bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.