bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive value of reactive hyperemic response on reperfusion on recovery of regional myocardial function after coronary angioplasty in acute myocardial infarction.
Authors: Suryapranata H , Zijlstra F , MacLeod D C , van den Brand M , de Feyter P J , Serruys P W
Published: June 2012

BACKGROUND

The objective of the study was to determine the coronary vasodilatory reserve in reperfused myocardium in patients with acute myocardial infarction and its relation to regional myocardial function.

METHODS AND RESULTS

The study population consisted of 22 patients with acute myocardial infarction who underwent successful coronary angioplasty. The vasodilatory reserve in the reperfused myocardium was assessed quantitatively using computer-assisted digital subtraction cine-angiography immediately after angioplasty and at follow-up angiography before hospital discharge. Myocardial contrast medium appearance time and density were determined before and after pharmacological hyperemia induced by an intracoronary injection of 12.5 mg papaverine. Global and regional left ventricular functions were determined from contrast angiography. After papaverine, the mean contrast medium appearance time decreased significantly from 3.5 +/- 0.7 to 2.7 +/- 0.7 cardiac cycles (P < .000005) immediately after successful coronary angioplasty and from 3.8 +/- 0.7 to 2.7 +/- 0.9 cardiac cycles (P < .000005) at angiography before hospital discharge. The mean contrast medium density increased significantly from 48.7 +/- 13.8 to 61.0 +/- 19.0 pixels (P < .003) and from 49.6 +/- 19.7 to 80.3 +/- 29.6 pixels (P < .000005), respectively. As a consequence, the calculated coronary flow reserve increased significantly from 1.8 +/- 0.7 to 2.6 +/- 1.0 (P < .0008). The global ejection fraction increased significantly from 52 +/- 12% to 58 +/- 14% (P < .03), primarily because of a significant improvement in the regional myocardial function of the infarct zone from 20.8 +/- 9.0% to 26.0 +/- 10.5% (P < .001). Coronary flow reserve correlated well with regional myocardial function both during the acute phase (R = .79, P < .002) and at follow-up angiography (R = .82, P < .000004). Interestingly, coronary flow reserve measurement on reperfusion, immediately after angioplasty, correlated significantly with regional myocardial function at follow-up angiography (R = .81, P < .00003).

CONCLUSIONS

The results indicate that there is a pharmacologically inducible vasodilatory reserve in reperfused ischemic myocardium after successful coronary angioplasty in patients with acute myocardial infarction and that this is increased at 10-day follow-up angiography. More important, the degree of reactive hyperemic response on reperfusion has a predictive value regarding the ultimate degree of recovery of regional myocardial function. Quantitative assessment of reperfusion may be useful in investigating the role of coronary reperfusion and salvage of myocardial function.
Long-term graft patency (3 years) after coronary artery surgery. Effects of aspirin: results of a VA Cooperative study.
Authors: Goldman S , Copeland J , Moritz T , Henderson W , Zadina K , Ovitt T , Kern K B , Sethi G , Sharma G V , Khuri S
Published: June 2012

BACKGROUND

The long-term success of coronary bypass surgery is dependent on graft patency after surgery. This trial was designed to determine if aspirin improved saphenous vein graft or internal mammary artery (IMA) graft patency between 1 and 3 years after coronary artery bypass grafting (CABG).

METHODS AND RESULTS

After receiving aspirin 325 mg/d for 1 year after CABG and undergoing a 1-year postoperative cardiac catheterization, patients were randomized to receive either aspirin (325 mg) or placebo for 2 additional years. Angiography was performed 3 years after surgery to determine the primary end point-saphenous vein graft patency in 288 patients and IMA graft patency in 167 patients. At 3 years after CABG, the saphenous vein graft occlusion rate was 17.0% (62 of 365) for patients treated with aspirin compared with 19.7% (74 of 376) for those who received placebo (P = .404). For saphenous vein grafts that were patent at 1 year, the occlusion rate at 3 years was 4.8% (15 of 313) for patients treated with aspirin compared with 4.2% (13 of 310) for patients who received placebo (P = .757). At 3 years, the IMA graft occlusion rate was 10.3% (8 of 78) for patients treated with aspirin compared with 7.9% (7 of 89) for patients who received placebo (P = .594). For IMA grafts that were patent at 1 year, the occlusion rate was 4.3% (3 of 70) for patients treated with aspirin compared with 2.5% (2 of 81) for patients who received placebo (P = .541).

CONCLUSIONS

These data suggest that aspirin treatment does not improve saphenous vein graft or IMA graft patency between 1 and 3 years after CABG.
Reconsideration of criteria for the Fontan operation. Influence of pulmonary artery size on postoperative hemodynamics of the Fontan operation.
Authors: Senzaki H , Isoda T , Ishizawa A , Hishi T
Published: June 2012

BACKGROUND

The outcome of the Fontan operation largely depends on the selection of patients because this procedure is a physiological correction. Among the several selection criteria for the Fontan operation, the importance of adequate size of the pulmonary artery remains controversial. In this series, in order to clarify whether the pulmonary artery size is indispensable or not as one of the selection criteria for the Fontan operation, we considered the physiological meaning of pulmonary artery size and investigated how it influenced postoperative hemodynamics of the Fontan operation.

METHODS AND RESULTS

In congenital heart disease of decreasing pulmonary blood flow, 40 patients were examined for this analysis. Pulmonary artery indexes (cross-sectional area of the right and left pulmonary arteries divided by body surface area) were measured as the expression of pulmonary artery size, and the relations of pulmonary artery index (PAI) to pulmonary vascular resistance (Rp) and compliance (Cp) were studied. There was no significant correlation between PAI and Rp, whereas a significant correlation was found between PAI and Cp (r = .71, P = .001). Furthermore, Cp influenced postoperative hemodynamics of the Fontan operation by affecting the peak central venous pressure (pCVP) and total impedance, which was the afterload to the ventricle. Impedance increased abruptly when PAI was < approximately 100 mm2/m2.

CONCLUSIONS

The smaller pulmonary artery size causes more disadvantageous hemodynamics after the Fontan operation, with resultant effects of the rise in pCVP and the increase in afterload to the single ventricle.
Plasma angiotensin-converting enzyme activity and carotid wall thickening.
Authors: Bonithon-Kopp C , Ducimetière P , Touboul P J , Fève J M , Billaud E , Courbon D , Héraud V
Published: June 2012

BACKGROUND

Mechanisms underlying the previously reported association between a deletion polymorphism in the gene encoding for angiotensin-converting enzyme (ACE) and the risk of myocardial infarction in low-risk subjects are unclear. The purpose of this case-control study was to examine the relation of plasma ACE activity to intimal-medial thickness of the carotid wall measured ultrasonographically in an apparently healthy population.

METHODS AND RESULTS

We determined plasma ACE activity in 80 pairs of subjects without any history of ischemic heart disease or any treatment of hypertension and diabetes. Cases and control subjects were defined on the basis of intimal-medial thickness measured in the common carotid arteries by B-mode ultrasound and were matched for sex, sonographer, and the presence of atheromatous plaques. Subjects were selected from a sample of 434 men and 602 women between 60 and 69 years old participating in an ongoing study on vascular aging (EVA). Subjects with intimal-medial thickening (cases) showed a slight but not significant increase in plasma ACE activity in comparison with control subjects (P < .16). However, after exclusion of subjects receiving lipid-lowering drugs, the mean plasma ACE activity became significantly higher in cases than in control subjects (29.9 +/- 7.7 U/L versus 27.5 +/- 8.0 U/L; n = 54 pairs, P < .03). The mean case-control difference in plasma ACE activity was further increased when analysis was restricted to pairs without carotid atheromatous plaques (n = 42 pairs). After adjustment for body mass index, smoking, and systolic blood pressure, the odds ratio for having carotid wall thickening based on 1 SD difference in log ACE was 2.29 (95% confidence interval, 1.16 to 4.52; P < .02).

CONCLUSIONS

The results of the study suggest that chronic exposure to high levels of plasma ACE could be involved in structural changes of the arterial wall.
Dyslipidemia and ischemic heart disease mortality among men and women with diabetes.
Authors: Goldschmid M G , Barrett-Connor E , Edelstein S L , Wingard D L , Cohn B A , Herman W H
Published: June 2012

BACKGROUND

We investigated whether the greater increased risk of ischemic heart disease mortality associated with diabetes among women compared with men could be explained by their more pronounced lipoprotein abnormalities.

METHODS AND RESULTS

Seventy-six men and 45 women with diabetes and 327 men and 496 women without diabetes were followed for an average of 16 years in a population-based study. Cox proportional hazards models were used to determine the relative hazard of ischemic heart disease mortality for changes in lipoprotein subfractions after adjustment for age, hypertension, obesity, smoking, exercise, alcohol consumption, and estrogen use (among women). The relative hazard of ischemic heart disease mortality among diabetic women was 1.76 (P = .10) for a 10-mg/dL decrement in high-density lipoprotein cholesterol (HDL-C) and 3.13 (P = .01) for a 1-U increment in log very-low-density lipoprotein cholesterol (VLDL-C). The risk of ischemic heart disease mortality among diabetic women relative to nondiabetic women for an HDL-C level of 50 mg/dL and a log(e) VLDL-C of 3 (about 20 mg/dL) were 4.1 and 3.4, respectively (P < .05). These lipoprotein changes were not associated with ischemic heart disease mortality among men or among nondiabetic women.

CONCLUSIONS

Excess ischemic heart disease mortality among diabetic women is partially explained by deleterious levels of HDL-C and VLDL-C. HDL-C levels of < or = 50 mg/dL and VLDL-C levels of > or = 20 mg/dL appear to predict ischemic heart disease mortality among these women and may help identify women who would benefit most from intervention.
A pilot, early angiographic patency study using a direct thrombin inhibitor as adjunctive therapy to streptokinase in acute myocardial infarction.
Authors: Lidón R M , Théroux P , Lespérance J , Adelman B , Bonan R , Duval D , Lévesque J
Published: June 2012

BACKGROUND

The success of streptokinase in acute myocardial infarction is hampered by the high failure rate to achieve early reperfusion. This study evaluates the possible benefit of Hirulog (Biogen, Cambridge, Mass), a direct thrombin inhibitor, as adjunct therapy to streptokinase to enhance early patency and prevent rethrombosis. Heparin has been shown to be of very limited benefits in this setting.

METHODS AND RESULTS

Forty-five patients were randomized to Hirulog or heparin (2:1 ratio). Coronary angiography documented a TIMI 2 or 3 flow after 90 minutes in 77% of the patients treated with Hirulog and streptokinase and in 47% of patients treated with heparin and streptokinase (P < .05) and after 120 minutes in 87% and 47% of patients, respectively (P < .01). TIMI 3 flow was established in 77% of patients with Hirulog compared with 40% with heparin (P < .02). The clinical outcome and the bleeding rate was also favorable to Hirulog; no reocclusion was observed at late angiography performed 4.7 days later.

CONCLUSIONS

Hirulog in this pilot study significantly improved the early patency rate of the infarct-related artery with a favorable clinical profile. This new direct thrombin inhibitor exhibits promise as adjunctive therapy to thrombolysis.
Dispersion of the QT interval. A marker of therapeutic efficacy in the idiopathic long QT syndrome.
Authors: Priori S G , Napolitano C , Diehl L , Schwartz P J
Published: June 2012

BACKGROUND

QT interval dispersion, measured as interlead variability of QT, is a marker of dispersion of ventricular repolarization and, hence, of cardiac electrical instability. We tested the hypothesis that dispersion of ventricular repolarization may be differently affected by interventions destined to provide complete or incomplete protection against malignant arrhythmias in patients with long QT syndrome (LQTS). Twenty-eight patients affected by the Romano Ward form of LQTS entered the study and were divided into three groups: LQTS patients before institution of therapy, patients who did respond to beta-blocker therapy, and patients who continued to have syncope and cardiac arrest despite beta-blockade and who underwent left cardiac sympathetic denervation. A group of 15 healthy volunteers served as control subjects.

METHODS AND RESULTS

Dispersion of QT and QTc were calculated using two indexes: the difference between the longest and the shortest value measured in each of the 12 ECG leads (QTmax-QTmin, QTcmax-QTcmin) and the relative dispersion of QT and QTc (standard deviation of QT/QT average x100, standard deviation of QTc/QTc average x100). Both indexes of dispersion of repolarization were higher in the LQTS patients than in control subjects; also, patients not responding to beta-blockers had a significantly higher dispersion of repolarization than responders. A cutoff value of 100 milliseconds for QTmax-QTmin had an 80% sensitivity and 82% specificity in discriminating between responders and nonresponders. A cutoff value of 6 for QT relative dispersion yielded similar results. The LQTS patients who did not respond to beta-blockade underwent left cardiac sympathetic denervation and thereafter remained asymptomatic (mean follow-up, 5 +/- 4 years). In this group, dispersion of repolarization was significantly reduced by the surgical denervation to values similar to that of the responders to beta-blockade.

CONCLUSIONS

These data indicate that QT dispersion is a useful clinical tool to predict efficacy of antiadrenergic therapy in LQTS patients.
Comparison of intravascular ultrasound and angiography in the assessment of myocardial bridging.
Authors: Ge J , Erbel R , Rupprecht H J , Koch L , Kearney P , Görge G , Haude M , Meyer J
Published: June 2012

BACKGROUND

In autopsy, myocardial bridging is a common finding. With coronary angiography, a systolic compression, mainly of the left anterior descending coronary artery, is observed in 1% to 3% of the patients. Controversy exists concerning the functional importance of this finding. To obtain a functional insight into the myocardial bridging, intravascular ultrasound and intracoronary Doppler were performed.

METHODS AND RESULTS

Intracoronary ultrasound and Doppler were performed in 14 patients with angiographic evidence of systolic vessel compression ("milking effect") in the left anterior descending coronary artery. The 4.8F, 20-MHz ultrasound catheter could not be advanced through the entire myocardial bridge segment in 6 of the 14 patients studied because the lumen was < 1.6 mm. In these patients, only the proximal parts of the bridge segment were scanned. The changes in cross-sectional shape during the cardiac cycle were determined for both the normal proximal segment and the bridge segment by use of a semiautomatic computer program. Intracoronary Doppler (20 MHz) was performed in 7 patients with a 3F catheter. A highly characteristic systolic eccentric or concentric compression with delayed relaxation in diastole of the myocardial bridging segment was clearly visualized in all patients. The cross-sectional lumen area variation was 40 +/- 25% in the bridging segments and 9 +/- 7% in the normal segments (P < .01). No atherosclerotic lesions were detected in the bridge or the distal segment in the 8 patients in whom the IVUS catheter was successfully advanced through the entire myocardial bridge. However, atherosclerotic plaques were found in the segments proximal to the bridge in 12 of 14 patients (86%). The resting mean flow velocity was 6.4 +/- 1.2 cm/s; the maximal mean flow velocity after intracoronary administration of 10 mg papaverine was 14.1 +/- 3.4 cm/s. The coronary flow velocity reserve was 2.2 +/- 0.7. A highly characteristic pattern showing a prominent peak in coronary velocity in early diastole was observed in 86% of patients, and this pattern was enhanced after injection of intracoronary papaverine.

CONCLUSION

Intravascular ultrasound demonstrated a characteristic systolic compression of the bridge segments. The delayed compression release may explain the characteristic sharp early diastolic peak in coronary flow velocity found with intracoronary Doppler in vessels with myocardial bridging. Reduced coronary flow reserve may be related to this phenomenon, possibly explaining signs of ischemia detected in some of the patients, but may alternatively be a result of the presence of atherosclerosis in the segment proximal to the bridge in these patients.
Mortality benefits and the implantable cardioverter-defibrillator.
Authors: Sweeney M O , Ruskin J N
Published: June 2012

The automatic implantable cardioverter-defibrillator (ICD) is highly effective in reducing sudden death rates in patients with life-threatening ventricular tachyarrhythmias. However, the magnitude of the ability of the ICD to improve overall survival is less certain. Data supporting the contention that the ICD prolongs survival are reviewed. It is evident that the mortality benefit consequent to the marked reduction in sudden death varies widely across subpopulations in a predictable manner. This observation reflects the powerful influence of other clinical factors that constrain survival in typical ICD patients. The implications for future studies on the ICD are discussed.
N-terminal proatrial natriuretic factor. An independent predictor of long-term prognosis after myocardial infarction.
Authors: Hall C , Rouleau J L , Moyè L , de Champlain J , Bichet D , Klein M , Sussex B , Packer M , Rouleau J , Arnold M O
Published: June 2012

BACKGROUND

Atrial natriuretic factor (ANF) is a peptide hormone secreted from cardiac atria in response to increased atrial pressure. Because of a longer half-life and greater stability, the N-terminal of ANF prohormone (N-terminal proANF) may be a better integrator of atrial peptide secretion than ANF itself. After myocardial infarction, elevation of ANF and other neurohormones has been associated with a poor prognosis. However, when left ventricular ejection fraction (LVEF) and other important clinical variables are included in multivariate analysis, the independent predictive value of these neurohormones has been reduced markedly.

METHODS AND RESULTS

To test the prognostic value of N-terminal proANF after myocardial infarction, its plasma concentration was measured a mean of 12 days after infarction in 246 patients in the Survival and Ventricular Enlargement (SAVE) Study. N-terminal proANF was a much stronger predictor of survival than ANF itself. Furthermore, in multivariate analysis of cardiovascular mortality and development of heart failure, N-terminal proANF in contrast to ANF and other neurohormones was still a powerful and independent predictor when the model included age, gender, prior myocardial infarction, hypertension, diabetes, use of thrombolysis, Killip class, infarct location, and LVEF.

CONCLUSIONS

The measurement of N-terminal proANF supplements presently used clinical and objective assessments and provides an important independent predictor of prognosis with respect to cardiovascular mortality and development of heart failure.
Human vascular smooth muscle cells contain functional estrogen receptor.
Authors: Karas R H , Patterson B L , Mendelsohn M E
Published: June 2012

BACKGROUND

The decreased incidence of coronary artery disease observed in postmenopausal women given estrogen (E2) replacement demonstrates an atheroprotective effect of E2 that is generally believed to be mediated by indirect, E2-induced changes in cardiovascular risk factor profiles. We hypothesized that the atheroprotective effect of E2 may be in part mediated by a direct effect of E2 on vascular smooth muscle cells (VSMCs). Therefore, a series of experiments was performed to determine whether human VSMCs contain a competent E2 receptor, a ligand-activated transcription factor known to mediate E2-induced effects in nonvascular cells.

METHODS AND RESULTS

Ribonuclease protection assays, with a probe derived from the human E2 receptor, were used to demonstrate E2-receptor mRNA in human saphenous vein VSMCs. To show that VSMCs contain E2-receptor protein as well as message, immunoblotting and immunofluorescence studies with a monoclonal anti-E2-receptor antibody were performed, and E2-receptor protein was detected by both methods. Transient transfection assays using a specific E2-responsive reporter system were used next to determine whether the VSMC E2 receptor is capable of E2-induced transcriptional transactivation. Initial studies using mammary artery-derived VSMCs resulted in a 2.4-fold increase in reporter activity in response to 10(-7) mol/L E2. Subsequent studies using saphenous vein VSMCs demonstrated increasing levels of reporter activation as the concentration of E2 was increased from 10(-9) mol/L (1.3-fold increase; SEM, 0.07; P = .05, n = 3) to 10(-7) mol/L (1.6-fold increase; SEM, 0.04; P = .002, n = 6). The specificity of the E2-induced transactivation of the reporter gene was shown by dose-dependent inhibition of transactivation by the pure E2 antagonist ICI 164,384 and by enhancement of the transactivation by simultaneous overexpression of the E2 receptor.

CONCLUSIONS

We have demonstrated for the first time that human VSMCs express E2-receptor mRNA and protein and that the E2 receptor in VSMCs is capable of estrogen-dependent gene activation. These data suggest a mechanism by which estrogen may directly alter VSMC function.
Norepinephrine-induced human platelet activation in vivo is only partly counteracted by aspirin.
Authors: Larsson P T , Wallén N H , Hjemdahl P
Published: June 2012

BACKGROUND

Epinephrine and mental stress may, via platelet stimulation, enhance the risk of thrombus formation. Norepinephrine is more likely than epinephrine to activate platelets in vivo because of higher levels in plasma but is less well studied in this respect. The antiplatelet drug of choice for patients with coronary artery disease, aspirin, may be less effective during sympathoadrenal activation. We therefore investigated platelet responses in vivo to exogenous norepinephrine with and without aspirin pretreatment.

METHODS AND RESULTS

Platelet aggregability in vivo was assessed in 11 healthy male subjects, by filtragometry ex vivo (which reflects platelet aggregability in vivo) and by measurements of plasma beta-thromboglobulin (beta-TG, which reflects platelet secretion). Norepinephrine infusions elevated venous plasma norepinephrine from 1.5 to 4 and 15 nmol/L, respectively, and enhanced platelet aggregability (filtragometry) concentration dependently (P < .001). Platelet secretion (beta-TG levels) increased during high-dose infusion (P < .01). Aspirin pretreatment (500 mg orally 12 hours earlier) reduced the excretion of 11-dehydrothromboxane B2 by 62 +/- 5% (P < .001) and attenuated platelet aggregability at rest (P < .05) but not the effect of norepinephrine infusion on platelet aggregability. Conversely, resting plasma beta-TG levels and the urinary excretion of high-molecular-weight beta-TG were not altered by aspirin pretreatment, whereas the norepinephrine-induced increase in plasma beta-TG was abolished.

CONCLUSIONS

Norepinephrine, at plasma levels easily attained during exercise, enhances platelet aggregability and platelet secretion in vivo in healthy humans. Aspirin may be less effective as an antithrombotic drug during sympathoadrenal activation in humans.
Determinants of severity of coronary artery disease in Australian men and women.
Authors: Wang X L , Tam C , McCredie R M , Wilcken D E
Published: June 2012

BACKGROUND

Factors predicting the occurrence of premature coronary artery disease (CAD) may not be quantitatively the same as those predicting CAD severity, particularly in women, in whom there have been few studies.

METHODS AND RESULTS

To determine factors predictive of severity of CAD and of angina pectoris, we documented atherogenic variables and the extent of CAD at angiography in 594 consecutively studied men and women aged 65 years or less. Severity was assessed from the number of involved major coronary arteries with significant (> 50%) luminal obstructions and from a coronary disease severity score. We related severity to quantitative and categorical atherogenic variables and assessed severity of angina (no angina, stable angina, or unstable angina) at the time of study in the same way. There were eight variables independently predictive of severity: in descending order of relative importance, male gender, diabetes, smoking dose, ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C), lipoprotein(a) [Lp(a)], age, positive family history, and hypertension. These correctly classified 43.3% of patients into no-, one-, two-, and three-vessel disease categories and accounted for 25.8% of variance of severity. Among 246 patients not taking lipid-lowering or beta-blocking drugs, these variables (in slightly different order) correctly classified 49.2% of patients and accounted for 36% of the variance. Among men (n = 427), seven significant variables correctly classified 39.3% of patients compared with 54.5% in women (n = 167). For those not taking the above drugs, these proportions were 49.4% and 65.4%, respectively. Among the quantitative variables, total smoking dose was the most predictive independent variable irrespective of current or ex-smoking habit and was more predictive in women than in men; of the lipid variables, high TC/HDL-C (or low HDL-C) and high Lp(a) were consistently highly predictive for all patients and in the subgroup analyses. Patients with unstable angina had higher coronary severity scores and Lp(a) levels and were more likely to have diabetes, hypertension, or a positive family history.

CONCLUSIONS

We conclude that the quantitative variables most relevant to severity of premature CAD and to its prevention in Australian men and women are total amount of lifetime smoking, TC/HDL-C (or HDL-C), and Lp(a) and that patients with unstable versus stable angina usually have more severe disease and higher Lp(a).
Ventricular systolic assessment in patients with dilated cardiomyopathy by preload-adjusted maximal power. Validation and noninvasive application.
Authors: Sharir T , Feldman M D , Haber H , Feldman A M , Marmor A , Becker L C , Kass D A
Published: June 2012

BACKGROUND

Noninvasive cardiac-specific analysis of contractile function in patients with dilated heart failure remains problematic. This study tests whether maximal power divided by the square of end-diastolic volume (PWRmx/EDV2, or preload-adjusted PWRmx) can provide such assessment.

METHODS AND RESULTS

To validate the load insensitivity of the PWRmx index and determine its response to contractile change, 24 subjects with chronic dilated cardiomyopathy underwent invasive pressure-volume catheterization study using the conductance catheter technique. Preload was transiently reduced by 30% using balloon occlusion of the inferior vena cava, and afterload impedance was lowered by 50%, induced by a bolus injection of nitroglycerin. Contractile state was varied by intravenous dobutamine, verapamil, or esmolol. PWRmx was calculated from the simultaneous product of ventricular pressure and rate of volume change (dV/dt), the latter derived from the volume catheter signal. PWRmx varied directly with preload but was minimally influenced by afterload. However, PWRmx/EDV2 was not significantly altered by either loading change. PWRmx/EDV2 did vary with contractility, correlating closely with changes in the end-systolic pressure-volume relation (r = .91, P < .001). To test the noninvasive application of this index, 12 additional patients were studied, with PWRmx/EDV2 derived from nuclear ventriculography combined with a novel method to measure central arterial pressures. Subjects received intravenous nitroprusside or dobutamine in random order. Ejection fraction increased similarly with both agents (+42.9 +/- 8.9% for dobutamine and +29.4 +/- 5.3% for nitroprusside, both P < .01). In contrast, PWRmx/EDV2 did not significantly change with nitroprusside but increased by 126 +/- 16.1% with dobutamine (P < .01).

CONCLUSIONS

Preload-adjusted PWRmx is a steady-state index of ventricular systolic function that is sensitive to inotropic state and minimally influenced by physiological changes in afterload impedance or volume load. It appears useful for noninvasive cardiac-specific analysis of acute drug effects.
Acute effects of nitric oxide on left ventricular relaxation and diastolic distensibility in humans. Assessment by bicoronary sodium nitroprusside infusion.
Authors: Paulus W J , Vantrimpont P J , Shah A M
Published: June 2012

BACKGROUND

In isolated mammalian cardiomyocytes, papillary muscle preparations, and ejecting hearts, nitric oxide (NO) or other cyclic GMP-elevating interventions increase diastolic cell length and reduce peak contractile performance by hastening onset of myocardial relaxation. In the present study, the effect of NO on left ventricular (LV) relaxation and diastolic distensibility was investigated in humans.

METHODS AND RESULTS

The NO donor substance sodium nitroprusside was infused during cardiac catheterization in the global coronary bed of the LV of patients (n = 13) investigated for chest pain who were without evidence of obstructive coronary artery or other cardiac disease. Sodium nitroprusside was infused intracoronarily at a dosage (< or = 4 micrograms/min) that was previously shown to be devoid of systemic effects when infused into the brachial artery to investigate the reactivity of the forearm vascular bed. The effect of this global intracoronary infusion of the NO donor sodium nitroprusside was assessed by sequential LV angiograms and tip-micromanometer pressure recordings. During global intracoronary nitroprusside infusion, there was a decrease in heart rate from 78 +/- 11 to 76 +/- 12 beats per minute (P < .05), in LV peak systolic pressure from 161 +/- 18 to 146 +/- 18 mm Hg (P < .001), and in time to onset of LV relaxation (interval from Q wave on the ECG to LV dP/dtmin) from 432 +/- 36 to 419 +/- 36 milliseconds (P < .01). In 7 patients in whom adequate sequential LV angiograms could be obtained, LV end-diastolic volume increased from 158 +/- 34 to 165 +/- 40 mL (P < .05), whereas LV end-diastolic pressure fell from 18 +/- 5 to 12 +/- 3 mm Hg (P < .02), and in 5 of these 7 patients, a downward shift of the diastolic LV pressure-volume relation was observed. In 5 patients, a right atrial infusion of sodium nitroprusside was performed either before (n = 2) or after the global intracoronary infusion. The decrease in LV peak systolic pressure observed during right atrial infusion was significantly smaller (P < .01) than during global intracoronary infusion.

CONCLUSIONS

The present study reveals reduced LV pressure development, an LV relaxation-hastening effect, and improved LV diastolic distensibility during global intracoronary infusion of the NO donor substance sodium nitroprusside. These effects appeared to be unrelated to systemic vasodilation or to pericardial constraint and could be explained by a direct myocardial effect of NO, probably through activation of guanylyl cyclase to increase cyclic GMP or through modification of other cellular proteins.
Enhanced endothelial adhesiveness in hypercholesterolemia is attenuated by L-arginine.
Authors: Tsao P S , McEvoy L M , Drexler H , Butcher E C , Cooke J P
Published: June 2012

BACKGROUND

We have shown that chronic administration of the nitric oxide (NO) precursor L-arginine normalizes NO-dependent vasodilation and markedly inhibits atherogenesis in a hypercholesterolemic rabbit model. We hypothesized that this antiatherogenic effect is due to modulation of endothelial adhesiveness by endothelium-derived NO.

METHODS AND RESULTS

New Zealand White rabbits were fed normal chow (Cont), a high-cholesterol diet (Chol), a high-cholesterol diet supplemented with L-arginine (Arg), or a normal diet supplemented with the NO synthase antagonist L-nitroarginine (L-NA) for 2 weeks. In additional studies, some animals receiving L-NA were also treated with hydralazine to normalize blood pressure. After 2 weeks, thoracic aortas were harvested, opened longitudinally, and placed in a culture dish with the endothelial surface exposed to medium containing WEHI 78/24 cells, a monocytoid cell line. After incubation with the monocytoid cells for 30 minutes on a rocking platform, the aortic segments were washed repeatedly to remove nonadherent cells and adherent cells counted by epifluorescent microscopy. Monocytoid cell binding to aortic endothelium was significantly increased in Chol (P < .001 versus Cont); binding was markedly reduced in arginine-fed hypercholesterolemic animals (P < .05, Arg versus Chol). Monocytoid cell binding to aortic endothelium was also significantly increased in L-NA (P < .05); hydralazine normalized blood pressure but did not reduce monocytoid cell binding. To confirm that alterations in NO activity modulate endothelial cell-monocyte interaction, the release of nitrogen oxides (NOx) by thoracic aortas was assessed by a chemiluminescent technique. The concentration of NOx in the conditioned medium from segments of Arg thoracic aortas was significantly greater than that from Cont aortas, whereas that from L-NA aortas was significantly less.

CONCLUSIONS

Hypercholesterolemia enhances the adhesiveness of aortic endothelium for monocytes; this effect is attenuated by dietary L-arginine. Conversely, inhibition of NO synthesis enhances monocyte binding. The results suggest that endothelium-derived NO plays an important role in regulating the endothelial adhesiveness for monocytes. Alterations in NO activity may play a critical role in atherogenesis.
Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat.
Authors: Schieffer B , Wirger A , Meybrunn M , Seitz S , Holtz J , Riede U N , Drexler H
Published: June 2012

BACKGROUND

After myocardial infarction, the noninfarcted left ventricle develops reactive hypertrophy associated with a depressed coronary flow reserve, myocardial interstitial fibrosis, and reduced capillary density. The present study investigated the comparative cardiac effects of chronic angiotensin-converting enzyme (ACE) inhibition and selective angiotensin II type 1 receptor (AT1) blockade in the rat model of myocardial infarction and failure.

METHODS AND RESULTS

Seven days after coronary ligation (MI), rats were randomized to enalapril (n = 8; 500 micrograms.kg-1.d-1), losartan (n = 9; 3 mg.kg-1.d-1), or placebo (n = 8) and treated for 6 weeks. Sham-operated rats (n = 10) served as controls. Coronary blood flow was measured with radiolabeled microspheres during baseline and maximal coronary dilation induced by dipyridamole (2 mg.kg-1.min-1 over 10 minutes). Right and left ventricular (LV) weight was increased in infarcted rats compared with sham-operated animals and enalapril- and losartan-treated MI rats. Minimal LV and right ventricular coronary vascular resistance was increased in MI rats but normalized with enalapril and losartan (LV:sham, 8.9; MI-placebo, 12.7; MI-enalapril, 9.2; MI-losartan, 8.8 mm Hg.mL-1.min-1.g-1, all P < .05 versus MI-placebo). Interstitial fibrosis determined from perfusion-fixed hearts was increased in infarcted rats but reduced by both enalapril and losartan. Myocardial capillary density improved with enalapril and losartan. In separate groups treated as above, plasma and tissue ACE activity was determined and demonstrated significantly higher ACE activity in noninfarcted LV tissue of MI-placebo rats compared with sham (0.64 vs 0.27 nmol.mg protein-1.min-1, P < .05). Enalapril and losartan reduced LV ACE activity (0.39 and 0.29 nmol.mg protein-1.min-1, P < .05 versus MI-placebo).

CONCLUSIONS

The present study demonstrates that both chronic ACE inhibition and AT1 receptor blockade (1) reduces cardiac hypertrophy, (2) restores minimal coronary vascular resistance in postinfarction reactive hypertrophy, and (3) attenuates the development of myocardial interstitial fibrosis in the noninfarcted LV. These results suggest that inhibition of generation of angiotensin II and AT1 receptor blockade are equally effective in preventing important features of ventricular remodeling after myocardial infarction.
Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction.
Authors: Jugdutt B I , Khan M I
Published: June 2012

BACKGROUND

Prolonged nitrate therapy during healing between 2 days and 6 weeks after anterior myocardial infarction has the potential for limiting further left ventricular remodeling (or changes in topography) and preserving function. Longterm therapy throughout healing over 6 weeks might be more beneficial than short-term therapy over the first 2 weeks after infarction.

METHODS AND RESULTS

The effect of prolonged nitrate therapy between 2 days and 6 weeks during healing after infarction on serial parameters of ventricular remodeling (scar expansion, scar thinning, ventricular dilation, and hypertrophy) and function (asynergy or akinesis plus dyskinesis and ejection fraction) by serial two-dimensional echocardiography, hemodynamics, postmortem topography (computerized planimetry, geometric maps, and radiographs), and collagen content (hydroxyproline) was studied in 64 instrumented dogs randomized 2 days after left anterior descending coronary artery ligation to various nitrate regimens (n = 32) over the first 2 weeks (subgroup 1: 2% transdermal nitroglycerin at 8 AM and 4 PM, n = 6; subgroup 2: 2% transdermal nitroglycerin plus 2.6 mg of sustained-release oral nitroglycerin at 8 AM, 3 PM, and 10 PM, n = 5; subgroup 3: oral isosorbide dinitrate, 30 mg at 8 AM and 4 PM, n = 11) or 6 weeks (subgroup 4: isosorbide dinitrate, n = 10) and in matching controls (n = 32). Nitrate therapy reduced left atrial pressure, mean arterial pressure, and the rate-pressure product compared with controls over the 6 weeks. Postmortem scar mass and hydroxyproline were similar in control and nitrate groups. However, scar stretching and thinning, cavity dilation, noninfarct wall hypertrophy, and apical bulging were less with nitrates, especially in the long-term subgroup 4. In vivo remodeling parameters between 2 days and 6 weeks after ligation showed that, compared with controls, nitrate therapy prevented further stretching of the asynergic segment, decreased the expansion index, decreased further scar thinning, prevented the increase in ventricular volumes, reduced the frequency of ventricular aneurysm, prevented the increase in ventricular mass, reduced the extent of asynergy, and improved ejection fraction. Although the beneficial effect on topography and function was seen in all nitrate subgroups, the overall benefit was greater with long-term therapy over 6 weeks (subgroup 4) than short-term therapy confined to the first 2 weeks (subgroups 1, 2, and 3).

CONCLUSIONS

Prolonged nitrate therapy, in various regimens during healing after infarction, effectively reduced left ventricular loading and prevented infarct thinning, further infarct expansion, progressive ventricular dilation, and the increase in mass. These effects were associated with decreased asynergy and improved ejection fraction. The beneficial effects were greater with long-term therapy over 6 weeks than short-term therapy over the first 2 weeks.
Changes in passive mechanical stiffness of myocardial tissue with aneurysm formation.
Authors: Gupta K B , Ratcliffe M B , Fallert M A , Edmunds L H , Bogen D K
Published: June 2012

BACKGROUND

Myocardium undergoes complex cellular and histochemical alterations after acute myocardial infarction. These structural changes directly affect the mechanical stiffness of infarcted and remote myocardia. Previous investigations of infarct stiffness have been limited to uniaxial testing, which does not provide a unique description of the tissue's three-dimensional material properties. This study describes the first serial measurements of biaxial mechanical properties of sheep myocardium after anteroapical infarction.

METHODS AND RESULTS

Anteroapical infarctions of 23.7 +/- 2.5% of the left ventricular mass were produced by coronary arterial ligation in sheep. Biaxial force-extension measurements were made on freshly excised squares (6.45 cm2) of remote, noninfarcted, and infarcted myocardia before and 4 hours, 1 week, 2 weeks, and 6 weeks after ligation. Adjacent myocardial samples were assayed for hydroxyproline content. Force-extension data and a derived constitutive equation were used to describe stresses and strains and material properties of each sample. In sheep, anteroapical infarctions evolve into thin left ventricular aneurysms that consist of predominantly fibrous tissue with disrupted groups of muscle cells encased in scar. In the infarct, Cauchy stresses at 15% extensions (control stresses: circumferential, sigma C, 19.4 +/- 3.3 g/cm2; longitudinal, sigma L, 54.8 +/- 34.8 g/cm2) increase within 4 hours, peak at 1 to 2 weeks (sigma C, 338.5 +/- 143.6 g/cm2; sigma L, 310.7 +/- 45.9 g/cm2), and then decrease 6 weeks after infarction (sigma C, 115 +/- 47.2 g/cm2; sigma L, 53.2 +/-28.9 g/cm2). Stresses in the remote myocardium follow a similar time course but to a lesser extent than the infarcted region. Hydroxyproline content, a measure of collagen content, does not correlate with infarct stiffness but progressively increases to 69.7 +/- 7.6 micrograms/mg after 6 weeks. Stress-extension curves demonstrate directional anisotropy of both infarcted and remote myocardia.

CONCLUSIONS

The findings indicate that infarcted myocardium becomes more stiff during the first 1 to 2 weeks after anteroapical infarction and then more compliant. The infarct also exhibits directional anisotropy. These observations underscore the importance of ventricular material properties during the remodeling process after acute myocardial infarction and may partially explain the progressive left ventricular dilatation and functional deterioration that occur in some patients after anteroapical infarction.
An enantiomer-enantiomer interaction of (S)- and (R)-propafenone modifies the effect of racemic drug therapy.
Authors: Kroemer H K , Fromm M F , Bühl K , Terefe H , Blaschke G , Eichelbaum M
Published: June 2012

BACKGROUND

Therapy with racemic compounds produces effects that can be attributed to both (S)- and (R)-enantiomers. Here we have tested the hypothesis that an enantiomer-enantiomer interaction would modulate the effects of treatment with a racemate, the antiarrhythmic propafenone. Previous studies have shown that while the enantiomers of propafenone exert similar sodium channel-blocking (QRS widening) effects, it is the (S)-enantiomer that produces beta-blockade; moreover, we have demonstrated recently that (R)-propafenone inhibits the metabolism of (S)-propafenone in vitro.

METHODS AND RESULTS

This single-blind, randomized study compared the effects of (R/S)-, (S)-, (R)-propafenone (150 mg q 6 hours for 4 days) and placebo on QRS duration (delta QRS) and on maximum exercise heart rate (delta HRmax), an index of beta-blockade. The clearance of (S)-propafenone was significantly lower (-55 +/- 24%, P < .001) during treatment with (R/S)-propafenone than with the (S)-enantiomer alone, and delta HRmax was significantly altered during (R/S)-propafenone (-8.8 +/- 6.6 beats per minute; P < .01) and during (S)-propafenone (-4.3 +/- 4.8 beats per minute; P < .01) but not during (R)-propafenone (-1.8 +/- 6.4 beats per minute) or placebo (0.3 +/- 7.1 beats per minute). In contrast, (R/S)-, (S)-, and (R)-propafenone all prolonged QRS compared with placebo.

CONCLUSIONS

These data indicate that (R)-propafenone impairs the disposition of (S)-propafenone in humans. As a result, the beta-blocking effects of 150 mg of racemic propafenone (75 mg of the [S]-enantiomer) were more pronounced than those of 150 mg of (S)-propafenone alone. Thus, the effects of racemic drug therapy are not necessarily those predicted by summation of the effects of the individual enantiomers.
A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association.
Authors: Stary H C , Chandler A B , Glagov S , Guyton J R , Insull W , Rosenfeld M E , Schaffer S A , Schwartz C J , Wagner W D , Wissler R W
Published: June 2012

The compositions of lesion types that precede and that may initiate the development of advanced atherosclerotic lesions are described and the possible mechanisms of their development are reviewed. While advanced lesions involve disorganization of the intima and deformity of the artery, such changes are absent or minimal in their precursors. Advanced lesions are either overtly clinical or they predispose to the complications that cause ischemic episodes; precursors are silent and do not lead directly to complications. The precursors are arranged in a temporal sequence of three characteristic lesion types. Types I and II are generally the only lesion types found in children, although they may also occur in adults. Type I lesions represent the very initial changes and are recognized as an increase in the number of intimal macrophages and the appearance of macrophages filled with lipid droplets (foam cells). Type II lesions include the fatty streak lesion, the first grossly visible lesion, and are characterized by layers of macrophage foam cells and lipid droplets within intimal smooth muscle cells and minimal coarse-grained particles and heterogeneous droplets of extracellular lipid. Type III (intermediate) lesions are the morphological and chemical bridge between type II and advanced lesions. Type III lesions appear in some adaptive intimal thickenings (progression-prone locations) in young adults and are characterized by pools of extracellular lipid in addition to all the components of type II lesions.
Novel cardiac myofilament desensitizing factor released by endocardial and vascular endothelial cells.
Authors: Shah A M , Mebazaa A , Wetzel R C , Lakatta E G
Published: June 2012

BACKGROUND

Recent studies suggest that both endocardial endothelium and coronary vascular endothelium influence myocardial contraction, but the mediators responsible and their mechanisms of action are not well defined.

METHODS AND RESULTS

We investigated the effects of cultured endocardial endothelial and vascular endothelial cell superfusate on contraction and intracellular calcium transients of isolated rat cardiac myocytes. Endothelial cell superfusate induced a potent negative inotropic effect, with a rapid reversible decrease in myocyte twitch amplitude, earlier twitch relaxation, and a significant increase in diastolic length. This effect was not associated with significant changes in intracellular calcium or pH; was not attributable to nitric oxide, prostanoids, cGMP, or protein kinase C activation; and did not involve pertussis toxin-sensitive G proteins. The activity was stable at 37 degrees C for several hours, was not destroyed by protease treatment, and was found in low-molecular-weight (< 1 kD) superfusate fractions.

CONCLUSIONS

These data suggest the tonic release by endothelial cells of a novel, stable factor that acts predominantly by reducing the response of cardiac myofilaments to calcium (ie, "desensitizes" them). This "desensitizing factor" could rapidly modulate cardiac contraction-relaxation coupling and diastolic tonus and exert distant effects because of its stability.