Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators.

BACKGROUND: The TIMI 14 trial tested the hypothesis that abciximab, the Fab fragment of a monoclonal antibody directed to the platelet glycoprotein (GP) IIb/IIIa receptor, is a potent and safe addition to reduced-dose thrombolytic regimens for ST-segment elevation MI. METHODS AND RESULTS: Patients (n=888) with ST-elevation MI presenting <12 hours from onset of symptoms were treated with aspirin and randomized initially to either 100 mg of accelerated-dose alteplase (control) or abciximab (bolus 0.25 mg/kg and 12-hour infusion of 0.125 microg. kg-1. min-1) alone or in combination with reduced doses of alteplase (20 to 65 mg) or streptokinase (500 000 U to 1.5 MU). Control patients received standard weight-adjusted heparin (70-U/kg bolus; infusion of 15 U. kg-1. h-1), whereas those treated with a regimen including abciximab received low-dose heparin (60-U/kg bolus; infusion of 7 U. kg-1. h-1). The rate of TIMI 3 flow at 90 minutes for patients treated with accelerated alteplase alone was 57% compared with 32% for abciximab alone and 34% to 46% for doses of streptokinase between 500 000 U and 1.25 MU with abciximab. Higher rates of TIMI 3 flow at both 60 and 90 minutes were observed with increasing duration of administration of alteplase, progressing from a bolus alone to a bolus followed by either a 30- or 60-minute infusion (P<0.02). The most promising regimen was 50 mg of alteplase (15-mg bolus; infusion of 35 mg over 60 minutes), which produced a 76% rate of TIMI 3 flow at 90 minutes and was tested subsequently in conjunction with either low-dose or very-low-dose (30-U/kg bolus; infusion of 4 U. kg-1. h-1) heparin. TIMI 3 flow rates were significantly higher in the 50-mg alteplase plus abciximab group versus the alteplase-only group at both 60 minutes (72% versus 43%; P=0.0009) and 90 minutes (77% versus 62%; P=0.02). The rates of major hemorrhage were 6% in patients receiving alteplase alone (n=235), 3% with abciximab alone (n=32), 10% with streptokinase plus abciximab (n=143), 7% with 50 mg of alteplase plus abciximab and low-dose heparin (n=103), and 1% with 50 mg of alteplase plus abciximab with very-low-dose heparin (n=70). CONCLUSIONS: Abciximab facilitates the rate and extent of thrombolysis, producing early, marked increases in TIMI 3 flow when combined with half the usual dose of alteplase. This improvement in reperfusion with alteplase occurred without an increase in the risk of major bleeding. Substantial reductions in heparin dosing may reduce the risk of bleeding even further. Modest improvements in TIMI 3 flow were seen when abciximab was combined with streptokinase, but there was an increased risk of bleeding.

Marked systemic hypotension depresses coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator.

OBJECTIVES: This study was designed to test the hypothesis that the level of aortic blood pressure affects the rate and extent of coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND: Although many studies have confirmed the efficacy of thrombolytic therapy in the treatment of acute myocardial infarction, the effects of altered blood pressure on coronary thrombolysis have not been studied. Because the aortic pressure represents the coronary artery inflow pressure, first principles predict that changes in blood pressure will affect the delivery of the thrombolytic agent and thus affect thrombolysis. METHODS: The effects of large changes in blood pressure on coronary thrombolysis were studied in a canine model. Coronary thrombosis was induced by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, 24 dogs were classified into three groups of 8 dogs each: Group 1 dogs underwent phlebotomy to adjust systolic blood pressure to 130 mm Hg; Group 2 dogs underwent phlebotomy to decrease systolic blood pressure to 75 mm Hg. Dogs in Group 3 also underwent phlebotomy to achieve a systolic blood pressure of 75 mm Hg and then received norepinephrine to increase this pressure to 130 mm Hg. After adjustment in blood pressure, all dogs received an infusion of rt-PA (0.25 mg/kg body weight) over 30 min through the left anterior descending artery catheter. In a fourth group of six dogs, the effect of altered blood pressure on the rate of coronary thrombolysis was assessed. RESULTS: In dogs in Groups 1 and 3, the rate and extent of coronary thrombolysis were significantly increased compared with values in Group 2. In each of the six Group 4 dogs the rate of coronary thrombolysis increased when norepinephrine increased systolic blood pressure from 75 to 130 mm Hg. CONCLUSIONS: These results indicate that a moderate increase in coronary inflow pressure increases the rate and extent of coronary thrombolysis compared with values during marked systemic hypotension.

Intraaortic balloon counterpulsation enhances coronary thrombolysis induced by intravenous administration of a thrombolytic agent.

OBJECTIVES: This study was designed to test the hypothesis that in the presence of moderate hypotension, intraaortic balloon counterpulsation would enhance coronary thrombolysis induced by intravenous administration of recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND: Although many studies have confirmed the efficacy of thrombolytic therapy in acute myocardial infarction, few have systematically investigated the effects of alterations in aortic pressure on coronary thrombolysis, and none have previously investigated the effects of intraaortic balloon counterpulsation on thrombolysis. METHODS: The effects of intraaortic balloon counterpulsation on aortic pressure, coronary blood flow and coronary thrombolysis were studied in a canine model. Coronary thrombosis was induced in eight dogs by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, dogs underwent phlebotomy to decrease systolic aortic pressure to approximately 90 mm Hg. After phlebotomy, during a 15-min interval of intravenous administration of rt-PA, coronary thrombolysis and coronary flow were determined during and in the absence of counterpulsation. RESULTS: Intraaortic balloon counterpulsation significantly increased aortic diastolic pressure. Corresponding to the increase in pressure, intraaortic balloon counterpulsation significantly increased the rate of rt-PA-induced coronary thrombolysis. Although not statistically significant, peak diastolic coronary flow tended to increase with counterpulsation. CONCLUSIONS: These results indicate that in the presence of moderate systemic hypotension, intraaortic balloon counterpulsation enhances the rate of rt-PA-induced coronary thrombolysis.

Validity of the hepatojugular reflux as a clinical test for congestive heart failure.

This study describes observations designed to test the validity of the hepatojugular reflux as an indicator of actual or incipient heart failure. The central venous pressure (CVP) could be predicted from the height of the jugular venous pulsations in 44 of 48 comparisons. In the remaining comparisons, discrepancies ranged from 5 to 7 mm Hg. In patients with normal resting cardiac function, abdominal compression did not cause an increase in CVP of greater than 2 mm Hg (2.7 mm H2O). In 16 of 19 patients with impaired function, CVP increased by greater than or equal to 3 mm Hg. The increase in CVP was estimated from neck veins to within 2 mm Hg in all but 3 instances. CVP stabilized by 10 seconds and did not change over the subsequent 60 seconds. Abdominal compression caused no consistent change in cardiac output. Changes in venous pressure could not be attributed to changes in esophageal pressure or to compression of the heart by elevation of the diaphragm. Observations were consistent with the hypothesis that an increase in right-sided cardiac filling pressures resulting from abdominal compression carried out as described here, reflects both the volume of blood in the abdominal veins and the ability of the ventricles to respond to increased venous return, and constitutes a useful clinical test for detecting congestive cardiac failure. An increase of 3 cm in the height of neck vein distention is a reasonable upper limit of normal.

Optimizing coronary thrombolysis with i.v. administration of recombinant tissue plasminogen activator. Single bolus vs double bolus vs front-loading.

This study was designed to compare the efficacy of coronary thrombolysis obtained with i.v. administration of three dose regimens of recombinant tissue plasminogen activator (rtPA). Although many studies have confirmed the efficacy of thrombolytic therapy in treatment of acute myocardial infarction, few prospective studies have been designed to determine which dose regimen optimizes the rate of coronary thrombolysis. A canine model was used. Coronary thrombosis was induced by injection of radioactive, autologous blood clots through a catheter placed in the left anterior descending coronary artery. Subsequently, 15 dogs were randomized into 3 groups of 5 dogs each. In group 1 dogs, 1.25 mg/kg of rtPA was administered i.v. as a bolus; in the group 2 dogs, 1.25 mg/kg of rtPA was administered over 60 min. The administration was "front loaded" so that 15% was administered as a bolus, 60% over 30 min, and 25% over 30 min; in group 3, 1.25 mg/kg of rtPA was divided into two i.v. boluses and administered 15 min apart. Coronary thrombolysis was assessed with a gamma camera. Despite differences in rate of administration of rtPA, at 15, 30, and 90 min after onset of treatment, extent of clot lysis was similar between groups. These results indicate that despite differences in dose regimens, rates of thrombolysis are similar when i.v. rtPA is relatively rapidly administered. Further, the similar rates of clot lysis over time between groups suggest both an effective upper limit to the dose-thrombolytic rate relationship and relatively high, sustained steady-state plasma concentrations of rtPA.

Thoracicoabdominal mechanics during resuscitation maneuvers.

The importance of intrathoracic pressure in generating blood flow during cardiopulmonary resuscitation has recently been emphasized. The purpose of this study was to investigate the factors involved in generating intrathoracic pressure. Studies were performed in anesthetized paralyzed dogs with the circulation intact. Balloon-tipped catheters were placed in the abdomen and esophagus for measurement of intra-abdominal and intrathoracic pressures and cannula placed in the airway for airway pressure. The following four maneuvers were studied: (1) chest compression with open airway; (2) chest compression with closed airway; (3) pulmonary inflation to transpulmonary pressure (TP) of 30 cm H2O (TP = 30); and (4) chest compression plus pulmonary inflation (TP = 30). We found that under static conditions, chest compression alone produced small positive intrathoracic pressures (9 +/- 8 cm H2O), but these could be increased by closing the airway pressure (18 +/- 6 cm H2O) or inflating the lungs (15 +/- 7 cm H2O). The combination of inflating the lung and compressing the chest produced the highest intrathoracic pressure (48 +/- 18 cm H2O; p less than 0.001). The pressure developed was highly variable and the distribution of pressures within the thorax was not uniform. As the intrathoracic pressure became large, a pressure gradient developed from thorax to abdomen, and the diaphragm everted; this pressure gradient could divert blood from the brain.

Effect of a mechanical vs a pharmacologic increase in aortic pressure on coronary blood flow and thrombolysis induced by IV administration of a thrombolytic agent.

This study was designed to compare the effect of a mechanical vs a pharmacologic increase in BP on coronary artery blood flow and thrombolysis induced by IV administration of recombinant tissue plasminogen activator. We employed a canine model of coronary thrombosis induced by injection of radioactive blood clot in the left anterior descending coronary artery. Subsequently, all dogs underwent phlebotomy to decrease systolic BP to 75 mm Hg and this decreased coronary blood flow by 50%. BP was increased to 130 mm Hg by norepinephrine (NE) infusion or by inflation of a Fogarty catheter placed in the descending aorta. Interventions with NE or with a Fogarty balloon catheter increased coronary artery blood flow to similar values and rates of coronary thrombolysis were similar. However, cardiac output was significantly higher with NE. These results indicate coronary clot lysis is dependent on perfusion pressure and coronary blood flow, not cardiac output.

Intravenous administration of recombinant tissue plasminogen activator. Optimizing the rate of coronary thrombolysis.

Although many studies have confirmed the efficacy of thrombolytic therapy in treatment of acute myocardial infarction, few studies have been designed to determine which dose regimen optimizes the rate of coronary thrombolysis. This study was designed to compare the efficacy of coronary thrombolysis obtained with intravenous administration of three dose regimens of recombinant tissue plasminogen activator (rtPA). The same total dose was administered as a bolus, over 30 min, or over 90 min. A canine model was employed. Coronary thrombosis was induced by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, 18 dogs were randomized into 3 groups of 6 dogs each. In group 1 dogs, 0.5 mg/kg of rtPA was administered intravenously as a bolus; in the group 2 dogs, rtPA was administered intravenously over 30 min (rtPA30); in the group 3 dogs, the drug was administered over 90 min (rtPA90). Coronary thrombolysis was assessed with a gamma camera. While at 100 min, the extent of clot lysis was similar between groups, 15 and 30 min after the start of rtPA administration, coronary thrombolysis was significantly less in the rtPA90 group. These results indicate that for a given total dose of rtPA, the rate of intravenous administration may significantly affect the rate of coronary thrombolysis.

Effect of low-molecular-weight heparin on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.

We employed a canine model of pulmonary embolism induced by radioactive blood clots to determine if low-molecular-weight heparin augments recombinant tissue plasminogen activator (rtPA)-induced thrombolysis. Following embolization, dogs were randomized: group 1 dogs received heparin; group 2 dogs received low-molecular-weight heparin; group 3 dogs received 1.5 mg/kg of rtPA over 45 minutes; group 4 dogs received rtPA 3 mg/kg over 45 minutes; and group 5 dogs received 1.5 mg/kg of rtPA plus low-molecular-weight heparin. Over three hours, little thrombolysis occurred in groups 1 and 2. In contrast, significant thrombolysis occurred in groups 3 to 5, 46 percent, 49 percent, and 46 percent, respectively (all p less than 0.01 compared with groups 1 and 2). We conclude that there is an upper limit to the dose-thrombolytic rate relationship with rtPA, and that low-molecular-weight heparin does not augment rtPA-induced thrombolysis.

Hemodynamic management in clinical acute hypoxemic respiratory failure. Dopamine vs dobutamine.

We investigated short-term hemodynamic effects of dopamine and dobutamine in eight patients with acute hypoxemic respiratory failure. We tested the hypothesis that for a similar increase in cardiac output, left ventricular filling pressure (pulmonary capillary wedge pressure [PCWP]) would increase with dopamine and decrease with dobutamine. Dopamine increased cardiac output (p less than 0.05), stroke volume (p less than 0.05), and PCWP (p less than 0.01). Cardiac output increased almost 20 percent when PCWP increased 50 percent with dopamine. In contrast, despite a mean 30 percent increase in cardiac output with dobutamine (p less than 0.01), PCWP decreased. In six of these patients, left ventricular end-diastolic volumes and end-systolic volumes were measured using scintigraphic techniques. In all patients, end-diastolic volume increased with dopamine (p less than 0.05); and in four of six, end-systolic volume increased. In contrast, with dobutamine, in five of six patients, end-diastolic volume decreased; and in all six patients, end-systolic volume decreased. There was a small increase in intrapulmonary shunt with both drugs. We conclude that if an inotropic agent is required to increase cardiac output in patients with acute hypoxemic respiratory failure, dobutamine is probably preferred over dopamine.

Coronary thrombolysis. Comparative effects of intracoronary administration of recombinant tissue plasminogen activator and urokinase.

We employed a canine model of coronary thrombosis, induced by injection of radioactive blood clot, via a catheter placed in the left anterior descending coronary artery, to compare effects of intracoronary administration of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) on rate and extent of coronary thrombolysis. Two doses of UK, 15,000 U/kg (UK15) and 30,000 U/kg (UK30) and two doses of rtPA, 0.25 mg/kg (rtPA.25) and 0.75 mg/kg (rtPA.75) were given. Drugs were infused over 45 min. Compared with the other regimens, rate and extent of coronary thrombolysis were significantly increased with rtPA.75. Also, despite a much higher dose of UK, coronary thrombolysis was similar with UK30 and rtPA.25. Compared with UK15, rate and extent of coronary thrombolysis were increased with rtPA.25. These results indicate that intracoronary administration of rtPA is superior to intracoronary UK in inducing thrombolysis.

Coronary thrombolysis with recombinant tissue plasminogen activator. Intracoronary vs intravenous administration.

We employed a canine model of coronary thrombosis, induced by injection of radioactive blood clot, via a catheter placed in the left anterior descending coronary artery, to compare effects of recombinant tissue plasminogen activator (rtPA) administered intravenously and administered directly into the coronary circulation. A control group did not receive rtPA. Compared with controls, both rtPA regimens induced coronary thrombolysis. However, compared with intravenous administration, rate and extent of coronary thrombolysis were increased with intracoronary administration. Most likely, the enhanced thrombolysis with intracoronary administration is explained by an increase in delivery of the drug to the thrombus.

Effects of hydralazine and increased cardiac output on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.

We employed a canine model of pulmonary embolism, induced by injection of autologous radiolabelled blood clots, to investigate effects of hydralazine and an increase in cardiac output per se on recombinant tissue plasminogen activator-induced thrombolysis. Emboli increased pulmonary artery pressure (PAP) and decreased CO from 2.7 to 1.8 L/min-1. Following embolization, dogs were randomly divided into three groups. Group 1 received .5 mg/kg of rtPA over 30 minutes. Group 2 received the same dose of rtPA and were pretreated with hydralazine to increase CO approximately 50 percent. In the group 3 dogs, CO was increased by opening a systemic A-V fistula. Following embolization, CO remained low in group 1, the mean 2 h time-averaged CO was 1.9 L/min-1. The CO was 2.9 and 3.1 L/min-1 in groups 2 and 3, respectively. Corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in CO augments rtPA-induced pulmonary thrombolysis.

Pulmonary vascular pressure-flow characteristics in canine pulmonary embolism.

We tested the hypothesis that, in canine embolic pulmonary hypertension, upstream transmission of increased left atrial pressure (LAP) is inversely related to the level of the pressure intercept (PI) obtained by extrapolation from the linear pulmonary vascular pressure-flow (P-Q) plot. P-Q coordinates were obtained by varying Q through systemic fistulas. Seven group 1 dogs were embolized with autologous blood clot to produce marked pulmonary hypertension and mean pulmonary arterial pressure (PAP), and PI increased from 15 to 41 mmHg (P less than 0.001) and from 8.8 to 31 mmHg (P less than 0.001), respectively. Before and after embolization we assessed effects of increased LAP, produced by inflation of a left atrial balloon, on PAP at constant Q. Embolization depressed the mean slope of this relationship from 0.78 to 0.16 (P less than 0.001). Subsequently, six group 2 dogs were embolized to produce moderate pulmonary hypertension with a mean PI of 22 mmHg. This value was significantly less than PI in group 1 (P less than 0.01). After embolization, the slope of the PAP-LAP relationship was greater in group 2 than group 1: 0.47 vs. 0.16 (P less than 0.01). We conclude that the upstream transmission of left atrial pressure is inversely related to PI and that marked embolic pulmonary hypertension produces an effective vascular waterfall.

Effects of left atrial pressure on the pulmonary vascular response to hypoxic ventilation.

We investigated the effects of hypoxic ventilation on the pulmonary arterial pressure- (P) flow (Q) relationship in an intact canine preparation. Mean pulmonary P-Q coordinates were obtained during hypoxic ventilation and during ventilation with 100% O2 at normal and at increased left atrial pressure. Specifically, we tested the hypothesis that, over a wide range, changes in left atrial pressure would alter the effects of hypoxic ventilation on pulmonary P-Q characteristics. Seven dogs were studied. When left atrial pressure was normal (5 mmHg), the mean value of the extrapolated intercept (PI) of the linear P-Q relationship was 10.9 mmHg and the slope (incremental vascular resistance, IR) of the P-Q relationship was 2.2 mmHg.l-1.min. Hypoxic ventilation increased PI to 18 mmHg (P less than 0.01) but did not affect IR. Subsequently, during ventilation with 100% O2, when left atrial pressure was increased to 14 mmHg by inflation of left atrial balloon, PI increased to 18 mmHg. IR was 1.6 mmHg.l-1.min. Again, hypoxic ventilation caused an isolated change in PI. Hypoxia increased PI from 18 to 28 mmHg (P less than 0.01). As in the condition of normal left atrial pressure, hypoxic ventilation did not affect IR. We conclude that, in an anesthetized intact canine preparation, hypoxic ventilation causes an isolated increase in the extrapolated pressure intercept of the pulmonary P-Q relationship. Furthermore the effects of hypoxic ventilation on pulmonary P-Q characteristics are not affected by the resting left atrial pressure.

Effects of flow on recombinant tissue plasminogen activator-induced pulmonary thrombolysis.

We employed a canine model of pulmonary embolism induced by injection of radioactive blood clots to investigate effects of changes in cardiac output (CO) on recombinant tissue plasminogen activator- (rtPA) induced pulmonary thrombolysis. Rate and extent of thrombolysis were assessed with a gamma camera. Eighteen dogs were studied. Emboli increased mean pulmonary arterial pressure and decreased CO from 2.6 to 1.9 l/min (P less than 0.001). Subsequently, dogs were randomly divided into three groups: group 1 received 0.5 mg/kg of rtPA over 30 min; 30 min before the same dose regimen of rtPA, in the six group 2 dogs, mean CO was increased to approximately 3.25 l/min by opening one systemic arteriovenous fistula; in the six group 3 dogs, before rtPA, mean CO was increased to approximately 4.5 l/min by opening two or three fistulas. After embolization, CO remained low in group 1; the mean 2-h time-averaged CO was 1.8 l/min. CO was much higher in groups 2 and 3 (3.3 and 4.6 l/min, respectively; both P less than 0.001 compared with group 1; and P less than 0.001, group 2 vs. group 3). Compared with group 1, corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in flow per se augments rtPA-induced pulmonary thrombolysis. Also, because thrombolysis was similar between groups 2 and 3, these results define an upper limit to the flow-thrombolytic relationship with rtPA.

Influence of walking volume on health benefits in women post-menopause.

The health benefits of physical activity are believed to be related more to exercise volume than to intensity. In this 24-wk study, we examined the effect of walking volume on aerobic fitness, serum lipids, and body composition in women post-menopause, a population at risk for coronary artery disease. Of 79 women randomly assigned to groups at the outset, 56 completed the study (mean age 61.3 +/- 5.8). Participants walked at an intensity of 60% peak oxygen uptake (VO2peak) for 60 min, 3 d.wk-1 (N = 19) or 5 d.wk-1 (N = 17), or remained sedentary (N = 20). Walking 3 or 5 d.wk-1 increased VO2peak (ml.kg-1.min-1) by 12% and 14%, respectively (P < 0.01). There were no changes in serum lipids in response to either program. Percent body fat decreased by 1.1% and 1.3% in those walking 3 and 5 d.wk-1, respectively; both changes significantly different from the control group (P < 0.05). Walking 5 d.wk-1 did not result in more health benefits than 3 d.wk-1, possibly due to a greater compensatory decline in activities other than the walking program, or greater discrepancies between actual and reported activity and food intake. Longer-duration programs, or simultaneous changes in diet, may be necessary to alter serum lipids in nonobese, normo-lipidemic women post-menopause.

An increase in low aortic pressure increases coronary artery flow and coronary thrombolysis induced by intravenous administration of recombinant tissue plasminogen activator.

PURPOSE: Our study investigated the effects of an increase in aortic pressure, induced by norepinephrine (NE) administration on coronary artery flow in a clotted artery, and rate of coronary thrombolysis induced by intravenous (i.v.) administration of recombinant tissue plasminogen activator (rtPA). METHODS: A canine model of coronary thrombosis, induced by intracoronary injection of radioactive autologous blood clots, was used to test the hypothesis that an increase in aortic blood pressure will increase coronary artery flow and the rate of clot lysis induced by i.v. administration of rtPA. RESULTS: After clot injection, 11 dogs were phlebotomized to decrease systolic aortic pressure to 75 mm Hg. Subsequently, .25 mg/kg of rtPA was administered intravenously over two 15-minute intervals, one during hypotension, and the other after NE infusion had increased systolic blood pressure to 130 mm Hg. In six dogs the hypotensive condition was studied first, and in five dogs the NE-induced normotensive condition was studied first. In all dogs, coronary artery flow and the rate of clot lysis were significantly increased in the normotensive condition. CONCLUSIONS: These results indicate that an increase in a low coronary artery perfusion pressure may enhance coronary artery flow and the rate of thrombolysis.

Retrieval of Silastic catheter fragment from heart in septic thromboembolism complicating aplastic anemia.

A 42-year-old man with aplastic anemia presented to hospital toxic and septic secondary to central Silastic catheter sepsis. The chronic indwelling catheter fractured during an attempt at removal and the distal remnant embolized to the right ventricular outflow tract and main pulmonary artery precipitating near cardiopulmonary collapse. The thrombosed catheter was successfully retrieved under fluoroscopy by an endovascular snare technique thus avoiding operative intervention in this immunosuppressed, thrombocytopenic and septic individual. The patient had an uneventful recovery.

Serum ferritin and heart disease: the effect of moderate exercise on stored iron levels in postmenopausal women.

OBJECTIVE: To determine the effect of a moderate exercise regimen on stored iron as measured by serum ferritin in previously sedentary postmenopausal women. DESIGN: Randomized assignment to one of three groups: a five day/week walking group (five-day group, n = 27); a three day/week walking group (three-day group, n = 27) or a sedentary group (control group, n = 25). SETTING: Community-based intervention. PARTICIPANTS: Women who were postmenopausal, over 50 years old, sedentary, not on hormone replacement therapy, nonsmokers, physically capable of exercising, without clinical signs of cardiovascular, pulmonary or metabolic disease, and not on medication that would affect iron metabolism. In addition, they had neither donated blood nor been transfused within the previous 12 months. All participants were screened volunteers who had responded to media advertisements. Seventy-nine participants met these criteria. Results are reported for 56 subjects (five-day group, n = 17; three-day group, n = 19; control group, n = 20) who completed the study. Their mean age was 61.3 +/- 5.8 years. INTERVENTION: The five-day group and the three-day group walked an average of 279 +/- 20 and 171 +/- 7 mins/week, respectively. Participants were counselled not to change their dietary intake. MAIN RESULTS: Following 24 weeks of walking, mean serum ferritin decreased significantly in the five-day group (P < 0.03), but not in the three-day group (P < 0.09) compared with controls. CONCLUSIONS: The extent of physical activity required to elicit a decrease in stored iron in postmenopausal women was determined. This may be clinically significant because stored iron increases significantly following menopause and excess stored iron have been cited as risk factors for coronary artery disease.