bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decrease in myocardial ryanodine receptors and altered excitation-contraction coupling early in the development of heart failure.
Authors: Vatner D E , Sato N , Kiuchi K , Shannon R P , Vatner S F 
Published: June 2012

BACKGROUND
Rapid ventricular pacing for 1 day reduced myocardial contractile function without inducing heart failure in conscious, chronically instrumented dogs. After 4 to 7 weeks of pacing, myocardial contractility was depressed further and overt signs of congestive heart failure, eg, ascites, dyspnea, and edema, were evident.

METHODS AND RESULTS
The mechanical restitution response, a physiological index of calcium release, was depressed at 1 day of rapid ventricular pacing. Postextrasystolic potentiation was also depressed by a similar amount, 14 +/- 3%, at 1 day after pacing. The response to isoproterenol 0.2 microgram/kg per minute was depressed by a significantly greater amount (P < .05), 52 +/- 7%, at 1 day after pacing. 3H-ryanodine receptor binding fell from 1013 +/- 25 to 808 +/- 42 fmol/mg after 1 day of pacing and remained depressed at similar levels (782 +/- 61 fmol/mg) at 4 to 7 weeks when heart failure was manifest. Ryanodine receptor affinity was unchanged from control values. Neither dihydropyridine binding nor affinity for 3H-PN200-110 was changed from control levels. Within 5 days after recovery from 1 day of pacing, physiological responses to isoproterenol, postextrasystolic potentiation, and mechanical restitution recovered, as did 3H-ryanodine binding density.

CONCLUSIONS
These findings suggest that the changes in excitation-contraction coupling and potentially the sarcoplasmic reticulum calcium release channel occur early in the development of heart failure and therefore may be important in the pathogenesis of the contractile abnormalities in this disease state.
Focal mechanisms underlying ventricular tachycardia during prolonged ischemic cardiomyopathy.
Authors: Pogwizd S M 
Published: June 2012

BACKGROUND
The present study was performed to define the mechanisms underlying spontaneously occurring ventricular arrhythmias in the failing heart.

METHODS AND RESULTS
Three-dimensional cardiac mapping from as many as 232 intramural sites was performed in five dogs with ischemic cardiomyopathy induced by multiple intracoronary embolizations. After 5 to 10 weekly embolizations with 90-microns latex microspheres into the left anterior and circumflex coronary arteries, left ventricular ejection fraction decreased from 63 +/- 3% to 22 +/- 3%. Subsequent weekly Holter monitoring of dogs in the conscious state demonstrated frequent multiform premature ventricular complexes (PVCs) (< or = 2000/d), couplets, and runs of ventricular tachycardia (VT) (< or = 70 beats in duration and < or = 560 beats per minute) in all dogs. Three-dimensional mapping of spontaneous rhythm for 60 minutes was performed an average of 6.4 weeks after the last embolization, during which time each dog demonstrated multiform PVCs, couplets, and runs of nonsustained VT at rates comparable to those in the conscious state. Mapping was of sufficient density to define the mechanism for 31 PVCs, 45 beats of ventricular couplets, and 99 beats of VT. Sinus beats preceding PVCs (n = 36) initiated in the septum and spread rapidly with a total activation time (46 +/- 1 milliseconds) that did not differ from that of sinus beats not preceding PVCs or VT (46 +/- 2 milliseconds, n = 10, P = .69). PVCs and the first beat of couplets or VT were initiated primarily in the subendocardium by a focal mechanism, based on the lack of intervening electrical activity between the termination of the preceding (sinus) beat and initiation of the ectopic beat (225 +/- 23 milliseconds), despite the presence of multiple intervening intramural recording sites. All subsequent beats of VT also were initiated by a focal mechanism, and their total activation time (89 +/- 1 milliseconds) did not differ from that of the initiating ectopic beats (86 +/- 2 milliseconds, P = .14), despite acceleration of VT to a cycle length of 200 milliseconds. Monomorphic VT was due to repetitive focal activation of subendocardial sites. Polymorphic VT was due to sequential focal activation from multiple sites arising in the subendocardium and, at times, in the subepicardium. Comparison of mapping data with results of detailed anatomic analysis of tissue demonstrated that focal sites of initiation exhibited patchy nontransmural fibrosis. Functional conduction delay of a moderate degree was evident only when fibrosis extended transmurally.

CONCLUSIONS
Spontaneously occurring PVCs, couplets, and VT in a model of ischemic cardiomyopathy are initiated and maintained by focal mechanisms with no evidence of macroreentry. Thus, therapeutic regimens to treat or prevent VT in the presence of ischemic cardiomyopathy will likely require interruption of these focal mechanisms.
Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection.
Authors: Skyba D M , Jayaweera A R , Goodman N C , Ismail S , Camarano G , Kaul S 
Published: June 2012

BACKGROUND
The purpose of this study was to determine whether myocardial perfusion can be quantified with myocardial contrast echocardiography using left atrial (LA) injection of contrast.

METHODS AND RESULTS
Based on a series of in vitro and in vivo experiments, the optimal dose of sonicated albumin microbubbles injected into the LA for establishing a linear relation between video intensity and blood volume in the anterior myocardium was determined. In 10 open-chest dogs, myocardial blood flow (MBF) was augmented by increasing myocardial blood volume (MBV) with an intravenous infusion of phenylephrine HCl. In the presence of this drug, left anterior descending artery stenosis was produced, followed by release of stenosis, to change MBF within the anterior myocardium. MBV was calculated by dividing radiolabeled microsphere-derived MBF by microbubble transit rate. There was close coupling between MBF and MBV in the anterior myocardium during LA injection of contrast (y = 1.0x-0.03, SEE = 1.07, r = .92, P < .001). An excellent correlation was also noted between background-subtracted peak video intensity and MBV (y = 0.24x + 0.73, SEE = 0.36, r = .88, P < .001). On multivariate analysis, background-subtracted peak video intensity correlated best with MBV.

CONCLUSIONS
Myocardial perfusion can be quantified from time-intensity curves derived from the anterior myocardium after LA injection of contrast. Background-subtracted peak video intensity in this situation correlates closely with MBV. When MBV and MBF are closely coupled, such as during inotropic stimulation of the heart, background-subtracted peak video intensity also correlates closely with MBF. Since there are similarities in the models of LA and venous injections, these data indicate that it may be feasible to quantify myocardial perfusion with myocardial contrast echocardiography after venous injection of contrast.
Arterial gene transfer to rabbit endothelial and smooth muscle cells using percutaneous delivery of an adenoviral vector.
Authors: Steg P G , Feldman L J , Scoazec J Y , Tahlil O , Barry J J , Boulechfar S , Ragot T , Isner J M , Perricaudet M 
Published: June 2012

BACKGROUND
Previous investigations in live animals convincingly established that arterial gene transfer, while feasible, was compromised by a low transfection efficiency. More recent studies have shown that transfection efficiency may be substantially augmented by the use of recombinant adenoviral vectors. Most in vivo transfections reported to date, however, have used direct (operative) administration of the adenoviral vector. Clinical applications of arterial gene transfer (such as prevention of restenosis), however, would require local percutaneous delivery of the transgene. The present study was designed to extend in vivo intraoperative findings to percutaneous delivery system and to assess whether gene transfer remains site specific.

METHODS AND RESULTS
A recombinant, replication-defective adenovirus modified to include an expression cassette for nucleus-targeted beta-galactosidase was introduced into rabbit iliac arteries in vivo using either a double-balloon catheter (DBC, n = 27) or a hydrogel-coated balloon catheter (HBC, n = 27). Contralateral arteries-normal, endothelium-denuded, or sham-transfected with a control adenoviral vector-served as controls. beta-Galactosidase expression was assessed by X-Gal staining. Cell-transduction efficiency was measured by morphometric analysis. Polymerase chain reaction (PCR) and histochemistry were used to detect the presence and/or expression of viral DNA in remote organs. Transgene expression was detected in all cases (46 of 46) between 3 and 14 days after transfection but was in no case detectable 28 days after transfection. In the DBC group, transgene expression was limited to endothelial cells when the endothelium was left intact and to rare medial cells (< 2.2%) when it had been removed. In contrast, HBC delivery resulted in transduction of up to 9.6% of medial smooth muscle cells (P = .0001). Optimized PCR and histochemistry failed to detect evidence of extra-arterial transfection except in a small number of cells (between 1 in 3 x 10(2) and 1 in 3 x 10(5) cells) in the livers of 2 animals in the DBC group.

CONCLUSIONS
(1) Efficient, adenovirus-mediated, arterial gene transfer to endothelial and/or smooth muscle cells is feasible by percutaneous, clinically applicable techniques. (2) Consistent transfection of medial smooth muscle cells may be achieved when the endothelial layer is abraded. (3) Medial transfection is more efficient when an HBC, rather than a DBC, is used. (4) Percutaneous delivery of the adenoviral vector via HBC results in site-specific arterial gene transfer. Very-low-level extra-arterial transfection may occur, however, when the DBC is used.
Accumulation of activated mast cells in the shoulder region of human coronary atheroma, the predilection site of atheromatous rupture.
Authors: Kaartinen M , Penttilä A , Kovanen P T 
Published: June 2012

BACKGROUND
Rupture in the shoulder region of a coronary atheroma is considered to be a sequel to local extracellular matrix degradation in this highly vulnerable site. Such degradation could be triggered by mast cells, which are filled with neutral proteases and are present in coronary atheromas. However, the distribution and phenotype of mast cells within coronary atheromas have not been studied.

METHODS AND RESULTS
Specimens of normal and atherosclerotic human coronary intima from 32 autopsy cases with ages ranging from 13 to 67 years were stained with monoclonal antibodies against the two major proteases of mast cells, tryptase and chymase. Of the tryptase-containing mast cells, a variable proportion (average, 40%; range, 0% to 100%) also contained chymase. In the normal coronary intimas, mast cells amounted to 0.1% of all nucleated cells. In the fatty streaks, this proportion was higher by 9-fold, and in the cap, core, and shoulder regions of atheromas by 5-, 5-, and 10-fold, respectively. Electron and light microscopic studies of mast cells in the shoulder region of atheromas revealed degranulation of mast cells, a sign of their activation, and moreover, that the proportion of activated mast cells was much higher (85%) in this region than in the normal intima (18%).

CONCLUSIONS
The far higher proportion (50-fold) of activated mast cells in the shoulder region of atheromas supports the hypothesis that mast cells, a cell type capable of triggering matrix degradation, actively participate in the destabilization and ensuing rupture of coronary atheromas and thus may trigger an acute coronary event.
Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators.
Authors: Rutherford J D , Pfeffer M A , Moyé L A , Davis B R , Flaker G C , Kowey P R , Lamas G A , Miller H S , Packer M , Rouleau J L 
Published: June 2012

BACKGROUND
In the Survival and Ventricular Enlargement (SAVE) trial, recurrent myocardial infarction (MI) was the most important predictor of a poor outcome and conferred a sevenfold increase in risk of death. The purpose of this study was to determine the predictors of recurrent MI in study participants and to examine the influence of the angiotensin-converting enzyme inhibitor captopril on this and other myocardial ischemic events.

METHODS AND RESULTS
The 2231 patients had survived the acute phase of MI (3 to 16 days) and had a radionuclide ventricular ejection fraction < or = 40%. Patients were randomly assigned to receive double-blind treatment with either placebo or captopril and were followed for an average of 42 months. The influence of captopril on recurrent MI, cardiac revascularization procedures, and hospitalization with unstable angina was examined. The likelihood of recurrent MI was greater in patients with an MI or functional disability before the index infarction and higher systolic pressure (all P < .001) but was not influenced by baseline left ventricular ejection fraction. Therapy with captopril reduced the risk of development of recurrent MI by 25% (95% confidence intervals, 5% to 40%; P = .015) and the risk of death after recurrent MI by 32% (95% confidence intervals, 4% to 51%; P = .029). Captopril-assigned patients were also less likely to require cardiac revascularization procedures (P = .010), but hospitalization for unstable angina was unaltered. When all three of these major coronary ischemic events were considered together, captopril therapy reduced the risk (14% risk reduction; 95% confidence intervals, 0% to 26%; P = .047).

CONCLUSIONS
In post-MI patients with asymptomatic left ventricular dysfunction, long-term administration of captopril reduced recurrence of MI and the need for cardiac revascularization but had no influence on the rate of hospitalization with a discharge diagnosis of unstable angina. The finding that the recurrence of MI was independent of left ventricular ejection fraction suggests that captopril could be useful in preventing recurrent MI in patients with more preserved left ventricular function. The need for cardiac revascularization was reduced in patients receiving long-term captopril therapy, suggesting either an anti-ischemic effect or the ability of the angiotensin-converting enzyme inhibitor to modify the atherosclerotic process in survivors of MI.
Morphological and quantitative angiographic analyses of progression of coronary stenoses. A comparison of Q-wave and non-Q-wave myocardial infarction.
Authors: Dacanay S , Kennedy H L , Uretz E , Parrillo J E , Klein L W 
Published: June 2012

BACKGROUND
The purpose of this study was to determine differences in coronary stenosis severity and morphology and time course of progression between Q-wave and non-Q-wave myocardial infarction (MI).

METHODS AND RESULTS
We studied 32 patients with new Q-wave MI and 38 patients with new non-Q-wave MI who underwent coronary angiography both before and after MI without interval revascularization procedures. Quantitative coronary angiographic analysis was performed by the caliper method, and morphological analysis of coronary angiograms was obtained before and soon after acute MI. Before infarction, the stenosis severity at the site of future MI was worse in Q-wave (44 +/- 25%) versus non-Q-wave (23 +/- 35%) MI patients (P < .01). Eccentric and irregular plaques were more common in Q-wave MI patients (18 of 32, 56%, versus 5 of 38, 13%; P < .001). Non-Q-wave MI patients were more frequently found to have significant collaterals after MI compared with Q-wave MI patients (18 of 38, 47%, versus 1 of 32, 3%; P < .001) despite no difference in post-MI stenosis severity. Analysis according to time interval after pre-MI angiography showed that 9 of 11 patients (82%) with Q-wave MI < 18 months later had a stenosis of > or = 50% versus 7 of 21 (33%) with an interval > 18 months (P < .05). By comparison, non-Q-wave MI patients tended to fall into two categories regardless of time of progression: Either minimal or no stenosis (< 20%) or else a severe stenosis (> 70%) was typically present.

CONCLUSIONS
The atheromatous plaque substrate is different in Q-wave and non-Q-wave MI. Non-Q-wave MI occurs typically at a site shown by pre-MI angiography to involve either minimal luminal narrowing or a severe stenosis before MI, which is usually nonulcerated. By comparison, Q-wave MI follows a moderate stenosis in which the plaque is eccentric and ulcerated. Such differences culminate in differences in thrombus lability and collateral development and consequently in different clinical profiles.
Independent control of skin and muscle sympathetic nerve activity in patients with heart failure.
Authors: Middlekauff H R , Hamilton M A , Stevenson L W , Mark A L 
Published: June 2012

BACKGROUND
Sympathetic excitation characterizes heart failure, but the underlying mechanisms remain unknown. Abnormal baroreflex restraint of sympathetic neural outflow has been proposed, since baroreflexes are known to be abnormal in heart failure. The purpose of this study was to determine if sympathetic activation in humans with heart failure is limited to regions governed by the baroreflexes or is generalized to other regions free from baroreflex control.

METHODS AND RESULTS
We report the first direct recordings of skin sympathetic nerve activity (free from baroreflex control) in humans with heart failure and compare simultaneous skin and muscle (baroreflex-dependent) sympathetic peroneal nerve activity in six patients with severe heart failure (mean left ventricular ejection fraction, 0.19 +/- 0.06) and in six age-matched normal control subjects. Although muscle sympathetic nerve activity was markedly increased in heart failure patients (heart failure versus controls, 69 +/- 3 versus 21 +/- 2 bursts per minute; P < .001), skin sympathetic nerve activity was not increased (heart failure versus controls, 12 +/- 1 versus 15 +/- 1 bursts per minute; P = NS).

CONCLUSIONS
The finding that skin sympathetic nerve activity in contrast to muscle sympathetic nerve activity is not increased in heart failure supports the concept that an altered reflex system, such as the baroreflexes, with nonuniform effects on muscle and skin sympathetic nerve activity, underlies sympatho-excitation in heart failure.
Appropriate sensing of ventricular fibrillation after failed shocks in a transvenous cardioverter-defibrillator system.
Authors: Ellis J R , Martin D T , Venditti F J 
Published: June 2012

BACKGROUND
Reduction in R-wave amplitude immediately after defibrillation shocks in an integrated shock/sense transvenous cardioverter-defibrillator (TCD) lead system has prompted concerns regarding adequate sensing after failed shocks. We therefore studied redetection characteristics for ventricular fibrillation after unsuccessful defibrillation shocks in a TCD system to determine if these observations have clinical relevance.

METHODS AND RESULTS
Fifty patients with this shock/sense TCD lead system underwent conversion testing of their TCD at several time intervals. There were a total of 142 failed shocks events recorded, including 10, 15, 70, and 47 events at implantation, predischarge, and 2- and 6-month testing, respectively. Initial detection time (IDT) and redetection time (RDT) for ventricular fibrillation were measured from event markers for all unsuccessful defibrillation shocks. To assess the effect of failed shocks on electrogram quality, 54 failed shock episodes were evaluated in 37 of the 50 patients by measuring electrograms during VF before and after shock. Mean RDT for the entire group was 5.3 +/- 3.5 seconds compared with an IDT of 4.5 +/- 3.3 seconds (P = NS). There were no significant differences between IDT and RDT at implantation or any follow-up testing period, despite a significant decline in R-wave amplitude from 8.1 +/- 3.5 to 6.8 +/- 2.8 mV (P < .0001) measured 3 to 6 seconds after shock delivery. Analysis of 8 individuals with any extended RDT (> or = 10 seconds) showed no significant differences in clinical or implantation characteristics when compared with 42 individuals without extended RDT.

CONCLUSIONS
In this integrated shock/sense TCD lead system, unsuccessful shock delivery has no significant effect on redetection of ventricular fibrillation at device implantation or up to 6 months of follow-up, despite an observed reduction in postshock R-wave amplitude. Therefore, the reported reduction in electrogram quality after a shock is of no practical importance because sensing of ventricular fibrillation does not appear to be compromised in this particular TCD system. Whether this applies to other implantable cardioverter-defibrillator pulse generators and lead systems with different sensing characteristics requires further evaluation.
Effect of capacitor size and pathway resistance on defibrillation threshold for implantable defibrillators.
Authors: Swerdlow C D , Kass R M , Chen P S , Hwang C , Raissi S 
Published: June 2012

BACKGROUND
The time constant of truncated exponential pulses used with implantable defibrillators is determined by the output capacitor size and defibrillation pathway resistance. The optimal capacitor size is unknown.

METHODS AND RESULTS
This study compared defibrillation threshold (DFT) for standard 120-microF capacitors (DFT120) and smaller 60-microF capacitors (DFT60) at implantation of cardioverter-defibrillators in 67 patients using epicardial electrodes (15 patients) or one of four transvenous electrode configurations (52 patients). Paired comparisons of DFT60 and DFT120 were made for 44 defibrillation pathways using monophasic pulses and for 53 pathways using biphasic pulses. Truncated exponential pulses with 65% tilt were used. Pooled data from all electrode configurations showed a significant inverse correlation between pathway resistance and the ratio of stored energy DFT60 to DFT120 (monophasic pulses: r = .75, P = .0001; biphasic pulses: r = .68, P = .0001). Data from all electrode configurations formed a continuum with 120-microF capacitors superior for low-resistance pathways and 60-microF capacitors superior for high-resistance pathways. For pathways with resistance < or = 40 omega, the modest advantage of 120-microF capacitors applied primarily to pathways with low DFTs: 8.2 +/- 6.1 versus 9.6 +/- 5.4 J (P = .001) for monophasic pulses and 4.1 +/- 2.8 versus 5.1 +/- 3.1 J (P < .02) for biphasic pulses. The greater advantage of 60-microF capacitors for pathways with resistance > or = 61 omega applied to pathways with higher DFTs: 12.4 +/- 4.3 versus 23.1 +/- 6.4 J (P = .0001) for monophasic pulses and 8.5 +/- 4.9 versus 12.5 +/- 6.4 J (P = .0001) for biphasic pulses. For pathways using monophasic 120-microF pulses versus 95% for 60-microF pulses. Similarly, the DFT was < or = 10 J for 48% of pathways using biphasic 120-microF capacitors versus 83% for 60-microF pulses.

CONCLUSIONS
In comparison with conventional 120-microF capacitors, 60-microF capacitors had clinically insignificant higher DFTs for low-resistance pathways and clinically important lower DFTs for high-resistance pathways. Optimal capacitance is inversely related to pathway resistance for clinical defibrillation pathways and waveforms.