bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive quantitative evaluation of the morphology of the major pulmonary artery branches in cyanotic congenital heart disease. Angiocardiographic and echocardiographic correlative study.
Authors: Hiraishi S , Misawa H , Hirota H , Agata Y , Horiguchi Y , Fujino N , Yi L H , Yashiro K , Nakae S , Kawada M
Published: June 2012

BACKGROUND

Precise noninvasive evaluation of pulmonary artery (PA) morphology is extremely important for medical and surgical management of patients with cyanotic heart disease. In this study, the accuracy of two-dimensional echocardiography combined with color Doppler flow mapping to assess the size, stenosis, and atresia of the major PA branches was examined using a new parasternal approach.

METHODS AND RESULTS

With the use of right and left high parasternal windows, we visualized each of the major portions along the right (R-PA) and left (L-PA) pulmonary arteries in 45 of the 47 examinations (96%) in 38 patients with cyanotic heart disease. The patients were between 13 days and 20 years old (mean age, 2.9 years). The internal diameters of the major PA branches were measured at three points along the R-PA (the proximal, mid, and distal portions) and at the proximal and distal portions on the L-PA in systole by both two-dimensional echocardiography and angiography. In addition, the diameter of the stenosis in the PA branch was measured. These PA values as determined by two-dimensional echocardiography correlated well with those obtained by angiography (r = .95 to .97). By two-dimensional echocardiography with color Doppler flow mapping, 17 of 19 lesions with stenoses or atresia of the major PA branches were predicted as defined by angiography (sensitivity, 89.5%; specificity, 100%). Differences between the distal parts of the L-PA and R-PA of > 30% in diameter were determined by angiography in 15 examinations and by two-dimensional echocardiography in 12 examinations (sensitivity, 80%; specificity, 97.4%).

CONCLUSIONS

Our technique permits noninvasive evaluation of the size, stenoses, and atresia of the major portions of the PA branches in patients with cyanotic heart disease both before and after surgery.
Differential expression of the cell adhesion molecules ICAM-1, VCAM-1, and E-selectin in normal and posttransplantation myocardium. Cell adhesion molecule expression in human cardiac allografts.
Authors: Tanio J W , Basu C B , Albelda S M , Eisen H J
Published: June 2012

BACKGROUND

Cell adhesion molecules (CAMs) have been implicated in cardiac allograft rejection. However, previous studies have used qualitative analysis of immunohistochemical data and did not exclude patients with infection or malignancy.

METHODS AND RESULTS

We analyzed 40 endomyocardial biopsy specimens from 25 cardiac transplant patients and 8 specimens from patients undergoing cardiac surgery. Patients with evidence of infection or malignancy were excluded. Specimens were stained with monoclonal antibodies against ICAM-1, E-selectin, VCAM-1, and PECAM-1 (which labels all vessels). ICAM-1 expression was assessed by counting ICAM-1-positive vessels and dividing by the total number of vessels (measured by PECAM staining). Specimens were scored as positive or negative for VCAM-1 and E-selectin. We also determined whether serum-soluble ICAM-1 levels (sICAM) correlated with rejection by evaluating 145 serum specimens from 48 cardiac transplant patients and 8 specimens from patients undergoing diagnostic cardiac catheterization. ICAM-1 was present on 50% to 60% of vessels in normal and nonrejecting specimens. Specimens with histologically significant rejection (focal moderate, moderate, or severe) had an increased percentage of ICAM-1-positive vessels: focal moderate, 77%; moderate/severe, 92% (P < .01). E-selectin expression did not differ between groups. VCAM-1 frequently was not present on rejecting specimens. No correlation was noted between sICAM levels and the presence or absence of rejection.

CONCLUSIONS

(1) ICAM-1 expression is strongly correlated with histologically significant cardiac allograft rejection. (2) The use of PECAM-1 staining as a vascular marker permits quantitative analysis of ICAM-1 expression. (3) VCAM-1 and E-selectin are not consistently increased during cardiac allograft rejection. (4) sICAM levels do not accurately reflect endomyocardial biopsy results.
Plasma apolipoprotein concentrations in young adults with a parental history of premature coronary heart disease and in control subjects. The EARS Study. European Atherosclerosis Research Study.
Authors: Rosseneu M , Fruchart J C , Bard J M , Nicaud V , Vinaimont N , Cambien F , De Backer G
Published: June 2012

The European Atherosclerosis Research Study (EARS) is a multicenter collaborative project within the European community. Its main objective is to study in young individuals the biological expression of a paternal history of premature coronary heart disease and to analyze the relative contribution of genetic and environmental factors to this expression. This study was carried out in 14 centers in 11 European countries, where the offspring of fathers who suffered a documented myocardial infarction before the age of 55 years (cases) were compared with age- and sex-matched control subjects. Plasma apolipoproteins A-I, B, A-II, A-IV, and E and lipoprotein (Lp) A-I lipoparticles were measured in this student population. Comparison of the values between cases and control subjects showed significantly higher apo B levels in cases compared with control subjects, and these differences were homogeneous throughout Europe. Regional differences were observed for apo E levels with an increasing north-south gradient, which was inversely related to that observed for triglycerides. A stepwise regression analysis including the lipid and apolipoprotein variables showed that apo B and triglycerides were the strongest discriminators between offspring of fathers with premature coronary heart disease and control subjects.
Is coronary flow reserve in response to papaverine really normal in syndrome X?
Authors: Chauhan A , Mullins P A , Petch M C , Schofield P M
Published: June 2012

BACKGROUND

An impaired coronary flow reserve in syndrome X has been demonstrated by many studies. Recently, however, a normal coronary flow reserve in response to papaverine was reported, but the number of patients in these studies was small. The aim of this study was to investigate whether coronary flow reserve in response to intracoronary papaverine is really impaired in syndrome X.

METHODS AND RESULTS

We investigated 53 syndrome X patients (typical angina, a positive exercise test, and completely normal coronary arteries on angiography) and 26 heart transplant patients with normal coronary arteries (control group). All antianginal medications were stopped 48 hours before the study. A 3.6F intracoronary Doppler catheter was positioned in the proximal left anterior descending coronary artery and was connected to a Millar velocimeter. The coronary blood flow velocity at rest and in response to a hyperemic dose of papaverine was measured. Coronary flow reserve was defined as the ratio of hyperemic coronary blood flow velocity in response to papaverine and resting coronary blood flow velocity. The coronary flow reserve (mean +/- SD) in the syndrome X group was 2.72 +/- 1.39. The coronary flow reserve in the control group was significantly higher at 5.22 +/- 1.26 (P < .01). In both groups there was no significant difference in the heart rate or the mean arterial pressure during the study.

CONCLUSIONS

Our study shows that coronary flow reserve in response to intracoronary papaverine is impaired in syndrome X patients.
Intramachine and intermachine variability in transesophageal color Doppler images of pulsatile jets. In vitro studies.
Authors: Fan P H , Anayiotos A , Nanda N C , Yoganathan A P , Cape E G
Published: June 2012

BACKGROUND

Color Doppler flow mapping is widely used as a marker of severity of valvular regurgitation, and the transesophageal approach has provided high-quality images in patients with poor acoustic windows. However, different instruments produce significantly variable images. Techniques that use jet spatial information to determine the severity of the lesion may need to be derived specifically for the instrument used. Given a lack of standardization of the many commonly used instruments, the goal of this study was to quantify variability between instruments by imaging well-defined jet flow fields created in vitro.

METHODS AND RESULTS

Pulsatile jets were created in vitro using a blood analogue fluid through physiological orifice diameters and imaged from a distal window using six commonly used color Doppler instruments. Transesophageal transducers (5.0 MHz) were used with all instruments studied. Peak jet areas were planimetered and averaged with systematic variations in Nyquist limit, color filter, and sector angle (which produced variations in frame rate). Changes in instrument settings produced significant variation in jet size for all instruments studied. Comparisons within instruments and among instruments were difficult because of preset and ambiguous setting levels. When comparisons were possible between similar settings, variability was dramatic (eg, 57% variability between instruments with very similar Nyquist limits).

CONCLUSIONS

A lack of standardized color Doppler instrument settings prohibits translation of jet area techniques from one instrument to another. This should be taken into consideration when using different machines for clinical study.
Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs.
Authors: Banai S , Jaklitsch M T , Shou M , Lazarous D F , Scheinowitz M , Biro S , Epstein S E , Unger E F
Published: June 2012

BACKGROUND

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is angiogenic in vitro and in vivo. It has been hypothesized that VEGF plays a role in myocardial collateral formation; however, the effects of VEGF on collateral flow to ischemic myocardium are unknown.

METHODS AND RESULTS

We studied the effect of VEGF on collateral blood flow in dogs subjected to gradual occlusion of the left circumflex coronary artery (LCx). Beginning 10 days after placement of an LCx-constricting device, VEGF 45 micrograms (n = 9) or saline (n = 12) was administered daily via an indwelling catheter in the distal LCx, at a point just beyond the occlusion. Treatment was maintained for 28 days. Collateral blood flow was determined with microspheres 7 days before treatment, immediately before treatment (day 0), and 7, 14, 21, and 28 days into the treatment period. Collateral blood flow was quantified during chromonar-induced maximal vasodilation and expressed as a collateral zone/normal zone (CZ/NZ) ratio. Treatment with VEGF was associated with a 40% increase in collateral blood flow (final CZ/NZ blood flow ratios of 0.49 +/- 0.06 and 0.35 +/- 0.02 in the VEGF-treated and control groups, respectively, P = .0037) as well as an 89% increase in the numerical density of intramyocardial distribution vessels (> 20 microns diameter) in the CZ (6.6 +/- 1.4 versus 3.5 +/- 0.7 vessels/mm2 in VEGF-treated and control dogs, respectively, P < .05).

CONCLUSIONS

We conclude that intracoronary VEGF enhances the development of small coronary arteries supplying ischemic myocardium, resulting in marked augmentation of maximal collateral blood flow delivery. These results demonstrate the feasibility of pharmacological enhancement of collateral growth and suggest a new therapeutic approach for the treatment of myocardial ischemia.
Origin and significance of double potentials near the atrioventricular node. Correlation of extracellular potentials, intracellular potentials, and histology.
Authors: McGuire M A , de Bakker J M , Vermeulen J T , Opthof T , Becker A E , Janse M J
Published: June 2012

BACKGROUND

Atrioventricular junctional (AV nodal) reentrant tachycardia can be cured by catheter ablation of the slow pathway, which is part of the reentrant circuit. Previous work has suggested that extracellular double potentials may help identify the site of the slow pathway, but the origin and significance of these potentials are controversial. The aim of this study was to identify the source of these potentials.

METHODS AND RESULTS

Studies were performed in isolated, blood-perfused porcine (n = 8) and canine (n = 4) hearts. Several methods were used to identify the origin of potentials: microelectrode recording, extracellular mapping, pacing from multiple sites, and light microscopy. Two types of double potentials, similar to those found in humans, were found in all hearts. LH potentials consisted of a low-frequency deflection followed by a high-frequency deflection during sinus rhythm or anterior septal pacing. HL potentials consisted of a high-frequency deflection followed by a low-frequency deflection. LH potentials were found close to the coronary sinus orifice. They were caused by asynchronous activation of the sinus septum and the region between the coronary sinus orifice and tricuspid annulus. HL double potentials were found along the tricuspid annulus. They were caused by asynchronous activation of two cell layers. The high-frequency component was caused by depolarization of atrial-type cells in the deep subendocardial layer. The low-frequency component was caused by depolarization of cells with nodal characteristics close to the endocardium. These cells were present around the entire tricuspid annulus, were not part of the compact AV node, and could be dissociated from the bulk of the atria by rapid atrial pacing.

CONCLUSIONS

LH potentials are caused by asynchronous activation of muscle bundles above and below the coronary sinus orifice. Their proximity to the site of the slow pathway is probably serendipity. HL double potentials are caused by asynchronous activation of atrial cells and a band of nodal-type cells close to the tricuspid annulus. The band of nodal-type cells is not part of the compact AV node and may represent the substrate of the slow AV nodal pathway.
Microwave catheter ablation of myocardium in vitro. Assessment of the characteristics of tissue heating and injury.
Authors: Whayne J G , Nath S , Haines D E
Published: June 2012

BACKGROUND

Radiofrequency (RF) catheter ablation lesion size has been limited by the small volume of tissue directly heated by the RF electrode. Microwave (MW) energy has been proposed as an alternative energy source to generate larger lesions because of its increased volume of direct tissue heating. To further characterize MW ablation of myocardium, we studied the temperature-versus-distance profiles during MW ablation in an in vitro model of perfused and superfused porcine right ventricular free wall.

METHODS AND RESULTS

Radial tissue temperatures in 19 isolated porcine right ventricles were measured and recorded with four fluoroptic thermometry probes placed within the myocardium at 2.5-mm radial increments from the catheter. The MW antenna catheters used were monopolar and helical-coil antennas resonating at 915 and 2450 MHz. Durations of energy delivery for a 915-MHz MW monopolar antenna (60 to 600 seconds) and a 4-mm-tip RF electrode (60 and 300 seconds) were varied to compare time courses of lesion formation. For each lesion, the temperature at the lesion border zone (the isotherm of irreversible tissue injury) was determined. Similar lesion size and temperature profiles were observed for 915- versus 2450-MHz MW antennas and monopolar versus helical-coil MW antennas. Lesion depth for the 915-MHz monopolar antenna increased monoexponentially with a half-time of 170 seconds. The isotherms for all MW antenna designs were not significantly different. The mean isotherm of irreversible tissue injury for MW lesions was not significantly different from the mean isotherm for RF lesions (54.4 degrees C versus 53.6 degrees C, respectively).

CONCLUSIONS

Microwave ablation has the potential to directly heat a greater volume of tissue than RF ablation but only with efficient MW antennas. The primary mechanism of tissue injury for both MW and RF ablation appears to be thermal.
Diurnal variation in blood pressure in patients with biventricular assist devices and retained, nonpumping native hearts.
Authors: Sehested J , Happe E , Ishino K , Hetzer R , Schiessler U , Schifter S
Published: June 2012

BACKGROUND

Studies indicate that centrally mediated rhythms in sympathetic tone play a prominent role in diurnal cardiovascular variability. Recent evidence from heart transplant recipients, in whom blood pressure does not decline during sleep despite normal variability in plasma norepinephrine, however, suggests that afferent cardiac nervous traffic is necessary for the generation of diurnal variability. This implies that in the presence of an innervated heart excluded from the systemic circulation, blood pressure would still decrease during sleep. To assess this hypothesis, we studied 24-hour blood pressure, heart rate, and neuroendocrine variability in patients with biventricular assist devices in whom the retained native hearts had ceased to pump.

METHODS AND RESULTS

Eight patients were free of medication and were studied every 3 hours. Pump rates and output were kept constant throughout the study. Blood pressure showed a significant decline during sleep, as did norepinephrine and epinephrine (all P < .05). Atrial natriuretic factor showed a significant increase around midnight (P < .01). Significantly elevated levels were found for all hormones studied except for aldosterone and endothelin.

CONCLUSIONS

Our results suggest that diurnal variations in cardiac function or in catecholamine levels (indicative of sympathetic activity) as found in cardiac transplant recipients alone are not responsible or sufficient for producing a nocturnal drop in blood pressure. The presence of an innervated heart appears crucial in this respect. This could be of importance for the understanding of circadian cardiovascular pathophysiology.
Improving detection of coronary morphological features from digital angiograms. Effect of stenosis-stabilized display.
Authors: Eigler N L , Eckstein M P , Mahrer K N , Whiting J S
Published: June 2012

BACKGROUND

We have developed a digital display method that stabilizes the motion of a stenosis in sequential frames of a coronary angiogram, allowing it to be scrutinized at high display frame rates. The purpose of this study was to determine whether this technique improves visual detection of low-contrast luminal morphological features.

METHODS AND RESULTS

An observer detection study was conducted using computer-simulated arterial segments containing known target features, inserted into clinical digital coronary angiograms. Four observers performed a forced-choice detection of a simulated filling defect in each of 320 angiograms using the conventional and stenosis-stabilized dynamic displays (at 7.5, 15, and 32 frames per second) and a single-frame static display (total of 8960 detections). In a second simulated clinical task, three observers detected a bridging stenotic lumen in 600 angiograms using the two displays (3600 detections). In a third experiment, two angiographers rated the likelihood of intraluminal thrombus in 89 right coronary digital angiograms by consensus reading with both dynamic displays. Detectability of the simulated filling defect was similar for both dynamic display methods at 7.5 frames per second (averaging twice that for static images). As display rate was increased to 32 frames per second, detectability for the conventional display declined, whereas the stabilized display detectability increased for all observers (P < .05). On average, stabilization allowed detection of filling defects equivalent to a 71% increase in feature contrast. Response time for the conventional display averaged 12.9 +/- 4.7 seconds. For the stenosis-stabilized display, response time fell with increased frame rate (P < .05) to 4.9 +/- 1.2 seconds at 32 Hz, similar to the time for static images (4.6 +/- 0.8 seconds). The detectability of the bridging stenotic lumen was increased by 62% with the stabilization compared with conventional dynamic display (P < .00001). Consensus reading of coronary angiograms showed differences between the two dynamic display methods (kappa = 0.11) that may be explained by an improvement in observer uncertainty. A rating of definite for thrombus present or absent was more frequent with the stabilized display (39% versus 15%, P < .0001).

CONCLUSIONS

These data suggest that stabilized display of coronary angiograms significantly increases detectability, reduces the time required for detection, and improves observer uncertainty for the presence of small luminal morphological features. The method of angiographic display may thus have an impact on clinical coronary angiographic interpretation.
Expression of type 1 plasminogen activator inhibitor in chronic pulmonary thromboemboli.
Authors: Lang I M , Marsh J J , Olman M A , Moser K M , Loskutoff D J , Schleef R R
Published: June 2012

BACKGROUND

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

METHODS AND RESULTS

To determine if the failure to lyse pulmonary thromboemboli is caused by the local expression of the primary inhibitor of tissue-type plasminogen activator (type 1 plasminogen activator inhibitor, PAI-1), levels of PAI-1 antigen and mRNA were analyzed by immunohistochemistry and in situ hybridization in specimens harvested from a series of patients during pulmonary thromboendarterectomies. Red, fibrin-rich thrombi within the thromboendarterectomy specimens were lined with a single layer of endothelial cells exhibiting high levels of PAI-1 antigen. Quantitation of the in situ hybridization signal revealed that a significant increase in PAI-1 mRNA was present in the endothelial cells lining the fresh thrombi in comparison to the signal present in the endothelial cells from noninvolved areas of patients' pulmonary arteries (n = 16, P < .001). In contrast, tissue-type plasminogen activator antigen levels were low in all samples. Yellowish-white thrombi were composed of smooth muscle cells and endothelial cells in numerous vessels that stained prominently for PAI-1 antigen. Both types of cells within the highly organized tissues also exhibited elevated PAI-1 mRNA levels in comparison to patient pulmonary artery specimens that were free of thrombus (n = 16, P < .02).

CONCLUSIONS

The prevalence of PAI-1 expression within pulmonary thromboemboli suggests that this inhibitory may play a role in the stabilization of vascular thrombi.
In vivo blockade of tumor necrosis factor-alpha in cholesterol-fed rabbits after cardiac transplant inhibits acute coronary artery neointimal formation.
Authors: Clausell N , Molossi S , Sett S , Rabinovitch M
Published: June 2012

BACKGROUND

We previously identified in piglet cardiac allografts an immunoinflammatory response in coronary arteries in which increased fibronectin regulated by interleukin-1 beta was associated with early evidence of intimal thickening. In the present study, we used rabbits to assess whether acute neointimal formation after cardiac transplantation was reduced by blockade of tumor necrosis factor (TNF)-alpha, which modulates interleukin-1 beta, or by cyclosporine A.

METHODS AND RESULTS

Sixteen rabbits underwent heterotopic cardiac transplantation and were given saline, TNF-soluble receptor (sr), or cyclosporine A. In host hearts from saline- or TNFsr-treated groups, few coronary arteries (approximately 13% to 16%) had intimal thickening, whereas values were higher in the cyclosporine A-treated group (approximately 30%). In donor hearts from the saline-treated group, however, approximately 68% of vessels had intimal thickening versus approximately 32% in TNFsr- and approximately 30% in cyclosporine A-treated groups (P < .01 for both). Severity of intimal thickening assessed quantitatively as percent vessel area was approximately 38% in the saline-treated group but reduced in TNFsr- and cyclosporine A-treated groups to approximately 22% and 18%, respectively (P < .01 for each). Immunohistochemistry revealed increased staining for major histocompatibility complex II, T cells, interleukin-1 beta, TNF-alpha, and fibronectin in donor coronary arteries from saline-treated animals when compared with TNFsr- and cyclosporine A-treated animals. Grade 3 myocardial rejection was observed in both saline- and TNFsr-treated groups, but only grade 1 was apparent in the cyclosporine A-treated group.

CONCLUSIONS

In vivo blockade of TNF-alpha suppresses the acute development of neointimal formation by selectively reducing the vascular immunoinflammatory reaction and accumulation of fibronectin, whereas cyclosporine A suppresses both the myocardial and the vascular immune reaction.
Alterations in coronary artery vascular reactivity of hypertensive Ren-2 transgenic rats.
Authors: Tschudi M R , Noll G , Arnet U , Novosel D , Ganten D , Lüscher T F
Published: June 2012

BACKGROUND

The renin-angiotensin system and endothelium-derived nitric oxide (EDNO) are important regulators of vascular tone. This study was designed to investigate endothelial and vascular smooth muscle function in coronary arteries of Ren-2 transgenic rats.

METHODS AND RESULTS

Left anterior descending coronary arteries and aortas were isolated from transgenic rats and Sprague-Dawley control rats at 6 (young) and 12 (adult) weeks of age and examined in myographs or organ chambers for isometric tension recording. Systolic blood pressure was significantly higher in transgenic rats (young, 229 +/- 6 mm Hg; adult, 239 +/- 8 mm Hg) than in control rats (young, 126 +/- 2 mm Hg; adult, 118 +/- 3 mm Hg; P < .005). N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-7) to 10(-4) mol/L) evoked marked endothelium-dependent contractions in coronary arteries (young, 52 +/- 8% of the contraction to 100 mmol/L KCl; adult, 40 +/- 8%) but not aortas (young, 3 +/- 1%; adult, 2 +/- 1%). In coronary arteries, this response was significantly smaller in adult (n = 9) than in young (n = 8, P < .05) control rats. Young transgenic rats (56 +/- 9%, n = 8) showed slightly stronger contractions in response to L-NAME than young control rats (NS), which almost totally disappeared in adult transgenic rats (6 +/- 3%, n = 7; P < .05 versus adult control rats; P < .01 versus young transgenic rats). Endothelium-dependent relaxations in response to acetylcholine (10(-9) to 10(-4) mol/L) were totally blocked by L-NAME (10(-4) mol/L) but were unaffected by the thromboxane receptor antagonist SQ30741 (10(-7) mol/L). This stimulated release of EDNO, endothelium-independent relaxations in response to the nitrovasodilator linsidomine (10(-9) to 10(-5) mol/L), and contractions in response to KCl (100 mmol/L) were comparable in all groups of rats.

CONCLUSIONS

Ren-2 transgenic rats develop fulminant hypertension that is associated with a selective decrease in endothelium-dependent contractions in response to L-NAME, whereas endothelium-dependent relaxations in response to acetylcholine as well as smooth muscle function remain unaffected.
New Na(+)-H+ exchange inhibitor HOE 694 improves postischemic function and high-energy phosphate resynthesis and reduces Ca2+ overload in isolated perfused rabbit heart.
Authors: Hendrikx M , Mubagwa K , Verdonck F , Overloop K , Van Hecke P , Vanstapel F , Van Lommel A , Verbeken E , Lauweryns J , Flameng W
Published: June 2012

BACKGROUND

Experiments were carried out using the new Na(+)-H+ exchange inhibitor (3-methylsulfonyl-4-piperidinobenzoyl)guanidine methanesulfonate (HOE 694) to assess the role of Na(+)-H+ exchange in myocardial ischemic and reperfusion injury.

METHODS AND RESULTS

Three groups of rabbit hearts (n = 5 in each) were perfused with blood and were subjected to 45 minutes of global normothermic (37 degrees C) ischemia, followed by 1 hour of reperfusion. Group 1 was the control group (vehicle only); in group 2, HOE 694 (1 mumol/L) was administered before ischemia (pretreatment group); and in group 3, HOE 694 was given only during reperfusion to separate actions exerted during ischemia from those specifically obtained during reperfusion. End-diastolic pressure rise at 1 hour of reperfusion was reduced by administration of HOE 694 starting before ischemia (from 52.2 +/- 8.5 mm Hg in group 1 to 17.6 +/- 4.5 mm Hg in group 2, P < .01) or starting on reperfusion (28.8 +/- 5.4 mm Hg in group 3, P < .05 versus group 1). Left ventricular developed pressure (LVDP) and its derivative (dP/dt) recovered better in HOE 694-pretreated hearts (LVDP, 79 +/- 9.9 mm Hg in group 2 versus 24.8 +/- 10 mm Hg in group 1; dP/dt, 1580 +/- 198 mm Hg/s versus 340 +/- 221 mm Hg/s, P < .01). In hearts treated only on reperfusion, some improvement was observed, which, however, did not reach statistical significance. Coronary flow on reperfusion was higher in groups 2 and 3 compared with controls, and no "no-reflow" was observed. Two additional groups of hearts were perfused with phosphate-free Krebs-Henseleit solution to enable studies with 31P nuclear magnetic resonance (NMR). ATP was better preserved in HOE 694-pretreated (62 +/- 4.9% of preischemic value) than in control hearts (44 +/- 3.3%) at the end of 30 minutes of reperfusion, and phosphocreatine resynthesis was higher (109 +/- 3.7% versus 86 +/- 5.4%). HOE 694 did not affect the time course of intracellular acidosis during ischemia but suppressed a small alkaline overshoot occurring early in reperfusion (pH 6.96 +/- 0.02 in HOE 694-pretreated hearts versus 7.14 +/- 0.05 in control hearts). Electron microscopy with Ca2+ staining of the blood-perfused hearts showed that clumping of Ca2+ aggregates in mitochondria was prevented by HOE 694.

CONCLUSIONS

Postischemic dysfunction was associated with a rise in end-diastolic pressure. This rise was effectively blocked by HOE 694. The drug was most effective when hearts were treated before ischemia, although partial protection was observed when administration was started on reperfusion. The action of HOE 694 strengthens the idea that Na(+)-H+ exchange during both ischemia and reperfusion contributes to contractile dysfunction.
Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction.
Authors: Sabbah H N , Shimoyama H , Kono T , Gupta R C , Sharov V G , Scicli G , Levine T B , Goldstein S
Published: June 2012

BACKGROUND

Recent clinical trials have suggested that therapy with angiotensin-converting enzyme inhibitors in asymptomatic patients with reduced left ventricular (LV) function can significantly reduce the incidence of congestive heart failure compared with patients receiving placebo. In the present study, we examined the effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF).

METHODS AND RESULTS

LV dysfunction was produced in 28 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after the last embolization, dogs were randomized to 3 months of oral therapy with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n = 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n = 7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/- 1%, P < .001) and LV end-systolic volume (ESV) and end-diastolic volume (EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/- 6 mL, P < .001, and 61 +/- 6 versus 78 +/- 8 mL, P < .002, respectively). In dogs treated with enalapril or metoprolol, LVEF remained unchanged or increased after therapy compared with before therapy (35 +/- 1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P < .05), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased significantly.

CONCLUSIONS

In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfunction and LV chamber dilation. Therapy with digoxin maintains LV systolic function but does not prevent progressive LV enlargement.
Arrhythmogenic influence of intracoronary thrombosis during acute myocardial ischemia.
Authors: Goldstein J A , Butterfield M C , Ohnishi Y , Shelton T J , Corr P B
Published: June 2012

BACKGROUND

Patients with acute coronary artery thrombosis often develop primary malignant ventricular arrhythmias (MVA) early after coronary occlusion. In contrast, acute ischemia induced by nonthrombotic balloon occlusion during routine coronary angioplasty rarely elicits such arrhythmias. This study was designed to assess the role of intracoronary thrombosis in arrhythmogenesis during acute ischemia.

METHODS AND RESULTS

We compared the incidence of MVA associated with acute left anterior descending coronary artery (LAD) thrombosis elicited in open-chest anesthetized dogs by electrical injury (n = 10) or intracoronary stent (n = 9) versus LAD balloon occlusion (n = 15). Compared with animals subjected to balloon occlusion, those with thrombotic occlusion had a significantly greater incidence of MVA, defined as nonsustained ventricular tachycardia (total duration > 10 seconds), sustained ventricular tachycardia, or ventricular fibrillation developing within the first 30 minutes of occlusion. In the combined thrombosis groups, MVA developed in 11 of 19 animals (58%) (6 of 10 dogs with electrical injury and 5 of 9 stent animals). In contrast, MVA occurred in only 1 of 15 animals (7%) subjected to balloon occlusion. This striking and significant difference in arrhythmias occurred despite the fact that radioactive microsphere perfusion analysis documented that the extent of left ventricular myocardium rendered ischemic was equal in all groups (percent of left ventricular myocardium with occlusion flow < or = 50% of baseline: electrical injury, 25.2 +/- 5.3%; stent, 27.1 +/- 3.6%; balloon, 34.3 +/- 11.6%; P = NS). Furthermore, there were no differences between the animals with thrombosis or balloon occlusion with respect to changes in echocardiographic parameters of left ventricular function, aortic pressure, or heart rate after occlusion.

CONCLUSIONS

These data provide evidence that despite equal magnitudes of jeopardized myocardial mass, acute ischemia induced by thrombotic coronary occlusion results in a greater incidence of MVA than does nonthrombotic balloon occlusion. These findings suggest that the process of intracoronary thrombosis itself exerts arrhythmogenic effects above and beyond the impact of ischemia on myocardium induced by coronary occlusion.
Digital angiographic assessment of the physiological changes to the regional microcirculation induced by successful coronary angioplasty.
Authors: Schühlen H , Eigler N L , Zeiher A M , Rombach M M , Whiting J S
Published: June 2012

BACKGROUND

Impulse response analysis of digital coronary angiographic images calculates a parameter known as the mean transit time of the microcirculation (Tmicro). This has been shown to accurately assess the regional microcirculatory response to proximal stenosis in relation to flow. Our goal was to apply impulse response analysis to patients undergoing successful angioplasty and to quantify the induced physiological changes with respect to quantitative angiographic measurements of stenosis dimensions.

METHODS AND RESULTS

We studied 24 patients before and after successful single-vessel percutaneous transluminal coronary angioplasty (PTCA). Minimal luminal stenosis area was increased from 0.9 +/- 0.6 before PTCA to 4.1 +/- 1.3 mm2 after PTCA (P < .0001). In all patients this was accompanied by an increase in the inverse of Tmicro (Tmicro-1), from 8.5 +/- 3.0 to 26.5 +/- 9.0 min-1 (P < .0001) with a linear correlation between Tmicro-1 and minimal luminal stenosis area (r = .73; SEE = 7.74). Stenosis flow reserve, estimated by integration of stenosis dimensions, increased in all patients from 1.8 +/- 1.0 to 4.5 +/- 0.4 after PTCA (P < .01). A comparison of Tmicro-1 with stenosis flow reserve revealed a nonlinear relation. In 16 patients undergoing PTCA of the left anterior descending or circumflex artery, contrast injections into the left main stem allowed simultaneous measurements of Tmicro-1 in the adjacent, nonstenotic artery. Adjacent artery Tmicro-1 did not change after PTCA (25.8 +/- 6.2 compared with 25.6 +/- 6.8 min-1 before PTCA; P = NS); moreover, Tmicro-1 of the dilated artery measured after PTCA was equivalent to the nonstenotic adjacent artery, indicating normalization of microcirculatory responses.

CONCLUSIONS

These data suggest that Tmicro-1 determined by digital angiographic impulse response analysis of a single contrast injection under resting flow conditions may be a practical method to assess the regional microcirculatory response to changes in stenosis severity effected by coronary angioplasty.
Circadian variation of sustained ventricular tachycardia in patients with coronary artery disease and implantable cardioverter-defibrillators.
Authors: Lampert R , Rosenfeld L , Batsford W , Lee F , McPherson C
Published: June 2012

BACKGROUND

While previous studies using epidemiological data and ambulatory ECG monitoring have shown peak occurrence of sudden death and nonsustained ventricular tachycardia in the morning, none have examined circadian variation of potentially life-threatening ventricular tachycardia (VT), nor has any study observed circadian behavior of any arrhythmias in individuals followed longitudinally. We used the event memory of multiprogrammable implantable cardioverter-defibrillators to evaluate the circadian pattern of sustained VT over time.

METHODS AND RESULTS

Data were reviewed from 32 consecutive patients with coronary artery disease and sustained VT who had received the Ventak PRX (CPI, Inc) cardioverter-defibrillator between May 1991 and August 1993 and had experienced at least one episode of VT terminated by their device. Mean follow-up was 14 +/- 7 months. Among the 2558 episodes recorded by the device logs, VT occurrence peaked between 6 AM and noon (P = .007 by ANOVA among four 6-hour time periods). Harmonic regression revealed a morning peak at 9 AM (P < .01). This morning peak occurred in patients with both frequent and infrequent events. Among 21 patients who experienced more than four VT events, 8 (38%) had an AM peak of VT occurrence (> 35% of VT between 6 AM and noon). Neither age, ejection fraction, event frequency, presenting arrhythmia, nor drug therapy distinguished patients who displayed the AM VT peak.

CONCLUSIONS

In patients with coronary artery disease, sustained VT displays circadian variation with peak frequency in the morning, similar to that for sudden death. Individual patients who display specific patterns of circadian variation over time can be identified using defibrillator logs. Investigation of circadian variation of other phenomena to elucidate mechanisms of VT should focus on these patients.
Enhanced detection of distinguishing features in signal-averaged electrocardiograms from patients with ventricular tachycardia by combined spatial and spectral analyses of entire cardiac cycle.
Authors: Kavesh N G , Cain M E , Ambos H D , Arthur R M
Published: June 2012

BACKGROUND

Signals generated by myocardium responsible for ventricular tachycardia (VT) contribute to the entire QRS complex, ST segment, and T wave and are spatially distributed over the entire torso. However, current methods of signal-averaged ECG analysis restrict interrogation to the terminal QRS complex, do not include data on the body surface distributions of the distinguishing features detected, and have a limited clinical value because of a low positive predictive accuracy. Accordingly, we tested the hypothesis that frequency analysis of the entire cardiac cycle of spatially selected ECGs based on isoharmonic maps of the body surface enhance the detection of the unique spectral features in signal-averaged ECGs that differentiate patients with from those without VT.

METHODS AND RESULTS

Isoharmonic maps of the body surface were calculated during sinus rhythm with the use of forward problem solutions for 32 patients with sustained VT, 30 without VT, and 10 healthy subjects and analyzed over a bandwidth of 0.05 to 470 Hz. Spectra of ECGs at the maximum and minimum of each patient's isoharmonic map of 1 to 7 Hz demonstrated a broadened bandwidth of significant separation (P < .05) for patients with from those without VT compared with the separation achieved with the use of Frank ECGs alone. Furthermore, the statistical significance within the bands of separation was greater for spatially selected ECGs compared with the Frank leads. Frank leads separated patients over the band from 11 to 84 Hz with a mean value of P = .0094. ECGs at the maximum of 1-to-7-Hz isoharmonic maps separated patients over the 8-to-111-Hz band with a mean value of P = .0062 (range, P < .05 to P < .0000001). ECGs at the minimum of 1-to-7-Hz isoharmonic maps extended the low-frequency end of the band of separation, which covered 0 to 69 Hz with a mean value of P = .0039 (range, P < .05 to P < .0000001). Subgroup analysis verified that results were independent of QRS duration.

CONCLUSIONS

Spectral analysis of ECGs that are spatially selected for each patient is superior to orthogonal ECGs and augments detection of distinguishing features in ECGs that identify risk of VT. The new data acquired from analysis of spatially selected ECGs from individual patients provide the information on the specific frequency bands and an improved ECG-lead system required to refine methods of analysis of the signal-averaged ECG.
Effect of hypercapnic acidemia on anisotropic propagation in the canine ventricle.
Authors: Vorperian V R , Wisialowski T A , Deegan R , Roden D M
Published: June 2012

BACKGROUND

Impulse propagation in the ventricle depends on both sodium channel availability and cell-to-cell coupling through gap junctions. Sodium channel block has been shown to depress conduction velocity (theta) more longitudinal (LONG) to than transverse (TRANS) to fiber orientation. Because exposure to CO2 produces intracellular acidosis and decreased gap junction conductance in vitro, we tested the hypothesis that increased PCO2 would result in preferential depression of transverse conduction in vivo.

METHODS AND RESULTS

In anesthetized dogs, when atrial pH was reduced to 6.70 +/- 0.04 by increasing the fraction of inhaled CO2 to 40%, theta TRANS fell from 0.23 +/- 0.04 to 0.19 +/- 0.02 m/s (-16 +/- 8%, P < .03), while theta LONG was unchanged (-3 +/- 7%, P = NS). In contrast, with the same degree of acidemia produced by HCl infusion, only theta LONG fell (-8 +/- 7%), coincident with a rise in serum K+.

CONCLUSIONS

The observed effect of CO2 on propagation in the intact heart is consistent with its previously described in vitro actions to uncouple cell-to-cell communication and may provide a model to study the role of cell-to-cell coupling in normal and abnormal propagation.
Effects of enalapril versus losartan on regression of volume overload-induced cardiac hypertrophy in rats.
Authors: Ruzicka M , Yuan B , Leenen F H
Published: June 2012

BACKGROUND

The role of nonhemodynamic cardiac trophic mechanisms differs not only between different models of cardiac hypertrophy but also within the same model for development versus maintenance of cardiac hypertrophy. Our previous studies pointed to a major role for the renin-angiotensin system (RAS) as a cardiac trophic stimulus in the remodeling of the heart in response to volume overload by aortocaval shunt or minoxidil treatment.

METHODS AND RESULTS

In the present study, we evaluated the effects of blockade of the RAS by the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor blocker losartan on left ventricular (LV) and right ventricular mass and LV dilation in relation to changes in central hemodynamics during the maintenance of minoxidil and aortocaval shunt-induced cardiac hypertrophy. Both blockers similarly decreased LV end-diastolic pressure (LVEDP) and LV peak systolic pressure, whereas cardiac output remained unchanged in both models of volume overload. This suggests a major contribution of improved LV performance and decreased afterload to the decrease in cardiac preload by the two blockers rather than decreased venous return. Both blockers reversed LV hypertrophy in parallel to their effects on LVEDP in both models of volume overload. In minoxidil-treated rats, the extent of reversal in LV mass and dilation by the two blockers was similar to "spontaneous regression" after discontinuation of minoxidil treatment.

CONCLUSIONS

These results indicate that in contrast to the development phase of cardiac hypertrophy, the RAS does not contribute to the maintenance of volume overload-induced cardiac hypertrophy in these two models via direct cardiac trophic effects. The RAS, however, maintains cardiac hypertrophy indirectly by contributing to the persistence of high filling pressures.
Fluid restitution and blood volume redistribution in anesthetized rabbits in response to vasoactive drugs.
Authors: Anderson S M , Rich G F , Roos C , Lee L P , Lee J S
Published: June 2012

BACKGROUND

Vasoactive drugs could alter the fluid restitution from the tissue and redistribute blood volume between the macrocirculation and microcirculation.

METHODS AND RESULTS

With bolus injections of vasoactive drugs in anesthetized rabbits, we measured the changes in blood and plasma density for the determination of the volume of restitution and redistribution. Epinephrine 3.5 micrograms/kg caused a fluid loss to the tissue, leading to a transient decrease in total blood volume by 2.30 mL/kg. Because of blood volume redistribution, the peak volume reduction was accompanied by a volume reduction of 0.81 mL/kg from the macrocirculation and 1.49 mL/kg from the microcirculation. Phenylephrine 70 micrograms/kg caused a peak reduction in total blood volume of 1.40 mL/kg (with 0.41 mL/kg from macrocirculation and 0.99 mL/kg from microcirculation). Nitroprusside 7 micrograms/kg increased the blood volume by 1.44 mL/kg (0.83 mL/kg macro and 0.61 mL/kg micro), nitroglycerin 7 micrograms/kg by 1.48 mL/kg (0.97 mL/kg macro and 0.51 mL/kg micro), and isoproterenol 7 micrograms/kg by 2.07 mL/kg (0.68 mL/kg macro and 1.39 mL/kg micro). All plasma (or blood) density changes measured for the five drugs (with epinephrine, phenylephrine, and nitroprusside done over a wide dosage range) correlated linearly with the drug-induced changes in arterial pressures.

CONCLUSIONS

These results indicate that vasoactive drugs alter total blood volume and the volume of microcirculation and macrocirculation.