Search PubMed⌕ Search

Biomedical subjects

M C Fishbein

Publications and source records attributed to M C Fishbein.

At least 199 records · Page 11Linked to original sources
PubMed1985

Synchronized diastolic coronary venous retroperfusion: results of a preclinical safety and efficacy study.

The safety and efficacy of a new clinical synchronized diastolic retroperfusion mechanical pump and autoinflatable balloon catheter was studied in 10 dogs during and after 6 hours of left anterior descending coronary artery occlusion. Eight other dogs served as the untreated control group. Infarct size measured by triphenyltetrazolium chloride, and expressed as a percent of area at risk, was significantly reduced by retroperfusion treatment (19 +/- 18 versus 58 +/- 36, p less than 0.01). Morphologic examination of the coronary sinus and cardiac veins did not demonstrate evidence of damage from synchronized retroperfusion. There was also no evidence of excess myocardial edema in either the jeopardized ischemic or normally perfused zones. There was no evidence of significant red cell hemolysis or platelet destruction from the treatment. Thus, it appears that synchronized diastolic retroperfusion is a safe and effective treatment of acute myocardial ischemia in experimental animals and warrants clinical testing.

Animals↗
PubMed1985

Early differentiation of infarcted and noninfarcted reperfused myocardium in dogs by quantitative analysis of regional myocardial echo amplitudes.

This study tests the hypothesis that ischemic but viable reperfused myocardium can be differentiated from infarcted reperfused myocardium by regional analysis of myocardial echo amplitudes. In eight closed-chest, anesthetized dogs, the left anterior descending coronary artery was occluded for 3 hours, followed by 1 hour of reperfusion, and sacrifice. Infarct size was measured by the triphenyl tetrazolium chloride technique in a 1-cm-thick mid-left ventricular transverse slice, and matched with a corresponding end-diastolic two-dimensional echo short-axis cross-section. Outlining of epi- and endocardial surfaces, along with construction of a mid-myocardial outline, allowed measurements of regional myocardial echo intensities and grey-level histograms in subendo- and subepicardial regions. In 36 eventually infarcted subendocardial segments (greater than 20% wall necrosis), average pixel intensity (arbitrary units) was 73.7 +/- 33.1 (SD) in control, 75.8 +/- 33.0 at 3 hours of occlusion, and 107.8 +/- 40.9 at 5 minutes, 105.5 +/- 38.9 at 15 minutes, and 101.1 +/- 37.6 at 60 minutes postreperfusion P less than 0.05 vs. control or occlusion); intensity in normal segments (no or less than 20% wall necrosis) was 60.0 +/- 18.6 in control, 57.4 +/- 20.3 at 3 hours of occlusion, and 63.5 +/- 14.8, 68.0 +/- 27.9, and 64.2 +/- 22.3 at 5, 15, and 60 minutes postreperfusion, respectively (no significant change). The skew of the grey-level distribution in infarcted subendocardial segments did not change from control (0.49 +/- 0.72) to 3 hours of occlusion (0.41 +/- 0.52), but decreased (shift to higher echo amplitude) significantly at 5 minutes (-0.31 +/- 0.53), 15 minutes (-0.22 +/- 0.50), and 60 minutes (-0.28 +/- 0.45) after reperfusion (P less than 0.05 vs. control or occlusion); in normal subendocardial segments, there was no significant change throughout the study. In 31 partly infarcted subepicardial segments (greater than 50% wall necrosis), changes in postreperfusion echo amplitudes were less significant. Average pixel intensity was 71.3 +/- 28.6 in control, 71.8 +/- 29.2 after coronary occlusion, and 89.2 +/- 35.3, 83.7 +/- 37.5, and 85.6 +/- 34.9 at 5, 15, and 60 minutes after reperfusion, respectively. It is concluded that reperfusion of irreversibly injured myocardium is associated with consistent early increase in regional myocardial echo intensities and changes in the grey-level distribution. Such alterations might be used to detect the extent of tissue necrosis within minutes after reperfusion.

Animals↗
PubMed1985

Demonstration of myoglobin and CK-M in myocardium. Comparison of five fixation methods and three immunohistochemical techniques.

The results of immunohistochemical staining vary depending on the tissue, fixative, antigen-antibody system, and immunohistochemical staining methods used. The purpose of this study was to evaluate the effect of different methods of fixation, different antigen-antibody systems, and different immunohistochemical methods on immunohistochemical staining of myocardium. Samples of normal fresh canine myocardium from six dogs were fresh frozen and fixed in 10% neutral buffered formalin, Bouin's, Bayley's and Carnoy's fixatives. Immunohistochemical staining for myoglobin and creatine kinase M was performed using the ABC (avidin-biotin complex) and indirect peroxidase-antiperoxidase (PAP) techniques. Tissues fixed in formalin showed the most intense specific staining for both antigens with the least background and nonspecific staining. All other fixation methods and frozen section techniques gave a more variable degree of specific positive staining and substantial background staining and/or nonspecific staining. ABC and PAP techniques gave similar results with both antigen-antibody systems and with each fixation method. Thus, no differences in specificity or sensitivity were observed between ABC and PAP techniques. Differences in staining intensity and pattern were related primarily to differences in fixation methods.

Animals↗
PubMed1984

Effects of late coronary artery reperfusion after myocardial necrosis is complete.

Early reperfusion salvages reversibly injured ischemic myocardium. Late reperfusion, after necrosis is complete, could be beneficial by accelerating healing, or the hemorrhage and contraction-band necrosis associated with reperfusion could impair healing. In closed-chest anesthetized dogs the left anterior descending coronary artery was occluded with a balloon-tipped catheter for either 1 day followed by reperfusion for 6 days (n = 9) or for 7 days without reperfusion (n = 9). All dogs were killed after 7 days. Pathologic changes were studied in transverse whole-mount ventricular histologic sections. When the two groups were compared, no differences were found in: (1) infarct size, 15.7 +/- 9.9% vs 10.2 +/- 8.6 (mean +/- SD); (2) number of transmural infarcts, 5 of 9 vs 6 of 9; (3) ratio of infarcted/normal wall thickness, 0.93 +/- 0.09 vs 0.95 +/- 0.13; (4) thickness of zone of collagen deposition at periphery of infarct, 1.69 +/- 1.16 mm vs 1.67 +/- 0.56; and (5) amount of hemorrhage, calcification, and inflammation. Thus, in this model, reperfusion after necrosis is complete did not improve or impair healing.

Animals↗
PubMed1984

Identification and localization of creatine kinase B and M in normal, ischemic and necrotic myocardium. An immunohistochemical study.

We utilized immunoperoxidase methods to study the distribution of CK-B and CK-M in normal, ischemic and necrotic myocardium. Human myocardium was obtained from autopsy (n = 10) and surgery (n = 16). Cardiac tissue from 22 dogs with experimental myocardial infarction induced by closed-chest coronary balloon occlusion and four dogs with myocardial ischemia without necrosis induced by a 50% reduction in left main coronary artery blood flow for 3 h were studied. Duration of occlusion was 45 min (n = 2), 3 h (n = 8), 5 to 6 h (n = 7), 15 to 24 h (n = 5). Highly purified anti-CK-B and M were prepared in our laboratory and obtained commercially. In all cases, control experiments were performed. Microscopically normal human and dog myocardium uniformly stained for CK-B and CK-M. Necrotic myocardium from patients with acute infarcts (10 to 24 h old) showed markedly reduced immunostaining. In dogs with 3 to 24 h occlusion immunostaining was significantly reduced for both CK-B and CK-M in regions confirmed to be necrotic by triphenyl tetrazolium chloride (TTC) and H & E staining. Myocardial necrosis was confirmed in the 3-h infarcts by electron microscopy (EM). In the four dogs with a 50% reduction in left main flow for 3 h, ischemia was demonstrated by glycogen loss in periodic acid-Schiff stained-sections; but there was no evidence of necrosis by EM or TTC, and there was no loss of immunostaining evident for CK-B and CK-M. Thus, using immunoperoxidase techniques, CK-B and CK-M were visualized in normal and ischemic myocardium, with decreased staining in necrotic tissue. These findings indicate that cell death is necessary for the demonstration of CK-M and CK-B loss from the myocardium by this technique.

Animals↗
PubMed1984

Myocytolysis (vacuolar degeneration) of myocardium: immunohistochemical evidence of viability.

Human myocardium with focal myocytolysis (vacuolar degeneration, colliquative myocytolysis) was examined by routine light microscopy and by immunoperoxidase staining techniques for creatine kinase (CK) M and B, myoglobin, lactate dehydrogenase (H4)(LDH-1), and aspartate aminotransferase (AST, GOT). Sections of myocardium were selected from autopsy and surgical specimens from patients with and without clinical morphologic evidence of ischemic heart disease. Areas of coagulation necrosis showed loss of enzyme staining, while both normal and myocytolytic cells stained darkly. These results indicate that fibers with myocytolysis retain enzymes and other proteins, indicating sarcolemmal integrity, which is not present in fibers with coagulation necrosis. The implication of these findings is that fibers with myocytolysis are viable; thus, myocytolysis may be a reversible form of myocardial alteration that does not necessarily lead to cell death and eventual myocardial fibrosis.

Adult↗
PubMed1984

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.

Animals↗
PubMed1984

Prostaglandin E1 coronary venous retroperfusion in acute myocardial ischemia: effects on regional left ventricular function and infarct size.

Prostaglandin E1 was administered by means of coronary venous synchronized retroperfusion and the effectiveness of the combined (prostaglandin-retroperfusion) system was examined during acute myocardial ischemia in 10 closed chest anesthetized dogs. Such treatment was administered between 30 minutes and 3 hours after occlusion of the proximal left anterior descending coronary artery. An equivalent series of 10 dogs with arterial blood retroperfusion alone and 9 untreated dogs served as control subjects. Standardized two-dimensional echocardiographic measurements of global and regional left ventricular function were performed in five short-axis cross sections. The global low left ventricular section and its profoundly ischemic anterolateral region exhibited distinctly improved systolic fractional area changes as a result of the prostaglandin E1 retroperfusion treatment between 30 minutes and 3 hours after occlusion (22.9 +/- 1.5 to 41.2 +/- 4.0% and 1.8 +/- 3.6 to 29.4 +/- 5.6%, respectively). In contrast, further deterioration in function was noted during an untreated equivalent coronary occlusion period (16.3 +/- 2.7 to 10.0 +/- 3.3% and 12.6 +/- 6.1 to 4.1 +/- 6.9%). Although arterial blood retroperfusion alone provided distinct benefits in the ischemic region of a midpapillary echo section (from 13.4 +/- 3.9 to 32.1 +/- 10.4%, p less than 0.05), no improvements were observed in profoundly jeopardized segments at the low left ventricular level (5.6 +/- 6.0 to 0.9 +/- 5.7%). Triphenyltetrazolium chloride delineation of infarction revealed significant myocardial salvage with prostaglandin E1 retroperfusion as compared with findings in untreated control dogs (3.7% +/- 1.3% of the left ventricle versus 9.3 +/- 1.9%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1984

Verification of myocardial contrast two-dimensional echocardiographic assessment of perfusion defects in ischemic myocardium.

Myocardial contrast two-dimensional echocardiography was used in 21 closed chest dogs to assess its ability to delineate the extent of underperfused acutely ischemic myocardium. An agitated saline-Renografin echocardiographic contrast agent was injected into the left main coronary artery after left anterior descending coronary artery occlusion, and the size of the contrast echo-free area characterizing the perfusion defect was outlined in short-axis cross sections of the left ventricle. In 13 dogs, monastral blue dye was injected after 45 minutes of coronary artery occlusion and before sacrifice to provide anatomic delineation of underperfused zones in equivalent sections. Perfusion defects assessed by contrast two-dimensional echocardiography correlated well with those delineated by monastral blue dye (r = 0.91). Contrast echocardiographic study was also performed in eight other dogs at 5 hours of occlusion, after which infarct size was measured with triphenyl-tetrazolium-chloride. Contrast echocardiographic outline of the perfusion deficiency correlated but slightly overestimated the extent of necrosis (r = 0.88). It is concluded that contrast two-dimensional echocardiography can detect and outline the underperfused "risk area" during acute coronary artery occlusion, and may also permit assessment of the extent of myocardial infarction.

Animals↗
PubMed1984

Distribution of LDH-1 in normal, ischemic, and necrotic myocardium. An immunoperoxidase study.

To study the distribution of lactate dehydrogenase (LDH-1) (H4) in normal, ischemic, and necrotic myocardium using the peroxidase-antiperoxidase technic, the authors studied formalin-fixed paraffin-embedded sections of human (n = 11) and canine (n = 28) myocardium. All normal control myocardium showed positive immunostaining for LDH-1 (H4). In infarcts 10 hours or more old, the histologically necrotic myocardium (by triphenyl tetrazolium chloride staining) (TTC) showed markedly diminished immunostaining. In 24-dogs ischemia was induced in a closed-chest model using a balloon-tipped catheter inflated in the left anterior descending coronary artery. In dogs with 3 hours or more of occlusion, myocardium that was necrotic by TTC staining, light and/or electron microscopy, showed diminished staining for LDH-1, while normal, control myocardium stained intensely. In four dogs, ischemia was induced by a controlled perfusion apparatus by which left main coronary flow was reduced by 50%. Ischemia without necrosis was documented by demonstration of glycogen loss with no light or electron microscopic evidence of necrosis. These ischemic fibers stained intensely for LDH-1, as did controls. Thus, by immunoperoxidase staining, LDH-1 can be demonstrated in normal human and canine myocardium. In experimental models of ischemia in dogs, tissue that was ischemic but not necrotic showed no diminished staining. LDH-1 loss can be detected in necrotic myocardium as early as 3 hours after coronary artery occlusion.

Animals↗
PubMed1984

Idiopathic restrictive cardiomyopathy.

This report details the clinical, hemodynamic, and morphologic data from four patients 59 to 77 years old (mean 66) with a primary restrictive cardiomyopathy. All patients had symptoms of congestive heart failure, jugular venous distention, and murmurs of mitral and tricuspid regurgitation. Four patients required pacemakers, three for the brady-tachy syndrome and one for complete heart block. Chest x-ray demonstrated cardiomegaly in all four patients and pulmonary congestion and/or pleural effusions in three. Echocardiographic examination documented left atrial enlargement in all patients, along with normal left ventricular internal dimensions. Global left ventricular systolic function was normal in all, and left and right ventricular filling pressures were elevated and similar in three. A dip and plateau pattern was present in the pressure tracings of two of three patients. Unlike previous reports of restrictive cardiomyopathy, in our four patients there was no specific morphologic cause noted at necropsy. Pathologic evaluation demonstrated biatrial dilatation in all patients, with thrombi present in the atrial appendages in three. Normal ventricular cavity size and mild right ventricular hypertrophy were present in all patients and mild-to-moderate left ventricular hypertrophy was present in two. There were no significant pericardial, endocardial, or valvular abnormalities and no infiltrative myocardial disorders were present. Light and electron microscopic studies demonstrated only interstitial fibrosis of the myocardium. A restrictive hemodynamic profile may be observed in the absence of specific infiltrative disorders and affected patients may exhibit a prolonged clinical course of 4 to 14 years (mean 9). However, in these patients congestive heart failure responded poorly to medical therapy or surgical correction of valvular regurgitation, which is common in this disorder.

Aged↗
PubMed1984

Distribution of cytosolic and mitochondrial aspartate aminotransferase in normal, ischemic, and necrotic myocardium. An immunohistochemical study.

We utilized immunoperoxidase methods to study the distribution of both cytosolic or soluble(s) and mitochondrial (m) aspartate aminotransferase (AspAT) in normal, ischemic, and necrotic myocardium. Human myocardium was obtained from autopsy (n = 9) and surgery (n = 6). Cardiac tissue from 26 dogs with experimental myocardial infarction induced by closed-chest balloon occlusion and four dogs with myocardial ischemia without necrosis induced by a 50% reduction in left main coronary artery flow for 3 hours were studied. Duration of occlusion was 45 minutes (n = 1), 3 hours (n = 11), 5 to 6 hours (n = 10), or 15 to 24 hours (n = 4). Highly purified m- and s-AspAT and specific antibodies were prepared in our laboratory. In all cases, control experiments were performed. Microscopically normal human and dog myocardium uniformly stained for m- and s-AspAT. Necrotic myocardium from patients with infarcts showed markedly reduced immunostaining. In those dogs with myocardial necrosis, all dogs with coronary occlusion of 5 to 24 hours, and eight of 11 dogs with 3-hour occlusions, immunostaining was significantly reduced for both s- and m-AspAT in regions confirmed to be necrotic by triphenyl tetrazolium chloride and hematoxylin and eosin staining. Myocardial necrosis was confirmed in the 3-hour infarcts by electron microscopy. In the four dogs with a 50% reduction in left main flow for 3 hours, and one dog with a 45-minute coronary occlusion, ischemia was demonstrated by glycogen loss in period acid-Schiff-stained sections but there was no evidence of necrosis by electron microscopy or triphenyl tetrazolium chloride staining and there was no loss of immunostaining evident for s- or m-AspAT. Thus, s- and m-AspAT were visualized in normal and ischemic myocardium with decreased staining in necrotic tissue using immunoperoxidase techniques. Loss of both s- and m-AspAT can be demonstrated in human myocardium and in experimental canine myocardium as early as 3 hours after coronary occlusion and appears to be specific for irreversible myocardial injury. No depletion of isoenzyme can be detected by immunohistochemical techniques in tissue that is ischemic but not necrotic. Furthermore, by these immunoperoxidase techniques, loss of s- and m-AspAT from necrotic myocardium appears to be simultaneous.

Animals↗
PubMed1983

Relation between functional response to nitroglycerin and extent of myocardial necrosis in dogs: mapping of the left ventricle by 2-dimensional echocardiography.

The relation between functional response to brief nitroglycerin infusions and extent of myocardial damage was studied sequentially in closed-chest dogs with acute occlusion of the left anterior descending coronary artery. Two-dimensional echocardiography was used to derive segmental left ventricular (LV) function (systolic fractional area change and systolic wall thickening), and this function was compared with the extent of necrosis measured 5 hours after occlusion in equivalent segments of corresponding pathologic slabs. Two-dimensional echocardiographic study before the dogs were killed indicated that remote nonnecrotic segments always responded to nitroglycerin by significant augmentation of segmental LV function. Segments in which necrosis was less than 40% showed a significant nitroglycerin-induced potentiation in segmental LV function. In contrast, segments in which necrosis was greater than 60% had no potentiation with nitroglycerin. In those segments in which eventual necrosis was 60 to 80%, significant nitroglycerin-induced augmentation in segmental LV function was observed only before and 30 minutes after the coronary occlusion. When the degree of necrosis was greater than 80%, no significant potentiation of segmental LV function was observed even as early as 30 minutes after occlusion. Thus, the degree of nitroglycerin-induced potentiation of segmental cardiac function is closely associated with the extent of myocardial necrosis in the particular ventricular segment. Two-dimensional echocardiography coupled with a nitroglycerin potentiation test might be useful for assessment of the viability of ischemic myocardium.

Animals↗
PubMed1983

Compensatory hypertrophy in the heart after myocardial infarction in the rat.

Hypertrophy after myocardial infarction would be a very important process for compensation of damaged myocardium and preservation of cardiac function. Fifty-four female Sprague-Dawley rats were studied 5 weeks after randomization to infarct operation, sham operation and control groups. At sacrifice, anteroapical infarcts ranging from 1 to 51% of left ventricle were present in the infarct operated group. When classified according to infarct size, groups with the largest infarcts (greater than 15 to 30% and greater than 30%) had significant (p less than 0.001) cardiac cellular hypertrophy in the noninfarcted myocardium of the septum and anterior walls (fiber diameter 15.9 +/- 2.3 and 14.5 +/- 2.3 microns, respectively) compared with the control group (12.0 +/- 1.8 microns). Because of cardiac hypertrophy, remaining noninfarcted myocardial area, as estimated from serial histologic sections of the heart, was normal in the greater than 15 to 30% infarct group (area 1.35 cm2) compared with the control group (1.43 cm2); however, because hypertrophy plateaued in the greater than 30% infarct group, myocardial area was significantly decreased (1.06 cm2, p less than 0.001), but was still more than expected without hypertrophy. We suggest that hypertrophy accompanies large infarction in the rat and is a compensation for preserving tissue volume lost by infarction. This compensatory response appears to have limitations, such that when very large amounts of myocardium become necrotic, there is not enough hypertrophy to return myocardial volume to normal.

Animals↗
PubMed1983

Prevention of ischemic injury and early reperfusion derangements by hypothermic retroperfusion.

Hypothermic synchronized retroperfusion was applied during coronary artery occlusion to determine its ability to alleviate junctional derangements of reperfusion and to reduce infarct size. The proximal left anterior descending coronary artery was occluded in 25 closed chest dogs for 3 hours and then reperfused for 7 days. Thirteen dogs with no reperfusion pretreatment served as a control group (Group A). In 12 dogs, hypothermic retroperfusion was applied from 30 minutes up to 3 hours of the occlusion period (Group B). Sequential two-dimensional echocardiographic and hemodynamic as well as metabolic measurements were performed. Compared with untreated control dogs, dogs with hypothermic synchronized retroperfusion had significantly reduced heart rate and rate-pressure product, decreased left ventricular volumes and improved ejection fraction during the occlusion period. Two-dimensional echocardiographically-derived ischemic zone systolic fractional area change and systolic wall thickening indicated significantly improved function as a result of retroperfusion. During the reperfusion period, untreated control dogs (group A) had more severe derangements in hemodynamics and wall motion than dogs treated by hypothermic retroperfusion (group B). Mortality was 30.7% in group A, 16.7% in group B and 7th day infarct size as percent of the left ventricle was 12.0 +/- 6.5 (mean +/- standard deviation) and 4.2 +/- 5.9, respectively (p less than 0.02). It is concluded that hypothermic synchronized retroperfusion applied after coronary occlusion and before reperfusion significantly improves cardiac function during occlusion, minimizes complications of reperfusion and reduces the ultimate infarct size. Because this form of circulatory assistance helps maintain cardiac function and delays the evolution of myocardial necrosis, its application may be beneficial during an evolving acute myocardial infarction before achievement of surgical or nonsurgical reperfusion.

Animals↗