bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasodilator responses of coronary resistance arteries of exercise-trained pigs.
Authors: Muller J M , Myers P R , Laughlin M H
Published: June 2012

BACKGROUND

The purpose of this study was to test the hypothesis that vasodilator responses of porcine coronary resistance arteries are increased by exercise training.

METHODS AND RESULTS

Yucatan miniature swine were randomly divided into groups of exercise-trained (ET) and sedentary (SED) control pigs. ET pigs were placed on a progressive treadmill training program lasting 16 to 20 weeks, and SED pigs remained inactive during the same time period. Coronary resistance arteries 64 to 157 microns in diameter were isolated for in vitro evaluation of relaxation responses to the endothelium-independent dilators sodium nitroprusside (1 x 10(-10) to 1 x 10(-4) mol/L) and adenosine (1 x 10(-10) to 1 x 10(-5) mol/L) and to bradykinin (1 x 10(-13) to 3 x 10(-7) mol/L), an endothelium-dependent agent. Relaxation responses to adenosine and sodium nitroprusside were not altered by exercise training. Endothelium-dependent relaxation to bradykinin was enhanced in coronary resistance arteries from ET pigs (IC50: ET, 0.07 +/- 0.02 nmol/L; SED, 1.59 +/- 0.09 nmol/L). To determine whether prostanoids and/or the nitric oxide synthase pathway were involved in the ET-induced changes in bradykinin-induced vasodilation, responses to bradykinin were examined in coronary resistance arteries from both ET and SED pigs in the presence of indomethacin and in the presence of nitro-monomethyl L-arginine (L-NMMA). Both indomethacin and L-NMMA produced significant inhibition of the bradykinin-induced relaxation in vessels from both groups. Despite decreased bradykinin-induced relaxation after indomethacin, bradykinin-induced vasodilation was still enhanced in vessels from the ET group. L-NMMA caused greater inhibition of the bradykinin-induced relaxation in coronary resistance arteries from ET pigs relative to arteries from SED pigs and eliminated the training-induced enhancement of the bradykinin responses.

CONCLUSIONS

These results suggest that exercise training enhances bradykinin-induced vasodilation through increased endothelium-derived relaxing factor/nitric oxide production by the L-arginine/nitric oxide synthase pathway.
Angiopeptin inhibits oncogene induction in rabbit aorta after balloon denudation.
Authors: Bauters C , Van Belle E , Wernert N , Delcayre C , Thomas F , Dupuis B , Lablanche J M , Bertrand M E , Swynghedauw B
Published: June 2012

BACKGROUND

Angiopeptin, a synthetic cyclic octapeptide analogue of somatostatin, reduces neointimal hyperplasia after balloon denudation of rabbit aorta if administered before injury. The aim of this study was to analyze the effect of angiopeptin pretreatment on the level of expression of the c-fos and c-jun protooncogenes, early markers of smooth muscle cell proliferation, after balloon denudation of rabbit aorta.

METHODS AND RESULTS

For histological analysis of the effect of angiopeptin on neointimal thickening after aortic balloon denudation, rabbits were randomized into three groups: group 1 (controls), twice-daily injections of saline begun 24 hours before balloon denudation (n = 9); group 2, twice-daily injections of angiopeptin 10 micrograms/kg begun 24 hours before balloon denudation (n = 9); and group 3, twice-daily injections of angiopeptin 10 micrograms/kg begun 1 hour after balloon denudation (n = 7). The degree of neointimal thickening 28 days after balloon denudation was significantly less in group 2 than in group 1 (neointimal area: group 1, 0.59 +/- 0.11 mm2; group 2, 0.22 +/- 0.05 mm2; P < .05. Neointima/media: group 1, 0.85 +/- 0.17; group 2, 0.23 +/- 0.05; P < .05). When angiopeptin was started 1 hour after denudation (group 3), however, the neointimal area (0.52 +/- 0.09 mm2) and the neointima/media ratio (0.76 +/- 0.10) were not statistically different from the control group. For analysis of protooncogene induction, rabbits received twice-daily subcutaneous injections of saline (n = 7), angiopeptin 10 micrograms/kg (n = 8), or angiopeptin 100 micrograms/kg (n = 4) begun 24 hours before balloon denudation. The animals were killed 30 minutes after balloon denudation, and total aortic RNA was hybridized with fos and jun probes. Expression of c-fos and c-jun was detected 30 minutes after injury; angiopeptin pretreatment at 20 micrograms.kg-1.d-1 induced a 41% reduction in c-fos expression and a 42% reduction in c-jun expression compared with control animals. The inhibitory effect at the higher dose of angiopeptin was similar.

CONCLUSIONS

Our results show that the inhibitory effect of angiopeptin on neointimal thickening is related to events that occur very early after injury and suggest that the inhibition of smooth muscle cell activation may be responsible, at least in part, for this effect.
Heart rate and force-frequency effects on diastolic function of the left ventricle in exercising dogs.
Authors: Miura T , Miyazaki S , Guth B D , Indolfi C , Ross J
Published: June 2012

BACKGROUND

Previous studies from our laboratory have shown pronounced augmentation of the force-frequency relation on myocardial contraction during exercise, but the influence of this effect on diastole has not been investigated.

METHODS AND RESULTS

Accordingly, the effect of changing heart rate on left ventricular (LV) relaxation, filling dynamics, and pressure-volume relations during exercise was studied in eight conscious dogs. The exercise heart rate was slowed from 208 +/- 21 (SD) to 163 +/- 11 beats per minute by injection of a specific sinus node inhibitor (UL-FS 49, or zatebradine, 0.6 mg/kg) during continuous exercise. Heart rate was then abruptly restored to the predrug level by atrial pacing during continued exercise. LV volume was calculated by use of implanted ultrasonic crystals, and LV pressure was determine with an implanted micromanometer. Comparing conditions after pacing back to a heart rate of 210 beats per minute with those obtained when the heart rate was slowed by atrial pacing, LV dP/dtmax was increased by 27% at the higher rate (P < .01), despite a marked decrease in LV end-diastolic pressure (24 +/- 4 versus 10 +/- 5 mm Hg, P < .01) and the time constant of isovolumic LV pressure decay (tau) was significantly shortened (19 +/- 5 versus 14 +/- 4 milliseconds, P < .01). The peak rapid filling rate in early diastole (PFR) was not significantly changed by increasing the heart rate, since it was maintained at the slower rate. During exercise, at the slowed heart rate the early portion of the diastolic pressure-volume curve was significantly shifted upward and to the right compared with that at the physiological heart rate, but the late portion of the curve was unchanged.

CONCLUSIONS

These data indicate that the negative inotropic effect of the force-frequency relation when heart rate was slowed during exercise caused pronounced impairment of LV relaxation and early filling dynamics. Conversely, an important component of the pronounced improvement of diastolic ventricular function during normal exercise was shown to result from exercise-induced enhancement of the positive inotropic effects of the force-frequency relation on myocardial contraction and relaxation.
Elucidation of Prinzmetal's variant form of preexcitation.
Authors: Munsif A , Scherlag B J , Lazzara R
Published: June 2012

BACKGROUND

In 1952, Prinzmetal induced preexcitation in the normal dog heart using subthreshold stimulation (SS) delivered to the right ventricle.

METHODS AND RESULTS

In 12 dogs we recorded ECG leads II, aVR, His (Hb) and proximal right bundle potentials with electrode catheters at the aortic root and a special electrode that was inserted through the right ventricular (RV) free wall. In 12 others, SS was delivered to the Hb area by a catheter placed under the septal leaflet of the tricuspid valve. During SS, the HV interval shortened from 35 +/- 4 milliseconds (mean +/- SD) to 19 +/- 7 milliseconds (P = .0001), but AH intervals were unchanged. The ECG showed delta waves with aberrant QRS complexes. Endocardial electrograms showed that the origin of activation in the preexcitation beats was localized to the muscle adjacent to the Hb or proximal right bundle. When vagal stimulation induced sudden AV block, no ventricular excitation was seen, confirming the subthreshold nature of the applied stimulation. By adjusting the levels of SS, latent forms of preexcitation could be induced, eg, early local septal muscle activation but no change in the ECG leads. Premature ventricular stimuli delivered to the RV apex or outflow tract could cause manifest preexcitation in the ECG leads or inhibit expression of latent preexcitation in endocardial recordings.

CONCLUSIONS

SS delivered to the RV apex or Hb area causes ventricular preexcitation, as shown previously by Prinzmetal et al. SS delivered at the insertion sites of an accessory pathway may facilitate localization of such abnormal connections, particularly when preexcitation is concealed.
Balloon angioplasty with stent implantation in experimental coarctation of the aorta.
Authors: Morrow W R , Smith V C , Ehler W J , VanDellen A F , Mullins C E
Published: June 2012

BACKGROUND

Balloon angioplasty of coarctation of the aorta is an effective method of treatment but is complicated by tearing of the aortic intima, formation of aneurysms, and restenosis. Stent placement at the time of balloon dilation could prevent restenosis and could also prevent progression of intimal tears to aneurysms. The purpose of this study was to evaluate the feasibility of balloon dilation and implantation of balloon-expandable stents in an experimental model of coarctation and to examine the effect of stent placement at the site of surgically created stenosis.

METHODS AND RESULTS

Coarctation of the aorta was surgically produced in 11 juvenile swine. Simultaneous coarctation angioplasty and stent implantation was performed in 10 animals 34 +/- 7.8 days after surgery. Repeat catheterization was performed 59 +/- 6 days after stent implantation. Five animals underwent reexpansion of stents with subsequent follow-up catheterization. Aortic specimens were examined by light microscopy and scanning electron microscopy. Coarctation angioplasty with stent implantation was successful in all, with an increase in coarctation diameter from 46 +/- 8.5% to 90 +/- 12.2% of proximal aortic diameter (P = .0001). Systolic pressure gradient decreased from 32 +/- 19.8 to 0.5 +/- 2.8 mm Hg (P < .001). All stents were patent at follow-up catheterization, with no evidence of intraluminal thrombosis. Reexpansion in five animals increased the stent diameter from a mean of 77.4 +/- 12.1% to 93 +/- 11.0% of proximal aortic diameter (P = .02). Gross examination of aortic specimens demonstrated formation of neointima over the stent wherever the stent struts were in contact with the aortic wall. The stent occupied a subintimal position and produced minimal compression of the underlying media. Medial compression was noted immediately beneath stent struts, but there was no evidence of intimal or medial dissection.

CONCLUSIONS

Balloon angioplasty with simultaneous implantation of balloon-expandable stents is effective in relieving aortic obstruction in experimental coarctation. Reexpansion of the rigid stent can be performed in an area of surgical aortotomy and coarctation without significant intimal or medial injury. Stent implantation may be useful in preventing restenosis and aneurysm formation after angioplasty of coarctation.
Myocardial blood flow at rest and during pharmacological vasodilation in cardiac transplants during and after successful treatment of rejection.
Authors: Chan S Y , Kobashigawa J , Stevenson L W , Brownfield E , Brunken R C , Schelbert H R
Published: June 2012

BACKGROUND

The relative intracoronary flow reserve has been found to be reduced during acute transplant rejection, but the effects of rejection on absolute flows at rest and during hyperemia have not been established previously. This has now become possible through noninvasive quantification of myocardial blood flow with positron emission tomography.

METHODS AND RESULTS

Myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia was quantified in 10 transplant patients (group A) during an acute, biopsy-proven rejection episode and again after successful immunosuppressive treatment and in 6 transplant patients (group B) without prior rejection episode. In group A patients, MBF during rejection averaged 1.7 +/- 0.3 mL.min-1.g-1 at rest and 2.5 +/- 0.9 mL.min-1.g-1 during hyperemia; after recovery, MBF at rest had declined to 1.2 +/- 0.3 mL.-1.g-1 (P < .001) but had increased to 3.9 +/- 1.1 mL.-1.g-1 (P < .001) during hyperemia. Flows after recovery from rejection were similar to those in the group B patients (0.9 +/- 0.2 and 3.9 +/- 0.7 mL.min-1.g-1). Flow reserve in the group A patients was only 1.5 +/- 0.5 during rejection but improved to 3.4 +/- 0.9 at recovery (P < .001) and thus remained lower than in the control patients (4.5 +/- 0.7, P < .05). Minimal coronary resistance during dipyridamole vasodilation was elevated during rejection (40 +/- 11 mm Hg.mL-1.min-1.g-1); after recovery, it no longer differed from that in the group B patients (26 +/- 11 versus 22 +/- 4 mm Hg.mL-1.min-1.g-1). MBF during rejection was increased relative to cardiac work, as demonstrated by significantly higher ratios of blood flow to rate-pressure product than those at recovery and in the control patients.

CONCLUSIONS

A decrease in hyperemic and an increase in resting myocardial blood flow, in excess to cardiac work, account for the previously reported reduction in coronary flow reserve. Because both alterations improve with antirejection treatment, they may reflect reversible alterations, presumably of endothelial function, local coagulation, and edema. The compromise in flow reserve and hyperemic flows may contribute to acute and chronic injury from rejection and thus provides a rationale for exercise restriction during rejection. The results further suggest a potential role for serial noninvasive flow measurements to guide immunosuppressive therapy.
Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition.
Authors: Good J M , Brady A J , Noormohamed F H , Oakley C M , Cleland J G
Published: June 2012

BACKGROUND

Contrary to expectation, most studies have demonstrated that initiation of an angiotensin-converting enzyme (ACE) inhibitor in conventional doses in patients with heart failure reduces the diuretic efficacy of furosemide. Recently, it has been suggested that single low doses (1 mg) but not high doses (25 mg) of captopril enhance furosemide-induced diuresis. It is not known whether the interaction between diuretics and ACE inhibitors are altered during long-term dosing.

METHODS AND RESULTS

Eight patients with heart failure treated with diuretics and ACE inhibitors for at least 3 months were studied. All patients were established on captopril 12.5 mg three times daily for 2 weeks before the study. Sodium intake was fixed before the study, and usual medication was withheld on study days. Intravenous furosemide was given on each of 2 study days to maintain a moderate, constant diuresis. Renal plasma flow and glomerular filtration rate (GFR) were determined using clearance techniques, and urine was collected hourly over 4 hours. Captopril 12.5 mg or placebo was given in a randomized, single-blind fashion at the end of the first hour. Compared with placebo, captopril reduced plasma concentrations of angiotensin II (23 +/- 18 versus 4 +/- 3 pg/ml 1 hour after dosing, P < .02) and systolic (131 +/- 31 versus 122 +/- 29 mm Hg, P < .01) and diastolic (74 +/- 15 versus 67 +/- 13 mm Hg, P < .05) blood pressures. GFR fell (55 +/- 24 versus 51 +/- 22 mL/min, P < .02) and effective renal plasma flow rose during the first (198 +/- 76 versus 231 +/- 49 mL/min) and second hours after dosing (185 +/- 69 versus 247 +/- 74 mL/min, P < .02). Similarly, urine volumes, in response to furosemide, increased after captopril (238 +/- 90 versus 283 +/- 111 mL, P < .05, and 245 +/- 78 versus 311 +/- 92 mL, P < .01, 1 and 2 hours after dosing). Urinary electrolyte concentrations fell, but total urinary sodium (22 +/- 7 versus 28 +/- 12 mmol/hr, P < .01) and chloride (20 +/- 6 versus 25 +/- 11 mmol/hr, P < .05) excretion increased in the 2 hours after dosing, as did fractional excretion of sodium (urinary sodium/urinary creatinine) (61 +/- 27 versus 75 +/- 36 mmol/mumol, P < .01).

CONCLUSIONS

Intense although transient ACE inhibition with captopril enhances the diuretic effects of furosemide during long-term ACE inhibition.
Impact of age on clinical outcome and postlytic management strategies in patients treated with intravenous thrombolytic therapy. Results from the TIMI II Study. TIMI II Investigators.
Authors: Aguirre F V , McMahon R P , Mueller H , Kleiman N S , Kern M J , Desvigne-Nickens P , Hamilton W P , Chaitman B R
Published: June 2012

BACKGROUND

Few thrombolytic studies have assessed whether patient age is an indication for routine postlytic cardiac catheterization and revascularization or evaluated the impact of age on 1-year outcome differences after acute myocardial infarction.

METHODS AND RESULTS

A secondary analysis of 3339 patients enrolled in the TIMI II trial was performed to identify differences in clinical and coronary angiographic findings and 1-year cardiac event rates among 841 patients < 50 years old, 1639 patients 50 to 64 years old, and 859 patients 65 to 75 years old. Differences in 1-year clinical outcome were assessed among patients randomly assigned to an invasive or a conservative postlytic strategy within each age group. The percentages of patients with a prior history of myocardial infarction, angina, congestive heart failure, hypertension, or diabetes mellitus or an infarction complicated at the time of study entry by shock, pulmonary edema, hypotension, rales more than one third of lung fields, or atrial fibrillation as well as the percentage of female patients (all P < .001) increased with age. Fewer older patients (65 to 75 years) received early (ie, < or = within 2 hours after symptom onset) treatment with recombinant tissue-type plasminogen activator (rTPA), and fewer were eligible for random assignment to immediate or deferred beta-blocker therapy (P = .01). The location of the infarct-related artery and the percentage of patients with patent (ie, TIMI flow grade 2 or 3) or "complete" (ie, TIMI flow grade 3) infarct-related artery flow did not vary with age. The percentage of patients with multivessel disease was greatest in the older patients (P = .001). Cumulative 1-year mortality was low in the youngest patients (2.8%; 99% confidence interval [CI], 1.6% to 4.7%) regardless of whether the infarct location was anterior (3.7%) or nonanterior (1.6%). The highest 1-year mortality occurred in the older patients (13.6%; 99% CI, 10.9% to 16.9%), particularly when the infarct location was anterior (18%). The 42-day rates of reinfarction (P = .85), death (P = .95), or death or reinfarction (P = .99) were similar in patients assigned to the invasive or conservative postlytic treatment strategy, regardless of age group.

CONCLUSIONS

Among patients with acute myocardial infarction treated with intravenous rTPA, heparin, and aspirin, there were age-related differences in time to treatment with thrombolytic therapy, use of beta-blockers, extent of coronary artery disease, and 1-year cardiac event rates. Routine use of cardiac catheterization and coronary revascularization does not improve immediate or 1-year outcome in terms of mortality or reinfarction compared with a more conservative strategy in young, middle-aged, or elderly patients similar to those enrolled in TIMI II.
Predicting and preventing sudden death from cardiac causes.
Authors: Gilman J K , Jalal S , Naccarelli G V
Published: June 2012

Sudden cardiac death usually occurs secondary to a ventricular tachyarrhythmia. Even under ideal circumstances only 20% of patients who have an out-of-hospital cardiac arrest survive to hospital discharge. Therefore, aggressive treatment and screening of high-risk patients are mandatory to improve survival rates. Risk stratification of high-risk patients, such as the post-myocardial infarction (MI) population, has been of limited value. Between 70% and 85% of "high-risk" post-MI patients, as defined by these screening tests, will not have a sustained ventricular tachyarrhythmia over several years of follow-up. The use of beta-blockers and possibly amiodarone may have some benefit in reducing mortality in high-risk patients after an MI. Several ongoing trials are studying the use of serial drug testing, amiodarone, and implantable cardioverter-defibrillators in reducing the incidence of sudden cardiac death in patients with potentially lethal ventricular arrhythmias. Although implantable cardioverter-defibrillators appear to be superior to antiarrhythmic drugs in reducing sudden cardiac death, total mortality may not be altered. In sustained ventricular tachyarrhythmias, sotalol and amiodarone appear to be superior to other drugs in preventing arrhythmia recurrence. Ongoing trials, such as the Antiarrhythmic Drug versus Implantable Device (AVID) trial may define the best strategy in these high-risk patients.
Correlation between cellular rejection of cardiac allografts and quantitative changes among T-cell subsets identified by V beta epitope expression.
Authors: Carlquist J F , Hammond M E , Yowell R L , Holland C , Swanson S , Anderson J L
Published: June 2012

BACKGROUND

Cellular rejection of an allograft is mediated in part by peripheral blood T cells. We tested the hypothesis that quantitative changes in T-cell subsets can be detected in the peripheral blood and that these changes correlate with rejection.

METHODS AND RESULTS

T-cell subset analysis was performed by flow cytometry using monoclonal antibodies recognizing six isotypic epitopes of the T-cell receptor beta-chain variable (V) region. These analyses were done at 7-day (mean) time intervals. Fluctuations within a given subset were determined by dividing the number of positive cells observed by the number of positive cells found on the previous analysis. For healthy volunteers observed over a period of 30 days, 119 of 120 subset ratios (99.2%) fell between 0.5 and 2.0. For patients, 57 of 240 subset ratios (23.8%) fell outside of this range (P < .004, chi 2). The occurrence of the abnormal ratios coincided more closely with cellular rejection (mean +/- SD, 7.7 +/- 6.2 days from a positive biopsy; median, 5 days; range, 0 to 28 days) than did the occurrence of normal subset ratios (mean +/- SD, 14.4 +/- 10.9 days from a positive biopsy; median, 11 days; range, 0 to 44 days; P < .005 by Mann-Whitney U test). Regression analysis confirmed a significant (P < .001, R = .91) temporal association between cellular rejection and abnormal subset fluctuations. No correlation was found between abnormal subset ratios and either vascular rejection or use of high-dose prednisone.

CONCLUSIONS

T-cell subset measurement may be a method of noninvasive monitoring of cellular rejection after transplantation and may provide insights into the physiology of graft rejection with the potential for the development of more specific immunosuppressive therapy.
Parallel analysis of tissue-type plasminogen activator and type 1 plasminogen activator inhibitor in plasma and endothelial cells derived from patients with chronic pulmonary thromboemboli.
Authors: Lang I M , Marsh J J , Olman M A , Moser K M , Schleef R R
Published: June 2012

BACKGROUND

Chronic thromboembolic pulmonary hypertension is the result of nonresolving pulmonary emboli that lead to chronic obstruction of the central pulmonary arteries.

METHODS AND RESULTS

To determine if the failure to lyse pulmonary thromboemboli is caused by an abnormality in the endothelial cell (EC)-associated fibrinolytic system, conditions were established to culture ECs from patient main pulmonary arteries during surgical pulmonary thromboendarterectomies and to analyze the conditioned media for levels of tissue-type plasminogen activator (TPA) and type 1 plasminogen activator inhibitor (PAI-1). Our data indicate that the levels of TPA antigen and PAI-1 activity in media conditioned by primary ECs harvested from areas free of thrombus were not significantly different between patients with chronic thromboemboli and organ donors. In 13 consecutive patients, no correlation was obtained in either the TPA antigen or PAI-1 activity level in a patient's plasma and the respective levels in media conditioned by the patient's pulmonary ECs. Moreover, patient pulmonary arterial ECs were observed to increase the secretion of TPA and PAI-1 in response to thrombin in a fashion similar to donor pulmonary artery ECs.

CONCLUSIONS

The data suggest that an inherent EC-mediated fibrinolytic imbalance is not a generalized phenomenon observed in pulmonary arteries of patients with chronic pulmonary thromboemboli.
Effects of thrombolytic therapy administered 6 to 24 hours after myocardial infarction on the signal-averaged ECG. Results of a multicenter randomized trial. LATE Ancillary Study Investigators. Late Assessment of Thrombolytic Efficacy.
Authors: Steinberg J S , Hochman J S , Morgan C D , Dorian P , Naylor C D , Theroux P , Topol E J , Armstrong P W
Published: June 2012

BACKGROUND

Thrombolytic therapy reduces mortality after acute myocardial infarction, even when treatment is initiated relatively late after onset of symptoms. The mechanism underlying this survival benefit is incompletely understood.

METHODS AND RESULTS

In a prospectively designed ancillary study of a randomized, placebo-controlled trial of late thrombolytic therapy (LATE), the signal-averaged (SA) ECG was recorded before hospital discharge in an effort to assess the effect of thrombolytic therapy on arrhythmia substrate. Three hundred ten patients were enrolled at 23 participating sites; 160 patients received placebo, and 150 patients received recombinant tissue-type plasminogen activator (rTPA) therapy 6 to 24 hours after onset of symptoms. Compared with placebo, rTPA tended to reduce the frequency of SAECG abnormality (filtered QRS duration > 120 milliseconds) by 37% (95% CI, -64%, +6%; P = .087) and the filtered QRS duration (105.7 +/- 13.8 versus 108.8 +/- 14.6 milliseconds, P = .05). In the prespecified subgroup of 185 patients with ST elevation on the qualifying ECG, rTPA resulted in a 52% reduction (95% CI, 4% to 77%, P = .011) of SAECG abnormality and a shorter filtered QRS duration (105.7 +/- 10.9 versus 110.7 +/- 15.9 milliseconds, P = .01). No benefit was seen in patients without ST elevation on ECG.

CONCLUSIONS

Late thrombolytic therapy produced a more stable electrical substrate, which probably represents an important mechanism of mortality benefit.
Limitation of infarct size and preservation of left ventricular function after primary coronary angioplasty compared with intravenous streptokinase in acute myocardial infarction.
Authors: de Boer M J , Suryapranata H , Hoorntje J C , Reiffers S , Liem A L , Miedema K , Hermens W T , van den Brand M J , Zijlstra F
Published: June 2012

BACKGROUND

Early and effective flow through the infarct-related vessel is probably of paramount importance for limitation of infarct size and preservation of left ventricular function in patients with acute myocardial infarction. Primary coronary angioplasty may offer advantages in these respects compared with thrombolytic therapy. The purpose of the present study was to assess the effects on estimated enzymatic infarct size and left ventricular function in patients with acute myocardial infarction randomly assigned to undergo primary angioplasty or to receive intravenous streptokinase.

METHODS AND RESULTS

We evaluated 301 patients with signs of acute myocardial infarction and without contraindications for thrombolysis who presented within 6 hours after onset of symptoms or between 6 and 24 hours if there was evidence of ongoing ischemia. One hundred fifty-two patients were randomly assigned to undergo primary angioplasty, and 149 patients were assigned to receive treatment with streptokinase (1.5 million U i.v.). Infarct size was estimated from enzyme release. Global left ventricular ejection fraction and regional wall motion, if possible in combination with exercise testing, were evaluated by radionuclide ventriculography before discharge. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 through the infarct-related vessel within 120 minutes after admission was achieved in 92% of all patients assigned to receive primary angioplasty therapy. Myocardial infarct size was 23% smaller in the angioplasty group compared with patients assigned to receive streptokinase (1003 +/- 784 versus 1310 +/- 1198 U/L, P = .012). Global left ventricular ejection fraction (50 +/- 9% versus 45 +/- 11%, P < .001) and regional wall motion in the infarct-related zones (42 +/- 14% versus 34 +/- 13%, P < .001) were better in the angioplasty group, which could mainly be contributed to myocardial salvage in the infarct-related areas. The observed differences were more pronounced in patients with an anterior wall myocardial infarction, although patients with a nonanterior infarct location also showed a beneficial effect of primary coronary angioplasty on left ventricular function compared with streptokinase therapy. Furthermore, the observed differences appeared to be more pronounced in patients presenting relatively early (within 2 hours) after onset of symptoms.

CONCLUSIONS

In patients with acute myocardial infarction, primary angioplasty results in a smaller infarct size and a better preserved myocardial function compared with patients randomized to receive treatment with intravenous streptokinase. This is probably due to early and optimal blood flow through the infarct-related vessel, as can be accomplished in a very high percentage of patients undergoing primary coronary angioplasty.
Randomized study of aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass surgery.
Authors: Rocha E , Hidalgo F , Llorens R , Melero J M , Arroyo J L , Páramo J A
Published: June 2012

BACKGROUND

Patients on cardiopulmonary bypass (CPB) have an increased susceptibility to postoperative bleeding. Previous reports using desmopressin acetate (DDAVP) for the prevention of postoperative bleeding have given contradictory results, whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery. This randomized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB.

METHODS AND RESULTS

One hundred nine of 122 eligible patients were randomized to four different groups: Group A (n = 28) received aprotinin starting with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6) KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3 micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of DDAVP, the first as in group B and an additional dose 6 hours after surgery; group D (n = 28) received no treatment. There was a marked reduction of postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in the aprotinin group compared with all other groups, whereas no significant effect was observed in either of the two DDAVP regimens. A significant reduction in the amount of blood used was observed only in the aprotinin group (P < .01). Of the plasma fibrinolytic components assayed, there was a significant reduction of the fibrin degradation product generation in the aprotinin group (P < .001), whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group. No side effects related to the study drugs were observed in any patient.

CONCLUSIONS

Aprotinin inhibited fibrinolysis; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial effect. Aprotinin offers a better alternative than DDAVP in the prevention of bleeding after CPB.
Sex-specific determinants of increased left ventricular mass in the Tecumseh Blood Pressure Study.
Authors: Marcus R , Krause L , Weder A B , Dominguez-Meja A , Schork N J , Julius S
Published: June 2012

BACKGROUND

Left ventricular hypertrophy (LVH) defined by either ECG or echocardiographic criteria is a risk factor for cardiovascular morbidity and mortality. A number of determinants of LVH have been described in previous studies, principally male sex, hypertension, obesity, and aortic valvular stenosis. We examined the distribution of LV mass (LVM) in a population of 18- to 42-year-old normotensive men and women who were free of valvular heart disease to establish sex-specific normal values for LVM index (LVMI) and to determine the correlates of LVMI.

METHODS AND RESULTS

LVM was derived from measurements obtained by M-mode echocardiography. Average LVMI is significantly greater in men (102.9 +/- 0.7 g/m2) than women (88.2 +/- 0.7 g/m2). By defining LVH as an LVMI greater than the 90th percentile, we developed sex-specific criteria for LVH: men, > 125.4 g/m2; women, > 110 g/m2. We found that LVH in men is associated with indices of enhanced sympathetic nervous system reactivity and with elevated fasting insulin and triglyceride levels, which may be caused by insulin resistance. In women, LVH was associated with higher body weight and obesity.

CONCLUSIONS

Before the onset of hypertension, increased LVMI appears to have different determinants in men and women. We suggest that early LVH in young men is a manifestation of hyperkinetic borderline hypertension, a state previously shown to be associated with increased sympathetic nervous system activity and insulin resistance. The hyperkinetic state is less prevalent in young women, in whom increased adiposity seems to be the predominant factor associated with LVH.
Serum antioxidants and myocardial infarction. Are low levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction?
Authors: Street D A , Comstock G W , Salkeld R M , Schüep W , Klag M J
Published: June 2012

BACKGROUND

In vitro, animal and epidemiological studies suggest that lipoprotein oxidation may play an important role in atherosclerosis. Antioxidants may protect against lipoprotein oxidation and in that way inhibit atherosclerosis and its clinical sequelae. To investigate this possibility, we examined the association between levels of several antioxidants and myocardial infarction using serum specimens collected 7 to 14 years before the onset of myocardial infarction.

METHODS AND RESULTS

A nested case-control design was used. Cases and control subjects were selected from the 25,802 persons who had donated 15 mL of blood in 1974 for a serum bank. Cases comprised 123 persons with a subsequent first diagnosis of myocardial infarction who ranged from 23 through 58 years of age in 1974 and who had had their first diagnosis of myocardial infarction during 1981 to 1988. Two groups of control subjects matched to the cases for sex and age were selected from donors to the serum bank, one from those with hospital admissions during the same period and the other from the total group of donors. Sera were assayed for four carotenoids (beta-carotene, lycopene, lutein, and zeaxanthin), alpha-tocopherol, and cholesterol. Because associations with these serum nutrients showed similar trends whether based on hospital or community controls, the two control groups were combined. There was a significantly increasing risk for subsequent myocardial infarction with decreasing levels of beta-carotene in 1974 (P value for trend, .02) and a suggestive trend with decreasing levels of lutein (P = .09). When the results were stratified by smoking status, the excess risk of myocardial infarction associated with low serum levels of carotenoids was limited to smokers. A protective association with higher levels of alpha-tocopherol was suggested only among persons with high levels of serum cholesterol.

CONCLUSIONS

Low serum levels of carotenoids were associated with an increased risk of subsequent myocardial infarction among smokers.
Platelet alpha-granule release in cocaine users.
Authors: Rinder H M , Ault K A , Jatlow P I , Kosten T R , Smith B R
Published: June 2012

BACKGROUND

Cocaine use has been associated with arterial occlusion resulting from platelet-rich thrombi and with an accelerated, often atypical atherosclerotic lesion that could be ascribed to platelet activation and platelet alpha-granule release.

METHODS AND RESULTS

Using a flow cytometric method to quantitate the percent of circulating activated platelets in whole blood (those that express the alpha-granule membrane protein P-selectin), we found that 5 of 25 samples from 12 long-term cocaine users had a baseline level of circulating activated platelets > 3 SD (range, 19% to 60%) above the mean (4.4 +/- 3.7%, mean +/- 1 SD) for 85 nonusers (sample n = 130). This subset resulted in a significantly higher mean baseline level of circulating activated platelets (11.8 +/- 14.4%) for all cocaine users (P = .01). By contrast, cocaine and its metabolites, at concentrations documented as obtainable during in vivo cocaine use (10(-7) to 10(-5) mol/L), had no effect on in vitro platelet activation or aggregation, either directly or in concert with platelet agonists. However, in experiments in which cocaine users received blinded infusions of placebo or cocaine, the mean percent of circulating activated platelets rose significantly (P < .05) after infusion of either placebo (peak 77 +/- 31%) or cocaine (peak 65 +/- 28%), the latter at doses resulting in peak plasma cocaine levels averaging < 10(-6) mol/L.

CONCLUSIONS

Long-term cocaine use in some subjects is intermittently associated with high basal levels of circulating platelets that have undergone alpha-granule release. The inability of cocaine and its metabolites at concentrations of 10(-7) to 10(-5) mol/L to cause platelet P-selectin expression in vitro in this study, coupled with the acute increase in circulating activated platelets observed in vivo after either cocaine or placebo infusion, suggests that in vivo platelet alpha-granule release associated with cocaine use may occur through indirect rather than direct effects of the drug.
Left ventricular wall thickness and regional systolic function in patients with hypertrophic cardiomyopathy. A three-dimensional tagged magnetic resonance imaging study.
Authors: Dong S J , MacGregor J H , Crawley A P , McVeigh E , Belenkie I , Smith E R , Tyberg J V , Beyar R
Published: June 2012

BACKGROUND

Regional performance of the hypertrophied left ventricle (LV) in hypertrophic cardiomyopathy (HCM) is still incompletely characterized with studies variably reporting that the hypertrophied myocardium is hypokinetic, akinetic, or has normal function. Different imaging modalities (M-mode or two-dimensional echocardiography) and methods of analysis (fixed or floating frame of reference for wall motion analysis) yield different results. We assessed regional function in terms of systolic wall thickening and shortening and related these parameters to end-diastolic thickness using tagged magnetic resonance imaging and the three-dimensional volume-element approach.

METHODS AND RESULTS

In 17 patients with HCM and 6 healthy volunteers, four parallel short-axis images with 12 radial tags and two mutually orthogonal long-axis images with four parallel tags were obtained at end diastole and end systole. After the LV endocardial and epicardial borders were traced, three-dimensional volume elements were constructed by connecting two matched planar segments in two adjacent short-axis image planes, accounting for translation, twist, and long-axis shortening. A total of 72 such volume elements encompassed the entire LV. From each of these elements, end-diastolic thickness and systolic function (fractional thickening and circumferential shortening) were calculated. The average end-diastolic thickness was 15.8 +/- 4.2 mm in patients with HCM, which was significantly greater than that in healthy subjects (8.6 +/- 2.1 mm, P < .001). Fractional thickening was significantly less in patients with HCM than in healthy subjects (0.31 +/- 0.22 versus 0.56 +/- 0.23, P < .001). There was a highly significant inverse correlation between fractional thickening and end-diastolic thickness that was independent of the type of hypertrophy or age group. Similar inverse relations were observed between circumferential shortening and end-diastolic wall thickness.

CONCLUSIONS

The myocardium in patients with HCM is heterogeneously thickened and the fractional thickening and circumferential shortening of the abnormally thickened myocardium are reduced compared with healthy subjects. The decrease in fractional thickening and shortening is inversely related to the local thickness.
Existence and role of substrate cycling between AMP and adenosine in isolated rabbit cardiomyocytes under control conditions and in ATP depletion.
Authors: Wagner D R , Bontemps F , van den Berghe G
Published: June 2012

BACKGROUND

Adenosine, a physiological coronary vasodilator, has been proposed to regulate coronary circulation according to myocardial oxygen demand. In the present study, we investigated the mechanisms of adenosine formation and utilization in isolated rabbit cardiomyocytes and, in particular, the existence and the role of substrate cycling between AMP and adenosine in the regulation of its concentration.

METHODS AND RESULTS

Rabbit cardiomyocytes were isolated by collagenase perfusion and incubated in HEPES-buffered Krebs-Henseleit solution at 37 degrees C, pH 7.4, in control conditions and in ATP depletion achieved by inhibiting glycolysis with 5 mmol/L iodoacetate. Under control conditions, adenosine accumulated at a rate of 4 pmol.min-1.10(-6) cells. The 13-fold elevation of adenosine accumulation induced by iodotubercidin (ITu), an inhibitor of adenosine kinase, proves that adenosine is normally recycled into AMP. This recycling involves 95% of the adenosine formed. In ATP depletion, adenosine accumulated at the rate of 335 pmol.min-1.10(-6) cells and was no longer rephosphorylated after 20 minutes, as shown by the absence of effect of ITu after this time interval. Moreover, adenosine was deaminated, as indicated by the twofold increase of its accumulation induced by deoxycoformycin (dCF), an inhibitor of adenosine deaminase. Both in control conditions and in ATP depletion, adenosine-dialdehyde, an inhibitor of S-adenosylhomocysteine (SAH) hydrolase, had no significant effect on adenosine formation, indicating that the transmethylation pathway is not an important source of adenosine in rabbit cardiomyocytes.

CONCLUSIONS

The results indicate that recycling of adenosine into AMP is essential for the maintenance of low, nonvasodilatory concentrations of the nucleoside under control conditions and that interruption of recycling plays an important role in elevating adenosine during ATP depletion.
Effects of reperfusion on ischemic right ventricular dysfunction. Disparate mechanisms of benefit related to duration of ischemia.
Authors: Laster S B , Ohnishi Y , Saffitz J E , Goldstein J A
Published: June 2012

BACKGROUND

Right ventricular free wall (RVFW) ischemia impairs global RV performance and may result in acute hemodynamic compromise. However, RV function and hemodynamic performance typically improve spontaneously over time. This study was designed to determine whether reperfusion facilitates recovery of function in the ischemic right ventricle.

METHODS AND RESULTS

Closed chest dogs underwent right coronary balloon occlusion for 1 hour (n = 9), 4 hours (n = 6), or 8 hours (n = 7). In all animals, occlusion depressed RVFW function and global RV performance. After 1 hour of ischemia, reperfusion led to immediate improvement in RVFW function and consequently global RV performance, with complete recovery over 4 weeks and scar in < 1% of total RVFW area. Reperfusion after 4- and 8-hour occlusions resulted in acute improvement in global RV performance but to a lesser extent and by different mechanisms, since RVFW contraction remained severely impaired. This disproportionate recovery of global RV function was attributable to diminished RVFW dyskinesis associated with reperfusion-induced increments in RVFW diastolic thickness (characterized histopathologically in 6 additional animals subjected to 4-hour occlusions but killed 1 hour after reperfusion by interstitial edema, contraction band necrosis, and hemorrhage). Although later reperfusion was associated with a slower pace and lesser extent of recovery, RVFW contraction improved markedly over time. At 4 weeks, there was trivial RVFW scar in 4-hour animals (2% of total RVFW area), and, although fibrosis was significantly greater in 8-hour animals (7% of RVFW area), infarction was minimal relative to the extent of jeopardized myocardium.

CONCLUSIONS

The responses of ischemic RV myocardium to reperfusion are complex, with disparate effects according to the duration of preceding ischemia. Early reperfusion results in prompt improvement in and subsequent complete recovery of RVFW contraction and global RV performance, with trivial or no RVFW scar. Late reperfusion leads to little acute recovery of RVFW function, but global performance improves owing to diminished RVFW dyskinesis associated with reperfusion-induced increments in RVFW diastolic thickness. Nevertheless, RVFW function improves over time, with minimal evidence of infarction. Therefore, reperfusion facilitates recovery of RV function and minimizes the extent of infarction even after prolonged ischemia.
Optical mapping of repolarization and refractoriness from intact hearts.
Authors: Efimov I R , Huang D T , Rendt J M , Salama G
Published: June 2012

BACKGROUND

Heterogeneities of repolarization (R) across the myocardium have been invoked to explain most reentrant arrhythmias. The measurement of refractory periods (RPs) has been widely used to assess R, but conventional electrode and extrastimulus mapping techniques have not provided reliable maps of RPs.

METHODS AND RESULTS

Guinea pig hearts were stained with a voltage-sensitive dye to measure fluorescence (F) action potentials (APs) from 124 sites with a photodiode array. AP duration (APD) was defined as the time between depolarization (dF/dt)max and R time points (ie, the time when AP returns to baseline or some percent thereof). However, R time points are difficult to determine because AP downstrokes are often encumbered by drifting baselines and motion artifacts, which make this definition ambiguous. In optical and microelectrode recordings, the second derivative of AP downstrokes is shown to contain an easily detected, unique local maximum. The correlation between the position of this maximum (d2F/dt2)max and R has been tested during altered AP characteristics induced by changes in cycle length, ischemia, and hypoxia. Under these various modifications of the AP, the time points of (d2F/dt2)max fell at 97.0 +/- 2.1% of recovery to baseline. Extrastimulus techniques applied to (1) isolated myocytes, (2) intact hearts, and (3) mathematical simulations indicated that (d2V/dt2)max coincided with the effective RPs of APs. The coincidence of RPs and (d2V/dt2)max was valid within 5 milliseconds, for resting potentials of -75 to -90 mV and extrastimuli three times threshold voltage.

CONCLUSIONS

Thus, optical APs and (d2F/dt2)max can be used to map activation, R, and RPs with AP recordings from a single heartbeat.