Massive right ventricular outflow tract aneurysm after ventriculotomy for subvalvular pulmonic stenosis associated with peripheral pulmonary arterial stenoses.
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Adult↗
Biomedical subjects
J E Saffitz
Publications and source records attributed to J E Saffitz.
Coronary arterial rupture during coronary angioplasty.
Although percutaneous transluminal coronary angioplasty (PTCA) appears to be a relative safe and effective procedure, reported complications include coronary occlusion and dissection with or without acute myocardial infarction. Herein, a hitherto unreported complication of PTCA is described.
Aged↗
Histiocytoid cardiomyopathy: a cause of sudden death in apparently healthy infants.
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Cardiomyopathies↗
Amyloidosis limited to small arteries causing angina pectoris and sudden death.
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Amyloidosis↗
Coronary artery spasm in intact dogs induced by potassium and serotonin.
Although coronary artery spasm has been implicated as an important cause of myocardial ischemia in humans, an animal model of reversible segmental coronary constriction has not been described. To provoke coronary spasm in open-chest dogs, selected vasoconstricting agents adsorbed to viscous ion exchange gels were applied topically to the surface of epicardial coronary arteries. The procedure provided a sustained localized release of drug, and minimized effects on contiguous myocardium or on the systemic circulation. Segmental arterial constrictor responses were evaluated by sonomicrometry, arteriography, and electromagnetic flow measurements. Potassium evoked sustained constrictions or spasms, and concomitantly reduced flow by -42 +/- 4% (SE; n = 34). Serotonin likewise produced sustained decreases in flow of -22 +/- 6% (SE; n = 5). Other constrictors, including norepinephrine and angiotensin, failed to evoke sustained constrictions. Spasms nearly abolished reactive hyperemic responses elicited by temporary complete occlusion of the artery. Intravenous nitroglycerin and dihydropyridine calcium antagonists promptly relieved the spasms. Scanning electronmicroscopic examination of the intimal surface of arteries undergoing sustained spasm revealed no platelet thrombi. Thus, nonthrombotic, vasodilator-sensitive segmental coronary spasms were elicited by endogenous constrictors which may play a role in regulating flow to ischemic myocardium.
Angiotensin II↗
Alpha adrenergic-mediated accumulation of calcium in reperfused myocardium.
Reperfusion of ischemic myocardium is associated with increases in total myocardial calcium (Ca+2), which may influence the ultimate extent of ischemic damage as well as the development of arrhythmias. Since reperfusion is also associated with enhanced alpha-adrenergic responsivity, this study was performed to determine the potential interactions between alpha-adrenergic receptors and myocardial calcium during reperfusion. Cats were subjected to 35 min of left anterior descending coronary artery occlusion and 10 min of reperfusion. Total myocardial calcium was measured by atomic absorption spectrometry. Intracellular calcium was calculated from measurements of extracellular space [( 3H]inulin). In control animals with reperfusion, total calcium increased from 0.32 +/- 0.03 to 0.65 +/- 0.05 mmol/100 g dry tissue (P less than 0.0001), while intracellular calcium increased from 0.15 +/- 0.03 to 0.40 +/- 0.05 mmol/100 g dry tissue (P less than 0.001). Pretreatment with the alpha-adrenergic blocking agents phentolamine or prazosin prevented the increase in total and intracellular calcium. Phentolamine and the aqueous soluble alpha 1-adrenergic antagonist BE-2254 administered as late as 2 min before reperfusion similarly attenuated the increase in tissue calcium. Although administration of BE-2254 2 min before reperfusion failed to block the reperfusion-induced increase in extracellular space, the increase in calculated intracellular calcium was prevented. beta-Adrenergic blockade with propranolol partially attenuated but did not prevent an increase in total tissue calcium. Labetalol, a combined alpha- and beta-adrenergic blocking agent completely blocked the increase in tissue calcium during reperfusion. Additional experiments performed after 70 min of ischemia with reperfusion demonstrated a 49% attenuation of the increase in tissue calcium with alpha-adrenergic blockade. Electron microscopy with pyroantimonate and x-ray microprobe analysis demonstrated a large increase in calcium precipitate in mitochondria after reperfusion in untreated animals. Though alpha-adrenergic blockade prevented the calcium deposition in mitochondria, other criteria of ischemia persisted. Thus, alpha-adrenergic blockade specifically prevents the increase in intracellular calcium during reperfusion in reversibly injured tissue, independent of alterations in extracellular space and tissue water.
Adrenergic alpha-Antagonists↗
Detection of cardiac transplant rejection with radiolabeled lymphocytes.
To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy.
Animals↗
Incorporation of radiolabeled lysophosphatidyl choline into canine Purkinje fibers and ventricular muscle. Electrophysiological, biochemical, and autoradiographic correlations.
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Animals↗
The arachidonic acid metabolic capacity of canine myocardium is increased during healing of acute myocardial infarction.
The relative capacity for metabolizing [14C]arachidonic acid into biologically active products was studied in microsomes prepared from both normal and infarcted regions of myocardium at three different times after circumflex coronary artery occlusion in the dog. At 3 days after infarction, when polymorphonuclear leukocytes were the predominant invading cell, the ability of infarcted left ventricle microsomes to produce arachidonic acid metabolites was greater than that of microsomes from normal areas of the same hearts. At 3 weeks after infarction, when macrophages were the predominant infiltrating cell and there was a proliferation of blood vessels and fibroblasts, there continued to be significant increases in the production of both prostacyclin (measured as 6-keto PGF1 alpha) and thromboxane (measured as TxB2). This enhanced production was still seen at 3 months after infarction at a time when histological examination of the tissue showed that it was still healing with both blood vessels and fibroblasts present. The production of 6-keto PGF1 alpha was 31.7 +/- 4 picomoles per milligram protein per hour (pmol/mg per hr) in noninfarcted regions of left ventricle, whereas the production was significantly increased to 71.7 +/- 15 at 3 days, 64.1 +/- 10 at 3 weeks, and 67.2 +/- 15 even at 3 months after infarction. The thromboxane synthetase activity rose significantly from 30.1 +/- 5 pmol mg per hr in noninfarcted regions to 73.7 +/- 18 at 3 days, 71.2 +/- 5 at 3 weeks, and 92.4 +/- 40 at 3 months. The enhanced ability to metabolize arachidonic acid may result from the inflammatory cell invasion or fibroblast activation which accompany healing of acute infarcts.
Animals↗
Monitoring of cardiac antirejection therapy with In-111 lymphocytes.
To determine whether lymphocytes labeled with indium-111 permit noninvasive assessment of antirejection therapy, we performed 40 allogeneic heterotopic cardiac transplants in rats. Antirejection therapy with azathioprine (30 mg/kg) and sodium salicylate (200 mg/kg) prolonged contractile function of the graft from 7.5 +/- 1.5 (s.d.) days in controls to 19.4 +/- 3.7 days in treated animals. Six to seven days after transplantation, autologous lymphocytes labeled with In-111 were injected intravenously in seven untreated and eight treated rats. Scintigraphy and organ counting were performed 24 hr after administration of labeled cells. At sacrifice all grafts in untreated rats exhibited contractile failure, whereas grafts in all treated rats were beating well. Transplants in untreated recipients exhibited marked accumulation of In-111 lymphocytes detectable scintigraphically, with ratios of 7.7 +/- 1.9 for the activity in the transplant over that in the native heart (HT/HO), as obtained by well counting. In contrast, accumulation was not scintigraphically detectable in transplants of treated rats, with HT/HO ratios of 2.6 +/- 1.8 (p less than 0.005). The results suggested that imaging with in-111-labeled lymphocytes will permit noninvasive assessment of antirejection therapy.
Animals↗
Percutaneous transluminal angioplasty. Radiological-pathological correlation.
Radiological and pathological assessment of the degree and extent of arterial injury caused by balloon angioplasty was performed in 20 renal arteries obtained at autopsy. Intact arteries were studied angiographically before and after dilatation and then examined histologically. Both normal and diseased arteries were subjected to varying degrees of dilatation. Damage ranged from minimal intimal disruption to major tears of the muscular media. Equivalent dilatory force created greater damage in the distal (muscular) than in the proximal (elastic) portion of the renal artery. There was no evidence of plaque remodeling or compression.
Aged↗
Autoradiography of phosphatidyl choline.
Saturated choline phosphatides are extracted during conventional tissue processing for electron microscopy. To facilitate autoradiographic subcellular localization of arrhythmogenic myocardial phospholipids, we evaluated tissue processing procedures for preservation of saturated phosphatidyl choline (PC). Suspensions, of a murine plasmacytoma were incubated with negative, unilamellar liposomes containing 14C-choline-labeled PC or 14C-1-palmitate dipalmitoyl PC. Extraction of radioactivity was monitored at each processing step by liquid scintillation spectrometry. Conventional fixation with glutaraldehyde and osmium tetroxide followed by acetone dehydration and Spurr's plastic embedding led to extraction of nearly all radioactivity. However, treatment of cells with 1.5% tannic acid after glutaraldehyde but before osmium tetroxide fixation preserved 93.1 +/- .6% of 14C-choline-labeled PC. Virtually identical results were obtained with dipalmitoyl PC. Autoradiography demonstrated no significant translocation of labeled PC from plasmacytoma cells to unlabeled avian erythrocytes, mixed in equal proportions after fixation but before dehydration and embedding.
Autoradiography↗
Separation of transcriptively active and inactive chromatin. Agarose gel chromatography.
Sheared chromatin fractionated by currently accepted methods of agarose gel exclusion chromatography, undergoes a limited and non-specific aggregation resulting from the high ionic strength and divalent cation concentration of the column elution buffer. Such aggregation causes the artifactual appearance of radioactively labeled, newly synthesized RNA within the column exclusion volume, erroneously suggesting an enrichment for actively transcribed chromatin. Claims for the efficacy of agarose gel exclusion as a method for separating template-active and -inactive chromatin are based largely on assays for active chromatin which rely on localization of specific molecular complexes of chromatin and nascent RNA. Under the conditions employed, the present studies invalidate this assay and thus cast considerable doubt on the agarose gel exclusion method itself.
Animals↗
Hydroxylapatite thermal fractionation of chromatin and DNA.
Chromatin and DNA from developing muscle cultures were fractionated by hydroxylapatite thermal chromatography on the basis of differential thermal stability. A thermal chromatography system was developed in which protein mediated thermal stability of chromatin DNA was maximally expressed. The resulting chromatin and DNA elution profiles were similar to thermal denaturation profiles in low ionic strength solution. Additional studies showed this system was able to detect protein stabilization of DNA in in vitro nucleohistone preparations. Although some protein remained bound to hydroxylapatite during chromatin thermal elution, it did not affect the denaturation or elution behavior of free DNA on the same column. These studies show that fragments of chromatin or DNA can be segregated on the basis of differential thermal stability by hydroxylapatite chromatography.
Animals↗
Attempted separation of transcriptively active and inactive chromatin by hydroxylapatite thermal chromatography.
Chromatin and purified DNA were fractionated by hydroxylapatite thermal chromatography. Fractions of varying thermal stability were tested for the proportions of transcribed sequences and repetitive sequences relative to the unfractionated genome. The first 80--85% of either total chromatin or purified DNA eluted from hydroxylapatite contained the same proportion of hybridizable sequences as total DNA. The remaining 15--20% of chromatin eluting at the highest temperatures was depleted of transcribed sequences. Analysis of the 20% highest melting fraction of purified DNA showed that, while the first two-thirds of this fraction contained the same proportion of transcribed sequences as unfractionated DNA, the last third, comprising about 6% of total DNA, was depleted of active sequences. Although no major differences were detected in nonrepetitive sequence complexity of chromatin fractions, there was a correlation between relative thermal stability and repetitive sequence content in fractions of both chromatin and DNA separated by thermal chromatography. Fragments eluting at higher temperatures contained a greater proportion of repetitive sequences, as indicated by a rapidly renaturing component. Most likely, the latest eluting fractions from both chromatin and purified DNA were enriched for a nontranscribed, highly reiterated, G+C rich satellite component of the chicken genome.
Animals↗
Pediatric endomyocardial biopsy performed solely with echocardiographic guidance.
Endomyocardial biopsy has had limited utilization for the diagnosis of myocardial disease in the pediatric population. Through the use of echocardiography for guidance, we attempted 155 consecutive biopsies in 33 patients. A successful biopsy was performed 151 times, including 48 (31%) in infants less than 6 months of age. Biopsies were performed with a right internal jugular approach using 3F, 5F, and 7F bioptomes. A combination of apical four-chamber and parasternal short-axis views could visualize the passage of the bioptome into the ventricle and the action of the jaws. There was no case of ventricular perforation. After biopsy one transplant recipient was left with an increase in the amount of preexisting tricuspid regurgitation by color flow mapping echocardiography. These results demonstrate that echocardiographically guided endomyocardial biopsies may be safely performed over a wide range of patient sizes. The increased portability, lack of radiation exposure, and the simultaneous visualization of the bioptome and chamber wall combined with these results indicate that echocardiographically guided endomyocardial biopsies should be considered the technique of choice for the pediatric population.
Adolescent↗
Detection of remote myocardial infarction with quantitative real-time ultrasonic characterization.
We have previously shown that the intrinsic properties of myocardium can be characterized quantitatively by the assessment of ultrasonic integrated backscatter. In this study we utilized a novel, real-time, two-dimensional system capable of quantitative integrated backscatter imaging to determine whether zones of remote myocardial infarction in dogs could be delineated definitively by ultrasonic tissue characterization. Detection of such zones in patients is needed as a basis for management decisions related to thrombolysis, angioplasty, and coronary surgery. Integrated backscatter was measured through the closed chest from 25 myocardial sites. Zones of infarction exhibited time-averaged integrated backscatter values approximately 10 dB (9.5 +/- 0.5 dB, standard error of the mean) greater than those in normal regions (p less than 0.001). In addition, the physiologic cardiac cycle--dependent variation of integrated backscatter was blunted significantly in zones of infarction [0.8 dB +/- 0.3 vs. 3.8 +/- 0.6 (p less than 0.01) for normal regions]. Ultrasonic results matched the histopathologic features assessed directly. Thus quantitative ultrasonic tissue characterization can differentiate infarcted tissue from normal myocardium and offers promise for quantitative detection of histopathology in vivo.
Animals↗
The role of myocardial gap junctions in electrical conduction and arrhythmogenesis.
Electrical activation of the heart requires cell-cell transfer of current via gap junctions, arrays of densely packed protein channels that permit intercellular passage of ions and small molecules. Because current transfer occurs only at gap junctions, the spatial distribution and biophysical properties of gap junction channels are important determinants of the conduction properties of cardiac muscle. Gap junction channels are composed of members of a multigene family of proteins called connexins. As a general rule, individual cells express multiple connexins, which creates the potential for considerable functional diversity in gap junction channels. Although gap junction channels are relatively nonselective in their permeability to ions and small molecules, cardiac myocytes actively adjust their level of coupling by multiple mechanisms including changes in connexin expression, regulation of connexin trafficking and turnover, and modulation of channel properties. In advanced stages of heart disease, connexin expression and intercellular coupling are diminished, and gap junction channels become redistributed. These changes have been strongly implicated in the pathogenesis of lethal ventricular arrhythmias. Ongoing studies in genetically engineered mice are revealing insights into the role of individual gap junction channel proteins in normal cardiac function and arrhythmogenesis.
Animals↗