Effect of aspirin and ticlopidine on plasma tissue factor levels in stable and unstable angina pectoris.

Patients with unstable angina have an increased activation of the coagulation system. Aspirin and ticlopidine given in combination may potentiate each other by the combination of different action mechanisms and may reduce the risk of coronary occlusion and clinical instability. Plasma tissue factor (TF) levels collected into the stenotic coronary artery may be an index of TF expression within the vasculature. In 160 patients undergoing angioplasty for a 81+/-5% coronary lesion, we measured TF in blood samples collected from a vein and from the coronary ostium. Immediately after and 10 minutes after the dilation procedures the samples were withdrawn also beyond the lesion. Heparin 150 U/kg was given as an anticoagulant. All patients were pretreated with 250 mg/day of aspirin. One hundred twenty patients were randomly assigned to receive 24, 48, or 72 hours of ticlopidine treatment (250 mg/twice daily). TF levels did not increase during angioplasty but there was a significantly higher TF expression in unstable than in stable patients, irrespective of the invasiveness of debulking procedures. When ticlopidine was given for 72 hours, TF levels were similar to normal laboratory values both in stable and unstable patients. This combined antiplatelet pretreatment may be of benefit in unstable angina patients, with a favorable cost/benefit ratio.

In-stent restenosis: long-term outcome and predictors of subsequent target lesion revascularization after repeat balloon angioplasty.

OBJECTIVES: We sought to evaluate the long-term clinical outcome of patients undergoing successful balloon angioplasty for in-stent restenosis, and to determine correlates of the need for subsequent target lesion revascularization (TLR). BACKGROUND: In-stent restenosis can be safely treated by repeat percutaneous intervention. Reported subsequent TLR rates have varied from 20% to 80% and seem related to the type of restenotic lesion. METHODS: The study population comprised 234 patients with follow-up data who were successfully treated with repeat balloon angioplasty for in-stent restenosis in 257 lesions between May 1995 and January 1998 at our institution. RESULTS: Clinical follow-up was available at 459 (286 to 693) days after the repeat procedure. Event-free survival was 78.5% and 74.6% at 12 and 24 months, respectively. Recurrent events occurred in 58 patients (24.8%), including 6 deaths (2.6%), 4 myocardial infarction (1.7%) and repeat target vessel revascularization in 50 patients (21.4%). Independent predictors of repeat TLR were time to in-stent restenosis <90 days (Hazard ratio 4.67, p < 0.001), minimal luminal diameter after repeat procedure (Hazard ratio 0.38, p = 0.034) and the angiographic pattern of in-stent restenosis (Hazard ratio 1.65, p = 0.036). CONCLUSIONS: Balloon angioplasty is an effective means of treating in-stent restenosis. The long-term results are acceptable particularly for focal restenotic lesions. Further restenosis is more common in patients with early initial recurrence, more proliferative lesions and a poorer angiographic result from repeat angioplasty.

Alpha-adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction.

BACKGROUND: AMI reperfusion by thrombolysis does not improve TIMI flow and LV function. The role of infarct-related artery (IRA) stenosis and superimposed changes in coronary vasomotor tone in maintaining LV dysfunction must be elucidated. METHODS AND RESULTS: Forty patients underwent diagnostic angiography 24 hours after thrombolysis. Seventy-two hours after thrombolysis, the culprit lesion was dilated with coronary stenting. During angioplasty, LV function was monitored by transesophageal echocardiography. Percent regional systolic thickening was quantitatively assessed before PTCA, soon after stenting, 15 minutes after stenting, and after phentolamine 12 microg/kg IC (n=10), the alpha1-blocker urapidil 600 microg/kg IV (n=10), or saline (n=10). Ten patients pretreated with beta-blockers received urapidil 10 mg IC. Coronary stenting significantly improved thickening in IRA-dependent and in non-IRA-dependent myocardium (from 27+/-15% to 38+/-16% and from 40+/-15% to 45+/-15%, respectively). Simultaneously, TIMI frame count decreased from 39+/-11 and 40+/-11 in the IRA and non-IRA, respectively, to 23+/-10 and 25+/-7 (P<0.05). Fifteen minutes after stenting, thickening worsened in both IRA- and non-IRA-dependent myocardium (to 19+/-14% and 28+/-14%, P<0.05), and TIMI frame count returned, in both the IRA and non-IRA, to the values obtained before stenting. Phentolamine and urapidil increased thickening to 36+/-17% and 41+/-14% in IRA and to 48+/-11% and 49+/-17% in non-IRA myocardium respectively, and TIMI frame count decreased to 16+/-6 and to 17+/-5, respectively. Changes were attenuated with beta-blocker pretreatment. CONCLUSIONS: Our finding that alpha-adrenergic blockade attenuates vasoconstriction and postischemic LV dysfunction supports the hypothesis of an important role of neural mechanisms in this phenomenon.

Postischemic left ventricular dysfunction is abolished by alpha-adrenergic blocking agents.

OBJECTIVES: We sought to evaluate the efficacy of alpha-adrenergic blocking agents in counteracting left ventricular (LV) dysfunction occurring after transient ischemia in humans. BACKGROUND: The mechanisms underlying postischemic LV dysfunction are largely unknown. METHODS: Percutaneous transluminal coronary angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. In 50 patients undergoing coronary stenting for 77+/-5% stenosis, LV function was monitored by transesophageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 microg/kg body weight of the alpha-blocker phentolamine intracoronarily, 15 patients received 600 microg/kg of the alpha1-blocker urapidil intravenously, 10 patients received the combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10 patients received saline. RESULTS: Fifteen minutes after successful coronary dilation, significant contractile dysfunction occurred in previously ischemic and nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coronary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34+/-9% to 45+/-8% and to 49+/-8%, respectively (p < 0.05). After the administration of propranolol combined with phentolamine, LV dysfunction remained unchanged (34+/-6%), as in control subjects. CONCLUSIONS: LV dysfunction occurs after PTCA, as described in animal models after ischemia. Alpha-blockers abolished LV, macrocirculatory and microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by combining alpha- and beta-blockers. The evidence of diffuse rather than regional dysfunction, together with the opposite effects of alpha- and beta-blockade, supports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction.

The alpha-1 adrenergic blocking agent urapidil counteracts postrotational atherectomy "elastic recoil" where nitrates have failed.

Calcium antagonist pretreatment and intracoronary high doses of nitrates (9 mg of isosorbide dinitrate) do not counteract coronary vasoconstriction occurring after rotational atherectomy. In 30 patients undergoing Rotablator atherectomy, intracoronary injection of the alpha 1-sympathetic blocker urapidil abolished or prevented significant vasoconstriction occurring 15 minutes after the procedure despite repeated injections of nitrates.

Ticlopidine and aspirin pretreatment reduces coagulation and platelet activation during coronary dilation procedures.

OBJECTIVES: It is unknown whether a therapeutic combination of aspirin (ASA) and ticlopidine might effectively decrease activation of hemostasis. BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA), rotational atherectomy and stent implantation are procedures that fracture or ablate endothelium and plaque, a situation that activates hemostasis. METHODS: In 85 patients undergoing PTCA for a 77.8 +/- 1% stenosis, we measured markers of coagulation and platelet activation (thrombin-antithrombin complexes [TAT], prothrombin fragment 1 + 2 [F1 + 2] serotonin and the presence of circulating activated platelets reacting with monoclonal antibodies against glycoproteins exposed on platelet membranes). Blood samples were drawn from a peripheral vein and from the coronary ostium before the procedures. Both immediately and 10 min after angioplasty, and 10 min afterward, samples were collected from a probing catheter (0.018 in, [0.46 cm]) positioned beyond the stenosis. All patients were being treated with antianginal drugs and ASA, 250 mg/day. Seventy of them had taken ticlopidine, 250 mg, twice daily for < or = 1 day (< or = 24 h) (n = 28) or for > or = 3 days (> or = 72 h) (n = 42). Heparin (150 U/kg) was administered before angioplasty. Thirty patients underwent PTCA; 15 of them were not treated with ticlopidine and 15 were given ticlopidine (> or = 72 h). Thirty-five patients had stent implantation, 20 rotational atherectomy. RESULTS: Before and during the procedures, there was greater thrombin generation (expressed by higher TAT and F1 + 2 plasma levels) in patients not taking ticlopidine or taking it for < or = 24 h (p < 0.05). Platelet activation and plasma serotonin levels were also significantly higher in the no ticlopidine or < or = 24-h ticlopidine groups. CONCLUSIONS: The combined use of ticlopidine, ASA and heparin effectively controls activation of coagulation in patients with stable or unstable angina undergoing coronary dilation.

[Primary failure of pericardial valvular heterografts]. / Défaillance primitive des hétérogreffes valvulaires péricardiques.

From July 1981 to October 1984, 79 Hancock pericardial valves were implanted in 74 patients surviving the hospital period and with a mean age of 64.2 years. Fifty-two patients underwent aortic valve replacement, 16 had mitral valve replacement, 5 bad a double replacement and 19 associated procedures were performed. The mean survival is 48 months. Until 1st June 1987, 11 primary failures have required reoperation (14.9%), 4 in the mitral position (4.6% patient-years), 7 in the aortic position (3.01% patient-years). The time to reoperation was 48.4 months for the aortic orifice and 36.5 months for the mitral orifice. The lesions most frequently encountered were tears (7 cases), calcifications (5 cases) and stretching of valvular tissue (2 cases); two patients died during the postoperative phase of this operation. Despite the small number of patients followed, this series demonstrates of high incidence of dysfunction due to primary tissue degeneration as, after the 5th year, the actuarial rate of absence of primary lesion is 85.3 +/- 8% with no significant difference between the aortic and the mitral orifices, although dysfunction appears to occur more rapidly in mitral prostheses. These results are much less favourable than those obtained with Ionescu bioprostheses in the aortic position of those obtained with porcine bioprostheses in either position. This justifies very regular clinical and echocardiographic follow-up of patients with Hancock pericardial valvular heterografts.

Changes in plasma fibronectin levels after cardiac and pulmonary surgery: role of cardiopulmonary bypass.

The changes in immunoassayable plasma fibronectin were studied during seven days after cardiac surgery with cardiopulmonary bypass (group A, 19 patients) or lung surgery without bypass (group B, 11 patients). In group A the fibronectin showed a series of rapid changes during the 24 perioperative hours. Simultaneous assessment of other plasma proteins (albumin, fibrinogen and immunoglobulin G) suggested that these changes mainly reflected hemodilution and hemoconcentration processes following the cardiopulmonary bypass, being influenced by the necessarily large transfusions of plasma. The fibronectin level decreased after day 1, with maximum depletion (averaging -32% of preoperative value) on day 3. Despite subsequent progressive rise, full restoration had not been reached by day 7. Group B did not show the initial rapid changes, but progressive fall in fibronectin level to a nadir on day 2 (-20% of preoperative) was followed by gradual return to outset value on days 4-5. The study demonstrated 1) that cardiac or lung surgery induces transient fibronectin depletion on days 2 to 3 postoperatively, and 2) that in surgery with cardiopulmonary bypass the decrease is significantly greater and more prolonged. It is proposed that this supplementary decrease is due to the large amounts of particulates of various origin entering the blood during the bypass.

[Transluminal angioplasty of the coronary vessels. Preliminary results]. / Angioplastie transluminale des coronaires. Résultats préliminaires.

Transluminal coronary angioplasty is a new therapeutic procedure perfected by Gruntzig in 1977 consisting of compressing atheromatous plaques and dilating the arterial lumen with an inflatable balloon-tipped catheter of fixed external diameter. This catheter is introduced into the coronary artery through a preformed catheter guide under radioscopic control. The authors describe their experience of 36 attempts at coronary angioplasty performed over a one year period. The stenosis was catheterised in 30 cases and a good immediate result was obtained in 28 patients (77%). The percentage narrowing was reduced from an average of 79 +/- 8% to 26 +/- 12% (p less than 0.001) and the trans stenotic gradient from 40 +/- 11 mm Hg to 4 +/- 8 mm Hg (p less than 0.001). No serious complications were observed during these procedures. The 8 other patients underwent aorto-coronary bypass surgery as an emergency (2 cases) or otherwise (5 cases). 26 patients with good immediate results are asymptomatic at medium term follow-up, 1 has improved from functional Class IV to II, and I has recurrent Class IV effort angina. 15 patients have been followed up after six months. 14 remain asymptomatic with negative maximal exercise stress testing; 1 has angina. 14/15 stenoses remain dilated, 1 stenosis has progressed (60%). 2 patients developed a new stenosis, 1 of whom underwent another angioplasty procedure (functional Class III). In the 13 remaining patient, clinical improvement was confirmed by exercise stress testing. With strict selection of patients and a prudent operative technique this method seems to be an attractive intermediate therapeutic procedure (over 60% good results at medium term) between medical and surgical management of patients with severe angina and a tight monotruncular stenosis.