Randomized trial of phosphodiesterase inhibitors versus catecholamines in patients with acutely decompensated heart failure.
(73/595)
Increased neurohormone and cytokine concentrations are associated with adverse outcome in patients with congestive heart failure, so minimizing these increases may improve outcome, even in the acute phase of decompensated heart failure. The present study was designed to test the hypothesis that phosphodiesterase inhibitors, but not catecholamines, could favorably affect neurohormone and cytokine profiles in patients with acutely decompensated heart failure. Twenty-nine patients underwent monitoring using a Swan-Ganz catheter and were randomly allocated to receive phosphodiesterase inhibitors (PDEI group, n=19) or catecholamines (CA group, n=10). Pulmonary capillary wedge pressure decreased significantly in both groups and cardiac output showed a slight, but not statistically significant increase, in both groups. There was a significant decrease in plasma brain natriuretic peptide concentration in the PDEI group, but not in the CA group, whereas plasma interleukin-6 concentration increased in the CA group, but not in the PDEI group. Phosphodiesterase inhibitors favorably affect neurohormone and cytokine concentrations in patients with acutely decompensated heart failure. (+info)
Pressure-derived collateral flow index as a parameter of microvascular dysfunction in acute myocardial infarction.
(74/595)
OBJECTIVES: The goal of this study was to examine the implications of the pressure-derived collateral flow index (CFIp) in acute myocardial infarction (AMI). BACKGROUND: Higher CFIp is associated with less severe myocardial ischemia during angioplasty in the non-infarcted heart. It remains unknown whether CFIp also identifies collateral function in AMI patients with and without no-reflow phenomenon. METHODS: The study population included 48 patients with a first AMI. After successful percutaneous transluminal coronary angioplasty (PTCA) stent, we measured mean aortic pressure (Pa), central venous pressure (Pv) and coronary wedge pressure (Pcw) of the infarct-related artery to calculate: CFIp = (Pcw - Pv)/(Pa - Pv). Myocardial contrast echocardiography (MCE) was performed with the intracoronary injection of microbubbles to assess myocardial perfusion. Left ventriculograms at days 1 and 28 were provided for the measurement of the regional wall motion (RWM, SD/chord). RESULTS: There was no difference in CFIp among subsets based on angiographic collateral grades (grade 0, 1, 2, 3; 0.28 +/- 0.07, 0.27 +/- 0.09, 0.27 +/- 0.08, 0.23 +/- 0.08, p = NS). The CFIp was significantly higher in patients with MCE no-reflow (n = 16) than in those with MCE reflow (n = 32) (0.34 +/- 0.07 vs. 0.23 +/- 0.06, p < 0.01). There was a significant inverse correlation between the extent of functional improvement (DeltaRWM[28 d-1 d]) and CFIp (r = 0.56, p < 0.01), implying that higher CFIp is associated with worse functional improvement. CONCLUSIONS: In AMI, CFIp is unlikely to reflect collateral function but seems to increase with the severity of microvascular dysfunction. Because higher CFIp was associated with poorer functional recovery, it provides a simple and useful estimate of clinical outcomes in AMI. (+info)
Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure.
(75/595)
BACKGROUND: Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V(1A) (vascular and myocardial effects) and V(2) receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. METHODS AND RESULTS: A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V(1a)/V(2) vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6+/-0.7, -5.4+/-0.7, and -4.6+/-0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) and right atrial pressure (-2.0+/-0.4, -3.7+/-0.4, and -3.5+/-0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11+/-17, 68+/-17, 152+/-19, and 176+/-18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. CONCLUSIONS: In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients. (+info)
Ventricular assist device in severe heart failure: effects on cytokines, complement and body weight.
(76/595)
AIMS: Inflammatory and immune activation and body wasting are important features of end-stage chronic heart failure. It is not known whether restoration of cardiac output by assist device implantation can improve these abnormalities. METHODS: We studied 48 patients (39 males; age 45+/-2 years) with NYHA class IV heart failure. All patients underwent ventricular assist device implantation for end-stage heart failure as a bridge to cardiac transplantation. Plasma levels of tumour necrosis factor alpha, and its receptors, interleukin-6, elastase, activated complement, and soluble CD14 receptors were measured at the time of operation and in survivors at 1 week (n=46), 40 days (n=35) and 90 days (n=26). Follow-up was for a minimum of 1 year. RESULTS: One-year survival was 35% (95% CI: 22-49%). Body mass index was the only predictor of survival (body mass index >25 (n=16); survival 63 (39-86) %; body mass index <25 (n=32); survival 22 (7.5-36) %: P=0.003). Tumour necrosis factor alpha fell from 9.66+/-1.33 pg x ml(-1) to 4.2+/-1.0 at 1 week (P=0.008), but returned to pre-operative levels at 90 days. Interleukin-6, activated complement and elastase fell progressively to 40 days, but were rising at 90 days. There was no change in tumour necrosis factor receptor. There was a gradual rise in CD14 (3.99+/-0.15 microg x ml(-1) at baseline, 5.02+/-0.39 at 90 days, P=0.006). After surgery, body weight fell from 80+/-2 to 73+/-2 kg by 1 month (P<0.001) and to 72+/-2 kg at 90 days. CONCLUSIONS: Ventricular assist device implantation results in a short-term fall in tumour necrosis factor alpha and interleukin-6, but no change in CD14 or tumour necrosis factor receptor, suggesting that the pathophysiological process resulting in inflammation was not altered by left ventricular assist device implantation. Low body mass index is related to poor outcome after assist device implantation, and no weight gain. (+info)
Reversal of cardiogenic shock by percutaneous left atrial-to-femoral arterial bypass assistance.
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BACKGROUND: Recovery of myocardial function after revascularization of acutely occluded coronary arteries may require several days. During this critical time, patients in cardiogenic shock may have low output. A newly developed percutaneous left ventricular assist device (VAD) may offer effective treatment for these patients by providing active circulatory support. METHODS AND RESULTS: Between May 2000 and May 2001, VADs were implanted in 18 consecutive patients who had cardiogenic shock after myocardial infarction. The device was connected to the patient's circulation by insertion of a 21F venous cannula into the left atrium by transseptal puncture; blood was returned to the iliac artery through an arterial cannula. Mean duration of cardiac assistance was 4+/-3 days. Mean flow of the VAD was 3.2+/-0.6 L/min. Before support, cardiac index was 1.7+/-0.3 L/min per m(2) and improved to 2.4+/-0.6 L/min per m(2) (P<0.001). Mean blood pressure increased from 63+/-8 mm Hg to 80+/-9 mm Hg (P<0.001). Pulmonary capillary wedge pressure, central venous pressure, and pulmonary artery pressure were reduced from 21+/-4, 13+/-4, and 31+/-8 mm Hg to 14+/-4, 9+/-3, and 23+/-6 mm Hg (all P<0.001), respectively. Overall 30-day mortality rate was 44%. CONCLUSIONS: A newly developed VAD can be rapidly deployed in the catheterization laboratory setting. This device provides up to 4.0 L/min of assisted cardiac output, which may aid to revert cardiogenic shock. The left ventricle is unloaded by diverting blood from the left atrium to the systemic circulation, making recovery more likely after an ischemic event. The influence of this device on long-term prognosis warrants further investigation. (+info)
Low molecular weight protamine as nontoxic heparin/low molecular weight heparin antidote (III): preliminary in vivo evaluation of efficacy and toxicity using a canine model.
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Heparin employed in cardiovascular surgeries often leads to a high incidence of bleeding complications. Protamine employed in heparin reversal, however, can cause severe adverse reactions. In an attempt to address this clinical problem, we developed low molecular weight protamine (LMWP) as a potentially effective and less toxic heparin antagonist. A homogeneous 1880-d peptide fragment, termed LMWP-TDSP5 and containing the amino acid sequence of VSRRRRRRGGRRRR, was derived directly from protamine by enzymatic digestion of protamine with thermolysin. In vitro studies demonstrated that TDSP5 was capable of neutralizing various anticoagulant functions of both heparin and commercial low molecular weight heparin preparations. In addition, TDSP5 exhibited significantly reduced crossreactivity toward mouse sera containing antiprotamine antibodies. TDSP5 showed a decrease in its potential in activating the complement system. All of these findings suggested the possibility of markedly reduced protamine toxicity for TDSP5. In this article, we conducted preliminary in vivo studies to further demonstrate the feasibility and utility of using LMWP as a nontoxic clinical protamine substitute. Dogs were chosen as test animals because they were known to magnify the typical human response to protamine. By using a full spectra of biological and clinical assays for heparin, including the anti-IIa and anti-Xa chromogenic assays and the activated partial, thromboplastin time and TCT clotting assays, TDSP5 showed that it could completely neutralize all these different anticoagulant functions of heparin in dogs. Although administration of protamine in dogs produced a significant reduction in mean arterial blood pressure (-14.9 mm Hg) and elevation in pulmonary artery systolic pressure (+5.0 mm Hg), the use of TDSP5 in dogs did not elicit any statistically significant change in any of the variables measured. Furthermore, the use of LMWP also significantly reduced the protamine-induced transient thrombocytopenic and granulocytopenic responses. The white blood cell counts and platelet counts decreased to 82.1% and 60.0% of baseline, respectively, in dogs given intravenous protamine compared to 97.8% and 88.6% of baseline in dogs receiving TDSP5. These preliminary findings indicated that LMWP could potentially provide an effective and safe means to control both heparin- and protamine-induced complications. (+info)
Initial experience with hyperoxemic reperfusion after primary angioplasty for acute myocardial infarction: results of a pilot study utilizing intracoronary aqueous oxygen therapy.
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OBJECTIVES: The purpose of this study was to evaluate the feasibility and safety of intracoronary hyperoxemic reperfusion after primary angioplasty for acute myocardial infarction (MI). BACKGROUND: Hyperoxemic therapy with aqueous oxygen (AO) attenuates reperfusion injury and preserves left ventricular (LV) function in experimental models of MI. METHODS: In a multi-center study of patients with acute MI undergoing primary angioplasty (PTCA), hyperoxemic blood (pO(2): 600 to 800 mm Hg) was infused into the infarct-related artery for 60 to 90 min after intervention. The primary end points were clinical, electrical and hemodynamic stability during hyperoxemic reperfusion and in-hospital major adverse cardiac events. Global and regional LV function was evaluated by serial echocardiography after PTCA, after AO infusion, at 24 h and at one and three months. RESULTS: Twenty-nine patients were enrolled (mean age: 58.9+/-12.6 years). Hyperoxemic reperfusion was performed successfully in all cases (mean infusion time: 80.8+/-18.2 min; mean coronary perfusate pO(2): 631+/-235 mm Hg). There were no adverse events during hyperoxemic reperfusion or the in-hospital period. Compared with baseline, a significant improvement in global wall motion score index was observed at 24 h (1.68+/-0.24 vs. 1.48+/-0.24, p < 0.001) with a trend toward an increase in ejection fraction (48.6+/-7.3% vs. 51.8+/-6.8%, p = 0.08). Progressive improvement in LV function was observed at one and three months, primarily due to recovery of infarct zone function. CONCLUSIONS: Intracoronary hyperoxemic reperfusion is safe and well tolerated after primary PTCA. These preliminary data support the need for a randomized controlled trial to determine if hyperoxemic reperfusion enhances myocardial salvage or improves long-term outcome. (+info)
Differential actions of vasopeptidase inhibition versus angiotensin-converting enzyme inhibition on diuretic therapy in experimental congestive heart failure.
(80/595)
BACKGROUND: Omapatrilat (OMA), a vasopeptidase inhibitor, simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase, which degrades vasodilatory factors (eg, ADM) and natriuretic peptides. Based on the beneficial cardiorenal and humoral properties of the natriuretic peptides, we hypothesized that an acute vasopeptidase inhibitor with or without diuretic would result in more favorable cardiorenal and hormonal actions than ACE inhibition plus diuretic (ACEI+D) in congestive heart failure. METHODS AND RESULTS: We compared the actions of OMA alone and with diuretic (OMA+D) to ACEI+D in a model of pacing-induced congestive heart failure. OMA+D decreased pulmonary arterial and pulmonary capillary wedge pressures to a greater level than OMA alone or ACEI+D. Glomerular filtration rate was lower with ACEI+D than with either OMA group. Plasma renin activity and aldosterone immediately increased with ACEI+D, whereas OMA+D resulted in higher plasma renin activity and a delayed increase in aldosterone. OMA alone did not increase plasma renin activity and aldosterone, but resulted in a sustained increase in plasma adrenomedullin, with higher urinary atrial natriuretic peptide, adrenomedullin, and cGMP excretions than with ACEI+D. CONCLUSIONS: Acute administration of OMA with or without diuretic results in more favorable cardiorenal and humoral responses in experimental congestive heart failure than does ACEI+D. There is no acute activation of renin and aldosterone with OMA alone such as occurs with ACEI+D and OMA+D. Thus, OMA with or without a diuretic possesses beneficial cardiorenal and humoral actions comparable to those observed with ACEI+D that can be explained by potentiation of natriuretic peptides. (+info)