Inhibition of tissue factor pathway during intermittent pneumatic compression: A possible mechanism for antithrombotic effect.
Intermittent pneumatic compression (IPC) devices are an effective prophylaxis against lower extremity deep vein thrombosis. Their antithrombotic effect has been attributed to a reduction in venous stasis and enhanced fibrinolysis. The initiating mechanism for blood coagulation is the tissue factor (TF) dependent pathway, which is inhibited by tissue factor pathway inhibitor (TFPI). We have investigated the effect of IPC on the TF pathway in 6 normal subjects and 6 patients with postthrombotic venous disease undergoing IPC for 120 minutes; all subjects were studied with each of 5 IPC devices. In normal subjects and patients, plasma factor VIIa (FVIIa) activity (the activated form of factor VII [FVII]) declined from mean values ranging 51 to 65 and 50 to 53 mU/mL before IPC with different devices to 10 to 13 and 20 to 22 mU/mL at 180 minutes, respectively (P<0.001 for all groups). FVII antigen levels were unchanged. Plasma TFPI (P<0.001) rose from mean baseline values ranging 69 to 79 and 57 to 61 ng/mL to 76 to 123 and 71 to 79 ng/mL at 180 minutes in normal subjects and patients, respectively (P<0. 001 for all groups). Plasma prothrombin fragment F1.2 levels showed minimal changes. There was an inverse relationship between TFPI and FVIIa in normal subjects (r=-0.31, P=0.001) and patients (r=-0.37, P<0.001). IPC results in an increase in plasma TFPI and decline in FVIIa. Inhibition of TF pathway, the initiating mechanism of blood coagulation, is a possible mechanism for the antithrombotic effect of IPC. (+info)
Effects of inertial load and countermeasures on the distribution of pulmonary blood flow.
We assessed the influence of cranial-to-caudal inertial force (+G(z)) and the countermeasures of anti-G suit and positive pressure breathing during G (PBG), specifically during +G(z), on regional pulmonary blood flow distribution. Unanesthetized swine were exposed randomly to 0 G(z) (resting), +3 G(z), +6 G(z), and +9 G(z), with and without anti-G suit and PBG with the use of the Air Force Research Laboratory centrifuge at Brooks Air Force Base (the gravitational force of the Earth, that is, the dorsal-to-ventral inertial force, was present for all runs). Fluorescent microspheres were injected into the pulmonary vasculature as a marker of regional pulmonary blood flow. Lungs were excised, dried, and diced into approximately 2-cm(3) pieces, and the fluorescence of each piece was measured. As +G(z) was increased from 0 to +3 G(z), blood flow shifted from cranial and hilar regions toward caudal and peripheral regions of the lung. This redistribution shifted back toward cranial and hilar regions as anti-G suit inflation pressure increased at +6 and +9 G(z). Perfusion heterogeneity increased with +G(z) stress and decreased at the higher anti-G suit pressures. The distribution of pulmonary blood flow was not affected by PBG. ANOVA indicated anatomic structure as the major determinant of pulmonary blood flow. (+info)
External pneumatic compression and fibrinolysis in abdominal surgery.
INTRODUCTION: External pneumatic compression (EPC) devices prevent lower extremity deep venous thrombosis by increasing venous flow and thereby reducing stasis. Early studies suggested that they also enhance systemic fibrinolytic activity and thus prevent thrombus formation; more recent studies have been conflicting. The hypothesis of this study was that EPC devices enhance systemic fibrinolysis or reduce postoperative fibrinolytic impairment in patients undergoing abdominal surgical procedures. METHODS: Each of 48 patients (98% male; mean age, 67 years) undergoing major intra-abdominal surgical procedures (36 bowel procedures, 12 aortic reconstructions) was prospectively randomized to one of three treatments for deep venous thrombosis prophylaxis: subcutaneous heparin injections (HEP group), use of a thigh-length sequential EPC device (EPC group), or both (HEP + EPC group). Antecubital venous samples were collected for measurement of systemic fibrinolytic activity on the day before surgery, after induction of anesthesia but before prophylaxis was initiated, and on postoperative days 1, 3, and 5. Fibrinolysis was assessed through measurement of the activities of the rate limiting fibrinolytic activator, tissue plasminogen activator, and its inhibitor plasminogen activator inhibitor-1 with amidolytic methods. RESULTS: On the day before surgery, plasminogen activator inhibitor-1 activity was elevated in all groups in comparison with that in age-matched and sex-matched controls (20.3 +/- 0.6 AU/mL). In the HEP group, plasminogen activator inhibitor-1 activity was further elevated above the value for the day before surgery on postoperative day 1 (28.5 +/- 4.3 AU/mL; P =.04) and postoperative day 3 (25.1 +/- 1.9 AU/mL; P =.07). No significant decrease in plasminogen activator inhibitor-1 activity occurred in either group treated with EPC devices in comparison with the HEP group at any time. There were no changes in tissue plasminogen activator activity postoperatively in the HEP group and no significant increases in either EPC group at any point. CONCLUSIONS: Reduced systemic fibrinolytic activity ("fibrinolytic shutdown") occurred in these patients after abdominal surgery; it was manifested as increased plasminogen activator inhibitor-1 activity. EPC devices did not enhance systemic fibrinolysis or prevent postoperative shutdown either by decreasing plasminogen activator inhibitor-1 activity or by increasing tissue plasminogen activator activity. These data suggest that EPC devices do not prevent deep venous thrombosis by fibrinolytic enhancement; effective prophylaxis is achieved only when the devices are used in a manner that reduces lower extremity venous stasis. (+info)
Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty.
BACKGROUND: Recent studies have shown that symptomatic venous thromboembolism after total hip arthroplasty most commonly develops after the patient is discharged from the hospital. Risk factors associated with these symptomatic thromboembolic events are not well defined. METHODS: Using administrative data from the California Medicare records for 1993 through 1996, we identified 297 patients 65 years of age or older who were rehospitalized for thromboembolism within three months after total hip arthroplasty. We compared demographic, surgical, and medical variables potentially associated with the development of thromboembolism in these patients and 592 unmatched controls. RESULTS: A total of 89.6 percent of patients with thromboembolism and 93.8 percent of control patients were treated with pneumatic compression, warfarin, enoxaparin, or unfractionated heparin, alone or in combination. In addition, 22.2 percent and 29.7 percent, respectively, received warfarin after discharge. A body-mass index (the weight in kilograms divided by the square of the height in meters) of 25 or greater was associated with rehospitalization for thromboembolism, with an odds ratio of 2.5 (95 percent confidence interval, 1.8 to 3.4). In a multivariate model, the only prophylactic regimens associated with a reduced risk of thromboembolism were pneumatic compression in patients with body-mass indexes of less than 25 (odds ratio, 0.3; 95 percent confidence interval, 0.2 to 0.6) and warfarin treatment after discharge (odds ratio, 0.6; 95 percent confidence interval, 0.4 to 1.0). CONCLUSIONS: In patients who underwent total hip arthroplasty, a body-mass index of 25 or greater was associated with subsequent hospitalization for thromboembolism. Pneumatic compression in patients with a body-mass index of less than 25 and prophylaxis with warfarin after discharge were independently protective against thromboembolism. (+info)
Intermittent pneumatic compression devices -- physiological mechanisms of action.
There are many reports of how IPC is used effectively in the clinical setting; including the prevention of deep venous thrombosis, improvement of circulation in patients with lower extremity arterial diseases, reduction of lymphoedema, and the healing of venous ulcers. However, despite the widely accepted use of IPC, it is still unclear how IPC actually exerts its beneficial effects. The exact physiological mechanisms of action are unknown. The clinical utility of IPC and the putative mechanisms by which IPC could exert its therapeutic effect will be reviewed. The paper will examine the mechanical effects of IPC exerted on the lower extremity, and the subsequent biochemical changes in the circulation. In vitro studies of the effects of mechanical stress such as compressive strain and shear on cultured endothelial cells, and their clinical relevance to IPC will also be reviewed. (+info)
Effects of exercise pressor reflex activation on carotid baroreflex function during exercise in humans.
1. This investigation was designed to determine the contribution of the exercise pressor reflex to the resetting of the carotid baroreflex during exercise. 2. Ten subjects performed 3.5 min of static one-legged exercise (20 % maximal voluntary contraction) and 7 min dynamic cycling (20 % maximal oxygen uptake) under two conditions: control (no intervention) and with the application of medical anti-shock (MAS) trousers inflated to 100 mmHg (to activate the exercise pressor reflex). Carotid baroreflex function was determined at rest and during exercise using a rapid neck pressure/neck suction technique. 3. During exercise, the application of MAS trousers (MAS condition) increased mean arterial pressure (MAP), plasma noradrenaline concentration (dynamic exercise only) and perceived exertion (dynamic exercise only) when compared to control (P < 0.05). No effect of the MAS condition was evident at rest. The MAS condition had no effect on heart rate (HR), plasma lactate and adrenaline concentrations or oxygen uptake at rest and during exercise. The carotid baroreflex stimulus-response curve was reset upward on the response arm and rightward to a higher operating pressure by control exercise without alterations in gain. Activation of the exercise pressor reflex by MAS trousers further reset carotid baroreflex control of MAP, as indicated by the upward and rightward relocation of the curve. However, carotid baroreflex control of HR was only shifted rightward to higher operating pressures by MAS trousers. The sensitivity of the carotid baroreflex was unaltered by exercise pressor reflex activation. 4. These findings suggest that during dynamic and static exercise the exercise pressor reflex is capable of actively resetting carotid baroreflex control of mean arterial pressure; however, it would appear only to modulate carotid baroreflex control of heart rate. (+info)
Effects of hypergravity and anti-G suit pressure on intraregional ventilation distribution during VC breaths.
The effects of increased gravity in the head-to-foot direction (+G(z)) and pressurization of an anti-G suit (AGS) on total and intraregional intra-acinar ventilation inhomogeneity were explored in 10 healthy male subjects. They performed vital capacity (VC) single-breath washin/washouts of SF(6) and He in +1, +2, or +3 G(z) in a human centrifuge, with an AGS pressurized to 0, 6, or 12 kPa. The phase III slopes for SF(6) and He over 25-75% of the expired VC were used as markers of total ventilation inhomogeneity, and the (SF(6) -- He) slopes were used as indicators of intraregional intra-acinar inhomogeneity. SF(6) and He phase III slopes increased proportionally with increasing gravity, but the (SF(6) -- He) slopes remained unchanged. AGS pressurization did not change SF(6) or He slopes significantly but resulted in increased (SF(6) -- He) slope differences at 12 kPa. In conclusion, hypergravity increases overall but not intraregional intra-acinar inhomogeneity during VC breaths. AGS pressurization provokes increased intraregional intra-acinar ventilation inhomogeneity, presumably reflecting the consequences of basilar pulmonary vessel engorgement in combination with compression of the basilar lung regions. (+info)
Home use of impulse compression of the foot and compression stockings in the treatment of chronic venous insufficiency.
PURPOSE: The use of intermittent pneumatic compression, in addition to elastic bandages or stockings, accelerates the healing of leg ulcers in patients with severe chronic venous insufficiency (CVI). There is recent evidence that impulse compression of the plantar venous plexus reduces post-traumatic ankle swelling and prevents postoperative venous thromboembolism. The purpose of this study was to evaluate the clinical and hemodynamic responses after home use of impulse foot compression for 3 months in patients already using therapeutic compression stockings for the management of CVI. METHODS: Twelve extremities from 9 patients with documented CVI, class 4 to 5 according to the Clinical, Etiology, Anatomy, Pathophysiology classification system, were included in this prospective cohort study. All patients were instructed to use a foot pump device at home for 2 hours a day for 3 months in addition to therapeutic compression stockings (30-40 mm Hg) worn during the day. The device was set to three cycles (3 seconds) of compression (120 mm Hg) per minute. A clinical scoring system was completed before foot compression and 1, 2, and 3 months thereafter. In addition, all patients underwent air plethysmography studies at the same time intervals, including venous volume, venous filling index, ejection fraction, and residual volume fraction. RESULTS: Patients reported significant improvement in their scores for swelling (P <.05) and pain (P <.04). Air plethysmography showed a reduction in venous volume and venous filling index, although these differences were not significant. Ejection fraction remained unchanged and residual volume fraction was significantly reduced (P <.05) compared with baseline. The foot compression devices were well tolerated by all the patients in the study. CONCLUSIONS: The use of home foot impulse compression plus elastic stockings significantly reduced the residual volume fraction as measured by air-plethysmography in a group of patients with severe CVI. This favorable hemodynamic response could, in part, explain the clinical improvement achieved by this combined treatment. However, this represents a preliminary pilot study that needs to be confirmed in future randomized controlled studies with more patients included. (+info)