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M Scheinman

Publications and source records attributed to M Scheinman.

At least 19 recordsLinked to original sources
PubMed2001

Glycine preserves function and decreases necrosis in skeletal muscle undergoing ischemia and reperfusion injury.

BACKGROUND: Glycine (GLY) is a neutral amino acid that has been shown to be cytoprotective in the kidneys of dogs and rabbits undergoing ischemia-reperfusion injury. To investigate whether GLY exhibits a protective effect on skeletal muscle subjected to ischemia and reperfusion injury, we used a well-described gracilis muscle model in canines. METHODS: Twelve adult mongrel dogs were subjected to 6 hours of ischemia in 1 randomly selected side. The dogs were randomized into 2 groups: group 1 (6 animals) underwent 15 minutes of perfusion with 2.2% GLY, and group 2 (6 animals) underwent 15 minutes of perfusion with normal saline solution (NS) only. Both groups had normothermic reperfusion for 1 hour along with the corresponding perfusate. Muscle biopsy specimens were taken, frozen in liquid nitrogen, and stored at -70 degrees C. Muscle injury was evaluated at 48 hours by measuring weight gain (edema), maximal contractile force, and percent of muscle necrosis. Adenosine triphosphate (ATP) and phosphocreatine (Pcr) (an energy store for ATP synthesis) levels were determined by using high performance liquid chromatography. RESULTS: In group 1, the average weight gain was 57% +/- 11.27% while in group 2 it was 100% +/- 12.48%. Maximal muscle contractile force was 712.5 +/- 68 g for group 1 and 511 +/- 27.91 g for group 2. The amount of muscle necrosis was 30 +/- 3.7% in group 1, as opposed to 63 +/- 10% in group 2. The ATP content was 0.07 +/- 0.03 nmol/mg wet tissue weight (post-ischemia with NS) and 0.21 +/- 0.08 nmol/mg wet tissue weight (post-ischemia with GLY). Pcr content was 0.19 +/- 0.04 mmol/mg wet tissue weight (post-ischemia with NS) and 0.27 +/- 0.04 micromol/mg wet tissue (post-ischemia and infused with GLY) (P <.05). CONCLUSIONS: These data show that GLY preserves muscle function, decreases edema and the amount of muscle necrosis and preserves energy stores in this canine model. Because GLY can be safely given systemically in human beings in higher concentrations than that given in our model, as it is given in parenteral nutrition, its mechanism of action should be further investigated for its potential use in the clinical setting of ischemia and reperfusion injury.

Adenosine Triphosphate↗
PubMed2001

Thiamine reverses hyperglycemia-induced dysfunction in cultured endothelial cells.

BACKGROUND: High levels of glucose have previously been shown to inhibit endothelial cell migration and increase secretion of the von Willebrand factor (vWF), a marker of endothelial cell damage. This study investigates whether thiamine, an important coenzyme in intracellular glucose metabolism, improves endothelial cell migration and decreases von Willebrand factor secretion under hyperglycemic conditions. METHODS: Bovine aortic endothelial cells (BAECs) were grown under physiological glucose (5.5 mmol/L) and hyperglycemic (13.8 mmol/L and 27.7 mmol/L) conditions with or without thiamine (200 micromol/L) supplementation. Endothelial cell migration was investigated in monolayers of BAECs that were wounded by scraping. The distance of migration, the number of migrating cells, and the surface area covered by the migrating cells were measured. Secretion of vWF by BAECs under physiological glucose and high glucose conditions with or without thiamine (200 micromol/L) supplementation was studied with enzyme-linked immunosorbent assay. RESULTS: Under hyperglycemic conditions, there was a significant decrease in the number of endothelial cells and an increase in the secretion of vWF (P <.001). Thiamine treatment limited this inhibitory effect of elevated glucose levels on BAECs. Glucose (27.7 mmol/L) significantly decreased the migration distance of BAECs into the wounded area to 4.0 +/- 1.4 cm, as compared with 6.2 +/- 0.3 cm in the control. Thiamine supplementation restored the migration distance by BAECs (6.94 +/- 0.7 cm) and the wound surface area covered (47.7 +/- 5.6 cm(2)) (P <.001). CONCLUSIONS: Hyperglycemia activates BAECs and promotes secretion of vWF, a marker of endothelial cell damage. Thiamine inhibits this endothelial cell activation and the effects of hyperglycemia on endothelial cell migration. This beneficial effect of thiamine limiting endothelial cell dysfunction is possibly through the diversion of glucose flux from anaerobic to aerobic pathways. The data from this study lead to the speculation that thiamine intake may mitigate or delay vascular complications of diabetes.

Animals↗
PubMed2000

Effect of p53 gene therapy combined with CTLA4Ig selective immunosuppression on prolonged neointima formation reduction in a rat model.

In a previous study, we have demonstrated a significant reduction of neointimal formation following adenovirus-mediated gene transfer of p53 to the injured rat carotid artery. The purpose of this study was to determine if the effect of p53 gene in reducing neointimal formation would still be present up to 8 weeks after arterial injury and whether it could be enhanced by adding immunosuppression. Cytotoxic T lymphocyte-associated antigen-4 Ig (CTLA41g), a novel immunosuppressive agent, is a recombinant soluble protein that blocks T cell-dependent immune response. Animals were divided into eight groups (n = 6 in each). In vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus encoding for wild-type p53 protein was applied at 8 x 10(10) pfu/mL. Control rats received adenovirus null at the same concentration. A daily dose of 300 microg of CTLA41g was given intraperitoneally, either once, twice, or three times. Expression of p53 was determined by Western blot analysis. Neointimal formation was assessed at 4 or 8 weeks by harvesting carotid arteries and determining the intima/media (I/M) ratio cross-sectional area measurements. p53 expression was confirmed by Western blot analysis. We concluded that adenovirus-mediated p53 gene transfer significantly decreases the formation of neointima up to 8 weeks following rat carotid injury. However, there is loss of effectiveness on neointimal formation inhibition as time elapses. When CTLA41g is added, there is significant improvement in results, with sustained neointimal formation inhibition at 8 weeks after the procedure.

Abatacept↗
PubMed2000

Comparison between supra- and infrainguinal inflow sites for infrapopliteal PTFE bypasses with complementary arteriovenous fistula and vein interposition.

PURPOSE: the purpose of this retrospective study was to evaluate whether an inflow source proximal to the inguinal ligament had an adverse effect on infrapopliteal bypasses with complementary arteriovenous fistula/vein interposition (AVF/VI) when compared to similar bypasses originating from the common femoral artery (CFA). PATIENTS AND METHODS: over the last seven years, 112 infrapopliteal PTFE bypasses with AVF/VI were performed in 103 patients. There were 58 men and 45 women with ages ranging from 47 years to 88 years (mean 71 years). Indication for surgery was critical ischaemia in all. Seventy-seven (69%) of these were secondary operations and 35 cases (31%) were primary. A 6-mm ringed PTFE graft was used in all cases. A complementary distal AVF/VI was added in all cases. In 56 cases, the bypass originated from the common femoral artery (group I) and, in the remaining 56, it originated from the external or common iliac artery (group II). RESULTS: the overall perioperative mortality rate was 3%. The cumulative primary patency rates at 1, 2 and 3 years were 66%, 63% and 53% for group I and 72%, 66% and 59% for group II, respectively (NS). CONCLUSIONS: these data show that infrapopliteal PTFE bypasses with AVF/VI have similar patency rates when originating from arteries proximal to the inguinal ligament or from the CFA.

Aged↗
PubMed1999

Ruptured versus elective abdominal aortic aneurysm repair: outcome and cost.

During a recent 30-month period, we repaired 10 ruptured abdominal aortic aneurysms (RAAA) at our institution. To evaluate the survival, postoperative morbidity, and financial impact of treating RAAA, we compared these patients with 10 randomly selected patients undergoing elective AAA (EAAA). Both groups were comparable for age, gender, and incidence of diabetes, hypertension, coronary artery disease, chronic obstructive pulmonary disease (COPD), and renal failure. Although we have noted a dramatic increase in survival for RAAA (90%), the morbidity continues to be unacceptably high (60%). Efforts should be made toward better detection of AAA prior to rupture as well as development of strategies to minimize or prevent these major complications. Potential average savings accrued from one patient undergoing EAAA repair rather than RAAA repair ($93,139. 21) can be used to perform screening abdominal ultrasound tests in patients at increased risk of having an AAA.

Aged↗
PubMed1999

p53 gene transfer to the injured rat carotid artery decreases neointimal formation.

PURPOSE: We studied the effect of adenovirus-mediated p53 gene transfer on the injured rat carotid artery to determine its ability to decrease the formation of neointima. METHODS: In vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus containing the gene encoding for wild-type p53 (AdWTp53) was applied in three concentrations: 8 x 10(10), 1.6 x 10(10), and 8 x 10(9) pfu/mL. Control rats received either adenovirus null (AdNull), 8 x 10(10) pfu/mL, or Medium-199 solution (vehicle). Expression of p53 was determined 4 days after gene transfer by Western blotting. Neointimal formation was assessed after 14 days by harvesting carotid arteries and determining the intima/media (I/M) ratio based on cross-sectional area measurement. Simultaneously, immunohistochemistry was done to detect the presence of p53 on smooth muscle cell nuclei. RESULTS: P53 expression was confirmed by Western blotting. There was a significant reduction in neointimal formation on all treated animals compared with controls. The highest dose of AdWTp53 (8 x 10(10) pfu/mL) resulted in a near-total arrest of neointimal formation (I/M = 0.09 +/- 0.03, mean +/- SEM) with P <. 0001 versus vehicle (I/M = 2.23 +/- 0.15) or AdNull (I/M = 2.12 +/-. 12). The intermediate dose of AdWTp53 (1.6 x 10(10) pfu/mL) resulted in an I/M value of 1.04 +/- 0.18, with P <.001 versus vehicle and P =.001 versus AdNull. The lowest dose (8 x 10(9) pfu/mL) resulted in an I/M value of 1.12 +/- 0.18, with P <.001 versus vehicle and P <. 002 versus AdNull. The immunohistochemistry was positive for the presence of p53 in rats infected with AdWTp53. CONCLUSIONS: Adenovirus-mediated gene transfer of p53 protein significantly decreases the formation of neointima in the rat carotid injury model. This may represent a potential therapy for restenosis in humans.

Adenoviridae↗
PubMed1999

The value and limitations of magnetic resonance angiography of the circle of Willis in patients undergoing carotid endarterectomy.

Magnetic resonance angiography is a useful technique to determine the patency of the circle of Willis when compared with conventional four-vessel angiography. The purpose of this study is to determine whether the integrity of the circle of Willis, assessed by magnetic resonance angiography, provides adequate collateral cerebral circulation during carotid endarterectomy and correlates with internal carotid artery back pressure. Over a recent 20-month period, 35 patients were studied preoperatively with magnetic resonance angiography of the carotid bifurcations of the circle of Willis and the vertebrobasilar system. All patients underwent standard carotid endarterectomy with intraoperative measurement of internal carotid artery back pressure. Patients with an internal carotid artery back pressure < 50 mmHg had an intraluminal shunt placed. Deficiencies in branches of the circle of Willis, the carotid bifurcation and the vertebrobasilar system determined by magnetic resonance angiography were correlated with internal carotid artery back pressure using Fisher's exact test. Only one patient had a completely intact circle of Willis. Eleven of 16 patients (69%) who had an internal carotid artery back pressure < 50 mmHg had an occluded A1 segment of the anterior cerebral artery combined with an occluded posterior communicating artery, whereas only five of 19 patients (26%) who had an internal carotid artery back pressure > 50 mmHg had similar findings (P < 0.03). Severity of occlusive disease of the contralateral internal carotid artery and the basilar artery did not independently predict internal carotid artery back pressure. An occluded anterior branch of the circle of Willis in combination with an occluded posterior branch of the circle of Willis is associated with an internal carotid artery back pressure < 50 mmHg. Although magnetic resonance angiography of the circle of Willis may provide valuable anatomic information, it is not sufficiently accurate to predict the need for carotid shunting and therefore its use cannot be justified on a routine basis.

Aged↗
PubMed1999

P53 gene transfer to the injured rat carotid artery promotes apoptosis.

BACKGROUND: In a previous study we have demonstrated significant reduction of intimal hyperplasia after adenovirus-mediated gene transfer of p53 protein to the injured rat carotid artery. The purpose of this study was to elucidate whether apoptosis is one of the mechanisms responsible for this reduction. Apoptosis, a physiologic cell death process that stabilizes cell numbers in tissues, can be independently induced by p53. METHODS: In vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus encoding for wild-type p53 protein (AdWTp53) was applied at 8 x 10(10) plaque-forming units/mL. Control rats received either adenovirus null at the same concentration or balloon injury alone. Arteries were harvested at 24 and 48 hours after the procedure. Apoptosis was detected in tissue sections by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Specimens were graded either negative or positive less than 10%, 10% to 20%, 20% to 30%, or greater than 30% according to the number of apoptotic cells in the medial or intimal layer per high power field. Specimens were also subjected to DNA agarose gel electrophoresis and transmission electron microscopy. RESULTS: With the TUNEL assay no apoptosis was visualized at 24 and 48 hours in the controls (n = 5 in each group), whereas in the AdWTp53 groups (n = 5 in each) all specimens presented apoptosis (P < .05, AdWTp53 vs controls). The average grade of apoptotic cells detected in the medial layer in the AdWTp53 groups was less than 10% to 20% at 24 hours and 20% to 30% at 48 hours. The DNA agarose gel electrophoresis failed to detect a DNA laddering pattern, characteristic of apoptosis. Electron microscopy revealed morphologic changes typical of apoptosis in the treated group, whereas specimens from control group did not reveal any apoptotic features. CONCLUSIONS: At 48 hours after balloon injury alone, no apoptosis was observed in the vessel wall. However, when p53 gene was transferred, apoptosis was visualized in all specimens with greater intensity at 48 hours after injury. Promotion of apoptosis may play a key role in the mechanism by which p53 gene decreases intimal hyperplasia.

Animals↗
PubMed1998

Combined coronary artery bypass grafting and abdominal aortic aneurysm repair.

BACKGROUND: We report here the results of combined coronary artery bypass grafting (CABG) and abdominal aortic aneurysm (AAA) repair and the factors associated with higher mortality following this procedure. METHODS: The authors performed a retrospective chart review of 26 patients who underwent combined CABG and AAA repair between March 1990 and October 1996. RESULTS: No postoperative myocardial infarction or major cardiac complications were noted. A morbidity rate of 38% (n = 10) and mortality rate of 11% (n = 3) were noted. Comparative analysis of nonsurvivors (n = 3) versus survivors (n = 23) revealed the following: ejection fraction (EF) was significantly lower (33% +/- 3% versus 44% +/- 14%, P < 0.05), duration of cardiopulmonary bypass (CPB) was significantly longer (239 +/- 122 minutes versus 141 +/- 54 minutes, P < 0.05), and incidence of postoperative respiratory failure (67% versus 17%, P = 0.001) were significantly higher in nonsurvivors. No differences in mean age, gender distribution, incidence of hypertension or diabetes were noted between the groups. CONCLUSIONS: Combined CABG and AAA repair protected patients from postoperative aneurysm rupture and myocardial infarction. Poor EF, prolonged CPB, and postoperative respiratory failure were associated with higher mortality.

Aged↗
PubMed1998

The effect of tumor necrosis factor binding protein and interleukin-1 receptor antagonist on the development of abdominal aortic aneurysms in a rat model.

PURPOSE: Tumor necrosis factor (TNF), interleukin 1 (IL-1), and matrix metalloproteases have been noted to be elevated in human abdominal aortic aneurysms (AAAs) as compared with normal and occlusive aortic disease. Because TNF and IL-1 have been shown to cause release of proteases that weaken the aortic matrix, it has been suggested that these cytokines may play a central role in the aortic dilatation process. To substantiate this hypothesis, we investigated the effects of TNF and IL-1 antagonists, tumor necrosis factor binding protein (TNF-BP) and interleukin-1 receptor antagonist (IL-1RA), on the development of AAAs in a well-described rat model. METHODS: Isolated segments of infrarenal aorta of 16 rats were perfused with porcine elastase. In the treated group, eight rats were given intravenous TNF-BP prior to elastase perfusion, at 48 hours and at 96 hours. In the control group, eight rats were given only intravenous vehicle at the same time intervals. Isolated segments of infrarenal aorta of an additional 16 rats were perfused with porcine elastase in a similar fashion. In the treated group, eight rats were given intraperitoneal IL-1RA prior to celiotomy and every eight hours. In the control group, eight rats were given only intraperitoneal vehicle at the same time intervals. On the sixth postoperative day, all rats underwent celiotomy and measurement of the infrarenal aortic diameter with a micrometer while the animal was alive. Aortic specimens were collected on day six for hematoxylin and eosin staining, trichrome staining, and gel polyacrylamide gel electrophoresis (PAGE) zymography. RESULTS: TNF-BP was completely able to block post elastase dilation, whereas IL-1Ra seemed to have no effect. Hematoxylin and eosin staining and trichrome staining revealed that animals treated with TNF-BP had less of an inflammatory response and preservation of the elastin and smooth muscles in the media of the aortic wall as compared with animals treated with IL-1RA or vehicle. Zymography was not able to detect significant protease activity in the aortic wall of any of the rats at six days. CONCLUSION: TNF-BP, but not IL-1RA, may inhibit the development of AAAs in this model.

Animals↗
PubMed1998

Saphenous vein thrombophlebitis (SVT): a deceptively benign disease.

PURPOSE: The association between deep vein thrombosis (DVT) and the hypercoagulable state is a well-established entity. However, the association between saphenous vein thrombophlebitis and coagulation abnormalities has not been investigated. Although thrombosis of varicose veins typically runs a benign course, phlebitis of the saphenous system may propagate to the deep system or saphenofemoral junction that requires more aggressive therapy. Given the potential similarity in clinical outcome between saphenous vein thrombophlebitis (SVT) and DVT, we have investigated the coagulation profile of patients presenting with isolated SVT. METHODS: Seventeen consecutive patients who presented to our vascular laboratory with isolated SVT had a coagulation profile performed that included antithrombin III (AT III), protein C (PC), protein S (PS) antigen and activity levels, activated protein C (APC) resistance, factor V DNA mutation, and coagulation factors II and X. All patients had duplex scans performed on both the superficial and deep venous systems. Patients with SVT only were treated with nonsteroidal antiinflammatory drugs (NSAIDs) and warm soaks as outpatients, whereas those patients found to have DVT or a clot at the saphenofemoral junction were fully anticoagulated with heparin and coumadin therapy. All 17 patients had at least one repeat coagulation profile performed up to 5 months after their SVT occurrence to ensure that the results of hypercoagulability were not transient. RESULTS: Ten (59%) of the 17 patients with SVT had abnormal coagulation profiles on initial presentation. All 10 patients who were hypercoagulable had repeat tests and 6 (35%) remained abnormal. Four patients who had abnormal results converted to normal values. Seven patients with normal coagulation profiles on initial presentation had repeat tests and all remained normal. CONCLUSION: The incidence of the hypercoagulable state in patients with SVT is high. Thirty-five percent of patients with isolated SVT had consistently abnormal coagulation profiles. Patients with SVT may be prone to the development of DVT or saphenofemoral junction thrombophlebitis and should be closely followed after the initial diagnosis of hypercoagulability.

Adult↗
PubMed1998

Hemodynamic instability following carotid endarterectomy does not affect early discharge.

Over the last few years, there has been increased emphasis on early discharge of patients following carotid endarterectomy in the United States. Recent studies have shown that short-stay hospitalization for carotid endarterectomy may be safe and cost-effective. However, this is not always possible because of reasons that are not clearly delineated. In order to optimize the early discharge of patients following carotid endarterectomy, an analysis of the causes of delayed discharges was performed in the present series. Since hemodynamic instability has been shown to be the most frequent complication following carotid endarterectomy, the authors investigated whether it was an important factor preventing early postoperative discharge. This study reviewed the data of 100 consecutive patients admitted for elective carotid endarterectomy. The incidence of post-carotid endarterectomy hemodynamic instability was 37% (n = 37), with hypertension occurring in 25 patients (68%) and hypotension occurring in 12 patients (32%). Hemodynamic instability tended to occur with the use of general anesthesia as compared with regional anesthesia. Hemodynamic instability did not correlate with pre-existent history of hypertension, nor with the type of drug used when general anesthesia was applied. All the patients were successfully treated either in the recovery room or in a monitored area. The average total length of stay was 1.65 days with 79% of the patients being discharged on the first postoperative day and 21% having delayed discharge ranging from 2 to 15 days (mean 4 days). The main reasons for delayed discharges were cardiac and urinary tract complications. Blood pressure instability accounted for only 2% of cases. Thus, these data show that hemodynamic instability does not significantly affect early discharge.

Aged↗
PubMed1997

Upper extremity versus lower extremity deep venous thrombosis.

BACKGROUND: In contrast to lower extremity deep venous thrombosis (LEDVT), it is widely believed that upper extremity deep venous thrombosis (UEDVT) is associated with minimal morbidity or mortality. METHODS: In an attempt to compare the two disease processes with respect to pulmonary embolism and mortality, we have reviewed records and performed interviews of 430 patients with LEDVT and 52 patients with UEDVT presenting to our institution between January 1994 and June 1995. RESULTS: Pulmonary embolism was documented by ventilation/perfusion lung scan in 9 of 52 patients (17%) with UEDVT and 33 of 430 patients (8%) with LEDVT (P <0.05). Twenty-five of the UEDVT patients (48%) died within 6 months of the diagnosis of UEDVT. Conversely, 14 patients (13%) in the LEDVT group died within 6 months of the diagnosis of LEDVT (P <0.0002). CONCLUSION: Contrary to previous reports, this study suggests that UEDVT is associated with a higher morbidity and mortality as compared with LEDVT. These data show that UEDVT has been an underrecognized predictor of morbidity and mortality.

APACHE↗
PubMed1997

Upper extremity deep venous thrombosis and its impact on morbidity and mortality rates in a hospital-based population.

PURPOSE: Although much attention has been focused on lower extremity deep venous thrombosis (LEDVT), there is a relative paucity of data regarding the impact of upper extremity deep venous thrombosis (UEDVT) on morbidity and mortality rates. To increase our knowledge with the latter disease, we have reviewed our experience at our institution with 170 patients who had brachial, axillary, and subclavian vein thromboses. METHODS: Over the past 5 years, UEDVT was diagnosed in 170 patients by duplex scanning. The indications for duplex examination were either upper extremity swelling (95%) or as part of the workup for pulmonary embolism (5%). There were 103 women (61%) and 67 men (39%), with ages ranging from 9 to 101 years (mean, 68 +/- 17 years). The diagnosis was made in 152 patients (89%) while they were admitted to the hospital and in 18 patients (11%) in the outpatient clinic. Risk factors included presence of a central venous catheter or pacemaker in 110 patients (65%), malignancy in 63 patients (37%), concomitant LEDVT in 19 patients (11%), and history of LEDVT in 18 patients (11%). Fifty-six patients (33%) had multiple risk factors, whereas 36 patients (21%) had no obvious risk factor. RESULTS: The 1-month and 3-month mortality rates for the entire study group were 16% and 34%, respectively. Patients who had concomitant LEDVT, were 75 years of age or older, and were not treated with anticoagulation medication had a significantly higher 1-month mortality rate. Patients whose diagnoses were made in the outpatient setting were statistically younger and had a lower 3-month mortality rate when compared with the patients whose diagnoses were made as inpatients. Pulmonary embolism was documented by ventilation/perfusion scan in 12 patients (7%). Although no patient in the group in which UEDVT was diagnosed on an outpatient basis was documented to have a pulmonary embolism and 12 patients (8%) in the inpatient group had pulmonary emboli, this difference was not statistically significant. Anticoagulation medication did not totally prevent pulmonary embolism in this review. All patients were followed-up for between 0 to 49 months (mean, 13 +/- 1 months). No swelling of the affected arm was observed in 145 patients (94%); four patients complained of mild intermittent swelling (2%), and seven patients reported significant swelling (4%). CONCLUSIONS: Contrary to previous reports, these data suggest that UEDVT is associated with a low incidence of postthrombotic upper extremity swelling, but a significant incidence of pulmonary embolism and rate of mortality. This review suggests that UEDVT is at least as serious a disease entity as LEDVT and should be managed as aggressively as LEDVT.

APACHE↗
PubMed1995

Multicenter trial of sotalol compared with procainamide in the suppression of inducible ventricular tachycardia: a double-blind, randomized parallel evaluation. Sotalol Multicenter Study Group.

Sotalol is the prototype class III agent that combines beta-blocking properties with the propensity to prolong the effective refractory period by lengthening the action potential duration. Its precise effect on the prevention of ventricular tachycardia-ventricular fibrillation (VTVF) compared to class I agents has not been evaluated in a blinded study. In a double-blind parallel-design multicenter study, the electrophysiologic and antiarrhythmic effects of intravenous and oral sotalol (n = 55) and procainamide (n = 55) were therefore compared in patients with VTVF inducible by programmed electric stimulation. Sotalol produced a greater effect on lengthening the ventricular effective refractory period (VERP). It prevented the inducibility of VTVF in 30% versus 20% for procainamide, but this was not significantly different. In an alternate therapy group (n = 41) of similar patients previously refractory to or intolerant of procainamide, intravenous sotalol prevented inducibility in 32%. The pooled overall sotalol efficacy rate was 31%. There was a significant relation between the increase in the VERP and the prevention of inducibility of VTVF (n = 56; p < 0.02). VERP of > or = 300 msec was critical for the prevention of VTVF inducibility. Thirteen sotalol and 6 procainamide responders from the randomized group and 30 from the nonrandomized groups completed 1 year of oral sotalol therapy follow-up. Life-table analysis of these patient in each group showed a trend in favor of sotalol; however, statistical analysis was not possible because of the small numbers of patients. Both sotalol and procainamide were well tolerated. In the randomized group there was one case of sudden death during treatment with sotalol and two cases of nonfatal torsades de pointes in the procainamide group and two in the sotalol group; in the nonrandomized alternate therapy group, there were 6 cases of nonfatal torsades de pointes. The data support the emerging role of sotalol in the control of symptomatic ventricular tachycardia and fibrillation.

Administration, Oral↗
PubMed1995

Current approaches in patients with ventricular tachyarrhythmias.

The article has summarized the studies and ongoing trials looking at the significance and treatment of ventricular tachyarrhythmias. In most instances, the presence of these arrhythmias is associated with an increased risk of future arrhythmic events. Electrophysiologic studies are helpful in risk stratification in patients with coronary artery disease but can be misleading in the setting of dilated cardiomyopathy and often produce nonspecific results in patients with HCM. The need for an invasive electrophysiologic study is crucial in the diagnosis of certain ventricular arrhythmias that are amenable to cure with radiofrequency catheter ablation, such as idiopathic ventricular tachycardia and BBR-VT. The correct approach for patients with SVT not amenable to catheter ablation remains to be determined. In deciding whether to use a device or drug therapy, however, one should take into consideration the degree of left ventricular dysfunction and the overall health status of the patient. For example, device implantation clearly reduces sudden death in patients with severe left ventricular dysfunction but may not change total mortality because these same patients may die of congestive heart failure. Device therapy might be more cost-effective for patients with less severe depression of left ventricular function.

Cardiac Complexes, Premature↗