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Biomedical subjects

D Zahger

Publications and source records attributed to D Zahger.

At least 19 recordsLinked to original sources
PubMed1997

Changing paradigms in thrombolysis in acute myocardial infarction.

Acute myocardial infarction occurs when a ruptured coronary artery plaque causes sudden thrombotic occlusion of a coronary artery and cessation of coronary artery blood flow. This paper reviews the underlying coronary pathology in progressive coronary atherosclerosis, mechanisms of plaque rupture and arterial occlusion and the time relationship between coronary occlusion and myocardial necrosis. Reperfusion can be achieved by chemical thrombolysis with different thrombolytic agents. Early lysis is achieved best by prehospital administration, a transtelephonic monitor, a mobile intensive care unit, active general practitioner treatment or by warning the emergency room of impending arrival of a patient. Thrombolytic therapy may be unsuccessful and not achieve Grade III TIMI flow in less than 4 h (or even 2 h) due to inadequate or intermittent perfusion or reocclusion. Adjuvant therapy includes aspirin and platelet receptor antagonists. Bleeding is a constant danger. Direct percutaneous transluminal coronary angioplasty (PTCA) may be as effective or better than chemical thrombolysis. Reperfusion protects the myocardium and salvages viable tissue. It also improves mechanical remodelling of the ventricle. Long-term follow-up has shown that quantum leaps of fresh coronary occlusion causes step-wise progression in patient disability and that further early, prompt reperfusion can salvage myocardium and prevent this inexorable progress of the disease.

Fibrinolytic Agents↗
PubMed1996

Smoking and prognosis after acute myocardial infarction in the thrombolytic era (Israeli Thrombolytic National Survey).

OBJECTIVES: This study sought to compare the relation between smoking and the 30-day and 6-month outcome after acute myocardial infarction in an Israeli nationwide survey. BACKGROUND: Studies before and during the thrombolytic era reported similar or lower early mortality after acute myocardial infarction in smokers than in nonsmokers. This finding is intriguing and may be misleading because numerous epidemiologic studies have clearly shown that smoking is an independent risk factor for atherosclerosis, myocardial infarction and death. METHODS: The study cohort comprised 999 consecutive patients with an acute myocardial infarction from a prospective nationwide survey conducted during January and February 1994 in all coronary care units operating in Israel. The prognosis of 367 patients (37%) who were smokers (current smokers and those who smoked up to 1 month before admission) was compared with that of 632 nonsmokers (past smokers or those who never smoked). RESULTS: Smokers were on average 10 years younger and were more frequently men and patients with a family history of coronary heart disease and inferior infarction and less frequently patients with a previous infarction or a history of angina, hypertension and diabetes than nonsmokers. Smokers also had a lower incidence of congestive heart failure on admission or during the hospital period. Thrombolytic therapy (49% vs. 40%, p < 0.01) and aspirin (89% vs. 80%, p < 0.001) were administered more frequently in smokers than nonsmokers. The crude 30-day (6.0% vs. 15.7%) and cumulative 6-month (7.9% vs. 21.5%) mortality rates were significantly lower (p < 0.0001 for both) in smokers than nonsmokers, respectively. However, after adjustment for age, baseline characteristics, thrombolytic therapy and invasive coronary procedures, the lower 30-day (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.43 to 1.29, p = 0.30) and 6-month (hazard ratio 0.84, 95% CI 0.54 to 1.30, p = 0.42) mortality rates in smokers and nonsmokers were not significantly different. The model had a power of 0.80 for OR 0.50, with alpha 0.1. CONCLUSIONS: In our nationwide survey, the seemingly better prognosis of smokers early after acute myocardial infarction was no longer evident after adjustment for baseline and clinical variables and may be explained by their younger age and a more favorable risk profile. Smokers develop acute myocardial infarction a decade earlier than nonsmokers. Efforts to lower the prevalence of smoking should continue.

Aged↗
PubMed1995

Incomplete recanalization as an important determinant of Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow after thrombolytic therapy for acute myocardial infarction. TEAM Investigators. Thrombolytic Trial of Eminase in Acute Myocardial Infarction.

The outcome of patients with Thrombolysis in Myocardial Infarction (TIMI) trial grade 2 flow is worse than that of patients with TIMI grade 3 flow after thrombolytic therapy for acute myocardial infarction. It is unclear whether TIMI grade 2 flow represents incomplete recanalization of the culprit lesion or poor distal runoff. The Thrombolytic Trial of Eminase (anistreplase) in Acute Myocardial Infarction (TEAM)-2 and TEAM-3 were randomized trials comparing anistreplase with streptokinase (TEAM-2, n = 370) or with alteplase (tissue plasminogen activator) (TEAM-3, n = 325). We compared the minimal luminal diameter of the culprit lesion in patients with TIMI grade 2 flow with that in patients with TIMI grade 3 flow both 90 minutes (TEAM-2) and 1 day (TEAM-3) after thrombolysis. Patients with TIMI grade 2 flow had a lower residual luminal diameter in the culprit lesion than patients with TIMI grade 3 flow (TEAM-2, 0.58 +/- 0.03 vs 0.79 +/- 0.02 mm, p = 0.0001; TEAM-3, 0.88 +/- 0.04 vs 1.17 +/- 0.03 mm, p = 0.0001, for patients with TIMI grades 2 and 3 flow). Residual percent stenosis was correspondingly higher in patients with TIMI grade 2 flow. At the early angiogram, 66% of patients with TIMI grade 2 flow, but only 35% of those with TIMI grade 3 flow, had a minimal luminal diameter of 0.6 mm (positive predictive value 87%, negative predictive value 35%). Incomplete recanalization of the culprit lesion may thus be an important determinant of TIMI grade 2 flow after thrombolysis. Whether more complete thrombolysis or rescue angioplasty improves outcome in these patients deserves evaluation.

Analysis of Variance↗
PubMed1995

VCL, an antagonist of the platelet GP1b receptor, markedly inhibits platelet adhesion and intimal thickening after balloon injury in the rat.

BACKGROUND: Arterial injury is immediately followed by platelet adhesion at the site of injury, a process that requires the interaction of subendothelial von Willebrand factor with the platelet GP1b receptor. VCL, a recombinant von Willebrand factor GP1b binding domain, inhibits platelet binding to von Willebrand factor. The aim of this study was to determine whether VCL inhibits platelet adhesion at the site of arterial injury and affects neointimal thickening after injury in rats. METHODS AND RESULTS: Sprague-Dawley rats were randomized to receive VCL, 4 mg/kg bolus followed by a continuous infusion of 2 mg.kg-1.h-1 for 72 hours, or an identical volume of saline. Balloon injury of the femoral artery was performed 15 minutes after the initial bolus injection of VCL. Scanning electron microscopy performed 1 and 3 days after injury indicated that VCL-treated rats had > 80% reduction in the number of platelets adherent to the vessel wall at the site of injury compared with controls (P < .003). Histological examination at day 14 showed that, compared with controls, VCL-treated rats had a 60% reduction in the intima-media ratio (0.21 +/- 0.03 versus 0.53 +/- 0.06, P = .001) and a reduced luminal area stenosis (12 +/- 3% versus 38 +/- 10%, P = .04). At 28 days after injury, there was no rebound of neointimal thickening in VCL-treated rats (intima-media ratio, 0.19 +/- 0.04; luminal stenosis, 17 +/- 5%). The difference between VCL-treated rats and control rats persisted but was attenuated (intima-media ratio, 0.19 +/- 0.04 versus 0.28 +/- 0.1, P = .162; luminal stenosis, 17 +/- 5% versus 31 +/- 5%, P = .058) as neointimal thickening regressed in untreated rats. With the use of proliferating cell nuclear antigen immunohistochemistry on day 3, VCL had no effect on smooth muscle cell (SMC) proliferation. CONCLUSIONS: Antagonism of the platelet GP1b receptor by VCL profoundly decreased platelet deposition at the site of balloon injury in the rat femoral artery. This effect was associated with a persistent reduction in neointimal thickening. The lack of effect of VCL on SMC proliferation suggests that the decrease in neointimal thickening may have been mediated through inhibition of SMC migration and/or modulation of the extracellular matrix.

Angioplasty, Balloon↗
PubMed1995

Absence of lethal reperfusion injury after 3 hours of reperfusion. A study in a single-canine-heart model of ischemia-reperfusion.

BACKGROUND: Whether reperfusion can cause necrosis of previously viable myocytes (lethal reperfusion injury) remains controversial. Numerous studies examined the ability of various agents to prevent or limit reperfusion injury, but the results were contradictory. In a single-canine-heart model of ischemia-reperfusion, we previously demonstrated that 5 minutes of reperfusion does not increase the transmural extent of necrosis. Since the 5-minute period of reperfusion is considered by some to be too short for the full manifestation of reperfusion injury, we reexamined the issue of lethal reperfusion injury using a modification of the single-heart model of ischemia-reperfusion that allowed extending the reperfusion period to 3 hours. METHODS AND RESULTS: In anesthetized, open-chest dogs, the distal half of the left anterior descending coronary artery (LAD) segment between the last diagonal branch and the apex was perfused via a shunt from the left carotid artery. The shunt was closed for periods of 90 to 180 minutes, depending on the ECG severity of ischemia, and reperfused for 3 hours. While the distal region was perfused from the carotid artery, the LAD was occluded proximal to the last diagonal branch for the same period of time as the distal region had been earlier. The time of occlusion was chosen such that the end of the occlusion period coincided with the end of the experiment. Thus, both regions of the LAD territory were subjected to identical periods of ischemia, but only the distal region was reperfused. At the end of the experiment, the boundary between the proximal (nonreperfused) and distal (reperfused) area was delineated by blue dye, and the heart was arrested, cut into slices 1 cm thick parallel to the LAD, and placed in triphenyltetrazolium chloride. The epicardial edges of necrosis in the reperfused and the nonreperfused regions were examined for any shift that might suggest a difference in the transmurality of necrosis. The areas of necrotic and viable myocardium were measured by planimetry within 1 cm on either side of the boundary. In all 14 dogs, the epicardial edges of necrosis ran as a single line across the boundary, and no shift was present. There was also no difference in the transmurality of necrosis between the reperfused and nonreperfused regions (64.9 +/- 20.7% versus 66.1 +/- 17.0% of left ventricular wall thickness, respectively, P = .32 by paired t test). CONCLUSIONS: In a single-canine-heart model of ischemia-reperfusion, there was no evidence of lethal reperfusion injury after 3 hours of reperfusion.

Animals↗
PubMed1995

How do smokers differ from nonsmokers in their response to thrombolysis? (the TIMI-4 trial)

Smokers with acute myocardial infarction appear to have a better outcome after thrombolysis than do nonsmokers. To identify factors that could contribute to this curious finding, we analyzed data from the Thrombolysis in Myocardial Infarction (TIMI-4) trial, in which 382 patients with acute myocardial infarction were randomized to tissue plasminogen activator, anistreplase, or both. Coronary angiography was performed 90 minutes and 18 to 36 hours after randomization, a myocardial perfusion scan was performed at 18 to 36 hours and before discharge, and a radionuclide ventriculogram was obtained before discharge. Angiographic and clinical outcome variables were determined in current smokers, ex-smokers, and nonsmokers, and regression analysis was used to correct for differences in baseline characteristics. The in-hospital mortality of current smokers was lower than that of ex-smokers and nonsmokers: 2.3% versus 5.2% versus 7.0%, respectively (p = 0.04 by paired comparison, current vs nonsmokers). Ninety minutes after randomization, the incidence of TIMI grade 3 flow was significantly higher in smokers than in ex-smokers and nonsmokers (55% vs 43% and 45%, p = 0.02); this difference was no longer observed at the second angiogram, nor did smokers differ from nonsmokers with respect to residual stenosis, thrombus grade, infarct size, ejection fraction, or recurrent ischemia. Because a strong inverse relation exists between TIMI grade 3 flow at 90 minutes and mortality, our findings suggest that the lower mortality of current smokers after thrombolytic therapy may be related to a higher incidence of early, complete reperfusion.

Double-Blind Method↗
PubMed1995

Thrombolysis in the era of the randomized trials.

Thrombolytic therapy in acute myocardial infarction is of established value in recanalizing the occluded coronary artery, reducing infarct size, and decreasing mortality. Here, we review the extensive information provided by large clinical trials on agent and patient selection, timing of treatment, adjuvant therapies, and complications. Early treatment is of prime importance. Tissue plasminogen activator is slightly superior to streptokinase, especially in young patients treated early. Intravenous heparin should be used in conjunction with tissue plasminogen activator, although its role when streptokinase is used is less clear. Aspirin, beta-blockers, and converting enzyme inhibitors are of proven value as adjunctive therapies; nitrates and magnesium are not. Newer antithrombotic and antiplatelet agents (eg, hirudin and glycoprotein IIb/IIIa receptor antagonists) may further improve results.

Combined Modality Therapy↗
PubMed1993

Early heart rate variability alterations after acute myocardial infarction.

In order to assess early changes in heart rate variability, we studied 81 patients with acute myocardial infarction during the initial 24 hours after thrombolytic therapy. The standard deviation of the mean heart rate and the low (0 to 0.05 Hz), mid (0.05 to 0.20 Hz), and high (0.20 to 0.35 Hz) frequency band power were evaluated with 24-hour ECG Holter recordings. We found diminished variance in the time domain and reduced power spectrum in the frequency domain compared with a group of 41 normal subjects (p < 0.01). Patients with anterior infarction had significantly (p < 0.01) higher heart rates and lower heart rate variability values than patients with inferior infarction. Reduction in heart rate variability occurred within the first 8 hours in patients with anterior infarction; a significant fall (p < 0.03) was especially noted in the high-frequency band after a decline in ST-segment elevation. Heart rate variability alterations in patients with inferior infarction were most evident in the final 8-hour interval. These findings may be viewed in terms of sympathovagal imbalance and may be related to clinical signs of intense autonomic nervous system activity that are observed early in the course of acute anterior and inferior myocardial infarction.

Aspirin↗