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Biomedical subjects

M C Fishbein

Publications and source records attributed to M C Fishbein.

At least 235 records · Page 13Linked to original sources
PubMed1980

Characterization of myocardial infarcts in the rat.

In 42 male Sprague-Dawley rats, the distribution of coronary arteries, the geometry of myocardial infarcts (MIs) and the involvement of the left ventricular papillary and trabecular muscles, after left coronary occlusion, were investigated. The septal branch was found to be responsible for the blood supply to the septum and, thus, occlusion of the left coronary artery, which spares the septal branch, results in an infarct that does not include the interventricular wall. Myocardial infarct size was measured by planimetry of histologic sections of serial slices of the left ventricle. There was no difference between the average percent of subepicardial (43% +/- 1%) and subendocardial (44% +/- 3%) infarction when the whole left ventricle was considered. Analysis of individual slices had shown that the infarcts comprised a greater percentage of left ventricular circumference at the apex than at the base in both layers of the myocardium. Toward the apex, more subendocardium was infarcted than subepicardium. The papillary and trabecular muscles are minimally involved in 75% of infarcts.

Animals↗
PubMed1979

Cardiac function and morphology with aging in the spontaneously hypertensive rat.

To determine the effects of a chronic pressure load on cardiac function and morphology, spontaneously hypertensive rats (SHR) and two normotensive strains of Wistar rats (WKY and NWR) were studied under ether anesthesia at 13, 25, 52, and 90 wk of age. Although resting cardiac index of the SHR was comparable to that of WKY and NWR at all ages, the peak cardiac output and peak stroke volume per gram of left ventricle determined during a rapid intravenous infusion of Tyrode solution was markedly reduced in the SHR only at 90 wk of age. Autonomic inhibition did not alter the peak stroke volume attained, but reduced peak cardiac output at all ages in each of the strains. Absolute left ventricular dimensions in the SHR increased out of proportion to body growth, consistent with concentric hypertrophy. As peak pumping ability markedly declined from 52 to 90 wk of age in the SHR, the free wall of the left ventricle greatly thickened whereas the septum remained unchanged. At this time the right ventricle also hypertrophied. This disproportionate thickening of the walls of the left ventricle and the hypertrophy of the right ventricle were reflected in measurements of their fiber diameters. These alterations in ventricular architecture may contribute to the decrease in pumping ability observed in long-standing hypertension.

Aging↗
PubMed1979

Temporary left ventricular bypass: factors affecting patient survival.

Circulatory support (range, 2 hours-8 days) was undertaken in eight cardiac surgical patients (with two survivors) exhibiting intractable cardiogenic shock. A paracorporeal, pneumatic, xenograft-valve pump was interposed between the left ventricular apex and ascending aorta. Pumping lowered left atrial and ventricular pressure while maintaining cardiac output (1.8--2.6 l/min/m2). Following implantation, plasma hemoglobin and erythrocyte mechanical fragility values were elevated but decreased to normal when renal function was not impaired. Mild thrombocytopenia was noted in three patients and was severe in five others with persistent hemorrhage. Anticoagulation agents were used during tapering of pump flow (three patients) after 100, 105 and 120 hours of bypass. Otherwise, for the major portion of the interval of mechanical circulatory support, anticoagulants were not administered. Despite this fact, no systemic embolization was detected in any of the patients. It appears that assist pump support can be life-saving in acute left ventricular failure in patients following cardiac surgery.

Adult↗
PubMed1979

Myocardial infarct size and ventricular function in rats.

To define the relationship between infarct size and ventricular performance, we performed hemodynamic studies in rats 21 days after left coronary artery occlusion. Ventricular performance was assessed under ether anesthesia by measurements of baseline hemodynamics and stressed performance as determined by the peak cardiac output and stroke volume obtained during intravenous volume loading and by the peak left ventricular developed pressure obtained during occlusion of the ascending aorta. Infarct size was determined by planimetry of the endocardial circumference of each of four histological slices of the left ventricle. Rats with small (4-30%) myocardial infarctions had no discernible impairment in either baseline hemodynamics or peak indices of pumping and pressure-generating ability when compared to the sham-operated, noninfarcted rats. Rats with moderate (31-46%) infarctions had normal baseline hemodynamics but reduced peak flow indices and developed pressure. Rats with infarctions greater than 46% had congestive heart failure, with elevated filling pressures, reduced cardiac output, and a minimal capacity to respond to pre- and after load stresses. The entire spectrum of postinfarction ventricular function was observed, from no detectable impairment to congestive failure. In this model of histologically healed myocardial infarction, the impairment of left ventricular function was directly related to the loss of myocardium.

Animals↗
PubMed1979

Mechanical and structural correlates of contracture induced by metabolic blockade in cardiac muscle from the rat.

We performed morphological studies of myocardial contracture to define its nature and relationship to mechanical changes occurring during metabolic blockade. Isolated rat papillary and trabecular muscles were stretched to the apices of their length-tension curves and stimulated to contract isometrically 12 times a minute at a temperature of 28 degrees C. Incomplete and total metabolic blockade were induced by 1 hour of hypoxia (95% N2, 5% CO2) or by hypoxia plus glycolytic blockade with iodoacetic acid, 10-4M, respectively. In oxygenated control preparations, mechanical performance was stable for the 60-minute experimental period. In preparations exposed to hypoxia, developed tension fell to 7 +/- 2% of prehypoxia values at 60 minutes. Contracture tension increased progressively to 2.5 +/- 0.4 g/mm2. With total metabolic blockade, developed tension declined to zero by 10 minutes, contracture tension rose to an average peak value of 5.3 +/- 0.4 g/mm2 by 15 minutes, and subsequently slowly declined. All preparations were fixed at Lmax in the muscle bath. Light and electron microscopic studies revealed focal irregularities of A, I, and Z bands with sarcomere malalignment, hypercontraction, and fiber disruption, which increased in severity with increasing metabolic blockade. Linear densities appeared in mitochondria following total metabolic blockade, but mitochondria appeared normal otherwise. Thus, myocardial contracture after metabolic blockade is a focal process beginning within the sarcomere; morphological alterations in the contractile apparatus correlate with mechanical changes and are more severe than those in the mitochondria.

Animals↗
PubMed1979

Effects of exerimental right ventricular hypertrophy on myocardial blood flow in conscious dogs.

The effects of right ventricular hypertrophy on the overall and regional distribution of myocardial blood flow in the absence of an elevated coronary arterial driving pressure were evaluated in 18 concscious dogs subjected to a chronic pressure overload of the right ventricle induced by pulmonary artery constriction. The sustained pressure overload for duration of 4--6 wk or 4--5 mo resulted in significant increases in right ventricular mass (45 and 110%, respectively) and right ventricular fiber diameter (22 and 60%, respectively). Moreover, the presence of moderate and severe hypertrophy was associated with marked increases in transmural blood flow per gram to the right ventricle proportional to the observed increases in mass, i.e., of 36 and 109%, respectively, from a normal value of 0.67 +/- 0.04 ml/min per g, whereas left ventricular blood flow remained unaltered from a normal value of 1.00 +/- 0.06 ml/min per g. Despite the large increase in blood flow per gram to moderately and severely hypertrophied right ventricle, no significant changes in the ratio of capillary:muscle fiber number were observe. These data suggest that the development of right ventricular hypertroph is characterized by a sustained compensatory response of the coronary circulation to the augmented work load and mass, and that is not associated with a proliferative response of the vasculature supplying the enlarged ventricle.

Animals↗
PubMed1978

Detection of myocardial ischemia in vitro by computed tomography.

The applicability of CT in the delineation of ischemic myocardium is defined. Twenty-six dogs had their left anterior descending coronary artery occluded, and radiolabeled microspheres were injected into the left atrium to measure myocardial blood flow. From 30 minutes to 7 weeks after coronary occlusion the hearts were excised and scanned in a CT head scanner. An unbiased observer divided selected CT scans slices into normal, abnormal, and borderline areas of attenuation coefficients; these were correlated with blood flow measurements and a progressive decrease in flow from normal to borderline and borderline to abnormal segments was found. As early as 2 hours after coronary arterial occlusion, areas of reduced attenuation coefficient, corresponding to regions of reduced blood flow, were seen. Areas of increased attenuation were seen in regions containing microcalcifications and fibrosis in several longer term experiments. Areas of reduced blood flow were visible immediately after coronary arterial occlusion with intravenous iodinated contrast material (1 ml/kg). CT detection of regions of reduced blood flow defined by radiolabeled microsphere is a promising means of detecting and sizing myocardial infarcts.

Animals↗
PubMed1978

Experimental myocardial infarction in dogs with normal coronary arteries. Angiographic resolution of coronary arterial emboli.

Percutaneous transcatheter embolization of the coronary arteries with autologous clot was performed in six dogs. The occlusions resolved completely within 14 days in the four surviving dogs. Postmortem examination revealed transmural myocardial infarction in two dogs and subendocardial infarcts in the other two. Histological sections showed no residual emboli in three dogs and a recanalized thrombus in an epicardial vessel in the fourth. These findings indicate that myocardial infarction can be produced by multiple occlusions of the distal coronary arterial branches, provided that common or contiguous myocardium is affected. The recanalized thrombus in one dog suggests that the thrombolytic process need not be complete for return to a normal angiographic appearance.

Angiography↗
PubMed1978

Depression of regional blood flow and wall thickening after brief coronary occlusions.

The effects of a 15-min coronary occlusion and subsequent reperfusion were investigated in conscious dogs previously instrumented for measurement of left ventricular pressure, dP/dt, regional wall thickening, electrograms, and myocardial blood flow. Coronary occlussion reduced overall left ventricular function only slightly but eliminated systolic wall thickening in the ischemic zone and reduced regional myocardial blood flow in the ischemic zone from 1.04 +/- 0.04 to 0.27 +/- 0.02 ml/min per g and the endo/epi flow ratio from 1.23 +/- 0.04 to 0.44 +/- 0.04, while S-T segment elevation increased from 1.1 +/- 0.3 to 8.2 +/- 0.9 mV. After release of the occlusion, S-T segment elevation disappeared within 1 min while reactive hyperemia in the previously occluded artery and a transient increase in cardiac diastolic wall thickness occurred and then subsided by 15 min. In contrast, systolic wall thickening and the endo/epi flow ratio remained significantly depressed for more than 3 h. Thus reperfusion after a 15 minute coronary occlusion results in a prolonged period of reduced regional myocardial blood flow, particularly in the endocardial layers, which correlates with the prolonged depression of regional myocardial shortening and wall thickening.

Animals↗
PubMed1978

Ventricular morphology and pumping ability of exercised spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) and two strains of normotensive Wistar rats were subjected to a 5 day/wk swimming program to determine whether the heart of the SHR could respond to an additional stimulus to cardiac growth. Swimming was tolerated well by all rats. Although body weight of the exercised groups was not significantly reduced, both the right and left ventricular weights of all exercised groups were increased. Left ventricular circumference and chamber volume were increased without a change in free wall thickness in all exercised groups. Ventricular performance was assessed by peak cardiac output and stroke volume attained during rapid intravenous volume loading, both before and after autonomic inhibition. After combined cholinergic and beta-adrenergic inhibition, all exercised rats had slower heart rates and higher peak stroke volume than respectively sedentary controls. Thus, exercised SHR had the same alterations in cardiac mass and performance as exercised normotensive rats. Despite the initial presence of left ventricular hypertrophy, the SHR responded appropriately to an additional stimulus for adaptive cardiac growth.

Animals↗
PubMed1978

Mummification of the infarcted myocardium by high dose corticosteroids.

There is evidence that glucocorticoids reduce infarct size but their use in myocardial infarction remains controversial because of their potential adverse effects on healing of the infarct. To investigate the healing process, rats received either four parenteral doses of 50 mg/kg of methylprednisolone (MP) or saline 5 min, 3,6 and 24 hr after coronary occlusion and their hearts were examined by light and electron microscopy 48 hr and seven days after occlusion. At 48 hr, in five untreated rats, only 12 +/- 7% of injured myocytes showed the persistence of striations and a relatively intact sarcolemma despite loss of nuclei and hence appeared "mummified" whereas in six MP-treated rats 72 +/- 8% of myocytes exhibited this appearance (P less than 0.001). In treated rats there were fewer phagocytes than in controls. At seven days, in seven MP-rats, mummified cells were still more prominent than in five untreated rats and there were fewer phagocytes and less collagen. In conclusion, high dose of MP delays the inflammatory process and retards the disintegration of necrotic myocytes, resulting in impaired healing.

Animals↗
PubMed1978

Endomyocardial disease and eosinophilia. Report of a case.

While an association between blood eosinophilia and endomyocardial disease has been recognized, the role of the eosinophil in the pathogenesis of the cardiac lesions remains uncertain. In a 69-year-old-man with large cell carcinoma of the lung, marked eosinophilia was stimulated by and progressed with the course of the neoplasm which was producing an eosinophil chemotactic factor. Peripheral blood eosinophils were vacuolated and degranulated while those in the bone marrow were morphologically normal. Clinical evidence of cardiac dysfunction developed one month prior to death. At autopsy, 12 months after the onset of symptoms, endomyocardial disease was present. There were numerous eosinophils in the damaged myocardium and surrounding the pulmonary neoplasm. In patients with endomyocardial disease and eosinophilia, the eosinophil may be directly cardiotoxic or a primary mediator of cardiac damage; therapeutic attempts to reduce the number of eosinophils might be benefit.

Aged↗
PubMed1978

Exercise-induced reduction in myocardial infarct size after coronary artery occlusion in the rat.

Chronic exercise (E) has been thought to be beneficial to the cardiovascular system by increasing energy production and utilization, improving myocardial contractility and increasing myocardial vascularity; whether or not any of these effects are beneficial to ischemic myocardium is uncertain. In this study, rats were forced to swim one hr/day, 5 days/wk for 5 weeks. They were sacrificed and the myocardial capillary bed was perfused with carbon black. Using a calibrated eyepiece grid, histologic sections of heart were examined to determine capillary/fiber ratios (C/F) and myocardial fiber diameter. C/F was increased by 30% in E rats [0.87 +/- 0.06 (mean +/- SE) (N = 4 rats)] when compared with sedentary controls (C) [0.67 +/- 0.04 (N = 4 rats), P is less than 0.05]. This training effect occurred in the absence of hypertrophy since there were no differences in ventricular weight (1.21 +/- 0.04 mg in E rats vs 1.16 +/- 0.03 mg in C rats) or in fiber diameter (13.0 +/- 0.2 mu in E rats vs 13.1 +/- 0.2 mu in C rats) in the two groups. An additional 27 E rats and 25 C rats underwent left coronary artery occlusion and were sacrificed 48 hr later. Myocardial infarct size was measured by planimetry of histologic sections of serial slices of left ventricle (LV). In the 27 E rats, 21.5 +/- 1.9% of the LV was infarcted compared with 31.3 +/- 2.6% in the 25 C rats (P is less than 0.005). Thus, infarct size was reduced by 30% in E rats. In the rat, exercise results in a reduction of myocardial infarct size after coronary artery occlusion which, at least in part, may be related to increased myocardial vascularity.

Animals↗
PubMed1978

Long-term preservation of ischemic myocardium after experimental coronary artery occlusion.

The results of experiments with indirect methods have suggested that various interventions reduce infarct size after coronary artery occlusion. To determine and quantify directly both the short- and long-term effects of several interventions on myocardial salvage without relying on indirect methods, the left coronary artery was occluded in 880 rats; they were then given either no treatment or one of the following interventions: (a) hyaluronidase, an enzyme that hydrolyzes interstitial glycoproteins, 1,500 National Formulary (NF) U/kg i.v. 5 min and 24 h after occlusion; (b) cobra venom factor, a protein that depletes the third component of complement, 20 U/kg i.v. 5 min after occlusion; (c) a glucocorticoid: hydrocortisone, 50 mg/kg i.v. 5 min after occlusion; or the five-fold more potent methylprednisolone (MP): (i) 50 mg/kg i.v. 5 min after occlusion or (ii) 50 mg/kg i.v. 5 min after occlusion followed by 50 mg/kg i.m. 3, 6, and 24 h after occlusion; or (d) reserpine, an agent that depletes the heart of catecholamines, 0.5 mg/kg i.m. once on each of the 3 days before occlusion. The animals were sacrificed either 2 days after occlusion, i.e., at the time of peak necrosis, or after 3 wk, i.e., after the infarct was completely healed. The amount of preserved myocardium was then assessed by two independent techniques: planimetric measurement of serial histologic sections and creatine kinase activity of the whole left ventricle. The amount of normal myocardium preserved at 21 days postocclusion was significantly increased, by 22.3+/-7.8% (P < 0.025) after the administration of hyaluronidase, by 25.3+/-5.8% (P < 0.005) after cobra venom factor, by 14.5+/-6.9% (P < 0.05) after hydrocortisone, by 20.8+/-8.2% (P < 0.025) after the single dose of MP, by 20.9+/-3.9% (P < 0.001) after the four doses of MP, and by 10.2+/-3.7% (P < 0.05) as a result of pretreatment with reserpine. The four doses of MP significantly thinned the infarct-by 25.6+/-2.9% (P < 0.001)-and although ventricular rupture did not occur, the intervention caused distension of the left ventricle as a result of stretching of the infarcted tissue during scar formation. Thus, myocardium acutely jeopardized by ischemia can be preserved on a long-term basis.

Animals↗
PubMed1978

Reduction by cobra venom factor of myocardial necrosis after coronary artery occlusion.

Components of the complement system are known to play an important role in the cytolytic process and in chemotaxis of leukocytes. Cobra venom factor specifically cleaves C3 activity via activation of the alternative (properdin) complement pathway. It does not act directly on C3. If C3 is involved in tissue necrosis after ischemic injury, cobra venom factor might reduce tissue damage after acute coronary occlusion. Accordingly, in 14 control dogs occlusion of the left anterior descending artery was carried out for 24 h. Epicardial electrograms were recorded 15 min after occlusion, and 24 h later transmural specimens for creatine phosphokinase activity (CPK) and for histological analysis were obtained from the same sites. In another 14 experimental dogs, 20 U/kg cobra venom factor was given intravenously 30 min after occlusion. Serum complement levels fell within 2-4 h to <20% of normal. In the control dogs, the relationship between ST-segment elevation and CPK activity 24 h later was: log CPK = -0.06 ST + 1.48 (n = 111 specimens, 14 dogs, r = 0.77). In the experimental dogs, log CPK = -0.024 ST + 1.46 (n = 111 specimens, 14 dogs, r = 0.60), showing significantly different slopes (P < 0.001), i.e., less CPK depression for any level of ST-segment elevation. Histologically, 69 of 71 sites (97%) with ST-segment elevation exceeding 2 mV in the control dogs showed signs of necrosis 24 h later, whereas in the experimental group only 43 of 79 sites (54%) with abnormal ST-segment elevations showed signs of necrosis (P < 0.0005). At the same time, it was shown that the administration of cobra venom factor did not alter cardiac performance, collateral blood flow to the ischemic myocardium or the clotting system, but infiltration of polymorphonuclear leukocytes into the myocardium was decreased. It is concluded that cobra venom factor, by reducing the amount of C3 and C5 substrate available for chemotactic factor generation, or other as yet undefined mechanisms, protects the ischemic myocardium from undergoing necrosis, as judged by histology and local CPK activity. Hence, a new approach to limiting the extent of myocardial infarcts after experimental coronary occlusion, based upon inhibition of complement-dependent inflammatory processes, is demonstrated.

Animals↗