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J G Webb

Publications and source records attributed to J G Webb.

At least 19 recordsLinked to original sources

One-year survival following early revascularization for cardiogenic shock.

CONTEXT: Cardiogenic shock (CS) is the leading cause of death for patients hospitalized with acute myocardial infarction (AMI). OBJECTIVE: To assess the effect of early revascularization (ERV) on 1-year survival for patients with AMI complicated by CS. DESIGN: The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) Trial, an unblinded, randomized controlled trial from April 1993 through November 1998. SETTING: Thirty-six referral centers with angioplasty and cardiac surgery facilities. PATIENTS: Three hundred two patients with AMI and CS due to predominant left ventricular failure who met specified clinical and hemodynamic criteria. INTERVENTIONS: Patients were randomly assigned to an initial medical stabilization (IMS; n = 150) group, which included thrombolysis (63% of patients), intra-aortic balloon counterpulsation (86%), and subsequent revascularization (25%), or to an ERV group (n = 152), which mandated revascularization within 6 hours of randomization and included angioplasty (55%) and coronary artery bypass graft surgery (38%). MAIN OUTCOME MEASURES: All-cause mortality and functional status at 1 year, compared between the ERV and IMS groups. RESULTS: One-year survival was 46.7% for patients in the ERV group compared with 33.6% in the IMS group (absolute difference in survival, 13.2%; 95% confidence interval [CI], 2.2%-24.1%; P<.03; relative risk for death, 0.72; 95% CI, 0.54-0.95). Of the 10 prespecified subgroup analyses, only age (<75 vs >/= 75 years) interacted significantly (P<.03) with treatment in that treatment benefit was apparent only for patients younger than 75 years (51.6% survival in ERV group vs 33.3% in IMS group). Eighty-three percent of 1-year survivors (85% of ERV group and 80% of IMS group) were in New York Heart Association class I or II. CONCLUSIONS: For patients with AMI complicated by CS, ERV resulted in improved 1-year survival. We recommend rapid transfer of patients with AMI complicated by CS, particularly those younger than 75 years, to medical centers capable of providing early angiography and revascularization procedures.

Aged↗

Unprotected left main coronary artery stenting for cardiac allograft vasculopathy.

Cardiac allograft vasculopathy is the leading cause of death after the first year of transplantation. Treatment outcomes with medication, balloon angioplasty, bypass surgery, and retransplantation have been disappointing. We present our initial experience with stenting of the left main coronary artery in the setting of allograft vasculopathy.

Angioplasty, Balloon, Coronary↗

Trends in cardiogenic shock: report from the SHOCK Study. The SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

AIMS: We analysed time trends in patient characteristics, management, and outcomes of cardiogenic shock complicating acute myocardial infarction in the international, prospective SHOCK Trial Registry and pre-study Registry. BACKGROUND: Despite therapeutic advances in its management, the incidence and high mortality of this complication has remained unchanged for decades. However, in recent years mortality was reported to decrease in one community concomitant with increasing use of revascularization. METHODS: Thirty-six centres registered 1380 patients with suspected cardiogenic shock complicating acute myocardial infarction from January 1992 to August 1997. Patient and myocardial infarction characteristics, haemodynamics, medications, procedure use, and vital status at discharge were recorded. RESULTS: In all, 79% of patients had shock due to predominant pump failure (non-mechanical aetiology). The aetiology, patient profile, and clinical characteristics of cardiogenic shock did not differ over time, except for increases in the incidence of prior bypass surgery (P=0.054) and transfers to tertiary centres (P=0.008). In all, 44% underwent revascularization (n=485), with angioplasty performed more often than bypass surgery (69% vs 31%). The revascularization rate increased over time (P=0.006) with a significant decrease in the time to revascularization (P=0.033). The use of Swan-Ganz catheterization decreased over time (P=0.018), as did the mean length of hospitalization (P=0.034). Overall in-hospital mortality was high (63%) but decreased over time in all patients (P=0.004) and those with pump failure (P=0.018). Mortality was lower for patients who underwent revascularization compared to those who were not revascularized (41% vs 79%, P<0.001). CONCLUSIONS: Cardiogenic shock complicating acute myocardial infarction is associated with a high mortality rate, but mortality decreased significantly from 1992 to 1997. This partly reflects the greater use of revascularization, which was associated with better outcomes. The reported international trend towards shorter admissions for myocardial infarction was also observed in this cohort.

Adult↗

Percutaneous coronary intervention for cardiogenic shock in the SHOCK Trial Registry.

BACKGROUND: The SHOCK Registry prospectively enrolled patients with cardiogenic shock complicating acute myocardial infarction in 36 multinational centers. METHODS: Cardiogenic shock was predominantly attributable to left ventricular pump failure in 884 patients. Of these, 276 underwent percutaneous coronary intervention (PCI) after shock onset and are the subject of this report. RESULTS: The majority (78%) of patients undergoing angiography had multivessel disease. As the number of diseased arteries rose from 1 to 3, mortality rates rose from 34.2% to 51.2%. Patients who underwent PCI had lower in-hospital mortality rates than did patients treated medically (46.4% vs 78.0%, P < .001), even after adjustment for patient differences and survival bias (P = .037). Before PCI, the culprit artery was occluded (Thrombolysis In Myocardial Infarction grade 0 or 1 flow) in 76.3%. After PCI, the in-hospital mortality rate was 33.3% if reperfusion was complete (grade 3 flow), 50.0% with incomplete reperfusion (grade 2 flow), and 85.7% with absent reperfusion (grade 0 or 1 flow) (P < .001). CONCLUSIONS: This prospective, multicenter registry of patients with acute myocardial infarction complicated by cardiogenic shock is consistent with a reduction in mortality rates as the result of percutaneous coronary revascularization. Coronary artery patency was an important predictor of outcome. Measures to promote early and rapid reperfusion appear critically important in improving the otherwise poor outcome associated with cardiogenic shock.

Aged↗

Adenylyl cyclase isoforms and signal integration in models of vascular smooth muscle cells.

Adenylyl cyclases present a potential focal point for signal integration in vascular smooth muscle cells (VSMC) influencing contractile state and cellular responses to vessel wall injury. In the present study, we examined the influence of the vasoactive peptide arginine vasopressin (AVP) on cAMP regulation in primary cultures of rat aortic VSMC and in the A7r5 arterial smooth muscle cell line. In cultured VSMC and A7r5 cells, AVP had no effect on basal cAMP but differentially affected beta-adrenergic receptor-induced activation of adenylyl cyclase. AVP synergistically increased (twofold) isoproterenol-stimulated cAMP production in VSMC but inhibited the effect of isoproterenol (50%) in the A7r5 cell line. The effects of AVP in both preparations were blocked when cells were pretreated with a selective V(1) vasopressin receptor antagonist. Moreover, the actions of AVP in both models were dependent on release of intracellular Ca(2+) and were mimicked by elevation of Ca(2+) with the ionophore A23187, suggesting that the responses to AVP involve Ca(2+)-mediated regulation of adenylyl cyclase stimulation. Adenylyl cyclase types I, III, and VIII are stimulated by Ca(2+)/calmodulin, whereas types V and VI are directly inhibited by Ca(2+). RNA blot analysis for effector isotypes indicated that both VSMC and A7r5 cells expressed types III, V, and VI. VSMC also expressed mRNA for type IV and VIII effectors, which could account for the cell-specific responses to peptide hormone and Ca(2+).

Adenylyl Cyclases↗

A metabolic fragment of bradykinin, Arg-Pro-Pro-Gly-Phe, protects against the deleterious effects of lipopolysaccharide in rats.

Extensive research has provided few therapeutic agents for the treatment of septicemia. Bradykinin, an endogenous vasodepressor hormone, is a key mediator in the hypotension seen with septicemia. The present investigation shows that a stable metabolic fragment of bradykinin, arginine-proline-proline-glycine-phenylalanine (RPPGF), prevents the deleterious effects of endotoxin [lipopolysaccharide (LPS); a component of the membrane of Gram negative bacteria], the signaling agent responsible for the effects of septicemia, in both anesthetized rats and in isolated rat aortic segments. Survival time of rats treated with LPS (12 mg/kg) was significantly (p < 0.05) prolonged by pretreatment with RPPGF [140.3 +/- 16 min (n = 10)] compared with rats receiving saline and LPS [93.2 +/- 8 min (n = 39)]. Prolongation of survival was not seen when rats were pretreated with either bradykinin or with PRGFP (proline-arginine-glycine-phenylalanine-proline). Isolated aortic segments treated with LPS (30 microg/ml) showed a significantly reduced ability to contract in response to phenylephrine compared with control segments not receiving LPS. Pretreatment of the segments with RPPGF significantly reversed the LPS-induced reduction in contractile response of the segments. Removal of the endothelial layer did not alter the protection provided by RPPGF. These results demonstrate the ability of a stable metabolic fragment of bradykinin, RPPGF, to protect against the deleterious effects produced by LPS. The findings presented here may provide the basis for a new developmental area for novel therapeutic agents in the treatment of septicemia.

Animals↗

Correlation of remote ST segment depression and coronary anatomy during acute coronary occlusion.

BACKGROUND: The appearance of remote ST segment depression (RSTD) on an electrocardiogram (ECG) is associated with more extensive infarction and a worse clinical outcome than when RSTD is absent. OBJECTIVE: To determine whether RSTD predicts coronary anatomy during acute coronary occlusion. It was hypothesized that RSTD is associated with the occlusion of a proximal lesion, an extensive artery and an artery without distal collateralization. PATIENTS AND METHODS: In 113 consecutive patients with single vessel disease undergoing percutaneous transluminal coronary angioplasty (PTCA), 12-lead ECGs (recorded at baseline and during balloon inflation) and angiographical data were analyzed independently. Patients with ST segment elevation in the primary territory and RSTD (greater than 1 mm ST depression at 80 ms after the J point) (group A) were compared with patients without RSTD (group B). Proximal lesions were defined as lesions located in the segments proximal to the acute marginal branch, first diagonal artery or first obtuse marginal branch. An extensive right coronary artery (RCA) was one that supplied the posterolateral wall; an extensive left anterior descending (LAD) artery was one that supplied the inferoapical wall; and an extensive circumflex artery was one that supplied the posterior descending artery. RESULTS: Fifty-four patients (48%) had PTCA of the proximal vessels, 43 patients (38%) had extensive target vessels and 11 patients (9.7%) had collaterals. Target vessels included 33% in RCA, 44% in LAD artery and 23% in circumflex artery. Forty-five patients (40%) developed RSTD during balloon inflation (group A). Patients in group A were more likely to have extensive vessels on the angiogram than those in group B (group A 49%, group B 31%; P=0.05). None of the patients in group A had collaterals to the culprit artery, while 16% of patients in group B did (P=0.003). The two groups were not significantly different with respect to the number of proximal lesions (group A 58%, group B 42%; P=0.08). Analysis performed according to the target artery revealed that RSTD was associated with occlusion of an extensive RCA during RCA occlusion (extensive RCA in group A 100%, group B 57%; P=0.006). For the LAD artery, RSTD was associated with proximal lesions (group A 74%, group B 41%; P=0.02) and absence of collaterals (group A 100%, group B 74%; P=0.01). CONCLUSIONS: During acute coronary occlusion, the presence of RSTD on 12-lead ECG was specific for the absence of collaterals. The presence of RSTD during RCA occlusion was strongly associated with an extensive RCA, suggestive of posterolateral wall ischemia. During LAD artery occlusion, the presence of RSTD was associated with proximal occlusion, which resulted in ischemia of the LAD artery and the major diagonal artery territories.

Acute Disease↗

Facilitation of stent retention and retrieval with an emboli containment device.

A potential consequence of unsuccessful stent delivery is dislodgment of the stent from the delivery catheter resulting in embolization. Recently, an angioplasty guidewire incorporating a distal occlusion balloon (GuardWire) has become available. We describe how, when used for the prevention of distal embolization of atheromatous or thrombotic particles, this device may facilitate retention and retrieval of undeployed stents.

Aged↗

Suture closure of femoral arterial puncture sites after coronary angioplasty followed by same-day discharge.

BACKGROUND: The purpose of this study was to determine whether immediate suture closure of 8F femoral arterial puncture sites can facilitate same-day discharge after coronary angioplasty. METHODS AND RESULTS: After coronary angioplasty, 100 patients were randomly assigned to immediate sheath removal with the double-suture Prostar-Plus device or delayed sheath removal with application of a c-clamp. After suture closure, mobilization at 4 hours after sheath removal and discharge 4 hours later were planned. Patients treated with the c-clamp had sheaths removed 4 hours after percutaneous transluminal coronary angioplasty, were mobilized 6 hours later, and discharged the following day. Patients were assessed for groin complications at 8, 24, and 72 hours. Overall, patients who received suture closure were mobilized at 7.1 +/- 5.3 hours and discharged 11. 15 +/- 6.22 hours after sheath removal versus 15.49 +/- 3.9 hours and 21.9 +/- 3.8 hours for patients with the c-clamp (P <.001). Initial failure of the suture device occurred in 5 patients, with 1 requiring surgery for an entrapped device. After the procedure, patients with suture closure more frequently had an ooze of blood (55% vs 24%, P <.001) and a trend to more overt external bleeding (10% vs 2%, P = not significant). Hematomas were reported by 20% of patients in both groups at 72 hours. Overall, patients preferred the suture closure method of sheath removal when assessed by a simple questionnaire. An economic analysis by cost minimization demonstrated potential hospital cost saving. CONCLUSIONS: Suture closure of 8F arterial puncture sites can facilitate early mobilization and same-day discharge and is considered acceptable by more patients compared with application of the c-clamp. There is potential to realize cost savings with a strategy of same-day discharge.

Angioplasty, Balloon, Coronary↗

Cardiogenic shock due to acute severe mitral regurgitation complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we use emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: Our objective was to define the outcomes of patients with cardiogenic shock (CS) due to severe mitral regurgitation (MR) complicating acute myocardial infarction (AMI). BACKGROUND: Methods for early identification and optimal treatment of such patients have not been defined. METHODS: The SHOCK Trial Registry enrolled 1,190 patients with CS complicating AMI. We compared 1) the cohort with severe mitral regurgitation (MR, n = 98) to the cohort with predominant left ventricular failure (LVF, n = 879), and 2) the MR patients who underwent valve surgery (n = 43) to those who did not (n = 51). RESULTS: Shock developed early after MI in both the MR (median 12.8 h) and LVF (median 6.2 h) cohorts. The MR patients were more often female (52% vs. 37%, p = 0.004) and less likely to have ST elevation at shock diagnosis (41% vs. 63%, p < 0.001). The MR index MI was more frequently inferior (55% vs. 44%, p = 0.039) or posterior (32% vs. 17%, p = 0.002) than that of LVF and much less frequently anterior (34% vs. 59%, p < 0.001). Despite having higher mean LVEF (0.37 vs. 0.30, p = 0.001) the MR cohort had similar in-hospital mortality (55% vs. 61%, p = 0.277). The majority of MR patients did not undergo mitral valve surgery. Those undergoing surgery exhibited higher mean LVEF than those not undergoing surgery; nevertheless, 39% died in hospital. CONCLUSIONS: The data highlight opportunities for early identification and intervention to potentially decrease the devastating mortality and morbidity of severe post-myocardial infarction MR.

Aged↗

Angiographic findings and clinical correlates in patients with cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to delineate the angiographic findings, clinical correlates and in-hospital outcomes in patients with cardiogenic shock (CS) complicating acute myocardial infarction. BACKGROUND: Patients with CS complicating acute myocardial infarction carry a grave prognosis. Detailed angiographic findings in a large, prospectively identified cohort of patients with CS are currently lacking. METHODS: We compared the clinical characteristics, angiographic findings, and in-hospital outcomes of 717 patients selected to undergo angiography and 442 not selected, overall and by shock etiology: left or right ventricular failure versus mechanical complications. RESULTS: Patients who underwent angiography had lower baseline risk and a better hemodynamic profile than those who did not. Overall, 15.5% of the patients had significant left main lesions on angiography, and 53.4% had three-vessel disease, with higher rates of both for those with ventricular failure, compared with patients who had mechanical complications. Among patients who underwent angiography, those with ventricular failure had significantly lower in-hospital mortality than patients with mechanical complications (45.2% vs. 57.0%; p = 0.021). Importantly, for patients with ventricular failure, in-hospital mortality also correlated with disease severity: 35.0% for no or single-vessel disease versus 50.8% for three-vessel disease. Furthermore, mortality was associated with the culprit lesion location (78.6% in left main lesion, 69.7% in saphenous vein graft lesions, 42.4% in circumflex lesions, 42.3% in left anterior descending lesions, and 37.4% in right coronary artery lesions), and Thrombolysis In Myocardial Infarction (TIMI) flow grade (46.5% in TIMI 0/1, 49.4% in TIMI 2 and 26% in TIMI 3). CONCLUSIONS: Patients who underwent angiographic study in the SHOCK Trial Registry had a more benign cardiac risk profile, more favorable hemodynamic findings and lower in-hospital mortality than those for whom angiograms were not obtained. Patients with CS caused by ventricular failure had more severe atherosclerosis, and a different distribution of culprit vessel involvement but lower in-hospital mortality, than those with mechanical complications. Overall in-hospital survival correlates with the extent of coronary artery obstructions, location of culprit lesion and baseline coronary TIMI flow grade.

Aged↗

The clinical profile of patients with suspected cardiogenic shock due to predominant left ventricular failure: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: We sought to evaluate the frequency of pulmonary congestion and associated clinical and hemodynamic findings in patients with suspected cardiogenic shock (CS). BACKGROUND: The prevalence of pulmonary congestion in the setting of CS is uncertain. METHODS: The 571 SHOCK Trial Registry patients with predominant left ventricular failure (LVF) were divided into four groups: Group A = no pulmonary congestion/no hypoperfusion = 14 (3%), Group B = isolated pulmonary congestion = 32 (6%), Group C = isolated hypoperfusion = 158 (28%) and Group D = congestion with hypoperfusion = 367 (64%). Statistical comparisons between Group C and D only, with regard to patient demographics, hemodynamics, treatment and outcome, were made. RESULTS: A significant proportion of patients with shock had no pulmonary congestion (Group C = 28%, 95% CI, 24% to 31%). Age and gender in this group were similar to Group D. Group C patients were less likely to have a prior MI (p = 0.028), congestive heart failure (p = 0.005) and renal insufficiency (p = 0.032), and the index MI was less likely to be anterior (p = 0.044). Cardiac output, cardiac index and ejection fraction were similar for the two groups but pulmonary capillary wedge pressure was slightly lower for Group C (22 vs. 24 mm Hg, p = 0.012). Treatment with thrombolysis, angioplasty and bypass surgery was similar in the two groups. In-hospital mortality rates for Groups C and D were 70% and 60%, respectively (p = 0.036). After adjustment, this difference was no longer statistically significant (p = 0.153). CONCLUSIONS: Absence of pulmonary congestion at initial clinical evaluation does not exclude a diagnosis of CS due to predominant LVF and is not associated with a better prognosis.

Aged↗

Impact of thrombolysis, intra-aortic balloon pump counterpulsation, and their combination in cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to investigate the potential benefit of thrombolytic therapy (TT) and intra-aortic balloon pump counterpulsation (IABP) on in-hospital mortality rates of patients enrolled in a prospective, multi-center Registry of acute myocardial infarction (MI) complicated by cardiogenic shock (CS). BACKGROUND: Retrospective studies suggest that patients suffering from CS due to MI have lower in-hospital mortality rates when IABP support is added to TT. This hypothesis has not heretofore been examined prospectively in a study devoted to CS. METHODS: Of 1,190 patients enrolled at 36 participating centers, 884 patients had CS due to predominant left ventricular (LV) failure. Excluding 26 patients with IABP placed prior to shock onset and 2 patients with incomplete data, 856 patients were evaluated regarding TT and IABP utilization. Treatments, selected by local physicians, fell into four categories: no TT, no IABP (33%; n = 285); IABP only (33%; n = 279); TT only (15%; n = 132); and TT and IABP (19%; n = 160). RESULTS: Patients in CS treated with TT had a lower in-hospital mortality than those who did not receive TT (54% vs. 64%, p = 0.005), and those selected for IABP had a lower in-hospital mortality than those who did not receive IABP (50% vs. 72%, p < 0.0001). Furthermore, there was a significant difference in in-hospital mortality among the four treatment groups: TT + IABP (47%), IABP only (52%), TT only (63%), no TT, no IABP (77%) (p < 0.0001). Patients receiving early IABP (< or = 6 h after thrombolytic therapy, n = 72) had in-hospital mortality similar to those with late IABP (53% vs. 41%, n = 64, respectively, p = 0.172). Revascularization rates differed among the four groups: no TT, no IABP (18%); IABP only (70%); TT only (20%); TT and IABP (68%, p < 0.0001); this influenced in-hospital mortality significantly (39% with revascularization vs. 78% without revascularization, p < 0.0001). CONCLUSIONS: Treatment of patients in cardiogenic shock due to predominant LV failure with TT, IABP and revascularization by PTCA/CABG was associated with lower in-hospital mortality rates than standard medical therapy in this Registry. For hospitals without revascularization capability, a strategy of early TT and IABP followed by immediate transfer for PTCA or CABG may be appropriate. However, selection bias is evident and further investigation is required.

Aged↗

Implications of the timing of onset of cardiogenic shock after acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to examine the implications of the timing of onset of cardiogenic shock (CS) after acute myocardial infarction (MI). BACKGROUND: Little information is available about the relationships between timing, clinical substrate, management and outcomes of shock. METHODS: The multinational SHOCK Trial Registry enrolled MI patients with CS from 1993 to 1997. Cardiogenic shock was predominantly attributable to left ventricular (LV) failure in 815 Registry patients for whom temporal data were available. We examined factors related to the timing of shock onset and the relation of temporal onset to in-hospital outcomes. RESULTS: Overall, shock developed a median of 6.2 h after MI symptom onset. Shock onset varied by culprit artery: left main, median 1.7 h; right, 3.5 h; circumflex, 3.9 h; left anterior descending (LAD), 11.0 h; saphenous vein graft, 10.9 h (p = 0.025). Early shock (< 24 h) occurred in 74.1% and was associated with chest pain at shock onset, ST-segment elevation in two or more leads, multiple infarct locations, inferior MI, left main disease and smoking. Late shock (> or = 24 h) was associated with recurrent ischemia, Q waves in two or more leads and LAD culprit vessel. Mortality was higher in patients with early versus late shock (62.6% vs. 53.6%, p = 0.022). CONCLUSIONS: Shock onset after acute MI occurred within 24 h in 74% of the patients with predominant LV failure. Mortality was slightly higher in patients developing shock early rather than later. Many factors influence when shock develops, which has implications for its management.

Aged↗

Outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: We wished to assess the profile and outcomes of patients with ventricular septal rupture (VSR) in the setting of cardiogenic shock (CS) complicating acute myocardial infarction (MI). BACKGROUND: Cardiogenic shock is often seen with VSR complicating acute MI. Despite surgical therapy, mortality in such patients is high. METHODS: We analyzed 939 patients enrolled in the SHOCK Trial Registry of CS in acute infarction, comparing 55 patients whose shock was associated with VSR with 884 patients who had predominant left ventricular failure. RESULTS: Rupture occurred a median 16 h after infarction. Patients with VSR tended to be older (p = 0.053), were more often female (p = 0.002) and less often had previous infarction (p < 0.001), diabetes mellitus (p = 0.015) or smoking history (p = 0.033). They also underwent right-heart catheterization, intra-aortic balloon pumping and bypass surgery significantly more often. Although patients with rupture had less severe coronary disease, their in-hospital mortality was higher (87% vs. 61%, p < 0.001). Surgical repair was performed in 31 patients with rupture (21 had concomitant bypass surgery); 6 (19%) survived. Of the 24 patients managed medically, only 1 survived. CONCLUSIONS: There is a high in-hospital mortality rate when CS develops as a result of VSR. Ventricular septal rupture may occur early after infarction, and women and the elderly may be more susceptible. Although the prognosis is poor, surgery remains the best therapeutic option in this setting.

Aged↗

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↗