Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.

Contribution of atmospheric nitrate to stream-water nitrate in Japanese coniferous forests revealed by the oxygen isotope ratio of nitrate.

Evaluation of the openness of the nitrogen (N) cycle in forest ecosystems is important in efforts to improve forest management because the N supply often limits primary production. The use of the oxygen isotope ratio (delta(18)O) of nitrate is a promising approach to determine how effectively atmospheric nitrate can be retained in a forest ecosystem. We investigated the delta(18)O of nitrate in stream water in order to estimate the contribution of atmospheric NO(3) (-) in stream-water NO(3) (-) (f(atm)) from 26 watersheds with different stand ages (1-87 years) in Japan. The stream-water nitrate concentrations were high in young forests whereas, in contrast, old forests discharged low-nitrate stream water. These results implied a low f(atm) and a closed N cycle in older forests. However, the delta(18)O values of nitrate in stream water revealed that f(atm) values were higher in older forests than in younger forests. These results indicated that even in old forests, where the discharged N loss was small, atmospheric nitrate was not retained effectively. The steep slopes of the studied watersheds (>40 degrees ) which hinder the capturing of atmospheric nitrate by plants and microbes might be responsible for the inefficient utilization of atmospheric nitrate. Moreover, the unprocessed fraction of atmospheric nitrate in the stream-water nitrate in the forest (f(unprocessed)) was high in the young forest (78%), although f(unprocessed) was stable and low for other forests (5-13%). This high f(unprocessed) of the young forest indicated that the young forest retained neither atmospheric NO(3) (-) nor soil NO(3) (-) effectively, engendering high stream-water NO(3) (-) concentrations.

Striking effect of left ventricular high filling pressure with mitral regurgitation on mitral annular velocity during early diastole. A study using colour M-mode tissue Doppler imaging.

AIMS: To evaluate the effect of considerably high left ventricular filling pressure with mitral regurgitation on mitral annular velocity during early diastole. SUBJECTS: Two hundred and forty-three patients who underwent cardiac catheterization for evaluation of chest pain. METHODS: Mitral annular velocity during early diastole was measured by colour M-mode tissue Doppler imaging. Patients were divided into the following three groups according to the cardiac catheterization data. Group A (n=147): patients having left ventricular relaxation time constant tau<46 ms and left ventricular end-systolic volume index <38 ml m(-2); group B (n=88): patients having tau>or=46 ms and/or end-systolic volume index >or=38 ml m(-2); group C (n=8): patients having mean pulmonary capillary wedge pressure >or=16 mmHg in addition to tau>or=46 ms and end-systolic volume index >or=38 ml m(-2). RESULTS: Mitral annular velocity during early diastole was significantly less in group B (4.8+/-1.4 cm s(-1)) than in group A (7.7+/-1.9 cm s(-1)). However, there was no significant difference between groups A and C (8.3+/-0.8 cm s(-1)). A transmitral E/A >1.0 was observed in 12/147 patients of group A, 10/88 of group B, and 8/8 of group C. The incidence of >or=Sellers' grade II mitral regurgitation was higher in group C than the others. CONCLUSIONS: A paradoxically faster mitral annular velocity during early diastole is found in patients having left ventricular dysfunction with moderate to severe mitral regurgitation and considerably high left ventricular filling pressure. Attention should be paid to an interpretation of mitral annular velocity during early diastole regarding left ventricular early diastolic performance in patients having mitral regurgitation with an E/A >1.0 in their transmitral flow.

Postural response of low-frequency component of heart rate variability is an increased risk for mortality in patients with coronary artery disease.

STUDY OBJECTIVES: We examined whether autonomic functions assessed by heart rate variability (HRV) during standardized head-up tilt testing (HUTT) predict risk for death in stable patients with coronary artery disease (CAD). DESIGN AND SETTING: Retrospective cohort study in medium-sized university general hospital. MEASUREMENTS AND RESULTS: In a cohort of 250 patients with CAD who were undergoing elective coronary angiography, we analyzed HRV during standardized HUTT under paced breathing with discontinuation of treatment with all medications. During a subsequent mean follow-up period of 99 months, there were 13 cardiac deaths and 12 noncardiac deaths. Cox regression analysis adjusted for cardiovascular risks revealed that increased postural change (supine to upright) in the power of low-frequency component (LF) power predicted an increased risk for cardiac death (relative risk [per 1-ln ms(2) increment], 4.36; 95% confidence interval, 1.64 to 11.6), while neither the high-frequency component nor its response to HUTT predicted any form of death. When the patients were trichotomized by the level of postural LF change (large drop, < or = - 0.6 ln[ms(2)]; small drop and rise, > 0 ln[ms(2)]), the three groups did not differ in terms of clinical features or CAD severity at baseline or coronary interventions during the follow-up period; however, the 8-year cardiac mortality rates were 0%, 6%, and 12%, respectively (p = 0.008 [log rank test]). Additionally, the difference was enhanced when analyzed excluding 64 patients who had been treated with a beta-blocker during the follow-up period (0%, 7%, and 15%, respectively; p = 0.006 [log rank test]). CONCLUSIONS: The postural response of HRV predicts the risk for death in patients with CAD. Postural LF increase (LF rise), in particular, is an independent risk factor for cardiac death.

Striking effect of left ventricular systolic performance on propagation velocity of left ventricular early diastolic filling flow.

Propagation velocity of left ventricular (LV) early diastolic filling flow (PVE) has been acknowledged as a useful parameter for LV early diastolic performance; however, the effect of LV systolic performance on PVE is not fully understood. Thus the purpose of this study was to investigate such an effect. Propagation of LV early diastolic filling flow was visualized by M-mode color Doppler imaging, and the slopes of the peak velocity tracings were measured as PVE in 150 patients who underwent coronary angiography. In cardiac catheterization, mean pulmonary capillary wedge pressure, time constant tau of LV pressure decay, LV end-systolic volume index, and LV ejection fraction were obtained. In univariate regression analysis, PVE significantly correlated with LV end-systolic volume index (r = -0.68, P <.001), LV ejection fraction (r = 0.66, P <.001), and time constant tau (r = -0.52, P <.001). In multivariate regression analysis, PVE was regressed by the LV end-systolic volume index, tau, and mean pulmonary capillary wedge pressure. The contribution of each parameter to the variance of the PVE was 46%, 3%, and 2%, respectively. A break-point linear regression analysis showed that the relation between the LV end-systolic volume index and PVE was much better characterized by a broken line than a straight line. The broken line had a steeper slope in patients with LV end-systolic volume index < or =41 mL/m(2) than in those with >41 mL/m(2). These findings suggest that PVE is determined mainly by LV systolic performance and partly by both LV relaxation and LV filling pressure. Left ventricular systolic performance may play a key role in generating a much faster PVE, especially in patients with relatively better LV systolic performance.

Ascorbic acid protects against peroxidative modification of low-density lipoprotein, maintaining its recognition by LDL receptors.

Peroxidatively modified low-density lipoprotein (LDL) may contribute to atherosclerotic processes; therefore, protecting LDL against peroxidation may thus reduce or retard the progression of atherosclerosis. We have evaluated the protective effects of ascorbic acid on copper-catalyzed LDL peroxidative modification. The protective effects of ascorbic acid on copper-catalyzed LDL peroxidative modification were examined by measurement of concentration of lipid hydroperoxides in LDL and by the provision of LDL cholesterol to lymphocytes via LDL receptor-mediated pathway. The measurement of concentration of lipid hydroperoxides in LDL showed that ascorbic acid inhibited peroxidative modification of LDL. Also, ascorbic acid preserved the ability of LDL to be recognized by LDL receptors in peripheral blood lymphocytes to the same extent as native LDL. These findings indicate that ascorbic acid may protect LDL against peroxidative modification, maintaining its ability to act as a ligand for LDL receptors in vivo.

The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure.

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (tau), LV end-systolic volume (V(ES)), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, tau, and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT(1)-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest.

Reduced ventricular response irregularity is associated with increased mortality in patients with chronic atrial fibrillation.

BACKGROUND-Variations in the ventricular response interval (VRI) during atrial fibrillation (AF) may be reduced in patients with adverse clinical outcomes. The properties of VRI dynamics associated with prognosis remain undetermined. METHODS AND RESULTS-In 107 patients with chronic AF (age, 64+/-9 years), we analyzed a 24-hour ambulatory ECG for VRI variability (SD, SD of successive differences, and SD of 5-minute averages) and VRI irregularity (Shannon entropy of histogram, symbolic dynamics, and approximate entropy of beat-to-beat and minute-to-minute fluctuations [ApEn(b-b) and ApEn(m-m)]). During a follow-up period of 33+/-16 months, 18 patients died (17%), 9 from cardiac causes, 7 from fatal strokes, and 2 from malignancies. Reductions in all VRI variability and irregularity measures were associated with an increased risk for cardiac death but not for fatal stroke. A significant association with cardiac death was also found for ejection fraction (relative risk, 1.10; 95% confidence interval [CI], 1.04 to 1.17, per 1% decrement) and ischemic AF (relative risk, 6.52; 95% CI, 1.62 to 26. 3). After adjustment for these clinical variables, all irregularity measures except symbolic dynamics had predictive value (relative risks [95% CIs] per 1SD decrement: Shannon entropy of histogram, 2. 03 [1.14 to 3.61]; ApEn(b-b), 1.72 [1.14 to 2.60]; and ApEn(m-m), 1. 90 [1.03 to 3.52]); however, the predictive power of variability measures was no longer significant. When the patients were stratified with the 33rd and 67th percentile values of ApEn(b-b) (1. 83 and 1.94, respectively), the 5-year cardiac mortality rates for the upper, middle, and lower tertiles were 0%, 13%, and 43%, respectively (log-rank test, P=0.04). CONCLUSIONS-Reduced VRI irregularity in a 24-hour ambulatory ECG has an independent prognostic value for cardiac mortality during long-term follow-up in patients with chronic AF.

Effects of atrial natriuretic peptide on left ventricular performance in conscious dogs before and after pacing-induced heart failure.

Atrial natriuretic peptide (ANP) has potent vasodilatory and natriuretic actions and may have therapeutic benefit in congestive heart failure (CHF). These benefits may be offset by a negative inotropic effect of ANP seen in isolated preparations. However, ANP's integrated effect on left ventricular (LV) contraction and relaxation, independent of loading conditions, both under normal conditions and after CHF, is not known. We studied six conscious dogs, instrumented to measure LV and left atrial pressures and to determine LV volume from three dimensions. ANP produced significant (P<.05) decreases in LV end-systolic pressure (101.2+/-11.8 versus 91.7+/-11.2 mm Hg, P<.05) in normal dogs and in dogs with CHF (93.1+/-6.4 versus 87.1+/- 4.4 mm Hg, P<.05). ANP also caused significant reductions of the slope of end-systolic pressure-end-systolic volume relation both before (7.0 +/-1.5 versus 6.3+/-1.5 mm Hg/ml) and after CHF (4.8+/-1.3 versus 4.4+/-1.2 mm Hg/ml, P<.05). Both before and after CHF, ANP slowed LV relaxation at matched end-systolic pressure. Before CHF, steady-state stroke volume and peak LV filling rate (dV/dt(max)) were reduced. However, after CHF, the fall in end-systolic pressure more than offset the load-independent LV depression, as stroke volume, the rate LV relaxation, and dV/dt(max) were increased and minimum LV pressure reduced. ANP has negative effects on LV contractility and relaxation both before and after CHF. However, after CHF, afterload reduction with ANP overcomes its negative effects, resulting in net improvement of LV ejection and relaxation. Thus, the direct cardiodepressant effects of ANP should not limit its usefulness in CHF.

Is the blood flow in the left ventricle during the isovolumic relaxation period a useful parameter of left ventricular systolic and early diastolic performance?

Left ventricular (LV) early diastolic performance is determined by LV behavior in the late systole to early diastole and may relate to the physical potential of patients. Isovolumic relaxation flow (IRF) velocity was obtained by continuous Doppler echocardiography in the left ventricle from the apex in 26 patients with atypical chest pain and 63 patients with coronary artery disease (CAD) with or without prior myocardial infarction (MI) who underwent cardiac catheterization. In each patient, a time constant of LV relaxation (tau) was calculated from the LV pressure waves obtained by a catheter-tipped micromanometer. The LV end-systolic volume index was measured using contrast left ventriculography. IRF velocity in patients having CAD with prior MI (24.8 +/- 5.4 cm/s) was significantly less than in those with atypical chest pain (41.2 +/- 9.6 cm/s). It was also significantly less than in patients having CAD without prior MI (37.3 +/- 6.8 cm/s). IRF velocity significantly correlated with the time constant tau (r = -0.42, p < 0.001) and LV end-systolic volume index (r = -0.84, p < 0.001). This study indicates that IRF velocity obtained by continuous Doppler echocardiography in the left ventricle provides important information regarding LV systolic performance and early diastolic performance.

Differentiation of abnormal relaxation pattern with aging from abnormal relaxation pattern with coronary artery disease in transmitral flow with the use of tissue Doppler imaging of the mitral annulus.

An abnormal relaxation pattern in transmitral flow velocity waveforms has been observed in older healthy subjects as well as in patients with heart disease. Accordingly, we investigated whether the hemodynamic differences between patients with coronary artery disease (CAD) with an abnormal relaxation pattern in transmitral flow (ratio of E-wave to A-wave velocities < 1.0) and healthy older subjects with an abnormal relaxation pattern can be distinguished with the use of mitral annular velocity (MAV) during early diastole. We measured MAV in the longitudinal direction of the heart during early diastole by M-mode color tissue Doppler imaging in 24 patients with atypical chest pain (defined as healthy subjects in this study) and 70 patients with CAD who underwent cardiac catheterization. In all patients a time constant of left ventricular pressure decay (tau) and the left ventricular (LV) end-systolic volume index were also measured. Twenty-one healthy subjects and 59 patients with CAD had an abnormal relaxation pattern in their transmitral flow. The age, heart rate, mean blood pressure, and ratio of E-wave to A-wave velocities were not different between the two groups. However, the tau was longer and the LV end-systolic volume index was greater in patients who had an abnormal relaxation pattern with CAD than in healthy subjects with an abnormal relaxation pattern. The MAV during early diastole was lower in the former than in the latter (5.8 +/- 1. 9 vs 9.8 +/- 1.9 cm/s, P <.001). Mitral annular velocity during early diastole by M-mode color tissue Doppler imaging can detect the differences in LV relaxation and LV systolic performance between the abnormal relaxation pattern with CAD and the physiologically abnormal relaxation pattern with aging, providing further information regarding the meaning of an LV abnormal relaxation pattern.

Prognostic value of heart rate variability during long-term follow-up in chronic haemodialysis patients with end-stage renal disease.

BACKGROUND: Mortality is high in chronic haemodialysis patients with cardiovascular disease, and many of them die suddenly. Reduced heart rate variability (HRV) is an increased risk for death in various populations, but its prognostic value in haemodialysis patients remains uninvestigated. METHODS: We analysed the associations between 24-h HRV measures and long-term mortality through a prospective follow-up of 31 chronic haemodialysis patients who underwent diagnostic coronary angiography. RESULTS: Of the 31 patients, at baseline, seven had a previous myocardial infarction, five had a history of congestive heart failure and 14 had significant (> or =75%) coronary stenosis (four had multi-vessel stenosis). During follow-up for 60+/-5 months, 14 patients died, 11 of them suddenly. A left ventricular ejection fraction of <0.45, multi-vessel coronary stenosis, ventricular tachycardia on 24-h ECG and decreased/abnormal 24-h HRV (triangular index <22 and abnormal Poincaré plot) carried a univariate risk of all-cause death, while the risk of sudden death was only correlated with decreased HRV (standard deviation of normal-normal R-R interval <50 ms, triangular index <22 and ultra-low frequency power <8.7 ln(ms2)). Multivariate analysis revealed that a triangular index <22 was the best predictor of increased risk for both all-cause and sudden death (hazards ratio (95% CI); 8.1 (1.3-48.6) and 12.6 (1.3-126.4), respectively) and that the association was independent of cardiac function, macrovascular diseases, ventricular arrhythmias and cardiovascular risk factors. The 5-year mortality when the triangular index was > or =22 or <22 was 33 or 88% for patients with coronary artery disease and 0 or 50% for those without. CONCLUSIONS: These results indicate that HRV has an independent prognostic value in chronic haemodialysis patients and identifies an increased risk for all-cause and sudden death.

Takayasu's arteritis accompanied with massive pericardial effusion--a case report.

A 40-year-old woman who had been treated for Takayasu's arteritis was admitted to the hospital with fever, fatigue, malaise, and severe chest pain. Computed tomography of the chest demonstrated massive pericardial effusion and bilateral pleural effusion. In laboratory data, the C-reactive protein was high at 22.0 mg/dL, and erythrocyte sedimentation rate was also high at 80 mm/hr. The diagnosis was pericarditis with a recurrence of the systemic inflammatory process of Takayasu's arteritis. The patient was treated with methylprednisolone pulse therapy. Her massive pericardial effusion disappeared without pericardiocentesis.

Evaluation of left ventricular early diastolic performance by color tissue Doppler imaging of the mitral annulus.

A noninvasive assessment of left ventricular (LV) diastolic performance by tissue Doppler imaging was performed in 56 patients (8 patients with atypical chest pain, 42 with coronary artery disease with a previous myocardial infarction, and 6 without a previous myocardial infarction) who underwent cardiac catheterization. Mitral annular velocity (MAV) during early ventricular diastole was obtained by M-mode color tissue Doppler imaging at the posterior corner of the mitral annulus. In each patient, the negative peak of the first derivative of LV pressure decay (peak -dP/dt) and a time constant of LV relaxation (tau) were calculated from the LV pressure waves obtained by a catheter-tip micromanometer. LV end-systolic volume index was measured from contrast left ventriculography. MAV during early diastole was significantly correlated with tau (r = -0.73, p <0.001), peak -dP/dt (r = 0.58, p <0.001), and LV end-systolic volume index (r = -0.63, p <0.001). On multivariate regression analysis with MAV during early diastole, tau and LV end-systolic volume index were selected as prime determinants (r = 0.80, p <0.001). These findings suggest that MAV during early diastole has a direct relation to LV elastic recoil as well as to LV relaxation. MAV during early diastole gives important information regarding LV behavior in late systole to early diastole where LV early diastolic performance is determined.

Extent of myocardial damage in regions with reverse redistribution at 3 h and at 24 h on 201Tl SPET: evaluation based on regional myocardial oxidative metabolism.

Reverse redistribution (RRD) of 201Tl is often observed in patients with recent myocardial infarction. However, the difference in the extent of myocardial damage between regions with 3-h RRD and those with 24-h RRD remains unknown. Accordingly, we investigated RRD from the standpoint of myocardial oxidative metabolism. Carbon-11 (11C) acetate dynamic myocardial PET scanning was performed at rest in 14 patients with recent myocardial infarction, and the clearance rate constant (Kmono) of 11C-acetate was calculated in 6-7 ROIs on the transaxial image in each patient using a monoexponential fit as an index of myocardial oxidative metabolism. Exercise 201Tl myocardial SPET was also performed. Ninety-two regions corresponding to the PET study were then classified based on the findings of transaxial 201Tl SPET imaging; that is, regions with reverse redistribution, regions with severely decreased 201Tl activity or no 201Tl activity on the 24-h delayed images, and regions with normal 201Tl activity throughout the study. Kmono in regions with reverse redistribution (0.051 +/- 0.009 min-1) was significantly lower than that in regions with normal 201Tl activity throughout the study (0.066 +/- 0.011 min-1) (P < 0.001) but significantly higher than that in regions with severely decreased or no 201Tl activity on the 24-h delayed images (0.037 +/- 0.003 min-1) (P < 0.001). Percent Kmono (i.e. Kmono in region with RRD/the mean of Kmono in all regions with a normal 201Tl SPET result) was significantly lower in the 3-h RRD regions (81.3 +/- 6.3%) than in the 24-h RRD regions (87.6 +/- 6.1%) (P < 0.05). Impairment of myocardial oxidative metabolism is observed in regions with RRD, suggesting that RRD corresponds to mild myocardial damage. Reverse redistribution on 24-h delayed images may indicate much milder myocardial damage compared with RRD on 3-h delayed images.

Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy.

OBJECTIVE: The positive inotropic effect of endothelin-1 (ET-1) on normal myocardial contraction may be altered in pathological states. The purpose of this study was to assess the direct effect of ET-1 on cardiomyocyte performance and its cellular mechanism in congestive heart failure (CHF). METHODS: We measured the plasma levels of ET-1 and compared the effects of ET-1 (10(-10)-10(-8) M) on contractile performance and the [Ca2+]i transient in the myocytes of left ventricles (LV) from 15 age-matched normal adult rats and 15 rats with isoproterenol (ISO)-induced CHF. RESULTS: With CHF, the plasma levels of ET-1 (19.7 +/- 6.3 vs. 4.1 +/- 0.5 fmol/ml, p < 0.05) were markedly elevated. In normal myocytes, superfusion of ET-1 caused significant increases in the systolic amplitude (SA, 8-16%) and the peak velocity of shortening (dL/dtmax, 20-35%; p < 0.01) without causing a change in the peak [Ca2+]i transient. In contrast, in myocytes from CHF rats, ET-1 produced significant reductions in SA (9-13%) and in the velocity of relengthening, dR/dtmax (10-14%; p < 0.05). The myocytes' dR/dtmax also decreased by 8-10% (p < 0.05). These changes were associated with a significant decrease in the peak [Ca2+]i transient (20-23%, p < 0.01). These responses to ET-1 were abolished by the incubation of myocytes with an ETA receptor antagonist (BQ123) or a protein kinase C (PKC) inhibitor (H-7 or staurosporine). CONCLUSION: ISO-induced CHF is associated with elevated plasma ET-1 and an altered cardiomyocyte response to ET-1. After CHF, ET-1 produces a direct depression of cardiomyocyte contractile performance that is associated with a significant decrease in the peak [Ca2+]i transient. These effects are likely to be mediated through ETA receptors and involve the PKC pathway.

Functional effects of endogenous bradykinin in congestive heart failure.

OBJECTIVES: The purpose of this study was to determine the level and functional effects of endogenous bradykinin in congestive heart failure (CHF). BACKGROUND: There is experimental evidence that bradykinin is increased in several cardiac disease states. However, it is unknown whether plasma levels of bradykinin are elevated in CHF. Further, the cardiac and vascular responses to bradykinin in CHF are unclear. METHODS: The circulating levels of bradykinin and the effects of endogenous bradykinin were assessed in eight instrumented, conscious dogs both before and after pacing-induced CHF. RESULTS: Before CHF, the plasma bradykinin level was 53.1 +/- 12.4 pg/ml. Blocking endogenous bradykinin with HOE-140 (0.3 mg/kg), a specific bradykinin B2-receptor antagonist, produced no significant alterations in heart rate, left ventricular (LV) end-systolic pressure (Pes), total systemic resistance (TSR), the time constant of LV relaxation (tau) or the maximal rate of LV filling (dV/dt(max)). However, coronary blood flow was significantly reduced (p < 0.05). LV contractile performance measured by the slopes of pressure-volume relations was unaffected. After induction of CHF, the plasma bradykinin level increased to 234.2 +/- 19.4 pg/ml (p < 0.05). Blocking endogenous bradykinin with HOE-140 reduced coronary blood flow and produced significant increases in Pes and TSR, prolonged tau, decreased dV/dt(max) and elevated minimal LV pressure and mean left atrial pressure. Furthermore, the slopes of pressure-volume relations (p < 0.05) were decreased, indicating depressed contractility with HOE-140 after CHF. CONCLUSIONS: Before CHF, endogenous bradykinin results in coronary dilation but has no effect on systemic arterial vasodilation or cardiac performance. After CHF, endogenous bradykinin is significantly increased and, acting through B2-receptors, produces coronary and arterial vasodilation and improves LV relaxation and contractile performance. Thus, endogenous bradykinin may play an important role in preserving cardiovascular function in CHF.

Left ventricular spherical dilation and regional contractile dysfunction in dogs with heart failure.

Left ventricular (LV) short- and long-axis contractile function and LV structural changes were serially measured in eight instrumented dogs during the development of congestive heart failure (CHF) induced by rapid right ventricular (RV) pacing. After 10 days of pacing, LV end-diastolic volume (VED) had not increased; however, the slope of LV end-systolic pressure-volume relation had decreased from 7.4 +/- 2.6 to 4.9 +/- 1.1 mmHg/ml (P < 0.05), and the slope of LV stroke work-VED relation had fallen from 78.4 +/- 9.1 to 64.2 +/- 7.2 mmHg (P < 0.05). The slopes of end-systolic pressure-dimension relation and the stroke work area-end-diastolic dimension relation in the short axes (i.e., anteroposterior and septal-lateral) had decreased by 30% (P < 0.05), whereas the slopes of the long-axis (i.e., apical-basal) relations were unchanged (not significant). After 20 days of pacing, VED had significantly increased by 14% due to selective dilation of the short axes by 7%, and LV global contractility had further declined with a 40% contractile depression in the short axes and a 25% contractile depression in the long axis. After 30 days, the long-axis dimension at end diastole was also significantly increased with a further increase in the short-axis dimensions. In contrast to the spherical dilation occurring during CHF, acute volume loading of normal animals produced symmetrical LV dilation. These observations suggest that heterogeneous contractile depression initiates the spherical end-diastolic chamber dilation in pacing-induced CHF.

Estimation of pulmonary capillary wedge pressure from M-mode mitral echograms.

We investigated whether the isovolumic relaxation time (IRT) and an interval from the start of opening to the maximal amplitude of the anterior mitral leaflet in early diastole (D-E interval) would be useful predictors of the pulmonary capillary wedge pressure (PCWP). We recorded M-mode mitral echograms and phonocardiograms in 33 patients (aged 38-70 years) with acute myocardial infarction (AMI) in the coronary care unit and in 34 patients (aged 40-75 years) with prior myocardial infarction (OMI) during cardiac catheterization. All patients underwent the insertion of a flow-directed pulmonary artery catheter to obtain the PCWP. We measured the IRT and the D-E interval from the phonocardiograms and the M-mode echograms. There was no significant correlation between the IRT and the mean PCWP (mPCWP) in patients with AMI and in patients with OMI. The D-E interval was significantly and inversely correlated with the mPCWP (r = -0.91, p <0.0001) in all patients. The regression equation was mPCWP = -0.42 x (D-E) +47.9. The D-E interval of < or = 75 ms indicated a high mPCWP (mPCWP > or = 18 mm Hg) with high sensitivity (96%) and specificity (88%). The derived equation was tested in a prospective group of 32 additional patients (aged 43-75 years). A significant correlation was observed between the predicted and measured mPCWP (r = 0.91, p <0.0001). Thus, the PCWP can be estimated by using the D-E interval derived from M-mode mitral echograms in patients in the coronary care unit and in patients with chronic heart disease.