presence of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗