bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of surgical relief of outflow obstruction on thallium perfusion abnormalities in hypertrophic cardiomyopathy.
Authors: Cannon R O , Dilsizian V , O'Gara P T , Udelson J E , Tucker E , Panza J A , Fananapazir L , McIntosh C L , Wallace R B , Bonow R O
Published: June 2012

BACKGROUND

To assess the impact of surgical relief of left ventricular outflow obstruction on myocardial perfusion abnormalities in patients with obstructive hypertrophic cardiomyopathy, 20 symptomatic patients who underwent a septal myectomy or mitral valve replacement were studied with assessment of myocardial perfusion during exercise by 201Tl emission computed tomography before and 6 months after surgery.

METHODS AND RESULTS

Before surgery, 15 patients had myocardial perfusion defects during exercise that completely normalized at rest, one patient had both reversible and fixed perfusion defects, two patients had fixed defects only, and two patients had normal exercise and rest thallium scans. After surgical relief of left ventricular outflow obstruction (basal gradient reduced from 62 +/- 40 to 7 +/- 12 mm Hg, p less than 0.001; peak provokable gradient reduced from 131 +/- 27 to 49 +/- 36 mm Hg, p less than 0.001), repeat exercise thallium studies showed complete normalization of perfusion defects in 11 patients, including the two patients with fixed defects alone before surgery, and improvement in the magnitude and distribution of perfusion defects in five additional patients. This was associated with a significant reduction in the number of patients with reversible regional defects (five patients compared with 13 patients before surgery, p = 0.026) and of patients with endocardial hypoperfusion (four patients compared with 12 patients before surgery, p = 0.024). Furthermore, increased lung uptake of thallium was noted in five patients after surgery, compared with 12 patients before surgery (p = 0.055). Only two patients with reversible perfusion defects before surgery had unchanged postoperative studies. However, four patients acquired new fixed defects as a consequence of surgery, and two of these four had the greatest severity and distribution of left ventricular hypertrophy by echocardiography. These four patients experienced a substantially greater decrease in ejection fraction (-26 +/- 15%) after surgery than the remaining patients (-3 +/- 14%, p less than 0.01).

CONCLUSIONS

Surgical relief of left ventricular outflow obstruction results in normalization or improvement of myocardial perfusion in the majority of patients with reversible and fixed perfusion defects by 201Tl scintigraphy. However, surgery may result in myocardial injury and scarring, with consequent decreased left ventricular ejection fraction in some patients.
Isolated presynaptic inotropic beta-adrenergic supersensitivity of the transplanted denervated human heart in vivo.
Authors: von Scheidt W , Böhm M , Schneider B , Reichart B , Erdmann E , Autenrieth G
Published: June 2012

BACKGROUND

The regulation of contractility of the transplanted heart depends on circulating catecholamines resulting from cardiac denervation. Supersensitivity to circulating catecholamines may result from loss of presynaptic neuronal uptake or upregulation of postsynaptic beta-adrenergic receptors.

METHODS AND RESULTS

Dose-response curves using the beta-adrenergic receptor agonists isoprenaline (no neuronal uptake) and epinephrine (neuronal uptake) were performed in vivo. The inotropic response was measured echocardiographically as the increase of fractional shortening (delta FS) and the increase of the systolic pressure/dimension ratio (delta P/D). The inotropic response to increasing doses of isoprenaline (5-20 ng/kg.min) was identical in 36 heart transplant recipients compared with 13 control subjects: delta FS during 20 ng/kg.min isoprenaline amounted to 18.2 +/- 6.2% versus 17.4 +/- 4.0% (NS) and delta P/D to 2.3 +/- 1.2 mm Hg/mm versus 2.2 +/- 0.5 mm Hg/mm (NS), respectively. A vagally mediated indirect negative inotropic effect in the innervated hearts was excluded by identical inotropic responses to isoprenaline in control subjects without and after atropine pretreatment. The inotropic response to increasing doses of epinephrine (10-40 ng/kg.min) was significantly augmented in 13 heart transplant recipients compared with 11 control subjects: delta FS during 40 ng/kg.min epinephrine amounted to 19.9 +/- 2.6% versus 8.6 +/- 2.0% (p less than 0.001) and delta P/D to 2.3 +/- 0.9 mm Hg/mm versus 0.6 +/- 0.3 mm Hg/mm (p less than 0.001), respectively. Pretreatment with desipramine (blockade of neuronal uptake) in control subjects resulted in a significantly increased inotropic response: delta FS during 40 ng/kg.min epinephrine amounted to 17.6 +/- 3.6% (p less than 0.001 versus untreated controls, NS versus heart transplant recipients) and delta P/D to 1.7 +/- 0.8 mm Hg/mm (p less than 0.001 versus untreated controls, NS versus heart transplant recipients).

CONCLUSIONS

These findings provide evidence against a postsynaptic inotropic supersensitivity or subsensitivity of the beta-adrenergic receptor-effector system of the transplanted denervated human heart in vivo. However, a marked presynaptic inotropic supersensitivity is present because of denervation-associated loss of neuronal catecholamine uptake.
High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation.
Authors: Ratnatunga C P , Edmondson S F , Rees G M , Kovacs I B
Published: June 2012

BACKGROUND

A unifying concept of explaining all pharmacological actions of aspirin by the irreversible blockage of the enzyme cyclooxygenase and therefore the inhibition of prostaglandin biosynthesis has left many unanswered questions.

METHODS AND RESULTS

Two hundred ninety-four patients taking 75 mg/day aspirin were tested 3 months after coronary artery bypass surgery. Platelet thromboxane formation (whole blood aggregation to arachidonate) was completely prevented in 80% of patients. Compared with matched healthy controls (n = 95), a significant platelet hyperreactivity was observed in patients (p less than 0.0001 versus less than 0.002). Ninety patients were advised to increase their daily dose of aspirin from 75 mg to 300 mg. Platelet reactivity retested 1 month after increasing the dose has significantly decreased (p = 0.0008; less than 0.0001), whereas it remained unchanged in those patients (n = 84) who continued with the same dose regimens. In normal subjects, ingestion of a single 600-mg aspirin significantly inhibited shear-induced platelet reaction.

CONCLUSIONS

It is concluded that aspirin does affect the platelet response to shear forces, but this requires higher dosage (greater than 300 mg/day), suggesting a mechanism probably different from that of interference with thromboxane formation.
Effect of alpha-adrenergic blockade with prazosin on large coronary diameter during exercise.
Authors: Baran K W , Bache R J , Dai X Z , Schwartz J S
Published: June 2012

BACKGROUND

Exercise-induced dilation of coronary resistance vessels is limited by alpha-adrenergic mechanisms. However, the effect of alpha-adrenergic mechanisms on large coronary arteries during exercise is not known.

METHODS AND RESULTS

In the present study, sonomicrometry was used to measure circumflex coronary arterial diameter during treadmill exercise before and after alpha 1-adrenergic blockade with prazosin in eight instrumented dogs. Before infusion of prazosin, exercise caused a fall in coronary vascular resistance (2.1 +/- 0.4 to 1.6 +/- 0.2 units, p less than 0.05) and dilation of the circumflex coronary artery (4.66 +/- 0.37 to 4.79 +/- 0.34 mm, p less than 0.05). Intracoronary infusion of prazosin during exercise caused a further decrease in coronary vascular resistance (1.6 +/- 0.2 to 1.4 +/- 0.2 units, p less than 0.05) and a further increase in circumflex coronary arterial diameter (4.79 +/- 0.34 to 4.83 +/- 0.34 mm, p less than 0.05). Intracoronary infusion of vehicle without prazosin during exercise did not cause a further decrease in coronary vascular resistance or increase in coronary diameter. Prazosin caused no significant increase in heart rate, aortic pressure, or coronary blood flow. Therefore, both small coronary resistance vessels and large epicardial coronary arteries dilated during exercise and dilated further after alpha-adrenergic blockade.

CONCLUSIONS

This finding indicates that alpha 1-adrenergic activity during exercise limits dilation of both large and small coronary arteries.
T wave changes persisting after ventricular pacing in canine heart are altered by 4-aminopyridine but not by lidocaine. Implications with respect to phenomenon of cardiac 'memory'.
Authors: del Balzo U , Rosen M R
Published: June 2012

BACKGROUND

Cardiac "memory" refers to changes in T wave polarity induced by ventricular pacing that persist long after resumption of normal atrioventricular conduction.

METHODS AND RESULTS

We studied the occurrence and mechanism of T wave changes in the open-chest anesthetized dog subjected to three discontinuous 20-minute periods of right ventricular pacing. ECG changes were recorded in the standard limb leads during normal conduction (prepacing) and three trains (T1, T2, and T3) of right ventricular pacing at a rate 50% higher than normal (pacing), each followed by a period of normal conduction (postpacing) lasting as long as necessary for T wave changes to return to control values. During each of these phases, heart rate, QRS, corrected QT (QTc) duration, and T wave amplitude were measured. In the first group (control), T wave inversions occurred during normal atrioventricular conduction after a period of right ventricular pacing. These T wave anomalies appeared in the absence of any change in heart rate, QRS, or QTc duration. The magnitude of the T wave amplitude change was significantly greater after each successive pacing period. Furthermore, the changes in T wave morphology persisted for a longer period after each successive pacing train. In a second experimental group, lidocaine, which depresses the sodium window current, was administered to six dogs that were subjected to the same pacing protocol. Lidocaine decreased the QTc interval and prolonged QRS duration but did not alter the magnitude of changes in T wave amplitude and time to recovery described in control animals during the three postpacing intervals. In contrast, in the third group, 4-aminopyridine, a drug that blocks the transient outward current (ito), abolished the changes in T wave morphology that occurred during any postpacing interval.

CONCLUSIONS

These results demonstrate that the manifestation of cardiac memory in the in situ dog heart is not altered by lidocaine but is abolished by 4-aminopyridine. Thus, cardiac memory may be based on a physiological property of the myocardium that is related to specific K+ channels.
Altered myocardial force-frequency relation in human heart failure.
Authors: Mulieri L A , Hasenfuss G , Leavitt B , Allen P D , Alpert N R
Published: June 2012

BACKGROUND

In congestive heart failure (idiopathic dilated cardiomyopathy), exercise is accompanied by a smaller-than-normal decrease in end-diastolic left ventricular volume, depressed peak rates of left ventricular pressure rise and fall, and depressed heart-rate-dependent potentiation of contractility (bowditch treppe). We studied contractile function of isolated left ventricular myocardium from New York Heart Association class IV-failing and nonfailing hearts at physiological temperature and heart rates in order to identify and quantitate abnormalities in myocardial function that underlie abnormal ventricular function.

METHODS AND RESULTS

The isometric tension-generating ability of isolated left ventricular strips from nonfailing and failing human hearts was investigated at 37 degrees C and contraction frequencies ranging from 12 to 240 per minute (min-1). Strips were dissected using a new method of protection against cutting injury with 2,3-butanedione monoxime (BDM) as a cardioplegic agent. In nonfailing myocardium the twitch tension-frequency relation is bell-shaped developing 25 +/- 2 mN/mm2 at a contraction frequency of 72 min-1 and peaking at 44 +/- 3.7 mN/mm2 at a contraction frequency of 174 +/- 4 min-1. In failing myocardium the peak of the curve occurs at lower frequencies between 6 and 120 min-1 averaging 81 +/- 22 min-1, and it develops 48% (p less than 0.001) and 80% (p less than 0.001) less tension than in nonfailing myocardium at 72 and 174 min-1, respectively. Between 60 and 150 min-1 tension increases by 107% in nonfailing myocardium, but it does not change significantly in failing myocardium. Peak rates of rise and fall of isometric twitch tension vary in parallel with twitch tension as stimulation frequency rises in nonfailing myocardium but not in failing myocardium.

CONCLUSIONS

The quantitative agreement between these results from isolated myocardium and those from catheterization laboratory measurements on intact humans suggest that alterations of myocardial origin, independent of systemic factors, may contribute to the above mentioned abnormalities in left ventricular function seen in dilated cardiomyopathy.
Sympathetic nervous function in human heart as assessed by cardiac spillovers of dihydroxyphenylglycol and norepinephrine.
Authors: Eisenhofer G , Esler M D , Meredith I T , Dart A , Cannon R O , Quyyumi A A , Lambert G , Chin J , Jennings G L , Goldstein D S
Published: June 2012

BACKGROUND

Measurement of cardiac norepinephrine spillover may indicate the amount of transmitter at neuroeffector sites but does not distinguish neuronal release or reuptake in determining this amount or provide information about other aspects of sympathetic function. This report examines how cardiac spillover of the norepinephrine metabolite dihydroxyphenylglycol (DHPG) provides additional distinct information about cardiac sympathetic function.

METHODS AND RESULTS

Arterial and coronary venous blood samples were taken during cardiac catheterization and intravenous infusion of [3H]norepinephrine in 57 subjects. Subjects were given intravenous yohimbine or underwent mental stress, handgrip exercise, and cycling exercise to activate sympathetic nerves or were given intravenous desipramine to block norepinephrine reuptake. Cardiac DHPG spillover (601 +/- 41 pmol/min) was eightfold greater than norepinephrine spillover (78 +/- 10 pmol/min) at rest and increased during sympathetic activation by 65% of the increase of norepinephrine. This and the desipramine-sensitive cardiac production of [3H]-labeled DHPG from [3H]norepinephrine indicated that 10.5 times more endogenous norepinephrine is recaptured than escapes into plasma; that more than 90% of recaptured norepinephrine is sequestered into storage vesicles; and that under resting conditions, most cardiac spillover of DHPG and turnover of norepinephrine are from metabolism of transmitter leaking from vesicles; the latter process is independent of exocytotic transmitter release with a rate at rest over 100-fold that of norepinephrine spillover and over 10-fold that of norepinephrine reuptake.

CONCLUSIONS

Cardiac spillover of DHPG provides information about processes close to or within sympathetic nerve endings that cannot be provided by measurements of norepinephrine spillover alone. This includes quantitative information about the role of neuronal uptake in terminating the actions of norepinephrine at neuroeffector sites and the importance of vesicular-axoplasmic exchange of norepinephrine as a dynamic process contributing to norepinephrine turnover.
Prevalence of circadian variations and spontaneous variability of cardiac disorders and ECG changes suggestive of myocardial ischemia in systemic arterial hypertension.
Authors: Zehender M , Meinertz T , Hohnloser S , Geibel A , Gerisch U , Olschewski M , Just H
Published: June 2012

BACKGROUND

Systemic hypertension is a well-known risk factor for coronary artery disease and sudden cardiac death. Recent interest focused on the presence of malignant ventricular arrhythmias (VA) and myocardial ischemia in hypertensive patients and provided a potential link for fatal tachyarrhythmic events.

METHODS AND RESULTS

We studied 150 untreated normokalemic hypertensive patients (56 +/- 9 years; 56 women and 94 men) without manifest coronary artery disease to determine prevalence, severity, and interaction of VA and significant ST segment changes induced by daily activities. One third of the patients were randomized to 4 weeks of placebo and restudied for spontaneous variability of the two parameters. All patients were included in a 3-year follow-up study. VA were observed in 129 of 150 hypertensive patients (86%) and peaked in the early morning and late afternoon. Twenty-two patients (15%) had ventricular pairs, and 20 patients (13%) had nonsustained ventricular tachycardia. Transient ST segment depression observed in 47 patients (33%; mean incidence, 2.7 +/- 0.8 episodes/24 hr) showed a characteristic circadian variation similar to VA and were asymptomatic in 93% of the episodes. At the time of transient ST segment depression, VA increased 4.6 times (p less than 0.01). After 4 weeks of placebo, marked variations in the incidence of VA (VA suppression rate -100%, or increase greater than 400%) were observed in 29% of the patients, and in 60% of all patients repetitive VA were present in only one of the two Holter recordings. Day-and-night variations of VA and transient ST segment changes were highly reproducible during the placebo period. After 3 years of follow-up, eight of 146 patients (5%) had suffered myocardial infarction, and five patients had died from cardiac events (three patients died from sudden cardiac death). Logistic regression analysis revealed left ventricular hypertrophy (relative risk, 6.1; p less than 0.01) and transient ST segment abnormalities during daily activities (relative risk, 4.4; p less than 0.05) to be of independent prognostic significance to predict cardiac events during follow-up instead of repetitive VA (relative risk, 1.3; NS).

CONCLUSIONS

VA associated with a high spontaneous variability and predominantly asymptomatic transient ST segment changes are common in hypertensives; the interaction of both risk factors may provide an important link for fatal VA. Antiarrhythmic therapy is not to be recommended in the majority of patients. Presence of left ventricular hypertrophy and transient ST segment changes were the most powerful predictors of cardiac events during the follow-up.
Baseline fibrinolytic state and the risk of future venous thrombosis. A prospective study of endogenous tissue-type plasminogen activator and plasminogen activator inhibitor.
Authors: Ridker P M , Vaughan D E , Stampfer M J , Manson J E , Shen C , Newcomer L M , Goldhaber S Z , Hennekens C H
Published: June 2012

BACKGROUND

Although isolated abnormalities of plasminogen activation and inhibition have been reported among selected patients with venous thrombosis, it is unclear whether these deficiencies of fibrinolysis are important risk factors for thromboembolic disease.

METHODS AND RESULTS

To evaluate whether baseline levels of endogenous tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) predict the future occurrence of venous thrombosis, levels of these proteins were measured in prospectively collected plasma samples from 55 participants in the Physicians' Health Study who later developed deep venous thrombosis or pulmonary embolism and from an equal number of age- and smoking-matched control subjects who remained free of vascular disease during a mean follow-up period of 60.2 months. Overall, there were no statistically significant differences between case patients and control subjects in baseline levels of PAI-1 (50.5 versus 59.5 ng/ml, p = 0.26), t-PA (13.4 versus 13.3 ng/ml, p = 0.94), or PAI-1:t-PA ratio (6.84 versus 6.58, p = 0.82). No evidence of a threshold effect or trend was seen when these data were analyzed by increasing quartiles of PAI-1 (p = 0.73), t-PA (p = 0.62), or PAI-1:t-PA ratio (p = 0.93). These results were unchanged after multivariate analysis that simultaneously controlled for other baseline cardiovascular risk factors.

CONCLUSIONS

In contrast to previous uncontrolled case series and smaller retrospective studies, these prospective data provide strong evidence that baseline fibrinolytic state, as measured by t-PA and PAI-1, does not predict the occurrence of future venous thrombosis.
Echo-wave termination of ventricular tachycardia. A common mechanism of termination of reentrant arrhythmias by various pharmacological interventions.
Authors: Brugada J , Boersma L , Abdollah H , Kirchhof C , Allessie M
Published: June 2012

BACKGROUND

Based on epicardial mapping, different mechanisms of termination of reentrant ventricular tachycardia by various pharmacological interventions are described.

METHODS AND RESULTS

In 40 Langendorff-perfused rabbit hearts, rings of anisotropic left ventricular epicardium were made by a cryoprocedure. Sustained monomorphic ventricular tachycardia based on continuous circus movement of the impulse around the ring was induced by programmed stimulation. Increasing doses of heptanol (n = 10), potassium (n = 10), tetrodotoxin (n = 6), RP62719 (a new class III drug) (n = 4), flecainide (n = 5), and propafenone (n = 5) were administered to terminate ventricular tachycardia. Epicardial mapping (248 points) was used to study the mechanism of termination of ventricular tachycardia. In 28 of 40 hearts, ventricular tachycardia terminated because the drugs produced complete conduction block of the impulse in a segment of the reentrant pathway. In the remaining 12 hearts (heptanol, n = 2; potassium, n = 3; tetrodotoxin, n = 2; RP62719, n = 2; flecainide, n = 1; and propafenone, n = 2), termination of ventricular tachycardia occurred by collision of the circulating impulse with a spontaneous antidromic wave front reflected within the circuit. This phenomenon occurred when the circulating impulse encountered an arc of functional conduction block that did not extend along the whole width of the ring. As a result, the impulse dissociated into a continuing orthodromic circulating wave and a returning antidromic echo-wave caused by microreentry within the ring.

CONCLUSIONS

Independent of their mechanisms of action, sodium channel blockers, electrical uncouplers, and class III drugs terminate reentrant ventricular tachycardia either by complete conduction block or by collision of the impulse with an echo-wave.
In vivo lymphocyte-mediated myocardial injuries demonstrated by adoptive transfer of experimental autoimmune myocarditis.
Authors: Kodama M , Matsumoto Y , Fujiwara M
Published: June 2012

BACKGROUND

To elucidate the mechanisms of immune-related myocardial injuries, we examined whether autoimmune myocarditis was passively transferable by use of humoral or cellular factors.

METHODS AND RESULTS

Active myocarditis was elicited in Lewis rats by immunization with human cardiac myosin fraction in complete Freund's adjuvant. This experimental myocarditis was characterized by macroscopic features such as pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac surface. Histologically, extensive myocardial necrosis and numerous inflammatory cell infiltrations were observed. Interestingly, multinucleated giant cells were frequently observed in the lesions. Transfer of the disease by the humoral factor was examined by use of fresh sera and immunoglobulin fraction of pooled sera from rats with severe myocarditis, and transfer by the cellular factor was tested by use of spleen cells and lymph node cells from the diseased rats. When naive Lewis rats were given 15.75 mg of immunoglobulin fraction, no particular change was observed in the hearts. Fresh sera also could not elicit myocarditis in recipient rats. In contrast, intravenous injection of spleen cells or lymph node cells that were cultured for 3 days in the presence of 1 microgram/ml of concanavalin A elicited severe myocarditis. The macroscopic and microscopic findings of passively transferred myocarditis are essentially the same as those found in actively induced myocarditis. Multinucleated giant cells were also observed in the lesions of transferred myocarditis.

CONCLUSIONS

This study demonstrates direct evidence for in vivo lymphocyte-mediated myocardial injuries.
Cost and health implications of cholesterol lowering.
Authors: Goldman L , Gordon D J , Rifkind B M , Hulley S B , Detsky A S , Goodman D W , Kinosian B , Weinstein M C
Published: June 2012

BACKGROUND

A broad, scientific consensus supports the role of cholesterol as a risk factor for coronary heart disease and agrees that lowering cholesterol levels will reduce coronary heart disease incidence. Cost-effectiveness analysis is a potentially powerful method for measuring the benefits to be achieved by expenditures of health care dollars.

METHODS AND RESULTS

The literature related to the effectiveness and cost-effectiveness of cholesterol lowering was reviewed. Application of cost-effectiveness methodology to the question of cholesterol reduction generally supports the use of population-wide educational programs and the aggressive use of cholesterol-lowering therapy for the secondary prevention of subsequent coronary events in persons with preexisting coronary heart disease. For primary prevention, however, therapy with medication has a favorable cost-effectiveness ratio only in identifiable high-risk persons, and the different costs of the various available medications should be taken into account. Therapy with medications, especially for primary prevention, would be more appealing if the price of the available medications were lower.

CONCLUSIONS

High priority should be given to research that could validate these cost-effectiveness projections as well as to further studies of the elderly and women, in whom direct data on the precise costs, risks, and benefits of interventions to lower cholesterol remain sparse.
In vivo assessment of vascular pathology resulting from laser irradiation. Analysis of 23 patients studied by directional atherectomy immediately after laser angioplasty.
Authors: Isner J M , Rosenfield K , White C J , Ramee S , Kearney M , Pieczek A , Langevin R E , Razvi S
Published: June 2012

BACKGROUND

The pathological consequences of cardiovascular laser irradiation have been studied extensively in vitro. Previous in vivo studies of laser-induced injury have included analyses of acute and/or chronic findings in experimental animals. Little information, however, is available regarding the acute effects of laser irradiation of human vascular tissues in vivo.

METHODS AND RESULTS

To determine the acute pathology resulting from laser irradiation of human vascular tissue in vivo, specimens retrieved from 23 patients by directional atherectomy immediately after laser angioplasty (19 peripheral and four coronary) were examined by light microscopy. Of the 23 patients, three (13.0%) were treated with a metal-capped ("hot-tip") fiber coupled to a continuous-wave neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using up to 18 W power and 18-305 seconds of cumulative exposure time; in all three patients (100%), thermal injury, including frank charring several cell layers thick, was seen along the luminal borders of the atherectomy specimen. In eight of the 23 patients (34.5%), laser angioplasty was performed using a 250-microseconds holmium:YAG laser at fluences up to 2,300 mJ/mm2, a repetition rate of 5 Hz, and 25-200 seconds of cumulative exposure; in seven of eight patients (85.5%), the atherectomy specimen showed signs of vacuolar injury consisting of central and satellite Alcian-blue-negative vacuoles. In two patients (25.0%), there was a "smudged" or "shredded" edge, whereas in one patient, frank signs of thermal injury were observed. Finally, in 12 of the 23 patients (52.2%), laser angioplasty was performed using a 120-nsec excimer laser at fluences up to 60 mJ/mm2, a repetition rate of 25 Hz, and a cumulative exposure time of 21-315 seconds. Pathological findings among these 12 patients were limited to nine patients (75%) in whom a weakly basophilic, smudged, and/or shredded appearance approximately one cell layer thick was observed along the luminal border of the atherectomy specimen and two patients (16.7%) with small foci of vacuolar injury. None of the atherectomy specimens retrieved after excimer laser angioplasty disclosed signs of thermal injury.

CONCLUSIONS

These findings document that acute pathological alterations resulting from in vivo laser angioplasty are variable, depending on the laser source used, and are similar to that predicted by experimental studies performed previously in vitro. The prognostic implications of these varying pathological features remain to be clarified.
Suppression of longitudinal versus transverse conduction by sodium channel block. Effects of sodium bolus.
Authors: Turgeon J , Wisialowski T A , Wong W , Altemeier W A , Wikswo J P , Roden D M
Published: June 2012

BACKGROUND

Arrhythmias resulting from treatment with sodium channel-blocking antiarrhythmic drugs have been successfully treated with sodium infusion, although the mechanism underlying this effect is uncertain.

METHODS AND RESULTS

In this study, we used a multielectrode array to examine the effects of O-desmethyl encainide (ODE), a potent sodium channel-blocking metabolite of encainide, on conduction in canine ventricle. ODE depressed both longitudinal and transverse conduction velocities in a plasma concentration-related fashion (r = -0.74, -0.60; p less than 0.001). At ODE concentrations less than or equal to 300 ng/ml (n = 34), conduction velocity was depressed to the same extent in the longitudinal (-21.9 +/- 8.4%, SD) and transverse orientations (-22.0 +/- 8.8%). However, at concentrations greater than 300 ng/ml (n = 17), conduction was significantly more impaired longitudinally than transversely (-44.5 +/- 11.7% versus -34.4 +/- 13.7%, p less than 0.02). In 12 animals with high concentrations (mean, 432 +/- 32 ng/ml), a 5-meq/kg bolus of sodium chloride over 1 minute immediately increased conduction velocity; this effect was significantly greater and longer lasting in the longitudinal orientation. In two animals, conduction block in the longitudinal orientation was documented at high plasma ODE and was immediately reversed by sodium bolus.

CONCLUSIONS

We conclude that the major effect of sodium in animals with excess sodium channel block is improvement of longitudinal propagation; this effect may underlie the antiarrhythmic action of sodium in the analogous clinical setting.
Microinjection of antibodies and expression vectors into living myocardial cells. Development of a novel approach to identify candidate genes that regulate cardiac growth and hypertrophy.
Authors: Shubeita H E , Thorburn J , Chien K R
Published: June 2012

BACKGROUND

Microinjection approaches in the cardiac cell context have allowed delivery of various calcium dyes and monitoring of short-term physiological responses. However, unlike other cell types, it has proved difficult to microinject myocardial cells without the concomitant loss of long-term cell viability.

METHODS AND RESULTS

An analysis of experimental variables was conducted to adapt microinjection techniques to the neonatal rat ventricular cell context. Among the variables optimized were the selection of culture dishes, plating substrate, microinjection parameters, and a variety of maneuvers to inhibit myocyte hypercontracture, injury, and consequent death after micropuncture. With the modified technique, the percentage of injected cells that maintained long-term viability (48 hours) increased from less than 1% to 30%. Similarly, an increased efficiency of gene transfer and expression (measured as the percentage of injected cells that express the delivered gene) was obtained after either cytoplasmic or nuclear injection of a beta-galactosidase expression vector into cardiac myocytes. Microinjection of marker immunoglobulin G does not interfere with the induction of the hypertrophic response or the expression of a coinjected atrial natriuretic factor promoter-luciferase reporter fusion gene construct.

CONCLUSIONS

To the best of our knowledge, this study provides the first description of the efficient microinjection of neonatal cardiac muscle cells with maintenance of long-term cell viability. The microinjection technique is now a viable approach to examine cause-and-effect relations between specific gene products and any defined feature or response of cardiac myocytes that can be assayed at a single-cell level.
Preconditioning does not attenuate myocardial stunning.
Authors: Ovize M , Przyklenk K , Hale S L , Kloner R A
Published: June 2012

BACKGROUND

Despite numerous reports that one or more episodes of brief coronary artery occlusion preconditions the myocardium and dramatically reduces myocardial infarct size produced by a subsequent prolonged ischemia, we recently demonstrated that preconditioning does not attenuate contractile dysfunction in the peri-infarct tissue. However, the specific effects of preconditioning on myocardium in which wall motion has not been compromised by the preconditioning regimen per se and is further submitted to a short ischemic insult (that is, not confounded by necrosis) remain unknown.

METHODS AND RESULTS

We addressed these issues in the canine model of myocardial stunning. Eighteen anesthetized dogs underwent 15 minutes of coronary occlusion followed by 3 hours of reperfusion. Before the 15-minute coronary occlusion, each dog received one of three treatments: no intervention (control group, n = 6), one episode of 5-minute coronary occlusion/5-minute reperfusion (PC5 group, n = 6), or one episode of 2.5-minute coronary occlusion/5-minute reperfusion (PC2.5 group, n = 6). Segment shortening (SS) in the ischemic/reperfused midmyocardium was monitored by sonomicrometry, and myocardial blood flow was assessed by injection of radiolabeled microspheres. All three groups were equally ischemic during the 15-minute coronary occlusion: Midmyocardial blood flow averaged 0.05 +/- 0.02, 0.07 +/- 0.04, and 0.08 +/- 0.03 ml/min/g in control, PC2.5, and PC5 groups, respectively. Before the 15-minute coronary occlusion, PC5 dogs exhibited significant stunning (SS = 55% baseline; p less than 0.01 versus control), whereas PC2.5 dogs did not (SS = 91% baseline; p = NS versus control). However, segment shortening during the subsequent 15-minute coronary occlusion was equally depressed at -25% to -42% of baseline values among the three groups. Furthermore, all three groups demonstrated a similar degree of stunning after reperfusion: SS at 3 hours after reflow averaged 24 +/- 12%, 34 +/- 16%, and 48 +/- 12% of baseline in control, PC2.5, and PC5 groups, respectively (p = NS). The degree of recovery of function after reperfusion correlated with the amount of midmyocardial blood flow during coronary artery occlusion. However, this relation was not different among the three groups: Specifically, for any given collateral flow during ischemia, preconditioning did not reduce the degree of stunning.

CONCLUSIONS

Preconditioning neither preserves contractile function during a reversible ischemic insult nor prevents myocardial stunning during the initial hours of reflow.
Effect of pulse separation between two sequential biphasic shocks given over different lead configurations on ventricular defibrillation efficacy.
Authors: Johnson E E , Alferness C A , Wolf P D , Smith W M , Ideker R E
Published: June 2012

BACKGROUND

Two sequential biphasic shocks delivered over separate lead configurations markedly improve defibrillation efficacy compared with a single shock alone. We investigated the effect of varying the intershock interval between sequential biphasic shocks on defibrillation.

METHODS AND RESULTS

Defibrillation thresholds (DFTs) were obtained in six dogs for shock separations ranging from 0.2 to 125 msec. The first shock was given from a catheter electrode in the right ventricular apex to a patch on the left lateral thorax; the second was from a small patch on the left ventricular apex to a catheter electrode in the right ventricular outflow tract. When the interval between shocks was less than or equal to 10 msec or greater than or equal to 75 and less than or equal to 125 msec, the mean DFTs were less than that previously found for the first shock by itself (4.2 versus 7.4 J, p = 0.002). At a separation of 50 msec, however, there was a marked rise in the DFT to 27 J. The mean DFT for the second shock at a delay of 50 msec was not different from the mean DFT previously found for the second shock by itself (7.2 versus 7.0 J). These results were confirmed in another six dogs using defibrillation probability-of-success curves. In 12 other dogs, probability-of-success curves were generated for delays between shocks as a percentage of the activation interval during ventricular fibrillation. Minimum defibrillation energy requirements were at two separations, 0.2 msec and 90% of the activation interval.

CONCLUSIONS

The optimal intershock interval between two sequential biphasic shocks is either less than or equal to 10 msec or greater than or equal to 75 and less than or equal to 125 msec. The marked rise in the DFT at a shock separation of 50 msec, requiring more energy than that for the first shock alone, suggests that the second shock at this time delay is likely to reinduce fibrillation after it is halted by the first shock until the second shock is strong enough to defibrillate independently of the first shock.
Doppler assessment of prosthetic valve orifice area. An in vitro study.
Authors: Baumgartner H , Khan S S , DeRobertis M , Czer L S , Maurer G
Published: June 2012

BACKGROUND

Although Doppler echocardiography has been shown to be accurate in assessing stenotic orifice areas in native valves, its accuracy in evaluating the prosthetic valve orifice area remains undetermined.

METHODS AND RESULTS

Doppler-estimated valve areas were studied for their agreement with catheter-derived Gorlin effective orifice areas and their flow dependence in five sizes (19/20-27 mm) of St. Jude, Medtronic-Hall, and Hancock aortic valves using a pulsatile flow model. Doppler areas were calculated three ways: using the standard continuity equation; using its simplified modification (peak flow/peak velocity); and using the Gorlin equation with Doppler pressure gradients. The results were compared with Gorlin effective orifice areas derived from direct flow and catheter pressure measurements. Excellent correlation between Gorlin effective orifice areas and the three Doppler approaches was found in all three valve types (r = 0.93-0.99, SEE = 0.07-0.11 cm2). In Medtronic-Hall and Hancock valves, there was only slight underestimation by Doppler (mean difference, 0.003-0.25 cm2). In St. Jude valves, however, all three Doppler methods significantly underestimated effective orifice areas derived from direct flow and pressure measurements (mean difference, 0.40-0.57 cm2) with differences as great as 1.6 cm2. In general, the modified continuity equation calculated the largest Doppler areas. When orifice areas were calculated from the valve geometry using the area determined from the inner valve diameter reduced by the projected area of the opened leaflets, Gorlin effective orifice areas were much closer to the geometric orifice areas than Doppler areas (mean difference, 0.40 +/- 0.31 versus 1.04 +/- 0.20 cm2). In St. Jude and Medtronic-Hall valves, areas calculated by either technique did not show a consistent or clinically significant flow dependence. In Hancock valves, however, areas calculated by both the continuity equation and the Gorlin equation decreased significantly (p less than 0.001) with low flow rates.

CONCLUSIONS

Doppler echocardiography using either the continuity equation or Gorlin formula allows in vitro calculation of Medtronic-Hall and Hancock effective valve orifice areas but underestimates valve areas in St. Jude valves. This phenomenon is due to localized high velocities in St. Jude valves, which do not reflect the mean velocity distribution across the orifice. Valve areas are flow independent in St. Jude and Medtronic-Hall prostheses but decrease significantly with low flow in Hancock valves, suggesting that bioprosthetic leaflets may not open fully at low flow rates.
Coronary reserve and exercise ECG in patients with chest pain and normal coronary angiograms.
Authors: Camici P G , Gistri R , Lorenzoni R , Sorace O , Michelassi C , Bongiorni M G , Salvadori P A , L'Abbate A
Published: June 2012

BACKGROUND

Coronary vasodilator reserve is reduced in some patients with a history of chest pain and angiographically normal coronary arteries. ECG changes suggestive of myocardial ischemia during exercise also can be demonstrated in a subset of these patients.

METHODS AND RESULTS

We have investigated the correlation between coronary vasodilator reserve, assessed with 13N-labeled ammonia and positron emission tomography, and the ECG during exercise stress in 45 patients with a history of chest pain, angiographically normal coronary arteries, and a negative ergonovine test. ST segment depression on the ECG during exercise was present in 29 of 45 patients. Mean resting left ventricular blood flow was 1.04 +/- 0.22 ml.min-1.g-1; it increased to 1.32 +/- 0.47 ml.min-1.g-1 (p less than 0.01 versus baseline value) during atrial pacing and to 2.52 +/- 0.96 ml.min-1.g-1 (p less than 0.01 versus baseline value) after dipyridamole (0.56 mg/kg i.v.). No regional flow defects could be demonstrated in any patient during pacing or after dipyridamole. Myocardial flows after dipyridamole, however, did not show a normal frequency distribution (Kolmogorov-Smirnov test), and two patient populations could be identified. Twenty-nine (67%) patients had a mean left ventricular flow of 3.02 +/- 0.33 ml.min-1.g-1 after dipyridamole (range, 2.13-5.46 ml.min-1.g-1), and 14 (33%) patients had a mean flow of 1.48 +/- 0.29 ml.min-1.g-1 (range, 1.06-2.04 ml.min-1.g-1, p less than 0.01 versus the "high-flow group").

CONCLUSIONS

Approximately one third of patients in our series showed a reduced coronary vasodilator reserve. Although 12 of 14 patients in the "low-flow group" had ST segment depression during exercise stress, 16 of 29 patients in the high-flow group also had ST segment depression during exercise stress. Therefore, despite a good sensitivity (86%) in identifying patients with a blunted increment of coronary flow, the ECG response during exercise stress appears to have a rather low specificity (45%). This suggests that factors other than reduced coronary reserve and myocardial ischemia may play a role in the genesis of the ST segment depression in these patients.
Lumen diameter of normal human coronary arteries. Influence of age, sex, anatomic variation, and left ventricular hypertrophy or dilation.
Authors: Dodge J T , Brown B G , Bolson E L , Dodge H T
Published: June 2012

BACKGROUND

Precise knowledge of the expected "normal" lumen diameter at a given coronary anatomic location is a first step toward developing a quantitative estimate of coronary disease severity that could be more useful than the traditional "percent stenosis."

METHODS AND RESULTS

Eighty-three arteriograms were carefully selected from among 9,160 consecutive studies for their smooth lumen borders indicating freedom from atherosclerotic disease. Of these, 60 men and 10 women had no abnormalities of cardiac function, seven men had idiopathic dilated cardiomyopathy, and six men had left ventricular hypertrophy associated with significant aortic stenosis. Lumen diameter was measured at 96 points in 32 defined coronary segments or major branches. Measurements were scaled to the catheter, corrected for imaging distortion, and had a mean repeat measurement error of 0.12 mm. When sex, anatomic dominance, and branch length were accounted for, normal lumen diameter at each of the standard anatomic points could usually be specified with a population variance of +/- 0.6 mm or less (SD) and coefficient of variation of less than 0.25 (SD/mean). For example, the left main artery measured 4.5 +/- 0.5 mm, the proximal left anterior descending coronary artery (LAD) 3.7 +/- 0.4 mm, and the distal LAD 1.9 +/- 0.4 mm. For the LAD, lumen diameter was not affected by anatomic dominance (right versus left), but for the right coronary artery, proximal diameter varied between 3.9 +/- 0.6 and 2.8 +/- 0.5 mm (p less than 0.01) and for the left circumflex, between 3.4 +/- 0.5 and 4.2 +/- 0.6 mm (p less than 0.01). Women had smaller epicardial arterial diameter than men (-9%; p less than 0.001), even after normalization for body surface area (p less than 0.01). Branch artery caliber was unaffected by the anatomic dominance but increased with branch length, expressed as a fraction of the origin-to-apex distance (p less than 0.001). Lumen diameter was not affected by age or by vessel tortuosity but was significantly increased among men with left ventricular hypertrophy (+ 17%; p less than 0.001) or dilated cardiomyopathy (+ 12%; p less than 0.001).

CONCLUSIONS

This is a reference normal data set against which to compare lumen dimensions in various pathological states. It should be of particular value in the investigation of diffuse atherosclerotic disease.
Balloon mitral commissurotomy after previous surgical commissurotomy. The National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry participants.
Authors: Davidson C J , Bashore T M , Mickel M , Davis K
Published: June 2012

BACKGROUND

Mitral restenosis after surgical mitral commissurotomy often occurs within 5-15 years, necessitating a repeat procedure. Balloon mitral commissurotomy (BMC) has been advocated as an alternative to repeat surgery for mitral restenosis.

METHODS AND RESULTS

The purposes of this study are to determine the short- and intermediate-term outcomes of patients undergoing BMC after previous surgical commissurotomy, to compare these patients with those undergoing balloon mitral commissurotomy as an initial procedure, and to elucidate the multivariate determinants of acute procedural and clinical outcome. Of 738 patients undergoing BMC as part of the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry, 133 underwent BMC after previous surgical mitral commissurotomy. Prospective data obtained included demographic, hemodynamic, echocardiographic, and clinical follow-up. BMC after previous surgical commissurotomy produced a significant reduction in transvalvular gradient from 13 +/- 5 to 6 +/- 3 mm Hg (p less than 0.0001) and an increase in mitral valve area from 1.0 +/- 0.3 to 1.8 +/- 0.8 cm2 (p less than 0.0001). BMC as an initial procedure increased valve area from 1.0 +/- 0.4 to 2.0 +/- 0.8 cm2 (p less than 0.0001) (p = 0.03 versus prior surgery). Baseline characteristics including mitral valve echo score were similar for both groups. Comparing 6-month status in patients with prior surgery to those without, 80% versus 90% were New York Heart Association (NYHA) functional class I or II (p = 0.004). Mortality was similar. In patients with previous mitral valve surgery, multivariate predictors of improvement in 6-month clinical status included the experience of the center (p = 0.006), lower echocardiographic score (p = 0.001), and lower left ventricular end-diastolic pressure (p = 0.008). Multivariate determinants of a final mitral valve area greater than or equal to 1.5 cm2 were a lower baseline NYHA functional class (p = 0.003) and lower mitral valve echocardiographic score (p = 0.008).

CONCLUSIONS

BMC after previous surgical mitral commissurotomy results in similar hemodynamic changes as in patients undergoing BMC as an initial procedure. Symptomatic improvement at 6 months is slightly less frequent in prior commissurotomy patients. Patients with favorable valvular morphology and preserved left ventricular function who undergo BMC in experienced centers are most likely to achieve symptomatic improvement after previous surgical commissurotomy. In general, BMC is an effective treatment for mitral restenosis after previous surgical commissurotomy.