Images in cardiovascular medicine. Cardiac hemochromatosis.
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Atrial Fibrillation↗
Biomedical subjects
E R Rodriguez
Publications and source records attributed to E R Rodriguez.
Cardiac myocyte differentiation induced by 3,5,3'-triiodo-L-thyronine (T3) in P19 teratocarcinoma cells is accompanied by preferential binding of RGG(T/A)CA direct repeats spaced by 4 base pairs in the DNA.
When treated with T3, P19 cells differentiate into ultrastructurally proven cardiac myocytes and express the cardiac ventricular specific marker ventricular myosin light chain 2V. This differentiation is irreversibly induced in culture during the first 48 hrs of exposure to T3. We studied the binding of P19-indigenous transcription factors of the Steroid-Thyroid-Retinoic superfamily of nuclear receptors to oligonucleotide response elements bearing direct, inverted and palindromic repeats of the consensus sequence RGG(T/A)CA. Electrophoretic mobility shift assays showed a preference in T3-treated P19 cells for binding RGG(T/A)CA "half sites" in direct repeat orientation separated by 4 base pairs. The specificity of binding was confirmed in competition experiments. This finding suggests that target genes bearing thyroid response elements spaced by 4 base pairs in their promoter regions play an important role in the cardiac differentiation induced by T3 in P19 teratocarcinoma cells.
Animals↗
3,5,3'-Triiodo-L-thyronine induces cardiac myocyte differentiation but not neuronal differentiation in P19 teratocarcinoma cells in a dose dependent manner.
P19 teratocarcinoma cells differentiate into neurons or muscle when treated with varying doses of retinoic acid, dimethylsulfoxide, thioguanine or butyrate. We induced cardiac differentiation in P19 cells by treating them with 3,5,3'-Triiodo-L-Thyronine (T3). P19 cells received doses of T3 ranging from 30 pM to 300 nM. The beating colonies were counted, and a dose response curve showed that the optimal concentration of T3 was 30 nM. The colonies beat rhythmically for 4-6 weeks, and the cardiac myocytes showed clearly evident cardiac-specific organelles such as nexuses and atrial granules. No evidence of neuronal or skeletal muscle differentiation was seen with any of the concentrations of T3 used. Reverse transcription-polymerase chain reaction showed these cells to express the cardiac ventricular specific marker myosin light chain 2V. T3 is capable of inducing P19 cells to differentiate, in a dose related manner, into spontaneously beating cardiac myocytes identified as such on the basis of ultrastructural criteria. The induction of differentiation is accompanied by expression of cardiac-specific genes. These findings suggest that perhaps genes bearing thyroid response elements in their promoter regions play an important role in the cardiac differentiation induced by T3 in P19 teratocarcinoma cells.
Animals↗
Reduction in reperfusion-induced myocardial necrosis in dogs by RheothRx injection (poloxamer 188 N.F.), a hemorheological agent that alters neutrophil function.
BACKGROUND: Reperfusion after prolonged coronary artery occlusion may be followed by additional myocardial necrosis persisting for hours to days. Potential mechanisms include neutrophil-mediated injury and compromised flow within the microcirculation of the reperfused myocardium. Poloxamer 188 is a nonionic surfactant with beneficial hemorheological and neutrophil-inhibitory properties. The purpose of the present study was to determine if poloxamer 188 is capable of reducing the myocardial injury associated with sustained reperfusion and to examine the effect of treatment duration. METHODS AND RESULTS: Three groups of closed-chest dogs underwent 90 minutes of left anterior descending coronary artery occlusion (angioplasty balloon) and 72 hours of reperfusion. Poloxamer 188, formulated as RheothRx Injection (Burroughs Wellcome Co), was given as a 75 mg/kg IV bolus 15 minutes before reperfusion followed by a 150 mg.kg-1.h-1 continuous IV infusion for 4 hours (n = 13) or 48 hours (n = 13); control dogs (n = 12) received saline for 48 hours. The 48-hour infusion of poloxamer 188 resulted in a 42% reduction in infarct size (as a percent of the area at risk) compared with the control group (25.0 +/- 4.2% versus 43.3 +/- 4.3%, P D .01), whereas the 4-hour group demonstrated a 25% reduction in infarct size compared with the control group (32.4 +/- 4.3%, P = .08). ANCOVA demonstrated that the 48-hour infusion of poloxamer 188 reduced myocardial infarct size independent of differences in collateral blood flow (P = .002 versus control). A trend toward infarct size reduction was observed in the 4-hour infusion group (P = .098 versus control by ANCOVA). Plasma creatine phosphokinase concentration was lower in both poloxamer 188-treated groups (P < .05 versus control). Global left ventricular ejection fraction at 72 hours of reperfusion was improved in the 48-hour infusion group compared with the control group (43 +/- 3.1% versus 33 +/- 2.0%, P < .05), whereas ejection fraction in the 4-hour group was 37 +/- 1.3% (P = NS versus control). Regional ventricular function was also significantly better in the 48-hour infusion group compared with the control group. In vitro studies demonstrated that at concentrations comparable to those achieved in vivo, poloxamer 188 inhibited neutrophil chemotaxis. This finding may represent a beneficial mechanism of action. CONCLUSIONS: A 48-hour infusion of poloxamer 188 reduced myocardial infarct size and improved left ventricular function in this dog model of 90 minutes of coronary artery occlusion and 72 hours of reperfusion. The finding that the 4-hour infusion of poloxamer 188 did not result in similar benefits suggests that additional reperfusion injury occurred between 4 and 48 hours.
Animals↗
Does being in the military affect nurses' perceptions of work life?
This study was a causal comparative investigation of military and civilian nurses' perceptions of selected aspects of work life. The Work Environment Scale, the Maslach Burnout Inventory and the Michigan Job Satisfaction Scale were administered to civilian and military samples matched on selected demographic variables. MANOVA procedures failed to reveal significant differences on measures of burnout and morale. Although military nurses were significantly more satisfied with issues of pay and fringe benefits, civilian nurses reported significantly greater job satisfaction, peer cohesion, supervisory support, decision making, autonomy, task orientation and opportunity to be innovative. These findings and suggested changes are discussed with attention to differences between the military and civilian work setting.
Adult↗
Cardiac myocytes and dendritic cells harbor human immunodeficiency virus in infected patients with and without cardiac dysfunction: detection by multiplex, nested, polymerase chain reaction in individually microdissected cells from right ventricular endomyocardial biopsy tissue.
Two hundred fifteen patients infected with human immunodeficiency virus (HIV) participated in a prospective longitudinal study of HIV-related heart disease. Evaluation included signal-averaged electrocardiography and echocardiography. Fifteen patients underwent endomyocardial biopsy, 5 had cardiovascular symptoms and 10 did not. Cardiac myocytes or dendritic cells were prepared by individual cell microdissection to sort them from other cell types such as interstitial cells or circulating blood elements. HIV proviral sequences were amplified in samples of 15 to 20 cells of each type by multiplex, nested, polymerase chain reaction and hybridized to 32P-labeled probes specific for regions within the gag and pol genes of HIV-1. The results showed the presence of HIV sequences in myocytes of 2 of 5 patients with cardiac symptoms and in 6 of 10 without. Thus, symptomatic HIV cardiomyopathy did not appear to be a direct consequence of the virus on myocardial cells. In dendritic cells, HIV sequences were detected in 5 of 5 patients with cardiac symptoms and in 8 of 10 with apparently normal ventricular function. Furthermore, dendritic cells were somewhat more numerous in the myocardium of symptomatic than asymptomatic patients. Our studies are the first to directly detect the HIV genome in purified cardiac myocytes from patients with and without cardiac dysfunction. Our findings do not support a direct role of the virus in myocardial dysfunction. However, the results do suggest that the interstitial dendritic cells may be involved in some manner in the development of cardiac dysfunction observed in HIV-infected patients.
Adult↗
Comparison of sensitivity for human cytomegalovirus of the polymerase chain reaction, traditional tube culture and shell vial assay by sequential dilutions of infected cell lines.
Although traditional tube culture (TTC) is still considered by many as the 'gold standard' for the laboratory diagnosis of human cytomegalovirus (HCMV), the shell vial assay (SVA) offers greater speed of detection. This technique utilizes immunofluorescence (IF) to detect early or immediate early nuclear antigens (IEA). The detection capabilities of these two tests were compared with the polymerase chain reaction (PCR), a technique that amplifies enzymatically selected DNA target sequences. Serial dilutions of crude culture harvests from 2 HCMV strains, Towne and a clinical urine isolate, were made up to 1:1 000,000. Ten-microliters aliquots of the original sample and each dilution were tested by PCR, TTC and SVA. For PCR, the nested-primer approach was used. Outer primers delimited a 721-bp sequence contained within the 2nd to 4th exons of the immediate-early protein. Inner nest primers delimited a 167-bp sequence in the third exon, detected by a 32P-labelled probe. The results show that: (1) control samples which contained all PCR reagents but no DNA were uniformly negative; (2) radiolabelled-probe detection (RPD) of PCR products is, on average, 100 x more sensitive than detection by ethidium bromide; (3) PCR is, on average, 100 x more sensitive than evaluation of cytopathic effect (CPE) in the TTC; (4) the predictive value of a negative SVA result is low compared to PCR.
Base Sequence↗
Atherogenic effect of barotrauma on in situ saphenous veins in monkeys.
The objectives of this study were to determine whether veins subjected to barotrauma in situ undergo lipid uptake and morphologic changes to the same extent as veins grafted into the arterial circulation. Saphenous veins in seven stump-tailed macaque monkeys were exposed bilaterally and were circumferentially dissected free from surrounding tissue only at isolated sites. Segments of the veins were distended for 1 minute at hydrostatic pressures of 125 or 350 mm Hg. An undistended segment served as control. A cephalic vein graft was interposed in the femoral artery for comparison with in situ veins. The animals were fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Saphenous veins and the cephalic vein grafts were explanted at 3 months for biochemical and histologic analyses. Cholesterol content in undistended saphenous veins was similar to that in veins distended at 125 or 350 mm Hg--105 +/- 15, 122 +/- 14, and 109 +/- 30 micrograms/100 mg wet tissue weight, respectively. Cholesterol content in cephalic vein grafts, 473 +/- 122 micrograms/100 mg, was greater (p less than 0.001) than in saphenous veins at all distention pressures studied. There was no difference among the distention pressures in the intimal fraction of saphenous vein wall, with the pooled value being 20% +/- 12%. This contrasted with the value of 59% +/- 11% in cephalic vein grafts (p less than 0.01). Endothelial coverage of the luminal surface in saphenous veins was similar among the levels of barotrauma, with the pooled value being 83% +/- 15%. Less of the lumen was covered with endothelium in cephalic vein grafts, 46% +/- 18% (p less than 0.01). Slightly more medial fibrosis was observed in cephalic vein grafts as compared with saphenous veins (p less than 0.05). These data demonstrate that barotrauma alone does not cause veins that remain in the venous system to undergo the lipid uptake or morphologic changes that occur in veins grafted into the arterial circulation in nonhuman primates.
Animals↗
Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. II. Modification of early changes by platelet inhibition with aspirin and dipyridamole.
The objective of this study was to determine the early influence of platelet inhibition on the histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. Cephalic vein grafts were interposed bilaterally in the femoral arteries of 15 stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. All animals received in combination aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Grafts were excised from five animals for analysis on each of postoperative days 3, 7, 14, 30, 60, and 90. In animals subjected to platelet inhibition, cholesterol content in the graft was 170 +/- 52 micrograms/100 mg at 90 days, 205% of the level in ungrafted vein (p less than 0.01). This change was small in comparison with the increase to 686% of ungrafted vein observed in our study of control animals. In stepwise regression analysis, cholesterol content of grafts was best predicted by prevalence of foam cells (r2 = 0.82), and the proportion of intima as a fraction of total wall area was best predicted by the presence of macrophages (r2 = 0.69). Platelet inhibition did not decrease the extent of intimal hyperplasia. The prevalence of adherent platelets (r = -0.72) and the amount of fibrin (r = -0.78) correlated inversely with the amount of endothelium present during the first 14 days. The strength of these correlations declined with time, despite persistent lack of endothelium in some areas. Medial fibrosis occurred to the same extent as in control grafts, as did the early appearance of platelet factor VIII and fibronectin and the lack of vasa vasorum at 3 days followed by reappearance at 7 days. These data demonstrate that platelet inhibition dramatically reduces lipid uptake by grafts in the first 90 days but has less influence over histologic or morphometric changes.
Animals↗
Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. I. Sequential changes within the first three months.
The objective of this study was to define the histologic and morphometric evolution that accompanies the increase in cholesterol content of vein bypass grafts in a nonhuman primate model. Cephalic vein grafts were interposed bilaterally in the femoral arteries of 15 stump-tailed macaque monkeys (Macaca arctoides), which were fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Grafts were excised from five animals for analysis on each of postoperative days 3, 7, 14, 30, 60, and 90. Cholesterol content increased from 69 +/- 24 micrograms/100 mg (mean +/- standard deviation) in ungrafted vein to 473 +/- 122 micrograms/100 mg in grafts 90 days after implantation (p less than 0.05). By stepwise regression analysis, cholesterol content was best predicted by abundance of foam cells (r2 = 0.82). Intima comprised 13% +/- 5% of the total cross-sectional area of the wall in ungrafted vein and 59% +/- 11% at day 90 (p less than 0.001). With cholesterol content excluded from the stepwise regression, intimal area was best predicted by the presence of foam cells (r2 = 0.39). There was consistently an increase in the prevalence of polymorphonuclear leukocytes on the luminal surface and in both the intima and media during the first 14 days after grafting. Vasa vasorum, which were always present in ungrafted vein, were sparse at 3 days but reappeared by day 7. Medial fibrosis occurred in grafts, and in the 30- to 90-day interval it was directly correlated with the number of adventitial vasa vasorum present (r = 0.64, p less than 0.05). Immunohistochemistry revealed prominent staining for both platelet factor VIII and fibronectin during the first month, with a gradual decline in staining intensity thereafter. The evolution of changes in vein bypass grafts documented in this report are in general agreement with graft changes observed in humans and support the validity of our model in evaluating the histologic correlates of increased graft cholesterol content.
Animals↗
Histologic, morphometric, and biochemical evolution of vein bypass grafts in a nonhuman primate model. III. Long-term changes and their modification by platelet inhibition with aspirin and dipyridamole.
The objectives of this study were to elucidate the long-term influence on vein bypass grafts of platelet inhibition and its late discontinuation. Cephalic vein grafts were interposed bilaterally in the femoral arteries of stump-tailed macaque monkeys fed a diet that sustains plasma cholesterol levels of approximately 225 mg/dl. Fifteen animals were divided into three groups of five animals each. Group I received no medications and served as a control group. Group II received for the full duration of the study a combination of aspirin, 80 mg/day, and dipyridamole, 50 mg/day. Group III received the same regimen of platelet inhibition as in group II during the first 9 months, but were not treated during the subsequent 9-month interval. Grafts were excised for analysis from groups I and II at both 9 and 18 months and from group III at 18 months. Cholesterol content in group I grafts was 470 +/- 89 micrograms/100 mg at 9 months and 388 +/- 127 micrograms/100 mg at 18 months. In group II grafts, cholesterol content was 208 +/- 72 micrograms/100 mg at 9 months (p less than 0.001 compared with group I) and 266 +/- 84 micrograms/100 mg at 18 months. In group III grafts, cholesterol content was 249 +/- 71 micrograms/100 mg at 18 months. Differences in cholesterol content among the three groups of grafts at 18 months were not found to be statistically significant. Stepwise regression analysis at 18 months showed that cholesterol content was best predicted by medial fibrosis (r2 = 0.66) followed by abundance of foam cells (increase in r2 = 0.26) in group I, by fibrin in group II (r2 = 0.63), and by prevalence of macrophages in group III (r2 = 0.74). In all groups, platelets, fibrin, and polymorphonuclear leukocytes were less abundant than they had been at 3 months. Cross-sectional area occupied by the intima was not influenced by platelet inhibition.
Animals↗
Rheologic genesis of aortic coarctation in a canine model.
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Animals↗
Ventricular aneurysms and other lesions produced by the struts of bioprosthetic valves implanted in sheep.
Damage to the posterolateral wall of the left ventricle was found in eight of approximately 700 sheep undergoing mitral valvular replacement as part of animal model studies of bioprosthetic valves. The damage consisted of left ventricular aneurysms in five animals, subacute rupture of the left ventricle in one, acute left ventricular laceration in one, and endocardial scarring in one. Six of the eight bioprostheses were bovine pericardial valves, including five low-profile valves and one standard valve; of the two porcine bioprostheses, one was intentionally oversized and the other was a low-profile supra-annular valve. In each of these animals the damage appeared to have been caused by contact between the most posterior strut of the bioprosthesis and the left ventricular wall.
Animals↗
Acute rejection after cardiac transplantation: detection by interstitial myocardial pH.
Intramyocardial pH was assessed as a potential marker for clinical evaluation and treatment of acute rejection following cardiac transplantation. Fifteen cats underwent forty operative procedures. Following intra-abdominal heterotopic heart transplantation, serial laparotomies were performed in the early (days 0 to 2), intermediate (days 5 to 7), and late (days 7 to 16) postoperative periods. Rejection was assessed by serial clinical examinations, ECG analyses, B-mode echocardiography, histological and ultrastructural analyses, and measurements of interstitial myocardial pH. Intramyocardial pH was measured by a new miniature (0.6 X 3.0 mm) fiberoptic pH transducer. At confirmed rejection, concomitant laparotomy and thoracotomy were performed and pH sensors were implanted in both native (anatomical) and graft hearts. Nine animals at rejection were given methylprednisolone and changes in graft and native heart pH were measured. The pH during absence of rejection, mild acute rejection, and severe acute rejection averaged 7.430 +/- 0.019, 7.233 +/- 0.040 (p less than .02), and 6.860 +/- 0.066 (p less than .02), respectively (mean +/- standard error of the mean). A progressive decline in pH was noted in each heart. In animals receiving steroids, graft heart pH increased over 90 minutes from 6.852 +/- 0.065 to 7.043 +/- 0.077 (p less than .05). Although pH decline may be secondary to either inflammatory or ischemic etiology, histological and ultrastructural analyses demonstrate a predominant inflammatory response with progressive mononuclear cell infiltration, interstitial edema, vascular wall edema, infiltration by polymorphonuclear neutrophil leukocytes, vacuolation of sarcoplasmic reticulum, and disarray of myocytes associated with falling pH. Degree of pH change correlated closely with degree of histological rejection, presence of ECG voltage decline, and change in wall thickness by ultrasound.
Acute Disease↗
Thermal effects of laser and electrical discharge on cardiovascular tissue: implications for coronary artery recanalization and endocardial ablation.
To determine the thermal responses of cardiovascular tissues to laser and electrical ablation, and to characterize the effects of different superfusing media and temperatures on target tissue temperatures and resulting extent of tissue injury, 184 laser and 15 electrical discharges were delivered to segments of human and canine aorta and canine ventricular endocardium. Tissue temperatures were measured 2 mm from the point of contact of laser fiber tip and tissue. When superfusing media consisted of whole blood or plasma at room temperature, a standard 40 J laser discharge caused peak arterial temperatures to rise 29.2 +/- 1.6 degrees C and 30 +/- 1.4 degrees C, respectively; however, tissue cooling was significantly slower in blood than in plasma. When saline solution was superfused, tissue temperatures rose by 11.4 +/- 2.2 degrees C, and tissue cooling occurred significantly faster than with either plasma or blood. The dimensions of the resulting aortic lesions were larger when blood (1.69 +/- 0.26 mm) was superfused than when plasma (1.39 +/- 0.04 mm) or saline (0.77 +/- 0.13 mm) was superfused (p less than 0.0001). Similar findings were observed with ventricular endocardium using blood or saline as the superfusing medium. In arterial tissue, superfusion with cold blood or saline solution resulted in lower peak temperature elevations (22 +/- 3.8 degrees C and 13.5 +/- 1.3 degrees C, respectively) and faster tissue cooling after laser discharge. Corresponding aortic lesion sizes were significantly smaller (1.4 +/- 0.03 and 0.5 +/- 0.02 mm, respectively) than when blood or saline medium was superfused at room temperature (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Transcatheter ablation: comparison between laser photoablation and electrode shock ablation in the dog.
To characterize and compare the effects of transcatheter laser and electrical energy on endocardium, 35 laser pulses were delivered to the endocardial surfaces of isolated canine hearts, and 33 endocardial lesions were produced by the transarterial delivery of either transcatheter laser irradiation or electrical shock in closed-chest anesthetized dogs. Laser-induced lesion dimensions in vitro and in vivo increased with increased total dose of energy; however, the lesions produced in vivo were different in morphology and were significantly larger than lesions produced by equivalent doses of energy delivered in vitro (p less than .05). Endocardial lesions produced in vivo by laser at 40 and 80 J (7.9 X 5.4 X 6.6 and 7.9 X 5.1 X 7.5 mm) were comparable in gross morphology and size to those produced by electrical shock at 100 and 200 J (8.5 X 6.6 X 6.6 and 10.0 X 8.5 X 8.2 mm, respectively; p = NS), but transcatheter electrode shock produced significantly more ventricular tachycardia (p less than .003), premature ventricular beats in the 7 min after energy discharge (p less than .05), and wall motion abnormality (p less than .005). Transcatheter laser photoablation can create controlled endocardial lesions with less energy and fewer deleterious effects than transcatheter electrode shock.
Animals↗
The relative influence of arterial pressure versus intraoperative distention on lipid accumulation in primate vein bypass grafts.
Atherosclerotic degeneration has been well documented to be the limiting factor for long-term function of aortacoronary vein bypass grafts. Injury, including that induced by pressure distention in preparation for grafting, is thought to play a role in this degeneration. Injury can be minimized by limiting the distending pressure, but vein grafts are chronically subjected to arterial pressures that far exceed native venous pressure. We evaluated the relative influence of arterial pressure and of higher pressure of distention on cholesterol and apolipoprotein-B accumulation by grafts in our established animal model of graft atherogenesis. Grafts were interposed in the femoral arteries of eight normolipemic stump-tailed macaque monkeys. Before insertion, each vein was distended at 125 mm Hg (arterial pressure) for 1 minute with autologous blood, followed by distention of one half of the vein at 350 mm Hg for 1 additional minute. Grafts and ungrafted control vein were removed 3 months later. Cholesterol concentration in grafts distended at 125 mm Hg was 213% (p less than 0.01) and apolipoprotein-B concentration was 430% (p less than 0.001) of that in ungrafted control veins, whereas in grafts distended at 350 mm Hg cholesterol was 250% (p less than 0.01) and apolipoprotein-B was 925% (p less than 0.001) of the control concentrations. Although morphologic differences between the two groups of grafts were less profound than biochemical differences, foam cells were observed more frequently in grafts distended at 350 mm Hg than in those distended at 125 mm Hg. These data demonstrate that chronic exposure to arterial pressure has a significant effect on graft cholesterol that is proportionally greater than that caused by intraoperative distention at moderate pressure. Nevertheless, the detrimental effects of excessive distending pressures should not be ignored.
Animals↗
Physiological cardiac pacing.
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Arrhythmias, Cardiac↗