Effects Of Coronary Artery Reperfusion Research Articles

Requiem for a Heavyweight

The development of rapid, automated, and accurate laboratory testing for creatine kinase MB (CK-MB) revolutionized the treatment of patients with acute cardiac events in the 1970s and 1980s.1 To clinicians, CK-MB values augmented a thorough history, physical, and ECG findings, and elevations rapidly became the gold standard for identifying cardiac injury.1 CK-MB allowed earlier diagnosis of acute myocardial infarction (AMI), and detection of reinfarction, and measurements could be used to provide a facile clinical estimate of infarct size. Elevations of CK-MB were never intended to be synonymous with myocardial infarction, only indicative of cardiac injury.1 However, because of the relative insensitivity of measurements, increased concentrations occurred predominantly with larger insults such those associated with acute ischemic heart disease. For that reason, AMI was rarely diagnosed, assuming appropriate timing of the samples, in the absence of a CK-MB elevation.2,3 CK-MB assays initially relied on the measurement of enzyme activity, but over time, improved accuracy and ease of use were established by the use of mass assays. Mass assays allowed earlier detection of abnormal values and improved both clinical sensitivity and specificity. However, mass assays unmasked an increased frequency of CK-MB elevations due primarily to skeletal muscle injury because of their increased sensitivity.4–6 Clinical use of the percent relative index was then initiated. This approach improved the specificity of elevations for cardiac muscle injury but was insensitive when concurrent cardiac injury and skeletal muscle injury were present because elevations from skeletal muscle often are of a large magnitude.7–10 A large number of analytical confounds such as macrokinases and interfering substances also were substantial problems with these assays.10,11 Attempts to standardize assays12 have been partially successful, but differences still exist between manufacturers and even between the same testing antibodies used on different analytical platforms (ie, …

Ultrasonic Integrated Backscatter Identifies Promptly Effects of Coronary Artery Reperfusion After Acute Myocardial Infarction

Ultrasonic Integrated Backscatter Identifies Promptly Effects of Coronary Artery Reperfusion After Acute Myocardial Infarction

Ultrasonic integrated backscatter identifies promptly effects of coronary artery reperfusion after acute myocardial infarction

Ultrasonic integrated backscatter identifies promptly effects of coronary artery reperfusion after acute myocardial infarction

Effect of Coronary Artery Reperfusion on Transmural Myocardial Remodeling in Dogs

The effects of reperfusion after coronary occlusion on transmural remodeling of the ischemic region early and late after nontransmural infarction must importantly affect the recovery of regional function. Accordingly, analysis of local volume and three-dimensional strain was performed using a finite element method to determine regional remodeling. Systolic and remodeling strains were measured using radiographic imaging of three columns (approximately 1 cm apart) of four to six gold beads implanted across the left ventricular posterior wall in 6 dogs. After a control study, infarction was produced by 2 to 4 hours of proximal left circumflex coronary artery occlusion followed by reperfusion. Follow-up studies were performed at 2 days, 3 weeks, and 12 weeks with the dogs under anesthesia and in closed-chest conditions. Biplane cineradiography was performed to obtain the three-dimensional coordinates of the beads. At 2 days, end-systolic strains were akinetic with loss of normal transmural gradients of shortening and thickening. Remodeling strains (RS) were determined by use of a nonhomogeneous finite element method by referring the end-diastolic configuration during follow-up studies to its control state at matched end-diastolic pressures and heart rates. Tissue volume at 2 days increased substantially, more at the endocardium (30 +/- 7%) than at the epicardium (5 +/- 12%, P < .01); the increase was associated with an average RS in the wall-thickening direction of 0.18 +/- 0.15 (P < .01) with all other RS near zero. At 12 weeks systolic function partially recovered, with normal wall thickening in the epicardium (radial strain, 0.081 +/- 0.056 [control] versus 0.113 +/- 0.088 [12 weeks]) but with dysfunction in the endocardium (0.245 +/- 0.108 [control] versus 0.111 +/- 0.074 [P < .01] [12 weeks]). This inability of the inner wall to recover function may be related to increased transmural torsional shear and negative longitudinal-radial transverse shear in the inner wall. Volume loss occurred at 12 weeks in the endocardium (-36 +/- 16%) corresponding to transmural gradients in longitudinal RS and both transverse shear RS. Negative longitudinal RS was greater at the endocardium (-0.20 +/- 0.10) than at the epicardium (-0.06 +/- 0.05, P < .01). These results indicate the presence of marked subendocardial edema 2 days after reperfusion following 2 to 4 hours of coronary occlusion. At 3 months after reperfusion, however, there was volume loss in the inner wall due to shrinkage along the myofiber direction with reduced transmural function and loss of longitudinal shortening, while both tissue volume and function recovered completely in the outer wall.

Time course of infiltration and distribution of neutrophils following coronary artery reperfusion in the rat

To investigate the effect of coronary artery reperfusion on neutrophil infiltration into the myocardium in a model of low-collateral blood flow, we studied hearts from five groups of anesthetized rats subjected to 1) permanent coronary occlusion for 2 hours, 2) permanent coronary occlusion for 3 hours. 3) 1 hour of occlusion followed by reperfusion for 1 hour, 4) 1 hour of occlusion followed by reperfusion for 2 hours, or 5) sham operation Sections from hearts were examined microscopically (=750 fields/section), the neutrophils counted, and their location determined. Reperfusion for 1 hour did not increase the number of neutrophils compared to 2 hours of permanent occlusion (80 ± 17/section vs 59 ± 16/section, P = NS. However, 2 hours of reperfusion significantly increased the number of neutrophils (529 ± 128/section) compared to either 1 hour of reperfusion (80 ± 17/section, P < 0.001) or 3 hours of permanent occlusion (121 ± 25/section, P< 0.01). The distribution of neutrophils changed over time: after 1 hour of reperfusion, neutrophils were located primarily in vessels (74% ± 5%), but after 2 hours, only 32% ± 6% were in vessels, with most neutrophils located within the interstitium or in myocytes. Neutrophils appeared to enter the tissue via the subepicardial vessels and stream toward the subendocardium. We conclude that neutrophils are initially located in vessels: by 2 hours of reperfusion, however, they are located mainly in the interstitium and in myocytes. Reperfusion greatly increased the number of neutrophils in the heart compared with permanent occlusion; however, the increase did not occur until after 2 hours of reperfusion.

Effect of coronary artery reperfusion on right ventricular infarction associated with acute inferior myocardial infarction

Effect of coronary artery reperfusion on right ventricular infarction associated with acute inferior myocardial infarction

Myocardial reperfusion in the pig heart model: infarct size and duration of coronary occlusion.

The effect of coronary artery reperfusion on infarct size was studied in a pig heart model. Forty four open chest pigs underwent occlusion of the mid-left anterior descending artery. Fifteen minutes after occlusion the animals were randomised to one of five groups: reperfusion at 30, 45, 60, or 90 min after occlusion (groups 1-4) or permanent occlusion (group 5). Twenty four hours after coronary occlusion the pigs were killed. The heart was sectioned in slices, which were incubated in triphenyl-tetrazolium. Mean(SEM) infarct sizes calculated by planimetry were 0.46(0.42), 2.85(1.14), 9.74(1.65), 8.93(1.37), and 13.17(1.17)% of left ventricular mass in the five groups. The transmural extension of the infarct was 14.6(11.4), 42.1(12.9), 87.4(6.6), 96.2(3.2), and 100(0)% and a transmurality index used as an estimate of the mean extension of the infarct relative to wall thickness was calculated to be 0.08(0.06), 0.32(0.10), 0.72(0.06), 0.79(0.04), and 0.92(0.02) respectively. Infarct size was similar in groups 3-5, but significantly smaller in groups 1 and 2 (p less than 0.05). Infarct size and the transmurality index correlated exponentially with the duration of the occlusion (r = 0.80, p less than 0.01; and r = 0.95, p less than 0.001 respectively). These results indicate that in the pig heart model submitted to an acute coronary occlusion cell viability may be less than that suggested by previous canine studies. This observation is probably related to a less well developed collateral blood flow in the pig heart and may provide an experimental model that better resembles certain clinical conditions.

Immediate rebound followed by deterioration of regional left ventricular function with coronary reperfusion

The immediate and early effects of coronary artery reperfusion initiated 1 and 3 hours after coronary artery occlusion were evaluated by two-dimensional echocardiographic measurements of overall and regional left ventricular function. A total of 29 anesthetized open chest dogs underwent one of the following: 1 hour occlusion followed by reperfusion (Group I, n = 9), 3 hour occlusion followed by reperfusion (Group II, n = 12) or 5 hour occlusion without reperfusion (Group III, n = 8). Serial two-dimensional echocardiography was performed at baseline; at 1, 3 and 5 hours of coronary occlusion; within 5 minutes of reperfusion; and at 2 hours of reperfusion. After occlusion, all groups manifested significant (p less than 0.01) increases in left ventricular diastolic and systolic area and decreases in left ventricular area ejection fraction. With coronary reperfusion, there was no improvement in these global variables in Groups I and II. However, immediately after reperfusion, there was improvement in the regional extent of dysfunction (Group I, 138 +/- 35 to 66 +/- 62 degrees, p less than 0.05; Group II, 156 +/- 51 to 85 +/- 77 degrees, p less than 0.05) as well as improvement in the regional degree of dyskinesia (p less than 0.05). These regional improvements were transient and resolved by 2 hours of coronary reperfusion. This immediate rebound of function was not associated with the duration of coronary occlusion, hemodynamic variables or ultimate infarct size. Thus, in the anesthetized open chest dog model, coronary artery reperfusion at 1 or 3 hours produces an immediate but transient improvement in regional systolic myocardial function.

Effects of Coronary Artery Reperfusion on Recovery of Regional Myocardial Function In Conscious Dogs

The effects of coronary artery occlusion and reperfusion at 1 h (1-h group), 2 h (2-h group) and 3-h (3-h group) were compared with a permanently occluded group (P group) on measurements of overall left ventricular (LV) and regional endocardial function over a 4-wk period. The experiments were conducted in conscious dogs 1–3 wk after recovery from instrumentation with solid-state LV pressure gauges, aortic and left atrial catheters, hydraulic occluders and Doppler flow transducers on the left circumflex coronary artery, and multiple pairs of ultrasonic transducers implanted in the endocardial third of the LV free wall to measure endocardial segment shortening. During coronary artery occlusion, similar haemodynamic effects were observed in each of the four groups. At 1 h after coronary artery occlusion, systolic shortening was depressed by over 100%. In the P group, systolic shortening remained depressed by 86 ± 6·8% 4 wk later. Considerable return of function occurred in the 1-h group—i.e., shortening remained depressed by only 30 ± 7·4%. Systolic shortening remained depressed by 58 ± 9·1% in the 2-h group and by 78 ± 5·6% in the 3-h group. Thus, in the conscious dog, coronary artery reperfusion at 1h after coronary artery occlusion results in substantial return of endocardial function in the most severely ischaemic myocardium. However, after 3 h of coronary artery occlusion, little salvage of regional endocardial myocardial function can be induced by acute reperfusion in this model.

Effects of coronary artery reperfusion on regional myocardial blood flow and function in conscious baboons.

The effects of coronary artery reperfusion initiated 1 hr and 3 hr after coronary artery occlusion were evaluated on measurements of overall and regional left ventricular function and on regional myocardial blood flow. These experiments were conducted in conscious baboons 2 to 3 weeks after recovery from instrumentation with a solid state left ventricular pressure gauge, aortic and left atrial catheters, a hydraulic occluder around the mid left anterior descending coronary artery, and pairs of ultrasonic transducers implanted in the endocardium of the left ventricular free wall or across the free wall to measure endocardial segment shortening and wall thickening, respectively. Coronary artery occlusion induced similar effects in both groups. At 1 hr after occlusion, the ischemic zone was characterized by severe and equal reductions in both endocardial (-97 +/- 1%) and epicardial (-95 +/- 4%) blood flows and complete loss of regional systolic function, which was replaced by paradoxical wall motion. Reperfusion initiated after 1 hr of ischemia was associated with a marked transient increase in endocardial (+386 +/- 51%) and epicardial (+544 +/- 79%) blood flows. During the subsequent 4 weeks, segment shortening and wall thickening tended to improve. However, at 4 weeks after reperfusion, segment shortening was still depressed by 45 +/- 12% and wall thickening by 58 +/- 14%. In contrast, reperfusion initiated after 3 hr of ischemia was not associated with a significant hyperemic response, and systolic segment shortening and wall thickening did not recover during the subsequent 4 week period.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of coronary artery reperfusion on relation between creatine kinase-MB release and infarct size estimated by myocardial emission tomography with thallium-201 in man

The quantitative relations between serum creatine kinase-MB isoenzyme (CK-MB) release and the final infarct size estimated by myocardial emission computed tomography with thallium-201 was assessed in 37 patients with a first acute transmural myocardial infarction who underwent intracoronary thrombolysis using urokinase 4.6 +/- 1.9 hours after the onset of symptoms. Serial CK-MB determinations were used to calculate the accumulated release of CK-MB (sigma CK-MB). Myocardial emission tomography with thallium-201 was performed 4 weeks after the onset, and infarct volume was measured from reconstructed tomographic images by computerized planimetry. The results are presented for two groups of patients: 11 patients with unsuccessful thrombolysis (group A) and 26 patients with successful thrombolysis (group B). An excellent linear relation was found for group A (sigma CK-MB = 6.4 X infarct volume + 47.7, r = 0.91), whereas a different linear relation was observed for group B (sigma CK-MB = 10.5 X infarct volume + 89.1, r = 0.80). Moreover, serum CK-MB activity reached a peak at 21.1 +/- 2.2 hours after the onset in group A and reached an earlier peak at 12.5 +/- 2.9 hours in group B (p less than 0.001). These data suggest that acute coronary recanalization alters the kinetics of CK-MB release, resulting in greater CK-MB release into the serum for equivalent infarct volume estimated by myocardial emission tomography with thallium-201. Thus, serum CK-MB time-activity curves after acute myocardial infarction may be influenced considerably by acute reperfusion, which is an important factor that should be incorporated in the interpretation of enzymatic estimates of infarct size in human patients.

Effects of coronary artery reperfusion on myocardial infarct size and survival in conscious dogs.

The effects of coronary artery reperfusion at 1 and 3 hours after coronary artery occlusion were examined on myocardial infarct size and survival in conscious dogs. Left circumflex coronary artery occlusion was induced by inflating an hydraulic occluder and confirmed thereafter by measuring the absence of coronary blood flow. Of the 77 dogs that underwent coronary artery occlusion, 18 died within 1 hour. Of the 59 remaining dogs, permanent coronary artery occlusion was carried out in 31 dogs, 12 underwent reperfusion after 1 hour and 16 underwent reperfusion after 3 hours. Survival at 1 week was enhanced significantly (p < 0.01) by reperfusion carried out at either 1 or 3 hours; only 29% of dogs with permanent coronary artery occlusion survived, whereas 83% and 75% of dogs survived 1 week with reperfusion at 1 hour and 3 hours, respectively. Average infarct size at 1 week was smaller in dogs with reperfusion (NS). The inability to reach statistical significance was most likely the result of two factors: (1) There was a marked variation in infarct size in dogs with permanent coronary artery occlusion--infarcts averaged 21.3 +/- 7.5% and ranged from 0.7-72.6% of the left ventricle. (2) Dogs that died 1-7 days after coronary artery occlusion had significantly (p < 0.05) larger infarcts (40 +/- 4% of left ventricle) than those that survived 1 week in any of the three groups. Thus, if all dogs had survived 1 week, a beneficial effect on infarct size could have been demonstrated. Nevertheless, coronary artery reperfusion at either 1 or 3 hours after coronary artery occlusion induces a striking beneficial effect on survival, which is of the utmost clinical significance.

Effect of coronary artery reperfusion on infarct size in swine

Several authors have reported a low mortality and salvage of ischemic myocardium in patients undergoing coronary revascularization after recent myocardial infarction. In this study, 20 surviving pigs with a coronary circulation similar to that of man were divided into two groups of 10 animals each. In the first group, the left anterior descending coronary artery (LAD) was ligated just beyond the first diagonal branch. Five animals were put to death at 24 hours and the remaining five animals, at 7 days. In the other group of 10 animals, the LAD was occluded just beyond the first diagonal branch and reperfused 3 hours after occlusion. Five of these animals were put to death at 24 hours and the remaining five animals, at 7 days. The left atrial pressure (LAP), heart rate, mean arterial pressure (MAP), and cardiac output were continuously monitored. Myocardial infarct size was determined planimetrically after the myocardium was sliced and stained with nitroblue tetrazolium. In five animals subjected to ligation for 24 hours, myocardial infarct size was 20.3 +/- 0.53 standard error mean (SEM) grams infarct per 100 gm left ventricular and septal mass (gm/100 gm LVS). In five animals subjected to occlusion, reperfusion in 3 hours, and death at 24 hours, the infarct size was 22.9 +/- 1.7 SEM gm/100 gm LVS. At 1 week in the ligated animals the infarction decreased to 15.5 +/- 1.7 SEM gm/100 gm LVS. In the reperfused animals at 1 week the infarction size was 14.5 +/- 1.7 SEM gm/100gm LVS. There was no significant difference in these values (Student's t test). Light and electron micrographs demonstrated hemorrhagic necrosis in every instance with reperfusion. Cardiac output, LAP, and MAP remained unchanged after reperfusion. These data suggest that in human beings without well-developed inherent collaterals sustaining myocardial infarction with coronary occlusion, that reperfusion as early as 3 hours after infarction would not be beneficial.

The loss of radioactive microspheres from canine necrotic myocardium.

The loss of radioactive microspheres from canine necrotic myocardium.

The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation.

The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation.

Effects of coronary artery reperfusion on myocardial infarct size calculated from creatine kinase.

The effects of coronary artery reperfusion at 1 and 3 h after occlusion on infarct size (IS) in the conscious dog were compared with a second group of dogs that were not reperfused (24 h occlusion). Infarct size was calculated from creatine kinase (CK) appearing in blood samples (IS(s)) and myocardial CK depletion (IS(m)), and determined from gross and histological inspection of the pathological tissue (IS(p)). Under both conditions, IS(m) correlated well with IS(p). In dogs with 24-h coronary occlusions, IS(s) correlated well with IS(m) (IS(s) = 14.26 + 1.18 x IS(m), r = 0.92). In reperfused dogs, the relationship remained linear but was altered (IS(s) = 15.33 + 2.07 x IS(m), r = 0.89). The slope was significantly greater, P <0.05, than that observed for dogs that were not reperfused, suggesting that more CK appeared in serum per gram of infarct. Similarly, significantly different relationships were observed in the reperfused and nonreperfused dogs, when IS(s) was compared with IS(p). Moreover, the configuration of the serial blood CK curve was changed significantly by reperfusion. In dogs with a 24-h occlusion, CK rose gradually to a peak at 11.4+/-0.5 h. In dogs reperfused at 3 h, CK rose sharply at 3 h and reached a peak at 6.8+/-0.5 h, significantly earlier (P <0.01) than occurred in dogs reperfused at 1 h, i.e., when the peak occurred at 4.2+/-0.4 h. The rapid appearance of CK in blood after reperfusion at 1 and 3 h suggested a washout phenomena. Thus, reperfusion alters the shape of the serial blood CK curve and results in a different linear relationship between calculated and measured infarct size, resulting in greater recovery of CK in blood per unit of infarcted myocardium.

The effect of coronary artery reperfusion on the extent of myocardial infarction

The effect of the reperfusion on myocardial infarction has been studied in the rat in order to assess the possible reversibility of myocardial damage. The present study deals with reperfusion of experimental myocardial infarction in the rat. Two groups of animals were compared: one was subjected to permanent ischemia and the other was subjected to ischemia of variable duration 1) hour to 24 hours). The differences between infarction caused by permanent ischemia and the evolution of infarction following reperfusion were studied by means of histologic (121 specimens) histoenzymatic (56 specimens), ECG (100 specimens), techniques and study of the mcirocirculation (70 specimens). The size of the infarctions caused by temporary ischemia was found to be significantly smaller in 60% of the cases as compared to the infarctions caused by permanent ischemia. Histoenzymatic study (phosphorylase activity and succinodehydrogenase activity) confirmed the existance of a marginal zone extending over one third of the surface of the ischemic myocardium: reperfusion permitted the salvage of this zone and thereby diminished the extent of necrosis. The latter findings were further confirmed by the ECG study showing earlier regression of ischemic ST changes following early reperfusion. Microcirculatory changes secondary to anoxia may account for the fact that, in a certain percentage of the cases, early reperfusion does not prevent extension of infarction.

Coronary artery reperfusion. I. Early effects on local myocardial function and the extent of myocardial necrosis.

The effects of coronary artery reperfusion 3 hr after coronary occlusion on contractile function and the development of myocardial damage at 24 hr was studied experimentally. In 14 control and 6 reperfused dogs, relationships between epicardial ST segment elevation 15 min after coronary occlusion and myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 hr later were examined. The electrocardiograms were recorded from 10 to 15 sites on the left ventricular epicardium and transmural samples for CPK and histology were obtained from the same sites where epicardial electrocardiograms had been recorded. An inverse relation existed between ST segment elevation (mv) 15 min after occlusion and log CPK activity (IU/ mg of protein) 24 hr later, log CPK = - 0.06ST + 1.26. In dogs subjected to coronary artery reperfusion, there was significantly less CPK depression (log CPK = - 0.01ST + 1.31, [P < 0.01]) than that expected from the control group. In the control group 97% of specimens showing ST segment elevations over 2 mv at 15 min showed abnormal histology 24 hr later. In contrast, in the reperfused group 43% of sites exhibiting elevated ST segment at 15 min showed abnormal histology 24 hr later. In six additional dogs it was shown that the paradoxical movement of the left ventricular wall could be reversed within 1 hr of perfusion. Therefore, by enzymatic and histologic criteria, as well as by functional assessment, coronary artery reperfusion 3 hr after occlusion resulted in salvage of myocardial tissue.