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Biomedical subjects

J G Webb

Publications and source records attributed to J G Webb.

At least 37 records · Page 2Linked to original sources
PubMed2000

Stimulation of beta-adrenergic receptors inhibits the release of tumor necrosis factor-alpha from the isolated rat heart.

OBJECTIVES: Beta-adrenergic receptor agonists such as isoproterenol inhibit production of tumor necrosis factor (TNF)-alpha in a number of cell types. Because the heart is a source of TNF-alpha, we hypothesized that isoproterenol would inhibit cardiac production of the cytokine. DESIGN: Analysis of cardiac release of TNF-alpha. SETTING: Medical research laboratory. SUBJECTS: Rats. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: With the approval of the Institutional Animal Care and Use Committee, rats were anesthetized and hearts were removed and perfused. After 30 mins, bacterial lipopolysaccharide (LPS) with or without isoproterenol was infused for 60 mins. At 30, 60, 90, 120, and 150 mins, coronary flow was measured and coronary effluent was analyzed for TNF-alpha. Cardiac production of TNF-alpha was expressed as pg/min. Cyclic adenosine monophosphate (AMP) in the coronary effluent was measured. TNF-alpha messenger RNA was determined in ventricular tissue. After 30 mins, TNF-alpha was undetectable in the coronary effluent However, 60 mins after the initiation of LPS infusion, TNF-alpha release was 875+/-255 pg/min and increased to 2164+/-721 pg/min at 150 mins. Simultaneous infusion of isoproterenol with LPS stimulated cyclic AMP release and inhibited TNF-alpha production. For instance, at 60 and 150 mins, TNF-alpha release was 75+/-38 and 58+/-29 pg/min, respectively (p < .05 vs. LPS alone). Simultaneous infusion of isoproterenol with LPS blocked the induction of TNF-alpha messenger RNA by LPS. Isoproterenol, begun 30 mins after the initiation of LPS infusion, still suppressed LPS-stimulated TNF-alpha release by 95% at 150 mins. Similar results were obtained with norepinephrine. CONCLUSIONS: Activation of beta-adrenergic receptors inhibits cardiac TNF-alpha release. This implies that cytokine production by the heart is inhibited by the sympathetic nervous system. In heart failure, the cardiac response to the sympathetic nervous system is impaired. This impairment may play a role in the high plasma levels of TNF-alpha found in heart failure.

Animals↗
PubMed2000

Coronary stenting without predilatation in a broad spectrum of clinical and angiographic situations.

BACKGROUND: Direct coronary stenting without balloon predilatation has the potential benefits of a reduced risk of extended dissections, reduced fluoroscopy exposure, reduced procedural time, and potential cost savings. With the availability of superior stents and delivery systems, we review our experience with direct stent deployments in a large selected patient cohort. METHODS: We prospectively studied 158 consecutive cases of attempted coronary stenting without balloon predilatation over a 1-year period. RESULTS: Indications for the procedure included unstable angina (71%), stable angina (24%) and acute myocardial infarction (5%). Target vessels were the anterior descending artery (56%), right coronary artery (30%), circumflex artery (8%), and vein grafts (6%). Pre-procedural TIMI flows were grade 3 (91.7%), grade 2 (5.8%), grade 1 (1.3%) and 0 (1.3%). Lesion types were graded A (27%), B (61%), and C (12%). Stent types included NIR Primo (80.4%), ACS Multi-Link RX Duet (10.1%), NIR (5.1%), and others (4.4%). Stents ranged from 3.0Eth 4.0 mm in diameter (median = 3 mm) and 8Eth 32 mm in length (median = 16 mm). Stents were successfully deployed in 155 cases (98.1%); 2 (1.3%) required predilatation and 1 (0.6%) deployed stent could not be expanded and was opened by rotablation. All except the rotablator case achieved final TIMI grade 3 flow, and 66% did not require further balloon dilatation. There were no deaths or cases of urgent bypass surgery. Case duration and radiation exposure in direct stenting (32.8 +/- 18.9 minutes and 6.7 +/- 6.2 minutes, respectively) compared favorably to those in a matched group of patients in conventional stenting (47 +/- 18 minutes and 11 +/- 7 minutes) and coronary angioplasty (40 +/- 12 minutes and 10 +/- 6 minutes) for single-lesion cases (p < 0.005). Creatine kinase elevation related to the procedure was observed in 5 patients. Subacute stent thrombosis occurred in 2 (1.3%) cases. CONCLUSION: Direct coronary stenting was successfully and safely accomplished in a variety of clinical situations in selected patients.

Aged↗
PubMed2000

Transient obstruction of the mitral valve by a massive thrombus complicating percutaneous valvuloplasty.

Percutaneous transseptal mitral valvuloplasty was attempted in a patient with severe rheumatic mitral stenosis. Introduction of the balloon into the left atrium resulted in thrombotic occlusion of the mitral valve. Circulatory arrest ensued. The thrombus was disrupted during cardiopulmonary resuscitation. Thrombolysis was administered and the patient recovered uneventfully.

Anticoagulants↗
PubMed2000

Isoproterenol inhibits bacterial lipopolysaccharide-stimulated release of tumor necrosis factor-alpha from human heart tissue.

Recent evidence suggests that inflammatory cytokines, particularly tumor necrosis factor alpha (TNF-alpha), may play a role in heart disease. Elevated plasma levels of the cytokine have been reported in congestive heart failure and severe angina and after myocardial infarction. The exact role of TNF-alpha in heart disease and how production is stimulated and regulated in the heart are current areas of investigation. Regarding regulation of production, isoproterenol elevates cyclic AMP and inhibits TNF-alpha release in macrophages. Therefore we hypothesized that stimulation of beta-adrenergic receptors of the sympathetic nervous system would inhibit release of the cytokine from heart tissue. With Institutional Review Board approval and patient consent atrial tissue was obtained during preparation for cardiac bypass. The tissue was divided into segments, placed in culture medium, and incubated for various times in the presence or absence of lipopolysaccharide (LPS) (20 microg/mL) and/or isoproterenol (1 microM). The medium was removed and analyzed for biologically active TNF-alpha by the L929 cell cytotoxicity assay. Tissue samples were weighed and TNF-alpha release was expressed as pg TNF-alpha/mg tissue. Initially, to determine the time course of release, measurements were made at 2, 5, 10, 15, 30, 60, 120, 180, and 360 minutes after the addition of LPS. Elevated TNF-alpha levels in the culture medium were reliably detected at 360 minutes after exposure to LPS. In atrial tissue obtained from seven patients TNF-alpha released into the culture medium at 360 minutes was 6 +/- 3 pg/mg tissue. In the presence of LPS, levels of the cytokine in the culture medium increased to 604 +/- 233 pg/mg tissue (P < 0.05 vs LPS alone). When isoproterenol and LPS were simultaneously added to the culture medium release of TNF-alpha was reduced by 87 per cent to 82 +/- 40 pg/mg tissue (P < 0.05 vs LPS alone). Our results show that activation of the beta-adrenergic receptor inhibits myocardial production of TNF-alpha. This finding suggests that the sympathetic nervous system inhibits production of the cytokine and that impaired sympathetic function in heart failure may play a role in the elevated levels of TNF-alpha.

Animals↗
PubMed1999

Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock.

BACKGROUND: The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. METHODS: Patients with shock due to left ventricular failure complicating myocardial infarction were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty. Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups. The primary end point was mortality from all causes at 30 days. Six-month survival was a secondary end point. RESULTS: The mean age of the patients was 66+/-10 years, 32 percent were women and 55 percent were transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87 percent underwent revascularization; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups (46.7 percent and 56.0 percent, respectively; difference, -9.3 percent; 95 percent confidence interval for the difference, -20.5 to 1.9 percent; P=0.11). Six-month mortality was lower in the revascularization group than in the medical-therapy group (50.3 percent vs. 63.1 percent, P=0.027). CONCLUSIONS: In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days. However, after six months there was a significant survival benefit. Early revascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenic shock.

Aged↗
PubMed1999

Mechanisms, management, and outcome of failure of delivery of coronary stents.

In a single-center experience, initial failure of attempted stent delivery was relatively infrequent (2.7%) but was associated with increased need for urgent coronary bypass surgery. Delivery failure was more likely with coiled stents and dislodgment from the delivery balloon was more likely with hand-mounted or radiolucent stents.

Angioplasty, Balloon, Coronary↗
PubMed1999

Balloon entrapment during side-branch angioplasty through a stent.

Entrapment of the distal tip of a balloon catheter occurred during attempted passage between the struts of a stent into a side branch. Traction on the balloon resulted in fracture of the catheter shaft requiring extraction with percutaneous retrieval forceps.

Angina Pectoris↗
PubMed1999

Retrieval and analysis of particulate debris after saphenous vein graft intervention.

OBJECTIVES: This study was designed to evaluate the composition and quantity of particulate debris resulting from vein graft intervention. BACKGROUND: Distal embolization and "no reflow" are frequent and important complications resulting from angioplasty of diseased saphenous vein grafts. Little is known about the composition and quantity of embolic particulate debris associated with vein graft intervention, and no intervention has been shown to protect against its clinical consequences. METHODS: A catheter system, designed to contain, retrieve and protect against distal embolization of this material, was evaluated during 27 percutaneous interventional saphenous vein graft procedures. Clinical, angiographic and pathologic analyses were performed. RESULTS: The duration of distal graft occlusion required to allow intervention and subsequent debris removal was 150 +/- 54 s, decreasing as experience was gained. Thrombolysis in Myocardial Infarction trial (TIMI) flow grade increased from 2.6 +/- 0.8 to 3.0 +/- 0.0. Creatine kinase (CK) rose above normal in three patients (11.1%) exceeding 3x normal in one (3.7%) resulting in the diagnosis of non-Q-myocardial infarction. Particulate material was identified following 21 of 23 procedures suitable for analysis. Particle size was 204 +/- 57 microm in the major axis and 83 +/- 22 microm in the minor axis. Particles consisted predominantly of soft acellular atheromatous material, such as that typically found under a fibrous cap. Semiquantitative analysis suggested that the quantity of particulate material was less following stenting than following balloon dilation. CONCLUSIONS: Particulate matter is commonly present following routine angioplasty and stenting of saphenous vein grafts. Containment, retrieval and analysis of this particulate debris are all feasible. Comparison to prior clinical experience is limited by small sample size. However, to the extent that these particles may contribute to distal embolization, no-reflow and infarction, such a system may contribute to the reduction of complications following vein graft intervention.

Aged↗
PubMed1999

The use of milrinone in pre-transplant assessment of patients with congestive heart failure and pulmonary hypertension.

BACKGROUND: Pulmonary hypertension in patients with congestive heart failure (CHF) is a risk factor for increased mortality after orthotopic cardiac transplantation. Reversibility of elevated pulmonary vascular resistance (PVR) by pharmacologic agents predicts improved outcomes. Milrinone, a phosphodiesterase inhibitor with vasodilating and positive inotropic properties, has been shown to lower PVR in one previous study. However, no study has documented outcomes after cardiac transplantation in patients in whom reversibility of pulmonary hypertension was demonstrated after administration of milrinone. METHODS: We retrospectively reviewed 19 patients with CHF and pulmonary hypertension defined as PVR > or = 3 Wood units, PVRI (pulmonary vascular resistance index) > or = 4 resistance units, or TPG (transpulmonary gradient = mean pulmonary artery pressure--mean capillary wedge pressure) > or = 12 mmHg being assessed for cardiac transplantation. A sub-group of 14 patients with severe pulmonary hypertension defined as PVR > or = 4, PVRI > or = 6 and TPG > or = 15 was also examined. Milrinone was administered as a bolus (50 ug/kg) and hemodynamic parameters were measured at 5, 10 and 15 minutes. Six patients received cardiac transplants. RESULTS: Administration of milrinone significantly lowered PVR, PVRI, mean pulmonary artery pressure (PAM)(all p = 0.002) and pulmonary capillary wedge pressure (PCWP)(p = 0.006). Cardiac output (CO) increased significantly (p = 0.001). TPG did not change (p = 0.33). In patients with severe pulmonary hypertension, the magnitude of these changes was greater. In addition, TPG was significantly lowered (p = 0.02). CONCLUSION: Milrinone lowered PVR by decreasing PAM and increasing CO significantly. In addition, PCWP was significantly lowered. These finding confirm both vasodilatory and inotropic effects of milrinone. Patients with severe pulmonary hypertension had more pronounced effects. There were no deaths in the group of patients proceeding to cardiac transplantation. Our study demonstrates the efficacy of milrinone in lowering PVR as well as suggesting safety in use in patients undergoing cardiac transplantation.

Adult↗
PubMed1999

Adverse events associated with balloon rupture during percutaneous coronary intervention.

BACKGROUND: Balloon rupture is a potential complication of coronary angioplasty. The literature is inconsistent regarding associated adverse consequences. The experience of St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, with balloon rupture is reviewed. PATIENTS AND METHODS: All patients who underwent percutaneous coronary intervention complicated by balloon rupture at St Paul's Hospital from April 1992 to March 1996 were identified from the hospital's database (Seattle Systems, Seattle, Washington). Procedural logs, database records, clinical charts and all cineangiograms were reviewed in detail. RESULTS: A total of 2984 patients had percutaneous coronary revascularization and 110 patients experienced balloon rupture. These occurred in 101 (92%) native coronary arteries and 9 (8%) occurred in saphenous vein grafts. Stents were deployed in 44 (40%) patients; 34 of the stents used were half Johnson & Johnson PS153 stents (Johnson & Johnson Interventinal Systems, Peterborough, Ontario). An event-free postangioplasty course during the index hospitalization was observed in 102 patients (93%); eight patients (7%) had one or more important adverse events postprocedure. These included three deaths (one following a dissection and out-of-catheterization laboratory occlusion, a second following an abrupt occlusion of another target artery and emergency bypass surgery, and another with cardiogenic shock postmyocardial infarction and an unaltered course following angioplasty); one urgent bypass surgery after a left main dissection; and two nonfatal myocardial infarctions (one patient had tamponade and one patient experienced congestive heart failure). Four of the eight events were directly related to the procedure. The rate of death and emergency bypass surgery with balloon rupture did not differ from that of patients without balloon rupture in the authors' centre (1.8% versus 1.4%, not significant). CONCLUSIONS: The majority of patients did not experience any adverse clinical outcomes and demonstrated good angiographic results after balloon rupture. The data did not detect an excess of major adverse events beyond that expected in a diverse general angioplasty population.

Angioplasty, Balloon, Coronary↗
PubMed1998

Groin complications associated with collagen plug closure of femoral arterial puncture sites in anticoagulated patients.

A retrospective study was conducted to determine the frequency and nature of groin complications when the Vasoseal (Datascope Corp., NJ) hemostasis device was used on 204 occasions to enable removal of the groin sheath in anticoagulated patients. The patients had undergone balloon angioplasty (53%), coronary stenting (20%), and diagnostic angiography (27%). Complications included vascular surgery in 5% including 2 embolized collagen plugs, failure to achieve hemostasis (2%), late external bleeding (2%), purulent discharge (1.5%), a minor ooze of blood (7%), hematomas >6 cm (6%), and hematomas < or = 6 cm (7%). One or more complications occurred with 64 of 204 (30.5%) uses. Multivariate analysis identified diagnostic angiography to be associated with a reduced risk of complications [odds ratio (OR) 0.25], while stent procedure (OR 2.7) and female gender (OR 2.5) were associated with increased risk. This complication rate is similar to other reported series except for a higher rate of vascular surgery. The high incidence of anticoagulation in our study patients (94%) may explain this difference. We recommend caution and adherence to the recommended technique when the device is used in anticoagulated patients.

Aged↗
PubMed1998

Interventional management of cardiogenic shock.

Management of the patient with cardiogenic shock requires rapid confirmation of the diagnosis and exclusion of potentially correctable conditions. Early echocardiography is helpful to exclude mechanical causes of shock, such as unsuspected severe mitral insufficiency. Thrombolytic therapy may help prevent shock, but its role in established shock is not clear. Intra-aortic balloon counterpulsation may be of value, particularly when used in conjunction with reperfusion therapy. Angiography can be performed at relatively low risk in shock patients. A window of opportunity is often available where revascularization may be of benefit.

Angiocardiography↗
PubMed1997

Usefulness of coronary stenting for cardiogenic shock.

Coronary stenting was performed in 15 selected patients with cardiogenic shock, with favorable clinical and angiographic outcomes. This experience suggests that coronary stenting may play an important adjunctive role in the management of cardiogenic shock and may improve outcome beyond that achieved with balloon angioplasty alone.

Aged↗
PubMed1997

Early and late assessment of the Micro Stent PL coronary stent for restenosis and suboptimal balloon angioplasty.

This prospective study represents the initial assessment of the Micro Stent PL (Arterial Vascular Engineering, Inc.) coronary stent. From one to three radiopaque stainless steel stents, each measuring 4 mm long, were premounted onto specially designed balloon catheters. A total of 123 stents were implanted in 41 patients without procedural failure or complications. Stent dislodgment proved a concern, with 7 of 123 stents (5.7%) moving > 3 mm from the site of placement and late downstream migration occurring in an additional patient. Subacute stent thrombosis occurred in two patients (5%). Six-month angiographic follow-up was available in 37 of 41 patients (90%). Minimal lumen diameter at baseline was 0.93 +/- 0.51 mm, increasing to 2.74 +/- 0.49 mm after stenting, and falling to 1.66 +/- 0.89 mm at 6 months; this represents a late loss of 60% of the initial gain. Restenosis, based on a binary definition of > 50% diameter stenosis, was documented in 18 patients (49%). Advantages of the Micro Stent PL include its radiopacity and marked ease of distal delivery. The potential for stent dislodgment has implications for future stent designs. The role of the Micro Stent PL in managing restenosis is unclear, but it appears useful in the management of dissection and threatened closure after balloon angioplasty.

Aged↗
PubMed1997

Adenylyl cyclase isoforms and vasopressin enhancement of agonist-stimulated cAMP in vascular smooth muscle cells.

The influence of arginine vasopressin (AVP) on agonist-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in vascular smooth muscle cells (VSMC) cultured from rat thoracic aorta. Incubation of VSMC with AVP for 60 s produced a 2- to 2.5-fold enhancement of isoproterenol-induced cAMP formation. AVP also increased cAMP stimulation by the prostaglandin I2 analogue iloprost. The effect of AVP to enhance agonist-stimulated cAMP formation was completely inhibited in cells pretreated with a selective antagonist of V1 vasopressin receptors but was not affected by blockade of V2 receptors. Inhibition of protein kinase C activation failed to alter the action of AVP to potentiate cAMP stimulation, but treatment of cells with calmodulin antagonists significantly attenuated this effect of the peptide. Moreover, depletion of Ca2+ stores with thapsigargin decreased AVP enhancement of isoproterenol-stimulated cAMP by > 70%. The action of AVP to increase cAMP stimulation was also demonstrated in freshly isolated strips of rat aorta where treatment with peptide produced a twofold increase in isoproterenol-stimulated cAMP formation. RNA blot analysis indicated expression in VSMC of mRNA encoding type III adenylyl cyclase, a Ca(2+)-calmodulin-sensitive isoform of the effector. Furthermore, when detergent-solubilized membrane extract was subjected to calmodulin affinity chromatography, a peak of adenylyl cyclase activity was identified which had affinity for calmodulin matrix in the presence of Ca2+. The results indicate that AVP activates V1 receptors in VSMC to enhance agonist-stimulated cAMP formation by a Ca(2+)-calmodulin-dependent mechanism and suggest that type III adenylyl cyclase may provide a focal point in the VSMC for cross talk between constrictor and dilator pathways.

Adenylyl Cyclases↗
PubMed1997

Angiotensin II potentiates vasodilation of rat aorta by cAMP elevating agonists.

We previously observed an effect of the Ca++-mobilizing peptide, angiotensin II (ANG II), to potentiate agonist-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in rat cultured aortic smooth muscle cells. Consequently, it was postulated that the relaxant effects of dilator agents that act through cAMP formation would be enhanced in the presence of ANG II. To test this idea, we examined the influence of ANG II on agonist-induced relaxation of rat isolated aortic rings. Angiotensin II (0.1 microM) evoked a transient increase in the tone of KCI (30 mM)-precontracted aortae that returned to the original level of induced tension after about 20 min. Subsequent application of isoproterenol caused a concentration-dependent relaxation that was significantly greater in preparations pretreated with ANG II than in time-matched controls. Similarly, isoproterenol-induced relaxations of aortae precontracted with either phenylephrine (1 microM) or endothelin 1 (3 nM) were also augmented after ANG II treatment. The principal action of ANG II was to enhance the maximal relaxation evoked by isoproterenol without affecting the EC50 value, irrespective of the contractile agent used. This potentiating effect of ANG II was not specific for beta adrenoceptor-mediated relaxation because the relaxant response to iloprost, a prostaglandin I2 analog, was also increased after ANG II treatment. The effect of ANG II to enhance isoproterenol-induced relaxation was maintained in endothelium-denuded preparations. However, ANG II did not enhance the relaxation of vessels evoked through either the direct elevation of cAMP levels by dibutyryl cAMP or the stimulation of cyclic 3',5'-guanosine monophosphate formation by sodium nitroprusside. The data indicate that exposure of rat aortae to the constrictor peptide ANG II enhances the vasodilation of these blood vessels by agonists that stimulate cAMP formation. Such cross-talk between constrictor and dilator pathways could represent an important mechanism in the modulation of vascular tone.

Angiotensin II↗