bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet cyclic GMP. A potentially useful indicator to evaluate the effects of nitroglycerin and nitrate tolerance.
Authors: Watanabe H , Kakihana M , Ohtsuka S , Enomoto T , Yasui K , Sugishita Y
Published: June 2012

BACKGROUND

The present study was designed to investigate the intracellular production of cyclic GMP (cGMP) in platelets in response to nitroglycerin and to determine the potential clinical value of platelet cGMP as an indicator of the effects of nitroglycerin and nitrate tolerance.

METHODS AND RESULTS

Platelet cGMP levels and the diameters of the coronary arteries before and 2 minutes after intracoronary injection of 200 micrograms nitroglycerin were measured in 15 patients who had previously received nitrates (nitrates group) and in 16 who had not received any nitrates (no-nitrates group). Platelet cGMP levels increased significantly after nitroglycerin injection in the two groups, but plasma cGMP levels and plasma atrial natriuretic peptide levels did not change. The percent increase in platelet cGMP levels and the percent dilatation of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries after nitroglycerin injection were higher in the no-nitrates group than in the nitrates group (platelet cGMP levels: artery, 74.2 +/- 18.3% versus 11.5 +/- 4.2%, P < .01; vein, 73.6 +/- 22.9% versus 9.0 +/- 3.1%, P < .01; coronary dilatation: LAD, 46.7 +/- 6.0% versus 9.9 +/- 2.5%, P < .01, LCx, 51.2 +/- 8.7% versus 6.1 +/- 3.0%, P < .01). The percent increase in platelet cGMP levels was significantly correlated with the percent dilatation of the coronary arteries (LAD: r = .90, P < .01; LCx: r = .92, P < .01) in the no-nitrates group and not in the nitrates group.

CONCLUSIONS

These results indicate that platelet cGMP can be used as an indicator for in situ evaluation of nitroglycerin effects and that patients who have received nitrates develop nitrate tolerance, which affects intracellular production of cGMP and vasodilation in the response to nitroglycerin.
Influence of cigarette smoking on human autonomic function.
Authors: Niedermaier O N , Smith M L , Beightol L A , Zukowska-Grojec Z , Goldstein D S , Eckberg D L
Published: June 2012

BACKGROUND

Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control.

METHODS AND RESULTS

We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change.

CONCLUSIONS

In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.
Unfavorable outcome in patients with primary electrical disease who survived an episode of ventricular fibrillation.
Authors: Wever E F , Hauer R N , Oomen A , Peters R H , Bakker P F , Robles de Medina E O
Published: June 2012

BACKGROUND

Prognosis in patients with ventricular tachyarrhythmia without structural heart disease (primary electrical disease) has been described as excellent. However, prognosis may be less favourable in the subgroup surviving an episode of ventricular fibrillation.

METHODS AND RESULTS

We prospectively followed 19 consecutive patients (age, 13 to 66 years; mean age, 33 years) who had survived an episode of documented ventricular fibrillation. Structural heart disease, preexcitation, and long QT syndromes were excluded by thorough cardiologic evaluation. All patients underwent 24-hour Holter monitoring, exercise testing, and programmed electrical stimulation according to a standardized protocol. Holter monitoring revealed episodes of ventricular tachyarrhythmia in 5 patients. Exercise testing reproducibly provoked ventricular tachycardia in 2 patients. Baseline programmed electrical stimulation yielded inducibility of rapid ventricular tachyarrhythmia in 10 patients (53%) and noninducibility in 9 (47%). Nine patients were discharged on antiarrhythmic drug therapy. A defibrillator was implanted in 10 patients. During 43-month follow-up (range, 5 to 85 months; median, 41 months), major arrhythmic events recurred in 7 patients (37%). Four of these patients had noninducibility at baseline programmed electrical stimulation. Two patients on antiarrhythmic drugs had recurrent cardiac arrest: one died suddenly and the other was successfully resuscitated from ventricular fibrillation and subsequently underwent defibrillator implantation. In the other 5 patients, termination of (pre)syncopal episodes was associated with defibrillator shocks. Termination of ventricular fibrillation was documented by Holter recording in one of these patients. Specific markers predictive of a recurrent event could not be identified, although 6 of 7 patients with recurrent events had experienced at least one episode of cardiac arrest or (pre)syncope before the index episode.

CONCLUSIONS

Patients with primary electrical disease presenting with ventricular fibrillation are at high risk of recurrence of major arrhythmic events during long-term follow-up. Noninducibility at baseline study does not predict an uneventful course. Also, early defibrillator implantation should be considered in these patients.
Influence of the status of the renin-angiotensin system on the effect of cilazapril on neointima formation after vascular injury in rats.
Authors: Clozel J P , Müller R K , Roux S , Fischli W , Baumgartner H R
Published: June 2012

BACKGROUND

Angiotensin converting enzyme (ACE) inhibition has been shown to prevent neointima formation after vascular injury in rats. However, clinical results evaluating restenosis after angioplasty have been negative. The goal of the present study was to evaluate the influence of the renin-angiotensin system (RAS) status on the effect of ACE inhibition on neointima formation.

METHODS AND RESULTS

Arterial injury was produced by ballooning the left carotid artery of rats, and neointima formation was evaluated by morphometry 2 weeks after ballooning. The effects of cilazapril were assessed in four experimental groups: normotensive rats, spontaneously hypertensive rats, hypertensive rats with a renal artery stenosis induced by clipping (two-kidney, one-clip rats), and hypertensive rats with uninephrectomy, high salt intake, and administration of deoxycorticosterone (DOCA). In parallel groups of rats, measurement of plasma renin activity was made in order to characterize (at least at the plasma level) the status of the RAS. As expected, renal artery stenosis markedly increased plasma renin activity, and DOCA decreased it to undetectable levels. Cilazapril had a marked preventive effect on neointima formation in normotensive rats, spontaneously hypertensive rats, and two-kidney, one-clip rats but was ineffective in DOCA rats.

CONCLUSIONS

We conclude that the status of the RAS has a major influence on the effect of cilazapril on neointima formation after vascular injury.
Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction?
Authors: Lincoff A M , Topol E J
Published: June 2012

Thrombolytic therapy significantly improves the natural history of acute myocardial infarction, but recent data suggest that current reperfusion strategies have yet to realize the maximum potential for reduction of mortality and salvage of ventricular function. Coronary patency rates as high as 85% assessed by angiography 90 minutes after initiation of treatment greatly overestimate the efficacy of thrombolytic regimens, as this conventional angiographic "snapshot" view does not satisfactorily reflect the dynamic processes of coronary artery recanalization and reocclusion or the adequacy of myocardial perfusion. In fact, only the unusual patient appears to achieve optimal reperfusion for acute myocardial infarction, with a substantial deterioration of benefit in many patients due to insufficiently early or rapid recanalization, incomplete patency with TIMI grade 2 flow or critical residual coronary stenoses, absence of myocardial tissue reflow despite epicardial artery patency, intermittent coronary patency, subsequent reocclusion, or reperfusion injury. Recently developed techniques to critically assess the quality of reperfusion, coupled with the introduction of novel pharmacological agents and an improved understanding of the roles and mechanisms of existing thrombolytic and adjunctive drugs, have provided the opportunity to overcome many of the present limitations of reperfusion therapy. Emerging strategies to achieve optimal reperfusion are directed at enhancement of the velocity and quality of thrombolysis, amelioration of the adverse effects of reperfusion, and use of alternative pathways to myocardial salvage.
Activation of human platelets by cocaine.
Authors: Kugelmass A D , Oda A , Monahan K , Cabral C , Ware J A
Published: June 2012

BACKGROUND

Cocaine ingestion has been associated with thrombosis of coronary as well as peripheral arteries, but the mechanism by which cocaine promotes thrombus formation is unknown. Accordingly, we determined whether cocaine activates human platelets by flow cytometric analysis of whole blood to which cocaine was added.

METHODS AND RESULTS

Activated platelets were detected by "two-color" flow cytometric analysis of the binding of fluorescently labeled antibodies directed against either platelet-associated fibrinogen or P-selectin, which are found on the surface of platelets only after stimulation. Platelets were distinguished from other constituents of whole blood by their ability to bind an anti-glycoprotein Ib antibody bound to both activated and resting platelets. Incubation of whole blood with cocaine, in concentrations of 10 microM to 13 mM, induced significant increases in both platelet-associated fibrinogen (range of increase, 45 +/- 12% to 125 +/- 40%) and P-selectin expression (36 +/- 15% to 112 +/- 24%). In platelets suspended in either buffer or plasma, however, P-selectin expression was detected only at the highest cocaine concentration (85 +/- 13% increase in plasma and 59 +/- 7% in buffer). Neither aspirin nor the ADP scavenger apyrase inhibited cocaine-induced P-selectin expression. Cocaine inhibited the uptake of 14C-radiolabeled serotonin by platelets (IC50, 8.7 microM). P-selectin expression and fibrinogen binding were found after the addition of cocaine alone to blood taken from some but not all donors; however, platelet activation in response to submaximal concentrations of the agonists ADP or epinephrine was enhanced by a low concentration of cocaine added to blood from every donor.

CONCLUSIONS

Cocaine, in concentrations similar to those found clinically, induces activation of individual platelets studied in whole blood from some but not all donors, and platelet response to physiological agonists is enhanced by cocaine. Thus, cocaine-induced platelet activation may contribute to thrombosis following cocaine ingestion.
Erythrocyte ion fluxes in essential hypertensive patients with left ventricular hypertrophy.
Authors: de la Sierra A , Coca A , Paré J C , Sánchez M , Valls V , Urbano-Márquez A
Published: June 2012

BACKGROUND

Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality in essential hypertension (EH). Several hemodynamic and nonhemodynamic factors have been involved in the development of LVH in hypertension, including abnormalities in cellular ion mobilization.

METHODS AND RESULTS

We measured different ion transport systems in erythrocytes from 50 patients with EH classified as having or not having LVH measured by M-mode echocardiography. Thirty-two EH patients (64%) exhibited criteria of LVH, and 18 (36%) did not. When the two groups were compared, patients with LVH were older (44.7 +/- 7.4 versus 37.6 +/- 9.2 years; P < .01) and exhibited higher rates of erythrocyte Na(+)-H+ exchange (9.8 +/- 4.1 versus 7.1 +/- 2.6 mmol.[L.cells.h]-1; P < .05) and higher intraerythrocyte Na+ content (8.5 +/- 1.3 versus 7.5 +/- 0.8 mmol/L per cell; P < .01). Systolic and diastolic blood pressure values, as well as biochemical, hormonal, and other erythrocyte ion transport systems studied did not differ between EH with or without LVH. The results of a multiple linear regression analysis using left ventricular mass index (LVMI) as the dependent variable showed that Na(+)-H+ exchange and the maximal rate of the Na(+)-K(+)-Cl- cotransport were the only two independently significant parameters associated with an increased LVMI.

CONCLUSIONS

The increased rate of the erythrocyte Na(+)-H+ exchange and the decreased maximal rate of the Na(+)-K(+)-Cl- cotransport system are both associated with the presence of LVH in EH patients. These abnormalities of ion transport pathways tend to increase the intracellular Na+ content and may be involved in the pathogenesis of LVH in EH.
Thallium reinjection demonstrates viable myocardium in regions with reverse redistribution.
Authors: Marin-Neto J A , Dilsizian V , Arrighi J A , Freedman N M , Perrone-Filardi P , Bacharach S L , Bonow R O
Published: June 2012

BACKGROUND

The clinical significance and pathophysiological mechanisms of reverse redistribution on stress-redistribution thallium-201 myocardial scintigraphy in patients with chronic coronary artery disease are unclear. Recent studies have shown that thallium-201 reinjection is a useful technique for the detection of myocardial viability in chronic coronary artery disease. In this investigation we determined whether thallium reinjection distinguishes viable from nonviable myocardium in regions with reverse redistribution.

METHODS AND RESULTS

We studied 39 patients with chronic stable coronary artery disease (age, 60 +/- 10 years), all of whom demonstrated reverse redistribution on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT). Reverse redistribution was defined as > or = 10% decrease in relative thallium-201 activity between stress and redistribution images and included either the worsening of a perfusion defect apparent on post-stress images or the appearance of a new defect on the redistribution images. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution study. Of 39 regions with reverse redistribution, 32 (82%) showed enhanced thallium-201 activity (> or = 10% increase) after reinjection. In the other 7 regions (18%), the scintigraphic defect persisted after reinjection. Abnormal Q waves were present in only 8 of 32 (25%) regions with enhanced thallium-201 uptake after reinjection compared with 5 of 7 (71%) regions not responding to reinjection (P < .05). Akinetic or dyskinetic wall motion was present in 3 of 32 (9%) regions showing enhanced uptake after reinjection, in contrast with 5 of 7 (71%) regions not responding to reinjection (P < .01). Critically stenosed or totally occluded coronary arteries supplied 24 of 29 (83%) regions with enhanced thallium-201 uptake after reinjection but only 2 of 7 (28%) regions not showing a positive response to reinjection (P < .05). Collateral circulation was detected in 23 of 29 (79%) regions with a positive thallium reinjection effect but in only 1 of the other 7 regions (P < .01). Sixteen of the 39 patients also underwent positron emission tomography using 18F-fluorodeoxyglucose (FDG) to assess glucose utilization and H2(15)O to assess regional blood flow. The 14 regions with reverse redistribution that responded to reinjection with enhanced thallium uptake all showed either normal patterns of FDG uptake and flow or an ischemic pattern with increased FDG uptake relative to flow. Reduced FDG uptake and reduced flow values were seen in the two regions not responding to thallium reinjection.

CONCLUSIONS

These observations indicate that reverse redistribution in chronic coronary artery disease usually reflects viable myocardium, critically dependent upon collateral circulation.
Experimental atrial septal defect closure with a new, transcatheter, self-centering device.
Authors: Das G S , Voss G , Jarvis G , Wyche K , Gunther R , Wilson R F
Published: June 2012

BACKGROUND

Despite two decades of research, a transcatheter atrial septal defect closure device is not available for clinical use. We have designed a new superelastic Nitinol-Dacron, double-disk, self-centering, atrial septal defect closure device and studied its efficacy in a canine model of atrial septal defects.

METHODS AND RESULTS

Atrial septal defects were created surgically in 20 adult dogs using either a 7.5-mm or 10-mm punch. Percutaneous transcatheter closures were attempted using a new device. The device sizes used were 20 mm in 6 dogs, 22 mm in 9, and 25 mm in 5 (22.1 +/- 1.9 mm, mean +/- SD). The stretched atrial septal defect diameter was 10.5 +/- 1.3 mm, and the device to stretched atrial septal defect diameter ratio was 2.1 +/- 0.3. Closures were successful in 19 studies and unsuccessful in 1. Angiography showed a left-to-right shunt in all 20 dogs before closure. Immediately after closure (n = 19), there were no shunts in 17 and trivial shunts in 2. Six dogs were followed for a period of 4.7 +/- 3.0 months (range, 2 to 8 months). The trivial shunt present in 1 animal immediately after closure had closed by the time of the repeat study. Spontaneous embolization of the device was not seen during follow-up. A solitary wire fracture was found 8 months after closure in 1 device. Light microscopy at 8 weeks in 3 dogs showed the devices to be covered by smooth endocardium, enmeshed in mature collagen tissue, with a minimal mononuclear cell infiltration. Retrievability was assessed by deliberately embolizing 4 devices in 2 dogs into the right atrium (n = 1) and pulmonary artery (n = 3). All devices were successfully retrieved with a snare.

CONCLUSIONS

This feasibility study demonstrates that this new self-centering atrial septal defect closure device has a number of design features that permit effective and safe closures in a canine model. These results support the investigation of this device in human clinical trials.
Effect of inotropic stimulation on the negative force-frequency relationship in the failing human heart.
Authors: Schwinger R H , Böhm M , Müller-Ehmsen J , Uhlmann R , Schmidt U , Stäblein A , Uberfuhr P , Kreuzer E , Reichart B , Eissner H J
Published: June 2012

BACKGROUND

In severe human heart failure, an increase in frequency of stimulation is accompanied by a reduced force of contraction in vivo and in vitro. The present study was aimed to investigate whether inotropic stimulation influences the inverse force-frequency relationship in failing human myocardium.

METHODS AND RESULTS

The effects of the cAMP-independent positive inotropic agents ouabain (0.01 mumol/L) and BDF 9148 (0.1 mumol/L) as well as the beta-adrenoceptor agonist isoprenaline (0.01 mumol/L and 0.1 mumol/L) on the force-frequency relationship in electrically driven papillary muscle strips from nonfailing (brain death, n = 5) and terminally failing (NYHA class IV, heart transplants, dilated cardiomyopathy, n = 22) human myocardium were studied. For comparison, we examined the effect of elevation of the extracellular Ca2+ concentration (3.2 mmol/L and 6.2 mmol/L). In nonfailing myocardium, force of contraction, peak rate of tension rise, and peak rate of tension decay increased, whereas time to peak tension and time to half relaxation decreased following an increase of stimulation frequency. In NYHA class IV, force of contraction gradually declined followed by changes of other parameters of isometric contraction. Moderate stimulation of contractility by isoprenaline (0.01 mumol/L) partly reversed the negative force-frequency relationship in NYHA class IV and preserved the positive force-frequency relationship in nonfailing myocardium. The addition of ouabain and BDF 9148 together restored completely the force-frequency relationship in NYHA class IV. In contrast, high concentrations of isoprenaline (0.1 mumol/L) and an elevation of the extracellular Ca2+ concentration enhanced the decline in force of contraction in the presence of higher stimulation frequencies.

CONCLUSIONS

It is concluded that functionally important changes occur in the intracellular Ca2+ handling, leading to the negative force-frequency relationship in terminally failing human myocardium. Interestingly, the negative force-frequency relationship can be restored by agents producing positive inotropic effects by elevation of the intracellular Na+ concentration. These findings suggest that hitherto unknown changes in the intracellular ionic homeostasis occur in the failing human heart. Even though increasing [Ca2+]i in failing heart cells may be detrimental, increasing [Na+bdi may be beneficial through a mechanism independent of an increase in [Ca2+]i.
Orthodromic capture of the atrial electrogram during transient entrainment of atrioventricular nodal reentrant tachycardia.
Authors: Satoh M , Miyajima S , Koyama S , Ishiguro J , Okabe M
Published: June 2012

BACKGROUND

The reentry circuit of atrioventricular nodal reentrant tachycardia (AVNRT) has not been fully demonstrated. We hypothesized that if an upper common pathway was present, the atrial electrogram could not be captured orthodromically during transient entrainment of AVNRT by rapid atrial pacing. Based on this hypothesis, the presence of an upper common pathway was investigated.

METHODS AND RESULTS

The atrial electrogram at the recording site of the His bundle potential was identified during induced AVNRT in 9 patients. To entrain AVNRT transiently, rapid pacing from the high right atrium and coronary sinus was applied at a cycle length 10 milliseconds shorter than that of AVNRT and repeated after a decrement of the paced cycle length in steps of 5 milliseconds until AVNRT was interrupted. In 5 of 7 patients, orthodromic capture of the atrial electrogram at the recording site of the His bundle potential was observed during transient entrainment of AVNRT by coronary sinus pacing, ie, the first postpacing interval of the atrial electrogram at the recording site of the His bundle potential was the same as the paced cycle length. In these 5 patients, the mean minimum paced cycle length capable of orthodromic atrial capture was 349 milliseconds, and the mean difference from the cycle length of AVNRT was only 16 milliseconds. During transient entrainment of AVNRT by high right atrial pacing, the atrial electrogram could not be captured orthodromically.

CONCLUSIONS

Observation of orthodromic capture of the atrial electrogram at the recording site of the His bundle potential by coronary sinus pacing ruled out the presence of an upper common pathway in AVNRT, and the concept that perinodal atrial tissue is involved in the reentry circuit of AVNRT was supported.
Determinants of the prognosis after a first myocardial infarction in a migrant Japanese population. The Honolulu Heart Program.
Authors: Yano K , Grove J S , Reed D M , Chun H M
Published: June 2012

BACKGROUND

Although numerous studies have been published on the prognostic assessment of myocardial infarction, little is known about determinants of the prognosis after a first myocardial infarction, especially regarding the role of standard risk factors for coronary heart disease (CHD) measured before the development of myocardial infarction.

METHODS AND RESULTS

In a prospective study of CHD among men of Japanese ancestry living in Hawaii, 457 patients with a first myocardial infarction (age range, 46 to 84 years) were identified during 20 years of follow-up. The relations of clinical variables and CHD risk factors to mortality in early (< 30 days) and two stages of late (30 days to 5 years and 5 to 10 years) periods after myocardial infarction in these patients were investigated. In multivariate analyses using logistic regression models (for early mortality) and Cox regression models (for late mortality), age at myocardial infarction and severe complications (Killip classes 3 and 4) were independent predictors of both early and late mortality (up to 5 years after myocardial infarction). In addition, ventricular arrhythmias predicted only early mortality, whereas anterior myocardial infarction, radiological evidence of cardiomegaly and/or pulmonary congestion, and intraventricular block predicted only late mortality (up to 5 years after myocardial infarction). Only age was an independent predictor of all-cause mortality more than 5 years after myocardial infarction. After adjusting for age at myocardial infarction and these clinical variables, preinfarction-measured risk factors such as 1-hour postload serum glucose (positively) and 1-second forced expiratory volume (inversely) were significantly associated with late mortality up to 5 years, whereas systolic blood pressure was the only independent predictor of late mortality after 5 years.

CONCLUSIONS

This study has confirmed the importance of age at myocardial infarction and clinical indicators of complications such as Killip class 3 or 4, radiological evidence of pulmonary congestion, and ventricular arrhythmias or intraventricular block as the prognostic determinants of myocardial infarction. In addition, some of the preinfarction-measured standard risk factors for CHD were found to predict long-term prognosis independent of age and clinical factors.
Intraventricular early diastolic filling during acute myocardial ischemia, assessment by multigated color m-mode Doppler echocardiography.
Authors: Stugaard M , Smiseth O A , Risöe C , Ihlen H
Published: June 2012

BACKGROUND

Color M-mode Doppler echocardiography has been suggested as a new noninvasive technique for assessing left ventricular diastolic function. The present study investigated intraventricular filling pattern by color M-mode Doppler in patients during percutaneous transluminal coronary angioplasty (PTCA). In a dog model of myocardial ischemia, the color M-mode flow pattern was related to indices of global and regional myocardial function.

METHODS AND RESULTS

From color M-mode images, the time difference (TD) between occurrence of peak velocity in the apical region and at the mitral tip was determined in 20 patients and eight anesthetized dogs during coronary occlusions. During PTCA, the timing of peak velocity was progressively delayed from mitral valve to apex. Consistent with this, the dog model showed delayed apical filling during coronary occlusion; TD increased from 18 +/- 4 to 71 +/- 9 milliseconds (P < .01). In the ischemic region, systolic shortening (sonomicrometry) decreased from 20 +/- 3% to -5 +/- 2% (p < .01). The one-third filling fraction decreased from 59 +/- 5% to 31 +/- 6% (P < .01) and correlated with TD (r = .85, P < .01). The time constant of isovolumic relaxation (tau) increased slightly and correlated with TD (r = .81, P < .01). Pacing tachycardia, caval constriction, and volume loading were performed to mimic the ischemia-induced changes in heart rate, stroke volume, and intracavitary filling pressure, respectively. There were no significant changes in TD or tau during these interventions.

CONCLUSIONS

Color M-mode Doppler echocardiography showed a marked delay of apical peak filling velocity during PTCA. The experimental data suggest that this reflects retarded filling of the ischemic ventricle. Thus, color M-mode Doppler may provide a useful method for assessing diastolic dysfunction.
Coronary angioplasty. Statewide experience in California.
Authors: Ritchie J L , Phillips K A , Luft H S
Published: June 2012

BACKGROUND

This report describes the in-hospital experience with percutaneous transluminal coronary angioplasty (PTCA) for the state of California in 1989. Data are derived from the statewide hospital discharge abstracts.

METHODS AND RESULTS

A total of 24,883 PTCAs were performed; most patients (70%) were men and most procedures were single vessel (87%). About one fifth (19%) of patients had a principal diagnosis of acute myocardial infarction (AMI). Overall mortality was 1.4% and was higher in the AMI group (4.2%) versus the non-AMI group (0.8%, P = .0001). Mortality was higher for AMI patients having PTCA on the day of or day after admission (5.5%) versus those treated later (2.6%, P = .0001). Five percent of patients had coronary artery bypass surgery (CABG) after PTCA; CABG was performed on the same day as PTCA in 61.7% of cases. Patients presenting with AMI were more likely to have CABG (7.1%) than non-AMI patients (4.5%, P = .0001). Mortality associated with CABG was 7.3% and was higher in the AMI group (12.0%) than in the non-AMI group (5.5%, P = .0001). Factors predictive of increased mortality by bivariate analysis included age > 63 years (2.1% mortality versus 0.8% < or = 63, P = .01), female sex (1.9% versus 1.2% for men, P < .01), and the presence of diabetes (1.9% versus 1.3% for nondiabetics, P < .05). Multiple logistic regression showed that timings of PTCA with respect to admission (P = .004) and age (P = .05) were predictors of mortality, but female sex was predictive only in the non-AMI group (P = .03). Mean hospital charges were $19,597 (+/- SD, $18,213). Forty-two percent of the 110 hospitals performed more than the recommended minimum of 200 cases per year. The requirement for CABG during the same admission or the combined adverse outcome of CABG and/or death was increased in the lower-volume centers for both AMI and non-AMI patients (P < .001), although mortality alone was not.

CONCLUSIONS

The mortality and need for CABG surgery in the statewide California PTCA experience is higher than that generally reported in the literature. In patients with an admitting diagnosis of AMI, the overall mortality was higher, as was the need for CABG and the associated CABG mortality. Most hospitals performed fewer than 200 PTCAs per year. Rates of CABG surgery and the combination of CABG and/or mortality, adjusted only for the presence or absence of AMI, were increased at the low-volume institutions.
Efficient and selective adenovirus-mediated gene transfer into vascular neointima.
Authors: Guzman R J , Lemarchand P , Crystal R G , Epstein S E , Finkel T
Published: June 2012

BACKGROUND

Previous attempts to target arterial smooth muscle cells (SMCs) for gene delivery using liposomal or retroviral methods were limited by low transfection efficiency. We therefore evaluated the efficiency of adenovirus-mediated gene delivery in cultured vascular SMCs and in an in vivo model of balloon injury-induced SMC cell proliferation.

METHODS AND RESULTS

We used a recombinant adenovirus, Ad.RSV beta gal, which contained the beta-galactosidase (beta-gal) histochemical marker gene. For in vitro studies, rat aortic SMCs were incubated in media containing Ad.RSV beta gal for 5 to 120 minutes. The proportion of SMCs expressing the beta-gal gene product increased from 25% (5-minute exposure) to 80% (120-minute exposure). For in vivo studies, uninjured and injured rat carotid segments were incubated with 0.5 to 1.0 x 10(9) pfu Ad.RSV beta gal for 45 minutes. Uninjured arteries showed adenovirus-mediated gene transfer limited to the endothelium. Injured arteries were exposed to adenovirus 0, 3, 7, or 12 days after injury. In these segments, beta-gal expression was minimal with infection at 0 or 3 days after injury but marked when infection was delayed until 7 or 12 days after injury. Neointimal cells constituted the dominant target of adenovirus gene transfer, with efficiency of gene transfer ranging from 10% to > 75%. Medial SMCs, whether covered or uncovered by neointimal cells, were minimally infected. Infection with a control adenovirus vector showed no beta-gal staining.

CONCLUSIONS

Recombinant adenovirus selectively targets neointimal cells with high-efficiency gene transfer. This suggests that adenovirus vectors should be useful in targeting cells for the delivery of genes whose products may be relevant to the treatment of restenosis.
Limitation of infarct expansion and ventricular remodeling by late reperfusion. Study of time course and mechanism in a rat model.
Authors: Boyle M P , Weisman H F
Published: June 2012

BACKGROUND

Reperfusion of acutely infarcted myocardium may be beneficial in limiting infarct expansion and ventricular remodeling even if established after the time that salvage of ischemic myocardium is possible.

METHODS AND RESULTS

To examine the permanency, time course, and mechanism of this effect of late reperfusion, 200 rats were randomized into one of four groups: (1) infarction with reperfusion after 1 to 2 hours, (2) infarction with reperfusion after 6 to 8 hours, (3) infarction without reperfusion, and (4) sham operation. Surviving rats were killed at either 7 days, when infarct expansion has plateaued, or 21 days, when infarct healing is complete. In both 7- and 21-day analyses, late reperfusion did not reduce infarct size or degree of transmural necrosis but significantly limited infarct expansion, as measured by an index based on infarct endocardial segment lengthening and infarct wall thinning (expansion index at 7 days: no reperfusion, 2.73 +/- 0.25, n = 13; reperfusion after 1 to 2 hours, 1.56 +/- 0.13, n = 23, P < .001; reperfusion after 6 to 8 hours, 1.78 +/- 0.15, n = 16, P = .002; at 21 days: no reperfusion, 3.45 +/- 0.39, n = 13; reperfusion after 1 to 2 hours, 2.21 +/- 0.24, n = 15, P = .01; reperfusion after 6 to 8 hours, 2.02 +/- 0.20, n = 9, P = .01). Reperfusion after 6 to 8 hours was equally effective in limiting expansion as reperfusion after 1 to 2 hours. Late reperfusion also significantly reduced ventricular remodeling at 21 days, as measured by an index based on left ventricular cavity dilatation and noninfarcted myocardial hypertrophy (remodeling index at 21 days: no reperfusion, 2.67 +/- 0.15, n = 13; reperfusion after 1 to 2 hours, 2.20 +/- 0.15, n = 15, P = .035; reperfusion after 6 to 8 hours, 2.12 +/- 0.10, n = 9, P = .012). Histological examination revealed that reperfusion accelerated the clearance of residual dead myofibrils, suggesting an increase in the rate of healing, and increased the degree of myocytolysis but did not change the final degree of infarct healing, tissue density, or viable subepicardial cells.

CONCLUSIONS

Late reperfusion causes a permanent reduction in postinfarction expansion that is present even after complete infarct healing. The time after coronary occlusion in which reperfusion is of benefit in reducing subsequent expansion and remodeling is substantially longer than previously established. The mechanism by which late reperfusion limits expansion may involve changing the rate of healing and the nature of myocardial necrosis but does not involve preserving subepicardial cells.
Combined ADP and thromboxane A2 antagonism prevents cyclic flow variations in stenosed and endothelium-injured arteries in nonhuman primates.
Authors: Yao S K , McNatt J , Cui K , Anderson H V , Maffrand J P , Buja L M , Willerson J T
Published: June 2012

BACKGROUND

This study was designed to test the hypothesis that clopidogrel, a potent inhibitor of platelet aggregation, can eliminate cyclic flow variations in stenosed and endothelium-injured coronary and femoral arteries in nonhuman primates.

METHODS AND RESULTS

We studied five anesthetized, open-chest baboons. Blood flow velocity in the coronary and femoral arteries was monitored by pulsed Doppler flow probes placed around the arteries. Cyclic flow variations were established by mechanically injuring the endothelium of the arteries and by narrowing the arteries with external constrictors. Clopidogrel (10 to 20 mg/kg i.v. bolus plus 2.5 mg.kg-1 x h-1 continuous infusion) was administered 60 minutes after cyclic flow variations were established. Clopidogrel abolished cyclic flow variations in the coronary and femoral arteries of all five baboons (frequency of cyclic flow variations, 0/h versus 14/h at baseline, P < .001). Then epinephrine was infused (maximum average dose, 2.2 micrograms.kg-1 x min-1 i.v.). Epinephrine did not restore cyclic flow variations in the coronary or femoral arteries of any baboon. Before treatment with clopidogrel, ADP, collagen, and U46619, a thromboxane A2 mimetic, induced dose-dependent platelet aggregation in vitro. Serotonin, however, did not induce platelet aggregation in vitro. Clopidogrel given in vivo completely inhibited ADP-induced platelet aggregation and significantly diminished collagen- and U46619-induced platelet aggregation in vitro.

CONCLUSIONS

Clopidogrel eliminates cyclic flow variations in stenosed and endothelium-injured coronary and femoral arteries of nonhuman primates at least in part by antagonizing the platelet proaggregatory effects of ADP and thromboxane A2.
Low iron-binding capacity as a risk factor for myocardial infarction.
Authors: Magnusson M K , Sigfusson N , Sigvaldason H , Johannesson G M , Magnusson S , Thorgeirsson G
Published: June 2012

BACKGROUND

In a recent Finnish study, ferritin was suggested to be an independent risk factor for acute myocardial infarction. This study suggested that high levels of iron stores might thus be atherogenic and possibly explain partly the sex difference in the incidence of ischemic heart disease.

METHODS AND RESULTS

A randomly selected group (n = 2036), men and women aged 25 to 74 years, were examined between June and September 1983. All classic risk factors for coronary artery disease were measured as well as basic hematologic parameters and the parameters of iron metabolism, ie, iron, total iron-binding capacity (TIBC), and ferritin. During the follow-up for 8.5 years, 81 subjects experienced acute myocardial infarction (63 men and 18 women). The differences in the iron parameters between men and women were almost exclusively seen in ferritin values (198 micrograms/L in men and 91 micrograms/L in women), whereas small differences were seen in TIBC. The Cox proportional hazards model was used to estimate the contribution of independent variables to the risk of myocardial infarction. TIBC was found to be a strong independent negative risk factor in men (RR = 0.95; 95% CI, 0.92 to 0.98), whereas ferritin (RR = 0.999; 95% CI, 0.997 to 1.001) or other iron parameters had no significant predictive power. Each increase in TIBC of 1 mumol/L was associated with a 5.1% decrease in the risk of myocardial infarction. The classic major risk factors, ie, blood pressure, smoking, total cholesterol, and high-density lipoprotein, had significant independent correlation with myocardial infarction. When Cox multivariate analysis was carried out on both sexes combined, TIBC was still an independent negative risk factor, and the logarithmic transform of ferritin had a weak negative correlation but was not statistically significant. Sex was in this group still a very strong risk factor after taking into account all classic risk factors as well as the parameters of iron metabolism.

CONCLUSIONS

This study suggests that transferrin, measured as TIBC, is an independent negative risk factor for myocardial infarction. Other parameters of iron metabolism, including ferritin, were not found to contribute to the risk.
Rheumatic fever and the HLA complex. A cosegregation study.
Authors: Gerbase-DeLima M , Scala L C , Temin J , Santos D V , Otto P A
Published: June 2012

BACKGROUND

Considering the controversial results published in the literature concerning associations between human leukocyte antigens (HLA) and rheumatic fever (RF), the purpose of the present study was to investigate by means of cosegregation analysis the participation of HLA genes in susceptibility to RF.

METHODS AND RESULTS

The sample reported here was composed of 51 affected and 66 healthy individuals belonging to 22 genetically informative families. The comparison (chi 2 goodness-of-fit test) of the observed numbers of identical-by-descent (IBD) HLA haplotypes among all affected individuals (siblings, cousins, and uncle/nephew and grandparent/grandchild type of pairs) with the expected ones under the assumption of independent segregation of HLA alleles and the presumptive RF susceptibility gene gave a value of P = .088. Since the number of subjects studied was relatively small and the rejection level obtained was near the usual .05 significance level, we calculated the expected HLA IBD scores in the 13 pairs of affected sibs of our sample for all possible frequencies of the presumptive RF susceptibility gene. This analysis allowed clear rejection of a recessive mode, considering susceptibility gene frequencies lower than 20%, whereas the observed values fitted very well a dominant mode of inheritance, with penetrance (K) values varying between 0.5 and 0.9 and a frequency of the susceptibility gene of at least 1%.

CONCLUSIONS

The present data support the hypothesis of an RF susceptibility gene within or very near the HLA complex.
Structural basis of end-stage failure in ischemic cardiomyopathy in humans.
Authors: Beltrami C A , Finato N , Rocco M , Feruglio G A , Puricelli C , Cigola E , Quaini F , Sonnenblick E H , Olivetti G , Anversa P
Published: June 2012

BACKGROUND

Ischemic cardiomyopathy is characterized by myocyte loss, reactive cellular hypertrophy, and ventricular scarring. However, the relative contribution of these tissue and cellular processes to late failure remains to be determined.

METHODS AND RESULTS

Ten hearts were obtained from individuals undergoing cardiac transplantation as a result of chronic coronary artery disease in its terminal stage. An identical number of control hearts were collected at autopsy from patients who died from causes other than cardiovascular disease, and morphometric methodologies were applied to the analysis of the left and right ventricular myocardium. Left ventricular hypertrophy evaluated as a change in organ weight, aggregate myocyte mass, and myocyte cell volume per nucleus showed increases of 85%, 47%, and 103%, respectively. Corresponding increases in the right ventricle were 75%, 74%, and 112%. Myocyte loss, which accounted for 28% and 30% in the left and right ventricles, was responsible for the difference in the assessment of myocyte hypertrophy at the ventricular, tissue, and cellular levels. Left ventricular muscle cell hypertrophy was accomplished through a 16% and 51% increase in myocyte diameter and length, whereas right ventricular myocyte hypertrophy was the consequence of a 13% and 67% increase in these linear dimensions, respectively. Moreover, a 36% reduction in the number of myocytes included in the thickness of the left ventricular wall was found. Collagen accumulation in the form of segmental, replacement, and interstitial fibrosis comprised an average 28% and 13% of the left and right ventricular myocardia, respectively. The combination of cell loss and myocardial fibrosis, myocyte lengthening, and mural slippage of cells resulted in 4.6-fold expansion of left ventricular cavitary volume and a 56% reduction in the ventricular mass-to-chamber volume ratio.

CONCLUSIONS

These results are consistent with the contention that both myocyte and collagen compartments participate in the development of decompensated eccentric ventricular hypertrophy in the cardiomyopathic heart of ischemic origin.
Short-coupled variant of torsade de pointes. A new electrocardiographic entity in the spectrum of idiopathic ventricular tachyarrhythmias.
Authors: Leenhardt A , Glaser E , Burguera M , Nürnberg M , Maison-Blanche P , Coumel P
Published: June 2012

BACKGROUND

Torsade de pointes is characterized not only by its particular ECG pattern but by its context of congenital or acquired long QT syndrome and the long coupling interval of the initial premature beat.

METHODS AND RESULTS

We observed 14 patients aged 34.6 +/- 10 years (mean +/- SD) with no structural heart disease who presented with syncope related to a typical ECG aspect of torsade de pointes. However, there was no evidence of long QT syndrome, and the torsade had the unusual particularity of an extremely short coupling interval of the first beat or of the isolated premature beats (245 +/- 28 milliseconds). In 10 cases they deteriorated into ventricular fibrillation. Four patients had a familial history of sudden death. Only 2 patients had a tachyarrhythmia inducible by programmed stimulation. At Holter recordings the heart rate variability was globally and significantly depressed, the vagal limb of the autonomic nervous system being predominantly affected. During a mean follow-up of 7 years there were 5 deaths (4 sudden). Nine patients are alive, 3 with implanted defibrillators and 6 treated with verapamil alone. Unlike the other types of antiarrhythmic agents including beta-blockers and amiodarone, verapamil is in our experience the only drug apparently active on the arrhythmias; however, it does not prevent sudden death.

CONCLUSIONS

The short-coupled variant of torsade de pointes should be identified because of their ECG pattern and the risk of sudden death in young adults with no structural heart disease.