Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined whether N-acetylcysteine, a low molecular weight compound used clinically to replenish glutathione, could limit tissue necrosis during acute myocardial infarction in hearts with minimal coronary collateral flow. Fifty rabbits underwent 45 mins ischemia with and without coronary reperfusion for 3h. Four groups were studied. Saline or N-acetylcysteine (140 mg/kg) was administered intravenously 10 mins before occlusion and continued for 35 mins after occlusion. The area at risk of necrosis was assessed with fluorescent particles and the area of tissue necrosis was defined using triphenyltetrazolium chloride staining. No differences were observed for tissue necrosis expressed as a percentage of the risk zone size (mean +/- SEM, 46.7 +/- 8.2% versus 46.3 +/- 8.2%) for saline and N-acetylcysteine treated rabbits subjected to 45 mins coronary occlusion. Tissue necrosis in rabbits with 45 mins ischemia followed by 3 h reperfusion was not significantly reduced with N-acetylcysteine treatment (36.4 +/- 5.1%) compared to untreated controls (36.5 +/- 6.4%). Risk zone size and hemodynamic parameters were similar between the treatment groups. Thus, treatment before and during short term coronary occlusion did not limit tissue necrosis during acute myocardial infarction.
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PMID:Effect of N-acetylcysteine on tissue necrosis during acute myocardial infarction in rabbits. 279 May 79

A fatty acid-binding protein (FABP) was purified from rabbit heart and characterized with respect to size, isoelectric point, and tissue distribution. This protein was found in red muscle, diaphragm, and aorta, as well as in the heart. Amino acid composition of rabbit heart FABP differed only slightly from the human and rat proteins. Rabbit heart FABP was shown to bind two molecules of fatty acid. A monoclonal antibody was developed and used to demonstrate the feasibility of a one-step purification with affinity chromatography. Cross-reactivity was found between the human protein and the rabbit antibody, and an immunoassay was developed to human heart FABP. Levels of human heart FABP in the plasma of patients with acute myocardial infarction were significantly elevated (83 +/- 9 micrograms/ml) compared with patients with pulmonary edema (52 +/- 7 micrograms/ml) and normal volunteers (28 +/- 5 micrograms/ml; p less than 0.05, mean +/- SEM).
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PMID:Rabbit heart fatty acid-binding protein. Isolation, characterization, and application of a monoclonal antibody. 279 Dec 32

We have previously reported that regional wall motion abnormalities in a canine model of acute myocardial infarction may show substantial improvement in the first 6 weeks after infarction. To determine whether the mechanism of this improvement in function is the result of scar contraction within the infarct, we studied the relationship between changes in regional wall motion defined by cross-sectional echocardiography and the regional concentration of radioactive microspheres injected immediately before coronary occlusion and sampled 6 weeks after occlusion. Eight dogs underwent serial echocardiographic and microsphere blood flow measurements immediately before and 30 minutes, 48 hours, 1 week, 3 weeks, and 6 weeks after ligation of the left anterior descending or the left circumflex coronary artery. Wall motion and blood flow were measured in the short-axis section of the left ventricle at the level of the midpapillary muscle in each 10-degree radial segment around the circumference of the ventricle. Infarct histology was assessed at 6 weeks by means of the same radial coordinate system. Control data were collected in a similar manner from four dogs that underwent sham operations and had no histologic evidence of infarction. In all of the animals with infarcts, but not in the sham animals, the calculated preocclusion endocardial and epicardial blood flow values in the histologic infarct zone (252 +/- 44 and 168 +/- 17 ml/min/100 gm, respectively, mean +/- SEM) were significantly higher than those in the normal opposite wall (endocardial: 106 +/- 3 ml/min/100 gm, p less than 0.01); epicardial: 108 +/- 3 ml/min/100 gm, p less than 0.01. The location and circumferential extent of myocardium showing this elevation of preocclusion blood flow correlated well (r = 0.93, p less than 0.001) with the location and circumferential extent of the histologic infarct. The amount of wall motion abnormality, measured from the "correlation plot area," decreased significantly from its maximum value of 39 +/- 3 degrees at 48 hours after coronary occlusion to 3 +/- 1 degrees (p less than 0.001) at 6 weeks after occlusion. The ratio of the preocclusion transmural blood flow in the infarct zone to that in the noninfarct zone, a measure of the condensation of the microspheres injected before coronary occlusion, and therefore of the degree of scar contraction at 6 weeks, correlated well (r = 0.83, p less than 0.01) with the recovery of wall motion 6 weeks after infarction.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationship of functional recovery to scar contraction after myocardial infarction in the canine left ventricle. 292 98

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.
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PMID:A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. 296 Aug 97

Increases in plasma creatine kinase-MB (MB CK) were correlated with the onset of coronary artery reperfusion determined angiographically in 32 patients with acute myocardial infarction who were treated with recombinant human tissue-type plasminogen activator (rt-PA). Reperfusion occurred in 14 (70%) of 20 patients with left anterior descending coronary artery occlusion and in 8 (73%) of 11 patients with right coronary artery occlusion. One patient had persistent left circumflex coronary artery occlusion. Plasma MB CK levels (radioimmunometric assay) did not increase significantly in patients with persistent occlusion, but increased by a mean (+/- SEM) of 8 +/- 1 and 6 +/- 1 times over pretreatment levels at the end of the infusion in patients with a reperfused left anterior descending and right coronary artery, respectively. When a greater than or equal to 2.5-fold increase in MB CK levels at the end of the rt-PA infusion was taken as evidence of reperfusion of the left anterior descending coronary artery, 13 (93%) of 14 patients with reperfusion and 5 (83%) of 6 with persistent occlusion were correctly identified. When a greater than or equal to 2.2-fold increase in MB CK levels was used to identify right coronary artery reperfusion, seven (89%) of eight patients with persistent occlusion were correctly identified. The sensitivity and specificity of these indexes, derived from and applied to the same patient group, were 91 and 89%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of coronary artery reperfusion with creatine kinase-MB determinations during thrombolytic therapy: correlation with acute angiography. 312 51

To define the role of arachidonate metabolites in evolving ischaemic myocardial damage 10 anaesthetised open chest dogs underwent 90 min occlusion of the left anterior descending coronary artery followed by 5 h reperfusion. Tissue extracts from ischaemic myocardium incubated in vitro were subjected to high pressure liquid chromatography for analysis of lipoxygenase products such as mono hydroxyeicosatetraenoic (HETE) acids and to radioimmunoassay for determining a cyclooxygenase product, thromboxane B2. In ischaemic myocardium the production of 12-HETE (120(35) ng.g-1, mean (SEM)) and thromboxane B2 (18.3(2.4) ng.g-1) was significantly higher than that in normal myocardium (13(2) ng.g-1, p less than 0.01, and 4.2(0.5) ng.g-1, p less than 0.001, respectively). 12-HETE production was linearly correlated with thromboxane B2 production in ischaemic myocardium (r = 0.718, p less than 0.02). The increased production of 12-HETE and thromboxane B2 was in proportion to infarct size as measured by a percentage risk area infarcted (r = 0.732, p less than 0.02, and r = 0.942, p less than 0.001, respectively). Similarly, the increase in production of these eicosanoids was related to the degree of leucocyte infiltration in ischaemic myocardium. These results indicate that altered arachidonate metabolism is strongly associated with the progression of ischaemic myocardial damage, suggesting important roles for these eicosanoids, which may be produced by blood corpuscles during the evolution of acute myocardial infarction.
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PMID:Increased production of arachidonate metabolites in an occlusion-reperfusion model of canine myocardial infarction. 312 3

Myoglobin (Mb) is a protein that enters rapidly and is rapidly cleared from plasma after coronary reperfusion. We sought to determine the accuracy with which a rapid rise in plasma [Mb] could predict successful coronary artery reopening in patients undergoing coronary arteriography in conjunction with attempted reperfusion in acute myocardial infarction. In 42 patients, plasma Mb levels were measured before and for at least 4 hours after attempted reperfusion. Thirty-five patients were successfully reperfused. In each, the plasma Mb level rose rapidly with peak [Mb] occurring at 111 +/- 8.1 (+/- SEM) minutes after application of therapy. In contrast, Mb levels rose more slowly in the seven patients who were not reperfused, with peak [Mb] occurring 360 +/- 61.4 minutes after attempted reperfusion. T25-100 (the time required for [Mb] to rise from 25% to 100% of peak value) was shorter in patients successfully reperfused (71 +/- 7.9 minutes) and longer (341 +/- 35.3 minutes) in patients in whom therapy was unsuccessful. A rapid rise in [Mb] after successful reperfusion was also evident by a more than 4.6-fold rise in [Mb] over the first 2 hours after reperfusion in all but five patients; in contrast, [Mb] rose by less than 4.6-fold over this same interval in every patient not successfully reperfused (sensitivity, 85%; specificity, 100%; predictive accuracy, 88%). We conclude that a rapid rise in plasma Mb level over the initial 2 hours after attempted reperfusion in acute myocardial infarction provides a useful index of successful reperfusion.
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PMID:Early noninvasive detection of successful reperfusion in patients with acute myocardial infarction. 319 89

In a double blind placebo controlled trial, 434 patients with suspected myocardial infarction were randomised to treatment with nifedipine (n = 217) or placebo (n = 217) within six hours from the onset of chest pain. During the treatment period of 48 hours, a 10 mg capsule containing nifedipine or placebo was given sublingually every four hours for 24 hours, then orally every four hours for the next 24 hours. Acute myocardial infarction was confirmed in 295 patients (146 in the nifedipine group and 149 in the placebo group). The median delay time to intervention with nifedipine in patients with acute myocardial infarction was 111 minutes. Infarct size was assessed by the estimation of release of creatine kinase isoenzyme MB and creatine kinase from blood samples taken every four hours for 48 hours. The total mean (SEM) creatine kinase MB released was 406.4 (27.2) IU/l in the nifedipine group and 345.7 (20.5) IU/l in the placebo group. Total mean (SEM) creatine kinase released was 2749.6 (165.1) IU/l in the nifedipine group and 2698.4 (145.9) IU/l in the placebo group. In hospital mortality was similar for both the nifedipine and placebo groups (6.6% and 5.8% respectively). Treatment with nifedipine in the early phase of acute myocardial infarction seems to have no effect on enzymatically measured infarct size.
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PMID:Effect of nifedipine on enzymatically estimated infarct size in the early phase of acute myocardial infarction. 328 77

The influence of nifedipine on left ventricular ejection fraction, infarct size, and infarct expansion was studied in a prospective, double blind, randomised, placebo controlled trial in 132 patients with low risk acute myocardial infarction of less than 12 hours duration, defined by an initial left ventricular ejection fraction greater than 35% and clinical Killip class of less than or equal to II. Sixty four patients were assigned to nifedipine 120 mg/day and 68 to placebo. Treatment was started on average (SEM) 8.0 (0.2) hours after onset of pain and continued for six weeks. Gated blood pool scans, thallium scans, and cross sectional echocardiograms were performed before treatment and at 10 days. There were no significant differences between the two groups in age, sex, cardiac risk factors, or use of other medications. Mean (SEM) global left ventricular ejection fraction was not different before treatment (nifedipine group 53 (2%), placebo group 55 (2%) and did not differ at 10 days (nifedipine group 54 (2%), placebo group 52 (2%). There were also no differences in regional wall motion or regional ejection fractions. Thallium defects quantified by computer analysis were similar in both groups before treatment (nifedipine 7.8 (0.7), placebo 7.9 (0.7)) and at 10 days (nifedipine 5.3 (0.7) placebo 5.3 (0.7)). In the subgroup of patients with transmural infarction who had good quality echocardiograms and serial studies (n = 30), there was no difference in mean (SEM) baseline infarct segment lengths between the two groups (nifedipine 70 (4) mm, placebo 65 (4) mm); however, the nifedipine group demonstrated no significant change in infarct segment length between the initial and 10 day studies ( + 0.6 (3) mm) while there was a significant increase in the infarct segment length in the placebo group (+ 7.8 (4) mm). The infarct segment length increased by >/= 1 cm in seven (47%) placebo patients but in only one (7%) nifedipine patient. The nifedipine group had a significant initial 10% decrease in mean arterial pressure whereas there was no change in the in the placebo group; this blood pressure difference persisted for 10 days. Thus although the early administration of nifedipine has no detectable effect on clinical outcome and infarction size, it may reduce early infarct expansion via an afterload reduction mechanism in patients with transmural infarction. These initial results must be interpreted with caution and need to be confirmed in a larger trial.
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PMID:Nifedipine in acute myocardial infarction: an assessment of left ventricular function, infarct size, and infarct expansion. A double blind, randomised, placebo controlled trial. 328 78

In a randomized study on early intracoronary thrombolytic therapy in patients with acute myocardial infarction (AMI), serial plasma enzyme activities were measured to analyze the rate of enzyme appearance in plasma with reference to treatment allocation, area at risk, and infarct size. Cumulative activities of alpha-hydroxybutyrate dehydrogenase (HBDH) appearing in plasma in the first 24 hours (Q24), 48 hours (Q48), and 72 hours (Q72) were calculated to obtain infarct size (= Q72) and rate of HBDH appearance in plasma (= Q24/Q72). Analyzed on the basis of "intention to treat" in 448 patients with AMI, the mean Q24/Q72 value (+/- SEM) was 0.653 +/- 0.011 in 230 patients receiving thrombolytic therapy; this value was significantly (p less than 0.001) higher than that observed in 218 patients receiving conventional therapy (0.504 +/- 0.012). In the thrombolysis group Q24/Q72 was independent of infarct size, whereas in the control group Q24/Q72 was negatively correlated with infarct size (r = -0.26; p less than 0.001). Plotted against the sum of ST segment elevations at admission (sigma ST) mean Q24 values were similar in both treatment groups, but mean Q48 and especially Q72 values were larger in the control group than in the thrombolysis group. We conclude that: (1) in reperfused infarctions the time course for development of infarct is accelerated in comparison to unreperfused infarcts; (2) this accelerated process of necrosis lasts about 40 to 50 hours, a duration that is hardly influenced by infarct size; and (3) the reperfusion-induced acceleration of enzyme release resembles the reoxygenation-induced enzyme release from anoxic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid enzyme release from acutely infarcted myocardium after early thrombolytic therapy: washout or reperfusion damage? 335 99


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