Objective evaluation of regional left ventricular wall motion during dobutamine stress echocardiographic studies using segmental analysis of color kinesis images.
(57/2962)
OBJECTIVES: To test the feasibility of objective and automated evaluation of echocardiographic stress tests, we studied the ability of segmental analysis of color kinesis (CK) images to detect dobutamine-induced wall motion abnormalities and compared this technique with inexperienced reviewers of conventional gray-scale images. BACKGROUND: Conventional interpretation of stress echocardiographic studies is subjective and experience dependent. METHODS: CK images were obtained in 89 of 104 consecutive patients undergoing clinical dobutamine stress studies and were analyzed using custom software to calculate regional fractional area change in 22 segments in four standard views. Each patient's data obtained at rest was used as a control for automated detection of dobutamine-induced wall motion abnormalities. Independently, studies were reviewed without CK overlays by two inexperienced readers who classified each segment's response to dobutamine. A consensus reading of two experienced reviewers was used as the gold standard for comparisons. In a subgroup of 16 patients, these consensus readings and CK detection of wall motion abnormalities were compared with coronary angiography. RESULTS: The consensus reading detected ischemic response to dobutamine in 43 of 1958 segments in 23 of 89 patients. Automated detection of stress-induced wall motion abnormalities correlated more closely with the standard technique than the inexperienced reviewers (sensitivity 0.76 vs. 0.55, specificity 0.98 vs. 0.94 and accuracy 0.97 vs. 0.92). When compared with coronary angiography in a subgroup of patients, analysis of CK images differentiated between normal and abnormal wall motion more accurately than expert readers of gray-scale images (accuracy of 0.93 vs. 0.82). CONCLUSIONS: Analysis of CK images allows fast, objective and automated evaluation of regional wall motion, sensitive enough for clinical dobutamine stress data and more accurate than inexperienced readers. This method may result in a valuable adjunct to conventional visual interpretation of dobutamine stress echocardiography. (+info)
Prediction of cardiac events after uncomplicated acute myocardial infarction by clinical variables and dobutamine stress test.
(58/2962)
OBJECTIVES: We sought to determine the relative prognostic power of several clinical and dobutamine stress test variables in patients after a first uncomplicated acute myocardial infarction (AMI). BACKGROUND: The value of dobutamine echocardiography (DE) for determining prognosis after AMI is not yet defined. In particular, the influence of dobutamine stress test response on the outcome of these patients is unknown. METHODS: A graded predischarge DE (from 5 to 40 microg/kg/min, plus atropine if needed) was performed in 245 patients (mean age 60 +/- 10 years) with a first uncomplicated AMI. RESULTS: At follow-up (17 +/- 13 months), an adverse outcome occurred in 40 patients: cardiac death in 7, nonfatal myocardial infarction in 9 (hard events = 16) and unstable angina requiring hospital readmission in 24. Significant predictors of adverse outcome by univariate analysis were positive DE, ischemic wall motion score index (WMSI), angina during DE and diabetes for all events, and positive DE, ischemic WMSI and age for hard events. At multivariate analysis, the only independent predictors of adverse outcome were positive DE, diabetes and angina during DE for all events, and positive DE and age for hard events. The presence of both age >60 years and a history of diabetes identified patients at high risk of cardiac events (event rate 37%), compared with patients <60 years and no diabetes (event rate 11%). In patients with intermediate risk (only one clinical risk factor, event rate 18%), DE added prognostic information (event rate 10% in the negatives, 25% in the positives and 35% in the positives with angina). CONCLUSIONS: After uncomplicated AMI, dobutamine stress test variables offer additional prognostic information to clinical data. (+info)
Comparison of stress/rest myocardial perfusion tomography, dipyridamole and dobutamine stress echocardiography for the detection of coronary disease in hypertensive patients with chest pain and positive exercise test.
(59/2962)
OBJECTIVES: Although different noninvasive tests have been proposed for detecting coronary artery disease (CAD) in patients with hypertension and chest pain symptoms, the relative performance of the available techniques has not been systematically assessed. BACKGROUND: Patients with hypertension frequently complain of chest pain and exhibit ischemic-like ST segment changes on the exercise electrocardiogram (ECG). However, the specificity of such changes for predicting significant CAD is very low, because these patients often exhibit a normal coronary angiogram. METHODS: In 101 patients with hypertension, chest pain and positive exercise ECG, we performed stress/rest myocardial single photon emission computed tomography with 99mTc-MIBI, dipyridamole and dobutamine stress echocardiography and coronary angiography. All patients had normal global ventricular function and 57 had left ventricular hypertrophy. All were kept on ACE inhibitors during the study period. RESULTS: No patients had significant side effects during perfusion scintigraphy. Dose-limiting side effects were observed in five patients with dipyridamole and in seven patients with dobutamine. Only 56% of study patients exhibited significant CAD. Sensitivity, specificity, accuracy, positive and negative predictive values were, respectively, 98%, 36%, 71%, 67% and 94% for perfusion scintigraphy, 61%, 91%, 74%, 90% and 64% for dipyridamole and 88%, 80%, 84%, 85% and 83% for dobutamine stress echocardiography. CONCLUSIONS: This study shows that stress echo in patients with hypertension yields a satisfactory diagnostic accuracy for identifying significant epicardial CAD. Our results indicate that dobutamine might be superior to dipyridamole. The low specificity of myocardial scintigraphy probably relates to the fact that this method traces perfusion abnormalities, not necessarily caused by epicardial CAD, possibly due to microvascular disease and not causing obvious wall motion abnormalities. (+info)
Reflex control of sympathetic activity during simulated ventricular tachycardia in humans.
(60/2962)
BACKGROUND: Ventricular tachyarrhythmias present a unique set of stimuli to arterial and cardiopulmonary baroreceptors by increasing cardiac filling pressures and decreasing arterial pressure. The net effect on the control of sympathetic nerve activity (SNA) in humans is unknown. The purpose of this study was to determine the relative roles of cardiopulmonary and arterial baroreceptors in controlling SNA and arterial pressure during ventricular pacing in humans. METHODS AND RESULTS: Two experiments were performed in which SNA and hemodynamic responses to ventricular pacing were compared with nitroprusside infusion (NTP) in 12 patients and studied with and without head-up tilt or phenylephrine to normalize the stimuli to either the arterial or cardiopulmonary baroreceptors in 9 patients. In experiment 1, the slope of the relation between SNA and mean arterial pressure was greater during NTP (-4.7+/-1.4 U/mm Hg) than during ventricular pacing (-3.4+/-1.1 U/mm Hg). Comparison of NTP doses and ventricular pacing rates that produced comparable hypotension showed that SNA increased more during NTP (P=0.03). In experiment 2, normalization of arterial pressure during pacing resulted in SNA decreasing below baseline (P<0.05), whereas normalization of cardiac filling pressure resulted in a greater increase in SNA than pacing alone (212+/-35% versus 189+/-37%, P=0. 04). Conclusions--These data demonstrate that in humans arterial baroreflex control predominates in mediating sympathoexcitation during ventricular tachyarrhythmias and that cardiopulmonary baroreceptors contribute significant inhibitory modulation. (+info)
In vivo inhibition of elevated myocardial beta-adrenergic receptor kinase activity in hybrid transgenic mice restores normal beta-adrenergic signaling and function.
(61/2962)
BACKGROUND: The clinical syndrome of heart failure (HF) is characterized by an impaired cardiac beta-adrenergic receptor (betaAR) system, which is critical in the regulation of myocardial function. Expression of the betaAR kinase (betaARK1), which phosphorylates and uncouples betaARs, is elevated in human HF; this likely contributes to the abnormal betaAR responsiveness that occurs with beta-agonist administration. We previously showed that transgenic mice with increased myocardial betaARK1 expression had impaired cardiac function in vivo and that inhibiting endogenous betaARK1 activity in the heart led to enhanced myocardial function. METHODS AND RESULTS: We created hybrid transgenic mice with cardiac-specific concomitant overexpression of both betaARK1 and an inhibitor of betaARK1 activity to study the feasibility and functional consequences of the inhibition of elevated betaARK1 activity similar to that present in human HF. Transgenic mice with myocardial overexpression of betaARK1 (3 to 5-fold) have a blunted in vivo contractile response to isoproterenol when compared with non-transgenic control mice. In the hybrid transgenic mice, although myocardial betaARK1 levels remained elevated due to transgene expression, in vitro betaARK1 activity returned to control levels and the percentage of betaARs in the high-affinity state increased to normal wild-type levels. Furthermore, the in vivo left ventricular contractile response to betaAR stimulation was restored to normal in the hybrid double-transgenic mice. CONCLUSIONS: Novel hybrid transgenic mice can be created with concomitant cardiac-specific overexpression of 2 independent transgenes with opposing actions. Elevated myocardial betaARK1 in transgenic mouse hearts (to levels seen in human HF) can be inhibited in vivo by a peptide that can prevent agonist-stimulated desensitization of cardiac betaARs. This may represent a novel strategy to improve myocardial function in the setting of compromised heart function. (+info)
Role of ATP-dependent K(+) channels in the electrical excitability of early embryonic stem cell-derived cardiomyocytes.
(62/2962)
Single, murine embryonic stem cell-derived early stage cardiomyocytes dissociated from embryoid bodies expressed two inward rectifier K(+) channels, I(K1) and the ATP dependent K(+) current. I(K1) exhibited low density in early stage cardiomyocytes, but increased significantly in late stage cells. In contrast, the ATP dependent K(+) current was expressed at similar densities in early and late stage cardiomyocytes. This current was found to be involved in the determination of the membrane potential, since glibenclamide depolarized early cardiomyocytes and exerted a positive chronotropic effect. Some cardiomyocytes displayed a bursting behavior of action potentials, characterized by alternating periods with and without action potentials. During the phases without action potentials, the membrane potential was hyperpolarized, indicating the involvement of K(+) channels in the generation of this bursting behavior. Extracellular recording techniques were applied to spontaneously contracting areas of whole embryoid bodies. In 20% of these bursting behavior similar to that seen in the single cells was observed. In regularly beating embryoid bodies, bursting could be induced by reduction of substrates from the extracellular medium as well as by superfusion with the positive chronotropic agents Bay K 8644 or isoproterenol. Perfusion with substrate-reduced medium induced bursting behavior after a short latency, isoproterenol and Bay K 8644 resulted in a positive chronotropic response followed by bursting behavior with longer latencies. The spontaneous bursting was blocked by glibenclamide. These experimental results suggest that intermittent activation of ATP dependent K(+) channels underlies the bursting behavior observed in single cardiomyocytes and in the whole embryoid body. Conditions of metabolic stress lead to the rhythmic suppression of action potential generation. Our data indicate that ATP dependent K(+) channels play a prominent role in the cellular excitability of early cardiomyocytes. (+info)
Myocardial oxygenation in vivo: optical spectroscopy of cytoplasmic myoglobin and mitochondrial cytochromes.
(63/2962)
The oxygenation state of myoglobin and the redox state of cytochrome c provide information on the PO(2) in the cytosol and mitochondria, respectively. An optical "window" from approximately 540 to 585 nm was found in the pig heart in vivo that permitted the monitoring of myoglobin and cytochrome c without interference from Hb oxygenation or blood volume. Scanning reflectance spectroscopy was performed on the surgically exposed left ventricle of pigs. Difference spectra between control and a total left anterior descending coronary artery occlusion revealed maxima and minima in this spectral region consistent with myoglobin deoxygenation and cytochrome c and b reduction. Comparison of in vivo data with in vitro fractions of the heart, including Hb-free tissue whole heart and homogenates, mitochondria, myoglobin, and pig red blood cells, reveals minimal contributions of Hb in vivo. This conclusion was confirmed by expanding the blood volume of the myocardium and increasing mean Hb O(2) saturation with an intracoronary infusion of adenosine (20 microgram. kg(-1). min(-1)), which had no significant effect on the 540- to 585-nm region. These results also suggested that myoglobin O(2) saturation was not blood flow limited under these conditions in vivo. Work jump studies with phenylephrine also failed to change cytochrome c redox state or myoglobin oxygenation. Computer simulations using recent physical data are consistent with the notion that myoglobin O(2) saturation is >92% under basal conditions and does not change significantly with moderate workloads. These studies show that reflectance spectroscopy can assess myocardial oxygenation in vivo. Myoglobin O(2) saturation is very high and is not labile to moderate changes in cardiac workload in the open-chest pig model. These findings indicate that myoglobin does not contribute significantly to O(2) transport via facilitated diffusion under these conditions. (+info)
Stimulation of the paraventricular nucleus modulates firing of neurons in the nucleus of the solitary tract.
(64/2962)
The present study assessed whether the baroreflex inhibition elicited by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) involves altered activity in the nucleus of the solitary tract (NTS). Unit recordings were made from 107 neurons in the NTS in anesthetized rabbits. Intravenous phenylephrine was used to induce a pressor response and to activate baroreflexes. Of the neurons that responded to pressor responses, two-thirds were excited and one-third was inhibited. Stimulation of the PVN inhibited 70% of the phenylephrine-responsive NTS neurons, with or without concurrent baroreceptor stimulation. When PVN stimulation was delivered concurrently with phenylephrine injection, more NTS neuronal inhibition and less excitation occurred than with phenylephrine alone. Usually PVN stimulation inhibited NTS neurons that were excited by pressor responses; less commonly, PVN stimulation excited NTS neurons that were inhibited by pressor responses. The findings are consistent with the view that PVN activation during the defense reaction inhibits baroreflexes by altering firing of NTS neurons. (+info)