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Biomedical subjects

D Mehta

Publications and source records attributed to D Mehta.

At least 73 records · Page 4Linked to original sources

Experimental models of accelerated atherosclerosis syndromes.

The processes of angioplasty restenosis, vein graft failure, and transplant atherosclerosis, collectively termed 'syndromes of accelerated atherosclerosis', have been the focus of significant clinical and experimental research. Limitations of clinical studies have forced emphasis onto experimental animal models for the purpose of determining pathophysiology and evaluation of potential therapeutic strategies. However, the apparent failure of many in vivo animal models to predict interventional outcome in humans has raised doubt over their suitability as models of these pathophysiological states. Similar criticism has befallen the use of in vitro techniques for elucidating pathophysiology of the cellular elements. An awareness of the shortcomings of the various experimental models in use would therefore seem prerequisite both to a more critical evaluation of data generated from their use, and to the development of truly effective therapeutic strategies for humans.

Animals↗

Influence of external stent size on early medial and neointimal thickening in a pig model of saphenous vein bypass grafting.

BACKGROUND: Late saphenous vein graft failure results from intimal and medial thickening due to migration and proliferation of vascular smooth muscle cells and superimposed atheroma. These changes may represent an adaptation by the vein to its insertion into the arterial system. Using a porcine model of arteriovenous bypass grafting, we recently demonstrated that supporting the graft with a nonrestrictive external Dacron velour stent significantly reduced intimal hyperplasia and total wall thickness. In the present study, we investigated the influence of different external stent sizes on graft wall dimensions and cell proliferation. METHODS AND RESULTS: Three stent sizes were tested: mildly restrictive, nonrestrictive, and oversized (5, 6, and 8 mm in diameter, respectively). Four weeks after grafting, total wall thickness was decreased 40% by 5-mm stents (P = .02), 66% by 6-mm stents (P = .0004), and 81% by 8-mm stents (P = .02 versus unstented grafts). Neointimal thickness was reduced almost 62% by 6-mm and 72% by 8-mm stents (both P = .01) but not by 5-mm stents. As a result, the encroachment of the intima into the lumen was reduced approximately 70% by 6- or 8-mm stents (P = .02 and P = .01 versus unstented grafts, respectively). Both neointimal and medial cell proliferation were significantly reduced by all three stents compared with unstented grafts. CONCLUSIONS: External stenting of saphenous vein bypass grafts reduces early intimal and medial hyperplasia. Oversized stents give equally profound suppression of intimal thickening, obviating the need for precise size matching with the graft and greatly simplifying the surgical procedure.

Animals↗

Value of quantitative measurement of signal-averaged electrocardiographic variables in arrhythmogenic right ventricular dysplasia: correlation with echocardiographic right ventricular cavity dimensions.

OBJECTIVES: We sought to investigate the relation between signal-averaged electrocardiographic (ECG) variables and the extent of right ventricular disease, as estimated by right ventricular enlargement during detailed echocardiography, in patients with arrhythmogenic right ventricular dysplasia. BACKGROUND: In patients with ventricular tachycardia of right ventricular origin, a normal signal-averaged ECG is indicative of "idiopathic" ventricular tachycardia, whereas an abnormal signal-averaged ECG is a specific marker for right ventricular disease, especially dysplasia. Signal-averaged ECGs in these patients are mildly to grossly abnormal. METHODS: Ten patients with the clinical diagnosis of arrhythmogenic right ventricular dysplasia were included. All patients had documented, sustained ventricular tachycardia, no coronary artery disease and a normal QRS duration of < or = 110 ms on routine 12-lead electrocardiography. Signal-averaged ECGs were recorded using time-domain analysis. Right ventricular cavity dimensions recorded during two-dimensional echocardiography were measured at the level of the inflow tract, midcavity and outflow tract. Signal-averaged ECG variables and echocardiographic measurements were correlated using linear regression analysis. RESULTS: Nine of 10 patients had abnormal signal-averaged ECGs. There was a consistent correlation between all signal-averaged ECG variables and the right ventricular cavity dimensions at the level of the midcavity. The correlation was most significant with the duration of the filtered QRS complex (p < 0.001 for QRS duration, p < 0.01 for late potential duration and p < 0.05 for root-mean-square voltage of the last 40 ms). There was no consistent correlation between the signal-averaged ECG variables and right ventricular dimensions at the level of the inflow and outflow tracts. CONCLUSIONS: The majority of patients with arrhythmogenic right ventricular dysplasia have abnormal signal-averaged ECGs. In the absence of bundle branch block, the extent of abnormality of signal-averaged ECG variables is in proportion to right ventricular cavity enlargement, and thus is indicative of the severity of right ventricular dysfunction.

Adult↗

Role of contractile protein activation in the length-dependent modulation of tracheal smooth muscle force.

The active isometric force developed by a muscle decreases at muscle lengths below an optimal length (Lo). However, when the length of an actively contracting muscle is abruptly decreased, a lower level of isometric force is reached during force redevelopment than when the contraction is initiated at the shorter length. This has been attributed to a deactivation of contractile proteins caused by shortening. In this study, intracellular Ca2+ and myosin light chain (MLC) phosphorylation were measured to assess the mechanisms for the modulation of isometric force caused by changing smooth muscle length before or during isometric contraction. The decline in isometric force between Lo and 0.5Lo was associated with decreases in MLC phosphorylation and intracellular Ca2+ during contractions elicited by acetylcholine or 60 mM KCl. Quick release of the muscle during contraction depressed force redevelopment at the shorter length but not MLC phosphorylation. We conclude that decreases in Ca(2+)-calmodulin-dependent MLC phosphorylation contribute significantly to the decline in isometric force at lengths below Lo, but the depression of contractility associated with the quick release of actively contracted smooth muscle is not caused by a shortening-induced deactivation of contractile proteins.

Acetylcholine↗

Thromboembolism following cardioversion of "common" atrial flutter. Risk factors and limitations of transesophageal echocardiography.

Based on multiple recent studies, anticoagulant therapy is recommended prior to elective cardioversion for patients with atrial fibrillation of more than 24 h duration. The value of anticoagulation in patients with atrial flutter, however, is less well established. Published recommendations for pericardioversion anticoagulation of atrial fibrillation often do not extend to patients with atrial flutter. We evaluated the risk of thromboembolism in our patient population undergoing cardioversion for atrial flutter. Over a period of 30 months, clinically indicated electrical cardioversions were performed in 41 patients with "common" atrial flutter. Sixteen of these patients underwent transesophageal echocardiograms immediately prior to cardioversion to exclude a left atrial thrombus. Three of the 41 patients with atrial flutter developed neurologic ischemic syndromes within 48 h of elective cardioversion. All three patients who developed ischemic neurologic complications had undergone transesophageal echocardiography immediately prior to cardioversion and did not have any evidence of left atrial clot. One patient had cardiomyopathy and the other two had left ventricular hypertrophy. Thus, electrical cardioversion without anticoagulation in patients with atrial flutter and associated heart disease is associated with a risk of thromboembolic events. A normal transesophageal echocardiogram is of doubtful value in prevention of thromboembolic complications.

Aged↗

Subpectoral implantation of ICD generators: long-term follow-up.

A nonthoracotomy surgical approach using an endocardial electrode and combined implantation of a subcutaneous patch and the implantable cardioverter defibrillator (ICD) generator in a subpectoral pocket has been described. We report the long-term follow-up results in patients undergoing implantation using this approach. The patient population consisted of 28 patients (22 men and 6 women) with a mean age of 59 +/- 12 years. The underlying heart disease consisted of coronary artery disease in 20 patients and dilated cardiomyopathy in 8 patients. Sustained ventricular tachycardia was the mode of presentation in 16 patients and sudden cardiac death in 12 patients. The mean left ventricular ejection fraction was 31% +/- 6%. The lead system consisted of an 8 French bipolar passive fixation rate sensing lead positioned at the right ventricular apex, an 11 French spring coil electrode positioned at the superior vena cava-right atrial junction (surface area 700 mm2), and submuscular placement of a large patch (surface area 28 cm2) on the anterolateral chest wall near the cardiac apex via a submammary incision. A defibrillation threshold of < or = 15 joules (J) was required for implantation. This criterion was not satisfied in five patients; thus, a limited thoracotomy was performed via the submammary incision, and the large patch was placed epicardially. The mean R wave amplitude was 12 +/- 3 mV, the mean pacing threshold was 1.0 +/- 0.5 V at 0.5 msec, and the mean defibrillation threshold was 12.6 +/- 3 J. ICD generators implanted were the Ventak-P in 17, PCD-7217 in 5, and the Cadence V-100 in 6 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Defibrillators, Implantable↗

Sinus node reentrant tachycardia.

This review article discusses the electrophysiological basis of sinus node reentry, clinical features of sinus node reentry, and the management of this uncommon tachycardia with drugs and ablative therapy. It also proposes the use of the term "sinoatrial reentrant tachycardia" for this form of tachycardia.

Animals↗

Selective preoperative endoscopic retrograde cholangiography with sphincterotomy avoids bile duct exploration during laparoscopic cholecystectomy.

A policy of preoperative endoscopic retrograde cholangiography (ERC) for suspected bile duct stones was used in 1507 patients considered for laparoscopic cholecystectomy in three district general hospitals. Altogether 306 patients underwent ERC, and bile duct cannulation was achieved in 276 (90%). Bile ducts were cleared by endoscopic sphincterotomy in 128 of 161 patients (79%) with proven duct stones. Laparoscopic cholecystectomy was completed in 1396 patients. Ten laparotomies were necessary for complications of laparoscopic cholecystectomy. The complication rate for endoscopic sphincterotomy/laparoscopic cholecystectomy was 2.7%, with no mortality. Overall, a combined endoscopic/laparoscopic approach succeeded in 1386 patients (92%). Fourteen patients (1%) had retained stones during a median of 14 months (range 1-42) follow up, all of which were removed by ERC/endoscopic sphincterotomy. If a policy of selective ERC before laparoscopic cholecystectomy is used for all patients with symptomatic gall stones, most will avoid an open operation and laparoscopic exploration of the bile duct is not necessary.

Adolescent↗

Long term results of fast pathway ablation in atrioventricular nodal reentry tachycardia using a modified technique.

OBJECTIVE: To assess immediate and long term success of "fast" pathway catheter ablation with graded use of radiofrequency energy in patients with classic atrioventricular nodal reentrant tachycardia (AVNRT) and evaluate clinical, procedure related, and electrophysiological features affecting long term results. DESIGN: 31 consecutive patients with classic AVNRT at electrophysiological study, who were candidates for radiofrequency ablation. Patients were followed for an average of 24 months after ablation. SETTING: All studies and ablations were performed in an electrophysiological laboratory under fluoroscopic guidance using standard electrophysiological techniques. INTERVENTION: Radiofrequency application was performed at the site of proximal His bundle electrogram with A:V ratio of > 1. It was started at 10 W with increment of 5 W to a maximum of 25 W at 60 s. With the onset of junctional rhythm, atrial pacing was begun in order to monitor the PR interval. Application was terminated prematurely with a non-conducted P wave, continued prolongation of the PR interval beyond 50% of the baseline, or a threefold rise in impedance. RESULTS: Successful ablation was possible in 30/31 patients (97%) with an average of seven applications (range 1-10). It was associated with significant prolongation of PR interval (P < 0.001) and AV Wenckebach cycle length (P = 0.01). Ventriculo-atrial conduction was abolished in 24/30 patients (82%) with successful ablation. Two patients developed transient complete heart block (3 and 12 min) and one persistent right branch block. Four patients had late recurrence. Presence of ventriculo-atrial block was the only electrophysiological index predictive of long term success (P = 0.01). CONCLUSIONS: Graded use of radiofrequency energy and atrial pacing to monitor PR interval decreases the risk of atrioventricular block in patients undergoing fast pathway ablation for AVNRT. Ventriculo-atrial block is predictive of long term success and should be a preferred end point for fast pathway ablation.

Adolescent↗

Short-term effect of epidermal growth factor (EGF) on sodium and glucose cotransport of isolated jejunal epithelial cells.

This study was undertaken to assess the short-term effects of EGF on sodium and glucose uptake, glucose metabolism and Na+/K(+)-ATPase activity in isolated enterocytes of rats. Jejunal cells exposed to EGF had a significantly greater total uptake of sodium compared to controls after 6 min. Kinetic analysis of glucose transport across BBMV's demonstrated similar Km values but a significant increase of the Vmax in vesicles prepared from cells first exposed to EGF as compared to controls. EGF was also associated with a significant increase in glucose metabolism of jejunal enterocytes after 15 min. The activity of Na+/K(+)-ATPase increased in jejunal enterocytes exposed to EGF. The increase in Na+/K(+)-ATPase activity of the cells following EGF exposure was not accompanied by an increase in immunodetectable total or assembled Na+/K(+)-ATPase protein. EGF's effect on enzyme activity was abolished by removing NaCl from the incubation solution, and by preincubating the enterocytes with phlorizin prior to addition of EGF. Preincubation with amiloride did not inhibit the effect of EGF on Na+/K(+)-ATPase. The results confirm that EGF promotes uptake of both sodium and glucose by the jejunal mucosal cells, and suggest the effect of EGF on glucose and sodium is mediated through the brush-border membrane glucose-sodium transporter. The increase in Na+/K(+)-ATPase activity that occurs with EGF appears to be secondary to a rise in intracellular Na+ concentration. The short-term effects of EGF on glucose and sodium transport by the small intestine may have potential therapeutic implications.

Amiloride↗

Ventricular tachycardias of right ventricular origin: markers of subclinical right ventricular disease.

The diagnosis of subclinical myocardial disease in patients with ventricular tachycardias of right ventricular (RV) origin and no overt cardiac abnormalities is important, inasmuch as the presence of RV cardiomyopathy or arrhythmogenic dysplasia can be associated with a poor prognosis. To this end the relative value of symptoms, ECG features of ventricular tachycardia, signal-averaged ECGs, and RV echocardiograms as compared with endomyocardial biopsy findings was prospectively evaluated. Twenty-seven patients with chronic ventricular tachycardias with a left bundle branch block-like morphology, presumed to be of RV origin, were studied. Clinical examination findings, 12-lead ECGs in sinus rhythm, radiographs of the chest, coronary angiograms, and left ventricular cineangiograms were normal in all patients. RV biopsies were abnormal in 11 patients (41%) with findings suggestive of RV dysplasia or cardiomyopathy. A multivariate analysis showed a significant correlation between an abnormal biopsy and sustained ventricular tachycardia (p < 0.05), tachycardia with a superior frontal plane axis (p < 0.001), an abnormal signal-averaged ECG (p < 0.05), and an abnormal RV echocardiogram (p < 0.001). An abnormal RV echocardiogram was both a sensitive (73%) and a specific (94%) indicator of an abnormal RV biopsy. Sustained tachycardia although sensitive (90%) had a low specificity (56%). In comparison, a superior frontal plane axis of ventricular tachycardia and an abnormal signal-averaged ECG were indicative of high specificity and low sensitivity for abnormal myocardial histologic findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Histopathological changes following laser ablation of a left-sided accessory pathway in a human.

Laser ablation was performed intraoperatively in a patient with coronary artery disease and Wolff-Parkinson-White syndrome. Histopathological evaluation of the laser ablation site revealed a transverse laser incision in the left atrial septum and mitral valve annulus. There was hemorrhage in the atrioventricular (AV) groove with interruption of a posterolateral AV connection. The laser lesion was confined largely to the atrial aspect of the AV annulus. We conclude that laser catheter ablation of accessory pathways is feasible in humans.

Atrioventricular Node↗

Prevalence of fetal exposure to cocaine in Toronto, 1990-1991.

There has been an increasing use of cocaine in North America among women of reproductive age. The potential effects of cocaine on the fetus have raised serious concerns about the health of large numbers of children exposed in utero to the drug. Using neonatal hair and urine tests for benzoylegconine (BE), we quantified the incidence of fetal exposure to cocaine among 600 babies born in 3 nurseries in Toronto from 1990-91. A total of 37 babies (6.25%) tested positive for cocaine exposure by either hair test, urine test, or both. The hair test detected 33 cases and failed to identify 4 babies who had low urine concentrations of BE. The urine test failed to identify 76% of the cases. In downtown Toronto, the overall rate of fetal exposure to cocaine was 12.5% (25/200), significantly higher than in the 2 suburban nurseries (3%; 12/400). Babies are born with hair which has grown during the last trimester of pregnancy; hence, our analysis identifies women who have used cocaine long after they became aware of pregnancy. Our figures translate to more than 5,000 babies annually in the greater Toronto area who are cared for postnatally by mothers regularly using cocaine. Because history and urine testing during delivery fail to identify the majority of these cases, most of these children are not likely to receive the appropriate medical and social services and follow-up.

Adolescent↗