Dynamics and source of endothelin-1 and interleukin-6 following coronary reperfusion in patients with acute myocardial infarction.

OBJECTIVES: The goals of this study were to determine the source of circulating endothelin-1 (ET-1) and interleukin-6 (IL-6) in acute myocardial infarction (MI) and to study the effects of coronary reperfusion (CR) on plasma levels of ET-1 and IL-6. METHODS: We serially measured plasma concentrations of ET-1 and IL-6 at different sampling sites before and after CR in patients with acute MI. A femoral vein (FV) catheter, a Swan-Ganz catheter, and a femoral artery (FA) catheter were placed in 25 patients with acute MI who were admitted within 12 hours after onset. For the measurement of ET-1 and IL-6 concentrations, blood samples from the FV, right atrium (RA), pulmonary artery (PA), and FA were collected before and 1 hour, 8 hours, and 24 hours after CR therapy. In 5 of the 25 patients, blood samples were collected through a coronary sinus (CS) catheter. We also assessed the gradient across 3 vascular beds (systemic, pulmonary, and coronary) as indices of the net release of ET-1 and IL-6 from those vascular beds. The maximal serum creatine kinase (CK) levels were assessed as an index of myocardial necrosis. RESULTS: ET-1 levels were higher in the FV than in the RA, PA, or FA. On CR, ET-1 levels peaked after 1 hour and returned to baseline by 24 hours. Calculated net release of ET-1 from the systemic vascular bed (ET-1 at FV-ET-1 at FA) was the highest among the 3 vascular beds. Plasma ET-1 levels correlated with hemodynamic parameters. Plasma IL-6 levels were similar among different sampling sites, whereas calculated net release of IL-6 from the coronary vascular bed was the highest among the 3 vascular beds. IL-6 levels increased throughout 24 hours after coronary reperfusion and closely correlated with maximal CK levels. CONCLUSIONS: The present study suggests that, in acute MI, the major source of ET-1 maintaining baseline plasma levels is the systemic vascular bed and that the ET-1 levels presumably reflect the congestion. ET-1 levels peaked 1 hour after CR. IL-6 increased for 24 hours after CR. The major source of IL-6 is the coronary vascular bed. Only a slight correlation was observed between plasma ET-1 and IL-6 levels.

Chronic direct stimulation of adenylyl cyclase induces cardiac desensitization to catecholamine and beta-adrenergic receptor downregulation in rabbits.

Chronic stimulation of beta-adrenergic receptors (betaARs) induces betaAR downregulation. However, it is not known whether continuous activation of adenylyl cyclase without direct stimulation of betaARs leads to receptor downregulation. This study investigated the effects of chronic stimulation of adenylyl cyclase with colforsin, on hemodynamic variables, and on myocardial betaAR density. In all, 55 rabbits received intravenous colforsin (1.6 microg/kg/min, n = 20), isoproterenol (ISO; 0.4 microg/kg/min, n = 16), or saline (n = 19) for two weeks. After chronic drug administration, responses of systolic (Delta% peak LV +dP/dt) and diastolic function (Delta% peak LV -dP/dt), and heart rate (Delta% heart rate), to acute administration of ISO (0.05 to 0.2 microg/kg/min) or colforsin (5 to 20 nmol/kg/min) were decreased compared to those before chronic administration. betaAR density in the colforsin group (69.8 +/- 13.8 fmol/ml protein) was less than that in the saline group (79.8 +/- 15.0 fmol/ml protein, P < 0.05), but was greater than that in the ISO group (56.3 +/- 8.4 fmol/ml protein, P < 0.05). Thus, chronic direct stimulation of adenylyl cyclase elicited systolic and diastolic functional desensitization to betaAR stimulation or adenylyl cyclase stimulation, and myocardial betaAR downregulation.

Effects of the patent false lumen on the long-term outcome of type B acute aortic dissection.

OBJECTIVE: To determine the most effective treatment, we performed a detailed comparative study of the clinical course of patients with type B aortic dissection with a patent or thrombosed false lumen who did not undergo surgery in the acute period. We examined the effect of patency of the false lumen on outcome. METHODS: Computed tomography scans of 138 patients with type B acute aortic dissection were reviewed. Of 138 patients, 110 were medically treated and survived the acute period. We focused on the outcome of these 110 patients, 62 with medically treated thrombosed false lumen (thrombosed group) and 48 with medically treated patent false lumen (patent group). We investigated factors influencing outcome among the 110 patients. The follow-up period was up to 10 years after the onset of aortic dissection. The three study endpoints were death from any cause, dissection-related death (aortic rupture, perioperative death, or death due to organ ischemia), and a dissection-related event (aortic rupture or surgery). In the patent group, we investigated factors influencing long-term outcome. RESULTS: Patency of the false lumen was an independent risk factor for dissection-related death (P = 0.038, hazard ratio=5.6, confidence interval=1.1-28) and for a dissection-related event (P = 0.000, hazard ratio=7.6, confidence interval=2.7-22) but not for death from any cause (P = 0.769, hazard ratio=1.2, confidence interval=0.45-2.91). In the patent group, location of the most dilated aortic segment at the distal arch was an independent risk factor for dissection-related death (P = 0.026, hazard ratio=13.6, confidence interval=1.4-135) and for a dissection-related event (P = 0.048, hazard ratio=2.6, confidence interval=1.0-6.9). CONCLUSIONS: Patency of the false lumen is a strong independent prognostic factor for type B aortic dissection. Location of the most dilated aortic segment at the distal arch is a significant risk factor in the patients with a patent false lumen.

Limitation of infarct size and ventricular remodeling in patients with completely reperfused anterior acute myocardial infarction--the potential role of ischemia time.

BACKGROUND: Experimental studies suggest that coronary reperfusion does not result in appreciable myocardial salvage beyond 3 to 4 h. HYPOTHESIS: The present study was undertaken to examine the potential role of ischemia time as a determinant of infarct size and cardiac function in humans. METHODS: Ninety patients (69 men, 21 women, aged 61 +/- 1 years) presented within 24 h of onset of a first anterior infarct had ST-segment elevation on electrocardiogram. All patients underwent coronary intervention within 24 h of onset of symptoms and obtained complete reperfusion of the infarct-related artery. RESULTS: Infarct size expressed as a percentage of the area at risk (IS/RA) and left ventricular end-diastolic volume (LVEDV) were significantly (p < 0.017) smaller and left ventricula rejection fraction (LVEF) assessed by left ventriculography (35 +/- 4 days) was significantly higher in patients treated within 4 h after onset (IS/RA:55 +/- 4%, LVEDV: 127 +/- 7 ml, LVEF: 62 +/- 2%) than in those treated 4 to 12 h (97 +/- 2%, 140 +/- 13 ml, 52 +/- 3%) and 12 to 24 h (93 +/- 2%,163 +/- 14 ml, 49 +/- 5%) after symptom onset. Left ventricular end-diastolic volume was significantly smaller in patients treated 4 to 12 h after onset than in those treated 12 to 24 h after onset. CONCLUSIONS: Patients with < 4 h of myocardial ischemia exhibited significant myocardial salvage and better left ventricular function and patients with 4 to 12 h of myocardial ischemia exhibited significantly smaller LVEDV than those with more prolonged ischemia, although there was no difference in final infarct size.

[Potential role of leptin and insulin resistance assessed by the glucose clamp technique in coronary artery disease].

OBJECTIVES: Leptin may correlate with insulin resistance and be an important factor in patients with coronary artery disease. Therefore, we examined whether plasma leptin levels and insulin resistance are linked with coronary artery disease. METHODS: Plasma leptin levels and insulin resistance, assessed by the hyperinsulinemic euglycemic clamp technique, were measured in control subjects (n = 12, mean age 62 +/- 10 years), and in patients with obstructive coronary artery disease (n = 15, mean age 64 +/- 8 years) or vasospastic angina (n = 12, mean age 62 +/- 12 years). RESULTS: Plasma leptin levels were significantly higher (p < 0.017) in patients with obstructive coronary artery disease (8.4 +/- 2.7 ng/ml) and vasospastic angina (7.9 +/- 2.1 ng/ml) than in patients without obstructive coronary artery disease (4.7 +/- 1.4 ng/ml). Mean glucose infusion rate was significantly (p < 0.017) lower in patients with obstructive coronary artery disease (4.39 +/- 1.78 mg/kg/min) and vasospastic angina (3.57 +/- 1.72 mg/kg/min) than in patients without obstructive coronary artery disease (8.74 +/- 1.05 mg/kg/min). The plasma levels of leptin were negatively correlated with mean glucose infusion rate (r = -0.67, p < 0.01). The other coronary risk factors were similar in these three groups. CONCLUSIONS: Plasma leptin levels are correlated with insulin resistance and may be associated with coronary artery disease.

[Left ventricular peak systolic pressure/end-systolic volume ratio change after dobutamine infusion for predicting left ventricular contractile reserve: comparison with Emax].

OBJECTIVES: Genuine left ventricular contractile function is difficult to assess in the clinical setting. Left ventricular peak systolic pressure/end-systolic volume (Pps/Ves) ratio may be misleading because this index takes no account of the left ventricular end-systolic point and V0 intercept in the pressure-volume relation geographic curve. End-systolic pressure-volume relation and maximum chamber elastance derived from left ventricular pressure-volume loops can provide reliable estimates of contractile function. However, the feasibility of this technique for clinical purposes is limited, because it requires instantaneous measurement of left ventricular pressure and volume. This study assessed the feasibility of using Pps/Ves ratio for predicting the left ventricular contractile reserve by direct comparison with maximum elastance (Emax) derived from left ventricular pressure-volume loops. METHODS: Studies were undertaken in 18 consecutive patients aged 60 +/- 9 years who underwent cardiac catheterization. On-line instantaneous left ventricular volume was derived from the acoustic quantification method by transthoracic echocardiography. Pps was determined by pressure manometer tipped wire and Ves was measured automatically from acoustic quantification software in an ultrasound system. Pps/Ves was compared with Emax derived from each simultaneous pressure-volume loop during inferior vena caval occlusion before and after dobutamine infusion. Emax was determined as the slope of end-systolic points for each loop with the use of an automated iterative linear regression technique. Left ventricular contractile reserve was assessed by evaluating its functional response to 10 micrograms/kg/min of dobutamine infusion. RESULTS: Pps/Ves showed significant correlation with Emax in all patients (r = 0.70, p < 0.0001). However, scattered distribution of V0 value differences were noted. Contractile reserve (Pps/Ves) showed strong correlation with contractile reserve (Emax) despite V0 value differences (r = 0.927, p < 0.0001). CONCLUSIONS: Pps/Ves change after dobutamine infusion may minimize individual V0 distribution. This simple index could be used to evaluate left ventricular systolic performance without requiring the left ventricular pressure-volume relationship and volume unloading maneuver.