bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-Induced Heat-Shock Preconditioning Improves Postischemic Ventricular Recovery After Cardiopulmonary Bypass
Authors: Maulik Nilanjana , Engelman Richard M. , Wei Zongjie , Liu Xuekun , Rousou John A. , Flack Joseph E. , Deaton David W. , Das Dipak K.
Published: June 2012

Background
Heat-stress preconditioning of mammalian heart has been found to confer protection against ischemic reperfusion injury. Heat shock is generally provided by warming the animal by mechanical means, which is often impractical in a clinical setting. Amphetamine, a sympathomimetic drug, can elevate the body temperature as a result of enhanced endogenous lipolysis. In this study, we examined the effects of heat shock induced by amphetamine on postischemic myocardial recovery in a setting of coronary revascularization for acute myocardial infarction.

Methods and Results
Adult Yorkshire swine were injected with amphetamine (3 mg/kg IM) (n=12), and body temperature was continuously monitored. For control studies, the pigs were injected with saline (n=12). Five swine in each group were killed after 3 hours to obtain biopsies of vital organs to measure heat-shock protein (HSP) mRNAs. After 40 hours, the remaining 7 pigs in each group were placed on cardiopulmonary bypass, and the isolated, in situ heart preparations were subjected to 1 hour of occlusion of the left anterior descending coronary artery followed by 1 hour of global hypothermic cardioplegic arrest and 1 hour of reperfusion. Postischemic myocardial performance was monitored by measuring left ventricular (LV) pressure, its dP/dt, myocardial segment shortening, and coronary blood flow. Cellular injury was examined by measurement of creatine kinase release. The antioxidant enzymes superoxide dismutase and catalase were also assayed. Amphetamine treatment was associated with the induction of mRNAs for HSP 27, HSP 70, and HSP 89 in all the vital organs, including heart, lung, liver, kidney, and brain. Amphetamine also enhanced superoxide dismutase and catalase activities in the heart. Significantly greater recovery of LV contractile functions was noticed, as demonstrated by improved recovery of LV developed pressure (61% versus 52%), LV dP/dt
max
(52% versus 44%), and segment shortening (46.2% versus 10%) and reduced creatine kinase release in the amphetamine group.

Conclusions
The results demonstrate that amphetamine can induce whole-body heat shock that can precondition the heart, enhancing cellular tolerance to ischemia-reperfusion injury. Amphetamine is a sympathomimetic drug that may be used for preconditioning.
Improved Protection of the Hypertrophied Left Ventricle by Histidine-Containing Cardioplegia
Authors: Takeuchi Koh , Buenaventura Percival , Cao-Danh Hung , Glynn Paul , Simplaceanu Elena , McGowan Francis X. , del Nido Pedro J.
Published: June 2012

Background
Myocardial hypertrophy has been shown to lead to increased susceptibility to ischemia with accelerated loss of high-energy nucleotides, greater accumulation of H
+
and lactate, and earlier onset of contracture.

Methods and Results
To determine whether promoting anaerobic glycolysis during ischemia by buffering H
+
results in improved preservation of the hypertrophied heart, we studied the effect of a histidine-containing solution (HBS) on recovery of contractile function and energetic state. Hypertrophied rabbit hearts (aortic banding at 10 days) were subjected to 40 minutes of 37°C ischemia and reperfusion in an isolated Langendorff model. This group was compared with groups receiving St Thomas solution and high-potassium Krebs buffer solution (KCl). Although both phosphocreatine (PCr) and ATP were lower in hypertrophied hearts by end-ischemia compared with nonhypertrophied age-matched controls, there was significantly higher PCr, ATP, and intracellular pH in the HBS group compared with the St Thomas and KCl groups. Recovery of left ventricular developed pressure was best in the HBS group (91% of preischemic values) as was end-diastolic pressure after 30 minutes of reperfusion. Lactate production was also significantly greater in the HBS group, suggesting augmentation of anaerobic glycolysis.

Conclusions
We concluded that administration of histidine-containing cardioplegia promotes anaerobic glycolysis and improves recovery of high-energy phosphates and contractile function in hypertrophied myocardium.
Ischemia-Induced Interleukin-8 Release After Human Heart Transplantation
Authors: Oz Mehmet C. , Liao Hui , Naka Yoshifuma , Seldomridge Alex , Becker David N. , Michler Robert E. , Smith Craig R. , Rose Eric A. , Stern David M. , Pinsky David J.
Published: June 2012

Background
Interleukin-8 (IL-8) secreted from endothelial cells is a powerful neutrophil chemoattractant and activator. We hypothesized that human endothelial cells deprived of oxygen would secrete IL-8, which might translate into elevated IL-8 production after cardiac ischemia. Furthermore, we hypothesized that coronary sinus (CS) IL-8 levels would be particularly high after cardiac preservation for transplantation, due to extended ischemic times.

Methods and Results
Human saphenous vein endothelial cells exposed to a hypoxic environment (P
o
2
<20 mm Hg) demonstrated a time-dependent release of IL-8 (measured by ELISA) into the culture supernatant as early as 4 hours after exposure. To determine whether cardiac preservation in humans was associated with IL-8 production, we obtained CS blood samples 5 minutes after reperfusion in a consecutive series of patients after they underwent cardiac transplantation (CTX, n=20) or elective cardiac surgery (non-CTX, n=21). CTX patients demonstrated significantly higher CS IL-8 levels than non-CTX patients (325±123 versus 50±17 ng/mL, respectively,
P
<.05). Further analysis of the CS samples revealed that a biochemical marker of myocyte injury (myoglobin) was similarly elevated in the CTX patients compared with the non-CTX patients (3340±625 versus 1151±525 ng/mL, respectively,
P
<.05).

Conclusions
These differences may reflect the longer ischemic times of CTX compared with non-CTX hearts (161±10 versus 80±6 minutes,
P
<.0001) and suggest that the neutrophil chemoattractant/activator IL-8 may contribute to myocyte injury after prolonged hypothermic cardiac ischemia, as occurs during human cardiac transplantation.
Optimal Timing of Coronary Artery Bypass Graft Surgery After Acute Myocardial Infarction
Authors: Braxton John H. , Hammond Graeme L. , Letsou George V. , Franco Kenneth L. , Kopf Gary S. , Elefteriades John A. , Baldwin John C.
Published: June 2012

Background
To assess optimal timing for coronary artery bypass graft surgery (CABG) after an acute myocardial infarction (AMI), all patients undergoing CABG without associated procedures at our institution from January 1, 1991, to July 30, 1992, were reviewed. Patients were divided into three groups based on time from infarct to revascularization. The control group consisted of patients operated on for angina refractory to medical management. Relative risks (incident infarction group divided by incident control group) were established for need of vasopressors, new balloon to separate from bypass, perioperative myocardial infarction, and hospital mortality.

Methods and Results
One hundred sixteen patients underwent CABG within 6 weeks of infarction. In the experimental group, 58 patients underwent CABG for non–Q-wave infarction, and 58 patients underwent CABG for Q-wave infarction. In the control group, 255 patients underwent surgery for angina without infarction. Patients were analyzed by group relative to the time between infarction and CABG. Patients were analyzed between infarction and CABG and assigned to one of three groups. Group 1 patients were revascularized within 48 hours; group 2, between 3 and 5 days; and group 3, after 5 days. Significance was determined by Fisher’s exact or Mantel-Haenszel χ
2
test where appropriate. Multivariate analysis was performed on statistics that were significant. All patients within all groups after Q-wave or non–Q-wave myocardial infarction had a significantly higher risk of needing an intra-aortic balloon pump and vasopressors to be weaned from bypass and a greater incidence of perioperative MI compared with control patients. Surgical mortality is highest immediately after Q-wave infarctions.

Conclusions
Patients with non–Q-wave infarction may undergo CABG relatively safely at any time. Acceptable timing for CABG after Q-wave infarction is after 48 hours.
Results of Revascularization in Patients With Severe Left Ventricular Dysfunction
Authors: Mickleborough Lynda L. , Maruyama Hiroshi , Takagi Yasushi , Mohamed Shanas , Sun Zhao , Ebisuzaki Lawrence
Published: June 2012

Background
In patients with coronary artery disease and poor ventricular function (ejection fraction, <20%), bypass grafting remains a surgical challenge. This study evaluates experience with isolated revascularization in such patients.

Methods and Results
In 79 consecutive patients (69 men, 10 women; average age, 59±9 years), preoperative ejection fraction was 18±5%. Indications for surgery were congestive heart failure (CHF) in 5 of 79 patients (6%), CHF and angina in 19 (24%), angina in 41 (52%), ventricular arrhythmias (VAs) in 8 (10%), and critical anatomy in 6 (8%). Some patients had prior VAs (23 of 79; 29%) or mitral regurgitation (18; 23%) and required emergent surgery (25; 32%). At surgery, temperature mapping ensured adequate distribution of antegrade cold cardioplegia, with 3.6±0.7 grafts per patient, including left internal mammary artery graft in 60 of 79 (76%) and endarterectomy in 14 (18%). Hospital mortality was 3.8%. Perioperative support included intra-aortic balloon pump in 18 of 79 (23%) and drugs for VAs in 28 (35%). Morbidity included myocardial infarction in 2 of 79 (2.5%) and stroke in 2 (2.5%). During follow-up, there were 19 late deaths. Actuarial survival was 94%, 82%, and 68% at 1, 2, and 5 years, respectively, and was similar in patients with severe angina, CHF, mitral regurgitation, or VAs. Freedom from sudden death was 100%, 98%, and 91% at 1, 2, and 5 years, respectively. Among survivors, angina improved in 84% and heart failure improved in 26%.

Conclusions
These data support bypass graft surgery in patients with severe LV dysfunction. With careful cardioplegic techniques, hospital mortality was low (3.8%). Long-term survival is encouraging, with good relief of symptoms in most patients. Perioperative VAs are frequent but respond to medical treatment, with only 23% of patients discharged on antiarrhythmic drugs. Five-year freedom from sudden death is 91%, with only 3 late sudden deaths in this series.
Is Sex a Factor in Determining Operative Risk for Aortocoronary Bypass Graft Surgery?
Authors: Mickleborough Lynda L. , Takagi Yasushi , Maruyama Hiroshi , Sun Zhao , Mohamed Shanas
Published: June 2012

Background
This study examines trends and sex differences in characteristics of patients referred for bypass graft surgery to identify factors associated with operative morbidity and mortality.

Methods and Results
Data were collected prospectively on consecutive patients (1132 men and 355 women). Over time, the proportion of patients >65 years old, with diabetes, or requiring urgent surgery, increased. Predictors of mortality were age >75 years, urgent surgery, and poor left ventricular (LV) grade. Women were older (62±9 versus 59±9 years,
P
<.001) and had more varicose veins (18% versus 7%,
P
<.001), diabetes (27% versus 18%,
P
<.001), hypertension (48% versus 41%,
P
<.05), peripheral vascular disease (16% versus 12%,
P
<.05), and more severe angina (
P
<.001). There were no sex differences in prior myocardial infarction (59% versus 62%) or need for urgent surgery (17% versus 18%). Women had a higher ejection fraction (51%±12% versus 47%±14%,
P
<.001) and fewer diseased vessels (2.4±0.7 versus 2.6±0.6,
P
<.001) and received fewer grafts (2.9±0.9 versus 3.3±0.8,
P
<.001). Women had smaller body size but were no more likely to have small target vessels (<1.5 mm). There was no sex difference in operative mortality (1.4% versus 1.1%), perioperative myocardial infarction (4.8% versus 3.5%), need for intra-aortic balloon pump (10% versus 8%), stroke (1.7% versus 1.4%), reexploration for bleeding (1.7% versus 1.7%), or leg infection (2.0% versus 1.4%). Women had fewer sternal wound infections (0.6% versus 2.2%,
P
<.05).

Conclusions
Predictors of mortality include advanced age, decreased LV function, and need for urgent surgery. With time, despite increasing age, associated diabetes, and increased urgent surgery, operative mortality has decreased. Women were older and had more diabetes and hypertension but less extensive disease and better LV function. Bypass graft surgery was associated with equally low mortality in women and men (1.4% versus 1.1%). Concern over increased operative mortality in women should not bias referral patterns for angiography and coronary bypass graft surgery.
Endoventricular Remodeling of Left Ventricular Aneurysm
Authors: Grossi Eugene A. , Chinitz Larry A. , Galloway Aubrey C. , Delianides Julie , Schwartz Daniel S. , McLoughlin David E. , Keller Norma , Kronzon Itzhak , Spencer Frank C. , Colvin Stephen B.
Published: June 2012

Background
Recent advances in surgical techniques for the repair of left ventricular aneurysms (LVAs) include the use of an endoventricular patch to exclude the aneurysm cavity. This technique has replaced conventional linear plication of the aneurysm. The endoventricular patch technique remodels the left ventricular cavity to a more physiological geometry that improves function.

Methods and Results
From December 1989 through November 1993, 45 patients underwent an LVA repair with an endoventricular patch. This procedure was performed in association with coronary artery bypass grafting in 40 patients. Twenty-eight patients (62.2%) also had nonguided encircling subendocardial incisions. Operative procedures included 7 emergency operations, 3 concomitant valve procedures, and a mean of 2.2 bypass grafts per patient. Eight patients had previous cardiac operations. Hospital mortality was 15.6% (7/45) for all patients and 9.1% (3/33) for nonemergent revascularization and LVA repairs. Ejection fraction improved from a mean of 25.8% preoperatively to 37.8% postoperatively; the mean New York Heart Association classification improved from 3.5 to 1.5. Of patients known to have preoperative arrhythmias (inducible or sudden death), 69% were not inducible postoperatively without antiarrhythmic medication. Survival from late cardiac death (including death of unknown origin) was 86.5% at 2 years. Freedom from documented ventricular arrhythmias was 94.3% at 2 years.

Conclusions
These results indicate that the patch endoaneurysmorrhaphy technique can provide an excellent functional and physiological outcome in patients with LVAs and severely impaired ventricular function.
Relation Between Symptom Duration Before Thrombolytic Therapy and Final Myocardial Infarct Size
Authors: Raitt Merritt H. , Maynard Charles , Wagner Galen S. , Cerqueira Manuel D. , Selvester Ron H. , Weaver W. Douglas
Published: June 2012

Background
Myocardial salvage is most likely to occur when thrombolytic therapy is administered within 4 to 6 hours of the onset of symptoms of myocardial infarction. The impact of delays within this early time period on final myocardial infarct size are unknown. The purpose of this study was to quantitate the relation between final myocardial infarct size and duration of symptoms before initiation of thrombolytic therapy in patients treated within 6 hours of symptom onset.

Methods and Results
The findings from patients in four prospective randomized trials of thrombolytic therapy were combined for analysis. The study population consisted of 432 patients presenting within 6 hours of onset of symptoms of first acute myocardial infarction who met ECG criteria that allowed estimation of myocardial area at risk before treatment with thrombolytic therapy and who had thallium-201 myocardial infarct–size measurements performed several weeks after infarction. ECG analysis revealed no difference in myocardium at risk for infarction as a function of duration of symptoms before initiation of thrombolytic therapy. In contrast, univariate and multivariate analysis showed that final infarct size was highly dependent on duration of symptoms before initiation of therapy. Each 30-minute increase in symptom duration before thrombolytic therapy was associated with an increase in infarct size of 1% of the myocardium. Final infarct size in patients treated 4 to 6 hours after symptom onset was indistinguishable from patients who did not receive thrombolytic therapy.

Conclusions
These findings suggest that for patients treated within 4 to 6 hours of the onset of symptoms, there is a progressive decline in the extent of myocardium salvaged as the duration of symptoms before therapy increases. These results support efforts to minimize the time delay between symptom onset and initiation of reperfusion therapy in all eligible patients.
l
-Arginine Induces Nitric Oxide–Dependent Vasodilation in Patients With Critical Limb Ischemia
Authors: Bode-Böger Stefanie M. , Böger Rainer H. , Alfke Heiko , Heinzel Doris , Tsikas Dimitrios , Creutzig Andreas , Alexander Klaus , Frölich Jürgen C.
Published: June 2012

Background
l
-Arginine is the precursor of endogenous nitric oxide (NO), which is a potent vasodilator acting via the intracellular second-messenger cGMP. In healthy humans,
l
-arginine induces peripheral vasodilation and inhibits platelet aggregation due to an increased NO production. Prostaglandin E
1
(PGE
1
) induces peripheral vasodilation via stimulating prostacyclin receptors.

Methods and Results
We investigated the effects of one intravenous infusion of
l
-arginine (30 g, 60 minutes) or PGE
1
(40 μg, 60 minutes) versus those of placebo (150 mL 0.9% saline, 60 minutes) on blood pressure, peripheral hemodynamics, and urinary NO
3
−
and cGMP excretion rates in patients with critical limb ischemia (peripheral arterial occlusive disease stages Fontaine III or IV). Blood flow in the femoral artery was significantly increased by
l
-arginine (+42.3±7.9%,
P
<.05) and by PGE
1
(+31.0±10.2%,
P
<.05) but not by placebo (+4.3±13.0%,
P
=NS). Urinary NO
3
−
excretion increased by 131.8±39.5% after
l
-arginine (
P
<.05) but only by 32.3±17.2% after PGE
1
(
P
=NS). Urinary cGMP excretion increased by 198.7±84.9% after
l
-arginine (
P
<.05) and by 94.2±58.8% after PGE
1
(
P
=NS). Both urinary index metabolites were unchanged by placebo.

Conclusions
We conclude that intravenous
l
-arginine induces NO-dependent peripheral vasodilation in patients with critical limb ischemia. These effects are paralleled by increased urinary NO
3
−
and cGMP excretion, indicating an enhanced systemic NO production. Increased urinary NO
3
−
excretion may be a sum effect of NO synthase substrate provision (
l
-arginine) and increased shear stress (PGE
1
and
l
-arginine).
Cholesterol Lowering and the Use of Healthcare Resources
Authors: Pedersen Terje R. , Kjekshus John , Berg Kåre , Olsson Anders G. , Wilhelmsen Lars , Wedel Hans , Pyörälä Kalevi , Miettinen Tatu , Haghfelt Torben , Færgeman Ole , Thorgeirsson Gudmundur , Jönsson Bengt , Schwartz J. Sanford
Published: June 2012

Background
Advances in the treatment of cardiovascular disease have increased costs; annual cardiovascular healthcare expenditure in the United States currently exceeds $100 billion. Physicians and third-party payers need to assess the economic impact of treatments that reduce cardiovascular morbidity and mortality.

Methods and Results
The Scandinavian Simvastatin Survival Study is a randomized, double-blind, placebo-controlled trial in which simvastatin reduced the risk of death by 30% (
P
=.0003) over the median follow-up period of 5.4 years in patients with previous myocardial infarction or stable angina pectoris as a result of a 42% reduction in the risk of coronary deaths (
P
=.00001). In the present report, data prospectively collected from hospital admissions were analyzed to evaluate the impact of simvastatin on healthcare resource use and perform a cost-minimization analysis. In the placebo group (n=2223), there were 1905 hospitalizations (average duration, 7.9 days) for acute cardiovascular events or coronary revascularization procedures among 937 patients, whereas in the simvastatin group (n=2221), there were 1403 such hospitalizations (average duration, 7.1 days) among 720 patients (all differences,
P
<.0001). The corresponding number of hospital days was 15 089 and 9951 in the two groups, respectively (34% reduction,
P
<.0001). In the United States, the resulting reduction in hospitalization costs over the 5.4 years of the trial would be $3872 per patient, reducing the effective cost of simvastatin by 88% to $0.28 per day.

Conclusions
In addition to reducing mortality and morbidity in coronary heart disease patients, simvastatin markedly reduces use of hospital services, thus offsetting most of its cost.
Atherosclerotic Arterial Remodeling in the Superficial Femoral Artery
Authors: Pasterkamp Gerard , Borst Cornelius , Post Mark J. , Mali Willem P.T.M. , Wensing Peter J.W. , Gussenhoven Elma J. , Hillen Berend
Published: June 2012

Background
In previous studies on atherosclerotic arterial remodeling, compensatory enlargement of the artery in response to plaque accumulation was inferred from pooled data based on one cross section per artery. We assessed local arterial remodeling individually by analyzing 45 artery segments at 0.5-cm intervals over a length of 10 to 15 cm.

Methods and Results
Twenty patients were studied by 30-MHz intravascular ultrasound (IVUS) before balloon angioplasty of the superficial femoral artery (370 cross sections), and 25 femoral artery segments were studied postmortem (551 cross sections). In each cross section, the area surrounded by the internal elastic lamina (IEL area) and the plaque area were measured. The IEL area was larger in the cross section with the largest plaque area than in the cross section with the smallest plaque area (32.5±13.0 and 32.0±11.5 mm
2
versus 28.9±9.7 [
P
=NS] and 26.7±10.1 [
P
<.05] mm
2
for IVUS and histology, respectively [mean±SD]). A significant positive correlation was found between plaque area and IEL area for the pooled data (
r
=.61 and
r
=.47 and slope=1.07 and 0.90 for IVUS and histology, respectively; both
P
<.001). In 12 of 20 and 16 of 25 individual arterial segments, however, no significant correlation was observed between plaque area and IEL area for IVUS and histology, respectively. A large variation was found in the correlation of the regression of plaque to IEL area (IVUS,
r
=−.40 to .89; histology,
r
=−.13 to .91) and slope (IVUS, −0.28 to 1.29; histology, −0.18 to 1.32).

Conclusions
In the majority of atherosclerotic femoral arteries, significant compensatory enlargement could not be determined. It is inferred that arterial remodeling in response to plaque formation may vary among individuals.
Symptoms of Depression, Acute Myocardial Infarction, and Total Mortality in a Community Sample
Authors: Barefoot John C. , Schroll Marianne
Published: June 2012

Background
Depression has been shown to adversely affect the prognosis of patients with established coronary artery disease, but there is comparatively little evidence to document the role of depression in the initial development of coronary disease.

Methods and Results
Study participants were 409 men and 321 women who were residents of Glostrup, Denmark, born in 1914. Physical and psychological examinations in 1964 and 1974 established their baseline risk factor and disease status and their level of depressive symptomatology. Initial myocardial infarction (MI) was observed in 122 participants, and there were 290 deaths during follow-up, which ended in 1991. A 2-SD difference in depression score was associated with relative risks of 1.71 (
P
=.005) for MI and 1.59 (
P
<.001) for deaths from all causes. These findings were unchanged after we controlled for risk factors and signs of disease at baseline. There were no sex differences in effect sizes.

Conclusions
High levels of depressive symptomatology are associated with increased risks of MI and mortality. The graded relationships between depression scores and risk, long-lasting nature of the effect, and stability of the depression measured across time suggest that this risk factor is best viewed as a continuous variable that represents a chronic psychological characteristic rather than a discrete and episodic psychiatric condition.
Sex Differences in Myocardial Infarction and Coronary Deaths in the Scottish MONICA Population of Glasgow 1985 to 1991
Authors: Tunstall-Pedoe Hugh , Morrison Caroline , Woodward Mark , Fitzpatrick Bridie , Watt Graham
Published: June 2012

Background
Scottish MONICA used medical and medicolegal records and World Health Organization MONICA Project criteria to register coronary events in 25- to 64-year-old residents of the high-incidence area of north Glasgow from 1985 to 1991.

Methods and Results
Age-standardized data from 3991 episodes of nonfatal definite myocardial infarction and coronary deaths in men (mean age, 55.5 years) were compared with 1551 in women (57.0 years). Many results, such as the overall 28-day fatality rates of 49.8% in men and 48.5% in women, showed insignificant differences. However, 74.3% of deaths in men occurred out of hospital versus 67.8% in women (
P
=.0004). After admission to hospital, fatality rates in women were 14% higher (
P
=.07) and after admission to coronary care, 22% higher (
P
=.04). Women were more often widowed. Fewer had a history of previous myocardial infarction, but the prevalence of angina pectoris, of smoking, and of chest pain in the attack was the same as in men; more had shock, syncope, and breathlessness. More consulted a doctor before admission to hospital, which delayed their coming under care. More men had ECG Q-wave progression, and more women had smaller ECG changes. This, and marginally reduced chances of direct admission to coronary care, of thrombolysis, of aspirin, and of β-blockers, did not explain women’s excess hospital fatality.

Conclusions
Acute coronary events appear to be recognized and treated fairly equally in men and women 25 to 64 years old in Glasgow, so differences are small but subtle. More men die suddenly out of hospital; the reason why more women die after arrival may be because the equivalent number of men have already died outside.
Value of Dynamic Respiratory Changes in Left and Right Ventricular Pressures for the Diagnosis of Constrictive Pericarditis
Authors: Hurrell David G. , Nishimura Rick A. , Higano Stuart T. , Appleton Christopher P. , Danielson Gordon K. , Holmes David R. , Tajik A. Jamil
Published: June 2012

Background
Conventional cardiac catheterization criteria for the diagnosis of constrictive pericarditis (CP) rely on equalization of intracardiac pressures and have many recognized limitations. Recently, Doppler echocardiographic methods have been used to examine dynamic respiratory changes of increased ventricular interdependence and dissociation of intrathoracic and intracardiac pressures for the diagnosis of CP. These pathophysiological features may be best delineated by cardiac catheterization. Therefore, we studied the accuracy of these dynamic respiratory changes in left ventricular and right ventricular pressure for the diagnosis of CP at cardiac catheterization.

Methods and Results
High-fidelity manometric catheters and respirometry were used to study 36 patients: 15 patients with surgically proven CP (group 1) and 21 patients with other causes of heart failure (group 2). Conventional cardiac catheterization variables used to establish the diagnosis of CP lacked sensitivity and specificity and failed to distinguish between these groups. However, the finding of discordance between right ventricular and left ventricular pressures during inspiration, a sign of increased ventricular interdependence, accurately distinguished patients in group 1 from those in group 2 (
P
<.05).

Conclusions
Examination of dynamic respiratory changes indicating increased ventricular interdependence may be helpful in the diagnosis of CP in the cardiac catheterization laboratory.
Influence of Comorbidity on the Outcome of Patients Treated for Out-of-Hospital Ventricular Fibrillation
Authors: Hallstrom Alfred P. , Cobb Leonard A. , Yu Ben Hui
Published: June 2012

Background
A number of factors have previously been shown to be predictive of survival from out-of-hospital ventricular fibrillation. These include witnessed collapse, prompt initiation of cardiopulmonary resuscitation, early application of defibrillation, and younger age. Arrests occurring away from home are also associated with improved survival. Additionally, hospital mortality after successful resuscitation has been related to a history of congestive heart failure as well as to some of the factors noted above. An association of prearrest comorbidity with outcome has not been systematically evaluated.

Methods and Results
We define here a comorbidity index, which is constructed from histories of chronic conditions as well as a number of recent symptoms in 282 victims of out-of-hospital VF. This indicator of comorbidity is strongly associated with outcome (
P
=.004). However, when analyzing a comprehensive set of predictors of survival after out-of-hospital ventricular fibrillation, including the index of comorbidity, we could identify overall only about one fourth of the variation that one might hope to account for.

Conclusions
Comorbidity appears to be an important (but usually overlooked) predictor of survival from out-of-hospital ventricular fibrillation. However, most of the statistical variability in predicting survival remains unexplained when we consider comorbidity in conjunction with previously identified predictors of survival.
Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Oral
l
-Arginine in Patients With Heart Failure
Authors: Rector Thomas S. , Bank Alan J. , Mullen Kathleen A. , Tschumperlin Linda K. , Sih Ronald , Pillai Kamalesh , Kubo Spencer H.
Published: June 2012

Background
Patients with heart failure have reduced peripheral blood flow at rest, during exercise, and in response to endothelium-dependent vasodilators. Nitric oxide formed from
l
-arginine metabolism in endothelial cells contributes to regulation of blood flow under these conditions. A randomized, double-blind crossover study design was used to determine whether supplemental oral
l
-arginine can augment peripheral blood flow and improve functional status in patients with moderate to severe heart failure.

Methods and Results
Fifteen subjects were given 6 weeks of oral
l
-arginine hydrochloride (5.6 to 12.6 g/d) and 6 weeks of matched placebo capsules in random sequence. Compared with placebo, supplemental oral
l
-arginine significantly increased forearm blood flow during forearm exercise, on average from 5.1±2.8 to 6.6±3.4 mL·min
−1
·dL
−1
(
P
<.05). Furthermore, functional status was significantly better on
l
-arginine compared with placebo, as indicated by increased distances during a 6-minute walk test (390±91 versus 422±86 m,
P
<.05) and lower scores on the Living With Heart Failure questionnaire (55±28 versus 42±26,
P
<.05). Oral
l
-arginine also improved arterial compliance from 1.99±0.38 to 2.36±0.30 mL/mm Hg (
P
<.001) and reduced circulating levels of endothelin from 1.9±1.1 to 1.5±1.1 pmol/L (
P
<.05).

Conclusions
Supplemental oral
l
-arginine had beneficial effects in patients with heart failure. Further studies are needed to confirm the therapeutic potential of supplemental oral
l
-arginine and to identify mechanisms of action in patients with heart failure.
Serotonin Stimulates the Expression of Thrombin Receptors in Cultured Vascular Smooth Muscle Cells
Authors: Schini-Kerth Valérie B. , Fisslthaler Beate , Van Obberghen-Schilling Ellen , Busse Rudi
Published: June 2012

Background
Thrombin has been implicated in the development of intimal thickening after balloon angioplasty. The action of thrombin on vascular cells involves the proteolytic activation of G protein–coupled receptors that are subjected to rapid and irreversible homologous desensitization. Hence, the amount and availability of thrombin-activatable receptors play a determinant role in thrombin responsiveness. The possibility that the platelet-derived product serotonin (5-HT) regulates expression of the thrombin receptor was examined in cultured rat aortic vascular smooth muscle cells.

Methods and Results
Thrombin receptor expression was assessed at the mRNA level by Northern blot analysis and functionally by measurement of the release of 6-ketoprostaglandin F
1α
. 5-HT significantly enhanced thrombin receptor mRNA levels in a time- and concentration-dependent manner, an effect that was abolished by 5-HT
2
receptor antagonists and by inhibition of protein kinase C but only slightly affected by inhibitors of protein tyrosine kinases. Enhanced thrombin receptor mRNA levels after exposure to 5-HT were associated with an increase in the thrombin-induced release of 6-ketoprostaglandin F
1α
.

Conclusions
5-HT stimulates the expression of thrombin receptors in vascular smooth muscle cells, probably via activation of 5-HT
2
receptors and the subsequent activation of protein kinase C and possibly also protein tyrosine kinases. The upregulation of the synthesis of plasma membrane thrombin receptors by 5-HT released from aggregating platelets at sites of vascular injury may potentiate the mitogenic and constrictor actions of thrombin in the vascular wall.
Coronary Thrombi Increase PTCA Risk
Authors: White Christopher J. , Ramee Stephen R. , Collins Tyrone J. , Escobar Alvaro E. , Karsan Arun , Shaw Dinesh , Jain Suresh P. , Bass Theodore A. , Heuser Richard R. , Teirstein Paul S. , Bonan Raoul , Walter Paul D. , Smalling Richard W.
Published: June 2012

Background
The presence of angiographically identified intracoronary thrombus has been variably associated with complications after coronary angioplasty. Angiography has been shown to be less sensitive than angioscopy for detecting subtle details of intracoronary morphology, such as intracoronary thrombi. The clinical importance of thrombi detectable by angioscopy but not by angiography is not known.

Methods and Results
Percutaneous coronary angioscopy was performed in 122 patients undergoing conventional coronary balloon angioplasty (PTCA) at six medical centers. Unstable angina was present in 95 patients (78%) and stable angina in 27 (22%). Therapy was not guided by angioscopic findings, and no patient received thrombolytic therapy as an adjunct to angioplasty. Coronary thrombi were identified in 74 target lesions (61%) by angioscopy versus only 24 (20%) by angiography. A major in-hospital complication (death, myocardial infarction, or emergency bypass surgery) occurred in 10 of 74 patients (14%) with angioscopic intracoronary thrombus, compared with only 1 of 48 patients (2%) without thrombi (
P
=.03). In-hospital recurrent ischemia (recurrent angina, repeat PTCA, or abrupt occlusion) occurred in 19 of 74 patients (26%) with angioscopic intracoronary thrombi versus only 5 of 48 (10%) without thrombi (
P
=.03). Relative risk analysis demonstrated that angioscopic thrombus was strongly associated with adverse outcomes (either a major complication or a recurrent ischemic event) after PTCA (relative risk, 3.11; 95% CI, 1.28 to 7.60;
P
=.01) and that angiographic thrombi were not associated with these complications (relative risk, 0.85; 95% CI, 0.36 to 2.00;
P
=.91).

Conclusions
The presence of intracoronary thrombus associated with coronary stenoses is significantly underestimated by angiography. Angioscopic intracoronary thrombi, the majority of which were not detected by angiography, are associated with an increased incidence of adverse outcomes after coronary angioplasty.
Air Travel and Adults With Cyanotic Congenital Heart Disease
Authors: Harinck Eric , Hutter Paul A. , Hoorntje Theo M. , Simons Marinus , Benatar Avram A. , Fischer Johan C. , de Bruijn Dagmar , Jan Meijboom Erik
Published: June 2012

Background
Concern has been expressed that a reduction of partial oxygen pressure during flight in commercial aircraft may induce dangerous hypoxemia in patients with cyanotic congenital heart disease.

Methods and Results
To evaluate the validity of this concern, the transcutaneous Sa
o
2
was measured in 12 adults with this type of heart disease and 27 control subjects during simulated commercial flights of 1.5 and 7 hours in a hypobaric chamber. Ten of those patients and 6 control subjects also were evaluated during two actual flights of approximately 2.5 hours in a DC-10 and an A-310, respectively. During the prolonged simulated and actual flights, the capillary blood pH, gases, and lactic acid were analyzed in the patients and during one of the actual flights also in the control subjects. During the simulated flights the Sa
o
2
was at all times lower in the patients than in the control subjects. However, the maximal mean actual percentage decrease, as compared with sea level values, did not exceed 8.8% in either patients or control subjects. During the actual flights, this maximal decrease in the patients was 6%. In-flight reduction of the capillary P
o
2
was considerable in the control subjects but not in the patients. It is our hypothesis that the lack of a significant decrease of the P
o
2
in the patients might possibly be due to a high concentration of 2.3 diphosphoglycerate in the red cells. The flights had no influence on the capillary blood pH, P
co
2
, bicarbonate, or lactic acid levels in either patients or control subjects.

Conclusions
Atmospheric pressure changes during commercial air travel do not appear to be detrimental to patients with cyanotic congenital heart disease.
RR Interval Variability in Irregular Monomorphic Ventricular Tachycardia and Atrial Fibrillation
Authors: Garcı́a-Alberola Arcadi , Yli-Mäyry Sinikka , Block Michael , Haverkamp Wilhelm , Martı́nez-Rubio Antonio , Kottkamp Hans , Breithardt Günter , Borggrefe Martin
Published: June 2012

Background
Algorithms to reject irregular tachyarrhythmias are available in implantable cardioverter-defibrillator devices to discriminate ventricular tachycardia (VT) from atrial fibrillation (AF). The hazard of underdetection of irregular monomorphic VTs using these algorithms has not yet been fully evaluated. The purpose of this study was to determine the ability of a commonly used stability algorithm to reject AF and to correctly detect VT with a high RR interval variability.

Methods and Results
The electrophysiological studies from 232 patients with induced monomorphic VT (cycle length >250 ms) and 21 with AF were reviewed. A preliminary analysis was performed to classify the VT episodes in irregular (successive RR differences >20 ms after 4 seconds from onset) or regular (otherwise). Three study groups were defined: group 1 (27 patients with irregular VT), group 2 (22 randomly selected patients with regular VT), and group 3 (21 patients with AF). A computer program analyzed the first 50 RR intervals of the induced VT (AF), resetting a VT counter if the interval was greater than a tachycardia detection interval (TDI) or if its absolute difference with the preceding three beats exceeded a programmed stability value (STAB). The VT was detected when the VT counter reached a preset number of intervals (NIDs). Different combinations of TDI, STAB, and NID were analyzed. All VTs in group 2 were correctly detected. In contrast, up to 10 VTs from group 1 were not detected when high NIDs and low STAB parameters were programmed. With usual values (10 to 16 beats and 50 to 60 ms, respectively), only 1 to 2 VTs remained undetected, but 20% to 50% had a detection delay >8 seconds. Undetected VTs were significantly slower than early detected VTs for most STAB and NID combinations. With usual stability and NID values, 10% to 20% of episodes of AF were inappropriately detected. Changes in TDI had a small impact on sensitivity and specificity when currently used values for stability were programmed.

Conclusions
An implantable cardioverter-defibrillator tachycardia detection algorithm with a stability criterion of 50 to 60 ms and 12 to 14 RR intervals is able to detect over 90% of monomorphic irregular VTs. Nevertheless, significant VT detection delays may arise, and inappropriate detection of AF cannot be totally prevented.
Nitric Oxide Inhibits Numerous Features of Mast Cell–Induced Inflammation
Authors: Gaboury Jeffrey P. , Niu Xiao-Fei , Kubes Paul
Published: June 2012

Background
We previously reported that mast cell degranulation causes histamine and P-selectin–dependent leukocyte rolling and platelet-activating factor (PAF)- and CD18-associated leukocyte adhesion, whereas others have reported serotonin-induced edema formation. The purpose of the present study was to determine whether nitric oxide (NO) could inhibit the mast cell–induced multistep recruitment of leukocytes and the associated microvascular dysfunction in single inflamed venules.

Methods and Results
Intravital fluorescence microscopy was used to demonstrate increased leukocyte rolling and adhesion and increased albumin extravasation in single 25- to 40-μm venules that were treated with the mast cell–degranulating agent compound 48/80 (CMP 48/80). The mast cell–induced histamine-dependent rolling and PAF-dependent adhesion were completely inhibited by the addition of the NO donor spermine NO. However, spermine NO did not directly inhibit histamine-induced leukocyte rolling and only partly affected PAF-induced leukocyte adhesion. Compound 48/80–activated mast cells evoked a significant increase in PAF-dependent neutrophil adhesion in vitro. Spermine-NO prevented the mast cell–dependent neutrophil adhesion but failed to affect direct adhesion with PAF. The mast cell–induced albumin leakage was also inhibited by the NO donor.

Conclusions
Taken together, these results suggest that exogenous NO can modulate leukocyte recruitment and microvascular permeability alterations elicited by mast cell activation and raises the possibility that the use of NO donors may be a reasonable therapeutic approach to reducing mast cell–dependent inflammation.
Extracellular Potassium Modulation of Drug Block of I
Kr
Authors: Yang Tao , Roden Dan M.
Published: June 2012

Background
Torsade de pointes often occurs with underlying hypokalemia and bradycardia. A common effect of many drugs producing torsade de pointes is block of the rapidly activating component of the cardiac delayed rectifier (I
Kr
). In this study, we evaluated the effect of changing extracellular potassium ([K
+
]
o
) on I
Kr
block by the nonspecific agent quinidine and by the specific I
Kr
blocker dofetilide.

Methods and Results
I
Kr
was measured in AT-1 cells, where contaminating outward currents are absent. The drug concentration producing 50% inhibition of I
Kr
tails (IC
50
) was strikingly [K
+
]
o
-dependent. Elevating [K
+
]
o
from 1 to 8 mmol/L increased the IC
50
for dofetilide block from 2.7±0.9 to 79±32 nmol/L and for quinidine block from 0.4±0.1 to 3.8±1.2 μmol/L.

Conclusions
(1) The increase in drug block with low [K
+
]
o
provides a mechanism to explain the link between hypokalemia and torsade de pointes. (2) Elevations in [K
+
]
o
occur with myocardial ischemia and with rapid pacing. Possible consequences of blunted drug block with high [K
+
]
o
include loss of drug efficacy with ischemia and with rapid pacing; the latter may contribute to “reverse use-dependent” action potential prolongation. Extracellular potassium is a critical determinant of drug block of I
Kr
, with substantial clinical implications.
Early Endothelial Dysfunction Predicts the Development of Transplant Coronary Artery Disease at 1 Year Posttransplant
Authors: Davis Stacy F. , Yeung Alan C. , Meredith Ian T. , Charbonneau François , Ganz Peter , Selwyn Andrew P. , Anderson Todd J.
Published: June 2012

Background
Accelerated coronary arteriosclerosis is the major obstacle to long-term survival after cardiac transplantation. Endothelial dysfunction is common early posttransplant. The relationship between early endothelial dysfunction and the development of allograft arteriosclerosis has not been analyzed serially with intravascular ultrasound in the same patients. We hypothesized that an early constrictor response to acetylcholine, indicative of endothelial dysfunction, may predict the development of transplant coronary arteriosclerosis.

Methods and Results
Endothelium-dependent vasomotion was assessed early posttransplant in 20 patients by serial intracoronary acetylcholine infusion, and the percent change in diameter was measured by quantitative angiography. The development of arteriosclerosis was studied by use of intravascular ultrasound in the same 20 patients by quantifying the changes in intimal index (ΔIi) and maximal intimal thickness [ΔMt] of 46 matched coronary segments between initial and 1-year follow-up studies. Coronary segments with endothelial dysfunction (constriction ≥5%; n=23) demonstrated a significantly greater increase in mean Ii and Mt by 1 year posttransplant compared with segments with normal endothelial function (n=23) (ΔIi=7±2% versus 2±1% [
P
<.05] and ΔMt=140±40 versus 50±20 μm [
P
<.05]). No other parameters examined predicted the development of allograft arteriosclerosis in the initial year posttransplant.

Conclusions
Paired studies that used intravascular ultrasound showed that early endothelial dysfunction predicts the development of allograft arteriosclerosis during the initial year posttransplant. This early pathophysiological feature is likely an important marker that could be useful in therapeutic trials.
Left Ventricular Fibromuscular Band Is Not a Specific Substrate for Idiopathic Left Ventricular Tachycardia
Authors: Lin Fun-Chung , Wen Ming-Shien , Wang Chun-Chieh , Yeh San-Jou , Wu Delon
Published: June 2012

Background
A fibromuscular band has been detected in patients with idiopathic left ventricular tachycardia, and this band has been suggested to be the anatomic substrate for the arrhythmia. Whether the fibromuscular band is a specific substrate for the tachycardia was systematically evaluated in a large group of consecutive patients with and without idiopathic left ventricular tachycardia.

Methods and Results
Conventional transthoracic two-dimensional echocardiography and multiplane transesophageal echocardiography were performed in 18 patients with idiopathic left ventricular tachycardia that was responsive to calcium blockers (group 1, tachycardia patients) and 40 patients with paroxysmal supraventricular tachycardia (group 2, control patients). There were 17 men and 1 woman, with a mean age of 29±11 years, in group 1 patients, and 21 men and 19 women, with a mean age of 42±12 years, in group 2 patients. The QRS morphology during tachycardia in group 1 patients displayed a pattern of right bundle-branch block with superior axis in 15 patients, indeterminate axis in 2 patients, and inferior axis in 1 patient. Radiofrequency ablation successfully eliminated the tachycardia in all 18 patients; the successful ablation site was located at the inferior apical septum in 11 patients, at the midseptum in 6 patients, and at the anterior lateral wall in 1 patient. Transthoracic echocardiography detected the fibromuscular band in 11 of the 18 patients, whereas multiplane transesophageal echocardiography detected the band in 17 of 18 patients. The fibromuscular band extended from the interventricular septum to the apex of the left ventricle. In group 2 patients, transthoracic echocardiography detected the fibromuscular band in 22 and multiplane transesophageal echocardiography detected the band in 35 of the 40 patients. The presence of a fibromuscular band in these two groups of patients was not statistically different.

Conclusions
The presence of a left ventricular fibromuscular band is not a specific anatomic substrate for idiopathic left ventricular tachycardia.