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Biomedical subjects

D Mehta

Publications and source records attributed to D Mehta.

At least 55 records · Page 3Linked to original sources
PubMed1998

Nitric oxide, prostacyclin and cyclic nucleotide formation in externally stented porcine vein grafts.

Non-restrictive, porous, external stents inhibit neointima formation in porcine vein grafts. Since the mechanisms underlying these effects are unknown we investigated the impact of this external stent on factors known to inhibit vascular smooth muscle cell proliferation: prostacyclin (PGI2), nitric oxide (NO), cAMP and cGMP formation in different regions of stented and unstented porcine vein grafts. Paired stented and unstented saphenous vein-carotid artery interposition grafting was carried out in Landrace pigs. One month after surgery, the vessels were excised and the formation of PGI2, cAMP and cGMP determined using radioimmunoassay and nitric oxide synthase (NOS) distribution studied using autoradiography and histochemistry. There were no significant differences between PGI2, cAMP and cGMP (nitroprusside-stimulated) formation in the medial/intimal regions of grafts of stented vein graft and ungrafted saphenous vein whereas all were significantly reduced in unstented vein graft. A23187-stimulated cGMP formation (mediated by NO release) and NOS content was significantly greater in the medial/intimal region of stented and unstented vein graft compared to ungrafted saphenous vein, indicating induction of endothelial NOS (eNOS) in both types of graft. This normalisation of the PGI2-cAMP axis and guanylyl cyclase activity in the medial/intimal region may contribute to the beneficial impact of the external stent on vein graft thickening. The increase in eNOS in both stented and unstented vein grafts mitigates against this isoform as playing a role in mediating the inhibitory effect of the stent on neointima formation. In the adventitia of both stented and unstented grafts there was an increase in PGI2, cAMP and cGMP formation compared to ungrafted saphenous vein, the production being greater in the stented compared to the unstented graft. In the adventitia of stented veini grafts, NOS, detected with NAPDH diaphorase staining, was associated with microvessels as well as with inflammatory cells. Taken together, these data are suggestive of a role for PGI2 and NO in promoting microangiogenesis in the adventitia of stented vein grafts which may in turn minimize graft hypoxia, an established contributory factor to neointima formation.

Animals↗
PubMed1998

A prolonged QRS duration on surface electrocardiogram is a specific indicator of left ventricular dysfunction [see comment].

OBJECTIVE: We sought to determine whether a prolonged QRS-interval duration is associated with decreased left ventricular (LV) systolic function. BACKGROUND: The 12-lead electrocardiogram (ECG) is a routine test for suspected cardiac disease. Although several scoring systems have been devised to estimate LV systolic function, no studies have examined the direct relationship between QRS duration alone and LV systolic function. METHODS: We analyzed the standard 12-lead surface ECG of 270 consecutive patients, referred for radionuclide ventriculography. Patients (n = 44) with bundle branch blocks, atrial flutter or fibrillation, pacemaker rhythm, recent myocardial infarction or bypass surgery, and patients on antiarrhythmic drugs were excluded. In the remaining patients (n = 226), we correlated the QRS duration on standard resting ECG, and the resting LV ejection fraction (EF), end-systolic and end-diastolic counts (ESC and EDC, respectively; LV volume indices), as obtained by radionuclide angiography. We used a multivariate analysis to identify independent predictors of reduced ventricular function entering QRS duration, the previously described R-wave score and clinical variables in our model. RESULTS: The QRS duration in the abnormal EF group was significantly longer than in the normal EF group (0.102 vs. 0.091 s, p < 0.0001). A QRS duration >0.10 s was highly specific (83.6%), but modestly sensitive (43.8%), for the prediction of abnormal EF. Furthermore, an abnormal EF was predicted with incrementally increased specificity (83.6% to 99.3%) and a corresponding decrease in sensitivity (43.8% to 13.8%) for each 0.01-s increase in the definition of prolonged QRS (from >0.10 to >0.12 s). Accordingly, the positive likelihood ratio for the prediction of decreased LV function was increased from 2.67 to 19.7 as the definition of prolonged QRS duration was increased from >0.10 to >0.12 s. In the multivariate analysis, a prolonged QRS duration and a low R-wave score were the only independent predictors of decreased LV systolic function. CONCLUSIONS: Prolonged QRS duration (>0.10 s) obtained from a standard resting 12-lead ECG is a specific, but relatively insensitive indicator of decreased LV systolic function. Further prolongation of the QRS had a higher specificity for decreased LV EF and a higher positive likelihood ratio for predicting abnormal LV EF.

Arrhythmias, Cardiac↗
PubMed1998

External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting.

Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited. Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferation and extracellular matrix deposition, followed later by superimposed atherosclerosis. These changes directly compromise graft blood flow and provoke thrombosis. Vein graft wall thickening may represent an adaptation imposed by arterial hemodynamic factors, and these factors have been shown to promote vascular smooth muscle cell migration and proliferation through activation of key mediators including platelet-derived growth factor (PDGF). Many pharmacological interventions aimed at preventing these long-term changes have proven unsuccessful in clinical evaluation. We recently demonstrated in a pig saphenous vein graft model that application of an external polyester stent to the outside of carotid interposition vein grafts reduced intimal hyperplasia and total wall thickness 1 month after implantation. However, it is not known whether the benefits of the stent are maintained in the longer term or what mechanisms underlie its effect. The present study therefore compared morphological changes and PDGF expression in stented grafts and contralateral unstented grafts in the same pigs, 6 months after graft implantation. Reduced medial thickening, neointima formation, and cell proliferation were sustained in externally stented grafts, and these effects were associated with a significant reduction in PDGF expression.

Animals↗
PubMed1998

Endothelin-1 and endothelin receptors in porcine saphenous vein-carotid artery grafts.

The regional distribution of endothelin-1 (ET-1) and its receptor subtypes (ETA and ETB) in porcine saphenous vein into carotid artery interposition grafts was studied 1 month after surgery and compared to ungrafted saphenous vein and carotid artery. ET-1 immunoreactivity was identified by immunohistochemistry and ET receptor subtypes were studied using in vitro autoradiography. In vein grafts, there was a higher density of ETA compared to ETB receptor binding in both the tunica media and the neointima. ETA binding to the tunica media of ungrafted saphenous vein was greater than that in the carotid artery or vein grafts, but greater in the vein graft compared to the carotid artery. Immunoreactive ET-1 was located in endothelial cells and throughout the neointima of the vein graft. Dense ETA and ETB binding was also associated with adventitial microvessels in the graft, and ETB binding was also identified to neutrophils, which accumulated at the subendothelium and within the adventitia. ETA receptors may play a role in vein graft thickening at the medial and neointimal vascular smooth-muscle cell level, whereas ETB receptors may play a role in microangiogenesis. The high levels of ETA receptors in the tunica media of ungrafted saphenous vein, relative to the carotid artery and vein graft, may also render this conduit susceptible to neointimal formation. These data indicate that studies of the effect of ET receptor antagonists on the pathobiology of vein graft disease are warranted.

Animals↗
PubMed1998

Late complications in patients with pectoral defibrillator implants with transvenous defibrillator lead systems: high incidence of insulation breakdown.

As the majority of ICDs with transvenous leads are now implanted in the pectoral region, complications associated with the technique are being identified. To determine the incidence of lead complications in patients with transvenous defibrillator leads and ICDs implanted in the pectoral region, 132 unselected consecutive patients with transvenous defibrillator leads had ICDs implanted in the pectoral region. Three lead systems were used: (1) lead system 1 (45 patients) consisted of a transvenous pacing sensing lead and a superior vena cava coil with a submuscular patch used for defibrillation; (2) lead system 2 (36 patients) utilized a CPI Endotak lead system; and (3) lead system 3 (51 patients) utilized a Medtronic Transvene lead system. Patients were followed for 3-54 months (cumulative 2,269, mean 18 months). The average duration of follow-up with the three systems was 32, 12 and 11 months, respectively. At 30 months follow-up, all three lead systems had a low incidence of complications. However, there was a 13% overall incidence (45% actuarial incidence) of erosion of the insulation of the pacing sensing lead of system 1 at 50 months of follow-up. All lead complications were seen in patients with ICDs whose weights were > 195 g and volumes > 115 cc. The erosion was probably a consequence of the pressure by the large ICD against the lead in the pectoral pocket. Follow-up with lead systems 2 and 3 is relatively short (average 12 months) but no lead erosions were seen. Pectoral implantation of ICDs with long transvenous leads and large generators is associated with a moderate risk of late complications in the form of insulation breaks caused by pressure of the generator against the leads. The use of less redundant leads coupled with smaller ICDs will probably eliminate this complication.

Defibrillators, Implantable↗
PubMed1998

Variable effects of adenosine on retrograde conduction in patients with atrioventricular nodal reentry tachycardia.

Adenosine has been demonstrated to reliably produce transient block of atrioventricular nodal (AVN) conduction, and has been advocated as a method of differentiating retrograde conduction via the atrioventricular node from accessory pathway conduction. However, the response of retrograde AVN to adenosine in patients with typical atrioventricular nodal reentry tachycardia (AVNRT) remains unclear. We evaluated 13 patients (mean age 45 +/- 20 years) with typical AVNRT prior to AVN modification. During right ventricular pacing, a rapid bolus of adenosine (0.2 mg/kg; maximum 18 mg) was administered. Adenosine sensitivity, defined by transient ventriculoatrial block, was observed in six patients, while in seven patients ventriculoatrial conduction was unaffected. An adenosine bolus administered during sinus rhythm or atrial pacing resulted in antegrade atrioventricular block in all the adenosine resistant patients in whom this was performed (n = 6). Comparisons of AVN electrophysiological characteristics between the adenosine sensitive and adenosine resistant patients were performed. There was no difference with respect to ventriculoatrial effective refractory period, ventriculoatrial Wenckebach, AVNRT cycle length, and His to atrial echo interval in AVNRT. However, there was a trend toward a longer antegrade fast pathway ERP in the adenosine sensitive group (P = 0.07). Electrophysiological properties do not predict retrograde AVN adenosine sensitivity. Adenosine does not cause retrograde AVN block in all patients with AVNRT, and therefore cannot reliably distinguish between retrograde conduction via the AVN or an accessory pathway.

Adenosine↗
PubMed1998

Uncommon atrial flutter: characteristics, mechanisms, and results of ablative therapy.

Thirty-seven patients with atrial flutter were studied with catheter mapping and radiofrequency ablation. Uncommon atrial flutter occurred in 20 out of 37 (54%) patients. Atrial endocardial mapping showed two types of uncommon atrial flutter. In 15 patients (group I) it was characterized by a single clockwise circuit whereas in 5 patients (Group II) it was characterized by the presence of more than one circuit and/or localized atrial fibrillation. RFA ablation was acutely successful in 14 out of 15 patients (93%) in Group I and in 2 out of 5 (40%) patients in Group II. On long-term follow-up a significantly larger number of patients in Group I versus Group II (86% vs 20%) remained free of atrial flutter recurrence. We conclude that uncommon atrial flutter is a heterogeneous entity involving one or more reentrant circuits. Uncommon atrial flutter with multiple circuits may not be suitable for RFA.

Adult↗
PubMed1998

Relationship between paxillin and myosin phosphorylation during muscarinic stimulation of smooth muscle.

The tyrosine phosphorylation of paxillin increases in association with force development during tracheal smooth muscle contraction, suggesting that paxillin plays a role in the contractile activation of smooth muscle [Z. L. Wang, F. M. Pavalko, and S. J. Gunst. Am. J. Physiol. 271 (Cell Physiol. 40): C1594-C1602, 1996]. We compared the Ca2+ sensitivity of the tyrosine phosphorylation of paxillin and myosin light chain (MLC) phosphorylation in tracheal muscle and evaluated whether MLC phosphorylation is necessary to induce paxillin phosphorylation. Ca(2+)-depleted muscle strips were stimulated with 10(-7)-10(-4) M acetylcholine (ACh) in 0,0.05, 0.1, or 0.5 mM extracellular Ca2+. In the absence of extracellular Ca2+, 10(-4) M ACh induced a maximal increase in paxillin phosphorylation without increasing MLC phosphorylation or force. Increases in extracellular Ca2+ concentration did not further increase paxillin phosphorylation. However, during stimulation with 10(-6) M ACh, paxillin phosphorylation increased with increases in extracellular Ca2+ concentration. We conclude that the tyrosine phosphorylation of paxillin can be stimulated by signaling pathways that do not depend on Ca2+ mobilization and that the activation of contractile proteins is not required to elicit paxillin phosphorylation.

Acetylcholine↗
PubMed1997

Left ventricular volume reduction surgery.

Left ventricular volume reduction has recently been introduced as a surgical treatment for end stage dilated cardiomyopathy. This operation involves the resection of a slice of viable left ventricular myocardium in order to reduce the wall tension imposed upon the contracting heart chamber. Early results are encouraging, but clinical evaluation on a larger scale is required. In the present article, we describe the indications, surgical principles and results of left ventricular volume reduction surgery with reference to our group's experience.

Animals↗
PubMed1997

Towards the prevention of vein graft failure.

Improved outcome after coronary bypass surgery over the last decade has been attributed largely to the increasing use of arterial conduits and their superior patency rates over that of saphenous vein grafts. In spite of this trend, autologous saphenous vein has remained an important and convenient conduit for a variety of operative scenarios, and is still used for more than 70% of grafts. As a result, vein graft failure continues to represent a significant clinical and economic burden upon the health care service. Between 15 to 30% of saphenous vein grafts occlude within the first year of surgery, increasing to over 50% after 10 years. By this time, more than 10% of patients will require further intervention to alleviate symptoms arising from occluded grafts and progression of native disease. Graft occlusion arises either from early thrombosis or the later onset of 'vein graft disease' and subsequent atherosclerotic changes.

Animals↗
PubMed1997

Staged minimally invasive direct coronary artery bypass and percutaneous angioplasty for multivessel coronary artery disease.

OBJECTIVE: Minimally invasive direct coronary artery bypass (MIDCAB) using the left internal mammary artery (IMA) to the left anterior descending (LAD) coronary artery can be performed with low operative risk. MIDCAB can be combined with percutaneous transluminal coronary angioplasty (PTCA) to treat patients with multivessel disease. We report here our experience with staged MIDCAB and PTCA in the management of a selected group of patients. METHODS AND RESULTS: 11 patients (9 males, mean age 64.6+/-8.7 years) with multivessel coronary artery disease received left IMA grafts to the LAD using the MIDCAB approach. There were no postoperative morbidity or mortality. All patients were extubated within 4 h of leaving the operating room with a mean ITU stay of 12.8 h. All patients but two underwent coronary angioplasty during the same hospital admission, 3.8+/-1.3 days after the MIDCAB procedure. Angiography confirmed IMA grafts patency in all patients, and complete revascularisation by PTCA of other coronary arteries was possible in all patients but one. Mean hospital stay was 5.9 days, and all patients remain free of angina at a mean follow-up period of 11.4 months. CONCLUSIONS: Staged MIDCAB and angioplasty is an experimental approach for the management of selected patients with multi-vessel coronary artery disease. Further experience is needed to clarify patient selection and the long-term outcome of this approach.

Aged↗
PubMed1997

Predictors of long-term survival in patients with malignant ventricular arrhythmias.

The study consisted of 369 patients (age 62 +/- 13 years) who presented to our institution from April 1984 to April 1994 for malignant ventricular arrhythmias presenting as sustained ventricular tachycardia (VT) in 57% of patients, ventricular fibrillation in 25% of patients, and syncope due to VT in 17% of patients. Coronary artery disease was present in 74% of patients, cardiomyopathy in 19% of patients, and no evident heart disease in 7% of patients. Two hundred twenty-one patients were given drug, therapy, 47 patients underwent arrhythmia surgery, and 75 patients had an implantable cardioverter-defibrillator (ICD). During a mean follow-up of 30 months (range 1 to 101), 66 patients (18%) died from a cardiac death of which 26 (39%) were sudden. Cox regression analysis was conducted utilizing a total of 19 variables (clinical and therapeutic) in the entire population and separately in patients with coronary artery disease and cardiomyopathy. The most significant variables (multivariate analysis) of survival from cardiac mortality in the entire population were: congestive heart failure (CHF) class (p = 0.0003), ejection fraction (p = 0.02), and the use of drug therapy (p = 0.03); in patients with coronary artery disease, CHF class (p = 0.0001) and ejection fraction (p = 0.0006); and in patients with cardiomyopathy, CHF class (p = 0.009) and sustained VT on Holter monitoring (p = 0.007). Kaplan-Meier survival rates from cardiac death were: significantly lower (p = 0.005) in patients with CHF class III and IV compared with CHF class I and II (25% vs 58%, p = 0.005) with drug therapy; marginally significant (47% vs 88%, p = 0.06) from 20 to 40 months in patients with an ICD; and nonsignificant in patients who underwent arrhythmia surgery (63% vs 71%). Patients with an ICD had a better expected survival (82%) than patients who had arrhythmia surgery (69%) and drug therapy (65%). Thus, in patients with malignant ventricular arrhythmias, CHF class was the most significant independent predictor of survival from cardiac mortality over all disease substrates, and therapy influenced survival depending on the CHF class. Patients in CHF class III and IV who underwent arrhythmia surgery or had an ICD had a better expected survival than those taking drug therapy, and the negative impact of antiarrhythmic therapy was most prominent in patients with CHF class III and IV.

Aged↗
PubMed1997

Nitric oxide synthase and adenylyl and guanylyl cyclase activity in porcine interposition vein grafts.

BACKGROUND: A high proportion of autologous saphenous vein grafts occlude as the result of intimal thickening. Blood vessels synthesize substances that may inhibit such intimal thickening. These include cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are stimulated by prostacyclin and nitric oxide, respectively. The prostacyclin-cAMP and nitric oxide-cGMP axes were therefore investigated in porcine vein grafts. METHODS: Saphenous vein-carotid artery interposition graft procedures were carried out in pigs. One month after the operation, ungrafted saphenous veins, vein grafts, and carotid arteries were excised, the formation of cAMP and cGMP was assessed by radioimmunoassay, and the nitric oxide synthase content was determined by autoradiography. RESULTS: The formation of cAMP and nitroprusside-stimulated cGMP was significantly diminished in vein grafts compared with ungrafted saphenous veins and carotid arteries. Calimycin-stimulated cGMP synthesis (nitric oxide release dependent) and the endothelial nitric oxide synthase content (autoradiography) were significantly elevated in vein grafts compared with ungrafted saphenous veins but were significantly less than those in carotid arteries. CONCLUSIONS: Adenylyl and guanylyl cyclase activity are down-regulated in vein grafts, which may contribute to the development of intimal and medial thickening. Nitric oxide release and endothelial nitric oxide synthase content are up-regulated in vein grafts, which is indicative of an adaptation to the arterial conditions of shear stress and pulsatile pressure.

Adaptation, Physiological↗
PubMed1997

Prevention of vein graft failure: potential applications for gene therapy.

The use of gene therapy in the clinical setting is believed to be a realistic option for the future. Many clinical trials are underway for treatment of disorders as diverse as cancer, peripheral vascular disease, and numerous monogenic disease. However, gene therapy for vein graft failure may be more distant due to the highly complex, multifactorial aetiology of the disease. Although many of the cellular mechanisms involved in vein graft failure have been reported, important barriers still need to be overcome before gene therapy could become a clinical reality. Further understanding of the molecular mechanisms involved in graft failure will lead to the identification of appropriate therapeutic genes. Moreover, limitations in the current delivery systems need to be overcome to allow efficient, safe delivery and expression of transgenes for the required length of time in vivo. However, currently available gene delivery vectors are extremely useful tools to help in our understanding of vein graft failure. In this review, we address the issues surrounding gene therapy with particular emphasis on its future potential to ameliorate long term vein graft occlusion.

Gene Transfer Techniques↗
PubMed1997

A pitfall in using far-field bipolar electrograms in arrhythmia discrimination in a patient with an implantable cardioverter defibrillator.

Analysis of stored electrograms from bipolar far-field electrodes is considered to be useful in differentiating supraventricular from ventricular arrhythmias. A case of inappropriate ICD shocks for sinus tachycardia is presented whereby successive shocks caused marked widening of the ventricular electrograms. Analysis of these stored electrograms, recorded from far-field bipolar electrodes, gave the false impression of ventricular tachycardia. The widening was due to the current of injury effects, probably a consequence of the large amount of intervening myocardium between the bipoles. While analyzing recordings from far-field bipolar electrodes is generally useful, it is not always reliable, for changes in electrogram morphology, relative to baseline rhythm, may result from other factors like current of injury.

Adult↗