bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered left ventricular chamber stiffness and isovolumic relaxation in dogs with chronic pulmonary hypertension caused by emphysema.
Authors: Gomez A , Unruh H , Mink S N 
Published: June 2012

BACKGROUND
In chronic obstructive lung disease, a right to left ventricular septal shift that occurs as a consequence of right ventricular pressure overload is the usual mechanism given to explain a decrease in left ventricular (LV) diastolic performance. The purpose of the present study was to examine the extent to which this mechanism could account for a decrease in LV diastolic function in a canine model in which pulmonary artery pressure was elevated to a level found in human disease.

METHODS AND RESULTS
Severe emphysema was produced in dogs by repeated instillations of the enzyme papain into the lung. To assess LV diastolic function, we used sonomicrometry, in which three pairs of subendocardial crystal transducers were implanted along the three orthogonal axes of the LV. LV end-diastolic dimensions and pressure-strain relations along the three axes, as well as the time constant of LV isovolumic relaxation (T), were measured before (baseline) and after 1 year of emphysema (post-1-year study). The results showed that after 1 year of pulmonary hypertension, LV pressure-strain relations were decreased along the septal-lateral and anterior-posterior axes, but a right to left ventricular septal shift was not detected. The relation of average midwall circumferential stress to midwall circumferential strain was used to describe the intrinsic compliance of the LV. The results showed that myocardial stiffness increased in emphysema but that chamber volume was not reduced. At the post-1-year study, T was abnormally increased in the emphysema group in response to augmented preload and afterload compared with preemphysema measurements.

CONCLUSIONS
We conclude that mechanisms other than ventricular interdependence may be operative in leading to altered LV diastolic filling in chronic emphysema.
Interstitial dendritic cells of the rat heart. Quantitative and ultrastructural changes in experimental myocardial infarction.
Authors: Zhang J , Yu Z X , Fujita S , Yamaguchi M L , Ferrans V J 
Published: June 2012

BACKGROUND
This study was undertaken to investigate the qualitative and quantitative changes that interstitial dendritic cells (IDC) of the heart undergo during the time course of experimental myocardial infarction.

METHODS AND RESULTS
Left coronary arterial ligations were performed in 43 rats that were killed 2, 4, 7, 14, and 21 days after surgery. Thirteen unoperated and 39 sham-operated rats were used as controls. Frozen sections were stained with monoclonal antibodies (OX 6 and W3/25) to identify and count IDC by light microscopy. Immunoelectron microscopy was also used to identify IDC. The number of IDC per mm2 of tissue section was calculated for all hearts. In hearts with myocardial infarction, IDC were counted in three areas: the center of the myocardial infarction, the border zone, and the noninfarcted left ventricle. In OX 6 antibody-stained preparations, the number of IDC per mm2 was 82 +/- 10 in the left ventricle of unoperated rats. Hearts with myocardial infarction showed marked increases in the numbers of IDC per mm2 in the border zone (796 +/- 79 at 7 days and 528 +/- 98 at 14 days). In the border zone, IDC often were associated with small clusters of T-helper lymphocytes, which reacted with W3/25 antibody (the rat homologue of human CD4). The center of the myocardial infarction showed an increase in IDC only on day 7 (120 +/- 18). By 21 days, IDC in the border zone were only slightly increased (159 +/- 15).

CONCLUSIONS
These findings suggest that IDC migrate to the myocardial infarction border zone. They participate in the activation of lymphocytes and in the initiation of immune responses and decrease in number as inflammation subsides and scarring develops.
Frequency domain measures of heart rate variability before the onset of nonsustained and sustained ventricular tachycardia in patients with coronary artery disease.
Authors: Huikuri H V , Valkama J O , Airaksinen K E , Seppänen T , Kessler K M , Takkunen J T , Myerburg R J 
Published: June 2012

BACKGROUND
Low heart rate variability (HRV) is associated with an increased risk of arrhythmic death and ventricular tachycardia (VT). The purpose of this study was to examine whether there is a temporal relation between changes in HRV and the onset of spontaneous episodes of VT in patients at high risk of life-threatening arrhythmias.

METHODS AND RESULTS
Components of HRV in the frequency domain were analyzed before the onset of 28 episodes of nonsustained VT (more than four impulses; duration < 30 seconds) and 12 episodes of sustained VT (> 30 seconds or requiring defibrillation) in 18 patients with coronary artery disease. Seven patients had survived cardiac arrest not associated with acute myocardial infarction, and 11 had a history of sustained VT. All frequency domain measures of HRV, i.e., total power (p < 0.001), high-frequency power (p < 0.05), low-frequency power (p < 0.01), very-low-frequency power (p < 0.01), and ultralow-frequency power (p < 0.05), were significantly lower before the onset of sustained VT than before nonsustained VT. Total power of HRV was also lower during the 1-hour period before the onset of sustained VT than the average 24-hour HRV (p < 0.05). An indirect correlation existed between the length of VT and the total power of HRV analyzed during the 15 minutes before the onset of VT (r = 0.54, p < 0.01). HRV had a trend toward increasing values before the onset of nonsustained VT (p < 0.01) but not before the sustained VT episodes. The ratio between low-frequency and high-frequency powers increased substantially before both nonsustained and sustained VT episodes (p = 0.06 and p = 0.05, respectively). The rate of VT or the coupling interval initiating the VT did not differ significantly between the nonsustained and sustained VT.

CONCLUSIONS
Spontaneous episodes of VT are preceded by changes in HRV in the frequency domain. Divergent dynamics of HRV before the onset of nonsustained and sustained VT episodes may reflect differences in factors that can facilitate the perpetuation of these arrhythmias.
Functional dissociation of cellular activation as a mechanism of Mobitz type II atrioventricular block.
Authors: Gonzalez M D , Scherlag B J , Mabo P , Lazzara R 
Published: June 2012

BACKGROUND
Several mechanisms have been advanced to explain Mobitz type II atrioventricular block in the ischemically damaged His-Purkinje system. Only recently, however, has an animal model been developed to study this form of conduction defect in vivo and in vitro.

METHODS AND RESULTS
Conduction defects were induced in anesthetized dogs by ischemic damage to the proximal His-Purkinje system after anterior septal artery ligation. Stable 2:1 atrioventricular block, localized within the His bundle or in the proximal bundle branches, was obtained in each dog by atrial pacing at an average rate of 239 +/- 20 beats per minute (n = 12). In vitro studies were then performed from the same hearts. Action potentials and electrograms were simultaneously recorded from the His bundle and the proximal right bundle branch at the site of damage. At slow rates of pacing (40-60 beats per minute), the action potential amplitude was 85 +/- 4 mV, and some cells (10 +/- 3%) showed dissociation from the electrical activity in the bundle. At fast rates (149 +/- 11 beats per minute), during 1:1 conduction, the frequency of cellular dissociation increased to 57 +/- 6% (p < 0.001), and the action potential amplitude decreased (-31 +/- 4%, p < 0.001). The frequency of dissociation closely correlated with the reduction in action potential amplitude (r = 0.87, p < 0.001). These changes were markedly attenuated once 2:1 block developed. The site of block was not constant but rather showed a dynamic behavior with spatial shifting in response to changes in pacing rate or the introduction of extrastimuli.

CONCLUSIONS
These results indicate that in the ischemically damaged proximal His-Purkinje system, an increase in rate leads to reduced and asynchronous cellular activation before 2:1 block. The latter provides a more stable activation pattern, because the frequency of dissociation is markedly reduced.
Circus movement atrial flutter in the canine sterile pericarditis model. Cryothermal termination from the epicardial site of the slow zone of the reentrant circuit.
Authors: Isber N , Restivo M , Gough W B , Yang H , el-Sherif N 
Published: June 2012

BACKGROUND
We have shown that atrial flutter (AF) in dogs with sterile pericarditis is commonly due to a single-loop reentrant circuit in the lower right atrium comprised of a functional or functional/anatomic obstacle and a slow zone of conduction (SZ) between the central obstacle and the atrioventricular (AV) ring. The goals of the present study were 1) to establish that the epicardial SZ is the critical component of circus movement AF and 2) to identify the optimal site within the epicardial SZ at which interruption of circus movement can be accomplished by ablative techniques.

METHODS AND RESULTS
We analyzed the atrial activation patterns during epicardial cooling of the SZ with as N2O-cooled probe in eight dogs (five with clockwise [CW] reentrant circuit, one with counterclockwise [CCW] reentrant circuit, and two with both CW and CCW reentrant circuits around the same pathway). In all eight dogs, cooling (-5 to +5 degrees C for 5-20 seconds) the narrow isthmus at the inferoposterior part of the SZ between the central obstacle and the AV ring reversibly terminated the reentrant circuit, whereas cooling outside this area failed to terminate the reentrant circuit. The circus movement was not observed to continue along alternate pathways when conduction in this critical zone was interrupted. Both CW and CCW reentrant circuits could be terminated from the same site within the SZ. Cooling resulted in slowing of conduction in the SZ (55 +/- 15 msec) in both CW and CCW reentrant circuits. Cooling-induced termination of CW reentrant circuits was characteristically associated with oscillations of conduction in the cooled zone of the last three cycles before termination and conduction block occurred within the cooled zone. The last "manifest" reentrant cycle was associated with the longest conduction delay in the cooled zone. However, this delay was not necessarily reflected in the length of the last reentrant cycle because of compensatory acceleration of conduction in the rest of the pathway. On the other hand, in CCW reentrant circuits, conduction block occurred abruptly at the distal border of the SZ and without significant oscillations of conduction.

CONCLUSIONS
The present study provides convincing evidence that single-loop circus movement in this model is critically dependent on an obligatory conduction in a SZ in the inferoposterior portion of the free right atrial wall between a functional obstacle and the AV ring. Because the atrial myocardium behaves electrophysiologically as a two-dimensional surface, the results of this study may help to guide the endocardial electrode catheter ablative technique for treatment of clinical AF.
Congestive heart failure alters receptor-dependent cAMP-mediated relaxation of canine pulmonary arteries.
Authors: Mathew R , Wang J , Gewitz M H , Hintze T H , Wolin M S 
Published: June 2012

BACKGROUND
Alterations in myocardial function and systemic vascular tone are well documented in congestive heart failure (CHF), but little information is available on the effects of CHF on pulmonary vessels. We examined the mechanisms of tone regulation of canine pulmonary arteries during pacing-induced CHF.

METHODS AND RESULTS
Rings 3-4 mm wide from lobar pulmonary arteries were prepared from normal dogs, dogs paced at 210 beats per minute for 3 weeks (paced group, nonfailure), and dogs also paced at 240 beats per minute during the fourth week to induce severe heart failure (CHF group). Contractile responses to 60 mmol/L KCl and phenylephrine and relaxation responses to acetylcholine, bradykinin (endothelium-dependent cyclic GMP [cGMP]-mediated), isoproterenol, arachidonic acid, prostacyclin (receptor-dependent cyclic AMP [cAMP]-mediated), forskolin (direct stimulator of adenylate cyclase), a forskolin analogue (devoid of adenylate cyclase-dependent activity), and RO 20-1724 (phosphodiesterase inhibitor) were characterized. The paced group did not show alterations in vascular reactivity. Contractile response to phenylephrine and cGMP-mediated relaxation responses were not altered in the CHF group; however, receptor-mediated cAMP-induced relaxation responses were significantly inhibited (p < 0.05). Relaxation responses to isoproterenol (10(-6) mol/L), arachidonic acid (10(-5) mol/L), and prostacyclin (10(-5) mol/L) were reduced by 56%, 72%, and 74%, respectively. The relaxation response to RO 20-1724 was not affected by CHF, and this probe did not enhance the impaired relaxation response to isoproterenol. Forskolin-induced relaxation was not altered, and the forskolin analogue produced minimal relaxation compared with forskolin.

CONCLUSIONS
These findings suggest that in pacing-induced CHF, canine pulmonary arteries show a selective defect in receptor coupling to cAMP-dependent relaxation mechanisms. There is no evidence of enhanced degradation of cAMP.
Coronary thrombolysis with recombinant staphylokinase in patients with evolving myocardial infarction.
Authors: Collen D , Van de Werf F 
Published: June 2012

BACKGROUND
Staphylokinase (STA), a protein with known profibrinolytic properties, is produced by transduced Staphylococcus aureus strains. In experimental animal models, recombinant staphylokinase (STAR) is less immunogenic and more active toward platelet-rich arterial blood clots than streptokinase.

METHODS AND RESULTS
In the present study, 10 mg STAR given intravenously over 30 minutes was found to induce angiographically documented coronary artery recanalization within 40 minutes in four of five patients with acute myocardial infarction. Plasma fibrinogen and alpha 2-antiplasmin levels were unaffected, and allergic reactions were not observed. Postinfusion disappearance of STAR antigen followed a biphasic mode with a t1/2 alpha of 6.3 +/- 0.6 minutes (mean +/- SD) and a t1/2 beta of 37 +/- 15 minutes, corresponding to a plasma clearance of 270 +/- 100 mL/min. Neutralizing antibodies against STAR could not be demonstrated at baseline and up to 6 days after infusion, but STAR neutralizing activity, which did not cross-react with streptokinase, was consistently demonstrable in plasma at 14-35 days.

CONCLUSIONS
STAR can induce clot-selective coronary thrombolysis in patients with evolving myocardial infarction without concomitant induction of a systemic lytic state. STAR, a small protein that can be easily produced by recombinant DNA technology, may therefore offer promise for thrombolytic therapy in patients with thromboembolic disease.
Characterization of ventricular fibrillation based on monophasic action potential morphology in the human heart.
Authors: Swartz J F , Jones J L , Fletcher R D 
Published: June 2012

BACKGROUND
Recent studies examining mechanisms of defibrillation have focused on prolongation of graded cellular response duration during refractory period stimulation. This mechanism assumes that defibrillation shocks interact with ventricular cells during the process of repolarization.

METHODS AND RESULTS
To test this assumption, we examined monophasic action potentials (MAPs) from 171 episodes of induced ventricular dysrhythmia associated with loss of systemic perfusion pressure in 22 patients undergoing nonthoracotomy defibrillator implantation. Ventricular fibrillation (VF)/polymorphic ventricular tachycardia (PVT), defined by an irregular limb lead I morphology, was present in 156 dysrhythmia episodes. Monomorphic ventricular tachycardia (VT), present in the remaining 15 episodes, was associated with regular limb lead morphology. All episodes were examined for MAP cycle length, variation, fractionation, and repolarization. VF/PVT cycle length was 215 +/- 28 msec, with a 14 +/- 7% (33 +/- 20-msec) cycle length variability. Nonfractionated MAP recordings were found in 122 of 156 VF/PVT episodes. Episodes characterized as VF by ECG criteria (n = 136) showed lack of MAP diastole and had a mean cycle length of 213 +/- 27 msec. Episodes characterized as PVT (n = 20) were associated with amiodarone therapy and had occasional MAP diastole and a significantly longer mean cycle length of 257 +/- 22 msec (p < 0.001). Monomorphic VT had a mean cycle length of 261 +/- 29 msec, minimal cycle length variation (1 +/- 3%), absence of MAP fractionation, and consistent degree of repolarization before restimulation.

CONCLUSIONS
These results suggest that human VF cycle length is limited by cellular refractory periods so that defibrillating shocks interact with cells primarily during their refractory period.
A communitywide perspective of sex differences and temporal trends in the incidence and survival rates after acute myocardial infarction and out-of-hospital deaths caused by coronary heart disease.
Authors: Goldberg R J , Gorak E J , Yarzebski J , Hosmer D W , Dalen P , Gore J M , Alpert J S , Dalen J E 
Published: June 2012

BACKGROUND
The purpose of the study was to examine overall differences and temporal trends therein between men and women regarding the incidence rates, in-hospital and long-term survival after initial acute myocardial infarction (AMI), and out-of-hospital deaths caused by coronary disease.

METHODS AND RESULTS
This nonconcurrent prospective study was carried out in 16 teaching and community hospitals in Worcester, Mass., in six time periods between 1975 and 1988. A total of 3,148 patients hospitalized with validated initial AMI comprised the study sample. The age-adjusted incidence rates of initial AMI increased between 1975 and 1981 in the two sexes, with a marked decrease thereafter; these rates declined by 26% in men and by 22% in women between 1975 and 1988. The overall unadjusted in-hospital case-fatality rates after initial AMI were significantly higher in women (21.7%) than in men (12.7%). Age- and multivariable-adjusted in-hospital case-fatality rates, however, were not significantly different for men compared with women (multivariate-adjusted OR, 0.90; 95% CI, 0.70, 1.16). No clear trends in in-hospital case-fatality rates were observed in men or women over the periods under study. There were no significant sex differences in the age-adjusted long-term survival rates of discharged hospital survivors of AMI. The multivariate-adjusted risk of total mortality among discharged hospital survivors, however, was significantly increased in men (multivariate-adjusted OR, 1.20; 95% CI, 1.03, 1.39); neither of the sexes experienced an improvement over time in long-term prognosis. The incidence rates of out-of-hospital deaths caused by coronary disease declined by 60% in men and 69% in women between 1975 and 1988.

CONCLUSIONS
The results of this multihospital, community-based study suggest declines in the incidence rates of AMI and out-of-hospital deaths caused by coronary disease in men and women over the period under study (1975-1988). No significant sex differences in in-hospital survival were observed, whereas a poorer long-term survival experience after hospital discharge was observed for men compared with women after controlling for potentially confounding prognostic factors.
Effect of disrupting the mitral apparatus on left ventricular function in dogs.
Authors: Shintani H , Glantz S A 
Published: June 2012

BACKGROUND
The importance of the mitral apparatus to left ventricular function has been suggested in clinical studies. The effect of disruption of the mitral apparatus on left ventricular diastolic and systolic properties has not been fully documented.

METHODS AND RESULTS
We investigated the end-diastolic and end-systolic pressure-volume and stroke work-end-diastolic volume relations and measured the isovolumic relaxation time constant (tau infinity) during nonfilling beats before and after disruption of the mitral apparatus under different loading conditions in 14 dogs using our recently developed volume-clamping technique for the in situ left ventricle. Disruption of the mitral apparatus increased left ventricular diastolic equilibrium volume (V0d) without changing the slope of the end-diastolic pressure-volume relation (Sd) and increased end-systolic pressure-volume relation dead volume (V0s) and volume-axis intercept of stroke work-end-diastolic volume relation (V0sw) without changing the slopes of these relations (maximum elastance, Ees, and Ssw). Disruption of the mitral apparatus increased tau infinity.

CONCLUSION
Disruption of the mitral apparatus increases the equilibrium volume without changing left ventricular diastolic stiffness or contractility and slows left ventricular relaxation. These results support and help explain the clinical observation that it is desirable to maintain the mitral apparatus during mitral valve replacement surgery.
Transdermal modification of platelet function. A dermal aspirin preparation selectively inhibits platelet cyclooxygenase and preserves prostacyclin biosynthesis.
Authors: Keimowitz R M , Pulvermacher G , Mayo G , Fitzgerald D J 
Published: June 2012

BACKGROUND
Even low doses of oral aspirin inhibit prostacyclin (prostaglandin [PG] I2) formation and cause gastrointestinal toxicity. We examined the skin as a novel route for continuous low-dose aspirin administration and selective inhibition of platelet cyclooxygenase in humans.

METHODS AND RESULTS
Aspirin 250 or 750 mg/d for 10 days induced a dose-dependent inhibition of serum thromboxane (TX) B2. At the highest dose, five of six subjects responded, with a mean reduction in serum TXB2 of 95 +/- 3% (P = .003). Urinary 2,3-dinor TXB2, an index of in vivo TXA2 formation, decreased by 68 +/- 7% and recovered slowly, consistent with inhibition of platelet cyclooxygenase in vivo. In contrast, PGI2 biosynthesis, determined as excretion of 2,3-dinor-6-keto PGF1 alpha, was 81 +/- 5% of baseline at 10 days. Intravenous bradykinin increased PGI2 biosynthesis 5.1 +/- 1.6-fold (n = 4) before aspirin treatment. Oral aspirin 75 mg/d for 14 days abolished bradykinin-induced PGI2 formation, whereas dermal aspirin 750 mg/d had no effect despite similar inhibition of TXA2 biosynthesis. In five subjects, plasma aspirin and salicylate were determined after a single application of 750 mg. Aspirin was absorbed slowly, with peak levels of 0.24 +/- 0.11 micrograms/mL at 3 hours. Salicylate levels peaked at 6 to 12 hours, with plasma levels of 0.79 +/- 0.14 micrograms/mL.

CONCLUSIONS
Thus, it is possible to achieve selective inhibition of platelet cyclooxygenase by aspirin applied to the skin. This approach may be applicable to other antiplatelet agents and be useful in patients at risk for gastrointestinal bleeding or toxicity.