PubMed Health⌕ Search

Biomedical subjects

J T Fallon

Publications and source records attributed to J T Fallon.

At least 163 records · Page 9Linked to original sources
PubMed1987

Detection of early necrosis in a canine model of low flow myocardial ischemia using 125I-antimyosin (Fab')2.

Low flow myocardial ischemia in the distribution of the left anterior descending coronary artery was established in 32 anesthetized dogs. The early development of irreversible myocardial injury was identified using 125I-antimyosin (Fab')2--a specific immunological marker of myocardial necrosis. The simultaneous injection of 131I-nonspecific (Fab')2 controlled for variables unrelated to specific antimyosin activity. It was also possible to calculate the relative uptake of 125I-antimyosin (Fab')2 in the ischemic area. In order to prevent recirculation of the (Fab')2, and to limit the time of exposure to the myocardium, the fragments were injected directly into the coronary circulation during diversion of the coronary sinus effluent. The antibody fragments were given either two, three or five hours after the onset of low flow in different groups of dogs and the animals were sacrificed 60 minutes later. Selective accumulation of 125I-antimyosin (Fab')2 in the ischemic area occurred between two and three hours after the onset of low flow ischemia indicating that necrosis was already established at this time. Macroautoradiographs of cross sections of the left ventricle and autoradiographs of microscopic sections of the ischemic myocardium independently confirmed selective accumulation of 125I-antimyosin (Fab')2 and hence necrosis, at three hours after the onset of low flow. In this study the use of 125I-antimyosin (Fab')2, in contrast to the use of histology, as a marker of necrosis avoided error due to sampling and also permitted the detection of cell death early during the ischemic process. The demonstration, within a narrow time frame, of early necrosis in this low flow preparation provides a potential model with which to evaluate agents for myocardial preservation in obstructive coronary disease.

Animals↗
PubMed1987

Myocardial damage delineated by indium-111 antimyosin Fab and technetium-99m pyrophosphate.

Technetium-99m-labeled pyrophosphate and radiolabeled antimyosin antibodies are two infarct localizing agents with apparently different kinetics of localization. To determine whether these agents localize in a similar fashion in early acute myocardial necrosis, we studied the simultaneous distribution of 111In-labeled antimyosin and 99mTc-labeled pyrophosphate in dogs after intracoronary (i.c.) (n = 9) or intravenous (i.v.) (n = 9) administration of a mixture of these two agents in a reperfused infarct model. The mean infarct size (+/- s.d.) delineated by pyrophosphate [20.2 +/- 14.1 (i.v.), 29.8 +/- 12.3 (i.c.)] was larger than that by antimyosin [14.2 +/- 11.3 (i.v.) (p = 0.05), 20.0 +/- 11.8 (i.c.) (p = 0.05)] which was larger than that by triphenyl tetrazolium chloride [13.9 +/- 8.0 (i.v.) (p = 0.05), 15.3 +/- 6.5 (i.c.) (p = 0.05)]. This overestimation persisted whether the radiopharmaceuticals were administered by intracoronary or intravenous injections, although the latter with antimyosin was only slightly larger (TTC:AM = 13.9:14.2) (p = n.s.). There was a good correlation, however, between antimyosin and pyrophosphate delineated infarct sizes in dogs with intracoronary injection (y = 0.82x + 13.33, r = 0.79) or i.v. injection (y = 1.208x + 3.01, r = 0.97) of the mixture of the two agents. Since the images of the 111In and 99mTc activities were obtained consecutively by identical methods, the overestimation of infarct size by pyrophosphate cannot be due to differences in spatial resolution of the techniques used. The differences in the areas of myocardial damage delineated by pyrophosphate and antimyosin in our study most probably denote the area of viable but compromised myocardium.

Animals↗
PubMed1986

Neonatal atria and ventricles secrete atrial natriuretic factor via tissue-specific secretory pathways.

The cellular mechanisms regulating secretion of the peptide hormone atrial natriuretic factor (ANF) differ in neonatal atrial and ventricular cardiocytes. We demonstrate that although both cell types synthesize and secrete ANF, only atrial cells store peptide in abundant secretory granules. Neonatal ventricular cells secrete ANF rapidly after synthesis and lack secretory granules. We propose that ventricular ANF is released by a constitutive secretory pathway whereas atrial ANF is stored and released by a regulated pathway. Furthermore, ventricular ANF mRNA and hormone concentrations decrease during the first week of life. Developmental variation in the use of ANF secretory pathways may reflect changing requirements for maintenance of intravascular volume and pressure. Tissue-specific modulation of hormone secretory pathways appears to be a novel response to developmentally induced changes in the requirements for a peptide hormone.

Animals↗
PubMed1986

Atrial natriuretic factor: assessment of its structure in atria and regulation of its biosynthesis with volume depletion.

Atrial natriuretic factor (ANF) is a polypeptide that has been isolated from mammalian atrial tissue with potent natriuretic, diuretic and spasmolytic properties. Details of its biosynthesis, cleavage, storage and release are not yet fully defined. Using sequence-specific anti-peptide antisera in immunocytochemical and radioimmunoassay studies, we demonstrated the presence in atrial granules of sequences corresponding to both the large molecular weight ("prohormone") form of ANF and the carboxyterminal peptide believed to be responsible for its biological activity. However, a peptide sequence spanning the proposed site of cleavage of the "signal peptide" from preproANF was undetected. In volume-depleted rats, a 28% decrease in the relative concentrations of atrial ANF mRNA was observed as compared to that of controls (P less than 0.01). There was, however, no significant difference observed between the two groups of animals with respect to atrial levels of ANF, as measured by radioimmunoassay. We conclude from these studies that proANF, but not preproANF, is stored in atrial granules. The concentration of stored ANF remains constant in volume-depleted rats despite a 28% reduction in ambient levels of ANF mRNA. The physiologic significance of these findings is discussed.

Animals↗
PubMed1986

The effect of phenothiazines upon maintenance of membrane integrity in the cultured myocardial cell.

The cultured myocardial cell provides a defined model for examining factors which are responsible for maintaining cellular viability and sarcolemmal integrity. Our data indicates that the spontaneous loss of myocyte membrane integrity is a calcium-dependent process and thus provides a method for examining the mechanism through which calcium exerts this effect. Antimyosin antibody staining and propidium iodide uptake were used to quantitate membrane integrity. The integrity of the cell membrane was inversely related to the calcium concentration in the culture medium. This loss of membrane integrity was calmodulin-dependent as demonstrated by the following: phenothiazines (trifluoperazine greater than chlorpromazine greater than promethazine) and structurally dissimilar calmodulin-inhibitors prevented the formation of sarcolemmal defects at concentrations similar to those known to inhibit calmodulin; phenothiazines and calcium demonstrated a competitive interaction with respect to this effect on membrane integrity. Electron microscopy confirmed the integrity of the sarcolemma of the cells exposed to high phenothiazine concentrations although metabolic alterations occurred in these cells as evidenced by an increased membrane permeability to the low molecular weight probe propidium iodide, degenerative changes in the fine structure of the mitochondria, the accumulation of autophagic vacuoles in the cytoplasm and the loss of contractile ability. These findings indicate that calmodulin inhibitory compounds are capable of preserving the membrane integrity of cardiac myocytes, interfering with a calcium-dependent process that is associated with the spontaneous attrition of these cells in culture. Significant intracellular alterations appear at high doses of these agents even while the sarcolemma is free of gross defects.

Animals↗
PubMed1986

Selective ablation of atheromas using a flashlamp-excited dye laser at 465 nm.

Ablation of human atheromas with laser pulses that had only a small effect on normal artery tissue was shown in vitro in air and under saline using 1-mu sec pulses at 465 nm from a flashlamp-excited dye laser. At this wavelength, there is preferential absorption in atheromas due to carotenoids. The threshold fluence for ablation was 6.8 +/- 2.0 J/cm2 for atheromas and 15.9 +/- 2.2 J/cm2 for normal aorta tissue. At a fluence of 18 J/cm2 per pulse, the ablated mass per unit of energy ranged from 161 to 370 micrograms/J for atheromas and from 50 to 74 micrograms/J for normal aorta tissue. Ablation products consisted of cholesterol crystals, shredded collagen fibers, and small bits of calcific material. Most debris was less than 100 micron in diameter, but a few pieces were as large as 300 micron. High-speed photography of ablation in air suggested explosive ejection of debris, caused by vapor formation, at speeds on the scale of 300 m/sec. Histological analysis showed minimal thermal damage to residual tissue. These data indicate that selective laser ablation of atheromas is possible in vitro.

Arteriosclerosis↗
PubMed1986

Scintigraphic quantification of myocardial necrosis in patients after intravenous injection of myosin-specific antibody.

The Fab fragments of antimyosin antibodies, labeled with 99mTc, were used in the scintigraphic examination of 30 patients with myocardial infarction. The ability to detect necrosis and determine its extent from the antimyosin scan were compared with the results of quantitative regional wall motion analysis by contrast ventriculography at 10 to 14 days and 99mTc-pyrophosphate imaging. Antimyosin images recorded by planar and single photon-emission computed tomography (SPECT) delineated areas of myocardial necrosis in 27 of 30 patients (90%) compared with a 91% sensitivity of pyrophosphate in 21 of 23 patients. Infarct size was determined by both antimyosin and pyrophosphate SPECT images. Results by both techniques showed a significant correlation with computer-derived hypokinetic segment length (r = .79 for both, p = .002) and peak creatine kinase (r = .9 for both, p less than .01). Although sensitivity for and correlations with markers of necrosis were similar with both techniques, infarct size by pyrophosphate SPECT was 1.7 times larger than infarct size by antimyosin SPECT (p less than .01). Certain zones in the infarct area were differentially labeled; the nature and irreversibility of injury within these zones remains to be clarified.

Antibodies↗
PubMed1986

Mural degeneration in the glutaraldehyde-tanned umbilical vein graft: incidence and implications.

After discovering an aneurysm in a glutaraldehyde-tanned umbilical vein (GTUV) graft that resulted in graft thrombosis, we reevaluated all patients from our institution who had GTUV grafts implanted for more than 2 years. Of 60 patients identified, 14 of 15 patients with patent grafts were recalled and had either digital subtraction or standard angiographic studies. Angiographic changes in the grafts were graded on a scale of 0 to 3, from normal (grade 0) to frank aneurysmal degeneration (grade 3). Eight grafts (57%) had frank aneurysmal (grade 3) changes, and three other grafts (21%) had preaneurysmal (grade 2) changes. Only one graft was angiographically normal. GTUV grafts undergo aneurysmal degeneration in a significant percentage of implants. Symptomatic aneurysms have presented with thrombosis and limb-threatening ischemia as well as rupture. GTUV aneurysms should be treated by complete graft resection, as segmental resection of diseased portions of grafts resulted in metachronous aneurysm recurrence. Because of the high incidence of GTUV degeneration, the clinical indications for the use of GTUV grafts should be seriously reevaluated, and we recommend that all patients with patent GTUV grafts for more than 2 years be evaluated for the presence of aneurysmal degeneration.

Aldehydes↗
PubMed1986

Effects of brief periods of myocardial ischemia on regional myocardial function and creatine kinase release in conscious dogs and baboons.

The effects of 15 min periods of coronary occlusion on global and regional myocardial function, plasma creatine kinase (CK) and isoenzyme MB CK activity and subsequent myocardial necrosis were studied in 15 conscious dogs and 9 conscious baboons. Overall left ventricular (LV) function was assessed with measurements of LV systolic and diastolic pressures, rate of change of LV pressure, LV dP/dt. Regional LV function was assessed with measurements of regional segment length and velocity of shortening and/or regional LV wall thickening. An implanted hydraulic occluder on either the left anterior descending or circumflex coronary artery was inflated for 15 min. This induced complete loss of segment length shortening and systolic wall thickening (ultrasonic transit time technique). With release of the occlusion and reperfusion, recovery of regional mechanical function was delayed, but did occur after 6 hrs. Serial plasma enzyme activity revealed a significant increase in total CK as well as MB CK. At autopsy, neither gross pathological evidence (TTC-technique) nor histological evidence of myocyte necrosis was observed. Thus, in the conscious dog as well as in the conscious baboon, short episodes of intense myocardial ischemia do not result in a permanent deficit of myocardial function or necrosis. However, during the early phase of reperfusion, significant depression of regional mechanical function is observed associated with significant appearance of total CK and MB CK in the blood.

Animals↗
PubMed1985

Biosynthesis and secretion of proatrial natriuretic factor by cultured rat cardiocytes.

Rat atrial natriuretic factor (ANF) is translated as a 152-amino acid precursor preproANF. PreproANF is converted to the 126-amino acid proANF, the storage form of ANF in the atria. ANF isolated from the blood is approximately 25 amino acids long. It is demonstrated here that rat cardiocytes in culture store and secrete proANF. Incubation of proANF with serum produced a smaller ANF peptide. PreproANF seems to be processed to proANF in the atria, and proANF appears to be released into the blood, where it is converted by a protease to a smaller peptide.

Amino Acid Sequence↗
PubMed1985

Active myocarditis in the spectrum of acute dilated cardiomyopathies. Clinical features, histologic correlates, and clinical outcome.

We studied the clinical features and course (average follow-up time, 18 months) of 27 patients with acute dilated cardiomyopathy (symptoms for less than 6 months) who were referred for endomyocardial biopsy. Almost 40 per cent of the patients subsequently had a rise in left ventricular ejection fraction (on average, from 0.21 to 0.41) and substantial improvement in heart failure; the remainder died or had chronic dilated cardiomyopathy. Biopsy revealed myocarditis in 18 patients, and this finding was especially common (89 per cent) in patients who had been ill for less than four weeks. But the biopsy specimen was negative in four patients whose clinical features and later course were diagnostic of myocarditis. Nine patients received immunosuppressive drugs, and four improved--a rate that did not differ from the rate of spontaneous improvement. Neither the histologic features of the biopsy specimen nor the clinical features at presentation were clearly correlated with subsequent improvement, whether or not immunosuppressive drugs were given. We conclude that many cases of unexplained dilated cardiomyopathy result from myocarditis. Definitive histologic confirmation depends on the duration of illness. The efficacy of immunosuppressive treatment must still be established.

Acute Disease↗
PubMed1985

Functional and pathologic effects of multiple echocardiographic contrast injections on the myocardium, brain and kidney.

Myocardial contrast echocardiography can define in vivo the area at risk for necrosis after coronary occlusion. However, if this technique is to be used, it cannot be intrinsically toxic to the heart or other critical organs. To determine the functional and pathologic effects of contrast echocardiography, six intracoronary, six intrarenal and six intracarotid artery injections of 2 to 6 cc of a commonly employed contrast agent (agitated Renografin-saline solution) were performed in five dogs. A sixth dog served as a sham to assess any deleterious effects of the model preparation. Two-dimensional echocardiographic images and electrocardiograms were recorded during intracoronary injections, and heart rate, blood pressure, left ventricular end-diastolic pressure and rate of rise of left ventricular pressure (dP/dt) were continuously monitored. At 24 hours, echocardiographic and hemodynamic measurements were repeated, the dogs were killed and the heart, brain and kidneys were removed and prepared for light microscopic examination. Quantitative analysis of left ventricular wall motion was performed on control, peak contrast, post-contrast and 24 hour studies. With each intracoronary injection, there were transient decreases in blood pressure (p = 0.05 versus control) and increases in left ventricular end-diastolic pressure (p = 0.04 versus control). These were associated with depression of wall motion in contrast-enhanced regions (p = 0.01 versus control) and ST-T segment changes on the electrocardiogram. No significant change in heart rate or left ventricular dP/dt was noted. All variables normalized with the clearance of the contrast effect and remained normal to 24 hours. Light microscopic examination revealed no myocardial or cerebral changes attributable to the contrast agent injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Creatine kinase release not associated with myocardial necrosis after short periods of coronary artery occlusion in conscious baboons.

The effects of 15 minute periods of coronary artery occlusion on plasma creatine kinase (CK) and CK-MB isoenzyme activity, regional myocardial function and subsequent myocardial necrosis were studied in six conscious baboons 2 to 3 weeks after recovery from instrumentation. Mid left anterior descending coronary artery occlusion induced complete loss of systolic wall thickening (ultrasound transit time technique) and decreases in epicardial (-93%) and endocardial (-96%) blood flows (microsphere technique). Reperfusion after 15 minutes resulted in complete recovery of regional function 24 hours later. Serial plasma enzyme activity revealed a significant increase in total CK from 71 +/- 11 to 976 +/- 158 U/liter and in CK-MB from levels that were too low to measure to 21.4 +/- 2.9 U/liter. At autopsy, neither gross pathologic evidence (triphenyltetrazolium chloride staining technique) nor histologic evidence of myocardial necrosis was observed. Thus, in the conscious baboon short episodes of myocardial ischemia are associated with a significant appearance of CK and CK-MB in the blood in the absence of cellular necrosis.

Animals↗
PubMed1985

Early detection of cardiac allograft rejection with proton nuclear magnetic resonance.

No reliable, noninvasive technique is currently available for the early detection of cardiac transplant rejection. In this study, pulse nuclear magnetic resonance (NMR) spectroscopy was used (20 MHz) to detect cardiac allograft rejection in rats. Proton spin-lattice relaxation time (T1), proton spin-spin relaxation time (T2), and water content were measured in both recipient and donor hearts at 2, 4, 6, and 8 days after transplantation. Pathologic specimens were scored on a 0 to 4+ scale of increasing evidence of rejection by light microscopy. Three kinds of heterotopic transplants were performed for a total of 90: (1) Lewis rats received Lewis rat isografts, (2) Lewis rats received Brown Norway rat allografts, and (3) Lewis rats received cyclosporin A-treated allografts (15 mg/kg/day). T1 in group 2 was significantly higher than that in group 1 as early as day 2 (670 + 25 vs 616 + 11 msec, p less than .001), when histologic scores were not different. T2 in group 2 was also higher than that in group 1 (48.0 +/- 5.0 vs 41.1 +/- 2.6, p less than .005). T1 and T2 in group 2 increased from day 4 and correlated well with the water content of the hearts (r = .70 and r = .75, respectively). Cyclosporin A completely suppressed the increase of T1 and T2 in group 2. Treatment with cyclosporin also suppressed the histologic rejection scores. Our data suggest that proton relaxation time measurement may be a sensitive technique for detecting the onset of rejection and examining the therapeutic effects of cyclosporin. NMR imaging, which highlights T1 and T2 separately, should provide a sensitive noninvasive means of assessing myocardial graft rejection.

Animals↗
PubMed1985

Myocardial recovery after hypothermic arrest: a comparison of oxygenated crystalloid to blood cardioplegia. The role of calcium.

We compared multidose crystalloid hyperkalemic cardioplegic solutions with and without added red cells in 24 canine hearts subjected to 5 hr of arrest at 10 degrees C. All cardioplegic solutions were fully oxygenated at 4 degrees C before delivery. Since blood cardioplegia contained Ca++ carried over with the red cells, Ca++ was added to the crystalloid solution in one group. The table below shows the hematocrit (HCT) and ionized Ca++ concentrations of the cardioplegic solutions, and coronary arteriovenous oxygen difference during infusion of cardioplegic solution (AVO2) (ml O2/100 ml). Recovery during reperfusion is shown as percent of prearrest left ventricular function (LVF) and prearrest myocardial ATP concentration.

Adenosine Triphosphate↗
PubMed1984

Effect of dextran and aspirin on platelet adherence after transluminal angioplasty of normal canine coronary arteries.

The effect of low-molecular-weight dextran and aspirin on platelet deposition after transluminal coronary angioplasty was studied in a normal canine model. Eighteen anesthetized, open-chest dogs were separated into 4 groups. All dogs received 3,000 units of intravenous heparin 10 to 20 minutes before the procedure. Dogs in Group 1 served as controls and were given no further treatment. Dogs in Group 2 received low-molecular-weight dextran by continuous intravenous infusion at a rate of 20 ml/hour for 1 hour before balloon inflation. Dogs in Group 3 were given 500 ml of low-molecular-weight dextran as an intravenous bolus over 1 hour, beginning 4 hours before the procedure. Dogs in Group 4 were fed 20 mg/kg of aspirin 3 hours before angioplasty. The dogs were killed 10 minutes after angioplasty and the arterial segments subjected to balloon inflation submitted for electron microscopic analysis. An additional group of 10 dogs was used to assess the bleeding times and platelet counts from control and drug-treated dogs. Drug treatment was associated with significant prolongation of the bleeding time and reduction in platelet number. Extensive endothelial desquamation in the area of balloon angioplasty was observed in all dogs. However, no appreciable qualitative difference in either the degree or extent of rapid platelet deposition to the exposed subendothelium was discernible between the control and any of the treatment groups. These results do not confirm previous observations with low-molecular-weight dextran. Further work on the initial and long-term platelet response after endothelial injury should be undertaken in a primate atherosclerotic model.

Angioplasty, Balloon↗
PubMed1984

Evaluation of a QRS scoring system for estimating myocardial infarct size. IV. Correlation with quantitative anatomic findings for posterolateral infarcts.

This study correlated the location and size of posterolateral myocardial infarcts (MIs) measured anatomically with that estimated by quantitative criteria derived from the standard 12-lead ECG. Twenty patients were studied who had autopsy-proved, single, posterolateral MIs and no confounding factors of ventricular hypertrophy or bundle branch block in their ECG. Left ventricular anatomic MI size ranged from 1 to 46%. No patient had a greater than or equal to 0.04-second Q wave in any electrocardiographic lead and only 55% had a 0.03-second Q wave. A 29-point, simplified QRS scoring system consisting of 37 weighted criteria was applied to the ECG. Points were scored by the ECG in 85% of the patients (range 1 to 8 points). MI was indicated by a wide variety of QRS criteria; 19 of the 37 criteria from 8 different electrocardiographic leads were met. The correlation coefficient between MI size measured anatomically and that estimated by the QRS score was 0.72. Each point represented approximately 4% MI of the left ventricular wall.

Adult↗