bluuebunny/crossref_metadata_2025 huggingface dataset:
Tailored thrombolytic therapy. A perspective.
Authors: Simoons M L , Arnold A E
Published: June 2012

BACKGROUND

In contrast with current standard regimens, it seems more appropriate to tailor thrombolytic therapy to individual patient characteristics. A proposed model for such tailored therapy is based on individual assessment of benefits and risks of thrombolytic therapy, taking into account the response of individual patients to the therapy given.

METHODS AND RESULTS

Potential benefits of thrombolysis in individual patients can be predicted by use of demographic patient characteristics (age, sex, history of previous infarction) together with indicators of the ischemic area at risk (total ST segment deviation) and treatment delay. Using these parameters, the number of "lives saved" by thrombolytic therapy for specific patient characteristics can be estimated. Similarly, the risk of intracranial hemorrhage during thrombolytic therapy can be estimated from the patient's age, blood pressure at admission, and body weight. Depending on benefit/risk estimates, a choice can be made between regimens with high, medium, or modest thrombolytic efficacy. Continuous multilead ECG ischemia monitoring and rapid assays of myocardial proteins in serum can be used to assess the occurrence or absence of reperfusion and to detect signs of reocclusion. Such data help to decide whether thrombolytic therapy should be continued or intensified or might be discontinued in individual patients before the total standard dose has been administered. Such tailored reduction of the total thrombolytic dose will reduce the risk for bleeding complications in some of the patients.

CONCLUSIONS

The concept of tailoring thrombolytic therapy and the models presented for benefit/risk assessment should be tested in clinical studies and may subsequently help the physician to select the optimal approach in individual patients.
Value of the P-wave signal-averaged ECG for predicting atrial fibrillation after cardiac surgery.
Authors: Steinberg J S , Zelenkofske S , Wong S C , Gelernt M , Sciacca R , Menchavez E
Published: June 2012

BACKGROUND

Atrial fibrillation (AF) is a commonly encountered arrhythmia in clinical practice, and it occurs frequently after cardiac surgery. The P-wave signal-averaged (SA) ECG noninvasively detects atrial conduction delay. Prior studies have described greater P-wave prolongation in patients with a history of AF, but prospective studies have not been performed.

METHODS AND RESULTS

Consecutive patients undergoing cardiac surgery were enrolled. The P-wave SAECG was recorded before surgery from three orthogonal leads using a sinus P-wave template and a cross-correlation function. The averaged P wave was filtered with a least-squares-fit filter and combined into a vector magnitude, and total P-wave duration was measured. Patients were observed after cardiac surgery for the development of AF. One hundred thirty patients were enrolled, and 33 (25%) developed AF 2.6 +/- 2.0 days after surgery. Patients with AF more often had left ventricular hypertrophy on ECG (P < .05) and had a lower ejection fraction (P < .05). The P-wave duration on the SAECG was significantly longer in the AF patients than in those without AF: 152 +/- 18 versus 139 +/- 17 milliseconds (P < .001). An SAECG P-wave duration > 140 milliseconds predicted AF with sensitivity of 77%, specificity of 55%, positive predictive accuracy of 37%, and negative predictive accuracy of 87%. The likelihood of experiencing AF was increased 3.9-fold if the SAECG P-wave duration was prolonged. P-wave SAECG results were independent of other clinical variables by multivariate analysis.

CONCLUSIONS

The P-wave duration recorded with the SAECG is a potent, accurate, and independent predictor of AF after cardiac surgery.
Defibrillating shocks delivered to the heart impair efferent sympathetic responsiveness.
Authors: Ito M , Pride H P , Zipes D P
Published: June 2012

BACKGROUND

Functional studies indicate that sympathetic efferents are located in the superficial subepicardium and vagal efferents are located in the subendocardium. It is possible that electrical shocks applied directly to the heart might affect the function of these autonomic nerves.

METHODS AND RESULTS

Low- (< or = 1 J), medium- (6 to 16 J), or high- (30 to 35 J) energy truncated monophasic exponential shocks, synchronized to the R wave during sinus rhythm, were delivered over implantable patches sutured inside the pericardium in anesthetized open-chest dogs. Shortening of ventricular effective refractory period (ERP), produced by bilateral ansae subclaviae stimulation (SS), was measured before and after shock delivery. High-energy shocks shifted the SS frequency-ERP response curves downward and to the right (P < .001) for sites beneath and apical to the patches; ERP shortening at basal sites remained unchanged. Such sympathetic attenuation occurred with shocks > 10 J but not with shocks < or = 10 J, was noted 15 minutes after the shock, and showed incomplete return to control values at 3 hours. Neither low- nor high-energy shocks affected norepinephrine dose-ERP response curves, indicating normal myocardial responsiveness. Low- and high-energy shocks did not attenuate bilateral cervical vagal stimulation-induced ERP prolongation. High-energy shocks delivered over patches sutured to the outside of the pericardium showed no effects on sympathetic response, suggesting a protective effect of the pericardium against shock-induced sympathetic attenuation.

CONCLUSIONS

DC shocks > 10 J delivered directly to the epicardium attenuated efferent sympathetic neural function. Such changes may affect electrophysiological, as well as hemodynamic, responses to sympathetic neural stimulation after cardioversion-defibrillation.
Body surface distribution of abnormally low QRST areas in patients with Wolff-Parkinson-White syndrome. Evidence for continuation of repolarization abnormalities before and after catheter ablation.
Authors: Hirai M , Tsuboi N , Hayashi H , Ito M , Inden Y , Hirayama H , Ito T , Yanagawa T , Sano H , Kondo T
Published: June 2012

BACKGROUND

Whether the Wolff-Parkinson-White syndrome (WPW) is associated with repolarization abnormalities is controversial. The QRST isointegral map (I-map) is theoretically independent of the activation sequence and dependent on repolarization properties. There have been no reports concerning the effects of radiofrequency (RF) catheter ablation of accessory pathway (AP) on repolarization properties analyzed by I-mapping.

METHODS AND RESULTS

I-maps were constructed from data recorded in 38 patients with WPW to investigate repolarization properties and their body surface distribution in a physiological state, without pharmacological influences, and in 13 ablated patients to elucidate the effects of RF ablation on repolarization properties. Patients were divided into three groups: group A, 15 patients with type A WPW (left-sided AP); group B, 10 patients with type B (right-sided AP); and group C, 13 patients who were successfully ablated. Group C consisted of three subgroups: subgroup CA, 7 patients with type A WPW; subgroup CB, 3 patients with type B WPW; and subgroup CC, 3 patients with concealed WPW. Controls consisted of 608 normals. Although I-maps of WPW were highly (r = .87) correlated with the mean normal I-map, the location of the minimum in groups A and B differed significantly from that in normals. The minimum was located over the upper right anterior chest in normal subjects, over the back in 82% of 22 patients with type A WPW including ablated patients (groups A+CA), and over the mid to lower right anterior chest in 62% of 13 patients with type B WPW including ablated patients (groups B+CB). Groups A+CA and B+CB had an abnormally low QRST area ("-2SD area") over the back and right anterior chest, respectively. The abnormally located minimum and the "-2SD area" were present in 7 of 10 ablated patients with manifest WPW (groups CA+CB). After RF ablation, the distribution of the minimum, initially abnormal, became normal over a period of days or weeks, and the "-2SD area" disappeared over 1 week in all 7 patients. Correlation coefficients between I-maps and the mean normal I-map increased after RF ablation.

CONCLUSIONS

(1) WPW is often associated with abnormalities in repolarization properties. (2) Repolarization abnormalities were located over the back in type A WPW and over the right mid to lower chest in type B WPW: (3) The abnormalities remain immediately after RF ablation and gradually normalize. These findings support the concept that ST-T abnormalities in 12-lead ECGs following RF ablation are attributable to "cardiac memory."
Menopausal status influences ambulatory blood pressure levels and blood pressure changes during mental stress.
Authors: Owens J F , Stoney C M , Matthews K A
Published: June 2012

BACKGROUND

Frequent and large cardiovascular and neuroendocrine responses to psychological stress are thought to enhance an individual's risk for cardiovascular diseases. Preliminary data suggest that levels of reproductive hormones affect the magnitude of stress responses, perhaps contributing to the protective effect of ovarian hormones on premenopausal women's rates of coronary heart disease.

METHODS AND RESULTS

Healthy middle-aged men and premenopausal and postmenopausal women performed a series of standardized mental and physical challenges while blood pressure, heart rate, plasma catecholamines, lipids, and lipoproteins were measured. Subjects then wore an ambulatory blood pressure monitor during two consecutive workdays. Results showed that postmenopausal women had larger mean +/- SEM stress-induced increases in systolic blood pressure (24.7 +/- 2.2 mm Hg) and diastolic blood pressure (14.3 +/- 1.0 mm Hg) compared with either premenopausal women (16.9 +/- 1.3 and 10.2 +/- 0.9 mm Hg) or men (17.7 +/- 1.5 and 10.9 +/- 1.1 mm Hg, respectively). Postmenopausal women and men had higher mean +/- SEM ambulatory diastolic blood pressure levels (75.5 +/- 3.2 and 76.4 +/- 1.8 mm Hg) than did premenopausal women (69.9 +/- 2.2 mm Hg). Large blood pressure responses during public speaking were associated with high cholesterol levels and low educational attainment.

CONCLUSIONS

Menopause is associated with enhanced stress-induced cardiovascular responses and elevated ambulatory blood pressure during the workday. These effects may contribute to the risk of cardiovascular morbidity and mortality after the menopause.
Identification of functional angiotensin II receptors on rat cardiac fibroblasts.
Authors: Villarreal F J , Kim N N , Ungab G D , Printz M P , Dillmann W H
Published: June 2012

BACKGROUND

Cardiac hypertrophy results in an increased deposition of the extracellular matrix (ECM) proteins fibronectin and collagen. Recent evidence indicates that angiotensin II (Ang II) might have an important role in the development of myocardial fibrosis accompanying cardiac hypertrophy. We sought to determine whether fibroblasts of cardiac origin (isolated from neonatal and adult animals) express receptors for Ang II and to examine the ability of this peptide to regulate fibronectin and collagen gene expression in a cultured adult cardiac fibroblast cell preparation.

METHODS AND RESULTS

Binding of 125I-Ang II to both neonatal and adult cardiac fibroblasts in culture was specific, reversible, and saturable, with the receptor evenly distributed over the cell population. Competition binding experiments with receptor-specific antagonists indicate that Ang II receptors found on both fibroblast types were of the AT1 subtype. Analysis of mRNA levels for the AT1 receptor indicates that adult cardiac fibroblasts express higher levels of the message than neonatal fibroblasts or cardiac myocytes. Addition of 10(-9) mol/L Ang II to adult cardiac fibroblasts resulted in an induction of ECM proteins above control levels, as determined through Northern blots and total collagen assays.

CONCLUSIONS

Results from this study indicate that neonatal and adult rat cardiac fibroblasts in culture express AT1 receptors for Ang II. Ang II stimulation of AT1 receptors results in an increased gene expression for ECM proteins. These data suggest that Ang II might have important regulatory roles over cardiac fibroblast function under normal and pathological conditions.
Activation of calcium currents in cardiac myocytes by empty beta-adrenoceptors.
Authors: Mewes T , Dutz S , Ravens U , Jakobs K H
Published: June 2012

BACKGROUND

The cardiac calcium channel is known to be modulated by catecholamines via beta-adrenoceptors acting through intermediary GTP-binding regulatory proteins (G proteins). In biochemical studies on isolated membranes and reconstituted systems, it has been demonstrated that various G protein-coupled receptors, including beta-adrenoceptors, can activate G proteins and also intracellular second messengers like cyclic AMP (cAMP) even in the absence of an agonist and that antagonists can block this empty receptor action. We examined electrophysiologically whether agonist-free beta-adrenoceptors can modulate L-type calcium currents (ICa) in intact cardiac myocytes.

METHODS AND RESULTS

Cardiomyocytes were isolated from ventricles of guinea pig and human hearts and from human right atrial appendage. The patch-clamp technique was applied in the single electrode mode to measure whole-cell ICa. Modulation of calcium currents by beta-adrenoceptor antagonists, without addition of an agonist, was studied in the absence and presence of the direct adenylyl cyclase activator forskolin and the cAMP analog adenosine cyclic 3',5'-monophosphorothioate (Sp-cAMPS). In the presence of forskolin (0.5 mumol/L), an agent known to sensitize the adenylyl cyclase signal transduction system for receptor regulation, addition of the beta 1-selective antagonist atenolol and the nonselective antagonist propranolol (but not of the beta 2-selective antagonist ICI 118,551) caused a marked reduction of ICa in a concentration-dependent and stereoselective manner. The inhibitory effect of atenolol was reversible after washing out and was found to be half maximal and maximal (50% reduction) at about 50 and 300 nmol/L, respectively. In the absence of forskolin, inhibition of ICa by atenolol was markedly less (18% at 10 mumol/L atenolol). Finally, in contrast to forskolin-stimulated currents, atenolol (1 mumol/L) did not reduce calcium currents activated by the protein kinase A activator Sp-cAMPS (0.1 mmol/L), causing by itself a similar increase in calcium currents as forskolin.

CONCLUSIONS

In isolated guinea pig and human cardiomyocytes, agonist-free beta-adrenoceptors are functionally active and can stimulate L-type calcium currents, an effect blocked by receptor-specific antagonists.
Left ventricular diastolic chamber stiffness and intramyocardial coronary capacitance in isolated dog hearts.
Authors: Watanabe J , Levine M J , Bellotto F , Johnson R G , Grossman W
Published: June 2012

BACKGROUND

Because the myocardium is perfused primarily during diastole, changes in diastolic properties of the left ventricle (LV) should influence the intramyocardial circulation.

METHODS AND RESULTS

We examined the influence of LV diastolic properties on the magnitude and localization of intramyocardial coronary capacitance by analyzing the coronary pressure-venous flow relation in isolated, isovolumic dog heart preparations. After sudden occlusion of the left coronary artery during a long diastole, we measured precapacitance and postcapacitance resistances (RPRE and RPOST) and calculated intramyocardial coronary capacitance (CIM) from RPOST and the time constant of the coronary venous flow decay. Using this method, we characterized the effects of coronary vasodilation, LV diastolic volume, and LV diastolic chamber stiffness on the coronary circulation. The magnitude of CIM increased from 0.09 +/- 0.01 to 0.24 +/- 0.20 mL.mm Hg-1 x 100 g-1 (P < .01) after adenosine-induced vasodilation, whereas both RPOST and RPRE decreased significantly. The ratio of RPOST to RPRE+RPOST decreased from 0.35 +/- 0.02 to 0.23 +/- 0.02 (P < .01), suggesting redistribution of CIM to the distal portion of the coronary vascular tree. An increase in LV volume and wall stress was imposed to increase LV diastolic pressure from 2 +/- 0.1 to 25 +/- 1 mm Hg: this increased RPOST significantly but not RPRE and decreased the magnitude of CIM. The resistance ratio did not change significantly. Increased LV diastolic chamber stiffness induced by hypoxic perfusion (isovolumic LV diastolic pressure increased from 11 +/- 1 to 28 +/- 1 mm Hg) raised RPOST and decreased the magnitude of CIM from 0.32 +/- 0.12 to 0.17 +/- 0.04 mL.mm Hg-1 x 100 g-1 (P < .05). The resistance ratio increased significantly from 0.21 +/- 0.05 to 0.33 +/- 0.05 with increased LV diastolic chamber stiffness. Adjustment of LV diastolic volume to lower diastolic pressure to 10 +/- 1 mm Hg did not alter these changes significantly, suggesting that an intrinsic increase in myocardial stiffness played a major role in these changes.

CONCLUSIONS

Extravascular compression by raised LV diastolic volume and/or increased LV diastolic chamber stiffness acted mainly on coronary vessels that determine intramyocardial capacitance and postcapacitance resistance.
Liposome-mediated gene transfer into human vascular smooth muscle cells.
Authors: Pickering J G , Jekanowski J , Weir L , Takeshita S , Losordo D W , Isner J M
Published: June 2012

BACKGROUND

Complexing recombinant DNA with cationic liposomes is a convenient means of introducing foreign genes into cells (lipofection) and could potentially form the basis for genetically modifying diseased blood vessels in patients. The mechanism of lipofection is incompletely understood, but it is recognized that the degree of successful gene transfer is highly dependent on cell type. To date, there has been no reported experience with lipofection of human vascular smooth muscle cells.

METHODS AND RESULTS

Primary cultures of human vascular smooth muscle cells were transfected under optimized conditions with a plasmid expressing either firefly luciferase (Luc) or nuclear-localized beta-galactosidase (NL-beta-gal). Cells were derived from either normal human internal mammary arteries (n = 6), fragments of primary atherosclerotic plaque (n = 4), or fragments of restenotic lesions (n = 5). Concurrent lipofection of rabbit vascular smooth muscle cells and NIH 3T3 cells was performed as well. Cultures derived from 15 patients all demonstrated positive expression of the reporter gene. Compared with NIH 3T3 cells, however, expression in human vascular smooth muscle cells was markedly reduced: in cells derived from internal mammary artery, Luc expression, normalized for protein content, was 123-fold lower than in NIH 3T3 cells, whereas the proportion of cells expressing NL-beta-gal was 30-fold lower. Luc expression in cells derived from restenotic tissue was significantly greater than from cells derived from primary plaque (P < .03). Within a given population of cells, the mitotic index of cells expressing the recombinant gene was significantly higher than the mitotic index for the total population of cells (P < .05). Finally, cotransfection experiments, in which lipofection of smooth muscle cells was performed using genes for NL-beta-gal and for human growth hormone, showed that among positive transfects, a high proportion of cells (23% to 36%) coexpressed both genes.

CONCLUSIONS

The efficiency of successful lipofection in human vascular smooth muscle cells in vitro is low. Transfection appears to be preferentially facilitated in cells derived from restenotic tissue, and specific properties of smooth muscle cells, including growth rates, appear to be critical for successful transfection. Further elucidation of cell properties that promote transfection is required to augment the efficiency of liposome-mediated gene transfer in human vascular cells.
Genotype-phenotype correlations in hypertrophic cardiomyopathy. Insights provided by comparisons of kindreds with distinct and identical beta-myosin heavy chain gene mutations.
Authors: Fananapazir L , Epstein N D
Published: June 2012

BACKGROUND

We have previously described two distinct mutations in the beta-myosin heavy chain gene with markedly different clinical presentations and outcome: The 908Leu-->Val mutation was associated with a low disease penetrance and a benign prognosis. In contrast, the 403Arg-->Gln mutation in a Caucasian kindred was associated with a 100% disease penetrance and high incidence of sudden cardiac death. Recently, another mutation, 606Val-->Met, has been reported to be associated with "near normal survival" and offered as evidence for the benign nature of neutral charge substitutions.

METHODS AND RESULTS

We report (1) a large kindred (245 family members at risk of inheriting the disease gene) with a 256Gly-->Glu mutation characterized by a similar disease penetrance in adults and in children (56% and 60%, respectively) and a cumulative sudden cardiac death rate of only 2% at 50 years of age, (2) a kindred with the 606Val-->Met mutation with four sudden cardiac deaths in eight affected individuals, and (3) a Korean kindred with the 403Arg-->Gln mutation. Although the disease occurred early and was associated with a high prevalence of myocardial ischemia in both of our kindreds with the 403Arg-->Gln mutation, no sudden cardiac death or syncope has occurred in the Korean kindred. Furthermore, in the Caucasian kindred, all patients had nonobstructive hypertrophic cardiomyopathy, but most of the patients in the Korean kindred had left ventricular outflow obstruction.

CONCLUSIONS

The conclusions are as follows: (1) Although several sudden cardiac deaths are sufficient to establish that a mutation is malignant, study of a large kindred is necessary to be certain that a mutation is benign. To date, only the 908Leu-->Val and the 256Gly-->Glu mutations satisfy this requirement. (2) The 256Gly-->Glu mutation demonstrates that not all mutations that result in a charge change are malignant. (3) Conversely, the 606Val-->Met mutation is malignant in some kindreds; hence, despite the absence of a charge change, minor substitutions in critical regions of beta-myosin heavy chain protein may also have serious consequences. (4) The diverse ethnic origins of the two 403Arg-->Gln kindreds provide evidence suggesting that the identical mutation occurred independently and was associated with different genetic backgrounds. Their distinct phenotypes underline the importance of modifying genes and nongenetic factors.
A comparison of low- with high-osmolality contrast agents in cardiac angiography. Identification of criteria for selective use.
Authors: Matthai W H , Kussmaul W G , Krol J , Goin J E , Schwartz J S , Hirshfeld J W
Published: June 2012

BACKGROUND

Controversy exists as to whether low-osmolality radiographic contrast agents, which have less detrimental pharmacological effects but are considerably more expensive than high-osmolality agents, should be used universally or only for selected high-risk patients.

METHODS AND RESULTS

A randomized, double-blind study was used to compare the frequency and severity of adverse events in 2245 consecutive patients undergoing diagnostic cardiac angiography. Two thousand one hundred sixty-six patients were successfully randomized to either iohexol, a low-osmolality contrast agent, or diatrizoate (as Hypaque 76), a high-osmolality agent. The end point event included clinically important adverse events (which jeopardized the patient or required aggressive treatment), contrast agent-related procedure abbreviations, and conversion to open-label contrast agent. Clinically important end point events were associated with increased age, New York Heart Association functional class, left ventricular end-diastolic pressure, arteriovenous oxygen difference, severity of coronary artery disease, and history of a previous reaction to contrast agent. End point events were less frequent in patients receiving iohexol (2.6% versus 4.6%; adjusted odds ratio, 1.59; 95% confidence interval, 0.97-2.60; P = .07). The difference in event frequency between iohexol and diatrizoate was confined to the highest-risk quartile of the patient population. An algorithm was developed to classify patients as being at high or low risk for an event based on patient age, New York Heart Association class, history of a prior contrast reaction, and left ventricular end-diastolic pressure. Application of this algorithm for selective use of low-osmolality agents only for high-risk patients to a theoretical population of 1000 patients reduced contrast agent costs 66% without increasing the frequency of contrast agent-related adverse events.

CONCLUSIONS

The advantages of low-osmolality contrast agents are clinically important in patients with severe heart disease but are not in less ill patients. Universal use of low-osmolality agents for cardiac angiography in an unselected population is not necessary. Appropriately guided selective use of low-osmolality contrast agents is feasible and has the potential to reduce cost substantially without compromising safety or effectiveness.
Isoform-specific regulation of myocardial Na,K-ATPase alpha-subunit in congestive heart failure. Role of norepinephrine.
Authors: Kim C H , Fan T H , Kelly P F , Himura Y , Delehanty J M , Hang C L , Liang C S
Published: June 2012

BACKGROUND

Myocardial ouabain-binding sites and Na,K-ATPase activity are reduced in congestive heart failure (CHF), but the mechanisms by which CHF reduces the Na,K-ATPase remain unknown. We proposed to investigate whether the changes are accompanied by isoform-specific reductions of the Na,K-ATPase alpha-subunit proteins in CHF and whether similar changes could be produced by exogenous norepinephrine administration.

METHODS AND RESULTS

CHF was induced in dogs by rapid ventricular pacing at a rate of 225 beats per minute for 8 weeks (protocol 1). A second group of dogs were paced at 100 beats per minute and served as controls. In protocol 2, norepinephrine was infused in normal dogs using a subcutaneous osmotic minipump for 8 weeks. The control dogs received normal saline through the pump. Animals were studied after 8 weeks of pacing or norepinephrine infusion. After the baseline hemodynamics and interstitial norepinephrine concentration had been obtained, the hearts were removed for measuring [3H]ouabain-binding sites and Na,K-ATPase alpha-subunit proteins using isoform-specific monoclonal antibodies.

RESULTS

Myocardial [3H]ouabain-binding sites were reduced in dogs with CHF and chronic norepinephrine infusion. The Western blot analysis showed that adult canine hearts possess both alpha 1 and alpha 3 isoforms of the Na,K-ATPase alpha-subunit but not the alpha 2 isoform protein. CHF and NE infusion had no effect on the Na,K-ATPase alpha 1-subunit protein but did reduce the alpha 3 isoform protein significantly. In addition, there was a significant inverse correlation between the amount of myocardial alpha 3 isoform protein and interstitial norepinephrine content in the dogs. In contrast, the specific activity of the sarcolemmal marker 5'-nucleotidase did not differ among the groups of animals.

CONCLUSIONS

The reduction of myocardial Na,K-ATPase in CHF is limited to the alpha 3 isoform. Furthermore, because similar changes in myocardial ouabain-binding sites and Na,K-ATPase alpha 3 isoform were produced by chronic norepinephrine infusion, the decrease in the Na,K-ATPase in CHF is most likely mediated via excess sympathetic stimulation.
Nitric oxide mediates flow-dependent epicardial coronary vasodilation to changes in pulse frequency but not mean flow in conscious dogs.
Authors: Canty J M , Schwartz J S
Published: June 2012

BACKGROUND

Although epicardial coronary arteries dilate in response to changes in flow, the mechanisms responsible for this and the mechanical stimuli that are sensed by the endothelium are not completely defined. We performed the present study to determine the importance of nitric oxide in eliciting epicardial dilation to sustained changes in mean flow and pulse frequency in the coronary circulation of conscious dogs.

METHODS AND RESULTS

Dogs were chronically instrumented with a circumflex coronary occluder, piezoelectric crystals to measure epicardial diameter, and a coronary artery catheter placed distal to the crystals for intracoronary drug infusion. Studies were conducted in dogs in the conscious state. We inhibited nitric oxide production by administering the arginine analog N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg IV), which attenuated the epicardial artery diameter changes to left atrial infusions of acetylcholine (10 micrograms/min) from 140 +/- 23 (+/- SEM) to 46 +/- 20 microns (P < .05). Epicardial dilation to sustained increases in mean coronary artery at a constant heart rate. Intracoronary adenosine increased mean flow to the same extent (180 +/- 21 versus 177 +/- 24 mL/min after L-NAME, P = NS), but inhibiting nitric oxide production had no effect on flow-mediated epicardial dilation, with coronary diameter increasing by 264 +/- 36 microns under control conditions and 294 +/- 67 microns after L-NAME (P = NS). In contrast, when pulse frequency was increased by pacing to a rate of 200 beats per minute, mean coronary flow increased to a similar level (78 +/- 9 versus 75 +/- 9 mL/min after L-NAME), but the epicardial diameter change to pacing was attenuated from 170 +/- 29 microns under control conditions to 54 +/- 23 microns after L-NAME (P < .01).

CONCLUSIONS

These results demonstrate that in vivo, nitric oxide production is primarily responsible for eliciting epicardial coronary vasodilation to endothelium-dependent agonists and changes in coronary flow pulse frequency. The failure of L-NAME to affect epicardial vasodilation during sustained increases in mean flow when pulse frequency is held constant suggests that additional mechanisms are involved in flow-mediated vasodilation of epicardial coronary arteries.
Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes.
Authors: Sun D , Nguyen N , DeGrado T R , Schwaiger M , Brosius F C
Published: June 2012

BACKGROUND

Acute myocardial ischemia is accompanied by an increase in glucose uptake and metabolism, which appears to be important in protecting myocardial cells from irreversible ischemic injury. Because insulin augments myocardial glucose uptake by inducing the translocation of glucose transporters from an intracellular compartment to the plasma membrane, we hypothesized that acute ischemia would trigger a similar translocation.

METHODS AND RESULTS

We used a subcellular fractionation method to separate intracellular membrane and plasma membranes from control, ischemic, and hypoxic Langendorff-isolated perfused rat hearts and determined the expression of the major myocardial glucose transporter, GLUT4, in these separated membrane fractions. We found that translocation of GLUT4 molecules occurred in ischemic, hypoxic, and insulin-treated hearts and in hearts that underwent ischemia plus insulin treatment. The percentages of GLUT4 molecules present on the plasma membrane in the different conditions were as follows: control, 18.0 +/- 2.8%; ischemia, 41.3 +/- 9.4%; hypoxia, 31.1 +/- 2.9%; insulin, 61.1 +/- 2.6%; and ischemia plus insulin, 66.8 +/- 5.7%. Among the statistically significant differences in these values were the difference between control and ischemia and the difference between ischemia alone and insulin plus ischemia.

CONCLUSIONS

Ischemia causes substantial translocation of GLUT4 molecules to the plasma membrane of cardiac myocytes. A combination of insulin plus ischemia stimulates an even greater degree of GLUT4 translocation. GLUT4 translocation is likely to mediate at least part of the increased glucose uptake of ischemic myocardium and may be a mechanism for the cardioprotective effect of insulin during acute myocardial ischemia.
Native beta-adrenergic support for left ventricular dysfunction in experimental mitral regurgitation normalizes indexes of pump and contractile function.
Authors: Nagatsu M , Zile M R , Tsutsui H , Schmid P G , DeFreyte G , Cooper G , Carabello B A
Published: June 2012

BACKGROUND

It is generally accepted that the adrenergic nervous system provides inotropic support for the failing heart. However, the magnitude of this support has never been studied extensively. The present study was performed to test the hypothesis that the adrenergic nervous system is capable of maintaining indexes of pump and contractile function in the normal range despite significant innate myocardial depression.

METHODS AND RESULTS

We used our model of experimental canine mitral regurgitation, which produces left ventricular dysfunction after 3 months of volume overload. We studied indexes of contractile function on and off beta-blockade at baseline and again on and off beta-blockade 3 months after chronic mitral regurgitation had induced significant contractile dysfunction. At baseline, acute beta-blockade caused insignificant reductions in the mass-corrected slope of the end-ejection stress-volume relation (EESVR), the end-systolic stiffness constant, and the ejection fraction-end-systolic stress and the mean velocity of circumferential fiber shortening (VCF)-end-systolic stress relations. After 3 months of chronic mitral regurgitation, all indexes of contractile function were normal in the unblocked state except for the VCF-stress relation, which was mildly reduced. However, after acute beta-blockade after 3 months of chronic mitral regurgitation, the EESVR fell to 303 +/- 27 versus 443 +/- 24 during acute beta-blockade before mitral regurgitation was created (P < .05), and the end-systolic stiffness constant was reduced to 2.54 +/- 0.15 versus 3.27 +/- 0.11 (P < .05). Only after beta-blockade was the ejection fraction-stress relation significantly reduced for dogs with chronic mitral regurgitation. The VCF-stress relation became markedly more abnormal. The viscosity-velocity relation of myocytes isolated from the ventricles of the dogs with mitral regurgitation confirmed that substantial innate contractile depression was present.

CONCLUSIONS

After 3 months of chronic mitral regurgitation, the adrenergic nervous system was able to maintain most indexes of contractile function in the normal range despite significant depression in innate contractile function. Thus, in the absence of beta-blockade, significant innate contractile depression may be obscured by adrenergic support.
Dependence of Gorlin formula and continuity equation valve areas on transvalvular volume flow rate in valvular aortic stenosis.
Authors: Burwash I G , Thomas D D , Sadahiro M , Pearlman A S , Verrier E D , Thomas R , Kraft C D , Otto C M
Published: June 2012

BACKGROUND

Valve areas derived by the Gorlin formula have been observed to vary with transvalvular volume flow rate. Continuity equation valve areas calculated from Doppler-echo data have become a widely used alternate index of stenosis severity, but it is unclear whether continuity equation valve areas also vary with volume flow rate. This study was designed to investigate the effects of changing transvalvular volume flow rate on aortic valve areas calculated using both the Gorlin formula and the continuity equation in a model of chronic valvular aortic stenosis.

METHODS AND RESULTS

Using a canine model of chronic valvular aortic stenosis in which anatomy and hemodynamics are similar to those of degenerative aortic stenosis, each subject (n = 8) underwent three studies at 2-week intervals. In each study, transvalvular volume flow rates were altered with saline or dobutamine infusion (mean, 10.3 +/- 5.1 flow rates per study). Simultaneous measurements were made of hemodynamics using micromanometer-tipped catheters, of ascending aortic instantaneous volume flow rate using a transit-time flowmeter, and of left ventricular outflow and aortic jet velocity curves using Doppler echocardiography. Valve areas were calculated from the invasive data by the Gorlin equation and from the Doppler-echo data by the continuity equation. In the 24 studies, mean transit-time transvalvular volume flow rate ranged from 80 +/- 33 to 153 +/- 49 mL/min (P < .0001). Comparing minimum to maximum mean volume flow rates, the Gorlin valve area changed from 0.54 +/- 0.22 cm2 to 0.68 +/- 0.21 cm2 (P < .0001), and the continuity equation valve area changed from 0.57 +/- 0.18 cm2 to 0.70 +/- 0.20 cm2 (P < .0001). A strong linear relation was observed between Gorlin valve area and mean transit-time volume flow rate for each study (median, r = .88), but the slope of this relation varied between studies. The Doppler-echo continuity equation valve area had a weaker linear relation with transit-time volume flow rate for each study (median, r = .51).

CONCLUSIONS

In this model of chronic valvular aortic stenosis, both Gorlin and continuity equation valve areas were flow-dependent indices of stenosis severity and demonstrated linear relations with transvalvular volume flow rate. The changes in calculated valve area that occur with changes in transvalvular volume flow should be considered when measures of valve area are used to assess the hemodynamic severity of valvular aortic stenosis.
Identification of concealed posteroseptal Kent pathways by comparison of ventriculoatrial intervals from apical and posterobasal right ventricular sites.
Authors: Martínez-Alday J D , Almendral J , Arenal A , Ormaetxe J M , Pastor A , Villacastín J P , Medina O , Peinado R , Delcán J L
Published: June 2012

BACKGROUND

The differential diagnosis of supraventricular tachycardia with concentric atrial activation usually requires the inducibility of sustained tachycardia and needs a complex and time-consuming electrophysiological evaluation. To develop a simple test to establish if ventriculoatrial conduction uses a posteroseptal accessory pathway or the normal conduction system, we compared the ventriculoatrial intervals during right ventricular pacing from apical and posterobasal sites.

METHODS AND RESULTS

Continuous pacing was performed from an apical and a posterobasal right ventricular site in 34 patients with retrograde conduction over the normal conduction system (group A) and in 22 patients with conduction over a posteroseptal accessory pathway (group B). During apical pacing, ventriculoatrial intervals in group A (176 +/- 40 milliseconds) were not significantly different than those in group B (197 +/- 47 milliseconds, P = NS). During posterobasal pacing, group B patients had significantly shorter ventriculoatrial intervals than group A patients (158 +/- 46 versus 197 +/- 39 milliseconds, P < .01). The difference between the ventriculoatrial interval obtained during apical pacing and that obtained during posterobasal pacing (ventriculoatrial index) discriminated between the two groups without overlapping: It was positive in all group B patients (39 +/- 19; range, +10 to +70 milliseconds) and negative in all except two group A patients (-21 +/- 13; range, -50 to +5 milliseconds; P < .001).

CONCLUSIONS

This ventriculoatrial index can identify accurately and in the absence of tachycardia whether concentric retrograde conduction is proceeding over a posteroseptal accessory pathway or over the normal conduction system.
Prospective, randomized comparison in humans of a unipolar defibrillation system with that using an additional superior vena cava electrode.
Authors: Bardy G H , Dolack G L , Kudenchuk P J , Poole J E , Mehra R , Johnson G
Published: June 2012

BACKGROUND

A unipolar defibrillation system using a single right ventricular (RV) electrode and the active shell or "CAN" of the implantable cardioverter-defibrillator itself situated in a left infraclavicular pocket has been shown to be as efficient in defibrillation as an epicardial lead system. The purpose of this study was to determine whether defibrillation efficacy can be improved further by adding a superior vena cava (SVC) electrode to this already efficient defibrillation system.

METHODS AND RESULTS

We prospectively and randomly compared the defibrillation efficacy of a simplified unipolar defibrillation system, RV-->CAN, with that of one incorporating a high SVC electrode, RV-->SVC + CAN, in 15 consecutive cardiac arrest survivors undergoing implantation of a presently available transvenous defibrillation system. The RV defibrillation electrode was a 5-cm coil located on a 10.5F lead used as the anode in both lead configurations examined. The active CAN was a 108-cm2 surface area shell of a titanium alloy pulse generator used as the cathode in both configurations and placed in a left infraclavicular pocket. The SVC electrode was a 6F 5-cm-long coil and was used as an additional cathode positioned at the junction of the SVC and the left innominate vein. The defibrillation pulse used was a 65% tilt, asymmetric biphasic waveform delivered from a 120-microF capacitor. The defibrillation threshold (DFT) stored energy, leading edge voltage, current, and pulsing resistance were measured for both lead systems. The single-lead unipolar system, RV-->CAN, resulted in a stored energy DFT of 7.4 +/- 5.2 J, and the three-electrode dual pathway system, RV-->SVC + CAN, resulted in a DFT of 6.0 +/- 3.4 J (P = .20). There was no difference in defibrillation efficacy with the more complicated three-electrode system over the unipolar system despite a decrease in pulsing resistance to 48.6 +/- 3.5 omega compared with 61.2 +/- 5.9 omega for the unipolar system (P < .0001) and a slight rise in delivered current to 6.3 +/- 1.8 A compared with 5.5 +/- 2.0 A for the unipolar system (P = .062).

CONCLUSIONS

The unipolar single-lead transvenous defibrillation system provides defibrillation at energy levels comparable to that reported with present epicardial lead systems. Coupling of this lead system to a third SVC electrode increases system complexity but offers little defibrillation advantage despite a large decrease in pulsing resistance and a modest increase in delivered current.
Treatment of ventricular tachycardia by transcatheter radiofrequency ablation in patients with ischemic heart disease.
Authors: Kim Y H , Sosa-Suarez G , Trouton T G , O'Nunain S S , Osswald S , McGovern B A , Ruskin J N , Garan H
Published: June 2012

BACKGROUND

Recurrent sustained ventricular tachycardia (VT) is not responsive to antiarrhythmic drugs in the majority of patients, who therefore need therapy with nonpharmacological methods. We evaluated prospectively the feasibility, safety, and efficacy of transcatheter radiofrequency (RF) ablation of VT in 21 selected patients with ischemic heart disease and VT.

METHODS AND RESULTS

Twenty-one patients with ischemic heart disease and recurrent, drug-refractory VT documented by 12-lead ECG were selected who had sufficient hemodynamic tolerance of VT to undergo transcatheter mapping. Documented clinical VT was reproduced by programmed cardiac stimulation (PCS), and the site of origin was localized by a combination of techniques, including pace mapping, activation-sequence mapping, recordings of middiastolic potentials, and application of resetting and entrainment principles. RF current at 55 V was applied (3.8 +/- 3.1 applications per patient) for as long as 30 seconds at a time to target sites. Twenty-four distinct clinical VTs (mean cycle length, 445 +/- 52 milliseconds) were mapped and ablated in 21 patients. In 17 of 21 patients (81%), the procedure was acutely successful, and the target clinical VT could no longer be induced by PCS after the procedure, whereas in 4 patients, clinical VT remained inducible. By contrast, VTs with shorter cycle length and different QRS morphology than the ablated VT could still be induced by PCS in 12 of 21 patients. One patient died in intractable congestive heart failure 10 days after the procedure, and the remaining 20 are alive at the end of the follow-up period. The majority of the patients continued to be treated with at least one additional mode of antiarrhythmic therapy; 12 patients were still taking antiarrhythmic drugs, and 9 patients received an implantable cardioverter/defibrillator. During a mean follow-up period of 13.2 +/- 5.0 months, 9 of 20 patients (45%) had recurrent VT. In 4 patients, the recurrent VT was different than the previously ablated one. Clinical VT recurred in all 4 patients in whom RF ablation had been acutely unsuccessful. Four patients with recurrent VT underwent repeat RF ablation procedures that were acutely successful and had no further recurrence.

CONCLUSION

Transcatheter RF ablation is feasible but has only moderately high efficacy in a small, selected group of patients with ischemic heart disease and drug-refractory, highly frequent, hemodynamically tolerated, sustained VT. In the majority of the patients, this treatment technique is palliative rather than definitive, and many of the patients continue to require other methods of antiarrhythmic therapy.
Prevalence and predictors of audible physiological third heart sound in a population sample aged 36 to 37 years.
Authors: Kupari M , Koskinen P , Virolainen J , Hekali P , Keto P
Published: June 2012

BACKGROUND

A physiological third heart sound (S3) is common in youth but allegedly very rare after the age of 40 years. The mechanism of its disappearance is not known. The aim of this work was to study the prevalence and predictors of physiological S3 in a population-based sample of persons approaching 40 years of age.

METHODS AND RESULTS

A random sample of 120 persons born in 1954 was invited; 93 (42 men) entered the study. Their physical activity, alcohol and tobacco consumption, and salt intake were quantified by diary follow-up. The presence of an S3 was determined by auscultation and confirmed by phonocardiography. Left ventricular (LV) size, mass, and systolic function were assessed by M-mode echocardiography and LV filling by Doppler velocimetry of transmitral flow. An audible S3 was detected in 22 subjects, 1 of whom had heart disease. The prevalence of physiological S3 was 23.1%. Subjects with physiological S3 had a lower body mass index (22.3 +/- 2.8 versus 24.6 +/- 4.1 kg/m2 [mean +/- SD], P = .005), lower heart rate (63 +/- 7 versus 68 +/- 10 beats per minute, P = .015), higher peak early diastolic transmitral velocity (67 +/- 10 versus 58 +/- 8 cm/s, P = .002), and higher acceleration of early diastolic velocity (717 +/- 148 versus 622 +/- 122 cm/s2, P = .012) than those without S3. No differences were noted in the lifestyle characteristics, blood pressure, or LV mass and systolic function. Body mass index and peak early diastolic transmitral velocity were independent predictors of physiological S3 in logistic regression analysis.

CONCLUSIONS

Nearly one fourth of persons approaching their forties still have an audible physiological S3. The presence of S3 is predicted by leanness and a high early diastolic LV inflow velocity; the disappearance of S3 is unlikely to be secondary to increasing blood pressure and relative LV hypertrophy, as is widely presented, but reflects a more primary age-related alteration of LV early diastolic function.