bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial and temporal linking of epicardial activation directions during ventricular fibrillation in dogs. Evidence for underlying organization.
Authors: Damle R S , Kanaan N M , Robinson N S , Ge Y Z , Goldberger J J , Kadish A H
Published: June 2012

BACKGROUND

It remains controversial as to whether electrical activation during ventricular fibrillation (VF) is organized. To detect the presence of organization in VF, the direction of epicardial activation (EA) at multiple sites was examined by using vector mapping. If VF is not a random process, EA direction at a given site should be related to adjacent sites and prior beats.

METHODS AND RESULTS

Thirteen dogs with healing myocardial infarction (MI) and four dogs without MI had VF induced by programmed stimulation. Using a plaque electrode array with a 2.5-mm interelectrode distance, 91 vector loops were created for each "beat" of VF. Direction of maximum EA was determined at each site for the first 10 consecutive beats of VF and for 10 consecutive beats recorded 5 seconds after VF was established. Spatial and temporal linking of EA directions was evaluated by the ability of activation direction at a given site to be predicted by activation directions at eight adjacent sites for the index beat and at eight adjacent sites and the site of interest for the preceding beat using stepwise linear regression. The strength of the model as reflected by the correlation coefficient (r) indicated the degree of linking. We determined 1) changes in the degree of linking over time during a given episode of VF (using a paired-difference t test), 2) differences in the degree of linking between the anterior and posterolateral walls in animals with (n = 4) and without (n = 4) MI (using two-way ANOVA), and 3) the effect of repeated inductions (n = 10) on the degree of linking (using one-way ANOVA with repeated measures). During 57 episodes of VF, r for each model ranged from 0.64 to 0.88 during the transition to VF to 0.39-0.78 during established VF (p < 0.0001 for the difference). The presence of MI, the site of recording, and repeated inductions did not affect the degree of linking. For each episode, spatial linking was more prominent than temporal linking.

CONCLUSIONS

Electrical activation during VF is organized. The degree of linking of EA directions during VF is not affected by the presence of MI, the site of recording, or repeated inductions of VF. During the first 5 seconds of VF, the degree of linking decreases.
Vascular injury and time course of smooth muscle cell proliferation after experimental holmium laser angioplasty.
Authors: Hassenstein S , Hanke H , Kamenz J , Oberhoff M , Hanke S , Riessen R , Haase K K , Betz E , Karsch K R
Published: June 2012

BACKGROUND

In vitro experiments have shown that holmium laser energy can effectively ablate even calcified plaque in human arterial vessels. Because high-energy densities from holmium lasers can easily be transmitted through quartz fibers, this solid-state laser has been suggested as an alternative intraluminal treatment of atherosclerotic plaque.

METHODS AND RESULTS

To develop an intimal plaque, 35 New Zealand White rabbits underwent electrical stimulation of their right carotid artery for 28 days. Subsequently, in 25 rabbits, holmium laser angioplasty (wavelength, 2.12 microns; pulse duration, 150 microseconds; energy density, 350 mJ/mm2) was performed. To study the morphological results, the vessels were excised after 7, 14, 28, and 42 days. Cross sections were analyzed in regard to laser-specific injury. Staining of alpha-actin was used to identify smooth muscle cells (SMCs). After bromodeoxyuridine labeling, the extent of proliferation (number of cells undergoing DNA synthesis) was determined by using a monoclonal antibody. Holmium laser ablation resulted in an initial decrease of the numbers of intimal cell layers in the early group (7 days after treatment: 5 +/- 1 cell layers with 76 +/- 39 microns; control: 13 +/- 3 cell layers with 144 +/- 44 microns). Quantification of SMCs undergoing DNA synthesis in the intima (control: 51 +/- 19 cells/mm2) showed a significant increase of labeled cells after 7 (216 +/- 74 cells/mm2, p = 0.003) and 14 days (281 +/- 139 cells/mm2, p = 0.011). Integrity of the internal elastic lamina was disrupted in all animals after intervention. Seven and 14 days after treatment, a considerable reduction of medial cell nuclei was found in 10 of 12 animals. SMC proliferation in the medial layer was increased within the first 2 weeks after laser ablation (168 +/- 113 cells/mm2; control: 8 +/- 4 cells/mm2; p = 0.023). Six weeks after holmium laser angioplasty, SMC proliferation had returned to control levels in the intima and remained increased in the medial layer. This proliferative response resulted in a significant increase of intimal thickening within 6 weeks after laser ablation (30 +/- 6 cell layers, 375 +/- 97 microns resp.; p = 0.001 each).

CONCLUSIONS

Holmium laser treatment leads to considerable vessel wall injury and results in SMC proliferation in the intimal and medial layer with a maximum of proliferative activity within the first 2 weeks. Subsequently, this results in considerable intimal and medial hyperplasia within 6 weeks after treatment.
Preoperative prediction of the outcome of coronary revascularization using positron emission tomography.
Authors: de Silva R , Yamamoto Y , Rhodes C G , Iida H , Nihoyannopoulos P , Davies G J , Lammertsma A A , Jones T , Maseri A
Published: June 2012

BACKGROUND

Previous assessments of myocardial viability using positron emission tomography (PET) relied on demonstration of glucose metabolism in hypoperfused asynergic segments using the glucose analogue [18F]2-fluoro-2-deoxyglucose (FDG). Recently, it was shown that myocardial viability could be assessed by calculating the water-perfusable tissue index (PTI) for the asynergic region. PTI represents the proportion of the myocardium that is capable of rapid transsarcolemmal exchange of water and thus perfusable by water. The aim of the present study was to assess myocardial viability by PET using PTI in patients undergoing coronary revascularization.

METHODS AND RESULTS

Twelve patients with chronic coronary artery disease and previous myocardial infarction were studied. Analysis of transmission (tissue density) and 15O-labeled carbon monoxide (blood pool), and 15O-labeled water (myocardial blood flow [MBF]) emission PET data enabled the simultaneous quantification of MBF (ml.min-1.g perfusable tissue-1) and PTI (gram of perfusable tissue per gram of total anatomic tissue). In addition, PET imaging with FDG after 75-g oral glucose load was performed in eight patients. Preoperative echocardiography identified 33 hypocontractile and 26 control segments. Follow-up echocardiography performed 3 to 5 months later demonstrated 26 of 33 segments with improved wall motion (recovery) and seven of 33 segments without improvement (nonrecovery). MBF in the control segments (0.97 +/- 0.22 ml.min-1.g perfusable tissue-1) was significantly higher (p < 0.001) than in both the recovery (0.73 +/- 0.18 ml.min-1.g perfusable tissue-1) and the nonrecovery (0.45 +/- 0.11 ml.min-1.g perfusable tissue-1) segments. PTI in the recovery regions (0.99 +/- 0.15) was > or = 0.7 in all cases and slightly less than in control regions (1.10 +/- 0.15, p < 0.02). FDG uptake in these regions was 92 +/- 17% (n = 13) of the uptake in control segments with normal wall motion. In the nonrecovery group, PTI was 0.62 +/- 0.06 (p < 0.02 versus control and recovery) and always < 0.7. In the one patient in whom a comparison with metabolic imaging was made, FDG uptake was 46% of the uptake in a reference region with normal wall motion.

CONCLUSIONS

These data showed that contractile recovery occurred only in segments where PTI was > or = 0.7, suggesting that > or = 70% of myocardial tissue in a given asynergic segment should be perfusable by water to enable contractile recovery. There was good agreement between the PTI and FDG methods for predicting improvements in regional wall motion after revascularization. Although further studies should be performed in a larger patient group, the preliminary results are promising and suggest that PTI may be a good predictor of contractile recovery after coronary revascularization.
Natural history and patterns of recovery of contractile function in single left ventricle after Fontan operation.
Authors: Sluysmans T , Sanders S P , van der Velde M , Matitiau A , Parness I A , Spevak P J , Mayer J E , Colan S D
Published: June 2012

BACKGROUND

Before the era of the Fontan procedure, the typical course of patients with single left ventricle (LV) consisted of heart failure and death during the second or third decade of life. Despite the advent of effective palliative therapy, ventricular dysfunction remains a significant clinical problem for these patients.

METHODS AND RESULTS

To investigate the causes of ventricular dysfunction in these patients and to determine whether Fontan-type repair reverses deterioration of LV function, the ventricular dimensions, volume, shape, wall stress, and systolic function were determined by echocardiography in 84 patients 0.2-35 years old with double-inlet single LV or tricuspid atresia. Measurements were obtained in 67 patients after palliation (arterial shunt or pulmonary artery band) and in 47 patients a median of 4.4 years after a Glenn (n = 9) or a Fontan operation (n = 38). Before a Fontan procedure, ventricular volumes were 2 to 3 times normal. Ventricular afterload, assessed as circumferential and meridional end-systolic wall stress, became abnormal after 2 years of age. With age, LV shape changed progressively from ellipsoidal to spherical, as indicated by the decrease in long axis:short axis ratio from normal (1.9) toward unity. Concomitantly, the ratio of circumferential to meridional end-systolic wall stress fell from 1.3 to unity, the ratio of a sphere at equilibrium. This age-related change in shape and load occurred in concert with progressive deterioration of LV systolic function and contractility. Aortic oxygen saturation, an indicator of pulmonary blood flow and therefore volume work in single-ventricle physiology, was inversely and independently correlated with contractility. In the group of patients in whom a Glenn or a Fontan operation was performed at < 10 years of age, ventricular dimensions, volumes, and wall stress diminished and LV function and contractility improved after surgery (p < 0.001). In patients undergoing surgery after 10 years of age, few had improvement of LV function after surgery. Postoperative ventricular function and contractility were inversely related to age at surgery and to aortic oxygen saturation measured before surgery.

CONCLUSIONS

Although Fontan-type repair of single ventricle early in life is associated with reversal of the abnormal contractile mechanics associated with age and volume load, this capacity for recovery diminishes with age at surgery.
Augmented forearm vasoconstriction during dynamic exercise in healthy older men.
Authors: Taylor J A , Hand G A , Johnson D G , Seals D R
Published: June 2012

BACKGROUND

We tested the hypothesis that the nonactive limb vasoconstriction evoked during large-muscle dynamic exercise becomes augmented with aging in humans.

METHODS AND RESULTS

Sixteen young control subjects (age, 26 +/- 1 year) and twelve older (65 +/- 1 year) healthy men with similar chronic physical activity levels were studied during supine leg cycling exercise. Both peak work load (1,100 +/- 60 versus 1,400 +/- 40 kpm/min) and peak O2 uptake (1.85 +/- 0.10 versus 2.38 +/- 0.07 l/min) were lower in the older men (p < 0.05). There were no differences in the two groups under conditions of quiet supine (basal) rest. During cycling for 5 minutes each at mild, moderate, and heavy submaximal intensities (approximately 45%, 65%, and 85% of peak O2 uptake), the increases in arterial blood pressure generally were similar in the young and older subjects; however, heart rate rose less in the older men (p < 0.05). Whole forearm blood flow (venous occlusion plethysmography) was lower and vascular resistance was higher (approximately 55-90%) in the older men at all loads (p < 0.05), but the steady-state forearm skin blood flow responses (laser Doppler velocimetry) were not different in the two groups. The increases in antecubital venous norepinephrine concentrations were greater in the older men at each work load (p < 0.05), although the plasma epinephrine responses were similar in the two groups. In other studies, 1) peak whole forearm reactive hyperemia and vascular conductance after sustained circulatory arrest (ischemia) were slightly (approximately 20%) but not significantly lower in the older men and 2) the forearm vasoconstrictor and plasma norepinephrine responses to a nonexercise sympathoexcitatory stimulus (limb immersion in ice water) tended to be blunted in the older men.

CONCLUSIONS

During brief, submaximal, large-muscle dynamic exercise, healthy older men demonstrate augmented forearm vasoconstriction that is probably caused by greater constriction of skeletal muscle resistance vessels; this appears to be mediated, at least in part, by increased sympathetic outflow. These altered sympathetic vasoconstrictor adjustments do not represent a nonspecific hyperresponsiveness to acute stress with human aging. Finally, the regulation of arterial blood pressure appears to be normal in these healthy older men.
Diastolic vibration improves systolic function in cases of incomplete relaxation.
Authors: Takagi T , Koiwa Y , Kikuchi J , Honda H , Hoshi N , Butler J P , Takishima T
Published: June 2012

BACKGROUND

Incomplete relaxation of the left ventricle (LV) affects LV filling, but the subsequent effect on LV systolic function remains unclear. We attempted to improve relaxation by applying oscillatory mechanical perturbation during diastole (diastolic vibration) and examined the extent to which systolic function improved.

METHODS AND RESULTS

Using 10 open-chest canine preparations, pacing tachycardia and administration of propranolol were imposed to induce various levels of incomplete relaxation. Myocardial length perturbation was induced with an oscillator attached to the LV surface (50 Hz, 1-mm amplitude) and was restricted to the period from the beginning of isovolumic relaxation to end diastole. At resting heart rates, diastolic vibration caused an immediate decrease in the time constant (T) of LV pressure fall without any influence on heart rate, LV peak systolic pressure (peak LVP), stroke volume (SV), LV peak positive dP/dt, and total systemic vascular resistance. With pacing tachycardia, diastolic vibration increased both peak LVP and SV at 160 beats per minute (before) and 120 beats per minute (after propranolol), simultaneously decreasing both T and LV diastolic pressures and increasing end-diastolic segment length. The increase in peak LVP and SV caused by diastolic vibration correlated with the T/diastolic interval (r = 0.82), the assumed index of severity of incomplete relaxation.

CONCLUSIONS

These results suggest that diastolic vibration accelerates the LV relaxation rate and that this increased relaxation improves systolic function through the Frank-Starling mechanism.
Effects of calcium channel blockers on calcium uptake in rat aortic valve allografts.
Authors: Thompson S A , Smith G B , Cobb S M , Walters K S , Behrendt D M
Published: June 2012

BACKGROUND

The life span of human aortic valve allografts is finite, and many fail because of cusp rupture or calcification. Subcellular changes occurring in aortic valves in response to transplantation include the uptake of calcium. This study uses a heterotropic rat aortic valve transplant model to determine whether the calcium channel blockers diltiazem and verapamil might attenuate leaflet calcification.

METHODS AND RESULTS

The 60 rats studied were divided into the following groups: 1) control: valves from normal, unoperated F1 generation of Lewis and Brown Norway cross (LBNF1) rats; 2) control: valves from syngeneic transplant combinations (Lewis/Lewis); 3) control: valves from allogeneic transplant combinations (LBNF1/Lewis, donor/recipient); 4) experimental: valves from allogeneic strain combinations treated with 30 mg/kg per day diltiazem; 5) experimental: valves from allogeneic strain combinations treated with 30 mg/kg per day verapamil. Drugs or saline (controls) were administered with osmotic pumps placed subcutaneously 2 days before transplantation. Animals were killed 3 weeks later, and the valves were harvested and prepared for calcium analysis. Energy-dispersive x-ray microanalysis was used to measure the calcium in a section of one leaflet from each valve studied. Paired t tests showed that allograft valves treated with diltiazem or verapamil contained significantly less calcium than allograft controls treated with saline (p < 0.001). When all five groups were subjected to one-way ANOVA, the valves in the allograft control group contained significantly more calcium than all other groups. All other groups were not different from each other.

CONCLUSIONS

The calcium channel blockers verapamil and diltiazem were effective in preventing early calcification that occurs in aortic valves after transplantation. Thus, these agents might play a role in prolonging the life of human aortic valve allografts.
Induction of endothelial cell expression of the plasminogen activator inhibitor type 1 gene by thrombosis in vivo.
Authors: Fujii S , Sawa H , Saffitz J E , Lucore C L , Sobel B E
Published: June 2012

BACKGROUND

We have shown previously that products from activated platelets can augment synthesis of plasminogen activator inhibitor type 1 (PAI-1) in cultured endothelial and hepatoma (Hep G2) cells in vitro and increase plasma PAI-1 activity in vivo in rabbits. Accordingly, the effects of activation of platelets associated with thrombosis and thrombolysis in vivo on plasma PAI-1 activity and expression of the PAI-1 gene in endothelium, liver, and other organs were characterized.

METHODS AND RESULTS

Endothelial injury giving rise to platelet-rich thrombi was induced with electrical stimulation in carotid arteries in rabbits. Clot lysis and recanalization were induced subsequently with intravenous tissue-type plasminogen activator (t-PA) and verified with Doppler flow probes. Plasma PAI-1 activity (mean +/- SD) increased from 6 +/- 2 arbitrary units (AU)/ml to 129 +/- 48 AU/ml (n = 15) within several hours after recanalization. When t-PA had failed to induce recanalization, the increase was much less (from 7 +/- 2 to 42 +/- 23 AU/ml, n = 11). To define mechanisms responsible for these changes, PAI-1 messenger RNA (mRNA) was evaluated by Northern blot analysis and localized in tissues by in situ hybridization. Strong and consistent induction of PAI-1 mRNA was evident in aorta, heart, and liver of animals subjected to thrombosis (twofold to threefold increases compared with values in controls), particularly in those in which thrombolysis had been induced (fourfold to sixfold). After thrombolysis, an intense, PAI-1 mRNA-specific signal was detected in endothelium of aorta, liver, and heart, with less intense signals in endothelium of lung, adrenals, and kidneys.

CONCLUSIONS

The increases in plasma PAI-1 activity follow a preceding increase in endothelial cell expression of the PAI-1 gene as reflected by PAI-1 mRNA levels. Thus, increased synthesis of endothelial cell PAI-1 after thrombosis and thrombolysis may attenuate endogenous fibrinolysis early after coronary thrombolysis, thereby potentiating early, thrombotic reocclusion.
Adenosine-sensitive ventricular tachycardia. Clinical characteristics and response to catheter ablation.
Authors: Wilber D J , Baerman J , Olshansky B , Kall J , Kopp D
Published: June 2012

BACKGROUND

Sustained ventricular tachycardia in the absence of structural heart disease may have diverse mechanisms. Termination of the tachycardia by adenosine suggests triggered automaticity as the etiology in many of these patients. We examined the clinical characteristics, electrophysiological responses, and results of catheter ablation in this patient subgroup.

METHODS AND RESULTS

Intravenous adenosine terminated sustained ventricular tachycardia in seven of 14 consecutive patients without evidence of structural heart disease. In each of these patients, the tachycardia had a left bundle branch block, inferior-axis QRS configuration and occurred predominantly during stress or exertion. A morphologically similar sustained tachycardia was induced in six of seven patients during programmed ventricular stimulation, although day-to-day reproducibility was poor. Signal-averaged ECGs were normal in all patients. Imaging with 123I-metaiodobenzylguanidine did not reveal focal abnormalities in any of five patients. A discrete site of origin was identified in the free wall of the pulmonary infundibulum in all patients. Limited application of direct current shocks (two patients) or radiofrequency energy (five patients) resulted in long-term abolition of spontaneous and inducible ventricular tachycardia in all patients.

CONCLUSIONS

Adenosine-sensitive ventricular tachycardia appears to arise from relatively discrete sites predominantly located in the free wall of the pulmonary infundibulum. The localized nature of this tachycardia renders it amenable to long-term cure by catheter ablation techniques.
Inhibition of accelerated coronary atherosclerosis with dehydroepiandrosterone in the heterotopic rabbit model of cardiac transplantation.
Authors: Eich D M , Nestler J E , Johnson D E , Dworkin G H , Ko D , Wechsler A S , Hess M L
Published: June 2012

BACKGROUND

Accelerated coronary atherosclerosis has become a critical problem in cardiac transplantation. Although the pathogenesis of this disease is unknown, hypercholesterolemia has been shown to be a major risk factor.

METHODS AND RESULTS

To study this problem, a hypercholesterolemic rabbit model of heterotopic cardiac transplantation was developed to study accelerated graft atherosclerosis. Based on suggestions in the literature, it was hypothesized that dehydroepiandrosterone (DHEA) may retard the progression of the disease. Using semiquantitative light microscopy, a predilection for the development of small vessel occlusive disease in the transplanted hearts was found. Chronic DHEA administration produced a 45% reduction in the number of significantly stenosed vessels in the transplanted hearts (p < 0.05) compared with controls and a 62% reduction in the nontransplanted hearts (p < 0.05), yielding an overall 50% reduction in the number of significantly stenosed vessels in both the transplanted and nontransplanted hearts. This reduction in luminal stenosis was observed in the absence of any significant alterations in lipid profiles.

CONCLUSIONS

It is concluded that chronic DHEA administration in a hypercholesterolemic rabbit model of heterotopic cardiac transplantation significantly retards the progression of accelerated atherosclerosis in both the transplanted heart and in the native heart.
Comparison of hemodynamic determinants for myocardial oxygen consumption under different contractile states in human ventricle.
Authors: Takaoka H , Takeuchi M , Odake M , Hayashi Y , Hata K , Mori M , Yokoyama M
Published: June 2012

BACKGROUND

Recently, several indexes such as tension-time index (TTI), tension-time or force-time integral (FTI), rate-pressure product (RPP), pressure-work index (PWI), and systolic pressure-volume area (PVA) have been developed as predictors of myocardial oxygen consumption in experimental and clinical studies. However, it is still unclear whether these indexes are reliable predictors of myocardial oxygen consumption under various contractile states in human hearts.

METHODS AND RESULTS

We assessed the relation between TTI, FTI, RPP, PWI, and PVA and myocardial oxygen consumption per beat (VO2) in 13 patients with heart disease during volume loading. Left ventricular (LV) volume and pressure were measured simultaneously by the conductance catheter with the tipped micromanometer technique. VO2 was calculated from arterial coronary sinus oxygen content difference, and coronary sinus blood flow was measured by the thermodilution method. After z transformation of the correlation coefficients, mean z value for the VO2-PVA relation (1.83 +/- 0.60) was greater than those for the VO2-TTI relation (1.22 +/- 0.66; p < 0.005), VO2-FTI relation (1.18 +/- 0.61; p < 0.05), VO2-RPP relation (0.95 +/- 0.65; p < 0.05), and VO2-PWI relation (1.24 +/- 0.58; p < 0.05). During dobutamine infusion (5 micrograms.kg-1.min-1) in five of the 13 patients, VO2 also correlated best with PVA (z = 1.70 +/- 0.89) compared with TTI (z = 1.43 +/- 0.86), FTI (z = 1.48 +/- 0.95), RPP (z = 1.00 +/- 0.53), and PWI (z = 0.88 +/- 0.80). The contractile efficiency (38 +/- 14% to 38 +/- 20%), the reciprocal of the slope of the VO2-PVA relation, remained unchanged, whereas the VO2,PVA 0.8 (VO2 at PVA = 0.8 J per beat/100 g LV) increased from 1.48 +/- 1.16 to 2.06 +/- 1.13 J per beat/100 g LV (p < 0.05). These results show the parallel upward shift of the VO2-PVA relation during dobutamine infusion. Because increases in the VO2-intercept represent the VO2 for the increased excitation-contraction (E-C) coupling associated with the augmented contractile state, the parallelism of the VO2-PVA relation could discriminate between VO2 for mechanical work (PVA-dependent VO2) and VO2 for E-C coupling (PVA-independent VO2).

CONCLUSIONS

The results of the present study indicate that PVA is a reliable and valuable predictor of myocardial oxygen consumption under different contractile states in human hearts. The VO2-PVA relation could provide useful information about mechanoenergetics in diseased human hearts.
Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels.
Authors: Treasure C B , Klein J L , Vita J A , Manoukian S V , Renwick G H , Selwyn A P , Ganz P , Alexander R W
Published: June 2012

BACKGROUND

Patients with hypertension and myocardial hypertrophy may have signs and symptoms of myocardial ischemia in the absence of obstructive coronary disease. Prior investigations have demonstrated impaired coronary flow reserve and have led to speculation that microvascular dysfunction might contribute to ischemia in these patients. Experimental studies have shown that the endothelium, an important regulator of microvascular tone, can be damaged by hypertension and is dysfunctional in cardiomyopathy. We hypothesized that endothelium-dependent vasodilation is impaired in the coronary microvasculature of patients with hypertension and ventricular hypertrophy.

METHODS AND RESULTS

We studied coronary microvascular responses in 10 patients with left ventricular hypertrophy secondary to essential hypertension (HTN) (mean arterial pressure at catheterization, 151/94 mm Hg; mean posterior wall thickness, 1.4 +/- 0.1 cm) and nine normal control subjects with no history of hypertension (mean arterial pressure at catheterization, 128/75 mm Hg; mean posterior wall thickness, 1.0 +/- 0.02 cm) using the intracoronary Doppler catheter and quantitative angiography to assess changes in coronary blood flow (CBF). All patients had normal left ventricular systolic function. To assess microvascular endothelial function, we infused the endothelium-dependent vasodilator acetylcholine (10(-8)-10(-6) M) and the endothelium-independent vasodilator adenosine (10(-6)-10(-4) M) into the left anterior descending coronary artery. In response to acetylcholine, CBF increased only 32 +/- 25% in HTN patients, whereas CBF increased 192 +/- 39% in normal control subjects (p = 0.003). CBF increased 465 +/- 93% in HTN patients and 439 +/- 41% in normal control subjects in response to adenosine (p = NS). The proportion of coronary flow reserve attributable to endothelium-dependent dilation (obtained from peak acetylcholine/peak adenosine flow response) was 48 +/- 9% in normal control subjects but only 7 +/- 8% in HTN patients (p = 0.008).

CONCLUSIONS

Endothelium-dependent vasodilation is markedly impaired in the coronary microvessels of patients with hypertension and ventricular hypertrophy. Loss of this vasodilator mechanism may contribute to disordered coronary flow regulation and the ischemic manifestations of hypertensive heart disease.
Residual coronary reserve despite decreased resting blood flow in patients with critical coronary lesions. A study by technetium-99m human albumin microsphere myocardial scintigraphy.
Authors: Parodi O , Sambuceti G , Roghi A , Testa R , Inglese E , Pirelli S , Spinelli F , Campolo L , L'Abbate A
Published: June 2012

BACKGROUND

Experimental data demonstrate the persistence of a transmural vasodilator reserve in the face of depressed resting myocardial perfusion. The present study was designed to determine whether resting myocardial hypoperfusion indicates exhausted coronary reserve (CR).

METHODS AND RESULTS

Fifteen patients with stable angina, isolated left anterior descending coronary artery (LAD) stenosis, and no previous myocardial infarction were evaluated by means of 99mTc human albumin microsphere scintigraphy. Regional myocardial perfusion and CR were assessed at baseline and after LAD papaverine (10-12 mg) by means of two microsphere injections in the left ventricle and compared with five normal subjects. Two 300-second scans were obtained with a mobile gamma camera positioned in the 70 degrees left anterior oblique projection; actual microsphere distribution after papaverine was obtained by image subtraction. The two arterial input functions (basal and papaverine) were measured from the first-pass time-activity curves and validated with the reference arterial sample technique. From the comparison of circumferential profile analysis between patients and normal subjects, nine patients (group 1A) showed perfusion defects at rest (reduction of percent radioactivity below 2 SD of normal subjects) in the LAD territory, and the other six (group 1B) showed homogeneous perfusion. CR (papaverine/resting perfusion) was 3.8 +/- 0.2 and 1.51 +/- 0.27 in normal subjects and in ischemic patients, respectively (p < 0.01). Despite resting hypoperfusion, group 1A showed a papaverine-recruitable CR similar to that of group 1B (1.57 +/- 0.33 and 1.43 +/- 0.16, respectively, p = NS).

CONCLUSIONS

In patients with stable angina pectoris, isolated LAD stenosis, and no previous myocardial infarction, microsphere scintigraphy disclosed a high incidence of resting perfusion defects; in those patients, a residual CR was observed despite decreased resting blood flow.
Characterization of double potentials during ventricular tachycardia. Studies during transient entrainment.
Authors: Olshansky B , Moreira D , Waldo A L
Published: June 2012

BACKGROUND

Double potentials have been recorded during reentrant tachycardias in animal models. Although they have also been recorded during ventricular tachycardia in humans, their meaning is uncertain.

METHODS AND RESULTS

We used transient entrainment as a method to help further understand the meaning of double potentials recorded during ventricular tachycardia in humans. Three patients with ventricular tachycardia (cycle lengths, 500, 450, and 290 msec) were studied. During transient entrainment of ventricular tachycardia (pacing cycle length, 470-260 msec), both double potential deflections were captured at the pacing cycle length. One deflection was captured with a short activation time, and the other deflection was captured with a long activation time. During ventricular pacing, the deflections were associated by the long rather than the short interdeflection interval. At termination of pacing, each double potential deflection was associated with separate but sequential QRS complexes, and each deflection maintained the same electrogram morphology at relatively "slow" overdrive pacing rates. The short interdeflection interval shortened further with faster pacing rates (to less than the ventricular refractory period), making it unlikely that both deflections of the double potential represent active depolarization of the same tissue. In two patients, at a critically rapid pacing rate, one of the double potential deflections changed morphology abruptly, associated with a shortened stimulus-to-double potential time interval (from 520 to 110 msec and from 530 to 240 msec, respectively), indicating a change in the direction of activation that caused that deflection. Interruption of ventricular tachycardia was associated with disappearance of the double potentials at the same recording site. The double potentials did not immediately bracket an area of slow conduction.

CONCLUSIONS

These data suggest that double potentials recorded only during ventricular tachycardia represent activation wave fronts on either side of an area of block within a reentrant circuit. Thus, double potentials recorded during ventricular tachycardia in these patients do not appear to represent slow conduction per se but rather appear to represent an area of block at the center of a reentrant circuit around which the reentrant wave front circulates.
Effect of subcutaneous sumatriptan, a selective 5HT1 agonist, on the systemic, pulmonary, and coronary circulation.
Authors: MacIntyre P D , Bhargava B , Hogg K J , Gemmill J D , Hillis W S
Published: June 2012

BACKGROUND

Sumatriptan (GR43175) is a selective 5-hydroxytryptamine (5HT1) receptor agonist effective in the acute treatment of migraine. Recent in vitro experiments suggest that it has vasoactive properties in vascular beds distinct from the cerebral circulation. The object of this study was to assess the vasoactive effects of the standard 6-mg subcutaneous dose of sumatriptan used in migraine on the systemic and pulmonary circulations and the coronary artery vasculature.

METHODS AND RESULTS

Ten patients undergoing diagnostic coronary arteriography were studied with digital subtraction angiography and invasive hemodynamic monitoring. After subcutaneous injection of sumatriptan, there was no significant change in heart rate or ECG morphology. There was a significant rise in the systemic (20%, p < 0.05 by ANOVA) and pulmonary artery (40%, p < 0.05 by ANOVA) pressures. There was no change in cardiac output, but there was a significant increase in total systemic (27%, p < 0.05) and total pulmonary vascular resistance (40%, p < 0.05). Sumatriptan caused a significant reduction (p < 0.001 by ANOVA) in mean absolute coronary artery diameter, from 4.36 +/- 1.60 mm at baseline to 3.67 +/- 1.49 mm (16%) at 10 minutes and to 3.63 +/- 1.49 mm (17%) at 30 minutes after injection. There were no clinical sequelae.

CONCLUSIONS

Sumatriptan, a 5HT1 receptor agonist administered by the subcutaneous route, causes a vasopressor response in the systemic and pulmonary arterial circulations and coronary artery vasoconstriction.
Tricuspid atresia presenting in infancy. Survival and suitability for the Fontan operation.
Authors: Franklin R C , Spiegelhalter D J , Sullivan I D , Anderson R H , Thoele D G , Shinebourne E A , Deanfield J E
Published: June 2012

BACKGROUND

The Fontan operation is the usual goal of therapy for children with tricuspid atresia. The influences of morphology and different management strategies on survival and subsequent suitability for this procedure are crucial but unstudied in an unselected population during the Fontan era.

METHODS AND RESULTS

The fates of 237 consecutive infants with tricuspid atresia were reviewed (1972-1987; median follow-up, 8.0 years). Overall actuarial survival was 72% at 1 year, 53% at 5 years, and 46% at 10 years. Univariate risk factor analysis established that discordant ventriculoarterial connections (24% of the group; relative risk, 2.7), pulmonary atresia (14%, 2.3), aortic arch obstruction (7%, 2.9), and subaortic stenosis (8%, 4.2) were associated with poor survival, whereas pulmonary stenosis (60%, 0.52), balanced pulmonary blood flow (9%, 0.25), and older age at presentation (33%, 0.42) were beneficial. Multivariate analysis allowed the creation of predictive patient-specific survival curves and two additive indexes. Survival was worse for patients who underwent banding of the pulmonary trunk with aortic arch repair than for other individual palliative procedures (p < 0.001). On retrospective review, 204 patients (86%) were judged suitable for a future Fontan procedure at presentation. However, 99 (48%) of these are known to have died before a Fontan operation or became unsuitable for such surgery during follow-up, mostly because of death after palliative surgery (23 patients, 11%), sudden death (18 patients, 9%), and new adverse features (32 patients, 16%) such as subaortic stenosis, pulmonary arterial distortion, and ventricular dysfunction.

CONCLUSIONS

Management in infancy must aim to ensure survival and maintain suitability for a Fontan-type operation. The accumulating incidence of adverse events with increasing age would argue in favor of undertaking definitive surgery in early childhood in most patients.
Effect of aspirin on coronary collateral blood flow.
Authors: Altman J D , Dulas D , Pavek T , Bache R J
Published: June 2012

BACKGROUND

Although aspirin exerts beneficial antiplatelet activity in patients with coronary artery disease, cyclooxygenase blockade produced by aspirin causes a potentially deleterious effect by interrupting endothelial production of prostacyclin. Collateral vessels that develop in response to coronary occlusion display prominent endothelial cell proliferation and undergo vasoconstriction in response to indomethacin. This study was performed to test the hypothesis that cyclooxygenase blockade with aspirin would cause constriction of coronary collateral vessels and that such vasoconstriction would be reversed with nitroglycerin.

METHODS AND RESULTS

Collateral vessel growth was induced by embolic occlusion of the left anterior descending coronary artery in dogs. Four to 6 months later, coronary collateral flow was measured as retrograde flow from the cannulated collateral-dependent artery. Aspirin (1 mg/kg i.v.) caused 70 +/- 8% blockade of the increase in coronary blood flow produced by intra-arterial arachidonic acid and decreased retrograde flow from 37 +/- 7 to 28 +/- 7 ml/min (p < 0.03). Increasing the dose of aspirin to 15 mg/kg i.v. caused 91 +/- 3% blockade of the response to arachidonic acid and further decreased retrograde flow to 21 +/- 4 ml/min (p < 0.01). After aspirin administration, nitroglycerin (150 micrograms/min i.c.) reversed the collateral constriction and increased retrograde flow to 37 +/- 10 ml/min (p < 0.01).

CONCLUSIONS

These data suggest that products of cyclooxygenase metabolism cause tonic vasodilation of well-developed coronary collateral vessels. Blockade of cyclooxygenase with even low-dose aspirin caused collateral vessel constriction with a decrease in collateral blood flow. However, nitroglycerin was able to fully reverse aspirin-induced collateral vasoconstriction and restore flow to the control level.
Signal-averaged electrocardiogram. Improved identification of patients with ventricular tachycardia using a 28-lead optimal array.
Authors: Ho D S , Denniss R A , Uther J B , Ross D L , Richards D A
Published: June 2012

BACKGROUND

Although the signal-averaged ECG (SAECG) is currently the best noninvasive test to identify patients with ventricular tachycardia (VT) following myocardial infarction (MI), it is still a relatively insensitive test. Body surface mapping has improved the sensitivity of ECG in detecting various cardiac diseases. This study applied body surface mapping to the SAECG in the form of a clinically practical, 28-lead optimal array and compared its sensitivity and specificity with those of an orthogonal array.

METHODS AND RESULTS

Two hundred twenty-three patients with previous MI (82 with inducible VT) underwent SAECG using 28 surface electrodes from which were obtained a three-lead orthogonal array and a 28-lead optimal array (optimal). From the orthogonal array, two QRS durations (QRSd) were obtained using the combined vector magnitude method (CVM) and the earliest onset to latest offset of the three individually filtered leads (individual). From the optimal array, 28 QRSd were obtained, each defined as the duration from the earliest onset of any of the 28 leads to the offset of each individually filtered lead. QRSd > 120 msec in > or = 3 leads was considered abnormal. For CVM and individual, QRSd of > 120 msec were considered abnormal. While the specificity of each method was comparable (84%, 86%, and 84% for CVM, individual, and optimal, respectively), the sensitivity of optimal (70%) was significantly greater than the sensitivity of CVM (54%) (p = 0.001) or individual (59%) (p = 0.004). The magnitude of improvement in sensitivity, 16% and 15%, respectively, was equal for anterior (n = 120) and inferior (n = 103) infarctions.

CONCLUSIONS

Body surface mapping using the 28-lead optimal array significantly improved the sensitivity of the SAECG without loss of specificity. The increased sensitivity was of equal magnitude for inferior and anterior infarctions. The superiority and practicality of the 28-lead optimal array make it worth pursuing as an option for further refinement in SAECG:
Superoxide dismutase restores contractile and metabolic dysfunction through augmentation of adenosine release in coronary microembolization.
Authors: Takashima S , Hori M , Kitakaze M , Sato H , Inoue M , Kamada T
Published: June 2012

BACKGROUND

This study was undertaken to test the hypothesis that administration of superoxide dismutase (SOD) restores the contractile and metabolic dysfunction in coronary microembolization and that these beneficial effects of SOD are attributable to the restoration of 5'-nucleotidase activity and subsequent augmentation of adenosine release.

METHODS AND RESULTS

In 78 dogs before and after an injection of microspheres (15 microns in diameter) into the left anterior descending coronary artery, regional coronary blood flow (CBF), fractional shortening (FS), and lactate extraction ratio (LER) were measured with and without administration of recombinant human SOD (50 micrograms/kg/min i.c.). In the untreated dogs (n = 6), both FS and LER decreased after coronary microembolization (2.0 x 10(5) microspheres per ml CBF [mL/min]). FS and LER decreased from 24.2 +/- 1.3% to 5.1 +/- 1.2% and from 23.0 +/- 1.1% to -10.5 +/- 2.9%, respectively. These ischemic changes were associated with coronary hyperemic flow (141 +/- 8 versus 92 +/- 1 mL/100 g/min) and adenosine release (5.8 +/- 0.5 versus 0.4 +/- 0.1 nmol/100 g/min). Pretreatment with SOD augmented the hyperemic flow to 164 +/- 4 mL/100 g/min and enhanced the release of adenosine (9.6 +/- 0.6 nmol/100 g/min) associated with improvement of functional and metabolic dysfunction (FS, 14.8 +/- 2.3%; LER, 15.1 +/- 3.1%). Administration of SOD at 10 minutes (n = 5) and 30 minutes (n = 5) after coronary embolization restored the contractile function and lactate metabolism (at 10 minutes: FS, 16.7 +/- 2.2% and LER, 16.7 +/- 3.9%; at 30 minutes: FS, 11.1 +/- 1.3% and LER, 7.2 +/- 3.1%). However, administration of SOD 60 minutes after coronary embolization (n = 6) did not restore the contractile and metabolic dysfunction. The restoration of the contractile and metabolic dysfunction by SOD treatment was blunted by adenosine receptor blockade with 8-phenyltheophylline (n = 5). Myocardial 5'-nucleotidase activity at 2 hours after embolization was restored with SOD treatment at 10 minutes (n = 5) and 30 minutes (n = 5) after embolization. However, SOD treatment at 60 minutes after embolization (n = 6) did not restore 5'-nucleotidase activity compared with the SOD pretreatment group. Furthermore, coronary submaximal vasodilation induced by papaverine (n = 5) and adenosine (n = 5) abolished the beneficial effects of SOD.

CONCLUSIONS

We conclude that 1) in sustained myocardial ischemia, SOD treatment attenuates ischemic injury caused by coronary microembolization by restoration of 5'-nucleotidase activity and augmentation of adenosine release; 2) this beneficial effect of SOD is observed even after coronary microembolization; and 3) the beneficial effects of SOD are attributable to coronary vasodilation produced by augmented adenosine release.
Magnetic resonance jet velocity mapping in mitral and aortic valve stenosis.
Authors: Kilner P J , Manzara C C , Mohiaddin R H , Pennell D J , Sutton M G , Firmin D N , Underwood S R , Longmore D B
Published: June 2012

BACKGROUND

Magnetic resonance (MR) phase-shift velocity mapping is an established method for measurement of nonturbulent intravascular flow. Shortening the echo time of the MR sequence to 3.6 msec allowed application of the technique to turbulent jet flow. The objective of this study was validation of MR jet velocity mapping in patients with cardiac valve stenosis.

METHODS AND RESULTS

We used a 0.5-T Picker MR machine to measure peak poststenotic jet velocity in 15 consecutive patients recruited with known valve disease (six mitral stenosis, three of these restudied after valvoplasty, and 11 aortic stenosis). On the same day as the MR study, these patients underwent independent Doppler echocardiographic measurement of peak jet velocity. The results of 10 further MR investigations of aortic stenosis are also reported and compared with Doppler studies performed within 6 months. Of the 29 MR studies, 28 (97%) produced interpretable velocity maps, the one failure being attributed to misplacement of the imaging slice in a case of severe aortic stenosis. Agreement between MR and Doppler measurements of peak jet velocity in the recruited group was as follows: n = 18; range, 1.4-6.1 m/sec; mean, 3 m/sec; mean of differences (MR-Doppler), 0.23 m/sec; standard deviation of differences, 0.49 m/sec.

CONCLUSIONS

In vivo MR peak jet velocity measurements agree well with those made by Doppler ultrasound. The technique, which is not subject to restricted windows of access and has potential for further refinements, could contribute to improved evaluation of stenoses, especially at locations where ultrasonic access is limited.