J. Vanhaecke

DOUBLE-BLIND RANDOMISED TRIAL OF INTRAVENOUS TISSUE-TYPE PLASMINOGEN ACTIVATOR VERSUS PLACEBO IN ACUTE MYOCARDIAL INFARCTION

In a double-blind randomised trial 129 patients with first myocardial infarction of less than 6 h duration were allocated to treatment with human recombinant tissue-type plasminogen activator (rt-PA) given intravenously over 90 min, or to placebo infusion. Coronary angiography at the end of this infusion showed that the infarct-related vessel was patent in 61% of 62 assessable coronary angiograms in the rt-PA-treated group compared with 21% in the control group. Treatment with rt-PA was not accompanied by any major complications. In the rt-PA group the circulating fibrinogen level at the end of the catheterisation was 52 +/- 29% (mean +/- SD) of the starting value.

Coronary thrombolysis with recombinant single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction.

Seventeen patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were treated with heparin combined with intravenous single-chain urokinase-type plasminogen activator (scu-PA), obtained by expression of the cDNA encoding mature human scu-PA in Escherichia coli. In eight patients, recombinant scu-PA (rscu-PA) was given as a 10 mg bolus followed by 30 mg over 1 hr. Recanalization was obtained in six patients, but with persistent delayed opacification of the vessel in four of these patients. During infusion, a plateau level of rscu-PA antigen in plasma of 3.4 micrograms/ml (median value, range 1.4 to 5.5) was reached. At the end of the infusion the alpha 2-antiplasmin level had decreased to 54% (median, range 22% to 82%) of the preinfusion level, the fibrinogen level to 89% (median, range 26% to 101%), and fibrinogen degradation products (FDPs) to 20 micrograms/ml (median, range 8 to 387). In nine patients, rscu-PA was administered as a 10 mg bolus followed by 60 mg over 1 hr. This resulted in recanalization with normal distal filling of the vessel in seven patients, within 46 +/- 17 min (mean +/- SD). During infusion the concentration of rscu-PA in plasma increased to a median value of 7.4 micrograms/ml (range 4.0 to 13.3). At the end of the infusion the alpha 2-antiplasmin level was 22% of baseline (range 5% to 47%), the fibrinogen level 45% (range 4% to 94%), and the concentration of FDPs 87 micrograms/ml (range 6 to 1034). No significant bleeding or short-term side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary thrombolysis and infarct size reduction after intravenous infusion of recombinant tissue-type plasminogen activator in nonhuman primates.

Occlusive thrombus was produced by thrombin-induced coagulation in the left anterior descending coronary artery (LAD) of 16 open-chest baboons. In six control animals, occlusive thrombosis persisting over a period of 4 h as evidenced by coronary arteriography resulted in large transmural infarction (63.1 +/- 3.5% of the perfusion area). In 10 animals, tissue-type plasminogen activator obtained by recombinant DNA technology (rt-PA) was infused systemically at a rate of 1,000 IU (10 micrograms)/kg per min for 30 min after 30-80 min of coronary thrombosis. Reperfusion occurred within 30 min in nine animals. In one animal, intravenous infusion was followed by an intracoronary infusion at the same rate, which resulted in thrombolysis within 8 min. In the rt-PA group, mean duration of occlusion before reperfusion was 77 +/- 24 min. Reocclusion occurred in one animal. Recanalization resulted in an overall reduction of infarct size (37.8 +/- 5.9%, P less than 0.05 versus controls). Residual infarction was related to the duration of occlusion (r = 0.80, P less than 0.01). Reperfusion was associated with reduced reflow. Myocardial blood flow in the perfusion area of the LAD was only 70% of normal after 4 h despite perfect angiographic refilling. The infusion of rt-PA was not associated with systemic activation of the fibrinolytic system, fibrinogen breakdown, or clinically evident bleeding. It is concluded that intravenous infusion of rt-PA may recanalize thrombosed coronary vessels without inducing systemic lysis. The extent of residual infarction is closely related to the duration of coronary artery occlusion before thrombolysis.

Reduction in infarct size and enhanced recovery of systolic function after coronary thrombolysis with tissue-type plasminogen activator combined with beta-adrenergic blockade with metoprolol.

The effect of beta-adrenergic blockade on the salvage and functional recovery of reperfused myocardium was investigated in anesthetized dogs. Immediately after thrombotic occlusion of the left anterior descending coronary artery, the cardioselective beta-blocking agent metoprolol was given intravenously at a dose of 0.5 mg/kg infused over 10 min. One hour after the onset of occlusion, recanalization was initiated by intravenous infusion of recombinant human tissue-type plasminogen activator (rt-PA, 10 micrograms/kg/min for 30 min). Anatomic infarct size expressed as percent of the left ventricular mass (I/LV), global ejection fraction, and mean systolic shortening of the segmental radii (SS) of the infarcted area were measured either after 24 hr or 1 week in six groups of six dogs each: group I (rt-PA + metoprolol, evaluated at 24 hr), group II (rt-PA + metoprolol, evaluated at 1 week, group III (rt-PA alone, evaluated at 24 hr), group IV (rt-PA alone, evaluated at 1 week), group V (persistent occlusion, evaluated at 24 hr), and group VI (persistent occlusion, evaluated at 1 week). The smallest infarcts were found in reperfused dogs given metoprolol, but the differences from dogs receiving rt-PA alone were not statistically significant (I/LV, expressed as mean +/- SEM: 5.5 +/- 0.9% in group I, 6.7 +/- 1.9% in group II, 15.4 +/- 5.0% in group III, 11.4 +/- 3.5% in group IV, 23.6 +/- 2.5% in group V, and 26.9 +/- 2.3% in group VI).(ABSTRACT TRUNCATED AT 250 WORDS)

Ridogrel in the setting of percutaneous transluminal coronary angioplasty

The safety of the combination of heparin and ridogrel therapy and its antiplatelet efficacy was examined in the setting of percutaneous transluminal coronary angioplasty (PTCA). In 32 patients without known aspirin intake for 10 days before PTCA, therapy with ridogrel (300-mg intravenous bolus) was begun just before PTCA and continued orally at a dose of 300 mg twice daily until discharge. Heparin was administered as a 10,000 IU bolus dose before PTCA and followed by an intravenous infusion at a rate of 1,000 IU/hour for 24 hours. Bleeding problems at the arterial entry site occurred in 13 patients, which required a blood transfusion in only 2 patients. One patient underwent emergency bypass surgery without specific problems of hemostasis. Ridogrel virtually eliminated thromboxane B2 from the serum (29,990 +/- 6,555 pg/0.1 ml before vs 63 +/- 7 pg/0.1 ml at 2 hours after ridogrel), with a concomitant increase in serum 6-keto-prostaglandin F1 alpha (511 +/- 34 pg/0.1 ml before vs 1,190 +/- 146 pg/0.1 ml at 24 hours after ridogrel). There were no acute reocclusions in the ridogrel-treated patients, whereas acute reocclusions occurred in 5.6% of the patients taking the standard aspirin + heparin regimen during the same period. Furthermore, at 6-month clinical follow-up patients treated with ridogrel compared favorably with those receiving standard treatment.

Out-patient versus in-hospital ambulatory 24-h blood pressure monitoring in heart transplant recipients

Objective: To study the effect of the environment—in-hospital vs out-patient situation—on blood pressure as measured by ambulatory blood pressure monitoring (ABPM).Patients and methods: Twenty-four hour ABPM was performed sequentially in-hospital and again 9u2009±u20093 days later on an out-patient basis, in 30 consecutive heart transplant recipients (27 men, median age 56 years, median time post-transplant 3 years). The same equipment was used on both occasions, without any interim change in medical treatment. Results: Both systolic and diastolic blood pressure were higher in-hospital than as an out-patient: +7u2009±u20097 and +6u2009±u20095 mmu2009Hg respectively for the 24-h average (Pu2009<u20090.001). daytime and night-time pressures were affected similarly. depending on the specific cut-off values used, 37 to 87% of the individual patients were hypertensive in-hospital; 31 to 73% of these had an acceptable blood pressure as an out-patient. the converse was very rare (0 to 3% of the total group). Conclusions: In heart transplant patients blood pressure as assessed from 24-h ABPM is lower in the home environment than during a hospital stay. The post-transplant attenuation of the circadian variation in blood pressure is not influenced by the environment. Checking an unsatisfactory in-hospital ABPM with an out-patient recording may obviate the need for an (intensified) antihypertensive treatment in a substantial number of patients.

Prevention of the “no reflow” phenomenon in the canine heart by mioflazine

SummaryThe effects of oral pretreatment with mioflazine (2.5 mg·kg−1) on regional myocardial reflow, infarct size reduction and hemodynamic recovery were studied in 24 anesthetized open-chest dogs undergoing 90 minutes of acute left anterior descending coronary artery (LAD) occlusion followed by 150 minutes of reperfusion.Regional myocardial blood flow was measured with tracer microspheres, and infarct size was determined by triphenyl tetrazolium chloride staining. Pretreatment with mioflazine resulted in a reduced diastolic aortic pressure (p<0.05) and an elevated cardiac output and LV dpdt max (p<0.05). These effects persisted throughout the experiment. In control animals (n=12) a hyperemic reflow response was found in the perfusion area of the LAD during the first minutes of reperfusion. After 150 min of reperfusion, however, the viable myocardium of the LAD area became underperfused, and almost no reflow was found in the infarcted zones.In the animals pretreated with mioflazine (n=12) the hyperemic response persisted throughout the reperfusion phase and the no-reflow phenomenon was prevented. Infarct size (expressed as percentage of perfusion area) tended to be smaller in this group: 23.7±12.4% versus 33.7±19.2% (p>0.05).Left atrial pressure increased during LAD occlusion in both groups but normalized completely in the drug-pretreated animals (p<0.05).It is concluded that pretreatment with mioflazine prevents the no-reflow phenomenon after reperfusion of an evolving infarction, tends to reduce infarct size and improves hemodynamic recovery.

URINARY PROTEOMIC SIGNATURES ASSOCIATED WITH BETA-BLOCKADE AND HEART RATE IN HEART TRANSPLANT RECIPIENTS

Objective: Heart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on &bgr;-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature. Design and method: In 336 HTx patients (mean age, 56.8 years; 22.3% women), we analyzed cross-sectional data obtained 7.3 years (median) after HTx. We recorded medication use, measured HR during right heart catheterization, and applied capillary electrophoresis coupled with mass spectrometry to determine the multidimensional urinary classifiers HF1 and HF2 (known to be associated with left ventricular dysfunction), ACSP75 (acute coronary syndrome) and CKD273 (renal dysfunction) and 48 sequenced urinary peptides revealing the parental proteins. Results: In adjusted analyses, HF1, HF2 and CKD273 (pu200a<u200au200a=u200a0.024) were higher in BB users than non-users with a similar trend for ACSP75 (pu200a=u200a0.06). Patients started on BB within 1 year after HTx and non-users had similar HF1 and HF2 levels (pu200a>u200au200a=u200a0.098), whereas starting BB later was associated with higher HF1 and HF2 compared with non-users (pu200a<u200au200a=u200a0.014). There were no differences in the urinary biomarkers (pu200a>u200au200a=u200a0.27) according to HR. BB use was associated with higher urinary levels of collagen II and III fragments and non-use with higher levels of collagen I fragments. Conclusions: BB use, but not HR, is associated with a urinary proteomic signature that is usually associated with worse outcome, because unhealthier conditions probably lead to initiation of BB. Starting BB early after HTx surgery might be beneficial.

Hart- en vaatziekten

Techniek om met behulp van elektrodekatheters die door de bloedbaan tot in het hart worden opgevoerd ritmestoornissen te behandelen. Door wisselstroom met een frequentie van 500 tot 700 kHz (cfr. radiogolven) te sturen door een elektrodetip die tegen het myocard aanligt, ontstaat er verhitting van het onderliggende weefsel en vernietiging hiervan. De aldus aangebrachte laesies zijn enkele millimeters groot en diep.