Identification of high risk patients after an acute myocardial infarction. Therapeutic approach for secondary prevention.
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Biomedical subjects
Publications and source records attributed to L G Ribeiro.
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The effects of enalaprilat (MK-422), an angiotensin converting enzyme inhibitor, were compared to those of SCRIP, a renin inhibitor, in experimentally induced left ventricular failure. In anesthetized dogs, acute left ventricular failure was induced by repeated embolization, via the left main coronary artery, with 50 microns plastic microspheres. Embolization significantly increased left ventricular enddiastolic pressure from 6 +/- 1 to 14 +/- 1 (p less than 0.05) mm Hg and decreased both left ventricular maximal dP/dt (3,135 +/- 338 to 1,636 +/- 126 mm Hg/second, p less than 0.05) and cardiac output (3.0 +/- 0.3 to 1.6 +/- 0.1 liters per minute, p less than 0.05). Embolization also significantly reduced heart rate and mean arterial pressure. These parameters remained stable after induction of heart failure. Forty-five minutes after embolization, 16 dogs received enalaprilat (100 microns/kg intravenously) and six dogs received SCRIP (100 microns/kg intravenously followed by 10 microns/kg per minute). Both agents caused similar reductions in left ventricular end-diastolic pressure (21 percent versus 26 percent) and total peripheral resistance (25 percent versus 32 percent) and rise in peak positive cardiac contractility, as measured by (dP/dt)/P, (12 percent versus 11 percent). The data suggest that inhibition of angiotensin II formation by two agents, each or which acts at a different point in the cascade, results in similar beneficial hemodynamic effects in dogs with acute left ventricular failure. In addition, angiotensin converting enzyme inhibition failed to further increase sodium excretion and glomerular filtration rate caused by embolization. In summary, inhibition of angiotensin II production by two different inhibitors of the renin system causes an improvement in left ventricular performance in a model of acute experimental left ventricular failure.
The effects of equiblocking doses of three beta-adrenergic blocking agents, propranolol, timolol and metoprolol, on myocardial infarct size were evaluated in 28 dogs after acute experimental coronary artery occlusion. Heart rate, arterial pressure and arterial free fatty acid concentration were measured in an attempt to evaluate their effects on the extent of myocardial injury. The zone at risk of infarction in each dog 1 minute after left anterior coronary artery occlusion was assessed by injecting highly radioactive albumin microspheres into the left atrium, and the hypoperfused zone was determined by autoradiography. After 15 minutes, the dogs were randomized into four groups: control dogs (n = 7), propranolol-treated dogs (1.2 mg/kg intravenously, n = 7), timolol-treated dogs (0.2 mg/kg intravenously, n = 7) and metoprolol-treated dogs (1.2 mg/kg intravenously, n = 7). After 6 hours, the dogs were killed. The left ventricle was sliced and stained with triphenyl-tetrazolium chloride for measurement on infarct size. The same slices were then autoradiographed for measurement of the hypoperfused zone. The percent of hypoperfused zone that evolved to infarction (the ratio of infarct size to hypoperfused zone) was 90.4 +/- 1.9% in the control group, 72.4 +/- 2.4% in the propranolol-treated dogs (p less than 0.05 versus control group); 57.9 +/- 4.4% in the timolol-treated dogs (p less than 0.01 versus control group; p less than 0.05 versus propranolol) and 54.4 +/- 3.7% in the metoprolol-treated dogs (p less than 0.01 versus control group; p less than 0.05 versus propranolol). Thus, propranolol, timolol and metoprolol reduced myocardial infarct size in dogs by 20, 36 and 40%, respectively, after experimental coronary artery occlusion. Metoprolol and timolol protected the ischemic myocardium more effectively than did propranolol.
Ventricular fibrillation and subsequent death frequently occur so soon after coronary artery occlusion that infarct size cannot be determined; thus the systematic study of their relationship is impossible. Recently, however, a technique has been developed that permits the assessment, in vivo, of the extent of the myocardial hypoperfused zone (HZ). Accordingly, in 55 open-chest dogs, 99mTc-labeled (8 mCi) albumin microspheres (15 microns in diameter) were injected into the left atrium 1 minute after coronary artery occlusion. The zone of hypoperfusion was analyzed in 28 dogs that had ventricular fibrillation (group A) and 27 dogs that had no ventricular fibrillation (group B). In group B, the HZ was 26.3 +/- 1.7% of the left ventricle vs 31.6 +/- 1.3% of the left ventricle in group A (p less than 0.05), showing that ventricular fibrillation occurred in dogs with larger zones of hypoperfusion.
Lidocaine has been shown to protect ischemic myocardium, but the degree of its effectiveness is not yet well established. Therefore, in this study, the effects of this drug on ultimate infarct size were examined quantitatively. Another member of the same class of drugs, droxicainide (ALS1249), DL-N-(2-hydroxyethyl)-pipecolinyl-2,6-dimethylanilide hydrochloride, is a new antiarrhythmic agent that has shown a good therapeutic index in the initial experimental studies. Accordingly, the effects of this drug on ultimate infarct size were examined and compared with those of lidocaine. Coronary artery occlusion was performed on 29 dogs. One minute later, technetium-99m labeled microspheres were injected into the left atrium for assessment of the hypoperfused zone (the zone at risk of infarction). Fifteen minutes after occlusion, the dogs were randomized into three groups: 9 dogs served as a control group, 10 were given lidocaine and 10 were given the same dosage of droxicainide. Six hours after occlusion, the dogs were sacrificed and the hearts cut into 3 mm thick slices and incubated in triphenyltetrazolium chloride to delineate the area of myocardial damage. Autoradiography of the same slices provided images of the areas of myocardial hypoperfusion. Thereafter, in each dog, the percent of hypoperfused area that evolved to necrosis was calculated. In control dogs, it was 85.6 +/- 2.0%; in lidocaine-treated dogs, 68.1 +/- 4.1% (p less than 0.01), a reduction of 20%; and in droxicainide-treated dogs, 50.1 +/- 5.3%, a reduction of 41% (p less than 0.001 versus control and p less than 0.005 versus lidocaine).
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Until recently, ECG accuracy in localizing acute myocardial infarction (AMI) could be assessed only by comparing the ECGs with autopsy findings. This approach, however, preselected patients, including only those who died. It is possible that this postmortem group of patients would be different from the whole population of patients with AMI. Myocardial imaging with 99mTc-pyrophosphate offers the advantage of directly localizing the region of injured myocardium in the acute phase of AMI. In 34 patients with confirmed AMI and focal uptake of 99mTc-pyrophosphate, serial ECGs were obtained and interpreted by two independent observers. The sensitivity and specificity of serial ECGs in determining the location of AMI in the five left ventricular (LV) wall segments were determined: (1) in the anterior wall sensitivity was 86.7% and specificity was 89.5%; (2) in the lateral wall sensitivity was 73.7% and specificity was 80.0%; (3) in the high lateral wall sensitivity was 80.0% and specificity was 87.5%; (4) in the inferior wall sensitivity was 87.5% and specificity was 100%; (5) in the "true" posterior wall sensitivity was 83.3% and specificity was 86.4%. Overall, in the 170 LV wall segments (five per patient) examined, scans localized with a sensitivity of 81.9% and a specificity of 88.8%. After four patients with LBBB were excluded, sensitivity increased to 87.1%. Overall, localization of AMI by serial ECG was accurate in 85.9% of the 34 patients included in the study.
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The goal of this investigation was to determine whether hyaluronidase administration can alter the size, morbidity, and mortality of experimental acute cerebral infarctions. Accordingly, the left common carotid artery was occluded in 1205 ether-anesthetized Mongolian gerbils. The gerbils were randomized into hyaluronidase-treated (4000 National Formulary units per kg., intravenously, 5 minutes after occlusion) or control groups. All were examined for clinical signs of cerebrovascular accident three times during the 24 hours and then decapitated, and each hemibrain was analyzed for its total creatine kinase activity. In the control group, 90 of 601 gerbils died, whereas in the hyaluronidase-treated group only 61 of 604 gerbils died. This reduction in mortality was highly significant (chi 2 = 6.53, p less than 0.02). In the surviving gerbils with cerebrovascular accidents, infarct size was calculated by creatine kinase depletion (normal right hemibrain creatine kinase minus infarcted left hemibrain creatine kinase divided by right hemibrain creatine kinase and corrected for "residual" (nondepletable) creatine kinase). In controls, infarct size was 36.5 +/- 1.8 per cent (n = 105), and in the hyaluronidase-treated gerbils it was significantly lower, 31.4 +/- 1.7 per cent (n = 117, p less than 0.05). Thus, in gerbils with experimental cerebrovascular accidents, hyaluronidase significantly reduced mortality (by one-third) and reduced "enzymatic" infarct size by 14.0 +/- 4.6 per cent (p less than 0.01).
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Using a very sensitive new technique, the effectiveness of hyaluronidase (HYL) in reducing infarct size (IS) was compared employing HYL obtained from bovine testicles and from fungi. One minute after coronary artery occlusion in dogs, highly radioactive microspheres were injected for autoradiographic assessment. The animals were then randomized into a control group and several HYL-treated groups. Six hours later all hearts were divided into 20 to 25, 3 mm-thick slices which were incubated in TTC to measure IS and thereafter autoradiographed to delineate the hypoperfused zone (HZ). The percent of HZ that evolved to necrosis (IS/HZ) was determined in each animal. In the control group, IS/HZ was 89.9 +/- 4.2% and was reduced by 17% (p less than 0.05) in the group treated with 500 units/kg of bovine HYL. With 500 units/kg of fungal HYL, IS/HZ was not reduced, but the higher dose of 5000 units/kg reduced IS/HZ by 26% (p less than 0.01). Thus dependence of HYL source is documented relative to the effectiveness of this salutary intervention for protecting ischemic heart muscle and limiting necrosis in acute myocardial infarction.
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The goals of this investigation were: 1) to examine the pattern of evolution of epicardial R wave voltage during the 24 h after experimental coronary artery occlusion; and 2) to determine whether hyaluronidase, an agent shown previously to reduce myocardial ischaemic injury, alters this evolution. Coronary artery occlusion was performed in 36 dogs. In the control dogs, the average R wave voltage (R) recorded over the ischaemic myocardium increased by 7.6 +/- 0.8 mV (P less than 0.001) from before to 15 min after coronary artery occlusion, then gradually returned to baseline over the ensuing 4 h. Subsequently, R wave voltage continued to fall, and 24 h after occlusion, R was 17.8 +/- 1.8 mV (P less than 0.001) less than before occlusion. In the hyaluronidase-treated dogs (500 NF units . kg-1), R recorded over the ischaemic myocardium increased similarly to the controls before hyaluronidase administration. However, in contrast to the control dogs, the administration of hyaluronidase 20 min after occlusion caused R to return to baseline over the ensuing 40 min and 24 h after occlusion, the treated animals lost significantly less R wave voltage than the controls (P less than 0.001).
A new method to determine left ventricular (LV) ejection fraction (EF) with wide-angle, two-dimensional echocardiography (2-D echo) has been developed using the parasternal long-axis, apical four-chamber and apical long-axis views. End-diastolic and end-systolic measurements of LV short axes at the base and mid-LV cavity in the parasternal long-axis view and at the upper, middle and lower thirds of the cavity in the apical views are made, from which an averaged minor axis at end-diastolic and at end-systole is calculated. Fractional shortening of the LV long axis (delta L) is estimated from apical contraction. Satisfactory 2-D echoes were obtained in 55 of 58 nonselected patients (all three views in 32 patients, two views in 22 and one view in one); 42 of 55 patients had coronary artery disease. EF by 2-D echo was compared with EF by gated cardiac blood pool imaging in all patients (r = 0.927, SEE = 6.7%) and to EF by single-plane cineangiography (angio) in 35 of 55 patients (r = 0.913, SEE = 7.4%). LV dyssynergy was frequently present and involved the apex in 29 of 55 patients. Using angio as the standard for evaluating wall motion at the apex, 2-D echo was 100% sensitive and specific in detecting abnormal apical wall motion. We conclude that EF can be determined accurately with 2-D echo in a large group of patients with and without dyssynergy by a simple method that eliminates the need for planimetry or computer assistance.