Regional cardiac sympathetic nerve dysfunction and the diagnostic efficacy of metaiodobenzylguanidine tomography in stable coronary artery disease

The present study endeavors to correlate regional myocardial sympathetic nerve dysfunction with reversible and persistent perfusion abnormalities and depressed regional wall motion, and to determine the diagnostic efficacy of radio-iodinated metaiodobenzylguanidine (MIBG) tomography for detecting coronary artery disease. In 28 consecutive patients with stable coronary artery disease and 7 patients with atypical chest pain but no coronary stenosis, regional MIBG uptake was semiquantitatively evaluated in 13 left ventricular segments early (30 minutes) and late (4 hours) after injection. Regional MIBG uptake was reduced in 68 of 90 segments (76%) showing reversible perfusion abnormality and 72 of 81 segments (89%) showing persistent abnormality 4 hours after injection. Although the sensitivity and negative predictive values of late MIBG scanning for detecting myocardial perfusion abnormalities were relatively high (82% and 85%, respectively), the specificity, positive predictive value, and kappa value were low (63%, 57%, and 0.41, respectively). Right coronary lesions were detected by late MIBG scanning with a high sensitivity (85%) but a low specificity (41%). Conversely, the sensitivities for detecting lesions in the other 2 major left coronary arteries were low (55%). The overall diagnostic accuracy of late MIBG scanning was 66% and the positive and negative predictive values and kappa value were low; 60%, 70%, and 0.31, respectively. Similarly, regional sympathetic dysfunction was observed in 42 of 49 asynergic segments (86%) on late MIBG scans, of which 32 segments were viable and 10 nonviable; but the low specificity (73%) and positive predictive value (44%) reduced the kappa value (0.43). Thus, regional cardiac sympathetic innervation is impaired in ischemic, asynergic but noninfarcted myocardium as well as in myocardium which is infarcted or has a persistent perfusion abnormality. The diagnostic efficacy of MIBG tomography to detect coronary artery disease, however, is limited probably because of nonspecific reductions of MIBG uptake in the inferior and posterolateral regions.     

Cardiac natriuretic peptides for diagnosis and risk stratification in heart failure: influences of left ventricular dysfunction and coronary artery disease on cardiac hormonal activation

BACKGROUND: Cardiac natriuretic peptides are activated in heart failure. However, their diagnostic and prognostic values have not been compared under the routine conditions of an outpatient practice. METHODS: We studied the diagnostic and prognostic value of plasma N- and C-terminal peptides of the atrial natriuretic factor prohormone (N-proANF and ANF respectively) and brain natriuretic peptide (BNP) to evaluate the severity of congestive heart failure (CHF) as reflected by the New York Heart Association (NYHA) classification and to predict its 2-year mortality. Peripheral plasma concentrations of the three natriuretic peptides were measured in 27 normal subjects (CTR), in 32 patients with coronary artery disease (CAD) and normal left ventricular ejection fraction and in 101 patients with chronic CHF in functional classes I and II (n = 61) or III and IV (n = 40). RESULTS: Plasma concentrations of the three peptides increased in the presence of CHF in relation to its severity (P < 0.01). BNP was unable to distinguish CTR from CAD, just as ANF could not differentiate CAD from CHF I-II; only N-proANF displayed a significant and continuous increase from CTR to CAD, CHF I-II and III-IV. Receiver-operating characteristic curves showed better evaluation of the degree of CHF by BNP than by ANF or ejection fraction (P < 0.05). Assessment of the 2-year prognosis revealed that N-proANF and BNP were the best independent predictors of outcome after the NYHA classification. These peptides identify a very high-mortality group. CONCLUSION: Plasma N-proANF and BNP concentrations are good indicators of the severity and prognosis of CHF in an outpatient practice. CAD does not stimulate BNP as long as ventricular dysfunction is not present, although increased N-proANF levels in this setting suggest an early humoral activation.     

Relationship between epicardial ST-segment elevation and myocardial ischemic damage after experimental coronary artery occlusion in dogs

The relationship between early and late epicardial electrocardiographic changes as well as those in regional myocardial blood flow (MBF) and the severity of myocardial damage was determined in 12 anesthetized dogs with left anterior descending coronary artery ligation. Radioactive microspheres (15 mum) were used to measure regional MBF at 15 min (early) and 24 h (late) after coronary occlusion. Severity of myocardial damage was assessed by the extent of myocardial creatine phosphokinase depletion 24 h after coronary ligation. There was a close linear correlation between myocardial creatine phosphokinase activity and regional MBF both early (r=0.93, 2P less than 0.001) and late (r=0.88, 2P less than 0.001). An inverse but less precise relationship existed between acute epicardial ST-segment elevation and early (r=-0.41, 2P less than 0.001), or late (r=0.35, 2P less than 0.05) regional MBF. Similarly, a weak correlation was found between myocardial creatine phosphokinase (IU/mg protein) at 24 h and early epicardial ST (millivolt) elevation (r=-0.36, 2P less than 0.02). In the center zones of the infarct with MBF 1/10 of normal, about 35% of the areas with normal QRS width had no epicardial ST-segment elevation 15 min after coronary occlusion. About 44% of the areas which developed pathological Q-waves in the electrocardiogram at 24 h had no ST elevation 15 min after coronary ligation. Late evolution of abnormal Q-waves occurred almost invariably in areas in which the early MBF was reduced to less than 50% of normal and in areas which subsequently had myocardial creatine phosphokinase levels reduced to less than 60% of normal. After coronary occlusion, the severity of the ultimate myocardial damage, which was directly proportional to the degree of reduction in MBF, was therefore not reliably predicted by the early epicardial ST-segment elevation. The data obtained in these studies suggest the need for caution in the use of acute ST-segment elevation as a predictive index of the extent or severity of myocardial ischemic damage.     

Impairment of exercise capacity and peak oxygen consumption in patients with mild left ventricular dysfunction and coronary artery disease

AIMS: Most studies in chronic heart failure have only included patients with marked left ventricular systolic dysfunction (i.e. ejection fraction < or =0.35), and patients with mild left ventricular dysfunction are usually excluded. Further, exercise capacity strongly depends on age, but age-adjustment is usually not applied in these studies. Therefore, this study sought to establish whether (age-adjusted) peak VO2 was impaired in patients with mild left ventricular dysfunction. METHODS: Peak VO2 and ventilatory anaerobic threshold were measured in 56 male patients with mild left ventricular dysfunction (ejection fraction 0.35-0.55; study population) and in 17 male patients with a normal left ventricular function (ejection fraction >0.55; control population). All patients had an old (>4 weeks) myocardial infarction. By using age-adjusted peak VO2 values, a 'decreased' exercise capacity was defined as < or = predicted peak VO2 - 1 x SD (0.81 of predicted peak VO2), and a severely decreased exercise capacity as < or = predicted peak VO2 - 2 x SD (0.62 of predicted peak VO2). RESULTS: Patients in the study population (age 52+/-9 years; ejection fraction 0.46+/-0.06) were mostly asymptomatic (NYHA class I: n=40, 76%), while 16 patients (24%) had mild symptoms, i.e. NYHA class II. All 17 controls (age 57+/-8 years) were asymptomatic. Mean peak VO2 was lower in patients with mild left ventricular dysfunction (23.6+/-5.7 vs 27.1+/-4.6 ml x min(-1) x kg(-1) in controls, P<0.05). In 75% of the study population patients (n=42) age-adjusted peak VO2 was decreased (NYHA I/II: n=29/13) and in 18% of them severely decreased (n=10; NYHA I/II: n=6/4). In contrast, only three patients (18%) in the control population had a decreased and none a severely decreased age-adjusted peak VO2. CONCLUSION: In patients with mild left ventricular dysfunction, who have either no or only mild symptoms of chronic heart failure, a substantial proportion has an impaired exercise capacity. By using age-adjustment, impairment of exercise capacity becomes more evident in younger patients. Patients with mild left ventricular dysfunction are probably under-diagnosed, and this finding has clinical and therapeutic implications.     

Porcine hepatic response to sepsis and its amplification by an adrenergic receptor alpha1 agonist and a beta2 antagonist

CDK9 has been recently shown to have increased kinase activity in differentiated cells in culture and a differentiated tissue-specific expression in the developing mouse. In order to identify factors that contribute to CDK9's differentiation-specific function, we screened a mouse embryonic library in the yeast two-hybrid system and found a tumor necrosis factor signal transducer, TRAF2, to be an interacting protein. CDK9 interacts with a conserved domain in the TRAF-C region of TRAF2, a motif that is known to bind other kinases involved in TRAF-mediated signaling. Endogenous interaction between the two proteins appears to be specific to differentiated tissue. TRAF2-mediated signaling may incorporate additional kinases to signal cell survival in myotubes, a cell type that is severely affected in TRAF2 knockout mice.     

Contrast magnetic resonance imaging in the assessment of myocardial viability in patients with stable coronary artery disease and left ventricular dysfunction

BACKGROUND: The utility of contrast MRI for assessing myocardial viability in stable coronary artery disease (CAD) with left ventricular dysfunction is uncertain. We therefore performed cine and contrast MRI in 24 stable patients with CAD and regional contractile abnormalities and compared MRI findings with rest-redistribution 201Tl imaging and dobutamine echocardiography. METHODS AND RESULTS: Delayed MRI contrast enhancement patterns were examined from 3 to 15 minutes after injection of 0.1 mmol/kg IV gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Comparable MRI and 201Tl basal and midventricular short-axis images were subdivided into 6 segments. Segments judged nonviable by quantitative and qualitative assessment of 201Tl scans showed persistent, systematically greater MRI contrast signal intensity than segments judged viable (P相似文献   

Echocardiography and fatty acid single photon emission tomography in predicting reversibility of regional left ventricular dysfunction after coronary angioplasty

It has often been proposed that young children are not capable of distinguishing mistakes from lies and that they do not discriminate between the reactions that are generated by innocent and negligent mistakes. In our investigation, children aged 3 to 5 years were asked to choose whether a perpetrator had made a mistake or had lied about a food's contact with contaminants and were required to indicate whether this choice would produce a neutral or a negative reaction in the facial expression of a bystander. In this context, many children distinguished mistakes from lies and displayed an incipient ability to discriminate between lies and negligent mistakes that often generate negative reactions and innocent mistakes that do not.     

Pulmonary responses to 5-hydroxytryptamine and endothelin-1 in a rabbit model of left ventricular dysfunction

OBJECTIVE: To determine whether pulmonary hypertension developed in a coronary artery-ligated rabbit model of left ventricular dysfunction (LVD) and to examine the effects of i.v. 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) on pulmonary arterial pressure (PAP). METHODS: Eight weeks after experimental coronary artery ligation or sham operation, ejection fractions were assessed by echocardiography. The rabbits were later anaesthetised and pulmonary arterial pressure was measured via a catheter inserted into the pulmonary artery via the right external jugular vein. 5-HT (1-400 micrograms/kg) and ET-1 (0.001-4 nmol/kg) were administered i.v. RESULTS: Ejection fraction was significantly decreased from 76.6 +/- 1.4% in sham-operated to 42.2 +/- 1.3% in coronary artery-ligated rabbits (n = 9 in each group; P < 0.001), consistent with LVD. Baseline mean pulmonary arterial pressure was significantly increased in the coronary artery-ligated group compared to the shams, (16.5 +/- 0.5 vs. 11.5 +/- 0.8 mmHg; P < 0.001). A significant degree of right ventricular hypertrophy was found in the coronary artery-ligated rabbits (0.70 +/- 0.04 g/kg final body weight (f.b.wt.), n = 8 cf. 0.48 +/- 0.02 g/kg f.b.wt. in sham-operated controls, n = 8; P < 0.001). There was a significant increase in the percentage of muscularised pulmonary vessels adjacent to alveolar ducts and alveoli < 60 microns i.d. in the LVD rabbits compared with their sham-operated controls (8.5 +/- 0.4 cf. 20 +/- 0.5%; P < 0.0005). 5-HT produced a greater response in the coronary artery-ligated rabbits (a maximum increase of 8.7 +/- 1.0 mmHg in mean pulmonary artery pressure vs. 4.6 +/- 1.5 mmHg for sham-operated controls; P < 0.05). ET-1 did not have any effect on pulmonary arterial pressure in either group. CONCLUSION: In the rabbit, LVD secondary to coronary artery ligation, causes right ventricular hypertrophy, pulmonary vascular remodelling, and an increased PAP consistent with the onset of pulmonary hypertension (PHT). The greater PAP response to i.v. 5-HT in the PHT group supports the hypothesis that this substance could be involved in the development of PHT. A role for ET-1 cannot be excluded, despite its lack of effect on PAP when intravenously administered in either group.     

Relation between coronary artery disease, aortic stiffness, and left ventricular structure in a population sample

With the use of the degenerated nucleotides that contain the conserved sequence of G protein-coupled receptor, we have identified a 648-bp clone (HDGRC02) from human genomic DNA with significant sequence homology to human neurotransmitter receptors. HDGRC02 was then used as a probe for the screening of full length gene. From human Lambda DASH II genomic library, a 1.6 Kb clone encoded a full length gene was isolated and named putative neurotransmitter receptor (PNR). PNR has a single open reading frame which predicts a 38.3 KD protein of 338 amino acids with seven transmembrane domain topography. The amino acid sequence of PNR exhibits considerable homology to the rat 5-HR1D receptor with 35% amino acid identity and 56% amino acid similarity. PNR also shows significant sequence homology to the 5-HT1D receptor from Japanese puffer fish fugu, to the 5-HT4L receptor from mouse, to the alpha-2 adrenergic receptor and to the D2 dopamine receptor. Northern blot analysis indicates that PNR is expressed in skeletal muscle and selected areas of the brain. A chromosome mapping study located the PNR gene with human chromosome band of 6q23. The findings in the present study demonstrate that PNR is a putative neurotransmitter receptor.     

Impact of severity of coronary artery stenosis and the collateral circulation on the functional outcome of dyssynergic myocardium after revascularization in patients with healed myocardial infarction and chronic left ventricular dysfunction

The inferoposterior region of the triangle of Koch is hypothesized to be the location of the atrial insertion of the slow atrioventricular (AV) nodal pathway. However, the actual site of conduction slowing in the slow AV nodal pathway is unknown. Entrainment mapping during AV nodal reentry can localize the reentrant pathway as follows: the AH interval measured from the mapping catheter = A'H (where A' is the exit site of the reentrant circuit) minus A'A (the conduction time from A' to the site of mapping); the SH interval during entrainment = SA' (the conduction time from stimulus into the reentry circuit) plus A'H. Thus, in all cases, the SH interval should be greater than or equal to the AH interval, and the deltaAH-SH should increase as distance and conduction time (SA' and A'A) from the reentry circuit increases. Fourteen patients with typical AV nodal reentry (cycle length 346 +/- 62 ms) and 1 with fast-slow (cycle length 430 ms) underwent activation and entrainment mapping from 8 to 12 sites in the triangle of Koch and coronary sinus. Pacing was performed at 2 to 3 mA above threshold, at a cycle length 10 ms shorter than tachycardia. A mapping site was defined as being in close proximity to the circuit if the deltaAH-SH was within 120% of the shortest 20th percentile deltaAH-SH value from all measured sites. In the 14 typical cases, 45 of 83 sites (54%) in the anatomic slow pathway region fulfilled criteria for close proximity to the reentry circuit compared with 13 of 50 sites (26%) outside of this region (p = 0.005). For these patients, the shortest SH interval measured from any entrainment site was 294 +/- 58 ms (89 +/- 10% of tachycardia cycle length, range 70% to 119%), indicating that the site of slow conduction in the slow pathway during AV nodal reentrant tachycardia was distal to all mapped sites. Thus, during typical AV nodal reentry, the "slow" pathway does not conduct slowly, and its insertion is located at or within the inferoposterior or midseptal regions in most cases.     

Accuracy of currently available techniques for prediction of functional recovery after revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease: comparison of pooled data

During the nonconceptive cycle in primates, progesterone is a likely intermediary for several LH-dependent events in the ovary including ovulation, luteinization of the follicle wall, and maintenance of the developed corpus luteum. To determine whether progesterone is an important local factor in the ability of chorionic gonadotropin (CG) to enhance luteal structure and function in early pregnancy, rhesus monkeys received hCG in a dose-escalating regimen (15-2880 IU twice daily) beginning on Day 9 of the luteal phase of the natural menstrual cycle to simulate the rapid rise in serum CG levels associated with early pregnancy. Some animals were concomitantly treated with the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) inhibitor trilostane (500 mg twice daily) to suppress progesterone production during gonadotropin stimulation. Corpora lutea were removed after 1, 3, 6, and 9 days of treatment (n = 3-4 per group); time-matched control tissues were obtained from untreated animals (n = 3 per group). Treatment with hCG prevented both the decrease in luteal wet weight (p < 0.05) and the histologic indices of luteal regression seen in controls during the menstrual cycle. However, coadministration of the progesterone synthesis inhibitor led to early declines in luteal wet weight (p < 0.05) and luteal cell size compared to treatment with hCG alone. Luteal progesterone receptor (PR) mRNA content increased (p < 0.05), but the percentage of cells staining positive for immunoreactive PR declined (p < 0.05) over the treatment interval in all groups. CG administration alone and in combination with trilostane increased PR staining intensity in some luteal cells within 1 day of treatment; intensely staining cells persisted around vascular elements after 9 days of treatment with hCG+trilostane but not with hCG alone. These data suggest that some, but not all, actions of CG to maintain the primate corpus luteum in early pregnancy are mediated by progesterone via a receptor-mediated pathway.     

Prognostic value of the amount of dysfunctional but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction. Investigators of this Multicenter Study

Reproductive aging in women is closely tied to the loss of ovarian follicles through atresia. The sentinel endocrinologic finding is the monotropic FSH rise, associated with a decline in ovarian inhibin B secretion. Fertility becomes significantly compromised long before overt clinical signs occur, such as cycle irregularity. Compromised fertility is primarily related to oocyte dysfunction. As women with regular cycles near the end of the reproductive years, the following changes are usually manifested: 1) the selection and development of a dominant follicle occurs earlier; 2) there is earlier ovulation; 3) there is a short follicular phase and total cycle length; and 4) ovarian steroid secretion is normal. The relationships, if any, between the monotropic FSH rise, accelerated follicular atresia, shortened follicular phase, and oocyte quality remain to be determined. The next phase of reproductive aging is the perimenopause. Lack of predictability is the rule with regard to the nature and duration of the perimenopause. Long cycles are interspersed with short ones, and intermittent ovulatory cycles are intermingled with periods that are hormonally indistinct from the postmenopausal state. Even after the last menstrual period, evidence of intermittent ovarian estradiol production may still be detected. Although fertility is severely compromised during the perimenopause, ovulation may occur without warning and contraception must be practiced if pregnancy is not desired. Further studies are needed to elucidate the factors contributing to oocyte abnormalities in women of advanced reproductive age, as well as the factors that determine the rate of follicle atresia and the length of the reproductive life span.     

Effects of late percutaneous transluminal coronary angioplasty of an occluded infarct-related coronary artery on left ventricular function in patients with a recent (< 6 weeks) Q-wave acute myocardial infarction (Total Occlusion Post-Myocardial Infarction Intervention Study [TOMIIS]--a pilot study)

The effect of late percutaneous transluminal coronary angioplasty (PTCA) of an occluded infarct-related artery on left ventricular ejection fraction was studied in patients with a recent, first Q-wave myocardial infarction in a prospective, randomized study. Forty-four patients (31 men and 13 women, mean age 58 +/- 12 years) with an occluded infarct-related coronary artery were randomized to PTCA (n = 25) or no PTCA (n = 19). Patients received acetylsalicylic acid, a beta blocker and an angiotensin-converting enzyme inhibitor unless contraindicated. Left ventricular ejection fraction was determined at baseline and 4 months. Coronary angiography was repeated at 4 months. Baseline ejection fraction measured 20 +/- 12 days after myocardial infarction was 45 +/- 12% in both groups. PTCA was performed 21 +/- 13 days after the event. The primary PTCA success rate was 72%. One patient in each group died before angiographic follow-up, which was completed in 37 of the remaining 42 patients (88%; 21 with and 16 without PTCA). At 4 months, the infarct-related artery was patent in 43% of PTCA patients and in 19% of no PTCA patients (p = NS). Reocclusion occurred in 40% of patients after successful PTCA. Secondary analyses showed that the change in left ventricular ejection fraction was significantly greater in patients with a patent infarct-related artery (+9.4 +/- 6.2%) than in those with an occluded artery (+1.6 +/- 8.8%; p = 0.0096). Baseline ejection fraction also independently predicted improvement in left ventricular ejection fraction (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)