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Biomedical subjects

K Prasad

Publications and source records attributed to K Prasad.

At least 19 recordsLinked to original sources
PubMed1999

AP180 and AP-2 interact directly in a complex that cooperatively assembles clathrin.

Clathrin-coated vesicles are involved in protein and lipid trafficking between intracellular compartments in eukaryotic cells. AP-2 and AP180 are the resident coat proteins of clathrin-coated vesicles in nerve terminals, and interactions between these proteins could be important in vesicle dynamics. AP180 and AP-2 each assemble clathrin efficiently under acidic conditions, but neither protein will assemble clathrin efficiently at physiological pH. We find that there is a direct, clathrin-independent interaction between AP180 and AP-2 and that the AP180-AP-2 complex is more efficient at assembling clathrin under physiological conditions than is either protein alone. AP180 is phosphorylated in vivo, and in crude vesicle extracts its phosphorylation is enhanced by stimulation of casein kinase II, which is known to be present in coated vesicles. We find that recombinant AP180 is a substrate for casein kinase II in vitro and that its phosphorylation weakens both the binding of AP-2 by AP180 and the cooperative clathrin assembly activity of these proteins. We have localized the binding site for AP-2 to amino acids 623-680 of AP180. The AP180/AP-2 interaction can be disrupted by a recombinant AP180 fragment containing the AP-2 binding site, and this fragment also disrupts the cooperative clathrin assembly activity of the AP180-AP-2 complex. These results indicate that AP180 and AP-2 interact directly to form a complex that assembles clathrin more efficiently than either protein alone. Phosphorylation of AP180, by modulating the affinity of AP180 for AP-2, may contribute to the regulation of clathrin assembly in vivo.

Adaptor Proteins, Vesicular Transport↗
PubMed1999

Variation in in-patient stroke management in ten centres in different countries: the INCLEN multicentre stroke collaboration.

BACKGROUND AND PURPOSE: Large within-country variations have been described in stroke management and there have been a few studies of between-country variation (in the USA and the UK). We designed a study to examine stroke management across a wide range of countries representing different stages of economic development. Large variations would suggest the need to explore methods of increasing the uptake of evidence-based stroke practice. METHODS: Members of the International Clinical Epidemiology Network (INCLEN) from 14 centres in ten countries agreed to review the records of the last 50 patients admitted to hospital with a clinical diagnosis of stroke. Information on demographic variables, the clinical diagnosis of stroke type, investigations performed and treatments given and the discharge destination of the patient were recorded and sent to the coordinating centre in Australia for analysis. RESULTS: There were statistically significant between-centre differences in the proportions of patients cared for by a neurologist, staying in hospital for at least ten days and having CT or MRI scans. Significant between-centre differences were also seen for treatment, for example, the use of aspirin in non-haemorrhagic stroke varied from 11 to 79%. The variation (for all interventions studied) was no longer statistically significant when examined within strata according to availability of facilities. CONCLUSIONS: The large variation between centres in the management of stroke is largely 'explained' by the availability of resources, even for interventions that do not depend on resource availability. It will be important to develop management guidelines that reflect evidence-based practice of relevance across a range of economic settings.

Age Factors↗
PubMed1999

Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed.

BACKGROUND: Secoisolariciresinol diglucoside (SDG) is a plant lignan isolated from flaxseed. Lignans are platelet-activating factor-receptor antagonists that would inhibit the production of oxygen radicals by polymorphonuclear leukocytes. SDG is an antioxidant. Antioxidants studied thus far are known to reduce hypercholesterolemic atherosclerosis. The objective of this study was to determine the effect of SDG on various blood lipid and aortic tissue oxidative stress parameters and on the development of atherosclerosis in rabbits fed a high-cholesterol diet. METHODS AND RESULTS: Rabbits were assigned to 4 groups: group 1, control; group 2, SDG control (15 mg. kg body wt-1. d-1 PO); group 3, 1% cholesterol diet; and group 4, same as group 3 but with added SDG (15 mg. kg body wt-1. d-1 PO). Blood samples were collected before (time 0) and after 4 and 8 weeks of experimental diets for measurement of serum triglycerides, total cholesterol (TC), and LDL, HDL, and VLDL cholesterol (LDL-C, HDL-C, and VLDL-C). The aorta was removed at the end of the protocol for assessment of atherosclerotic plaques; malondialdehyde, an aortic tissue lipid peroxidation product; and aortic tissue chemiluminescence, a marker for antioxidant reserve. Serum TC, LDL-C, and the ratios LDL-C/HDL-C and TC/HDL-C increased in groups 3 and 4 compared with time 0, the increase being smaller in group 4 than in group 3. Serum HDL-C decreased in group 3 and increased in group 4 compared with time 0, but changes were lower in group 3 than in group 4. SDG reduced TC and LDL-C by 33% and 35%, respectively, at week 8 but increased HDL-C significantly, by>140%, as early as week 4. It also decreased TC/LDL-C and LDL-C/HDL-C ratios by approximately 64%. There was an increase in aortic malondialdehyde and chemiluminescence in group 3, and they were lower in group 4 than in group 3. SDG reduced hypercholesterolemic atherosclerosis by 73%. CONCLUSIONS: These results suggest that SDG reduced hypercholesterolemic atherosclerosis and that this effect was associated with a decrease in serum cholesterol, LDL-C, and lipid peroxidation product and an increase in HDL-C and antioxidant reserve.

Animals↗
PubMed1999

Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training.

BACKGROUND: The function of local renin-angiotensin systems in skeletal muscle and adipose tissue remains largely unknown. A polymorphism of the human angiotensin converting enzyme (ACE) gene has been identified in which the insertion (I) rather than deletion (D) allele is associated with lower ACE activity in body tissues and increased response to some aspects of physical training. We studied the association between the ACE gene insertion or deletion polymorphism and changes in body composition related to an intensive exercise programme, to investigate the metabolic effects of local human renin-angiotensin systems. METHODS: We used three independent methods (bioimpedance, multiple skinfold-thickness assessment of whole-body composition, magnetic resonance imaging of the mid-thigh) to study changes in body composition in young male army recruits over 10 weeks of intensive physical training. FINDINGS: Participants with the II genotype had a greater anabolic response than those with one or more D alleles for fat mass (0.55 vs -0.20 kg, p=0.04 by bioimpedance) and non-fat mass (1.31 vs -0.15 kg, p=0.01 by bioimpedance). Changes in body morphology with training measured by the other methods were also dependent on genotype. INTERPRETATION: II genotype, as a marker of low ACE activity in body tissues, may conserve a positive energy balance during rigorous training, which suggests enhanced metabolic efficiency. This finding may explain some of the survival and functional benefits of therapy with ACE inhibitors.

Adipose Tissue↗
PubMed1999

Homocysteine, a Risk Factor for Cardiovascular Disease.

Fasting hyperhomocysteinemia is an independent risk factor for coronary artery disease, stroke, peripheral vascular atherosclerosis, and for arterial and venous thromboembolism. The risk for cardiovascular disease with homocysteine is similar to conventional risk factors. The interaction of hyperhomocysteinemia with hypertension and smoking is strong and the combined effect is more than multiplicative. The combined effect of homocysteine and cholesterol is additive. Homocysteine produces atherosclerosis, thromboembolism, and vascular endothelial cell injury. Vascular dysfunction produced by homocysteine may be due to endothelial cell damage. Homocysteinemia-induced atherosclerosis is probably due to various factors including endothelial cell injury, inability to sustain S-nitroso-homocysteine formation because of imbalance between production of nitric oxide by dysfunctional endothelium and homocysteine, smooth muscle cell proliferation, and thromboembolism. There is strong evidence that endothelial cell injury is associated with oxidative stress produced by homocysteine. Hyperhomocysteinemia is associated with numerous conditions, including coronary disease, stroke, peripheral vascular disease (carotid artery and cerebrovascular atherosclerosis), venous thrombosis, renal disease, diabetes mellitus, and organ transplant. Folic acid, vitamin B12 and B6 have been shown to be beneficial in reducing plasma homocysteine levels. Folic acid is specifically very effective, safe and inexpensive.

Journal Article↗
PubMed1999

Intratesticular varicocele: evaluation using conventional and Doppler sonography.

OBJECTIVE: The aim of this study was to describe the conventional and Doppler sonographic appearances of intratesticular varicoceles and to determine their occurrence. SUBJECTS AND METHODS: One thousand forty men with various testicular problems were examined using conventional and Doppler sonography, and the incidence of intratesticular varicocele and other conditions was recorded. Eighteen patients with intratesticular varicoceles were further examined, allowing us to study the various sonographic and Doppler parameters of this rare entity. RESULTS: Intratesticular varicocele was identified in 18 (1.7%) patients. The condition was bilateral in seven patients and unilateral in 11. Of 25 testes involved, 12 (48%) were right-sided and 14 (56%) were isolated without any ipsilateral extratesticular varicocele. The shape of the intratesticular varicocele was tubular in 21 cases and oval in five; one patient had both oval and tubular varicoceles. Diameters ranged from 2 to 8 mm (mean, 3.1 mm). Mean venous flow velocity was 2.8 cm/sec and had an inverse relationship to the diameter of the intratesticular varicocele. CONCLUSION: Intratesticular varicocele is seen in fewer than 2% of the symptomatic population. The condition has a characteristic sonographic appearance of dilated tubular intratesticular veins with a proximity to the mediastinum testis. Variations from previously published reports included presentation with an oval shape, more frequent bilateral occurrence, greater number of isolated right-sided intratesticular varicoceles, and fewer associations with an extratesticular varicocele.

Adult↗
PubMed1999

Surgical results and complications of mitomycin C-augmented trabeculectomy in refractory developmental glaucoma.

BACKGROUND AND OBJECTIVE: To evaluate the surgical results and complications of mitomycin C-augmented trabeculectomy in refractory developmental glaucoma. PATIENTS AND METHODS: The authors reviewed the charts of all patients of refractory developmental glaucoma who underwent mitomycin C-augmented trabeculectomy (0.4 mg/ml for 3 minutes) between September 1990 and August 1995. Thirty-eight eyes of 29 patients were included in the study; 34 eyes (89.5%) had refractory primary congenital glaucoma with documented failure of primary surgery, 2 eyes (5.3%) had Axenfeld-Rieger syndrome and 2 eyes (5.3%) had aniridia. The main outcome measures in this study were preoperative and postoperative intraocular pressures (IOPs),visual acuities, bleb characteristics, success rate, time of surgical failure, and complications. RESULTS: The IOP (mean +/- SD) reduced from a preoperative level of 32.6 +/- 11.8 mm Hg to 12.3 +/- 7.3 mm Hg (P <0.0001) with the percentage reduction in IOP being 56%. Kaplan-Meier survival analysis showed that the success probability at 18 months was 65%, which was maintained till 30 months of follow-up. The bleb was characterized by its large, elevated, avascular, transparent appearance in all the eyes. There were no intraoperative complications. The postoperative complications included hyphema (absorbed one week) in 8 eyes (21%), uncontrolled IOP in 8 eyes (21%), shallow anterior chamber in 3 eyes (7.9%), hypotony without visual loss in one eye (2.6%) and retinal detachment in 2 eyes (5.2%) which was surgically repaired successfully. Visual acuity was maintained in all cases after surgery. None of the patients developed mitomycin-C related late bleb-leakage or endophthalmitis. CONCLUSION: Treatment of refractory developmental glaucoma with mitomycin C-augmented trabeculectomy is effective and safe with an acceptable rate of complications.

Adolescent↗
PubMed1999

Protection of coronary angioplasty-induced oxidative stress by Isovue used during angioplasty.

BACKGROUND: Oxygen free radicals (OFRs) have been implicated in ischemic-reperfusion cardiac injury. Use of percutaneous transluminal coronary angioplasty (PTCA) has created renewed interest in salvation of ischemic myocardium. The PTCA procedure is similar to the ischemia-reperfusion model. It is possible that OFRs are increased following PTCA. However, OFR-related cardiac complications are uncommon and the evidence for lipid peroxidation is conflicting. PATIENTS AND METHODS: In this study the levels of plasma malondialdehyde, OFR-producing activity of polymorphonuclear leukocytes (PMNL-CL) and blood antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) were measured in peripheral venous blood of 50 consecutive patients with stable angina undergoing elective PTCA. The ability of Isovue (used during PTCA) and of streptokinase (used during thrombolysis) to scavenge OH in the high performance liquid chromatography method and to reduce OH-induced lipid peroxidation were also assessed. Patients were divided into three groups: group 1, single vessel PTCA; group 2, two or more vessel PTCA; and group 3, combined single and multivessel PTCA. RESULTS: The results indicated that there was an increase in PMNL-CL (22% to 44%) and a decrease in plasma malondialdehyde (33% to 40%) at 60 mins following PTCA. The activity of antioxidant enzymes remained unaltered. Isovue scavenged OH in a concentration-dependent manner and was complete at a concentration below that used in patients. Streptokinase, on the other hand, was ineffective in scavenging OH. CONCLUSIONS: These results suggest that, in spite of increased production of OFR by polymorphonuclear leukocytes and unaltered activity of antioxidant enzymes, lipid peroxidation decreased. Lack of lipid peroxidation may have been due to the OH-scavenging property of Isovue. The observed differences in OFR-related complications between PTCA and thrombolytic therapy may have been due to the antioxidant activity of Isovue.

Adult↗
PubMed1998

QT dispersion and risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy.

This study examines the relation of QT dispersion (QTd) on a surface electrocardiogram (ECG) to clinical features and established risk factors of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HC). One hundred fifty-six consecutive patients with HC (91 men, mean age 41+/-15 years, range 7 to 79) and 72 normal subjects (41 men, mean age 39+/-9 years, range 20 to 60) were studied. Standard 12-lead ECGs were recorded from each subject using a MAC VU electrocardiograph. Patients with nonsinus rhythm, atrioventricular conduction block, QRS duration > 120 ms, age < 15 years, and low amplitude T waves were excluded from the analysis (n=51). Another 22 patients who were receiving amiodarone and/or sotalol therapy were also excluded. QT interval and QTd were measured using automated analysis in the remaining 83 patients (46 men, age 40+/-14 years, range 16 to 76). QT interval (406+/-38 ms), QTc interval (432+/-27 ms), and QTd (43+/-25 ms) were significantly greater in patients with HC than in normal controls (386+/-31 ms, 404+/-16 ms, 26+/-16 ms, respectively) (p <0.0001). QTd was significantly greater in patients with HC with chest pain compared with asymptomatic or mildly symptomatic patients (50+/-28 ms vs 37+/-20 ms, p=0.02). Increased QTd was found in patients with dyspnea New York Heart Association functional classes II/III than in those with dyspnea New York Heart Association functional class I (50+/-27 ms vs 38+/-22 ms, p=0.04). QTd was weakly correlated with maximum left ventricular wall thickness (r=0.228, p=0.038). No significant association was found between QTd and any risk factors for SCD. Thus, patients with HC have increased QTd. The QTd correlates with symptomatic status. Assessment of QTd might provide complementary clinical characterization of patients with HC but its relation to SCD remains uncertain.

Adolescent↗
PubMed1998

Probing the phosphoinositide binding site of the clathrin assembly protein AP-2 with photoaffinity labels.

The relative binding specificities of the subunitsof bovine assembly protein AP-2 for the phosphatidylinositol polyphosphates (PtdInsPn) and inositol polyphosphates (InsPn) were determined by photoaffinitylabeling. Three types of benzophenone-containing photoprobes were employed: (i) the water-solubleP-1- or P-2-tethered p-benzoyldihydrocinnamoyl-InsPn (BZDC-InsPn) analogs, (ii) P-1-linked phosphotriester PtdInsPn analogs that sampled the interface between the water and lipid phases, and (iii) sn-1-O-acyl-linked PtdInsPn analogs that interacted with proteins penetrating the bilayer. The InsPn and PtdInsPn probes bind with highest selectivity and affinity to the two alpha subunit isoforms, with certain probes and conditions resulting in strong labeling of the 50-kDa mu subunit. Three main conclusions were reached: (i) head group recognition predominated over acyl chain recognition, (ii) the PtdInsPn binding site of alpha-AP-2 prefers more highly phosphorylated species, and (iii) the protein-acyl chain interactions showed high capacity but low selectivity.

Adaptor Proteins, Vesicular Transport↗
PubMed1998

Fumarate modulates bacterial flagellar rotation by lowering the free energy difference between the clockwise and counterclockwise states of the motor.

Switching flagellar rotation from one direction to another is an essential part of bacterial chemotaxis. Fumarate has been shown to possess the capacity to restore to flagella of cytoplasm-free, CheY-containing bacterial envelopes the ability to switch directions and to increase the probability of reversal in intact cells. Neither the target of fumarate action nor the mechanism of function is known. To distinguish between the two potential targets of fumarate, the response regulator CheY and the flagellar switch-motor complex, we compared flagellar rotation between isogenic strains that lacked CheY and had either low or high levels of fumarate. The difference in the fumarate levels was due to a deletion of the genes encoding the enzymes that synthesize and metabolize fumarate; succinate dehydrogenase and fumarase, respectively. The strains were in a gutted background (i.e. a background deleted for the cytoplasmic chemotaxis proteins and some of the receptors), and switching was achieved by carrying out the measurements at 2.5 degreesC, where it has been demonstrated that gutted cells switch spontaneously. The flagellar rotation of the strain with the highest level of fumarate was the most clockwise-biased and had the highest reversal frequency, indicating that fumarate is effective even in the absence of CheY. Fumarate reduced the free energy difference of the counterclockwise-to-clockwise transition and had no appreciable effect on the activation energy of this transition. Similar observations were made at room temperature, provided that intracellular CheY was present. In a wild-type background, both mutants made rings on semi-solid agar typical of normal chemotaxis. Taken together, the results suggest that the target of fumarate is the switch-motor complex, that fumarate acts by increasing the probability of the clockwise state, and that a fumarate level as low as that found in succinate dehydrogenase mutants is sufficient for normal chemotaxis.

Bacterial Proteins↗
PubMed1998

Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid.

Flaxseed (Type I flaxseed) with 51-55% alpha-linolenic acid in its oil and richest source of plant lignans, has been shown to reduce hypercholesterolemic atherosclerosis by 46% without lowering serum lipids. Antiatherogenic activity was claimed to be due to its alpha-linolenic acid and/or lignan content. If alpha-linolenic acid component of flaxseed is responsible for antiatherogenic activity, then, CDC-flaxseed (Type II flaxseed) which has similar oil and lignan content but has very little (2-3% of the total oil) alpha-linolenic acid would have no antiatherogenic effect. An investigation, therefore, was made of Type II flaxseed on high cholesterol diet-induced atherosclerosis and serum lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C)] in rabbits. Rabbits were assigned to four groups: Group I, Control; Group II, Type II flaxseed diet (7.5 g/kg orally daily); Group III, 1% cholesterol diet; Group IV, 1% cholesterol diet supplemented with Type II flaxseed (7.5 g/kg orally daily). Blood samples were collected before (0 time) and after 4 and 8 weeks of experimental diets for measurement of serum lipids. Aorta was removed at the end of 8 weeks for assessment of atherosclerotic plaques. Serum TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C were lower in Group IV as compared to Group III by 14 and 31%, 17 and 32%, 28 and 34% and 24 and 32%, respectively, at 4 and 8 weeks. HDL-C was not affected by Type II flaxseed in hypercholesterolemic rabbit. TG and VLDL-C were markedly increased in Group IV as compared to Group III. Type II flaxseed reduced the development of atherosclerosis by 69%. Histological changes in the atherosclerotic regions were qualitatively similar in Groups III and IV. Results indicate that reduction in hypercholesterolemic atherosclerosis by Type II flaxseed is due to a decrease in serum TC and LDL-C. In conclusion, antiatherogenic activity of Type II flaxseed is not due to alpha-linolenic acid.

Animals↗
PubMed1998

Increased oxidative stress in rat liver and pancreas during progression of streptozotocin-induced diabetes.

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. There are many reports indicating the changes in parameters of oxidative stress in diabetes mellitus. In this study we aimed to identify whether oxidative stress occurs in the liver and pancreas in the initial stages of development of diabetes. 2. We therefore investigated the lipid peroxide level (thiobarbituric acid-reactive substances, TBARS) and activities of antioxidant enzymes [superoxide dismutase (SOD), catalase and glutathione peroxidase] in liver and pancreas of control and streptozotocin-induced diabetic rats at various stages of development of diabetes. 3. Male Sprague-Dawley rats were divided into two groups: group I, control (n = 42) and group II, diabetic (n = 42). Each group was further subdivided into seven groups consisting of six rats each. Rats in these subgroups were studied at weekly intervals (0 to 6 weeks). Plasma glucose levels, TBARS levels and activities of antioxidant enzymes were measured in liver and pancreas at various time intervals. 4. There was a significant (P < 0.05) and progressive increase in TBARS levels of liver and pancreas in the diabetic group. Total SOD and Cu-Zn-SOD activity increased (P < 0.05) with progression of diabetes while Mn-SOD activity showed no significant change in either tissue. Catalase and glutathione peroxidase activities increased significantly (P < 0.05) in liver and pancreas. 5. Immunohistochemical study of pancreatic islet revealed a decrease in the expression of insulin with progression of diabetes. However, glucagon and somatostatin showed an increase in immunoreactivity and a difference in their distribution pattern. 6. The findings of the present study suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively. In conclusion, the structural damage to these tissues or complications of diabetes mellitus may be due to oxidative stress.

Animals↗
PubMed1998

Dipyridamole stress thallium-201 perfusion abnormalities in patients with hypertrophic cardiomyopathy. Relationship to clinical presentation and outcome.

AIMS: Thallium-201 perfusion abnormalities are common in patients with hypertrophic cardiomyopathy and may be associated with an adverse prognosis in the young. The aim of this study was to prospectively determine the relationship between thallium-201 defects during dipyridamole stress to clinical presentation and outcome in a large consecutive series of patients with hypertrophic cardiomyopathy. METHODS/RESULTS: Thallium-201 single photon computed tomography was performed in 216 patients with hypertrophic cardiomyopathy during dipyridamole stress (0.5 mg. kg-1). Fixed perfusion defects occurred in 25%, and reversible defects in 22%. A combination of defects was present in 7%. Fixed defects were associated with: a history of syncope (17 of 46 with, vs 36 of 170 without syncope, P = 0.03); larger left ventricular end-diastolic (46.9 +/- 7.4 mm vs 43.3 +/- 6.4 mm; P = 0.001) and end-systolic dimension (30.2 +/- 8.4 mm vs 24.5 +/- 5.9 mm, P < 0.0001); increased left atrial diameter (46.1 +/- 8.1 mm vs 40.5 +/- 7.7 mm, P < 0.0001); lower fractional shortening (35.9 +/- 10.4% vs 43.8 +/- 8.6%, P < 0.0001): and lower maximal exercise oxygen consumption (24.2 +/- 8.1 ml. min-1. kg-1 vs 29.4 +/- 8.8 ml. min-1. kg-1, P < 0.0003). Reversible defects did not correlate with symptomatic status, but were associated with: larger left atrial dimensions (44.5 +/- 8.1 mm vs 41.0 +/- 8.0 mm; P = 0.009) and greater maximal left ventricular wall thickness (24.0 +/- 7.0 mm vs 20.6 +/- 7.0 mm, P = 0.003). The mean follow up time was 41 +/- 21 months, range 0.6-124. There was no association between any thallium-201 abnormality and disease related death in young or adult patients. CONCLUSION: The present study shows that fixed thallium-201 perfusion defects detected during dipyridamole stress in patients with hypertrophic cardiomyopathy are associated with syncope, larger left ventricular cavity dimensions and reduced exercise capacity. Although the event rate was relatively small, there was no evidence for an association between thallium-201 defects and survival.

Adolescent↗
PubMed1998

Initiating sequences in exercise induced idiopathic ventricular tachycardia of left bundle branch-like morphology.

Initiating sequences for VT may infer the underlying arrhythmogenic mechanisms. This study examines the initiating sequences of exercise induced idiopathic VT of left bundle branch block-like (LBBB-like) morphology and makes an attempt to relate these to clinical aspects and the mechanisms of arrhythmia. Thirty-two patients (mean age 33.4 +/- 13.2 years; 18 men) with exercise induced VT in the absence of structural cardiac abnormality on history, clinical examination, and noninvasive and invasive investigations were divided into two groups on the basis of the initiating sequence of VT on exercise. Group I consisted of patients with long-short sequence of RR intervals prior to the onset of VT (initiating/preinitiating cycle length ratio < or = 0.78). Group II consisted of patients without changes in cycle length prior to VT. Group I mechanism would suggest delayed afterdepolarizations (DADs) or reentry whereas group II mechanism triggered activity due to early afterdepolarizations. Fourteen patients (group I) had long-short sequence and 18 patients (group II) were without cycle length changes prior to VT initiated during exercise. VT axis was inferior in all 18 patients in group II but only in 9 patients in group I (P = 0.02). In these predefined patient groups, sustained monomorphic VT could not be initiated by programmed stimulation in any patient in group I, whereas four patients in group II had inducible VT. Patients in group II also had higher incidence of sustained VT on ambulatory monitoring (P < 0.05). The two groups did not differ in other respects. This study demonstrates the existence of at least two possible mechanisms of initiation of exercise induced idiopathic VT of LBBB-like morphology. VT initiated without cycle length changes is more common, more likely to have an inferior axis suggesting an outflow tract origin, and is probably related to triggered activity secondary to DADs. VT initiated with a long-short sequence is more often nonsustained and may have a superior axis suggesting an origin from the body or septal region of the ventricle. The two groups, therefore, exhibit differences in electrophysiological characteristics that may aid classification and therapy of this arrhythmia.

Adult↗