Monomorphic ventricular tachycardia caused by arsenic trioxide therapy for acute promyelocytic leukaemia.

Arsenic trioxide has become the treatment of choice for patients with acute promyelocytic leukaemia. Cardiovascular toxicity is known to occur with this therapy, in particular heart rhythm disorders due to QT interval prolongation. We present a case of ventricular arrhythmia with no QT prolongation in a patient receiving arsenic trioxide therapy.

Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment.

The demonstration that angiogenic growth factors can stimulate new blood vessel growth and restore perfusion in animal models of myocardial ischemia has led to the development of strategies designed for the local production of angiogenic growth factors in patients who are not candidates for conventional revascularization. The results of recent clinical trials of proangiogenesis gene therapy have been disappointing; however, significant limitations in experimental design, in particular in gene transfer strategies, preclude drawing definitive conclusions. In the REVASC study cardiac gene transfer was optimized by direct intramyocardial delivery of a replication-deficient adenovirus-containing vascular endothelial growth factor (AdVEGF121, 4 x 10(10) particle units (p.u.)). Sixty-seven patients with severe angina due to coronary artery disease and no conventional options for revascularization were randomized to AdVEGF121 gene transfer via mini-thoracotomy or continuation of maximal medical treatment. Exercise time to 1 mm ST-segment depression, the predefined primary end-point analysis, was significantly increased in the AdVEGF121 group compared to control at 26 weeks (P=0.026), but not at 12 weeks. As well, total exercise duration and time to moderate angina at weeks 12 and 26, and in angina symptoms as measured by the Canadian Cardiovascular Society Angina Class and Seattle Angina Questionnaire were all improved by VEGF gene transfer (all P-values at 12 and 26 weeks < or =0.001). However, if anything the results of nuclear perfusion imaging favored the control group, although the AdVEGF121 group achieved higher workloads. Overall there was no significant difference in adverse events between the two groups, despite the fact that procedure-related events were seen only in the thoracotomy group. Therefore, administration of AdVEGF121 by direct intramyocardial injections resulted in objective improvement in exercise-induced ischemia in patients with refractory ischemic heart disease.

Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb/IIIa receptors. Evaluation of Platelet IIb/IIIa Inhibition in Stenting Investigators.

BACKGROUND: Inhibition of the platelet glycoprotein IIb/IIIa receptor with the monoclonal-antibody fragment abciximab reduces the acute ischemic complications associated with percutaneous coronary revascularization, whereas coronary-stent implantation reduces restenosis. We conducted a trial to determine the efficacy of abciximab and stent implantation in improving long-term outcome. METHODS: A total of 2399 patients were randomly assigned to stent implantation and placebo, stent implantation and abciximab, or balloon angioplasty and abciximab. The patients were followed for six months. RESULTS: At six months, the incidence of the composite end point of death or myocardial infarction was 11.4 percent in the group that received a stent and placebo, as compared with 5.6 percent in the group that received a stent and abciximab (hazard ratio, 0.47; 95 percent confidence interval, 0.33 to 0.68; P<0.001) and 7.8 percent in the group assigned to balloon angioplasty and abciximab (hazard ratio, 0.67; 95 percent confidence interval, 0.49 to 0.92; P=0.01). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.70 (95 percent confidence interval, 0.48 to 1.04; P=0.07). The rate of repeated revascularization of the target vessel was 10.6 percent in the stent-plus-placebo group, as compared with 8.7 percent in the stent-plus-abciximab group (hazard ratio, 0.82; 95 percent confidence interval, 0.59 to 1.13; P=0.22) and 15.4 percent in the angioplasty-plus-abciximab group (hazard ratio, 1.49; 95 percent confidence interval, 1.13 to 1.97; P=0.005). The hazard ratio for stenting plus abciximab as compared with angioplasty plus abciximab was 0.55 (95 percent confidence interval, 0.41 to 0.74; P<0.001). Among patients with diabetes, the combination of abciximab and stenting was associated with a lower rate of repeated target-vessel revascularization (8.1 percent) than was stenting and placebo (16.6 percent, P=0.02) or angioplasty and abciximab (18.4 percent, P=0.008). CONCLUSIONS: For coronary revascularization, abciximab and stent implantation confer complementary long-term clinical benefits.

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.

The role of glycoprotein IIb/IIIa platelet inhibition in percutaneous coronary intervention in the stent era.

In autumn 1996, shortly after the platelet glycoprotein (GP) IIb/IIIa inhibitor abciximab was approved for clinical use by the Health Protection Branch of Health Canada, seven interventional cardiologists met in a roundtable forum to review the use of abciximab in percutaneous transluminal coronary angioplasty (PTCA). While a compelling body of data was presented that argued strongly for adjunctive abciximab in conventional balloon angioplasty, the participants found in difficult to extrapolate the findings to contemporary interventional practice dominated by stent implantation. This uncertainty stemmed from the lack of clinical trials of abciximab during the stent era. Concerns were also raised that the unrestricted use of two expensive therapeutic modalities (stent implantation and GP IIb/IIIa inhibition) would place severe strains on catheterization laboratory budgets. The general consensus was that, pending the availability of further data, abciximab should probably be reserved for selected at-risk patients. This article summarized the roundtable discussions to provide cardiologists' perspectives on the use of abciximab in interventional practice. An overview of platelet physiology and the rationale for GP IIb/IIIa receptor inhibition; a summary of the results of recent randomized clinical trials that assessed the efficacy of abciximab in PTCA; an account of how stents became the most prevalent technique used in coronary intervention; a summary of the available data evaluating abciximab in conjunction with stent implantation; and a synopsis of the conference discussions are included.

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.

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.

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.

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.

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.

Walking program reduces elevated cholesterol in women postmenopause.

OBJECTIVE: To examine the effect of a moderate exercise regimen on total serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), body composition and cardiovascular fitness (VO2 max) in mildly hyperlipidemic women, postmenopause. DESIGN: Randomized assignment to walking (n = 24) or control (n = 16) groups. SETTING: Community based intervention. PARTICIPANTS: Over 300 volunteers were screened to obtain the sample of 40 eligible women. Participants were mildly hyperlipidemic, postmenopause (mean age 62.0 +/- 5.7 years), sedentary, nonsmokers and not on hormone replacement therapy. Results are reported for the 25 subjects (15 walkers, 10 controls) who completed the study. INTERVENTION: Exercisers walked an average of 54.3 +/- 7.7 mins/day, 4.9 +/- 1.7 days/week, at an intensity of 54% maximum heart rate reserve, for six months. Participants were counselled not to change their diets. MAIN RESULTS: Total serum cholesterol, triglyceride, total serum cholesterol: HDL-C ratio, weight and fat mass decreased significantly in the walkers compared with the controls (P < 0.05), as did body mass index (P < 0.01). Walking resulted in a significant increase in VO2 max (P < 0.01). Changes in serum lipids were significantly related to changes in body fat, but not to change in aerobic fitness. There were no changes in dietary intake. CONCLUSIONS: A moderate intensity exercise program induces favourable alterations in total serum cholesterol and other atherogenic indices in hyperlipidemic women postmenopause, and these changes are related more to loss of body fat than to increased fitness level.

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.

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.

Effects of progressive vascular occlusion on slope and intercept of the pulmonary artery pressure-flow relationship.

Pulmonary hemodynamics may be described by mean pulmonary arterial pressure (PAP)-cardiac output (CO) plots. The slope of the PAP-CO relationship may define the incremental resistance (IR), and the extrapolated pressure intercept (P(I)), the effective outflow pressure. The authors investigated the effects of progressive pulmonary vascular occlusion on the IR and P(I) of the PAP-CO plot. Nine experimental and nine time control dogs were studied. In the former group, PAP-CO plots were obtained in three conditions: (1) Baseline, (2) following occlusion of the right pulmonary artery, and (3) following occlusion of the right pulmonary artery and blood flow to the left upper lobe. Following progressive occlusion, there was a corresponding increase in the IR of the PAP-CO plot, from 1.95 to 3.62 to 5.16 mmHg.1-1.min (all P < 0.05). In contrast to the increase in IR, P(I) remained constant. Over the same interval, there were no changes in IR or P(I) in the time control group. These findings indicate that changes in the slope of the PAP-CO plot correspond to changes in the number of parallel vascular units.

Thrombolytic therapy in cardiogenic shock: effect of increased aortic pressure and rapid tPA administration.

OBJECTIVES: To investigate the effect of an increase in aortic pressure combined with rapid tissue plasminogen activator infusion on hemodynamic stability and patency of the infarct-related artery in patients with acute myocardial infarction complicated by profound hypotension or cardiogenic shock. BACKGROUND: Thrombolytic therapy improves mortality in relatively stable patients with acute myocardial infarction but not in patients with cardiogenic shock. Recent canine studies have demonstrated that a moderate increase in low aortic pressure improves thrombolysis. Conceivably, then, decreased thrombolytic efficacy in cardiogenic shock is due, at least in part, to a low aortic pressure impairing delivery of the thrombolytic agent. PATIENTS AND METHODS: For patients presenting within 6 h of an acute myocardial infarction complicated by profound hypotension or cardiogenic shock, an inotropic agent was rapidly administered to increase the systolic aortic pressure to approximately 110 mmHg, and 100 mg of tissue plasminogen activator was administered intravenously over 45 to 60 mins. RESULTS: Eight consecutive patients meeting the study criteria were treated over 18 months. In six of eight patients, the inotropic agent increased systolic blood pressure over 10 mins, from a mean of 64 +/- 12 mmHg to 102 +/- 12 mmHg. In the two patients whose blood pressure did not increase, early angiography in one demonstrated occlusion of the infarct-related artery, and both of the patients died. In the other six patients there was clinical and hemodynamic evidence of early reperfusion, and infarct-related arteries were patent on angiography. These six patients survived at least 30 days, with four having a favourable clinical outcome and two having a functional limitation due to heart failure. CONCLUSIONS: These results are consistent with experimental data indicating that an increase in aortic pressure combined with rapid tissue plasminogen activator infusion may increase thrombolytic efficacy when an acute myocardial infarction is complicated by profound hypotension or cardiogenic shock.

Effect of rate of administration of recombinant tissue plasminogen activator on efficacy of coronary thrombolysis.

The authors employed a canine model of coronary thrombosis, induced by injection of radioactive blood clot, via a catheter placed in the left anterior descending (LAD) coronary artery, to compare effects of different rates of administration of recombinant tissue plasminogen activator (rtPA) on efficacy of coronary thrombolysis. In one group of dogs 0.75 mg/kg of rtPA was administered via the catheter placed in the LAD coronary artery over fifteen minutes. In a second group of dogs the same dose of rtPA was administered over forty-five minutes. Compared with the group in which the drug was administered over forty-five minutes, by thirty and forty-five minutes after onset of treatment, the extent of coronary thrombolysis was significantly greater (P < 0.05) in the group who received the drug over fifteen minutes. These results demonstrate that the rate of intracoronary administration of rtPA may significantly affect thrombolytic efficacy.

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.

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.