Activation of the coagulation system in women with mitral stenosis and sinus rhythm.
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Adult↗
Biomedical subjects
M Lesch
Publications and source records attributed to M Lesch.
Mitochondrial abnormalities in myocardium of dogs with chronic heart failure.
The number, size and structural integrity of mitochondria (MIT) were evaluated in the myocardium of 12 dogs with chronic heart failure (CHF) produced by sequential intracoronary microembolizations (EMB). Tissue specimens for transmission electron microscopy were obtained from the left ventricular (LV) free wall, septum and right ventricular free wall 3 to 4 months after the last EMB. Comparisons were made with samples obtained from identical sites in 9 control dogs. In dogs with CHF, LV ejection fraction decreased from 61 +/- 1% at baseline (prior to EMB) to 22 +/- 2% 3 to 4 months after the last EMB (P < 0.01) while plasma norepinephrine (PNE) concentration increased from 364 +/- 12 pg/ml to 837 +/- 150 pg/ml (P < 0.01). The number of MIT in an area of 100 square sarcomeres was greater in CHF dogs compared to controls (92 +/- 5 vs 64 +/- 2) (P < 0.001); whereas the average size of MIT was smaller (0.53 +/- 0.03 vs. 0.78 +/- 0.04 microm2) (P < 0.001). Injury ranging in severity from matrix depletion to myelinization and membrane disruption was present in 27 +/- 4% of MIT of CHF dogs compared to only 3 +/- 1% of MIT of controls (P < 0.001). MIT abnormalities were present to the same extent in all three regions of the heart. The severity of MIT injury, assessed on the basis of an injury index, was significantly higher in CHF dogs with PNE > or = 600 pg/ml (0.64 +/- 0.07) compared to CHF dogs with PNE < 600 pg/ml (0.32 +/- 0.08) (P < 0.01). Among CHF dogs, the MIT injury index was linearly related to PNE concentration (r = 0.57, P < 0.05), LV ejection fraction (r = 0.57, P < 0.05) and LV end-diastolic pressure (r = 0.57, P < 0.05). These data indicate that profound MIT abnormalities are present in the myocardium of dogs with CHF and are related to PNE concentration and to the severity of LV dysfunction.
Animals↗
Phonological codes are used in integrating information across saccades in word identification and reading.
A major issue in reading is the extent to which phonological information is used in visual word perception. The present experiments demonstrated that phonological information acquired on 1 fixation from a word in the parafovea is used to help identify that word when it is later fixated. A homophone of a target word, when presented as a preview in the parafovea, facilitated processing of the target word seen on the next fixation more than a preview of a word matched with the homophone in visual similarity to the target word. This facilitation was observed both in the time to name an isolated target word and in the fixation time on the target word while silently reading a sentence; the preview was virtually never consciously identified in either task. Because the visual similarity of the preview to the target also plays a part in the facilitative effect on the preview, however, codes other than phonological codes are preserved across saccades.
Humans↗
Incidence and clinical significance of transient creatine kinase elevations and the diagnosis of non-Q wave myocardial infarction associated with coronary angioplasty.
To assess the incidence and clinical significance of elevated total plasma creatine kinase (CK) and MB isoenzyme fraction after apparently successful coronary angioplasty, a prospective study of 272 consecutive elective procedures was undertaken. Total CK (normal less than 100 IU/liter) and CK MB isoenzyme (normal less than 4%) were measured immediately after successful completion of the procedure and every 6 h for 24 h. All nonelective procedures and results not fulfilling all American Heart Association/American College of Cardiology Task Force guideline criteria for a successful result were excluded from analysis. Of the 272 elective procedures, 249 (92%) were successfully; abnormally elevated CK or CK MB serum levels, or both, were found in 38 (15%) of the successful outcomes. Three patterns of abnormal enzymes were identified: 15 patients with CK greater than or equal to 200 IU/liter and CK MB greater than or equal to 5% (group 1), 4 patients with CK greater than or equal to 200 IU/litter and CK MB less than or equal to 4% (group 2) and 19 patients with CK less than 200 IU/liter and CK MB greater than or equal to 5% (group 3). The three groups were distinguishable by the nature of the complications causing the enzyme release (in particular, the etiology and clinical manifestations). There were significantly more clinically apparent events in group 1 than in the other groups (13 of 15 versus 11 of 23, p less than 0.01) and more events associated with persistent electrocardiographic changes (p = 0.05) and chest pain (p less than 0.05). However, no clinically important sequelae were recognizable in any group at hospital discharge. Thus, abnormal cardiac serum enzyme release after apparently successful coronary angioplasty is 1) relatively common; 2) has many possible causes, including both minor complications and early reversibility of impending major complications; and 3) results in no permanent clinical sequelae.
Adult↗
Hypertrophy of isolated adult feline heart cells following beta-adrenergic-induced beating.
Catecholamine-induced beating and myocardial hypertrophy were evaluated in isolated adult feline cardiomyocytes maintained in culture for up to 30 days. Adult feline cardiomyocytes were used in this study because they displayed several unique characteristics that facilitated assessment of factors regulating cardiomyocyte hypertrophy in vitro. These characteristics included the following. 1) A single heart provides a high yield of 20-40 x 10(6) calcium-tolerant rod-shaped myocytes. 2) In culture, isolated adult feline cardiomyocytes maintain a stable population of differentiated myocytes that could be maintained without the dramatic loss of cell number, DNA content, or cell structure seen in adult rat cardiomyocyte cultures. 3) Cultured feline cardiomyocytes remained quiescent in culture unless appropriately stimulated to begin beating. 4) Sustained regular beating activity could be readily initiated up to 3 wk in culture by addition of 1 x 10(-5) M isoproterenol, other beta-adrenergic agonists, or agents known to elevate adenosine 3',5'-cyclic monophosphate. Beating could be maintained indefinitely in the presence of isoproterenol, but ceased upon removal of isoproterenol from the medium. Initiation of beating in 7-day-old cultures resulted in a profound restructuring of cardiomyocyte morphology compared with quiescent cultures. Beating heart cells were 66% larger with increased protein content, and they had significantly greater development of striated myofibrillar structure than quiescent myocytes at the same age in culture. We conclude that maintenance of an organized myofibrillar structure in cultured adult cardiac myocytes requires activation of intrinsic beating. Cardiomyocyte hypertrophy also develops following beta-adrenergic activation of beating, but it is unclear whether beating per se is required for inducing hypertrophy in isolated adult cardiomyocytes in vitro.
1-Methyl-3-isobutylxanthine↗
Morphometric evaluation of the contractile apparatus in primary cultures of rabbit cardiac myocytes.
Rabbit cardiac myocytes remain quiescent for more than 1 month when cultured at low density. During this period, myofibrillar volume density declines sixfold as myofibrils are disassembled or degraded and are replaced by actin and alpha-actinin-positive, myosin-negative structures that resemble myofibrils but lack thick filaments. Such structures are termed minute myofibrils. The length of the sarcomeres in these altered myofibrils is significantly less than length values obtained from freshly isolated heart cells or from contracting myocytes. A number of high density cultures develop spontaneous, synchronous contraction during the second week of culture. Myofibrillar volume density is stabilized when beating begins, and no further decline is observed in the succeeding weeks of culture. Such contracting myocytes display myofibrils typical of normal heart with no visible evidence of minute myofibrils. The volume density of the transverse tubular system also declines significantly in both beating and nonbeating myocytes, and its reduction appears more closely correlated with cell spreading than with beating per se. No quantitative changes in volume density of mitochondria or sarcoplasmic reticulum could be documented, but the structural organization of the sarcoplasmic reticulum seems to be greatly influenced by the physiological state of the heart cell. The present observations document the importance of mechanical factors in regulating the integrity of the contractile apparatus in cardiac myocytes and emphasize the utility of the cultured heart cell to directly investigate structure-function relations in individual myocytes.
Animals↗
Post myocardial infarction risk stratification: 1991 perspective.
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Humans↗
Comparative analysis of coronary angiographic morphology following restenosis.
The site and angiographic morphology of restenotic lesions following initially successful coronary angioplasty (PTCA) were compared to the original pre-PTCA stenosis and the immediate post-PTCA result. Forty-seven patients with 55 restenoses were analyzed. All patients with repeat angiography for recurrent ischemia 1 to 12 months post-PTCA documenting restenosis were included. Two orthogonal angiographic views best showing the initial lesion, immediate post-PTCA result, and the restenosis lesion, were selected and matched for angulation and cardiac cycle phase. Individual frames were traced and magnified. Restenosis lesions were similar in morphology to the pre-PTCA lesions in 29 of 55 (53%) and to the post-PTCA lesions in only 25 of 55 (46%) (p = NS). However, when the lesions with residual post-PTCA stenosis of greater than 25% luminal diameter narrowing were excluded from the analysis, the post-PTCA lesion morphology was similar to restenosis morphology in 25 of 30 (83%), whereas pre-PTCA and restenosis morphology was similar in only 15 of 30 (50%) lesions (p less than 0.01). Subgroup analysis revealed that when the restenosis occurred at the same site as the original lesion (group 1), post-PTCA morphology was significantly better (p = 0.01) in predicting restenosis morphology, 15 of 17 (88%), than was pre-PTCA morphology, 8 of 17 (47%). When the restenosis occurred greater than 5 mm distant from the original site (group 2), there was no significant difference in the association between pre-PTCA versus post-PTCA morphology and restenosis morphology. Thus restenosis morphology is usually dissimilar to the pre-PTCA stenosis morphology.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Balloon dilatation of symptomatic subacute intimal dissection presenting as restenosis.
Repeat percutaneous transluminal coronary angioplasty (PTCA) for subacute intimal dissections that produce symptoms after a period of 1 month or more is reluctantly performed for fear of extension and abrupt closure. Patients were identified with demonstrated intimal dissections (intimal contrast staining or frank intimal flap) at the time of initial PTCA who returned a mean of 17.5 weeks (range 9 to 50) later with recurrent chest pain. Repeat angiography revealed luminal compromise due to dissection rather than restenosis in 22 patients. Of these, 17 underwent repeat PTCA. Elective bypass surgery without attempted PTCA was chosen in the other 5 patients because of extensive intimal dissections (greater than 2 balloon lengths) or involvement of critical branches. In the group of 17 patients who had repeat PTCA, 10 (group 1) had a frank intimal flap without persistent contrast staining after the initial PTCA, while 7 (group 2) had both persistent staining and a flap. Successful PTCA was performed in 13 of these 17 patients (76%). There were 2 abrupt closures and 2 unsatisfactory luminal openings. One of these patients required urgent coronary bypass surgery. All 10 group 1 patients had successful repeat procedures versus only 3 of 7 group 2 patients (p = 0.01). The 3 patients with the greatest degree of luminal compromise immediately after the initial PTCA had failed repeat PTCA attempts. These results suggest that repeat PTCA for subacute intimal dissections presenting as restenosis can be successfully performed in selected patients, and that the presence of contrast staining and the degree of luminal compromise by the dissection may be predictive of outcome.
Aged↗
Amiodarone in patients with previous drug-mediated torsade de pointes. Long-term safety and efficacy.
The safety and efficacy of long-term amiodarone therapy were examined in 12 patients who had previously developed torsade de pointes as a complication of previous antiarrhythmic therapy. The QTc intervals were determined at the time of torsade de pointes (570 +/- 40 ms), after 7 days of amiodarone loading (490 +/- 70 ms), and after 3 months of chronic amiodarone administration (580 +/- 80 ms). Compared to a drug-free control period, QTc was significantly prolonged (P less than 0.05) at the time of torsade de pointes, after amiodarone loading, and after 3 months of amiodarone therapy. The QTc intervals at the time of torsade de pointes and after chronic amiodarone treatment were not significantly different. At 16 +/- 7 months of follow-up, all patients remained free of subsequent torsade de pointes, syncope, or sudden death. In addition, 5 of 6 patients with a history of sustained ventricular tachycardia remained free from arrhythmic recurrence despite persistence of inducible ventricular tachycardia during programmed stimulation studies done before discharge. We conclude that amiodarone can often be used safely and effectively in patients who have previously had an episode of drug-mediated torsade de pointes. Amiodarone-induced QTc prolongation, even when marked, does not predict recurrent torsade de pointes. These observations also suggest that the propensity for a drug to produce this arrhythmia is dependent on other electrophysiologic effects in addition to its ability to simply lengthen repolarization.
Adult↗
Angiographic coronary morphology in postinfarction angina.
To investigate the pathophysiologic relevance of angiographically irregular coronary stenoses in postinfarction angina (PIA), we analyzed the clinical course and coronary angiograms of 73 patients studied within 30 days of infarction. Coronary lesions were classified as smooth or irregular. Thirty-six patients had PIA (Group 1) and 37 had an uncomplicated course (Group 2). Irregular lesion(s) in patent infarct-related arteries were found in 77% of Group 1 vs. 24% of Group 2 patients (P less than 0.005). Irregular lesion(s) in any coronary artery were found in 58% of Group 1 versus 19% of Group 2 patients (P less than 0.002). Other univariate predictors of PIA included older age, hypertension, angina before myocardial infarct, lower peak creatine kinase, three-vessel disease, and higher modified Gensini score. Multivariate analysis ranked lesion irregularity as the strongest predictor of PIA. Our data suggests that ruptured atherosclerotic plaques may be important in the pathogenesis of PIA. It is possible that lesion irregularity is associated with an active process and/or a residual thrombus, which may be responsible for postinfarction angina.
Angina Pectoris↗
Protein synthesis and degradation during regression of thyroxine-induced cardiac hypertrophy.
To characterize changes in rates of protein turnover during regression of thyroxine-induced left ventricular hypertrophy, New Zealand White rabbits received intravenous thyroxine (200 micrograms/kg/d) for 9 days. Thyroxine was withheld, and in vivo protein turnover was evaluated on the 10th, 15th and 20th days. Animals not receiving thyroxine served as controls. Heart rate, blood pressure, and rate-pressure product were measured to correlate changes in cardiac work with protein turnover rates during the development and regression of hypertrophy. Thyroxine administration produced left ventricular hypertrophy by increasing the rate of protein synthesis (from 37.9 +/- 8.9 to 64.1 +/- 15.3 mg/day; P less than 0.05) to a greater degree than protein degradation (from 29.8 +/- 8.9 to 48.2 +/- 15.3 mg/day for control and thyroxine-treated animals, respectively; P less than 0.05). Cessation of thyroxine administration resulted in an eventual return of left ventricular mass to that of normally growing control animals. The major observation noted during thyroxine withdrawal was a return of protein synthetic rates to normal. Absolute rates of protein degradation remained elevated, whereas fractional protein degradative rates (i.e. the fraction of total protein degraded per day) were unchanged by the administration and withdrawal of thyroxine. These results indicate that suppression of both physiological and hormone-induced growth following cessation of thyroxine resulted from a decrease in cardiac protein synthetic rates and an increased rate of flux through the protein degradative pathway(s), while fractional rates of protein degradation (and thus average protein half-life) remained unchanged. The development and regression of thyroxine-induced hypertrophy correlated with thyroxine-mediated alterations in cardiac work.
Animals↗
Effects of cysteine protease inhibitors on rabbit cathepsin D maturation.
To examine the effects of cysteine protease inhibitors on cathepsin D intracellular transport, proteolytic processing, and secretion, primary cultures of rabbit cardiac fibroblasts were grown to confluence and exposed (24 h) to media containing leupeptin (0-10 mM), E 64 (0-10 mM), or chloroquine (0-50 microM). Cathepsin D maturation was then evaluated in pulse-chase biosynthetic labeling experiments. None of the three agents affected the charge modification of procathepsin D (Mr 53,000) within the Golgi apparatus. However, all three agents interfered with the subsequent proteolytic processing of procathepsin D isoforms to active cathepsin D (Mr 48,000). Both leupeptin and E 64 caused the intracellular accumulation of large amounts of a Mr 51,000 processing intermediate (not detectable in control fibroblasts). Trace amounts of this intermediate were also detected in chloroquine-treated cells. Combined activity assay and radioimmunoassay of cell lysates indicated that this partially processed form of cathepsin D possessed proteolytic activity. Whereas low medium concentrations of leupeptin (10-100 microM) but not E 64 appeared to stimulate procathepsin D secretion, neither agent appeared to have a major effect on the rate of proenzyme secretion at doses required to inhibit proteolytic maturation (1-10 mM). Furthermore, pretreatment of cells with 10 mM leupeptin appeared only to delay, but not prevent, the intracellular transport of cathepsin D to lysosomes. In contrast, chloroquine increased procathepsin D secretion in a dose-dependent manner, diverting the majority of newly synthesized procathepsin D from the intracellular protease(s) responsible for proteolytic processing. These results suggest that cysteine proteases participate in the proteolytic maturation of procathepsin D during the transport of newly synthesized enzyme to lysosomes, but cysteine protease-mediated proteolytic processing is not required for cathepsin D activation or lysosomal translocation.
Animals↗
Low heart rate variability and sudden cardiac death.
Our results indicate the following. 1. HRV is markedly depressed in inducible SCD survivors, a group at high risk of a subsequent episode of SCD. 2. Studies on patients who developed SCD during Holter monitoring indicate that HRV is depressed prior to SCD. 3. HRV is markedly depressed in inducible "asymptomatic ventricular ectopy" patients, with the degree of reduction paralleling that observed in inducible SCD survivors. In contrast, HRV of noninducible "asymptomatic ventricular ectopy" patients did not differ statistically from normal. 4. The findings provide additional evidence that cardiac parasympathetic function is depressed in patients prone to development of SCD and that altered autonomic function contributes to the development of electrical instability in such individuals. This accords with findings that such risk factors for sudden death as coronary artery disease, myocardial infarction, congestive failure, and hypertension all have been associated with reduced parasympathetic activity or attenuation of parasympathetically mediated reflexes. It is tempting to believe that diminished cardiac parasympathetic activity, perhaps by failing to counter excess sympathetic activity, contributes to SCD. 5. It may be inferred that HRV measurements have potential for serving as an independent predictor of inducibility in response to programmed ventricular stimulation and that they could represent a noninvasive screen for patients referred for evaluation of risk of SCD because of asymptomatic ventricular ectopy or other causes. In a larger sense, the data suggest that HRV measurements may provide information pertinent to the identification of individuals at increased risk of SCD that is independent of that provided by other risk factors. Given the human and economic stakes, further study is clearly warranted.
Death, Sudden↗
Programmed electrical stimulation to determine the need for antiarrhythmic therapy in patients with complex ventricular ectopic activity.
Patients with complex ventricular ectopy (greater than or equal to Lown grade III) and organic heart disease (OHD) are at increased risk for sudden cardiac death. Despite this fact, many such patients will remain free of symptomatic ventricular arrhythmia and thus are unnecessarily exposed to antiarrhythmic drug toxicity and arrhythmic potentiation. Programmed stimulation (PS) was used to direct therapy in 88 patients with asymptomatic ventricular ectopy complicating OHD. Thirty-three had inducible ventricular tachycardia (VT) and underwent treatment. The 55 patients without inducible VT (less than or equal to 6 repetitive ventricular responses) are the focus of this study. Three patients required treatment for persistent cardiac awareness. The remaining 52 have been followed for 22 months off antiarrhythmic drugs and all have remained free of subsequent major arrhythmic events. Therefore, in patients with complex ventricular ectopy, OHD, and absence of prior symptomatic ventricular arrhythmia, PS identifies patients at low risk for future disabling or life-threatening arrhythmic episodes and patients with absence of inducible VT can usually be managed without antiarrhythmic drugs.
Adult↗
Cardiac protein synthesis and degradation during thyroxine-induced left ventricular hypertrophy.
Assessment of cardiac protein metabolism in thyroxine-induced left ventricular hypertrophy requires measurements of both protein synthesis and degradation. In vivo protein degradative rates can best be measured as the difference between rates of protein synthesis and growth. Accordingly, rates of left ventricular protein accumulation were determined in growing rabbits, and in animals administered intravenous L-thyroxine (200 micrograms X kg-1 X day-1) for up to 15 days. Left ventricular protein fractional synthetic rates in euthyroid and thyroxine-treated rabbits were measured by continuous infusion of [3H]leucine (200 mu Ci/h X 6 h), and results converted to milligrams protein synthesized and degraded per day. Thyroxine administration produced left ventricular hypertrophy by increasing the rate of total protein synthesis (35.7 +/- 2.0, 71.0 +/- 7.0, and 62.6 +/- 4.0 mg of left ventricular protein synthesized per day for 0-, 3-, and 9-day, thyroxine-treated rabbits, respectively). However, the increased rate of total protein synthesis was greater than the measured rate of total protein accumulation (8.1 vs. 15.9 mg protein/day for euthyroid and thyroxine-treated animals), indicating that left ventricular protein degradative rates were increased as well. These studies indicate that accelerated proteolysis may be important in the molecular and architectural remodeling of the rapidly hypertrophying heart during thyrotoxicosis.
Animals↗
Lysosomal changes during thyroxine-induced left ventricular hypertrophy in rabbits.
By use of a combined morphologic, immunocytochemical, and biochemical approach, this study demonstrates the changes in the lysosomal vacuolar apparatus that accompany thyroxine-induced cardiac hypertrophy. During the 1st wk of thyroxine administration, immunocytochemical studies revealed a decline in cathepsin D within many myocytes, but an increase within interstitial cells. These events transpired with only a modest rise in cathepsin D activity. During the 2nd wk, cathepsin D reappeared within most myocytes and continued to increase within the interstitial population and was associated with a general rise in lysosomal enzyme activity. These data demonstrate the importance of employing both immunocytochemical and biochemical approaches to evaluate the status of the lysosomal vacuolar apparatus, and suggests that the lysosomal vacuolar apparatus may be involved in the apparent remodeling that attends rapid cardiac growth, which may represent one component of the enhanced rates of proteolysis documented in this model of cardiac hypertrophy.
Animals↗
Acquired cyanotic heart disease secondary to traumatic tricuspid regurgitation. Case report with a review of the literature.
A case of traumatic tricuspid insufficiency leading to right atrial enlargement and to a patent foramen ovale with right to left shunting is presented. Six similar cases previously reported are reviewed. The time course of clinical deterioration was related to the type of tricuspid valve damage incurred. Papillary muscle rupture led to surgery within a year, whereas less severe chordal damage allowed a more benign course that lasted from 10 to 25 years from the time of injury to the time of surgery. Surgical repair of the incompetent tricuspid valve and closure of the atrial septal defect led to significant improvement. The diagnostic usefulness of radionuclide imaging and echocardiography is demonstrated in this case. A mechanism of right to left interatrial shunting in the presence of normal pulmonary arterial pressures is proposed; this invokes phasic increases in right atrial pressure from tricuspid insufficiency and streaming of blood from the inferior vena cava into the left atrium across a patent foramen ovale in a manner that resembles conditions in the fetal circulation.
Adult↗