Infarct Size In Group Research Articles

Monitoring intravenous recombinant tissue plasminogen activator thrombolysis for acute ischemic stroke with diffusion and perfusion MRI.

Intravenous recombinant tissue plasminogen activator (rtPA) administration is an effective therapy for ischemic stroke when initiated within 3 hours and possibly up to 6 hours after symptom onset. To improve patient selection, a fast diagnostic tool that allows reliable diagnosis of hemorrhage and ischemia, vessel status, and tissue at risk at an early stage may be useful. We studied the feasibility of stroke MRI for the initial evaluation and follow-up monitoring of patients undergoing intravenous thrombolysis. Stroke MRI (diffusion- and perfusion-weighted imaging [DWI and PWI, respectively], magnetic resonance angiography, and T2-weighted imaging) was performed before, during, or after thrombolysis and on days 2 and 5. We assessed clinical scores (National Institutes of Health Stroke Scale [NIHSS], Scandinavian Stroke Scale [SSS], Barthel Index, and Rankin scale) at days 1, 2, 5, 30, and 90. Furthermore, we performed volumetric analysis of infarct volumes on days 1, 2, and 5 as shown in PWI, DWI, and T2-weighted imaging. Twenty-four patients received rtPA within a mean time interval after symptom onset of 3.27 hours and stroke MRI of 3.43 hours. Vessel occlusion was present in 20 of 24 patients; 11 vessels recanalized (group 1), and 9 did not (group 2). The baseline PWI lesion volume was significantly larger (P=0.008) than outcome lesion size in group 1, whereas baseline DWI lesion volume was significantly smaller (P=0.008) than final infarct size in group 2. Intergroup outcome differed significantly for all scores at days 30 and 90 (all P<0.01). Intragroup differences were significant in group 1 for change in SSS and NIHSS between day 1 and day 30 (P=0.003) and for SSS only between day 1 and day 90 (P=0.004). Stroke MRI provides comprehensive prognostically relevant information regarding the brain in hyperacute stroke. Stroke MRI may be used as a single imaging tool in acute stroke to identify and monitor candidates for thrombolysis. It is proposed that stroke MRI is safe, reliable, and cost effective; however, our data do not prove this assumption. Early recanalization achieved by thrombolysis can save tissue at risk if present and may result in significantly smaller infarcts and a significantly better outcome.

Endotoxin and ischemic preconditioning: TNF-alpha concentration and myocardial infarct development in rabbits.

Ischemic preconditioning (IP) and prior exposure to lipopolysaccharides (LPS) reduce infarct size (IS) and serum tumor necrosis factor-alpha (TNF-alpha) concentration resulting from myocardial ischemia-reperfusion in rabbits. The decrease in TNF-alpha might relate to an induced TNF-alpha inhibitory serum activity (TNF-alpha-ISA). We analyzed TNF-alpha and TNF-alpha-ISA during 30 and 180 min ischemia and reperfusion, respectively, in anesthetized rabbits either untreated (group 1, n = 7), preconditioned (5 and 10 min ischemia and reperfusion, respectively, group 2, n = 9), or exposed to LPS 72 h before ischemia (group 3, n = 9). TNF-alpha-ISA was assessed by coincubating LPS-stimulated rabbit blood with serum of groups 1-3 and measuring TNF-alpha (WEHI assay). With a comparable area at risk, IS in group 1 was 36.9 +/- 11.1 (SD)%, and it was reduced to 13.1 +/- 11.6% and 17.3 +/- 11.3% (both P < 0.05) in groups 2 and 3, respectively. TNF-alpha was increased during ischemia-reperfusion in group 1 but remained unchanged in rabbits subjected to IP or LPS. TNF-alpha-ISA was detected during ischemia-reperfusion in group 2 (29% and 38% of maximum inhibition, respectively) and during baseline, ischemia and reperfusion in group 3 (51%, 46%, 48% of maximum inhibition, respectively) but was absent in group 1. Cardioprotection by IP and LPS is associated with a reduced TNF-alpha and an induced TNF-alpha-ISA during ischemia-reperfusion.

Early detection of the no-reflow phenomenon in reperfused acute myocardial infarction using technetium-99m tetrofosmin imaging.

Evaluation of myocardial perfusion in the early stage of acute myocardial infarction (MI) is clinically important for adjunctive therapies to minimize infarct size. To determine the role of early scintigraphic detection of impaired myocardial reperfusion after primary coronary angioplasty (PTCA) in patients with acute MI, semiquantitative technetium-99m tetrofosmin single-photon emission tomographic (SPET) imaging was performed before primary PTCA (before; area at risk), 60 min after PTCA (after) and at 1 month (1 M; final infarct) in 35 patients with acute MI. The left ventricle was divided into 13 segments and the defect score was calculated as the sum of the perfusion defect of each segment, from 3 (complete defect) to 0 (normal perfusion). A significant myocardial perfusion change after PTCA was defined as a change in the defect score (before minus after PTCA) of >/=4. The echocardiographic asynergic score was defined as the number of asynergic (severe hypokinetic or akinetic) segments corresponding to the analogous segments on SPET images, and recovery of wall motion was calculated as absolute change in the asynergic score (before PTCA minus 1 M). Among the 35 patients, 15 (43%) had a change in the defect score of <4 (no reflow: group 1) while 20 had a change in the defect score of >/=4 (reflow: group 2). There were no significant differences between the two groups with respect to the time between admission to PTCA, revascularization time, collateral grade or Thrombolysis in Myocardial Infarction (TIMI) flow grade before PTCA. Despite the lack of a difference in area at risk between the two groups (group 1 = 12.8+/-4.3 and group 2 = 15.1+/-4.7), final infarct size in group 1 was significantly larger compared with that in group 2 (8.1+/-4.3 vs 4.9+/-3.0, P<0.001). Recovery of wall motion was significantly smaller in group 1 than in group 2 (4.3+/-1.7 to 3.5+/-1.5 vs 4. 1+/-2.1 to 1.6+/-1.6, P<0.001). In conclusion, a small change (<4) in defect score (scintigraphic no-reflow phenomenon) after primary PTCA indicates persisting impaired myocardial perfusion or irreversible cellular damage just after PTCA which is associated with poor recovery of wall motion, as compared with that observed in cases of reflow (>/=4 in defect score).

Importance of platelets in myocardial injury after reperfusion in the presence of residual coronary stenosis in dogs

Residual coronary stenosis is common after successful thrombolysis for acute infarction. We investigated the role of platelets and the influence of a residual critical stenosis during early reperfusion in survival of reperfused myocardium. The left anterior descending coronary artery was occluded for 90 minutes and reperfused for 6 hours in 5 groups of dogs, 3 with a residual critical stenosis (groups 1 through 3) and 2 without (groups 4 and 5). Thrombocytopenia was produced by an antiserum in groups 2, 3, and 5; group 3 was also made neutropenic by another antiserum. Platelets (groups 1 and 4) and neutrophils (groups 1, 2, 4, and 5) labeled with indium 111 were reinjected at occlusion. Collateral flow was estimated with radioactive microspheres and was statistically similar among groups. Infarct size (percentage of area at risk), revealed by triphenyltetrazolium, was more severe (49.4% ± 4.0%; p < 0.05) with stenosis (group 1) than without stenosis (group 4: 29.5% ± 4.6%). Platelet depletion reduced infarct size in group 2 (28.6% ± 6.3%; p < 0.05 vs group 1) with stenosis, but not in group 5 without stenosis (24.5% ± 6.2% vs group 4: 29.5% ± 4.6%). Neutropenia (group 3) did not decrease infarct size in thrombocytopenic dogs. Neutrophil accumulations in reperfused myocardium were similar among groups, but platelets accumulated in greater numbers in reperfused infarcts with stenosis (group 1: 338,581 ± 52,857/gm; p < 0.05) than without stenosis (group 4: 153,445 ± 23,949/gm). Therefore a critical stenosis at reperfusion compromises myocardial salvage and increases infarct size by means of a platelet-mediated mechanism.

Cardiac protection by ischaemic preconditioning is not mediated by myocardial stunning

Previous studies have shown that cardiac protection by ischaemic preconditioning wanes before contractile function recovers; thus stunning is insufficient to cause preconditioning. To test whether reduced contractile effort is necessary for preconditioning induced protection, the effect on myocardial infarct size of restoring contractile function with dobutamine was examined in preconditioned and control dogs. In two experimental groups (groups P and P+D), preconditioning was produced by four 5 min occlusions of the left anterior descending coronary artery, each separated by 5 min of reperfusion. Contractile function was assessed by sonomicrometry 5 min after completion of the preconditioning protocol. In group P+D, dobutamine (average dose = 5 micrograms.kg-1.min-1) was then infused intravenously to restore systolic shortening to baseline. The artery then was reoccluded for 40 min of sustained ischaemia followed by 4 d of reperfusion. Two additional groups of non-preconditioned control dogs (groups C and C+D) also underwent 40 min of coronary occlusion and 4 d of reperfusion. Group C+D received a dobutamine infusion beginning 15 min before and during the 40 min occlusion to match the dobutamine received in group P+D, whereas group C received normal saline. Preconditioning caused mild postischaemic contractile dysfunction (50% decrease in systolic shortening) which was easily reversed by dobutamine treatment. Dobutamine also increased both the rate-pressure product and the left ventricular dP/dt in both treated groups (C+D and P+D). Histological infarct size was 12.3(SEM 2.0)% of the area at risk in the untreated control group (n = 11), and was reduced to 4.4(1.7)% in the untreated preconditioning group (n = 8; p < 0.05). Dobutamine increased non-preconditioned infarct size (group C+D) to 22.1(3.4)% (n = 7; p < 0.05). Infarct size in the dobutamine treated preconditioning group (P+D) was not significantly different from infarct size in group P (n = 8), at 6.1(2.5%). In preconditioned hearts, dobutamine restored postischaemic contractile function but did not increase infarct size significantly. Thus reduced contractile effort is not required for the cardioprotective effect on ischaemic preconditioning.

Quantification of myocardial infarct size after coronary reperfusion by serum cardiac myosin light chain II in conscious dogs.

The effects of early coronary artery reperfusion on the relation between the extent of myocardial infarction and serum levels of cardiac myosin light chain II or plasma creatine kinase levels were evaluated in the conscious dog. Hydraulic occluders were placed on the left anterior descending arteries of 38 dogs. Seven to 10 days later, myocardial infarction was produced. Coronary reperfusion was performed 3 hours (group A1, n = 13) and 6 hours (group A2, n = 12) after the occlusion. In the other 13 dogs, coronary occlusion was sustained throughout the course of the experiment (group B). Seven days after the occlusion, the heart was cut from the apex to the base into 4-mm slices, and infarct size was determined macroscopically. Rapid appearance and early peaking of creatine kinase were observed in group A. Cumulative release of creatine kinase significantly correlated with infarct size in group A (infarct size ranged from 0.1 to 20.1 g, r = 0.90) and group B (from 0.6 to 26.8 g, r = 0.91). However, since creatine kinase release in group A was greater in comparison with that from infarcts of the same size in group B, the slope of the regression line for group A was significantly steeper (p less than 0.05). Cardiac myosin light chain II appeared as early as creatine kinase did and continued to be elevated for 7 days. A very close relation was observed between infarct size and total cardiac myosin light chain II release (r = 0.87 for group A, and r = 0.88 for group B) or peak level of light chain II (r = 0.85 for group A, and r = 0.81 for group B). In addition, the slopes of the regression lines for infarct size and both peak and total release of light chain II did not differ between group A and group B. On histological examination, viable myocardium was frequently observed in the epicardium of the ischemic area in group A1; therefore, infarct size was greater in group B than in group A1 (p less than 0.05). Also, myocardial creatine kinase content in the epicardium of the center of the ischemic area in group A1 was greater than that in group B. Cardiac myosin light chain II release in group A1 was less than that in group B, whereas no difference was found in plasma creatine kinase release among groups A1, A2, and B.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and Safety of Thrombolysis with Intravenous Streptokinase Initiated Prior to Ambulance Transport from Community Hospital to Tertiary Health Care Center

We studied the safety and efficacy of thrombolytic therapy for acute myocardial infarction initiated prior to ambulance transport. Two treatment regimens were compared in a prospective design: 40 patients (group A) received intravenous streptokinase 5 ± 105 IU (SK‐IV) prior to and during ambulance transport and were compared with 36 patients (group B) in whom the same dosage of streptokinase was given after arrival in our hospital. In all patients immediate coronary angiography was performed, followed by intracoronary streptokinase administration. Infarct size was assessed by cumulative release of α‐hydroxybutyrate dehydrogenase. Apart from three episodes of ventricular fibrillation no procedure‐related complications occurred during transport. Median time to SK‐IV was 70 minutes in group A versus 125 minutes in group B (P &lt; 0.001). At first visualization the infarct‐related vessel was patent in 23 patients (58%) in group A and in 6 patients (17%) in group B (P &lt; 0.001). Anterior wall infarction median infarct size in group A was 32% smaller than that in group B (P &lt; 0.05). We conclude that SK‐IV started before ambulance transport is safe, accelerates early reperfusion rate, and consequently leads to a further limitation of infarct size in patients with anterior wall infarction. (J Interven Cardiol 1989:2:3)

Antiinflammatory Agent BW 755 C in Ischemic Reperfused Porcine Hearts

The effect of the antiinflammatory compound BW 755 C on myocardial infarctions was evaluated in regionally ischemic reperfused hearts of 35 pigs. The left anterior descending coronary artery was occluded distally in 23 anesthetized pigs for 45 min and was reperfused for 24 h. The BW 755 C (10 mg/kg) was intravenously injected prior to ischemia in seven pigs (group A). A second dose of BW 755 C (5 mg/kg) was given after 4 h of reperfusion. Group B consisted of eight animals. They were treated with BW 755 C immediately before (10 mg/kg i.v.) and after 4 h of reperfusion (5 mg/kg). Another eight pigs served as controls. At the end of the experiments, infarct size was determined as the ratio of the infarcted myocardium (tetrazolium stain) over the risk region (fluorescent dye). Leukocyte infiltration of the risk region was histologically quantitated in one slice of each experiment. In a second set of experiments recovery of regional myocardial function of the risk region was determined by sonomicrometry during 2 weeks of reperfusion. The BW 755 C (10 mg/kg) was injected intravenously in six pigs before ischemia and at a dose of 5 mg/kg after 4 h of reperfusion. Six pigs served as controls. Hemodynamic parameters and total leukocyte blood count did not differ between the groups. Treatment protocol of group A reduced the infarct size from 72 +/- 13% (control group) to 50.9 +/- 12% (p less than 0.005). Infarct size of group B (65 +/- 16%) did not differ from control experiments. Leukocyte infiltration of the risk region was only attenuated in group A (p = 0.01) compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of early coronary patency on the evolution of myocardial infarction: a prospective arteriographic study.

The effects of early spontaneous coronary patency on the evolution of myocardial infarction were evaluated in 41 patients. They had coronary arteriography (mean (SEM)) 3.1 (0.2) hours after the onset of chest pain with repeat studies 90 minutes and three days later. In 12 (29%) patients the infarct related coronary artery was patent at the first arteriogram (group 1). A further 10 patients, nine of whom received thrombolytic treatment, showed early recanalisation of the infarct related coronary artery within 90 minutes of treatment (group 2). In the remainder the infarct related coronary artery was persistently occluded (group 3). Baseline values for infarct location, the sum of ST elevation in all leads, QRS scores, and serum creatine kinase activity did not permit discrimination between the groups. Nevertheless, patterns of ST segment change and enzyme release in group 1 were closely similar to those that occurred in response to thrombolysis in group 2. Thus compared with group 3, groups 1 and 2 showed earlier 50% reduction in the sum of peak ST elevation in all leads and earlier peaking of serum creatine kinase activity. Importantly, creatine kinase release was significantly attenuated in group 1, rising to a peak serum activity (mean (SEM)) of only 1242 (415) IU/1. Analysis of angiographic left ventricular ejection fractions at three days indicated limitation of infarct size in groups 1 and 2 compared with group 3. Mean (SEM) ejection fraction, however, was best preserved in group 1 (62(6)%) and in this group the frequency of non-Q wave infarction was higher than in groups 2 and 3. Thus in patients who present with a patent infarct related coronary artery early during infarction: (a) there is a reduction in the pattern of infarct size as reflected by attenuation of release of creatine kinase, preservation of left ventricular ejection fraction, and a relatively high frequency of non-Q wave infarction; (b) patterns of ST segment change and creatine kinase release resemble those that occur after successful thrombolytic treatment, suggesting that early coronary patency is the result of spontaneous recanalisation of a previously occluded artery.

Increased regional end-diastolic wall thickness early after reperfusion: A sign of irreversibly damaged myocardium

Two-dimensional echocardiographic measurements of regional left ventricular end-diastolic wall thickness and systolic wall thickening were studied during coronary artery occlusion and early after reperfusion and compared with measurements of regional myocardial infarct size. In 25 closed chest anesthetized dogs with left anterior descending coronary artery occlusion followed by reperfusion, the occlusion period was 3 minutes in group I (n = 4), 20 minutes in group II (n = 4), 60 minutes in group III (n = 5) and 180 minutes in group IV (n = 12). Infarct size in groups III and IV was quantitated using the triphenyltetrazolium chloride technique. After coronary occlusion, wall thickening was replaced by thinning in the center of the ischemic region at the midpapillary echographic short-axis section, and no improvement in function occurred up to 60 minutes after reperfusion, except in group I. Ischemic zone end-diastolic wall thickness did not change significantly from control to the end of the coronary occlusion period, except Group IV. At 60 minutes after reperfusion, end-diastolic wall thickness increased only slightly in groups I and II (by 7.2 and 0.24%, respectively), but a marked increase was observed in groups III and IV (by 41 and 50%, respectively). The percent change in ischemic zone end-diastolic wall thickness from before reperfusion to 60 minutes after reperfusion correlated well with the amount of myocardial necrosis in corresponding segments (r = 0.936, standard error of estimate = 11.4%); an increase in segmental end-diastolic wall thickness of more than 25% was generally associated with 20% or more segmental necrosis. It is concluded that significantly increased regional end-diastolic wall thickness early after reperfusion is associated with irreversibly damaged myocardium, and this might be used as an index of myocardial salvage.