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Biomedical subjects

M Lesch

Publications and source records attributed to M Lesch.

At least 37 records · Page 2Linked to original sources
PubMed1996

Evidence for presence and hormonal regulation of protein phosphatase inhibitor-1 in ventricular cardiomyocyte.

Protein phosphatase inhibitor-1 (PPI-1) has been shown to be present in heart tissue and smooth muscle. Whether PPI-1 is present in cardiomyocytes is not known. The purpose of this study was to determine whether PPI-1 is present and is hormonally regulated in cardiomyocytes. A trichloroacetic acid (TCA) extract enriched in PPI-1 was isolated from guinea pig ventricular cardiomyocytes. The TCA extract inhibited the activity of type 1 protein phosphatase by 20 +/- 4% (n = 3 expts). On phosphorylation by the catalytic subunit of adenosine 3', 5'-cyclic monophosphate-dependent protein kinase, the extent of this inhibition was augmented to 4.5-fold. Dephosphorylation of the phosphorylated TCA extract by type 2 protein phosphatase reduced inhibition to 2 +/- 0.2% (n = 3 expts). To determine whether isoproterenol increases phosphorylation of PPI-1 in cardiomyocytes, the TCA extracts were prepared from cardiomyocytes treated with 1 microM isoproterenol and from untreated cardiomyocytes. The inhibitory activity of the TCA extract in untreated cardiomyocytes was 25 +/- 3% (n = 3 expts) and increased to 75 +/- 2% (n = 3 expts) in isoproterenol-treated cardiomyocytes. With the use of a rabbit skeletal muscle PPI-1 antibody, immunoblots of the TCA extract of cardiomyocytes identified a 28-kDa protein. A 28-kDa protein was also immunoprecipitated from a TCA extract isolated from isoproterenol-treated 32P-labeled cardiomyocytes. The immunoprecipitation was blocked by the addition of excess amounts of purified rabbit skeletal muscle PPI-1. Isoproterenol-treated cardiomyocytes increased the phosphorylation of the 28-kDa protein by 232 +/- 20% (n = 3 expts) compared with untreated cardiomyocytes. We conclude that 1) the 28-kDa protein is PPI-1, 2) PPI-1 is present in ventricular cardiomyocytes, and 3) PPI-1 is hormonally regulated. A decrease in type 1 protein phosphatase activity through phosphorylation of PPI-1 may be an important pathway for augmenting cardiac contractility.

Animals↗
PubMed1996

Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure.

It is often speculated that progressive deterioration of left ventricular function in heart failure is due to ongoing loss of viable cardiocytes. In this study, we examined the possibility that cardiocyte loss in heart failure may be due, in part, to apoptosis, an active process of gene-directed cellular self-destruction. Studies were performed in left ventricular tissue obtained from 10 dogs with chronic heart failure produced by multiple intracoronary microembolizations (left ventricular ejection fraction 27 +/- 1%) and from 5 normal dogs. Evidence for cardiocyte apoptosis was based on transmission electron microscopy criteria and on in situ immunohistochemical labeling of nuclear DNA fragmentation. There was no evidence of apoptotic cardiocytes in normal dogs. Features of cardiocyte apoptosis were observed in dogs with heart failure primarily in regions bordering old infarcts. Electron microscopic features of cardiocyte apoptosis included (1) intact sarcolemma and inner organelles in the presence of compaction and segregation of nuclear chromatin into sharply delineated masses that about the nuclear envelope, (2) intact sarcolemma in the presence of cytoplasm shrinkage, blebbing, and nuclear fragmentation, and (3) intact sarcolemma in the presence of complete disorganization of inner organelles and disappearance of nucleolemma. A count of all of the apoptotic bodies positively labeled for nuclear DNA fragments showed that 11% were of cardiocyte origin confirmed by positive labeling with striated muscle antimyosin antibody. We conclude that morphological and biochemical features of cardiocyte apoptosis exist in the left ventricular myocardium of dogs with chronic heart failure.

Animals↗
PubMed1996

Reversal of end-stage heart failure is predicted by long-term therapeutic response rather than initial hemodynamic and neurohormonal profile.

BACKGROUND: Long waiting list periods for heart transplantation have led to clinical improvements for some patients resulting in their removal from the waiting list. This study sought to determine what characteristics differentiated those patients with a good clinical outcome from those who continued to need a transplant. METHODS: The initial and final serial (every 3 months) right heart catheterization data of 60 patients awaiting transplantation were retrospectively analyzed, and the patients were divided into two groups: group A, patients who were taken off the list in follow-up because of improvement (n = 18 of 60), and group B who continued to require transplantation or died (n = 42 of 60). RESULTS: For Group A, there were significant declines in right atrial pressure (9 +/- 4 to 4 +/- 3 mm Hg, initial versus final, p = 0.001), systolic pulmonary arterial pressure (51 +/- 17 to 34 +/- 6 mm Hg, p = 0.0001), with an increase in electron in ejection fraction (20% +/- 4% to 34% +/- 10%, p = 0.005). The change in cardiac output and norepinephrine level was not statistically significant. For Group B, there were no changes in the initial and final values of right atrial pressure, systolic pulmonary arterial pressure, pulmonary capillary wedge pressure, or norepinephrine levels. A significant rise in ejection fraction from 17% +/- 22% +/- 8%, p = 0.003 did occur. The majority of patients in group A (12 of 18) had idiopathic dilated cardiomyopathy. In contrast, an ischemic etiology was found in the majority of group B patients (25 of 42). CONCLUSIONS: This study shows that transplant waiting list outcome cannot be predicted from a patient's initial hemodynamic or neurohormonal presentation. Rather, those patients capable of reversing their hemodynamic derangements with therapy over time are most likely to sustain a favorable clinical outcome. It appears that patients with idiopathic rather than ischemic cardiomyopathy respond more favorably to medical interventions with improved prognosis.

Adult↗
PubMed1995

Cytoprotective effects of CI-959 in the rat gastric mucosa: modulation of leukocyte adhesion.

BACKGROUND & AIMS: CI-959 is an anti-inflammatory agent that inhibits neutrophil adhesion, respiratory burst, and mast cell histamine release in vitro. In view of the emerging role of neutrophils in gastric erosive damage, the goals of this study were to assess the gastric cytoprotective effects of CI-959 and identify the mechanism responsible for this action. METHODS: Cytoprotective effects in the rat nonsteroidal anti-inflammatory drug and ethanol erosion models were assessed using image analysis. The in vivo effects of CI-959 on gastric acid secretion, arachidonic acid metabolism, and intracellular sulfhydryl and leukocyte adhesion were also examined. RESULTS: CI-959 protected prophylactically against the erosive damage induced by aspirin, indomethacin, and ethanol with 50% effective doses (ED50s) of 0.05, 1.0, and 0.07 mg/kg administered orally, respectively. When administered after indomethacin or ethanol, CI-959 had no effect on the healing of erosive damage. CI-959 did not alter gastric acid secretion, arachidonic acid metabolism, or intracellular sulfhydryl levels. In vivo, CI-959 blocked leukocyte adhesion in intravital microscopy studies using indomethacin (ED50, < 5 mg/kg orally) or platelet-activating factor (50% inhibiting concentration, approximately 10 mumol/L) as the adhesion stimulus. CONCLUSIONS: The most likely mechanism responsible for the cytoprotective effects of CI-595 is its inhibitory effects on leukocyte trafficking and/or adhesion.

Animals↗
PubMed1994

Abnormalities of contractile structures in viable myocytes of the failing heart.

We examined the incidence and severity of abnormalities of contractile structures of residual viable cardiomyocytes in the left ventricular free wall, septum and right ventricular free wall of 10 dogs with chronic heart failure produced by multiple intracoronary microembolizations and in septal biopsies of 13 patients with chronic heart failure. The abnormalities were evaluated by transmission electron microscopy and classified as either (i) type-1, defined as complete interruption of myofibrils; (ii) type-2, defined as disconnection of end-sarcomeres from the intercalated disc; or (iii) type-3, sarcomere abnormalities defined as Z-bands irregularities and/or focal myofilament disarray. In the left ventricular free wall of dogs, type-1 abnormalities were present in 33 +/- 8% of myocytes, type-2 in 26 +/- 8%, and type-3 in 63 +/- 9%. The incidence of a type-3 abnormality but not type-1 or type-2 was greater in the left ventricular wall compared with the septum and right ventricular wall (P < 0.05). Among abnormal myocytes, 29 +/- 3% of myofibrils were interrupted, 18 +/- 4% of end-sarcomeres were disconnected from the intercalated disc and 12 +/- 2% of sarcomeres were abnormal. The severity of a type-1 but not type-2 or type-3 abnormalities was greater in the left ventricular wall compared with the septum and right ventricular wall. A similarly high incidence of abnormalities was observed in septal myocytes of patients. The results indicate that abnormalities of contractile structures are common among viable myocytes of the failing heart. The incidence of these abnormalities is sufficiently high to warrant serious consideration of their potential role in the progression of left ventricular dysfunction that characterizes the heart failure state.

Actin Cytoskeleton↗
PubMed1993

Thrombolytic therapy for unstable angina.

Thrombolytic therapy for unstable angina has not gained acceptance as a primary treatment for unstable angina (UA) despite the evidence showing a reduction in mortality when these agents are given for myocardial infarction. The purpose of this review is to examine the clinical value of thrombolytic therapy for UA. The multiple lines of evidence supporting intracoronary thrombus formation as a key mechanism in the pathogenesis of UA are reviewed. Studies examining the effect of thrombolytic therapy on angiographic endpoints have shown little effect on the extent of luminal narrowing, but do reveal a decrease in angiographically detected thrombus. Twelve randomized, controlled trials of thrombolytic agents in 611 UA patients with predefined clinical endpoints have been published. These trials varied widely in design and adjunctive therapy both in treated and control grops. Review of these trials show a tendency to fewer clinical events such as death, infarction, and need for revascularization in treated patients, with a corresponding increase in bleeding complications. Clinical efficacy of thrombolytic therapy cannot be excluded by the available data, perhaps in part because of insufficient numbers of patients treated. Determination of the net clinical value of thrombolytic therapy must await larger and more definitive trials.

Angina, Unstable↗
PubMed1993

Catecholamines modulate protein turnover in cultured, quiescent rabbit cardiac myocytes.

When rabbit ventricular myocytes were cultured for 1 wk and then exposed to alpha- and/or beta-adrenergic agonists, such nonbeating heart cell preparations disclosed increased protein-to-DNA ratios and elevated RNA content, indicative of cellular hypertrophy. Norepinephrine, isoproterenol, and phenylephrine provoked hypertrophy with norepinephrine eliciting a greater response than isoproterenol or phenylephrine. Specific alpha- and beta-antagonists blocked growth by inhibiting catecholamine-induced changes in protein turnover. Each catecholamine enhanced the fractional rate of protein synthesis within 48 h; however, changes in growth rates appeared to be modulated, in part, by alterations in protein degradation. Even though rates of total protein and actin synthesis resembled values measured in vivo, myosin heavy chain fractional rate of synthesis was only 22% of in vivo levels. Double label immunofluorescence microscopy further illustrated that catecholamine treatment accelerated myofibrillar disruption in these quiescent heart cells. These observations suggested that in the absence of beating, neurohumoral modulation of contractile protein turnover was not associated with the maintenance of myofibrillar integrity even though catecholamines induced cellular hypertrophy.

Animals↗
PubMed1993

Decreased proportion of type I myofibers in skeletal muscle of dogs with chronic heart failure.

BACKGROUND: Whether biochemical and histological abnormalities of skeletal muscle (SM) develop in patients with chronic heart failure (HF) remains controversial. In the present study, dogs with chronic HF were used to examine potential alterations of SM fiber type, fiber size, number of capillaries per fiber (C/F), beta-adrenergic receptor density (Bmax), and fiber ultrastructural integrity. METHODS AND RESULTS: HF was produced in 17 dogs by sequential intracoronary microembolizations. Biopsies of the lateral head of the triceps muscle were used in all studies. Type I and type II fibers were differentiated by myofibrillar ATPase (pH 9.4 or 4.2). Bmax was assessed by radioligand binding and SM ultrastructure by transmission electron microscopy. Comparisons were made with biopsies obtained from nine control dogs. The percentage of SM type I fibers was reduced in HF dogs compared with control dogs (19 +/- 2% versus 32 +/- 5%) (p < 0.001), whereas the percentage of SM type II fibers was increased (81 +/- 2% versus 68 +/- 5%) (p < 0.001). The change in fiber type composition was not associated with a preferential atrophy or hypertrophy of either fiber type. There was no difference in SM Bmax (198.9 +/- 14.3 versus 186.8 +/- 17.3 fmol/mg protein) or in C/F (5.37 +/- 0.26 versus 5.84 +/- 0.21) between HF dogs and control dogs. No ultrastructural abnormalities were present in SM fibers of HF dogs. CONCLUSIONS: In dogs with HF, there is a decrease in the relative composition of the slow-twitch type I SM fibers and an increase in fast-twitch type II fibers. The shift in fiber type composition is not associated with preferential atrophy of either fiber type or with a reduction in C/F, beta-adrenergic receptor density, or structural abnormalities of the myofibers.

Angiography↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗