Biomedical subjects

W Y Lew

Publications and source records attributed to W Y Lew.

At least 19 recordsLinked to original sources

PubMed1999

Effects of mutant and antisense RNA of phospholamban on SR Ca(2+)-ATPase activity and cardiac myocyte contractility.

BACKGROUND: The delayed cardiac relaxation in failing hearts has been attributed to a reduced activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2). Phospholamban (PLB) inhibits SERCA2 activity and is therefore a potential target to improve the cardiac performance in heart failure. METHODS AND RESULTS: Mutants of PLB (Adv/mPLB) or antisense RNA of PLB (Adv/asPLB) was expressed in cardiac myocytes by recombinant adenovirus, and their effects on SERCA2 activity and myocyte contractility were studied. One mPLB, K3E/R14E, pentamerized with endogenous PLB in neonatal myocytes and resulted in a 45% increase in the affinity of SERCA2 for Ca(2+) and 27% faster diastolic Ca(2+) decline as determined by SR (45)Ca uptake assays and by indo 1-facilitated Ca(2+) transient measurement, respectively. Edge-detection analysis of adult myocyte contractility showed a 74% increase in fractional shortening, accompanied by 115% increase in velocity of relengthening and 25% decrease in time to half-maximal relengthening. In parallel, infection of neonatal cardiac myocytes by Adv/asPLB decreased the endogenous PLB level by 54%, which was associated with a 35% increase in Ca(2+) affinity of SERCA2 and 21% faster diastolic Ca(2+) decline. However, in adult cardiac myocytes, Adv/asPLB failed to significantly alter the endogenous PLB level, the SERCA2 activity, or most of the contractile parameters. CONCLUSIONS: K3E/R14E is a dominant negative mutant of PLB that disrupts the structural integrity and function of the endogenous PLB and consequently enhances SERCA2 activity and myocyte contractility. In neonatal myocytes, the decrease in steady-state abundance of PLB by asPLB also leads to increased SERCA2 activity.

Adenoviridae↗

PubMed1999

Phospholamban-to-SERCA2 ratio controls the force-frequency relationship.

The force-frequency relationship (FFR) describes the frequency-dependent potentiation of cardiac contractility. The interaction of the sarcoplasmic reticulum Ca2+-adenosinetriphosphatase (SERCA2) with its inhibitory protein phospholamban (PLB) might be involved in the control of the FFR. The FFR was analyzed in two systems in which the PLB-to-SERCA2 ratio was modulated. Adult rabbit cardiac myocytes were transduced with adenovirus encoding for SERCA2, PLB, and beta-galactosidase (control). After 3 days, the relative PLB/SERCA2 values were significantly different between groups (SERCA2, 0.5; control, 1.0; PLB, 4.5). SERCA2 overexpression shortened relaxation by 23% relative to control, whereas PLB prolonged relaxation by 39% and reduced contractility by 47% (0.1 Hz). When the stimulation frequency was increased to 1.5 Hz, myocyte contractility was increased by 30% in control myocytes. PLB-overexpressing myocytes showed an augmented positive FFR (+78%), whereas SERCA2-transduced myocytes displayed a negative FFR (-15%). A more negative FFR was also found in papillary muscles from SERCA2 transgenic mice. These findings demonstrate that the ratio of phospholamban to SERCA2 is an important component in the control of the FFR.

Animals↗

PubMed1999

Angiotensin II exacerbates lipopolysaccharide-induced contractile depression in rabbit cardiac myocytes.

In sepsis, lipopolysaccharide (LPS) depresses cardiac function by inducing production of nitric oxide (NO) and its second messenger cGMP. LPS also stimulates ANG II production. We hypothesized that ANG II modulates the cardiac response to LPS. Adult rabbit cardiac myocytes incubated with LPS (10 ng/ml) had increased cardiac cGMP after 6 h (but not within 1 h) [527 +/- 43 vs. 316 +/- 27 (SE) fmol/mg protein in controls, n = 16 each group, P < 0.05]. This was associated with depressed cell shortening with no alterations in Ca2+ transients (indo 1 fluorescence), indicating a decreased myofilament responsiveness to Ca2+. ANG II (100 nM) alone had no effect. However, ANG II with LPS produced higher cGMP levels (1,025 +/- 113 fmol/mg protein, n = 16, P < 0.05 vs. LPS alone), more severe contractile depression, impaired Ca2+ handling, and decreased mitochondrial activity (MTS assay). We conclude that ANG II and LPS have synergistic effects on the activation of NO-cGMP pathways to induce dose-dependent impairments in excitation-contraction coupling in cardiac myocytes.

Angiotensin II↗

PubMed1998

Cellular mechanisms for the slow phase of the Frank-Starling response.

Following a step increase in sarcomere length, isometric cardiac muscle tension increases instantaneously by the Frank-Starling mechanism. In isolated papillary muscle and myocytes, there is an additional significant rise in developed tension over the following 15 min due to an unknown mechanism. This slow change in tension could not be explained by mechanical heterogeneity of the muscle preparations or by an increase in myofilament sensitivity to Ca2+. The slow change in tension was not dependent on sarcoplasmic reticulum Ca2+ loading assessed with rapid cooling contractures, and was not significantly altered by sarcoplasmic reticulum Ca2+ depletion (ryanodine) or inhibition of sarcoplasmic reticulum Ca2+ reuptake (cyclopiazonic acid). We used the Luo-Rudy ionic model of the ventricular myocyte together with a model of the length-dependent myofilament activation by Ca2+ to examine the effects of step changes in the parameters of sarcolemmal ion fluxes as possible mechanisms for the slow change in stress. The slow increase in tension was simulated by step changes in the Na+-K+ pump or Na+ leak currents, suggesting that the slow change in stress may be caused by length induced changes in Na+ fluxes. The model also predicted a slow increase in the magnitude of the initial repolarization during phase 1 of the action potential. The combination of experimental and computational models used in this investigation represents a valuable technique in elucidating the cellular mechanisms of fundamental processes in cardiac excitation-contraction coupling.

Animals↗

PubMed1998

Mechanisms of length history-dependent tension in an ionic model of the cardiac myocyte.

The ionic model of the ventricular myocyte developed by Luo and Rudy (Circ. Res. 74: 1071-1096, 1994) was used to investigate potential mechanisms of the slow changes in stress (SCS) that follow step changes in muscle length. A step change in myofilament sensitivity alone caused an immediate increase in active tension, but no SCS. The effects of additional step changes in the parameters of sarcolemmal ion fluxes were examined for each ion flux in the model. Changes in the coefficients of Ca2+ or K+ channels did not produce SCS. SCS was produced by step changes in parameters of the Na(+)-K+ pump or the Na+ leak current. This simulated mechanism was mediated through a slow increase in intracellular Na+ concentration and a resulting increase in systolic Ca2+ entry through the Na+/Ca2+ exchanger. The model reproduced the effects of several experimental interventions such as sarcoplasmic reticulum Ca2+ depletion, "diastolic" length changes, and changes in extracellular Ca2+. Thus SCS in cardiac muscle may be caused by length-induced changes in sarcolemmal Na+ fluxes.

Action Potentials↗

PubMed1997

Depyrogenation of digestive enzymes reduces lipopolysaccharide tolerance in isolated cardiac myocytes.

The isolated myocyte is useful for examining the direct cardiac effects of substances such as lipopolysaccharide (LPS) and cytokines. However, the digestive enzymes used for standard cell isolation procedures are contaminated by several hundred ng/ml LPS. We depyrogenated the digestive enzymes with a series of Triton X-114 and Polymyxin B washes to remove 99.7-99.9% of the LPS. This lowered LPS contamination levels from 100-300 ng/ml to 0.15-0.70 ng/ml, while maintaining good quality cell isolations from the left ventricle of New Zealand white rabbits. We evaluated whether brief exposure to LPS contaminant levels, as occur during standard cell isolations, induces LPS tolerance. Cardiac myocytes (isolated with depyrogenated enzymes) were pre-exposed to 100 ng/ml LPS for 1 h, washed, then exposed to a challenge dose with 100 ng/ml LPS. The LPS challenge dose induced a time-dependent decrease in cell shortening over 6 h in myocytes without pre-exposure, but not in myocytes pre-exposed to an earlier dose of LPS. We examined whether LPS tolerance develops in myocytes isolated with untreated enzymes, compared with depyrogenated enzymes. In myocytes isolated with untreated enzymes, there was a significant decrease in cell shortening after 6 h exposure to 1000-10 000 ng/ml LPS. In myocytes isolated with depyrogenated enzymes, it required only 5-50 ng/ml LPS to induce a comparable cardiac depression. We conclude that brief exposure to LPS contaminant levels, which occur with standard cell isolation procedures, induces a hyporesponsiveness or tolerance to subsequent doses of LPS in isolated cardiac myocytes.

Animals↗

PubMed1997

Lipopolysaccharide induces cell shrinkage in rabbit ventricular cardiac myocytes.

The effects of 10 ng/ml of lipopolysaccharide (LPS) on cell volume were examined in rabbit left ventricular myocytes. The myocytes were isolated with depyrogenated digestive enzymes (< 0.7 ng/ml of LPS) to minimize tolerance. Myocyte cross-sectional area (CSA) did not change after 1 h of LPS. However after 8 h, the CSA decreased to 0.93 +/- 0.01 (SE) of the baseline CSA (time = 0) in 19 LPS-exposed myocytes compared with 1.00 +/- 0.01 in 13 control myocytes (P = 0.0015). LPS-induced cell shrinkage was completely blocked by coincubation with 1 mM N-monomethyl-L-arginine, indicating a nitric oxide-mediated mechanism. Cardiac guanosine 3',5'-cyclic monophosphate (cGMP) did not change after 1 h but increased 6 h after LPS (548 +/- 31 vs. 312 +/- 20 fmol/mg protein in control cells; P < 0.05). After 8 h, bumetanide (10 microM for 30 min), a Na+/K+/2Cl- cotransport inhibitor, decreased the CSA in 15 control myocytes to 0.92 +/- 0.02 of the baseline CSA. However, in 19 myocytes with a CSA of 0.93 +/- 0.01 of baseline after 8 h of LPS, the addition of bumetanide caused no additional cell shrinkage. We conclude that low levels of LPS increase cardiac cGMP to inhibit Na+/K+/2Cl- cotransport, causing significant cell shrinkage in cardiac myocytes.

Animals↗

PubMed1997

Endothelin-1 ameliorates contractile depression by lipopolysaccharide in cardiac myocytes.

Lipopolysaccharide (LPS) induces cardiac depression by activating nitric oxide pathways to increase guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of nitric oxide. Endothelin-1 (ET-1) may interact with nitric oxide pathways. We hypothesized that ET-1 modulates LPS-induced contractile depression in cardiac myocytes. Adult rabbit cardiac myocytes exposed to LPS (10 ng/ml) developed decreased cell shortening after 6 h, with an increase in cardiac cGMP levels [606 +/- 36 (SE) fmol/mg protein] compared with control myocytes (360 +/- 26 fmol/mg protein, P < 0.05). LPS effects were completely blocked by coincubation with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (1 mM). Coincubation with ET-1 (10 nM) attenuated the contractile depression and increase in cGMP with LPS (482 +/- 28 fmol/mg protein, P < 0.05 vs. LPS alone). ET-1 alone did not alter cGMP levels (350 +/- 30 fmol/mg protein). ET-1 effects on contractile function were blocked by BQ-123 (10 microM), a selective ET-1 type A receptor antagonist. We conclude that ET-1 ameliorates LPS-induced contractile depression in cardiac myocytes by attenuating LPS effects on nitric oxide-cGMP pathways.

Animals↗

PubMed1997

Lipopolysaccharide depresses cardiac contractility and beta-adrenergic contractile response by decreasing myofilament response to Ca2+ in cardiac myocytes.

Lipopolysaccharide (LPS) plays a key role in the pathogenesis of sepsis. Cardiac function and the inotropic response to beta-adrenergic stimulation are impaired in sepsis. We hypothesized that LPS, in clinically relevant levels (1 ng/mL), directly depresses contractility and beta-adrenergic responses in cardiac myocytes. Cardiac myocytes were isolated from the left ventricle of adult rabbits using digestive enzymes (collagenase and protease). We depyrogenated the enzymes (LPS contamination lowered from 100 to 300 ng/mL to < 0.7 ng/mL) to minimize development of LPS tolerance during cell isolation. After 6 hours of incubation with 1 ng/mL LPS, there was a decrease in the extent of active cell shortening with no change in Ca2+ transients (measured with indo 1 fluorescence), indicating decreased myofilament responsiveness to Ca2+. This was related to NO pathways, since cGMP (a second messenger of NO) increased in cardiac myocytes and LPS effects were completely reversed with a 1 mmol/L NG-monomethyl-L-arginine (L-NMMA, a NO synthase inhibitor). LPS did not alter the intracellular Ca2+ response to beta-adrenergic stimulation with isoproterenol but attenuated the contractile response (maximal cell shortening, 15.5 +/- 1.0% versus 23.3 +/- 1.1% in control myocytes; P < .001). LPS attenuation of the contractile response to isoproterenol was restored completely by L-NMMA and almost completely restored (to 86% of the control response) by an inhibitor of cGMP-dependent protein kinase. We conclude that LPS depresses cardiac contractility and the contractile response to beta-adrenergic stimulation by a NO-cGMP-mediated decrease in myofilament responsiveness to Ca2+. The direct effects of low levels of LPS on cardiac myocytes may contribute to cardiac depression and hemodynamic decompensation during sepsis.

Actin Cytoskeleton↗

PubMed1996

Endotoxin-induced cardiac depression is associated with decreased cardiac dihydropyridine receptors in rabbits.

Endotoxin depresses left ventricular (LV) contractility independently of alterations in loading conditions, acidosis, or hypoxia (Hung and Lew, 1993a). We evaluated if endotoxin-induced LV depression is associated with a decrease in functional L-type calcium channels, as reflected by the number of dihydropyridine receptors measured by [3H]-PN200-110 binding. New Zealand white rabbits were instrumented with sonomicrometers to measure the end-systolic pressure-volume relationship after i.v. saline (group 1, n = 6), 5 micrograms/kg endotoxin (group II, n = 6), or 10 micrograms/kg endotoxin (group III, n = 6). The end-systolic volume (ESV) measured at a matched end-systolic pressure did not change significantly over 6 h in group I (ESV changed by < 5 +/- 2% S.E.) and group II (ESV changed by < 3 +/- 2%), but increased markedly in group III (ESV increased 70 +/- 24%, P < 0.05), indicating LV systolic depression. We measured [3H]-PN200-110 binding in crude membrane homogenates from the left ventricle. There was a dose-dependent decrease in Bmax: 75 +/- 5 fmol/mg protein in group I, 62 +/- 3 fmol/mg in group II, and 56 +/- 5 fmol/mg in group III (P = 0.02 by ANOVA). Since the majority of dihydropyridine receptors are functional L-type calcium channels in rabbits (Lew et al., 1991), we conclude that a decreased number of dihydropyridine receptors contributes to endotoxin-induced LV depression.

Animals↗

PubMed1996

Serum tumor necrosis factor-alpha does not mediate endotoxin-induced myocardial depression in rabbits.

Tumor necrosis factor-alpha (TNF-alpha) is an endogenous mediator for several effects of endotoxin. To evaluate whether TNF-alpha mediates endotoxin-induced left ventricular (LV) dysfunction, we measured LV function (sonomicrometers) and serum TNF-alpha (cytolytic assay) in anesthetized rabbits given endotoxin (100 micrograms/kg iv). In the control group (n = 8), systolic depression (defined by a > 10% increase in end-systolic volume at a matched end-systolic pressure) developed in four rabbits and diastolic dilation (> 10% increase in end-diastolic volume at a matched end-diastolic pressure) developed in three rabbits. Neither the increase in end-systolic volume nor the increase in end-diastolic volume correlated with the increase in TNF-alpha, which reached a peak of 2,875 +/- 762 U/ml. In a second group of rabbits (n = 7), a goat polyclonal anti-rabbit antibody to TNF-alpha was given 30-60 min before endotoxin. Anti-TNF-alpha antibody alone did not alter LV function. Although the TNF-alpha response to endotoxin was effectively blunted (peak TNF-alpha remained < 100 U/ml), all seven rabbits developed systolic depression (P = 0.08 compared with control group) and diastolic dilation (P = 0.03). We conclude that serum TNF-alpha does not mediate endotoxin-induced LV systolic depression or diastolic dilation in this model.

Animals↗

PubMed1995

Active force in rabbit ventricular myocytes.

Although recent technical advances have established the feasibility of force measurements in single cardiac myocytes, the physiological relevance of this model has not been fully evaluated. We measured active force and sarcomere length in single rabbit left ventricular myocytes and compared their physiological responses to changes in stimulus interval, calcium concentration and sarcomere length to results from isolated papillary muscles. Myocytes were attached to two poly-L-lysine-coated glass plates and force was measured with a capacitive force transducer (Cambridge 406A). Stable recordings from a continuously contracting myocyte could be maintained for over 1 h. In five cells, increasing stimulus interval significantly decreased active force development. This force-stimulus interval relation was similar to that obtained from papillary muscles. In one cell, we obtained a force-length relation that was similar to force-length relations from multicellular preparations. Active stresses (active forces normalized by cross-sectional area) were of similar magnitude when comparing myocytes (at slack length) and papillary muscles (at 85% of Lmax). These results confirm the physiological relevance of force measurements obtained from intact mammalian cardiac myocytes.

Analysis of Variance↗

PubMed1995

Asynchrony and ryanodine modulate load-dependent relaxation in the canine left ventricle.

Load-dependent relaxation was studied in six anesthetized dogs by inflating an intra-aortic balloon to increase peak left ventricular (LV) pressure by 1-20 mmHg within a single cardiac cycle. A series of timed and graded pressure loads was produced by inflating the balloon either during diastole (early loads) or midsystole (midsystolic pressure loads). The rate of LV pressure fall was measured with the time constant (tau). There was a significant increase in tau with 63 midsystolic pressure load [tau increased 1.4 +/- 0.1% (SE)/mmHg increase in peak LV pressure] but not with 67 early pressure loads (-0.5 +/- 0.1%/mmHg). This difference remained with LV pacing-induced asynchrony (tau increased 1.8 +/- 0.1%/mmHg with 54 midsystolic pressure loads compared with -0.2 +/- 0.1%/mmHg with 56 early pressure loads) and after 5 micrograms/kg of intravenous ryanodine (tau increased 1.0 +/- 0.2%/mmHg with 58 midsystolic pressure loads compared with -0.7 +/- 0.1%/mmHg with 59 early pressure loads). When compared with control, asynchrony significantly augmented and ryanodine significantly attenuated the effects of midsystolic pressure loads. In conclusion, asynchrony and ryanodine modulate the extent of load-dependent relaxation in the intact left ventricle.

Animals↗

PubMed1995

Endotoxin-induced left ventricular depression is blocked by nitrogen mustard or dimethylthiourea in rabbits.

We examined endotoxin-induced myocardial depression in 31 anesthetized rabbits using left ventricular end-systolic and end-diastolic pressure-volume relationships (sonomicrometers). In the control group, endotoxin (100 micrograms/kg iv) induced systolic depression (> 10% increase in end-systolic volume at matched end-systolic pressure) in 9 of 16 and diastolic dilation (> 10% increase in end-diastolic volume at matched end-diastolic pressure) in 8 of 16 rabbits within 7 h, unrelated to hypotension, acidosis, or hypoxia. Seven rabbits were pretreated with nitrogen mustard (1-2 mg/kg iv 4 and 2 days before) to decrease circulating neutrophils and monocytes by 98%. Endotoxin did not induce systolic depression in any rabbit (P = 0.01 compared with control), and diastolic dilation developed in one rabbit (P = 0.12). In eight rabbits pretreated with dimethylthiourea (DMTU; 500 mg/kg iv 30 min before), an intracellular free radical scavenger, systolic depression developed in one (P = 0.05) and diastolic dilation in five (P = 0.44). We conclude that cells inhibited by nitrogen mustard (e.g., neutrophils, monocytes, or macrophages) mediate endotoxin-induced left ventricular systolic depression. DMTU inhibited endotoxin-induced systolic but not diastolic dysfunction.

Animals↗

PubMed1995

Sarcoplasmic reticulum in cardiac length-dependent activation in rabbits.

After a step increase in length of rabbit right ventricular papillary muscles, active stress increased immediately followed by a further slow increase in stress over 15-20 min. We studied the contribution of the sarcoplasmic reticulum (SR) to the slow change in stress (SCS) after changing muscle length from 85 to 95% of length at which active force development was maximal. SCS amounted to 32.5 +/- 12.2% mean +/- SD, n = 19) of the total increase in active stress. This was associated with a 13.2 +/- 8.7% increase in calcium content of the SR as estimated with rapid cooling contractures (P < 0.0001, n = 19). However, SCS was not dependent on SR calcium content. There was no significant attenuation in SCS after SR calcium depletion with ryanodine (n = 6), SR Ca(2+)-adenosinetriphosphatase inhibition with cyclopiazonic acid (n = 6), or combined treatment with ryanodine and cyclopiazonic acid (n = 3). We conclude that, in the rabbit, SR calcium content increases slowly after a step increase in cardiac muscle length but the slow changes in active stress are not dependent on the sarcoplasmic reticulum.

Animals↗

PubMed1994

Cardiac myocyte function and left ventricular strains after brief ischemia and reperfusion in rabbits.

BACKGROUND: After a brief episode of ischemia, myocardial function may be depressed for prolonged periods despite reperfusion. The mechanisms of postischemic dysfunction differ depending on the experimental model. Regional ischemia and reperfusion in the intact animal provide a clinically relevant model, but experimental variables are difficult to control. Experimental conditions can be well controlled in isolated cardiac muscle and myocyte preparations, but these models are limited by the assumptions used to mimic ischemia and reperfusion. This study combines the unique advantages of both preparations. We characterized in vivo alterations in regional two-dimensional finite strains with ischemia and reperfusion produced in the intact animal, then isolated cardiac myocytes from the region with postischemic dysfunction to characterize in vitro function of postischemic myocytes. METHODS AND RESULTS: In seven anesthetized rabbits, three piezoelectric crystals were inserted in a triangular array to measure two-dimensional finite strains around the large coronary artery in the left ventricular anterior free wall. After 15 minutes of ischemia and reperfusion, strains were depressed at a stable level approximately 30% to 40% below control values between 1 and 6 hours after reperfusion. The direction of maximal shortening deformations was midway between circumferential and longitudinal directions during control and did not shift after reperfusion. In a second group of five rabbits, cardiac myocytes were isolated from the region with postischemic dysfunction after 15 minutes of ischemia and 45 minutes of reperfusion. We compared in vitro function in 45 postischemic myocytes with 48 cardiac myocytes isolated from five normal rabbits. Each rabbit (postischemic and control) contributed 9 +/- 1 (SD) myocytes to the study. All myocytes were studied within 1 hour after myocyte isolation (approximately 3 to 5 hours after reperfusion for postischemic myocytes). Myocytes were stimulated at 0.5 Hz and perfused with 2 mmol/L [Ca2+] Tyrode's solution to measure unloaded cell shortening. There was significantly less shortening in postischemic myocytes (12.4 +/- 2.1%) than control myocytes (16.2 +/- 1.2%). Maximal cell length (Lmax) was significantly longer in postischemic (134 +/- 7 microns) than control myocytes (122 +/- 7 microns), as was minimum cell length (Lmin) (118 +/- 8 versus 103 +/- 9 microns, respectively). The duration of shortening (time from stimulation to Lmin) was significantly shorter in postischemic (279 +/- 56 milliseconds) than control myocytes (405 +/- 44 milliseconds). Peak rates of cell shortening (-dL/dt) and lengthening (+dL/dt) did not differ. CONCLUSIONS: In rabbits, 15 minutes of ischemia produced a stable depression in finite strains for 1 to 6 hours after reperfusion, with shortening deformations reduced by approximately 30% to 40% without a shift in direction. Cardiac myocytes isolated from postischemic myocardium display functional impairments in vitro similar to those measured in vivo, with an approximately 25% reduction in unloaded myocyte shortening and decreased contraction duration. This indicates that ischemia and reperfusion induce intrinsic impairments in contractility independently of external loading conditions. This model may be useful for examining cellular mechanisms of postischemic myocardial dysfunction.

Animals↗

PubMed1993

Spindle cell lipoma of the breast: a case report and literature review.

Fine-needle aspiration cytology (FNA) was performed on a breast lump in a 66-year-old female, clinically thought to be a carcinoma. The cytological findings were reported as suspicious of malignancy. Subsequent histological examination showed a tumour macroscopically and microscopically identical with six other cases previously described as benign spindle cell tumours of the breast. This report highlights yet another diagnostic pitfall in FNA cytology of the breast. The presence of floret cells in this case has not been previously reported but supports the concept that this lesion is the same as a spindle cell lipoma, from which it is virtually indistinguishable on light microscopy. The lesion affects both male and female breast, is predominantly single but may be multiple, and follows a benign course. Local excision is curative.

Aged↗

PubMed1993

Temporal sequence of endotoxin-induced systolic and diastolic myocardial depression in rabbits.

Twelve anesthetized rabbits received endotoxin (175 +/- 38 micrograms/kg i.v., mean +/- SD) to evaluate the temporal sequence of alterations in left ventricular (LV) function. LV volume was calculated from LV minor- and long-axis diameters, and wall thickness was measured with sonomicrometers. Hypotension, acidosis, and hypoxia were immediately corrected to eliminate these causes of myocardial depression. LV dilation developed early (1.2 +/- 0.5 h) with a significant (21 +/- 23%) increase in end-diastolic volume measured at a LV end-diastolic pressure of 5 +/- 6 mmHg. The LV stiffness did not change, and the LV dilation did not progressively worsen. Significant systolic depression developed later (2.8 +/- 1.0 h) with a 32 +/- 22% increase in end-systolic volume measured at a LV end-systolic pressure of 69 +/- 9 mmHg. The late preterminal phase (4.1 +/- 0.8 h) was characterized by a progressive increase in end-systolic volume (73 +/- 41% above control) and a significant (53 +/- 34%) increase in tau, the time constant of LV pressure fall. Diastolic abnormalities (LV dilation and increased tau) were not attributable to depressed contractility or altered hemodynamics. We conclude that endotoxin impairs systolic and diastolic LV function with distinct differences in time course. This suggests that contractility, relaxation, and passive LV properties are impaired by different endotoxin-mediated pathways and/or have different sensitivities to endotoxin.

Animals↗