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Biomedical subjects

H Rastegar

Publications and source records attributed to H Rastegar.

At least 19 recordsLinked to original sources

Alpha 2-adrenoceptor and NO mediate the opioid subsensitivity in isolated tissues of cholestatic animals.

1. Our previous report showed that in acute cholestasis, the subsensitivity to morphine inhibitory effect on electrical-stimulated contractions develops significantly faster in guinea-pig ileum (GPI) and in mouse vas deferens (MVD) (45.2 and 29.9 times, respectively) compared with non-cholestatic subjects. 2. The possible contribution of alpha2-adrenoceptor and nitric oxide (NO) pathways on the development of tolerance was assessed in GPI and MVD of cholestatic subjects. 3. Daily administration of naltrexone (20 mg kg(-1)), yohimbine (5 mg kg(-1)), and Nomega-nitro-l-arginine methyl ester (l-NAME) (3 mg kg(-1)) to cholestatic animals significantly (P-value < 0.05) inhibited the process of subsensitivity in all groups. 4. Consistent with the literature, it was concluded that both the alpha2-adrenergic system and NO have close interaction with the opioid system and may underlie some of the mechanisms involved in the subsensitivity development to opioids in acute cholestatic states.

Analgesics, Opioid↗

Mesenteric vascular bed responsiveness in bile duct-ligated rats: roles of opioid and nitric oxide systems.

Changes in vascular responsiveness are proposed as the basis for some of the cardiovascular complications in cholestasis. Cholestasis is also associated with accumulation of endogenous opioid peptides and evidence of overproduction of nitric oxide (NO). The possible role of NO or opioid system in cholestasis-induced mesenteric vascular bed responsiveness was investigated. Bile duct-ligated and sham-operated rats were treated for 6 days with either normal saline, naltrexone, an opioid antagonist (20 mg/kg/day) or L-NAME (N(omega)-nitro-L-arginine methyl ester), a nitric oxide synthase inhibitor (3 mg/kg/day). After 7 days, the superior mesenteric artery was cannulated and the mesenteric vascular bed was perfused according to the McGregor method. Baseline perfusion pressure of the mesenteric vascular bed was decreased in bile duct-ligated compared to sham-operated animals. ED(50) of phenylephrine-induced vasoconstriction was increased, but vasoconstriction R(max) was not different in the vascular bed of bile duct-ligated rats and of sham-operated ones. Acetylcholine-induced vasorelaxation was impaired in bile duct-ligated rats (increased ED(50) and decreased vasorelaxation R(max)). Sodium nitroprusside-induced vasorelaxation was not different between bile duct-ligated and sham-operated rats, implying that the smooth muscle components of vasorelaxation were intact. Chronic treatment with L-NAME partially restored both the acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction response in bile duct-ligated rats. Naltrexone treatment also partially restored the acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in bile duct-ligated rats. There is impaired acetylcholine-induced vasorelaxation in cholestatic rats, probably due to a defect in endothelial function. This study also provided evidence for the involvement of increased opioidergic tone and NO overproduction in cholestasis-induced vascular hyporesponsiveness.

Acetylcholine↗

Time-dependent reduction of acetylcholine-induced relaxation in aortic rings of cholestatic rats.

Changes in vascular responsiveness are the basis for some of the cardiovascular complications in cholestasis. Since the duration of cholestasis is important in determining the degree of the complications, we investigated the time-course dependent evolution of vascular relaxation responsiveness in the aortic rings of cholestatic rats. Acetylcholine-induced endothelium-dependent relaxation was investigated in the isolated aortic rings of unoperated, sham-operated and two-, five-, seven- and fourteen-day bile-duct ligated rats. There was a significant reduction in acetylcholine-induced relaxation of the aortic rings by the second day after the bile-duct ligation operation, compared to those of unoperated and sham-operated groups, but more reduction still occurs in 5- and 7-day bile-duct ligated groups, reaching a plateau by the seventh day. The relaxation response to sodium nitroprusside in the aortic rings of the unoperated and the 7-day bile-duct ligated rats did not differ, implying the intact smooth muscle component of the relaxation pathway. L-NAME ( N(omega)-nitro-L-arginine methyl ester), a nitric oxide (NO) synthase inhibitor, attenuated the acetylcholine-induced relaxation in both groups (unoperated and bile-duct ligated), while L-arginine prevents this inhibitory effect. Indomethacin potentiated the acetylcholine-induced relaxation in the aortic rings of the bile-duct ligated rats while it has no effect on unoperated controls, providing evidence for the possible role of vasoconstrictor prostanoids in cholestasis-induced reduction in acetylcholine-induced relaxation. These results state that the reduced acetylcholine-induced relaxation in the cholestatic aortic rings during the first week, when no portal hypertension was reported to be present, may be due to the decreased acetylcholine-induced NO release from endothelium or increased NO inactivation.

Acetylcholine↗

Clinical benefits of endoscopic vein harvesting in patients with risk factors for saphenectomy wound infections undergoing coronary artery bypass grafting.

OBJECTIVE: The influence of endoscopic harvesting techniques on the prevalence of leg-wound complications after coronary artery bypass grafting remains to be defined for patients at high risk for the development of wound infections. METHODS: Among 1473 patients undergoing coronary artery bypass grafting who had the saphenous vein harvested by either a continuous incision or skip incisions leaving intact skin bridges, we determined the prevalence of wound infections to be 9.6%. The following variables were entered into logistic regression analysis to identify significant risk factors that might be predictive of wound infection: diabetes, peripheral vascular disease, obesity, renal failure, steroid use, age, sex, and type of closure. We then prospectively randomized 132 patients found to be at high risk of wound infection to either endoscopic vein harvesting or a continuous open incision. RESULTS: Univariate analysis showed female sex (P =.04), diabetes (P <.001), and obesity (P <.001) to be predictors of wound infection. In a multivariate model diabetes (P =.02) and obesity (P =.001) were independent predictors. In patients at high risk, the prevalence of wound infection was 4.5% for the endoscopic group versus 20% for the open group (P =.01). Vein procurement time was greater in the endoscopic group (65 minutes vs 32 minutes, P <.001), as was the number of vein repairs required (2.5 vs 0.6, P <.001). CONCLUSION: The use of endoscopic vein harvesting decreases the prevalence of postoperative leg-wound infections in high-risk patients with diabetes and obesity. Whether this translates into an economic benefit that justifies the additional cost of that technology requires further analysis.

Aged↗

Subsensitivity to opioids is receptor-specific in isolated guinea pig ileum and mouse vas deferens after obstructive cholestasis.

The rate and degree of subsensitivity development to morphine (mu-opioid receptor, preferred, but not selective agonist) and U50488H (highly selective kappa-opioid receptor agonist) were assessed in vitro on guinea pig ileum (GPI) of cholestatic animals 2, 5, and 7 days after bile duct ligation. In addition to this phenomenon of morphine, the effects of U50488H and SNC 80 (highly selective delta-opioid receptor agonist) were studied in vitro on mice vas deferens (MVD) of cholestatic animals 2, 5, 7, 10, and 15 days after bile duct ligation. The IC(50) for each compound was determined in these preparations. The ratio of the IC(50) in bile duct-ligated animals to sham and control animals provides a quantitative index for the degree of subsensitivity development to each agonist. For any given time, the highest degree of subsensitivity to morphine was observed in GPI of cholestatic animals, whereas in MVD obtained from the cholestatic animals, the highest degree of subsensitivity developed to inhibitory effect of SNC 80. The subsensitivity development in cholestatic animals was time dependent; in GPI the maximum subsensitivity developed after 7 days of the operation, whereas the maximum subsensitivity in MVD developed 15 days after bile duct ligation. Moreover, subsensitivity to exogenous acetylcholine and norepinephrine in GPI and MVD, respectively, did not develop in the presence of subsensitivity to opioids in cholestatic animals. Significant accumulation of endogenous opioids in plasma of cholestatic animals has been shown in several studies and this may account for a significant development of subsensitivity to inhibitory effects of opioid agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Perioperative and long-term results with mapping-guided subendocardial resection and left ventricular endoaneurysmorrhaphy.

BACKGROUND: Surgical ablation of the arrhythmogenic focus in patients with life-threatening ventricular tachyarrhythmias can be curative. However, the surgical techniques have been plagued by a high perioperative mortality rate (averaging approximately 12%). Reconstruction of the left ventricle may reduce mortality. METHODS AND RESULTS: Reconstruction of the left ventricle with a pericardial patch, or endoaneurysmorrhaphy, was performed with mapping-guided subendocardial resection for recurrent ventricular tachycardia in 25 patients over a 5-year period. Postoperatively, electrophysiological studies were conducted to assess the results of surgery, which were further evaluated during long-term follow-up with survival analyses. The study included 25 patients, 60 +/- 9 years of age, with coronary artery disease, discrete left ventricle aneurysms, and malignant ventricular tacharrhythmias. Left ventricular ejection fraction was 24 +/- 6% preoperatively. Left ventricular endocardial mapping, endocardial resection, and endoaneurysmorrhaphy were performed in all patients. There was no operative or postoperative (30-day) mortality. Postoperative ventricular tachycardia was induced in 2 of the 25 patients (8%); left ventricular function increased to 32 +/- 9% (range, 19% to 52%). At a mean follow-up of 37 +/- 16 months (range, 6 to 65 months), there had been 6 deaths, including 1 sudden cardiac death, 2 congestive heart failure deaths, and 3 noncardiac deaths. Analysis of multiple variables failed to identify predictors of postoperative inducibility, sudden cardiac death, cardiac death, or total mortality. CONCLUSIONS: Endoaneurysmorrhaphy with a pericardial patch combined with mapping-guided subendocardial resection frequently cures recurrent ventricular tachycardia with low operative mortality and improvement of ventricular function. Long-term follow-up demonstrates low sudden cardiac death rates.

Aged↗

Surgical treatment of systemic atheroembolism from the thoracic aorta.

BACKGROUND: Surgical procedures performed exclusively for atheroembolic events arising from the thoracic aorta rarely have been reported. Presented here are 2 patients who underwent successful operation for these problems. METHODS: The clinical presentation, diagnostic evaluation and surgical approach to 2 patients with different embolic sources in the thoracic aorta are presented. One patient had experienced three strokes and was noted by multiplane transesophageal echocardiography to have protruding atheromas with ulcerations in the transverse arch and origin of the brachiocephalic vessels. The transverse arch was replaced using hypothermic circulatory arrest with individual reimplantation of the brachiocephalic vessels. The second patient presented with "blue toe" syndrome from mobile atheromas in the mid-descending thoracic aorta defined by transesophageal echocardiography. A localized debridement was performed using simple aortic cross-clamping. RESULTS: Both patients had uneventful postoperative courses and had no further atheroembolic events. CONCLUSIONS: When standard diagnostic modalities do not delineate an embolic source for either stroke or peripheral embolization, transesophageal echocardiography is recommended as an excellent means of identifying atheromas in the thoracic aorta that could be the source for emboli. Once these lesions are identified, a surgical procedure should be performed to prevent further embolization.

Aorta↗

Fully transvenous cardioverter defibrillators: rare need for subcutaneous patch with two newer-generation systems.

In published series of nonthoractomy ICDs, there has invariably been a need for combining transvenous lead(s) with a subcutaneous patch to obtain adequate DFTs. Since the newer generation transvenous lead ICD systems became available for clinical investigation, we have tested and implanted 38 such systems in patients with drug-refractory malignant ventricular arrhythmias who were first seen with aborted sudden death (n = 10), syncope (n = 3), or sustained ventricular tachycardia (n = 25). These patients (mean age 60 +/- 15 years) had coronary artery disease (n = 25), congenital heart disease (n = 1), or cardiomyopathy (n = 12) as the underlying heart disease and a mean left ventricular ejection fraction of 34% +/- 16%. Seventeen (45%) patients had previous cardiac surgery (coronary bypass and/or valve replacement). The transvenous lead system included the Endotak C (single) lead of CPI (n = 27) or the EnGuard double-lead system of Telectronics (n = 11). The integrated pace/sense/defibrillation lead(s) were usually introduced via the left cephalic vein; after endocardiac positioning and testing, the leads were tunneled to the abdominal pocket in which the ICD device was implanted. DFTs were adequate for all patients (100%) and averaged 13.5 +/- 5.4 J (range 2.4 to 25 J). A subcutaneous patch or array was needed in only three patients. Because of protocol requirements, a subcutaneous patch or electrode array was intraoperatively tested in another three patients but was finally not implanted because better DFTs were achieved with the transvenous lead-alone configuration. The leads were combined with second-generation devices in 12 patients and third-generation ICDs in 26 (68%) patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of various calcium channel blockers on guinea-pig isolated common bile duct.

1. The inhibitory effects of various calcium channel blockers; nifedipine, verapamil, diltiazem and a heterogenous compound, dantrolene, have been investigated on isolated common bile duct from guinea-pig. 2. All the compounds tested induced a concentration-dependent reduction of the amplitude of contractile response to electrical stimulation or increasing the calcium concentration of the bathing media. 3. Nifedipine was the most potent compound whereas the least potent was dantrolene; verapamil and diltiazem had intermediate potency. 4. The IC50 values for these compounds were calculated as: nifedipine 3.68 x 10(-9) M; verapamil, 4.93 x 10(-8) M; diltiazem, 4.2 x 10(-7) M; and dantrolene 5.51 x 10(-5) M. 5. All the compounds displaced the concentration-response curve of calcium chloride to the right in a concentration-dependent manner. Among the compounds studied, nifedipine had the highest and dantrolene had the lowest potency. 6. These results indicate the striking pharmacological effects of the calcium channel blockers on the common bile duct and may indicate a possible role for these compounds in the treatment of biliary colic.

Animals↗

Clinical and hemodynamic performance of the 19-mm Carpentier-Edwards porcine bioprosthesis.

Because of concerns about the hemodynamic performance of 19-mm porcine valves, we retrospectively reviewed the clinical results and echocardiographic studies of 52 consecutive patients who received a 19-mm Carpentier-Edwards porcine bioprosthesis (model 2625) for aortic valve replacement from 1986 through 1991. Nearly 87% of the patients were women, the mean age was 69 years, and the mean body surface area was 1.63 +/- 0.27 m2. Seventy-three percent of the patients had pure aortic stenosis, 96% were in New York Heart Association classes III and IV, and 56% underwent urgent or emergent operation. Overall hospital mortality was 7.7% with a late mortality of 8.3% at a mean follow-up of 25 +/- 18 months. No patient experienced a valve-related complication, and 95% of surviving patients were in New York Heart Association classes I and II. Two-dimensional and Doppler echocardiography performed during the first postoperative week revealed a maximal instantaneous gradient of 44.7 +/- 13.0 mm Hg. In 43 patients for whom additional data were available, the mean gradient was 26.4 +/- 8.2 mm Hg with an effective orifice area of 0.85 +/- 0.18 cm2. This study defines the normal range of postoperative gradients across the 19-mm Carpentier-Edwards porcine valve and demonstrates that patients receiving this valve can achieve significant clinical improvement despite the presence of high transvalvular gradients measured by echocardiography.

Adult↗

Effects of coronary artery bypass grafting on ventricular arrhythmias: results with electrophysiological testing and long-term follow-up.

Myocardial revascularization was performed in 56 patients with coronary artery disease who presented with ventricular tachycardia (VT) (n = 39) or ventricular fibrillation (n = 17). There were 46 men and 10 women, aged 65 +/- 10 years. Three vessel (n = 42) or left main disease (n = 4) was present in 82%. Left ventricular ejection fraction averaged 36% +/- 11%. Electrophysiological studies were performed preoperatively in all patients; 50 (89%) had inducible ventricular arrhythmias. Sustained monomorphic VT was induced in 40 patients (cycle length 284 +/- 61 msec). Reproducible symptomatic nonsustained VT was induced in four patients and ventricular fibrillation in six patients, while six patients had no inducible arrhythmia. Preoperatively the patients with inducible VT failed 3.3 +/- 1.2 drug trials during electrophysiological studies. In addition to coronary bypass, 22 patients also received an automatic implantable cardioverter defibrillator (ICD), 26 patients received prophylactic ICD patches, and 1 patient had resection of a false aneurysm. There were no perioperative deaths. Postoperative electrophysiological studies were performed in all 56 surgical survivors. Ventricular tachyarrhythmia could not be induced in the six patients who had no inducible VT preoperatively and in 13 of 40 (33%) with preoperatively inducible sustained VT or in 19 of 50 (38%) patients with any previously inducible ventricular arrhythmia, thus a total of 25 patients (45%) had no inducible VT postoperatively. Of the remaining, 11 patients were treated with antiarrhythmic drugs alone, 11 had already received an ICD (combined with drugs in 7), and another 9 received the ICD postoperatively (combined with drugs in 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Analysis of photoproducts, free radicals, and particulate debris generated during in vivo argon laser myoplasty.

Catheter-guided laser myoplasty in a closed ventricle has been advocated for the treatment of hypertrophic cardiomyopathy, ablation of arrhythmogenic foci, and transmyocardial laser revascularization of ungraftable regions of ischemic myocardium. The purpose of this study was to evaluate the nature of particulate debris and photoproducts generated in vivo. Accordingly, cardiopulmonary bypass was established in four dogs without active cooling and an apical left ventricular vent was placed. In two dogs, a laser catheter was inserted into the cardioplegia-arrested left ventricle through the left atrial appendage and across the mitral valve. In the other two dogs the laser catheter was inserted into a perfused, fibrillating left ventricle retrograde across the aortic valve. Myocardial ablation of the ventricular septum was performed using continuous argon-ion laser irradiation (8-10 watts, 4-11 minutes) and blood samples were drawn through the ventricular vent. The final ablation in each dog was done during a separate ventricular flush with a chemical "spin trap" capable of detecting free radicals. Analysis of ventricular effluent revealed levels of carboxyhemoglobin and hydrogen cyanide which were well below accepted clinical toxic limits. Microparticulate debris (2-300 femtoliter) was not detected. Evidence of trace free radical generation was suggested in one of four dogs. In conclusion, closed ventricular argon laser myoplasty did not generate clinically significant levels of the toxic photoproducts we measured, or microparticulate debris. These in vivo findings suggest that the clinical application of catheter-based laser myoplasty will not be limited by the generation of these toxic photoproducts or microembolic debris.

Animals↗

Accuracy of rhythm classification using a data log system in implantable cardioverter defibrillators.

Because the presence or absence of symptoms alone may be insufficient to correctly diagnose the rhythm for which implantable cardioverter defibrillator therapy is delivered, we hypothesized that the addition of data log information available in Telectronics ATP 4210 may improve the accuracy of rhythm classification. With this system the recorded ventricular electrogram cycle length is reported on a beat-to-beat basis immediately before, during, and after the tachyarrhythmia is detected. Using this information recorded from the data log in 32 separate tachyarrhythmia episodes in 20 patients, we compared the sensitivity, specificity, and predictive accuracy of rhythm classification on the basis of symptoms alone, data log alone, and data log combined with symptoms. While classification based on symptoms alone is highly specific (10/10 episodes), it is insensitive and has an overall predictive accuracy of 53%. By contrast, data log is sensitive (90%) and specific (91%) with better predictive accuracy (94%) than symptoms alone (P = 0.002). The addition of symptoms to information on beat-to-beat cycle length from data log resulted in a slight increase in predictive accuracy.

Data Collection↗

Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery.

To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias.

Adult↗