bluuebunny/crossref_metadata_2025 huggingface dataset:
“Stable” Ventricular Tachycardia Is Not a Benign Rhythm
Authors: Raitt Merritt H. , Renfroe Ellen Graham , Epstein Andrew E. , McAnulty John H. , Mounsey Paul , Steinberg Jonathan S. , Lancaster Scott E. , Jadonath Ram L. , Hallstrom Alfred P.
Published: June 2012

Background
—Sustained ventricular tachycardia (VT) can be unstable, can be associated with serious symptoms, or can be stable and relatively free of symptoms. Patients with unstable VT are at high risk for sudden death and are best treated with an implantable defibrillator. The prognosis of patients with stable VT is controversial, and it is unknown whether implantable cardioverter-defibrillator therapy is beneficial.

Methods and Results
—Screening for the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial identified patients with both stable and unstable VT. Both groups were included in a registry, and their clinical characteristics and discharge treatments were recorded. Mortality data were obtained through the National Death Index. The mortality in 440 patients with stable VT tended to be greater than that observed in 1029 patients presenting with unstable VT (33.6% versus 27.6% at 3 years; relative risk [RR]=1.22;
P
=0.07). After adjustment for baseline and treatment differences, the RR was little changed (RR=1.25,
P
=0.06).

Conclusions
—Sustained VT without serious symptoms or hemodynamic compromise is associated with a high mortality rate and may be a marker for a substrate capable of producing a more malignant arrhythmia. Implantable cardioverter-defibrillator therapy may be indicated in patients presenting with stable VT.
Role of Rho-Associated Kinase in Neointima Formation After Vascular Injury
Authors: Shibata Rei , Kai Hisashi , Seki Yukihiko , Kato Seiya , Morimatsu Minoru , Kaibuchi Kozo , Imaizumi Tsutomu
Published: June 2012

Background
—The Rho/Rho-associated kinase (Rho-kinase) system is implicated in various cellular functions, including migration, proliferation, and apoptosis. Because a possible role of the system is suggested in neointima formation after vascular injury, we sought to examine whether a new specific Rho-kinase inhibitor, Y27632, prevents neointima formation of the balloon-injured rat carotid artery, and if so, to investigate the effects of Y27632 on migration, proliferation, and apoptosis of smooth muscle cells (SMCs) in the injured artery.

Methods and Results
—Y27632 was administered intraperitoneally from 1 day before to 14 days after vascular injury. Treatment with Y27632 inhibited phenylephrine-induced Rho-kinase activation in the carotid artery on the basis of immunoblotting against the phosphorylated myosin-binding subunit of myosin phosphatase. Y27632 markedly prevented neointima formation at days 7 and 14. In controls, BrdU
+
proliferating and TUNEL
+
apoptotic SMCs were transiently and coincidentally increased in the neointima, with a peak at day 7. Y27632 significantly increased the neointimal TUNEL
+
SMCs at days 7 and 14, but not BrdU
+
SMCs. Y27642 significantly decreased the number of intimal SMCs at day 4, while not affecting the number of BrdU
+
or TUNEL
+
SMCs. Reendothelialization after balloon injury was not significantly affected by Y27632 at days 7 and 14.

Conclusions
—Y27632 inhibited neointima formation by enhancing SMC apoptosis and probably by suppressing early SMC migration. Therefore, a role of Rho-kinase is suggested in neointima formation after vascular injury.
Mitochondria as Targets for Nitric Oxide–Induced Protection During Simulated Ischemia and Reoxygenation in Isolated Neonatal Cardiomyocytes
Authors: Rakhit Roby D. , Mojet Mart H. , Marber Michael S. , Duchen Michael R.
Published: June 2012

Background
—As shown previously, exposure to NO donors initiates protective mechanisms in cardiomyocytes that persist after removal of the donor, a form of pharmacological preconditioning. Because NO also affects mitochondrial respiration, we studied the effect of NO on mitochondrial Ca
2+
uptake.

Methods and Results
—Neonatal rat ventricular myocytes in primary culture were exposed to 1 hour of simulated ischemia and 1 hour of reoxygenation (sI/R). Pretreatment with the NO donor
S
-nitroso-
N
-acetyl-penicillamine (SNAP) (1 mmol/L for 90 minutes), followed by washing and incubation for 10 to 30 minutes, reduced sI/R-induced cell death to 25.4% compared with control (propidium iodide exclusion assay,
P
<0.001). Short (10-second) exposures to SNAP reversibly suppressed mitochondrial respiration without a detectable change in mitochondrial potential. In contrast, treatment with SNAP for 90 minutes caused a modest but sustained mitochondrial depolarization, as judged by JC-1 fluorescence. SNAP pretreatment limited cellular Ca
2+
overload during ischemia (fura-2 ratio rose to 226±40% versus 516±170% of baseline, n=5,
P
<0.05) and prevented loss of cell membrane integrity during reoxygenation. SNAP pretreatment also significantly reduced the ability of mitochondria to accumulate Ca
2+
in the face of a similar cytosolic Ca
2+
load (peak rhod-2 fluorescence 133±4% versus 166±7% of baseline at similar fluo-3 levels,
P
=0.0004, n=52 and 25, respectively).

Conclusions
—Pretreatment with an NO donor induces a modest, sustained mitochondrial depolarization and protects cardiomyocytes from sI/R injury. The demonstrated reduction in mitochondrial Ca
2+
uptake possibly reduces cytosolic Ca
2+
overload, providing a likely mechanism for NO-induced protection.
Transdermal Estrogen Replacement Therapy Decreases Sympathetic Activity in Postmenopausal Women
Authors: Vongpatanasin Wanpen , Tuncel Meryem , Mansour Yasser , Arbique Debbie , Victor Ronald G.
Published: June 2012

Background
—Menopause heralds a dramatic increase in incident hypertension, suggesting a protective effect of estrogen on blood pressure (BP). In female rats, estrogen has been shown to decrease sympathetic nerve discharge (SND) and BP. SND, however, has not been recorded during estrogen replacement therapy (ERT) in humans.

Methods and Results
—In 12 normotensive postmenopausal women, we conducted a randomized crossover placebo-controlled study to test whether chronic ERT caused a sustained decrease in SND and BP. Twenty-four-hour ambulatory BP, SND, and arterial baroreflex sensitivity were measured before and after 8 weeks of transdermal estradiol (200 μg/d), oral conjugated estrogens (0.625 mg/d), or placebo. To test the acute effects of estrogen on SND, additional studies were performed in the same women receiving intravenous conjugated estrogens or sublingual estradiol. After 8 weeks of transdermal ERT, the basal rate of SND decreased by 30% (from 40±4 to 27±4 bursts per minute,
P
=0.0001) and ambulatory diastolic BP fell by 5±2 mm Hg (
P
=0.0003). In contrast, SND and BP were unaffected either by 8 weeks of oral ERT or by acute estrogen administration. Neither transdermal nor oral ERT had any effects on baroreflex sensitivity.

Conclusions
—In normotensive postmenopausal women, chronic transdermal ERT decreases SND without augmenting arterial baroreflexes and causes a small but statistically significant decrease in ambulatory BP. Sympathetic inhibition is evident only with chronic rather than acute estrogen administration, implying a genomic mechanism of action. Because the effects of transdermal ERT are larger than those of oral ERT, the route of administration may be an important consideration in optimizing the beneficial effects of ERT on BP and overall cardiovascular health.
Cytomegalovirus Infection With Interleukin-6 Response Predicts Cardiac Mortality in Patients With Coronary Artery Disease
Authors: Blankenberg Stefan , Rupprecht Hans J. , Bickel Christoph , Espinola-Klein Christine , Rippin Gerd , Hafner Gerd , Ossendorf Manfred , Steinhagen Katja , Meyer Jürgen
Published: June 2012

Background
—Prospective data relating previous exposure to cytomegalovirus (CMV) to the risk of cardiac mortality are controversial. We investigated the effect of previous exposure to CMV infection on the risk of future cardiac disease–related death in relation to an underlying inflammatory response.

Methods and Results
—Coronary angiography was performed in 1134 subjects, and 989 patients with documented coronary artery disease were studied prospectively. CMV-IgG titers and interleukin (IL)-6 levels were measured before angiography. Increasing titers of CMV correlated with the elevation of IL-6 levels (
P
<0.001) after adjustment for possible confounders. All patients were followed up for a median of 3.1 years (maximum 4.3 years). During follow-up, 96 patients died, 70 of cardiac disease. Overall, CMV seropositivity was not related to cardiac mortality after adjustment for confounding variables (
P
=0.19). In contrast, in patients with elevated IL-6 levels (≥11.9 pg/mL, median level), CMV seropositivity was independently associated with a 3.2-fold (95% CI 1.4 to 7.3,
P
=0.007) increase in risk of future cardiac death, whereas in individuals without IL-6 elevation, previous CMV infection had no effect on cardiac mortality.

Conclusions
—CMV seropositivity in patients with an inflammatory response is independently associated with future cardiac mortality, whereas this association is lost in patients who do not demonstrate an inflammatory response. These data support the hypothesis that the atherosclerotic effects of CMV are mediated through an underlying inflammatory response.
Oxygenated Carotenoid Lutein and Progression of Early Atherosclerosis
Authors: Dwyer James H. , Navab Mohamad , Dwyer Kathleen M. , Hassan Kholood , Sun Ping , Shircore Anne , Hama-Levy Susan , Hough Greg , Wang Xuping , Drake Thomas , Merz C. Noel Bairey , Fogelman Alan M.
Published: June 2012

Background
—Carotenoids are hypothesized to explain some of the protective effects of fruit and vegetable intake on risk of cardiovascular disease. The present study assessed the protective effects of the oxygenated carotenoid lutein against early atherosclerosis.

Methods and Results
—Epidemiology: Progression of intima-media thickness (IMT) of the common carotid arteries over 18 months was determined ultrasonographically and was related to plasma lutein among a randomly sampled cohort of utility employees age 40 to 60 years (n=480). Coculture: The impact of lutein on monocyte response to artery wall cell modification of LDL was assessed in vitro by quantification of monocyte migration in a coculture model of human intima. Mouse models: The impact of lutein supplementation on atherosclerotic lesion formation was assessed in vivo by assigning apoE-null mice to chow or chow plus lutein (0.2% by weight) and LDL receptor–null mice to Western diet or Western diet plus lutein. IMT progression declined with increasing quintile of plasma lutein (
P
for trend=0.007, age-adjusted;
P
=0.0007, multivariate). Covariate-adjusted IMT progression (mean±SEM) was 0.021±0.005 mm in the lowest quintile of plasma lutein, whereas progression was blocked in the highest quintile (0.004±0.005 mm;
P
=0.01). In the coculture, pretreatment of cells with lutein inhibited LDL-induced migration in a dose-dependent manner (
P
<0.05). Finally, in the mouse models, lutein supplementation reduced lesion size 44% in apoE-null mice (
P
=0.009) and 43% in LDL receptor–null mice (
P
=0.02).

Conclusions
—These epidemiological, in vitro, and mouse model findings support the hypothesis that increased dietary intake of lutein is protective against the development of early atherosclerosis.
Glimepiride, a Novel Sulfonylurea, Does Not Abolish Myocardial Protection Afforded by Either Ischemic Preconditioning or Diazoxide
Authors: Mocanu Mihaela M. , Maddock Helen L. , Baxter Gary F. , Lawrence Christina L. , Standen Nicholas B. , Yellon Derek M.
Published: June 2012

Background
—The sulfonylurea glibenclamide (Glib) abolishes the cardioprotective effect of ischemic preconditioning (IP), presumably by inhibiting mitochondrial K
ATP
channel opening in myocytes. Glimepiride (Glim) is a new sulfonylurea reported to affect nonpancreatic K
ATP
channels less than does Glib. We examined the effects of Glim on IP and on the protection afforded by diazoxide (Diaz), an opener of mitochondrial K
ATP
channels.

Methods and Results
—Rat hearts were Langendorff-perfused, subjected to 35 minutes of regional ischemia and 120 minutes of reperfusion, and assigned to 1 of the following treatment groups: (1) control; (2) IP of 2× 5 minutes each of global ischemia before lethal ischemia; or pretreatment with (3) 30 μmol/L Diaz, (4) 10 μmol/L Glim, (5) 10 μmol/L Glib, (6) IP+Glim, (7) IP+Glib, (8) Diaz+Glim, or (9) Diaz+Glib. IP limited infarct size (18.5±1% vs 43.7±3% in control,
P
<0.01) as did Diaz (22.2±4.7%,
P
<0.01). The protective actions of IP or Diaz were not abolished by Glim (18.5±3% in IP+Glim, 22.3±3% in Diaz+Glim;
P
<0.01 vs control). However, Glib abolished the infarct-limiting effects of IP and Diaz. Patch-clamp studies in isolated rat ventricular myocytes confirmed that both Glim and Glib (each at 1 μmol/L) blocked sarcolemmal K
ATP
currents. However, in isolated cardiac mitochondria, Glim (10 μmol/L) failed to block the effects of K
ATP
opening by GTP, in contrast to the blockade caused by Glib.

Conclusions
—Although it blocks sarcolemmal currents in rat cardiac myocytes, Glim does not block the beneficial effects of mitochondrial K
ATP
channel opening in the isolated rat heart. These data may have significant implications for the treatment of type 2 diabetes in patients with ongoing ischemic heart disease.
Use of the Internal Mammary Artery Graft and In-Hospital Mortality and Other Adverse Outcomes Associated With Coronary Artery Bypass Surgery
Authors: Leavitt Bruce J. , O’Connor Gerald T. , Olmstead Elaine M. , Morton Jeremy R. , Maloney Christopher T. , Dacey Lawrence J. , Hernandez Felix , Lahey Stephen J.
Published: June 2012

Background
—There is clear evidence that patients having coronary artery bypass graft surgeries with an internal mammary artery (IMA) have better long-term survival. Some studies have suggested a short-term protective effect as well but, because older and sicker patients are less likely to receive an IMA graft, there has been concern that the apparent protective effect of the IMA on short-term mortality has been confounded by other risk factors. This study was intended to examine the independent effect of IMA grafts on in-hospital mortality while adjusting for patient and disease factors.

Methods and Results
—We studied the use of the left IMA (LIMA) in 21 873 consecutive, isolated, first-time coronary artery bypass graft procedures from 1992 through 1999. A total of 87% of the patients received a LIMA graft. LIMA graft use was associated with a significantly decreased risk of mortality. The crude odds ratio for death (LIMA versus no LIMA) was 0.26 (95% confidence intervals, 0.22, 0.31;
P
<0.001). LIMA grafts were protective across all major patient and disease subgroups. The odds ratios by subgroup ranged from 0.13 to 0.48. After adjustment for all major risk factors, the odds ratio for death was 0.40 (95% confidence intervals, 0.33, 0.48;
P
<0.001). Rates of cerebrovascular accident, return to cardiopulmonary bypass, return to the operating room for bleeding, and mediastinitis or sternal dehiscence requiring surgery were also less in the LIMA group, although not significantly so.

Conclusions
—These data suggest that in addition to its well-documented patency and long-term beneficial effect, LIMA grafting has a strong protective effect on perioperative mortality.
Plasminogen Activator Inhibitor-1 and Its Cofactor Vitronectin Stabilize Arterial Thrombi After Vascular Injury in Mice
Authors: Konstantinides Stavros , Schäfer Katrin , Thinnes Therese , Loskutoff David J.
Published: June 2012

Background
—The origin and contribution of plasminogen activator inhibitor-1 (PAI-1) and its cofactor vitronectin (VN) to arterial thrombosis/thrombolysis in vivo is controversial.

Methods and Results
—Ferric chloride was used to induce carotid artery injury in 97 wild-type (WT), 84 PAI-1−/−, and 84 VN−/− mice. Complete thrombotic occlusion was observed in 70% of PAI-1−/− mice versus 92% of WT (
P
<0.001) and 87% of VN−/− (
P
=0.015) mice. In vessels that occluded, mean times to occlusion were significantly longer in PAI-1−/− than in WT or VN−/− mice. The initial thrombotic response of VN−/− mice was similar to that of WT mice, but their thrombi were unstable and frequently embolized. As a result, the patency rate of carotid vessels 30 minutes after injury was as high in VN−/− mice (36%) as in PAI-1−/− mice (which demonstrate progressive thrombolysis) and significantly higher than that of WT mice (12%;
P
=0.013). Histochemical and reverse transcription–polymerase chain reaction studies revealed an early upregulation of PAI-1 mRNA and protein expression in the thrombus and the vessel wall, which persisted for ≥1 week. VN protein also accumulated after injury, but VN mRNA levels remained low at all times.

Conclusions
—PAI-1 and VN participate in the thrombotic response to arterial injury by preventing premature thrombus dissolution and embolization. The accumulation of PAI-1 in the thrombus/vessel wall after injury may result, at least in part, from local synthesis, whereas the VN protein appears to be derived from plasma.
Absence of P-Selectin, but Not Intercellular Adhesion Molecule-1, Attenuates Neointimal Growth After Arterial Injury in Apolipoprotein E–Deficient Mice
Authors: Manka David , Collins Robert G. , Ley Klaus , Beaudet Arthur L. , Sarembock Ian J.
Published: June 2012

Background
—We tested the hypothesis that apolipoprotein (apo)E-deficient (apoE−/−) mice with targeted disruption of the
intercellular adhesion molecule-1
(
ICAM-1
) or
P-selectin
gene (apoE−/− ICAM-1−/− or apoE−/− P-selectin−/− mice, respectively) are protected from neointima formation after arterial injury through inhibition of monocyte trafficking to sites of endothelial denudation.

Methods and Results
—ApoE−/−, apoE−/− ICAM-1−/−, or apoE−/− P-selectin−/− mice were fed an atherogenic Western diet for 5 weeks and underwent wire denudation of the left common carotid artery after 1 week of feeding. The absence of P-selectin in apoE−/− mice inhibited neointima formation by 94% (
P
<0.0001) after arterial injury and reduced the intima-to-media ratio compared with the presence of P-selectin in apoE−/− mice. ICAM-1 deficiency did not protect against plaque formation after injury. Large numbers of macrophages were found in the neointima and media of apoE−/− and apoE−/− ICAM-1−/− mice. In contrast, almost no macrophages were found in the media or neointima of injured apoE−/− P-selectin−/− arteries.

Conclusions
—These findings demonstrate that the complete absence of P-selectin, but not ICAM-1, markedly reduces plaque area and suggest that P-selectin is critical for monocyte recruitment to sites of neointima formation after arterial injury.
Role of Functional Block Extension in Lesion-Related Atrial Flutter
Authors: Tomita Yasushi , Matsuo Kunihiro , Sahadevan Jayakumar , Khrestian Celeen M. , Waldo Albert L.
Published: June 2012

Background
—A line of block in the right atrium (RA) between the venae cavae is necessary to obtain classic atrial flutter (AFL). We tested the hypothesis that the location of that line of block would determine whether the AFL reentrant circuit would be due to single-loop reentry or figure-of-8 reentry.

Methods and Results
—Simultaneous mapping from 392 sites (both atria and the atrial septum) was performed in 13 normal dogs before and after creating a linear lesion on the RA free wall. The lesion was 1 to 1.5 cm anterior and parallel to the crista terminalis (7 dogs) or posterior and close to the crista terminalis region (6 dogs). Sustained AFL (>2 minutes) was then induced. In 4 dogs with an anterior lesion, the AFL reentrant circuit traveled around the lesion (lesion reentry). In 9 dogs (3 with anterior lesions and 6 with posterior lesions), the AFL reentrant circuit included the anterior RA free wall, the atrial septum, and Bachmann’s bundle (single-loop reentry). In these 9 dogs, the fixed line of block was extended to the superior and/or inferior vena cava by a functional line of block, thereby preventing lesion reentry. No figure-of-8 reentry was induced.

Conclusions
—In this model, the location of a fixed line of block and its functional extension determine the type of AFL reentry. These data provide an explanation for the chronic AFL that occurs in some patients after surgical repair of congenital heart lesions.
Beneficial Effects of Pentoxifylline in Patients With Idiopathic Dilated Cardiomyopathy Treated With Angiotensin-Converting Enzyme Inhibitors and Carvedilol
Authors: Skudicky Daniel , Bergemann Annette , Sliwa Karen , Candy Geoffrey , Sareli Pinhas
Published: June 2012

Background
—We previously reported beneficial effects of pentoxifylline, a xanthine-derived agent known to inhibit the production of tumor necrosis factor-α, in patients with idiopathic dilated cardiomyopathy treated with diuretics, digoxin, and ACE inhibitors. Since then, 3 large clinical trials showed important clinical benefits of β-blockers in this population. Therefore, we designed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and β-blockers, the addition of pentoxifylline would have an additive beneficial effect.

Methods and Results
—In a single-center, prospective, double-blind, randomized, placebo-controlled study, 39 patients with idiopathic dilated cardiomyopathy were randomized to pentoxifylline 400 mg TID (n=20) or placebo (n=19) if they had a left ventricular ejection fraction <40% after 3 months of therapy with digoxin, ACE inhibitors, and carvedilol. Primary end points were New York Heart Association functional class, exercise tolerance, and left ventricular function. Patients were followed up for 6 months. Five patients died (3 in the placebo group). Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group (
P
=0.01), with an increment in exercise time from 9.5±5 to 12.3±6 minutes (
P
=0.1). Left ventricular ejection fraction improved from 24±9% to 31±13%,
P
=0.03, in the treatment group.

Conclusions
—In patients with idiopathic dilated cardiomyopathy, the addition of pentoxifylline to treatment with digoxin, ACE inhibitors, and carvedilol is associated with a significant improvement in symptoms and left ventricular function.
Optical Mapping of Ventricular Defibrillation in Isolated Swine Right Ventricles
Authors: Wang Nina C. , Lee Moon-Hyoung , Ohara Toshihiko , Okuyama Yuji , Fishbein Gregory A. , Lin Shien-Fong , Karagueuzian Hrayr S. , Chen Peng-Sheng
Published: June 2012

Background

—

Investigators who studied ventricular defibrillation by use of optical mapping techniques failed to observe an initial defibrillation event (isoelectric window or quiescent period) shown by electrode mapping studies. This discrepancy has important implications for the mechanisms of defibrillation. The purpose of the present study was to demonstrate an optical equivalent of an isoelectric window after a near-threshold defibrillation shock.

Methods and Results

—

We studied 10 isolated, perfused swine right ventricles. Upper limit of vulnerability was determined by shocks on T waves. A 50% probability of successful defibrillation (DFT50) was determined with an up-down algorithm. Immediately after unsuccessful defibrillation shock, new wavefronts were generated. When the shock strength was low, immediate reinitiation of reentry and ventricular fibrillation might occur without a postshock isoelectric window. However, if the shock strength was within 50 V of DFT50 (near-threshold), a synchronized activation occurred, followed by organized repolarization that ended 64±18 ms after shock. After a period of quiescence (18±24 ms), activation recurred 83±33 ms after shock and reinitiated ventricular fibrillation. Similar patterns of activation, including a quiescent period, were observed after shock was applied on the T wave of the paced beat that induced ventricular fibrillation. Upper limit of vulnerability correlated well with DFT50.

Conclusions

—

In isolated swine right ventricles, an optical equivalent of an isoelectric window exists after near-threshold defibrillation shocks. These findings support the idea that a near-threshold defibrillation shock terminates all activation wavefronts but fails to halt ventricular fibrillation because the same shock reinitiates ventricular fibrillation after an isoelectric window.
Reentrant ventricular arrhythmias in the late myocardial infarction period: mechanism by which a short-long-short cardiac sequence facilitates the induction of reentry.
Authors: el-Sherif N , Gough W B , Restivo M
Published: June 2012

The electrophysiological mechanism by which a short-long-short stimulated cardiac sequence facilitates the induction of ventricular tachyarrhythmia was investigated in dogs 4 days after ligation of the left anterior descending coronary artery. In these dogs, reentry develops in the surviving electrophysiologically abnormal epicardial layer that overlies the infarct zone when premature stimulation results in a critically long arc of functional conduction block. The activation wavefront circulates around both ends of the arc, coalesces, and conducts slowly distal to the arc before reactivating sites proximal to the arc to initiate a figure-eight reentrant circuit. Epicardial isochronal activation maps and effective refractory periods (ERPs) were determined during three different stimulation protocols: A, a basic train of eight beats at a cycle length of 300 msec followed by a single premature stimulus (S2); B, a basic train of eight beats at a cycle length of 300 msec with abrupt lengthening of the last cycle of the train before S2 to 600 msec; C, a basic train of eight beats at a cycle length of 600 msec followed by S2. Protocol B was found to result in a differential lengthening of ERP at adjacent sites within the border of the epicardial ischemic zone, whereas protocols A and C induced, respectively, comparable shortening and lengthening of ERPs at the same sites. The differential lengthening of ERPs at adjacent sites resulted in an increased dispersion of refractoriness so that a premature stimulus induced functional conduction block between those sites. The development of a longer arc of conduction block and, hence, a longer reentrant pathway as well as slower conduction of the circulating wavefront during protocol B allowed more time for refractoriness to expire proximal to the arc and for the circulating wavefront to reexcite those sites to initiate reentry. The lengthening of ERP, associated with a single long cycle (protocol B), ranged from 44% to 79% of the total increase in ERP after a series of eight long cycles (protocol C). Epicardial sites with longer ERPs located close to the center of the ischemic zone showed more lengthening of refractoriness during protocol B compared with more normal sites near the border of the ischemic zone. This strongly suggests that the increased dispersion of refractoriness during protocol B is caused by the shorter memory of ischemic myocardium to the cumulative effects of preceding cycle lengths.
Quality of life after bypass surgery for unstable angina. 5-year follow-up results of a Veterans Affairs Cooperative Study.
Authors: Booth D C , Deupree R H , Hultgren H N , DeMaria A N , Scott S M , Luchi R J
Published: June 2012

To assess the effect of bypass surgery on outcome from unstable angina, 468 patients were randomized to medical treatment (237 patients) or surgery plus medical treatment (231 patients) and have been followed for comparison of survival, cardiac end points, and quality of life; the latter end point is discussed in the present report. Data were available at 3 and 5 years for 80% and 82% of patients in the medical group, respectively, and 77% and 80% of patients in the surgery group, respectively. At 3 months after randomization to therapy, 79.8% of patients in the surgery group reported subjective improvement, compared with 58% of the medical group, 12.6% of the surgery group reported no change compared with 24.5% of the medical group, and 5.5% of the surgery group reported worsening compared with 24.5% of the medical group (p less than 0.01 by chi 2). Similar data were found for chest pain status, and the benefit to the surgery group remained statistically significant through 5 years of follow-up. Crossover rate to surgery was 43% by 5 years. Treadmill duration was increased in the surgery group compared with the medical group (6.5 +/- 0.25 versus 5.3 +/- 0.25 minutes at 6 months, p less than 0.01), and a significant difference was again demonstrated at 3 and 5 years. A trend toward decreased recurrence of unstable angina was present in the surgery group at 1 year (six of 168 [3.6%] versus 13 of 187 [6.9%] in the medical group, p = 0.158), but the two groups were similar at 3 and 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Exercise training improves left ventricular systolic function in older men.
Authors: Ehsani A A , Ogawa T , Miller T R , Spina R J , Jilka S M
Published: June 2012

To determine whether endurance exercise training can improve left ventricular systolic function in older men, 10 healthy sedentary men (64 +/- 3 years old; mean +/- SD) were studied. Training consisted of endurance exercise 4 +/- 0.3 days per week for 11.8 +/- 2.5 months at a progressively increasing intensity of 60-80% of maximal O2 uptake (Vo2max) with additional brief bouts of exercise equal to 93 +/- 13% of Vo2max. Vo2max increased from 29.6 +/- 4.1 to 37.2 +/- 5.7 ml/kg/min (p less than 0.001). Percent body fat was decreased (17.8 +/- 3.6% versus 15.6 +/- 3.6%; p less than 0.001). Before training, left ventricular ejection fraction, determined by electrocardiographic-gated equilibrium blood pool imaging, increased only modestly during exercise (from 66.3 +/- 6.7% at rest to 70.6 +/- 6.9% at peak exercise). After training, the increase in ejection fraction during exercise was significantly greater (from 67 +/- 4.8% at rest to 77.6 +/- 7.5% at peak exercise) than that observed before training and was similar to that in young sedentary men (64 +/- 7% at rest versus 74 +/- 9% at peak exercise). Although the changes in systolic pressure from rest to exercise were similar, end-systolic volume decreased significantly at peak exercise after (51 +/- 12 versus 38 +/- 13 ml; p less than 0.005) but not before (46 +/- 8 versus 43 +/- 13 ml; p = NS) training with a shift in the end-systolic volume-systolic blood pressure relation to the left compatible with enhanced inotropic state.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms contributing to increased synthesis of plasminogen activator inhibitor type 1 in endothelial cells by constituents of platelets and their implications for thrombolysis.
Authors: Fujii S , Hopkins W E , Sobel B E
Published: June 2012

We recently hypothesized that after pharmacologically induced coronary thrombolysis, increased activity of plasminogen activator inhibitor type 1 (PAI-1) retards recanalization, contributes to early reocclusion, or both. This hypothesis was based on the increased elaboration of PAI-1 that we observed in cultured liver cells exposed to growth factors releasable from platelets activated at sites of thrombosis in vivo. PAI-1 released locally is particularly likely to attenuate lysis of thrombi that are targets of thrombolytic drugs. Accordingly, the present study was performed to determine whether synthesis of PAI-1 by endothelial cells is augmented by products of platelets. Lysates from platelets (0.5-8.0 x 10(4)/mm3 media, i.e. less than 10% of the concentration of platelets in blood) increased synthesis and release of PAI-1 into both the extracellular matrix and conditioned media (by 2.8-fold and 3.3-fold within 6 and 24 hours, respectively). Synthesis of neither tissue-type plasminogen activator nor overall protein increased. Increased synthesis of PAI-1 was confirmed by immunoprecipitation of [35S]PAI-1 after metabolic labeling of cells. The increased elaboration of PAI-1 was consistent with increased transcription as reflected by the observed increase in PAI-1 mRNA of 2.2-fold in 4 hours. Effects of platelet lysates were simulated by transforming growth factor beta (TGF-beta), known to be present in platelet alpha-granules and released with platelet activation. Antibody to TGF-beta reduced the stimulation of PAI-1 synthesis by TGF-beta, as expected, by 82%.(ABSTRACT TRUNCATED AT 250 WORDS)
Loss of endothelial pertussis toxin-sensitive G protein function in atherosclerotic porcine coronary arteries.
Authors: Shimokawa H , Flavahan N A , Vanhoutte P M
Published: June 2012

Pertussis toxin, an irreversible inhibitor of some G proteins, inhibits endothelium-dependent relaxations to certain agonists in porcine coronary arteries. In the present study, the effects of the toxin were examined on endothelium-dependent and -independent relaxations of hypercholesterolemic and atherosclerotic porcine coronary arteries to assess the functional state of the endothelial pertussis toxin-sensitive G protein. Male Yorkshire pigs were maintained on either a regular diet (control group, n = 7) or a 2% high-cholesterol diet (cholesterol-fed group, n = 7) for 10 weeks. After the initial 2 weeks of maintenance, animals in both groups underwent balloon catheter removal of the endothelium of the left anterior descending or left circumflex coronary arteries. Endothelium-dependent responses were examined in vitro after 10 weeks of maintenance; at this time, a full lining of endothelial cells in both left coronary arteries was confirmed histologically. In arteries with endothelium of the control group (normal responses), pertussis toxin significantly inhibited the endothelium-dependent relaxations to serotonin, UK14304 (a selective alpha 2-adrenergic receptor agonist), and thrombin but not those to ADP, bradykinin, or the calcium ionophore A23187. In previously denuded arteries of the control group (effects of endothelial regeneration alone) or intact arteries of the cholesterol-fed group (effects of hypercholesterolemia alone), the relaxations to serotonin, UK14304, and thrombin were impaired significantly; those relaxations were impaired further in previously denuded arteries of the cholesterol-fed group (effects of atherosclerosis). The inhibitory effects of pertussis toxin were significantly reduced after endothelial regeneration and in hypercholesterolemia and were almost absent in atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Load dependence of left ventricular diastolic pressure-volume relations during short-term coronary artery occlusion.
Authors: Applegate R J
Published: June 2012

We evaluated the effect of altered loading conditions on left ventricular (LV) diastolic pressure-volume relations during acute coronary artery occlusion that was produced by inflation of an intracoronary balloon. Open-chest anesthetized dogs (n = 18) were instrumented so that LV pressure (micromanometer) and LV volume (conductance) could be measured without disturbing the pericardium. The effects of brief periods of occlusion (1-2 minutes) were assessed under steady-state conditions before and after dextran infusion with the pericardium present and absent and during vena caval occlusion. Under steady-state conditions before dextran infusion with the pericardium removed, at an LV end-diastolic pressure (EDP) of 8.4 +/- 1.4 mm Hg, occlusion resulted in a rightward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 2.7 +/- 2.3 mm Hg; delta LVEDV, 6.3 +/- 4.7 ml, both p less than 0.05 versus control). After dextran infusion (LVEDP, 20.9 +/- 6.0 mm Hg), occlusion resulted in a rightward and upward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 5.8 +/- 4.4 mm Hg; delta LVEDV, 4.2 +/- 3.0 ml, both p less than 0.05 versus control). At low cardiac volumes before dextran infusion, the intact pericardium did not affect the response to occlusion. By contrast, after dextran infusion in the presence of an intact pericardium, LVEDP significantly increased (delta, 6.4 +/- 3.6 mm Hg, p less than 0.05) but LVDEV did not (delta, 0.7 +/- 1.5 ml, p = NS). There was a parallel upward shift in the diastolic portion of the LV pressure-volume loop that was eliminated by removal of the pericardium. Thus, the change in LV diastolic pressure and volume during occlusion varied and depended on the baseline cardiac volume and presence of the pericardium. Before dextran infusion with the pericardium present and absent, coronary artery occlusion did not alter the LV diastolic chamber stiffness parameter, which was calculated from the diastolic interval of an averaged steady-state beat (0.040 +/- 0.019 versus 0.036 +/- 0.015 mm Hg/ml, p = NS). After dextran infusion with the pericardium present and absent, coronary artery occlusion increased the LV diastolic chamber stiffness parameter (0.057 +/- 0.034 and 0.074 +/- 0.034 mm Hg/ml, both p less than 0.05 versus controls, respectively). Vena caval occlusion eliminated the shifts in the diastolic portion of the LV pressure-volume loop with the pericardium present and absent.(ABSTRACT TRUNCATED AT 400 WORDS)
Coronary blood flow in dogs with contractile dysfunction due to experimental volume overload.
Authors: Carabello B A , Nakano K , Ishihara K , Kanazawa S , Biederman R W , Spann J F
Published: June 2012

BACKGROUND

Abnormalities in coronary blood flow are responsible for stress-induced reductions in contractile function in pressure overload hypertrophy. Less is known about coronary blood flow in volume overload. In this study, we tested the hypothesis that coronary blood flow abnormalities were responsible for contractile abnormalities in experimental volume overload hypertrophy.

METHODS AND RESULTS

We examined coronary blood flow at rest and during pacing in seven dogs with contractile dysfunction secondary to chronic experimental mitral regurgitation (average regurgitant fraction at 3 months, 0.58 +/- 0.05). After 3 months of mitral regurgitation, left ventricular mass had increased from 92 +/- 8 g at baseline to 118 +/- 10 g (p less than 0.002). The slope of the end-ejection stress-volume relation, one of our indexes used to estimate contractile function, had fallen from 5.4 +/- 0.3 at baseline to 3.0 +/- 0.3 at 3 months of mitral regurgitation (p less than 0.001). In the mitral regurgitation dogs, coronary blood flow at rest was similar to that of control dogs (endocardial blood flow: control dogs, 1.33 +/- 0.12 ml/min/g; mitral regurgitation dogs, 1.16 ml/min/g, p = NS; epicardial blood flow at rest: control dogs, 1.30 +/- 0.16 ml/min/g; mitral regurgitation dogs 1.13 +/- 0.2 ml/min/g, p = NS). With pacing-induced stress, coronary blood flow increased appropriately in control and mitral regurgitation dogs. Ultrasonic dimension gauges placed in the endocardium and epicardium demonstrated no further deterioration in ventricular function during pacing in the mitral regurgitation dogs. In a separate group of five control dogs and five dogs with mitral regurgitation and left ventricular dysfunction, coronary blood flow was examined in the conscious closed-chest state at rest, during adenosine infusion, and during rapid atrial pacing (240 beats/min). Blood flow increased similarly in both groups during pacing and adenosine infusion.

CONCLUSIONS

We conclude that in dogs with mitral regurgitation that have developed contractile dysfunction, abnormalities in coronary blood flow do not explain the resting contractile dysfunction. Furthermore, studies during pacing-induced stress and coronary vasodilation with adenosine demonstrate that substantial coronary blood flow reserve is present in this type of volume overload hypertrophy.
Ten-year incidence of myocardial infarction and prognosis after infarction. Department of Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery.
Authors: Peduzzi P , Detre K , Murphy M L , Thomsen J , Hultgren H , Takaro T
Published: June 2012

BACKGROUND

The 10-year incidence of myocardial infarction (fatal and nonfatal) and the prognosis after infarction were evaluated in 686 patients with stable angina who were randomly assigned to medical or surgical treatment in the Veterans Administration Cooperative Study of Coronary Artery Bypass Surgery.

METHODS AND RESULTS

Myocardial infarction was defined by either new Q wave findings or clinical symptoms compatible with myocardial infarction accompanied by serum enzyme elevations with or without electrocardiographic findings. Treatment comparisons were made according to original treatment assignment; 35% of the medical cohort had bypass surgery during the 10-year follow-up period. The overall cumulative infarction rate was somewhat higher in patients assigned to surgery (36%) than in medical patients (31%) (p = 0.13) due to perioperative infarctions (13%) and an accelerated infarction rate after the fifth year of follow-up (average, 2.4%/yr in the surgical group versus 1.4%/yr in the medical group). The 10-year cumulative incidence of death or myocardial infarction was also higher in surgical (54%) than in medical (49%) patients (p = 0.20). According to the Cox model, the estimated risk of death after infarction was 59% lower in surgical than in medical patients (p less than 0.0001). The reduction in postinfarction mortality with surgery was most striking in the first month after the event: 99% in the first month (p less than 0.0001) and 49% subsequently (p less than 0.0001). The estimated risk of death in the absence of infarction was nearly identical regardless of treatment (p = 0.75). Exclusion of perioperative infarctions did not alter the findings.

CONCLUSIONS

Although surgery does not reduce the incidence of myocardial infarction overall, it does reduce the risk of mortality after infarction, particularly in the first 30 days after the event (fatal infarctions).
Results and follow-up after percutaneous pulsed laser-assisted balloon angioplasty guided by spectroscopy.
Authors: Geschwind H J , Aptecar E , Boussignac G , Dubois-Randé J L , Zelinsky R , Poirot G , Tomaru T
Published: June 2012

BACKGROUND

Few data are available on the long-term outcome of patients who undergo laser-assisted balloon angioplasty for recanalization of occluded peripheral arteries. Because the cost of laser angioplasty is high, the value of the method should be carefully analyzed before it can be considered a routine method for recanalization. The purpose of this study was to evaluate the early and late results of laser-assisted balloon angioplasty in patients who could not be recanalized by conventional techniques.

METHODS AND RESULTS

Laser angioplasty was performed in 66 patients with total occlusion of the iliofemoral artery in whom mechanical techniques failed to recanalize the obstructed vessel. The system consisted of a pulsed dye laser operated at 480 nm, 2 microseconds/pulse, 5 Hz, 50 mJ/pulse coupled into a 0.021-in. laser catheter. The treatment laser was connected with a diagnostic laser to induce tissue fluorescence for spectroscopic analysis via the same fiber. The treatment laser was emitted only when atheromatous tissue was recognized. After a pilot hole was created by laser emission, dilatation was performed to enlarge the channel. The mean length of occlusion was 8.8 +/- 6.1 cm. The primary success rate was 82%. It did not depend on the length of occlusion but was greater in non-calcified than in calcified lesions (88% versus 71%, p less than 0.03). Complications included seven early reocclusions that could be recanalized and eight perforations without clinical sequelae. At a mean 18-month follow-up, 64% of the laser-treated arteries remained patent. The rate of patency was related neither to the length of the occlusion nor to calcifications but was lower in patients who had early reocclusion (p less than 0.02).

CONCLUSIONS

Pulsed dye laser-assisted balloon angioplasty is effective for recanalization of totally occluded arteries that cannot be treated by conventional means. The efficacy is limited by calcifications. The long-term patency rate is acceptable given the severity of the lesions.
Concept of maximal flow ratio for immediate evaluation of percutaneous transluminal coronary angioplasty result by videodensitometry.
Authors: Pijls N H , Aengevaeren W R , Uijen G J , Hoevelaken A , Pijnenburg T , van Leeuwen K , van der Werf T
Published: June 2012

BACKGROUND

In the setting of percutaneous transluminal coronary angioplasty (PTCA), immediate information about the result of the intervention is important, whereas morphological parameters are often less reliable than in diagnostic coronary arteriography. Recently, a new videodensitometric method was introduced and validated in animal experiments, which allows accurate comparison of maximal myocardial perfusion between situations with different degrees of stenosis. This method uses mean transit time (Tmn) of the contrast agent at maximal hyperemia as a parameter for maximal flow and is strictly in accordance with indicated dilation theory.

METHODS AND RESULTS

In 40 patients with angina pectoris, single-vessel disease, and a positive exercise test at the time of acceptance for PTCA, this approach was applied for evaluation of the improvement of maximal flow achieved by the PTCA. Maximal vasodilation was induced immediately before and 15 minutes after PTCA by intracoronary administration of papaverine, and digital angiographic studies were performed. By special breath-holding instruction, almost motionless, triggered image acquisition was possible during 15-20 heartbeats. Excellent subtraction images could be obtained, and reliable determination of Tmn at maximal hyperemia was possible in 33 patients both before and after PTCA. The ratio between maximal flow after and before PTCA, called maximal flow ratio (MFR), was represented by the ratio between Tmn before and after the intervention and compared with the results of exercise testing 24-48 hours before and 7-10 days after the procedure. After correction for pressure changes, MFR was 2.2 +/- 1.5 for the 33 dilated vessels and 1.0 +/- 0.2 for 25 normal vessels serving as a control. In 94% of all patients, an MFR value of more than 1.6 or less than 1.6 discriminated between presence or absence of reversal of exercise test result from positive to negative. If on-line judgment of success was based upon angiographic parameters or measurement of trans-stenotic pressure gradient, the relation with noninvasive functional improvement was present only in 66% and 74% of all patients, respectively. A definite range of what can be called normal Tmn at maximal hyperemia could be distinguished, and post-PTCA values for successfully dilated arteries returned completely to this normal range.

CONCLUSIONS

Accurate comparison of maximal myocardial perfusion before and after PTCA is possible in man, improvement of maximal flow is highly related to functional improvement as indicated by exercise test results, and, therefore, this method provides a straightforward way for on-line evaluation of the result of the intervention.