bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term results after balloon pulmonary valvuloplasty.
Authors: McCrindle B W , Kan J S
Published: June 2012

BACKGROUND

The objective of this study was to determine the long-term outcome of patients after percutaneous balloon pulmonary valvuloplasty (BPV) treatment of congenital pulmonary valve stenosis.

METHODS AND RESULTS

This study represents a case series with duration (mean +/- SD) of follow-up of 4.6 +/- 1.9 years. Forty-six patients with a median age of 4.6 years (range, 3 months to 56 years) had BPV at one academic institution between June 1981 and December 1986. Mean peak systolic pressure gradients from the right ventricle to the pulmonary artery were as follows: before BPV, 70 +/- 36 mm Hg; immediately after BPV, 23 +/- 14 mm Hg; at intermediate follow-up by cardiac catheterization or Doppler echocardiography at less than 2 years after BPV, 23 +/- 16 mm Hg (n = 33); and at long-term follow-up by Doppler at more than 2 years after BPV, 20 +/- 13 mm Hg (n = 42). BPV acutely reduced the gradient to less than 36 mm Hg for 41 of 46 (89%) patients. Available gradients at long-term follow-up were less than 36 mm Hg for 36 of 42 (86%) patients without additional procedures. A patient age of less than 2 years at the initial BPV was a significant risk factor for gradients over 36 mm Hg at follow-up.

CONCLUSIONS

BPV provides long-term relief of pulmonary valvular obstruction in the majority of patients. Close follow-up of patients who require BPV at less than 2 years of age is warranted.
Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog.
Authors: Lim C S , Chapman G D , Gammon R S , Muhlestein J B , Bauman R P , Stack R S , Swain J L
Published: June 2012

Gene therapy approaches have been suggested for the treatment of cardiovascular disease. Recently, direct transfer of the gene encoding beta-galactosidase into peripheral arteries of the pig has been demonstrated. To determine whether this approach is applicable to other arterial beds and to other species, we first evaluated the use of beta-galactosidase as a marker protein in the canine model. We demonstrate that variable but substantial endogenous beta-galactosidase-like activity is induced by manipulation of canine peripheral arteries, which precludes the use of this marker protein in evaluating the efficiency of gene transfer in this model. A marker gene encoding firefly luciferase was then evaluated, and background luciferase activity was found to be low in the dog even after arterial manipulation. Using the luciferase gene, we then demonstrated lipid-mediated gene transfer directly into both coronary and peripheral arteries of the intact dog. These results indicate the feasibility of in vivo gene transfer into coronary arteries and demonstrate the use of the luciferase marker protein in quantifying recombinant protein expression following gene transfer in canine models. This simple and effective method for direct in vivo gene transfer into coronary and peripheral arteries may be applicable to the localized production of therapeutically important proteins for the treatment of cardiovascular diseases.
Oxidized low density lipoproteins inhibit relaxations of porcine coronary arteries. Role of scavenger receptor and endothelium-derived nitric oxide.
Authors: Tanner F C , Noll G , Boulanger C M , Lüscher T F
Published: June 2012

BACKGROUND

We studied the effects of low density lipoprotein (LDL) on endothelium function.

METHODS AND RESULTS

Porcine epicardial and intramyocardial coronary arteries suspended in organ chambers for isometric tension recording were exposed to LDL for 2 hours and were then washed. In epicardial coronary arteries, oxidized LDL (30-300 micrograms/ml) but not native LDL or lysolecithin inhibited endothelium-dependent relaxations to serotonin, thrombin, and aggregating platelets (5,000-75,000/microliter). Endothelium-dependent relaxations to bradykinin and A23187 and endothelium-independent relaxations to SIN-1 were unaffected by oxidized LDL. In intramyocardial coronary arteries, oxidized LDL had no appreciable effect on relaxations to serotonin. The effect of oxidized LDL on the response to serotonin in epicardial coronary arteries was completely prevented by dextran sulfate (10 micrograms/ml). The inhibitory effect of oxidized LDL persisted in the presence of pertussis toxin. Similar to the lipoproteins, L-NG-monomethyl arginine (L-NMMA) reduced relaxations to serotonin but not to bradykinin in epicardial coronary arteries. In the presence of L-NMMA, oxidized LDL further reduced the response to serotonin. In arteries in which relaxations to serotonin were inhibited by oxidized LDL, L-arginine but not D-arginine induced a full relaxation. Pretreatment with L-arginine potentiated relaxations to serotonin in arteries exposed to oxidized LDL.

CONCLUSIONS

Thus, oxidized LDL activates the scavenger receptor on endothelial cells and inhibits the receptor-operated nitric oxide formation in epicardial but not in intramyocardial coronary arteries. The mechanism is not related to dysfunction of a Gi protein but is related to a reduced intracellular availability of L-arginine. The reduced nitric oxide formation at sites of early atherosclerotic lesions may favor platelet aggregation and vasospasm, both of which are known clinical events in patients with coronary artery disease.
Mechanism of coronary vasodilation produced by bradykinin.
Authors: Pelc L R , Gross G J , Warltier D C
Published: June 2012

BACKGROUND

Bradykinin has been demonstrated to be an endothelium-dependent vasodilator in the cerebral circulation of the mouse, but the actions of bradykinin on regional tissue perfusion in the canine coronary circulation have not been studied.

METHODS AND RESULTS

The mechanism of coronary vasodilation by bradykinin was studied in open-chest, anesthetized dogs. The role of cyclooxygenase stimulation, bradykinin B2 receptor activation, and endothelium-derived relaxing factor in bradykinin-mediated vasodilation was studied in separate groups of dogs. Bradykinin was infused intracoronarily so as to avoid changes in systemic hemodynamics capable of altering the regional distribution of coronary blood flow (radioactive microspheres). Bradykinin produced a preferential increase in subendocardial blood flow. Pretreatment with indomethacin had no effect on bradykinin-mediated increases in total left ventricular flow or the transmural distribution of coronary blood flow. Blockade of bradykinin B2 receptors with the competitive antagonist [Thi5,8, D-Phe7]-bradykinin attenuated both the increase in total flow and redistribution of perfusion to the subendocardium produced by bradykinin. Inhibition of endothelium-derived relaxing factor with quinacrine, occlusion/reperfusion, or NG-monomethyl L-arginine attenuated the total increase in left ventricular flow and blocked the redistribution of flow to the subendocardium produced by bradykinin.

CONCLUSIONS

The present results demonstrate that intracoronary infusion of bradykinin produces a preferential increase in blood flow to the subendocardium via stimulation of B2 receptors and the release of an endothelium-dependent relaxing factor that may be nitric oxide.
Roles of P2-purinoceptors in the cardiovascular system.
Authors: Ralevic V , Burnstock G
Published: June 2012

Characterization of P2-purinoceptor subtypes has facilitated understanding of the many diverse effects produced by purine nucleotides. P2X-Purinoceptors are located on vascular smooth muscle where they mediate vasoconstriction resulting from ATP released as a cotransmitter with noradrenaline from sympathetic nerves. P2Y-Purinoceptors are usually located on the vascular endothelium where they have a role as mediators of vascular relaxation by locally produced ATP. In some vessels, P2Y-purinoceptors are also located on the smooth muscle, perhaps in association with purinergic or sensory nerves, where they can elicit direct relaxation to neuronally released ATP. The net effect of ATP and its analogues on isolated vessels or on vascular beds will be the results of actions mediated by P2X- and P2Y-purinoceptor subtypes, although changes in vascular tone and in integrity of nerves and endothelial cells may alter the balance of the response. Such changes have been observed in diseased states (e.g., atherosclerosis) and may have important implications for the involvement of P2-purinoceptors in, for example, vasospasm. The development of selective and potent antagonists to P2X- and P2Y-purinoceptors has so far remained elusive, and their therapeutic potential can only be guessed.
HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men.
Authors: Salonen J T , Salonen R , Seppänen K , Rauramaa R , Tuomilehto J
Published: June 2012

BACKGROUND

We investigated the association of cholesterol concentrations in serum high density lipoprotein (HDL) and its subfractions HDL2 and HDL3 with the risk of acute myocardial infarction in 1,799 randomly selected men 42, 48, 54, or 60 years old.

METHODS AND RESULTS

Baseline examinations in the Kuopio Ischaemic Heart Disease Risk Factor Study were done during 1984-1987. In Cox multivariate survival models adjusted for age and examination year, serum HDL cholesterol of less than 1.09 mmol/l (42 mg/dl) was associated with a 3.3-fold risk of acute myocardial infarction (95% confidence intervals [CI], 1.7-6.4), serum HDL2, cholesterol of less than 0.65 mmol/l (25 mg/dl) was associated with a 4.0-fold risk of acute myocardial infarction (95% CI, 1.9-8.3), and serum HDL3 cholesterol of less than 0.40 mmol/l (15 mg/dl) was associated with a 2.0-fold (95% CI, 1.1-4.0) risk of acute myocardial infarction. Adjustments for obesity, ischemic heart disease, other cardiovascular disease, maximal oxygen uptake, systolic blood pressure, antihypertensive medication, serum low density lipoprotein cholesterol, and triglyceride concentrations reduced the excess risks associated with serum HDL, HDL2, and HDL3 cholesterol in the lowest quartiles by 52%, 48%, and 41%, respectively. Additional adjustments for alcohol consumption, cigarettes smoked daily, smoking years, and leisure time energy expenditure reduced these excess risks associated with low HDL, HDL2, and HDL3 cholesterol levels by another 26%, 24% and 21%, respectively.

CONCLUSIONS

Our data confirm that both total HDL and HDL2 levels have inverse associations with the risk of acute myocardial infarction and may thus be protective factors in ischemic heart disease, whereas the role of HDL3 remains equivocal.
Effect of diltiazem on symptomatic and asymptomatic episodes of ST segment depression occurring during daily life and during exercise.
Authors: Théroux P , Baird M , Juneau M , Warnica W , Klinke P , Kostuk W , Pflugfelder P , Lavallée E , Chin C , Dempsey E
Published: June 2012

BACKGROUND

Silent myocardial ischemia is an adverse prognostic marker in patients with coronary disease; however, controlled data on the effect of treatment are sparse and contradictory, and the relations among the occurrence of ST segment depression, drug efficacy, and heart rate are unclear.

METHODS AND RESULTS

Sixty patients with stable coronary artery disease, a positive treadmill exercise test and asymptomatic ST segment depression on ambulatory electrocardiographic recording were assessed in a multicenter, double-blind, placebo-controlled, cross-over trial. Treadmill exercise tests and 72-hour electrocardiographic recordings were obtained at the end of two 2-week treatment periods with sustained-release diltiazem 180 mg b.i.d. or equivalent placebo. Episodes of asymptomatic ST depression decreased by 50% or more in 70% of the patients from a median number of 4.5 (range, 0-19) to 1.5 (range, 0-13) (p = 0.0001); their cumulative duration also decreased from 78.5 (range, 0-60) to 24.5 (range, 0-411) minutes (p = 0.001). No circadian variation was found in the efficacy of diltiazem. The occurrence of ischemic type ST segment depression was modulated by changes in heart rate rather than by absolute heart rate. Diltiazem also improved exercise test end points but to a lesser extent. Time to ST segment depression increased to 341 +/- 148 from 296 +/- 154 seconds (p = 0.005). Although less frequent with diltiazem administration (45 versus 54 patients, p less than 0.03), exercise-induced ST depression was more often asymptomatic (98% versus 72% of patients, p less than 0.0001).

CONCLUSIONS

Diltiazem reduces the frequency and severity of ischemic type ST depression in patients with stable coronary artery disease.
Hemodynamic effects of octreotide in patients with autonomic neuropathy.
Authors: Hoeldtke R D , Davis K M , Joseph J , Gonzales R , Panidis I P , Friedman A C
Published: June 2012

BACKGROUND

The somatostatin analogue, ectrootide, is being used to treat postprandial hypotension in patients with autonomic neuropathy. Although the therapeutic effect of the drug is presumably secondary to a splanchnic vasoconstrictor action, its effect on splanchnic hemodynamics has never been characterized in patients with autonomic neuropathy. Moreover, it is unknown whether octreotide acts on other vascular beds in this group of patients or whether it affects cardiac output. We, therefore, measured splanchnic, forearm, and systemic vascular resistance and cardiac output before and after administering octreotide (0.4 microgram/kg s.c.) to patients with idiopathic autonomic neuropathy and diabetic autonomic neuropathy.

METHODS AND RESULTS

Splanchnic blood flow was determined from the clearance of indocyanine green in seven patients. We observed that octreotide decreased splanchnic blood flow (from 850 +/- 77 to 664 +/- 48 ml/min, p less than 0.005), increased mean blood pressure (from 97 +/- 6 to 115 +/- 3 mm Hg, p less than 0.005), and increased splanchnic vascular resistance (from 0.118 +/- 0.012 to 0.18 +/- 0.018 mm Hg/ml/min, p less than 0.005). Forearm blood flow was measured by plethysmography in 13 patients. Octreotide increased forearm vascular resistance in patients with idiopathic autonomic neuropathy (n = 8) from 19.1 +/- 1.0 to 27.2 +/- 3.8 mm Hg/ml/min/100 ml forearm volume (p less than 0.01) and from 25.2 +/- 3.9 to 41.0 +/- 6.8 mm Hg/ml/min/100 ml (p less than 0.01) in patients with diabetic autonomic neuropathy (n = 5). Cardiac output was measured by two-dimensional echocardiography. Octreotide administration increased cardiac output in five of six patients with idiopathic autonomic neuropathy (from 4.4 +/- 0.4 to 5.0 +/- 0.5 l/min, p less than 0.02) and five of five patients with diabetic autonomic neuropathy (from 3.8 +/- 0.4 to 5.1 +/- 0.4 l/min, p less than 0.02). Systemic vascular resistance increased in patients with idiopathic autonomic neuropathy from 21.2 +/- 2 to 24.9 +/- 2.6 (p less than 0.05) but did not change in patients with diabetic autonomic neuropathy.

CONCLUSION

The pressor effect of octreotide in patients with autonomic neuropathy is associated with increased splanchnic and forearm vascular resistance and with increased cardiac output.
Effective thrombolysis without marked plasminemia after bolus intravenous administration of vampire bat salivary plasminogen activator in rabbits.
Authors: Gardell S J , Ramjit D R , Stabilito I I , Fujita T , Lynch J J , Cuca G C , Jain D , Wang S P , Tung J S , Mark G E
Published: June 2012

BACKGROUND

The use of recombinant tissue-type plasminogen activator (t-PA) in thrombolytic therapy is frequently associated with significant fibrinogenolysis. In contrast, recombinant vampire bat salivary plasminogen activator (Bat-PA) displays strict fibrin specificity, an attribute that could be desirable in a fibrinolytic agent.

METHODS AND RESULTS

The efficacy and fibrin selectivity of Bat-PA was evaluated and compared with that of t-PA using a rabbit model of femoral arterial thrombosis. Administration of 8.1, 14, and 42 nmol Bat-PA/kg by bolus intravenous injection restored flow in 50%, 75%, and 80% of the rabbits, respectively. The incidence of reperfusion after bolus intravenous injection of 14 and 42 nmol t-PA/kg was 15% and 78%, respectively. The maximal femoral artery reperfusion flows were equivalent after treatment with 42 nmol Bat-PA/kg or 42 nmol t-PA/kg, but the time to reach maximal flow for Bat-PA was approximately one half that of t-PA. Furthermore, the rapid restoration of flow by 42 nmol Bat-PA/kg, in contrast to equimolar t-PA, was accomplished without fibrinogenolysis and with only small decreases in the plasminogen and alpha 2-antiplasmin levels. Equipotent doses of Bat-PA and t-PA both resulted in approximate 2.5-fold increases in the template bleeding times of aspirin-pretreated rabbits. The clearance of Bat-PA from rabbits exhibited biexponential elimination kinetics; approximately 80% was cleared by the relatively slow beta phase (half-life of 17.1 minutes). Overall, Bat-PA was cleared approximately fourfold slower than t-PA.

CONCLUSIONS

Bolus intravenous administration of Bat-PA would facilitate prompt initiation of thrombolytic therapy, and the avoidance of plasminemia could result in fewer and less severe bleeding complications.
Immunohistochemical localization of basic and acidic fibroblast growth factors in the developing rat heart.
Authors: Spirito P , Fu Y M , Yu Z X , Epstein S E , Casscells W
Published: June 2012

BACKGROUND

We used biochemical and immunohistochemical techniques to investigate the expression and distribution of immunoreactive basic and acidic fibroblast growth factors (bFGF and aFGF, respectively) in the hearts of rat embryos (11-20 days of gestation) and of postnatal rats (1-35 days after birth). Our purpose was to assess the relation between the cellular distribution of these growth factors and histogenetic and morphogenetic events in the developing heart.

METHODS AND RESULTS

Western-blot analysis of heparin-bound material from neonatal heart extracts identified a single band with a molecular weight of approximately 18 kD for both bFGF and aFGF. Five antibodies for bFGF and three for aFGF showed superimposable distribution of immunoreactive bFGF and aFGF in the heart at each stage examined. At the cellular level, these peptides were localized in the cytoplasm and extracellular matrix. In the myocytes, immunostaining was positive throughout the embryonic and neonatal periods. In the majority of the mesenchymal cells of the cushions and endothelial cells of endocardium and vessels, staining was also positive. In the smooth muscle cells of the aorta, other large arteries, and coronary arteries, immunostaining was intensely positive at early stages of development but became faint or negative with increasing cell differentiation.

CONCLUSIONS

The wide distribution of immunoreactive bFGF and aFGF that we identified in the developing rat heart suggests that these growth factors play an important role in heart cytodifferentiation and morphogenesis. Their superimposable distribution may reflect functional interaction. The progressive changes in their distribution suggest a changing role for these peptides during organogenesis.
Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart.
Authors: Liu G S , Thornton J , Van Winkle D M , Stanley A W , Olsson R A , Downey J M
Published: June 2012

BACKGROUND

Preconditioning (5 minutes of ischemia followed by 10 minutes of recovery) renders the heart very resistant to infarction from subsequent ischemia. This study tests whether adenosine receptors might mediate preconditioning protection.

METHODS AND RESULTS

We examined the effect on infarct size of pretreatment with either of two adenosine receptor antagonists in both control and preconditioned in situ rabbit hearts. Hearts underwent 30 minutes of regional ischemia plus 3 hours of reperfusion, and infarct size was measured with tetrazolium. Infarct size averaged 39% of the zone at risk in controls but only 8% in preconditioned hearts. Preconditioned and nonpreconditioned hearts receiving either blocker had infarcts not different in size from the controls. A 5-minute intracoronary infusion of adenosine was as effective as 5 minutes of ischemia in protecting parabiotically perfused isolated hearts against infarction from a 45-minute ischemic insult. Similarly, intracoronary infusion of N6-1-(phenyl-2R-isopropyl)adenosine, an A1-selective adenosine receptor agonist, at a dose that delayed conduction but did not dilate the coronary vessels, also limited infarct size. The protection disappeared when we reduced the coronary concentration of drug by intravenous infusion of adenosine, indicating that cardiac rather than peripheral receptors were involved in the protection.

CONCLUSIONS

We conclude that adenosine released during the preconditioning occlusion stimulates cardiac A1 receptors, which leaves the heart protected against infarction even after the adenosine has been withdrawn.
Neutrophil accumulation in ischemic canine myocardium. Insights into time course, distribution, and mechanism of localization during early reperfusion.
Authors: Dreyer W J , Michael L H , West M S , Smith C W , Rothlein R , Rossen R D , Anderson D C , Entman M L
Published: June 2012

BACKGROUND

We have previously demonstrated that chemotactic factors released from the ischemic canine myocardium peak early during reperfusion and that they elicit neutrophil adherence reactions in vitro that are dependent on the CD18 glycoprotein family. In this study we investigated the hypothesis that neutrophil localization in ischemic canine myocardium in vivo occurs over a similar time course during early reperfusion and involves a CD18-dependent mechanism.

METHODS AND RESULTS

We occluded the circumflex coronary artery for 1 hour in acute, open-chest dogs, followed by reperfusion for 1, 2, 3, or 4 hours. Regional myocardial blood flow was determined using radiolabeled microspheres, and localization was traced using technetium-99m-labeled autologous neutrophils. In the first hour of reperfusion, neutrophil localization occurred preferentially within the subendocardial region and was inversely related to flow. Neutrophil localization diminished across the ischemic myocardium from endocardium to epicardium but remained negatively related to flow in the midmyocardial region. Regardless of flow, little neutrophil localization occurred in the subepicardial region. Neutrophil localization was greatest in the first hour of reperfusion and diminished thereafter. By 4 hours of reperfusion, the rate of localization was markedly attenuated relative to 1 hour. Dogs given anti-CD18 monoclonal antibody R15.7 (1 mg/kg i.v.) before occlusion underwent 1 hour of occlusion followed by 1 hour of reperfusion. When compared with 1-hour reperfusion controls, the R15.7-treated dogs demonstrated significant attenuation of neutrophil localization in the subendocardial region.

CONCLUSIONS

These data support the concepts that rapid neutrophil localization during reperfusion occurs within regions of previous myocardial ischemia and that neutrophils preferentially localize within the subendocardial region. The rate of neutrophil localization is greatest within the first hour after the initiation of reperfusion, and localization is, at least in part, CD18 dependent. Therapies directed against neutrophil-mediated reperfusion injury should be initiated with these considerations in mind.
Circumferential myocardial shortening in the normal human left ventricle. Assessment by magnetic resonance imaging using spatial modulation of magnetization.
Authors: Clark N R , Reichek N , Bergey P , Hoffman E A , Brownson D , Palmon L , Axel L
Published: June 2012

BACKGROUND

Conventional cardiac imaging methods do not depict true segmental myocardial shortening, since they cannot determine segment length between fixed points in the myocardium.

METHODS AND RESULTS

We used electrocardiographically gated magnetic resonance imaging with spatial modulation of magnetization to noninvasively "tag" the myocardium with dark stripes at uniform 7-mm intervals center to center at end diastole. We then determined end-systolic stripe separation and thereby calculated circumferential shortening. When end systole was not reached in the first image series, a second temporally overlapped series starting in late systole was used to determine late-systolic shortening. Septal, anterior, lateral, and inferior segments were assessed at endocardium, midwall, and epicardium on five midventricular short-axis sections each in 10 normal volunteers. A transmural gradient in circumferential shortening was observed, with the percentage of endocardial segment shortening consistently greater than epicardial segment shortening (epicardial, 22 +/- 5%; midwall, 30 +/- 6%; and endocardial, 44 +/- 6%; p less than 0.0001 by analysis of variance). Circumferential shortening varied from apex to base with slices closer to the base of the left ventricle showing less shortening at the midwall (28 +/- 9%) and endocardium (39 +/- 6%) than more apical slices at the midwall (34 +/- 13%) and endocardium (49 +/- 9%) (p less than 0.05 and p less than 0.01, respectively, by analysis of variance).

CONCLUSIONS

Transmural and longitudinal heterogeneity of circumferential shortening is present in the normal human left ventricle. Magnetic resonance imaging with spatial modulation of magnetization is a powerful new tool for assessment of circumferential shortening and provides information unobtainable with conventional imaging methods.
Radiofrequency catheter ablation of the atrioventricular junction from the left ventricle.
Authors: Sousa J , el-Atassi R , Rosenheck S , Calkins H , Langberg J , Morady F
Published: June 2012

BACKGROUND

The purpose of this study was to describe a new technique for catheter ablation of the atrioventricular junction using radiofrequency energy delivered in the left ventricle.

METHODS AND RESULTS

Catheter ablation of the atrioventricular (AV) junction using a catheter positioned across the tricuspid annulus was unsuccessful in eight patients with a mean +/- SD age of 51 +/- 19 years who had AV nodal reentry tachycardia (three patients), orthodromic tachycardia using a concealed midseptal accessory pathway, atrial tachycardia, atrial flutter (two patients), or atrial fibrillation. Before attempts at catheter ablation of the AV junction, each patient had been refractory to pharmacological therapy, and four had failed attempts at either catheter modification of the AV node using radiofrequency energy or surgical and catheter ablation of the accessory pathway. Conventional right-sided catheter ablation of the AV junction using radiofrequency energy in six patients and both radiofrequency energy and direct current shocks in two patients was ineffective. The mean amplitude of the His bundle potential recorded at the tricuspid annulus at the sites of unsuccessful AV junction ablation was 0.1 +/- 0.08 mV, with a maximum His amplitude of 0.03-0.28 mV. A 7F deflectable-tip quadripolar electrode catheter with a 4-mm distal electrode was positioned against the upper left ventricular septum using a retrograde aortic approach from the femoral artery. Third-degree AV block was induced in each of the eight patients with 20-36 W applied for 15-30 seconds. The His bundle potential at the sites of successful AV junction ablation ranged from 0.06 to 0.99 mV, with a mean of 0.27 +/- 0.32 mV. There was no rise in the creatine kinase-MB fraction and no complications occurred. An intrinsic escape rhythm of 30-60 beats/min was present in seven of the eight patients. Each patient received a permanent pacemaker and has been asymptomatic during 3-13 months of follow-up.

CONCLUSIONS

Catheter ablation of the AV junction can be achieved effectively and safely using radiofrequency energy delivered in the left ventricle when the conventional right-sided approach is unsuccessful.
Percutaneous excimer laser coronary angioplasty of lesions not ideal for balloon angioplasty.
Authors: Cook S L , Eigler N L , Shefer A , Goldenberg T , Forrester J S , Litvack F
Published: June 2012

BACKGROUND

Excimer laser coronary angioplasty is a new, investigational technique for treating coronary artery stenoses. Initial reports have demonstrated acute efficacy and relative safety of this procedure, but have not addressed the effect of lesion type on acute success and complication rates.

METHODS AND RESULTS

In the first 100 patients undergoing percutaneous excimer laser coronary angioplasty at our institution, acute laser success was obtained in 84% and procedural success was obtained in 94%. There were six acute closures during laser angioplasty and one myocardial infarction. Two patients required emergency coronary bypass surgery. Sixty-five percent of patients had lesions not ideal for balloon angioplasty because of lesion morphology (tubular, diffuse, or chronic total occlusion) or ostial location. There were 10 tubular stenoses, 29 diffuse lesions, 18 chronic total occlusions, and eight ostial lesions, including five aorto-ostial lesions. In this nonideal subgroup, the acute success rate with laser was 86% (72% of chronic total occlusions and 91% of non-totally occluded lesions), and the procedural success rate was 94%. There were three acute occlusions during laser angioplasty but no myocardial infarctions, emergency bypass surgeries, or deaths. One coronary artery perforation occurred without clinical sequelae. Laser angioplasty was successful in four of six lesions (67%) in which balloon angioplasty had failed. Laser success was obtained in 10 of 11 (91%) moderately or heavily calcified stenoses. Eight eccentric lesions and two lesions on bends were successfully treated without dissection or perforation. No side branch occlusions occurred in the 15 patients in whom one or more major branches originated within the lesion treated. Adjunctive balloon angioplasty was performed in 47% of cases, usually to obtain a larger final luminal diameter. Need for adjunctive balloon angioplasty decreased to 36% after a larger (2.0 mm) laser catheter became available. Twenty-eight percent of the 105 lesions treated were American College of Cardiology/American Heart Association classification type A, 47% were type B, and 25% were type C. Laser and procedural successes were obtained in 83% and 97% of type A, 88% and 96% of type B, and 85% and 88% of type C lesions, respectively.

CONCLUSIONS

In our initial experience, excimer laser angioplasty was found to be acutely effective and safe therapy for lesions identified as not ideal for balloon angioplasty. This technique may provide a useful adjunct or alternative to balloon angioplasty in selected patients.
Effects of aging, gender, and physical training on peripheral vascular function.
Authors: Martin W H , Ogawa T , Kohrt W M , Malley M T , Korte E , Kieffer P S , Schechtman K B
Published: June 2012

BACKGROUND

Blood pressure and total peripheral resistance increase with age. However, the effect of age on vasodilatory capacity has not been characterized.

METHODS AND RESULTS

To delineate the effects of aging, gender, and physical training on peripheral vascular function, we measured blood pressure during submaximal and maximal treadmill exercise and measured blood pressure, calf blood flow, and calf conductance (blood flow/mean blood pressure) at rest and during maximal hyperemia in 58 healthy sedentary subjects (men aged 25 +/- 5 and 65 +/- 3 years and women aged 27 +/- 5 and 65 +/- 4 years) and in 52 endurance exercise-trained subjects (men aged 30 +/- 3 and 65 +/- 4 years and women aged 27 +/- 3 and 65 +/- 3 years). Systolic and mean blood pressures were higher at rest, during maximal calf hyperemia, and during submaximal exercise of the same intensity in the older than in the younger subjects of the same gender and exercise training status (p less than 0.01). The magnitude of the age-related effect on blood pressure during exercise was greater in women than in men (p less than 0.01). Diastolic blood pressure during submaximal exercise was also higher in the older than in the younger subjects (p less than 0.05) but not in women treated with estrogen replacement. In contrast, systolic and mean blood pressures during submaximal work were lower in physically conditioned subjects than in sedentary age- and gender-matched subjects (p less than 0.05) but not in older women. Increased age was associated with reduced maximal calf conductance in women (p less than 0.01) but not in men. However, calf vasodilatory capacity was higher in trained than in untrained subjects (p less than 0.01), regardless of age and gender. There was a significant inverse relation between maximal calf conductance and systolic, diastolic, and mean blood pressures during submaximal exercise (r = -0.31 to -0.53, p less than 0.01) and a direct relation between maximal calf conductance and maximal oxygen uptake (r = 0.66, p less than 0.0001).

CONCLUSIONS

Thus, for healthy subjects between the ages of 25 and 65 years, there is an interactive effect between age and gender and an independent effect of physical training on peripheral vascular function.
Hypercholesterolemia enhances macrophage recruitment and dysfunction of regenerated endothelium after balloon injury of the rabbit iliac artery.
Authors: Weidinger F F , McLenachan J M , Cybulsky M I , Fallon J T , Hollenberg N K , Cooke J P , Ganz P
Published: June 2012

BACKGROUND

We studied the effects on and possible interaction of balloon denudation and hypercholesterolemia on large arteries in the rabbit with special regard to structure and vascular reactivity.

METHODS AND RESULTS

New Zealand White rabbits fed a 1% cholesterol diet or a standard diet for 14 weeks underwent balloon denudation of the left iliac artery 4 weeks before death. Both the balloon-injured and the control iliac arteries were harvested for in vitro studies of vascular reactivity, for immunohistochemical staining with monoclonal antibodies directed at smooth muscle cells and macrophages, and for scanning electron microscopy. Balloon injury caused intimal smooth muscle proliferation with little macrophage infiltration and was followed by recovery of endothelium-dependent vasodilator function within 4 weeks. Hypercholesterolemia caused macrophage-rich lesions confined to the intima with moderate impairment of endothelial vasodilator function. Balloon injury in the setting of hypercholesterolemia caused intimal smooth muscle cell proliferation and intense macrophage infiltration throughout the arterial wall and severe impairment of endothelial vasodilator function. Scanning electron microscopy confirmed regrowth of the endothelium in all balloon-injured vessels. In the balloon-injured arteries of hypercholesterolemic animals, the regenerated endothelium exhibited areas of atypical morphology not seen after balloon injury or hypercholesterolemia alone.

CONCLUSIONS

The present study shows that balloon injury, hypercholesterolemia, and their combination cause distinct lesions and functional disturbances. An arterial balloon injury in the setting of hypercholesterolemia produces a diffuse inflammatory response that is accompanied by a sustained impairment of endothelial function and a marked proliferative response.
Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor.
Authors: Haskel E J , Torr S R , Day K C , Palmier M O , Wun T C , Sobel B E , Abendschein D R
Published: June 2012

BACKGROUND

This study was designed to determine whether arterial reocclusion after thrombolysis can be prevented by lipoprotein-associated coagulation inhibitor (LACI), a physiological inhibitor of tissue factor-induced coagulation mediated by the extrinsic pathway.

METHODS AND RESULTS

Thrombosis was induced in femoral arteries of anesthetized dogs with the use of anodal current to elicit extensive vascular injury and formation of platelet-rich thrombi in one artery and with thrombogenic copper wire to elicit fibrin-rich thrombi without appreciable vascular injury in the contralateral artery. Recanalization of both vessels was induced with t-PA (1.7 mg/kg i.v. over 1 hour) and verified with Doppler flow probes. Reocclusion occurred within 2 hours in seven of seven arteries with electrical injury-induced thrombosis and in four of seven arteries with copper wire-induced thrombosis in the absence of LACI. In dogs given infusions of recombinant DNA-produced LACI (225 micrograms/kg over 15 minutes, followed by 4 micrograms/kg/min i.v.) after completion of the infusion of t-PA, no reocclusion occurred during the 2-hour interval of observation in any of the five arteries subjected to electrical injury (p less than 0.001), and cyclic partial occlusions were nearly abolished (0.4 +/- 0.4/hr in LACI-treated dogs compared with 13.7 +/- 5.5/hr in saline-treated dogs, p less than 0.0001). In contrast, reocclusion occurred in two of five arteries with indwelling copper wires, and cyclic partial occlusions were unaffected despite LACI. LACI prolonged the partial thromboplastin time modestly (1.7 +/- 0.2 x baseline) but did not affect platelet counts or aggregation assessed ex vivo.

CONCLUSIONS

Inhibition of the extrinsic pathway of coagulation with LACI prevents thrombotic arterial reocclusion after thrombolysis in vessels subjected to extensive vascular injury. Our results demonstrate that activation of the extrinsic pathway plays a critical role in thrombotic reocclusion and that LACI provides a highly targeted approach to facilitate sustained recanalization without directly inhibiting platelets.
Cerebral vasoconstriction during head-upright tilt-induced vasovagal syncope. A paradoxic and unexpected response.
Authors: Grubb B P , Gerard G , Roush K , Temesy-Armos P , Montford P , Elliott L , Hahn H , Brewster P
Published: June 2012

BACKGROUND

To determine the effect of vasovagally mediated syncope on the cerebral circulation, transcranial Doppler sonography was used to assess changes in cerebral blood flow velocity during head-upright tilt-induced syncope.

METHODS AND RESULTS

Thirty patients (17 men and 13 women; mean age, 43 +/- 22 years) with recurrent unexplained syncope were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of intravenous isoproterenol (1-4 micrograms/min), in an attempt to provoke bradycardia, hypotension, or both. Transcranial Doppler sonography was used to assess middle cerebral artery systolic velocity (Vs), diastolic velocity (Vd), ratio of systolic to diastolic velocities, pulsatility index (PI = Vs-Vd/Vmean), and resistance index (RI = Vs-Vd/Vs) before, during, and after tilt. Syncope occurred in six patients (20%) during the baseline tilt and 14 (46%) during isoproterenol infusion (total positives, 66%). In the tilt-positive patients, concomitant with the development of hypotension and bradycardia, transcranial Doppler sonography showed a 75 +/- 17% decrease in diastolic velocity, unchanged systolic velocity, a 46 +/- 17% decrease in mean velocity, a 295 +/- 227% increase in pulsatility index, and a 73 +/- 34% increase in resistance index.

CONCLUSIONS

These findings reflect increased cerebrovascular resistance secondary to arteriolar vasoconstriction distal to the insonation point of the middle cerebral artery. This is paradoxic because the expected response of the cerebral circulation to hypotension is vasodilation. We conclude that abnormal baroreceptor responses triggered during vasovagal syncope result in a derangement of cerebral autoregulation with paradoxic vasoconstriction in the face of increasing hypotension.
Abnormal vasomotor changes early after coronary angioplasty. A quantitative arteriographic study of their time course.
Authors: el-Tamimi H , Davies G J , Hackett D , Sritara P , Bertrand O , Crea F , Maseri A
Published: June 2012

BACKGROUND

To study the impact of percutaneous transluminal coronary angioplasty (PTCA) on coronary vasomotion, we prospectively analyzed spontaneous changes in coronary diameter and the response to the cold pressor test and intracoronary nitroglycerin in 11 patients subjected to successful single-vessel PTCA.

METHODS AND RESULTS

All antianginal medications were stopped 48 hours before each study. The minimum diameter of the PTCA segment and the diameter of a distal segment in the angioplastied vessel and of a segment in a control vessel not manipulated by the balloon catheter or guide wire were measured by computerized edge detection immediately before PTCA and 5 minutes after, 4 hours after, and 8 days after PTCA. At 4 hours, PTCA and distal segments were constricted by 38 +/- 9% and 16 +/- 5%, respectively, compared with the values at 5 minutes (p less than 0.01). Before angioplasty, the cold pressor test caused vasoconstriction of PTCA and distal segments by 23 +/- 6% (p less than 0.0001) and 15 +/- 4% (p less than 0.008), respectively, but no constrictor response was elicited at 5 minutes or 4 hours after angioplasty. Eight days after PTCA, the basal coronary diameters were similar to those observed 5 minutes after PTCA and the response to the cold pressor test was similar to that observed before PTCA. All segments dilated significantly with nitroglycerin at all times, and no vasoconstriction changes were found in the control segments.

CONCLUSIONS

Four hours after PTCA, transient spontaneous vasoconstriction of the PTCA and distal segments occurs, which is so intense that the cold pressor test does not cause any further constriction. These abnormalities resolve within 8 days of PTCA.
Differential effects of heptanol, potassium, and tetrodotoxin on reentrant ventricular tachycardia around a fixed obstacle in anisotropic myocardium.
Authors: Brugada J , Mont L , Boersma L , Kirchhof C , Allessie M A
Published: June 2012

BACKGROUND

The aim of this study was to test the hypothesis that electrical uncoupling and depression of the fast sodium channels have differential effects on propagation of the electrical impulse relative to the fiber orientation.

METHODS AND RESULTS

In a model of reentrant ventricular tachycardia (VT) (mean cycle length, 144 +/- 13 msec) around a ring of anisotropic myocardium in 10 Langendorff-perfused rabbit hearts, the effects of extracellular K+ concentration [( K+]o) and heptanol were studied. [K+]o and heptanol each had a dose-dependent effect on VT cycle length. However, high [K+]o slowed the VT mainly by depressing longitudinal conduction, whereas heptanol preferentially depressed transverse conduction. The ratio between longitudinal and transverse conduction velocities progressively decreased with high [K+]o and progressively increased with heptanol. Heptanol terminated VT at a mean concentration of 3.5 +/- 0.5 mM. The cycle length before termination was 446 +/- 120 msec (p less than 0.001). In eight of 10 experiments, termination occurred by failure of conduction during transverse propagation. VT terminated at a mean [K+]o of 11.6 +/- 1.8 mM. The cycle length before termination was 493 +/- 341 msec (p less than 0.01). In seven of 10 cases, termination occurred by failure of conduction during longitudinal propagation. In the remaining five episodes (two with heptanol and three with high [K+]o), termination occurred by collision of the reentrant beat with an antidromic impulse being reflected within the ring. In a separate series of six hearts, tetrodotoxin was administered during VT. Like high [K+]o, tetrodotoxin prolonged the cycle length of the VT by preferentially slowing longitudinal conduction, and VT was terminated by longitudinal block.

CONCLUSIONS

During reentrant VT, electrical uncoupling of cells by heptanol or modification of active membrane properties by high [K+]o or tetrodotoxin has a differential depressing effect on propagation of the impulse relative to the fiber orientation.
Efficacy of permanent pacing in the management of high-risk patients with long QT syndrome.
Authors: Moss A J , Liu J E , Gottlieb S , Locati E H , Schwartz P J , Robinson J L
Published: June 2012

BACKGROUND

From the international long QT syndrome (LQTS) study, 30 patients with corrected QT interval (QTc) of more than 0.44 second 1/2 were identified who had permanent pacemakers implanted for management of recurrent syncope or aborted cardiac arrest.

METHODS AND RESULTS

Pacemakers were implanted on average 7 years after the onset of the first syncopal episode. Most of the patients were female (87%), the average age at implantation was 19 +/- 13 years, the mean QTc was 0.55 +/- 0.08 second, and 57% were receiving antiadrenergic treatment for LQTS when the pacemaker was placed. Using birth as the time origin, the median cardiac event rate was significantly (p less than 0.001) reduced by pacing from 0.5 to 0 events per patient per year, with 21 patients experiencing no cardiac events during an average pacemaker follow-up of 49 months per patient. In 10 patients in whom the demand atrial pacing rate was faster than the intrinsic sinus rate, the average heart rate was increased 23 beats/min (from 58 to 81 beats/min) with pacing with reduction in the QT interval from 0.59 seconds to 0.46 seconds.

CONCLUSIONS

The beneficial effects of pacing in high-risk LQTS patients probably relate to the prevention of bradycardia, pauses, and the shortening of long QT intervals--factors that are known to be arrhythmogenic in this syndrome. Permanent cardiac pacing reduces the rate of recurrent syncopal events in high-risk LQTS patients, but it does not provide complete protection.
Unsuspected echocardiographic abnormality in the long QT syndrome. Diagnostic, prognostic, and pathogenetic implications.
Authors: Nador F , Beria G , De Ferrari G M , Stramba-Badiale M , Locati E H , Lotto A , Schwartz P J
Published: June 2012

BACKGROUND

The idiopathic long QT syndrome (LQTS) is characterized by electrocardiographic abnormalities and by a high incidence of lethal arrhythmias. The present case/control study demonstrates the frequent occurrence of unusual and specific ventricular wall motion abnormalities in LQTS and their association with history of syncope or cardiac arrest. These anomalies were present in 23 of 42 LQTS patients (55%) and in two of 42 healthy controls (5%, p less than 0.0001) matched for age, sex, height, and weight.

METHODS AND RESULTS

Two new measurements were developed to assess quantitatively the abnormalities observed. The first, Th1/2, is an index of the rapidity of the early contraction phase; the second, TSTh, is an index of the presence of a slow movement in the late thickening phase. Th1/2 was smaller in LQTS patients (15.0 +/- 4.1 versus 19.9 +/- 3.9% of the cardiac cycle, p less than 0.001), indicating that they reach half-maximal systolic contraction more rapidly than controls. TSTh was greater in LQTS patients (9.37 +/- 6.82 versus 2.88 +/- 4.46%, p less than 0.001), indicating that they spend more time at a very low thickening rate. A peculiar double peak pattern of late thickening was present in 11 patients and in no controls. These abnormalities were more frequent in symptomatic than in asymptomatic patients (20 of 26, 77%, versus three of 16, 19%, p less than 0.005; relative risk, 2.75). They were not affected by beta-blockade or by left cardiac sympathetic denervation. The same echocardiographic abnormalities were produced by right stellectomy in nine of nine anesthetized dogs, were not dependent on cycle length, and were not modified by subsequent left stellectomy.

CONCLUSIONS

This study demonstrates a previously unsuspected abnormality in the ventricular contraction pattern of LQTS patients and, for the first time, provides evidence that a noninvasively detected cardiac abnormality is associated with a higher risk for syncope/cardiac arrest. The experimental reproduction of this echocardiographic abnormality by right stellectomy indicates that this newly found clinical characteristic of LQTS does not contradict the "sympathetic imbalance" hypothesis.