bluuebunny/crossref_metadata_2025 huggingface dataset:
Can serial exercise testing improve the prediction of coronary events in asymptomatic individuals?
Authors: Josephson R A , Shefrin E , Lakatta E G , Brant L J , Fleg J L
Published: June 2011

An abnormal ST segment response to treadmill exercise has a low predictive value for future coronary events (angina pectoris, nonfatal myocardial infarction, or cardiac death) in apparently healthy individuals. To determine whether the conversion from a normal to an abnormal ST segment response might identify individuals at high risk for a future coronary event, we analyzed the results of serial exercise tests performed at 2-4-year intervals in 726 male and female volunteers, aged 22-84 years (mean, 55.1 years), from the Baltimore Longitudinal Study of Aging (BLSA). All subjects were free of cardiovascular disease at entry by history, physical examination, and resting 12-lead electrocardiogram. Over a mean overall follow-up of 7.4 years, coronary events occurred in 34 of 178 (19.1%) of those with an abnormal ST response to exercise versus 30 of 548 (5.5%) in those with a normal response (p = 0.001). Angina pectoris was the most common presenting coronary event regardless of ST segment exercise response. Among individuals with an abnormal ST segment response, the incidence of events was virtually identical between those with an initially abnormal response (group 1) and those who converted from a normal to an abnormal response (group 2), 19.8% versus 18.5%. After adjustment for standard coronary risk factors by proportional hazards regression analysis, the risk of a coronary event relative to subjects with persistently normal ST segment responses (group 3) remained nearly identical in the two groups, 2.72 in group 1 (p less than 0.003) and 2.80 in group 2 (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
Quantification of jet flow by momentum analysis. An in vitro color Doppler flow study.
Authors: Thomas J D , Liu C M , Flachskampf F A , O'Shea J P , Davidoff R , Weyman A E
Published: June 2011

Previous investigations have shown that the size of a regurgitant jet as assessed by color Doppler flow mapping is independently affected by the flow rate and velocity (or driving pressure) of the jet. Fluid dynamics theory predicts that jet momentum (given by the orifice flow rate multiplied by velocity) should best predict the appearance of the jet in the receiving chamber and also that this momentum should remain constant throughout the jet. To test this hypothesis, we measured jet area versus driving pressure, flow rate, velocity, orifice area, and momentum and showed that momentum is the optimal jet parameter: jet area = 1.25 (momentum).28, r = 0.989, p less than 0.0001. However, the very curvilinear nature of this function indicated that chamber constraint strongly affected jet area, which limited the ability to predict jet momentum from observed jet area. To circumvent this limitation, we analyzed the velocities per se within the Doppler flow map. For jets formed by 1-81-mm Hg driving pressure through 0.005-0.5-cm2 orifices, the velocity distribution confirmed the fluid dynamic prediction: Gaussian (bell-shaped) profiles across the jet at each level with the centerline velocity decaying inversely with distance from the orifice. Furthermore, momentum was calculated directly from the flow maps, which was relatively constant within the jet and in good agreement with the known jet momentum at the orifice (r = 0.99). Finally, the measured momentum was divided by orifice velocity to yield an accurate estimate of the orifice flow rate (r = 0.99). Momentum was also divided by the square of velocity to yield effective orifice area (r = 0.84). We conclude that momentum is the single jet parameter that best predicts the color area displayed by Doppler flow mapping. Momentum can be measured directly from the velocities within the flow map, and when combined with orifice velocity, momentum provides an accurate estimate of flow rate and orifice area.
Effects of nitroprusside on myocardial blood flow and oxygen consumption in conscious lambs with an aortopulmonary left-to-right shunt.
Authors: Toorop G P , Hardjowijono R , Dalinghaus M , Gerding A M , Koers J H , Zijlstra W G , Kuipers J R
Published: June 2011

We studied the effect of vasodilation on regional myocardial blood flow and oxygen consumption of the left ventricular free wall by infusing 10 micrograms/kg/min sodium nitroprusside into 7-week-old conscious lambs with and without aortopulmonary left-to-right shunts. Resting myocardial oxygen consumption in the 13 shunt lambs was significantly higher than in the nine control lambs (989 +/- 104 [+/- SEM] vs. 432 +/- 41 mumol/min/100 g left ventricle). This was achieved by a significantly higher left ventricular myocardial blood flow (294 +/- 33 vs. 143 +/- 16 ml/min/100 g left ventricle) because the arteriovenous oxygen concentration difference across the left ventricular free wall was similar in shunt and control lambs. Infusion of nitroprusside did not significantly change myocardial oxygen consumption and regional myocardial blood flows at 10 and 50 minutes after the onset of the infusion. This occurred despite a substantial drop in aortic and left atrial pressures and stroke volume, which decreases wall stress as well as external work of the left ventricle. Heart rate, however, increased significantly. We postulate that, during infusion of nitroprusside, the potential decrease in myocardial oxygen consumption due to a decrease in wall stress and external work of the left ventricle is neutralized by the consequences of the increased heart rate. In view of this and because of its hemodynamic effects, we do not consider sodium nitroprusside useful in the treatment of circulatory congestion in patients with left-to-right shunts, normal arterial pressures, and normal systemic blood flows.
Flunarizine allows differentiation between mechanisms of arrhythmias in the intact heart.
Authors: Vos M A , Gorgels A P , Leunissen J D , Wellens H J
Published: June 2011

The calcium antagonist flunarizine suppresses pathologic accumulation of calcium intracellularly without affecting the fast sodium or the slow calcium channel. To establish its value in differentiating between mechanisms of arrhythmias in the canine heart, the effect of flunarizine was investigated on ventricular tachycardia (VT) induced by ouabain intoxication or occurring 16-24 hours after occlusion of the left anterior descending coronary artery. Four groups of dogs were studied. Group 1 consisted of 13 animals with VT induced by ouabain intoxication (triggered-activity group). Group 2 included nine dogs in whom VT developed 16-24 hours after occlusion of the left anterior descending coronary artery (abnormal automaticity group). Group 3 included six dogs with normally conducted sinus beats, whereas group 4 consisted of six animals having a ventricular escape rhythm. With the exception of group 3, all dogs had surgically induced complete atrioventricular block. All animals were studied while conscious and without premedication. In groups 1 and 2, 2-3 mg/kg flunarizine was given intravenously after VT had persisted for at least 20 minutes. In groups 3 and 4, 2 mg/kg flunarizine was given after the rhythm was registered for 20 minutes. The cycle lengths of the different rhythms were compared before and after flunarizine. In group 1, flunarizine increased the cycle length of the VT from 300 +/- 30 to 410 +/- 50 msec (p less than or equal to 0.001). Termination of VT was seen in 11 out of 13 animals. In group 2, flunarizine resulted in a nonsignificant shortening of the RR interval from 450 +/- 60 to 440 +/- 60 msec. Persistent termination was observed in only one of nine dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers.
Authors: Fleg J L , Gerstenblith G , Zonderman A B , Becker L C , Weisfeldt M L , Costa P T , Lakatta E G
Published: June 2011

Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardiac events developed in 9.8% of subjects and consisted of 20 cases of new angina pectoris, 13 myocardial infarctions, and seven deaths. Events occurred in 7% of individuals with both negative 201Tl and ECG, 8% of those with either test positive, and 48% of those in whom both tests were positive (p less than 0.001). By proportional hazards analysis, age, hypertension, exercise duration, and a concordant positive ECG and 201Tl result were independent predictors of coronary events. Furthermore, those with positive ECG and 201Tl had a 3.6-fold relative risk for subsequent coronary events, independent of conventional risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Factors associated with pericardial effusion in acute Q wave myocardial infarction.
Authors: Sugiura T , Iwasaka T , Takayama Y , Matsutani M , Hasegawa T , Takahashi N , Inada M
Published: June 2011

To elucidate the clinical characteristics associated with pericardial effusion in the early phase of myocardial infarction, 330 patients with acute Q wave infarction were studied. According to echocardiography, 83 patients had pericardial effusion on the third day of hospitalization, and careful auscultation revealed that a pericardial rub was absent in 45 patients and was present in 38 patients. Based on seven clinical variables, multivariate analysis was performed to determine the important variables related to the occurrence of pericardial effusion with and without pericardial rub. Pulmonary capillary wedge pressure and left ventricular segments with advanced asynergy were the significant factors related to the occurrence of pericardial effusion without a pericardial rub. The presence of ventricular aneurysmal motion, left ventricular segments with advanced asynergy, and alveolar arterial oxygen difference were related to pericardial effusion with a pericardial rub. Therefore, a hemodynamic factor was the major mechanism associated with the increase in extravascular myocardial fluid and the consequent occurrence of hydropericardia in the absence of a pericardial rub, whereas an increase in the microvascular permeability in the myocardium with excessive fluid exudating through the irritated epicardial surface was the mechanism related to pericardial effusion with a pericardial rub in the early phase of acute myocardial infarction.
Continuous 24-hour assessment of the neural regulation of systemic arterial pressure and RR variabilities in ambulant subjects.
Authors: Furlan R , Guzzetti S , Crivellaro W , Dassi S , Tinelli M , Baselli G , Cerutti S , Lombardi F , Pagani M , Malliani A
Published: June 2011

In this study, we tested the hypothesis that the neural control of circulation in humans undergoes continuous but in part predictable changes throughout the day and night. Dynamic 24-hour recordings were obtained in two groups of ambulant subjects. In 18 hospitalized patients free to move, direct high-fidelity arterial pressures and electrocardiograms were recorded, and in an additional 28 nonhospitalized subjects, only electrocardiograms were obtained. Spectral analysis of systolic arterial pressure and of RR interval variabilities provided quantitative markers of sympathetic and vagal control of the sinus node and of sympathetic modulation of vasomotor tone. With this approach, the low-frequency (approximately 0.1 Hz) component of RR interval and systolic arterial pressure variabilities is considered a marker primarily of sympathetic activity, whereas the high-frequency (approximately 0.25 Hz) component of RR interval variability, related to respiration, seems to be a marker primarily of vagal activity. We observed a pronounced and consistent reduction in the markers of sympathetic activity and an increase in those of vagal activity during the night. In the invasive studies, while the subjects were still lying in bed after waking up, the markers of sympathetic activity rose rapidly and concomitantly with a simultaneous vagal withdrawal. Noninvasive studies confirmed the early morning rise of the markers of sympathetic activity and the circadian pattern of sympathovagal balance. These data indicate that the ominously increased rate of cardiovascular events in the morning hours may reflect the sudden rise of sympathetic activity and the reduction of vagal tone.
Intraoperative Doppler color flow mapping for decision-making in valve repair for mitral regurgitation. Technique and results in 100 patients.
Authors: Stewart W J , Currie P J , Salcedo E E , Lytle B W , Gill C C , Schiavone W A , Agler D A , Cosgrove D M
Published: June 2011

Mitral valve repair provides substantial advantages over mitral valve replacement in patients with severe mitral regurgitation. However, because of the possibility of persistent regurgitation, an intraoperative technique is needed to provide an immediate and accurate assessment of the adequacy of the repair before closure of the chest. One hundred patients with pure mitral regurgitation were studied with intraoperative epicardial Doppler color flow mapping immediately before and after valve repair. Intraoperative assessment of the severity of mitral regurgitation showed good agreement with preoperative left ventriculography and with standard precordial Doppler echocardiography before and after surgery. Postrepair intraoperative Doppler studies showed satisfactory surgical results in 92 patients. Postrepair intraoperative Doppler studies in the remaining eight patients demonstrated unsatisfactory results: persistent significant regurgitation in four, systolic anterior motion of the mitral valve with dynamic left ventricular outflow tract obstruction in three, and a persistent flail leaflet in one. In six of the eight patients, further surgery was performed during the same thoracotomy. In two patients, the intraoperative postrepair Doppler findings of persistent regurgitation were confirmed on precordial Doppler studies within 5 days, and mitral reoperation was required. Intraoperative epicardial Doppler color flow mapping provided a "safety net" that ensured a successful outcome in all 100 patients by providing the surgeon with a direct means to assess the success of the operation and the need for further surgery.
Characterization of acute experimental left ventricular thrombi with quantitative backscatter imaging.
Authors: Vandenberg B F , Kieso R A , Fox-Eastham K , Kerber R E , Melton H E , Collins S M , Skorton D J
Published: June 2011

Two-dimensional echocardiography is an excellent technique for detecting left ventricular thrombi, however, acute clot is sometimes difficult to differentiate from adjacent myocardium and intracavitary signals. We hypothesized that quantitative assessment of the acoustic properties of acute left ventricular thrombi using a quantitative backscatter imaging system would permit the differentiation of thrombus from adjacent myocardium and intracavitary echoes. Acute, experimental left ventricular thrombi in seven dogs were evaluated with a quantitative backscatter imaging system that allowed the measurement of relative integrated backscatter and cyclic (i.e., diastolic minus systolic) variation in integrated backscatter. Coronary ligation abolished the cyclic variation in relative backscatter that occurred in normal myocardium. The end-diastolic relative backscatter in the thrombus (16.9 +/- 1.3 dB) was significantly higher than in apical myocardium (13.2 +/- 0.6 dB, p less than 0.05). There was no significant difference in the cyclic variation in relative backscatter among thrombus, ischemic myocardium, or intracavitary blood. Thus, the quantitative assessment of the acoustic properties of left ventricular thrombi can be useful in their detection and in the differentiation from myocardium and intracavitary signals.
Conduction velocity depression and drug-induced ventricular tachyarrhythmias. Effects of lidocaine in the intact canine heart.
Authors: Anderson K P , Walker R , Lux R L , Ershler P R , Menlove R , Williams M R , Krall R , Moddrelle D
Published: June 2011

Depression of myocardial conduction velocity can be an important mechanism of action of antiarrhythmic drugs but it can also facilitate arrhythmogenesis. We used lidocaine in an anesthetized canine preparation to address the hypothesis that drug-induced rate-dependent conduction velocity depression causes ventricular tachyarrhythmias. A closely spaced square array of 64 electrodes was used to determine conduction velocity longitudinal and transverse to epicardial ventricular fiber direction. Lidocaine caused rate-dependent decreases in conduction velocity that were proportionately greater in the longitudinal direction at the shortest pacing cycle lengths. Conduction velocity depression developed rapidly in the presence of lidocaine with a new steady state present by the second beat of the rapid train. Recovery from rate-dependent depression of conduction velocity was exponential with a time constant of 122 +/- 20 msec (mean +/- SD) in the longitudinal direction and 114 +/- 30 msec in the transverse direction; this difference was not significant. The relation between conduction velocity depression and ventricular arrhythmias was assessed by pacing for 3 minutes at cycle lengths of 1,000, 500, 300, and 250 msec, and for 1 minute at a cycle length of 200 msec. Arrhythmias did not occur in the baseline period in the dogs that received lidocaine, nor in 12 control dogs that were subjected to the same stimulation protocol except that saline was administered in place of lidocaine. Sustained polymorphic ventricular tachycardia (VT) occurred in six of 16 dogs given lidocaine. VT occurred in the presence of relatively high plasma lidocaine concentrations (8.4 +/- 2.3 micrograms/ml) and only at pacing cycle lengths of 300 msec or shorter. The dogs that developed VT demonstrated greater rate-dependent depression of conduction velocity than the other dogs, and activation patterns obtained just before the onset of VT showed marked conduction disturbances. Furthermore, QRS prolongation, loss of one-to-one capture, and increasingly distorted activation patterns preceded the onset of VT during fixed-rate pacing, suggesting progressive sodium channel block. In summary, rate-dependent conduction velocity depression and nonuniform activation were associated with VT in this model and can be responsible for some arrhythmias induced by antiarrhythmic drugs.
Aurintricarboxylic acid in a canine model of coronary artery thrombosis.
Authors: Strony J , Phillips M , Brands D , Moake J , Adelman B
Published: June 2011

Platelet thrombus formation occurs at sites of severe arterial narrowing where shear stress is elevated. Shear stress appears to induce platelet aggregation in vitro by means of initiation of von Willebrand factor binding to platelet glycoprotein Ib. Recent in vitro studies have demonstrated that aurintricarboxylic acid can inhibit shear stress-induced platelet aggregation. This effect is mediated by aurintricarboxylic acid binding to von Willebrand factor; this binding results in inhibition of von Willebrand factor interaction with glycoprotein Ib. In this study, we examined the effect of aurintricarboxylic acid on platelet-dependent cyclic flow reductions (CFRs) in a canine coronary stenosis model. In dose-response experiments, six animals received 4 mg/kg aurintricarboxylic acid by bolus infusion, followed by 1 mg/kg every 10 minutes. Total inhibition of CFRs was observed in all animals after 6.7 mg/kg aurintricarboxylic acid; CFRs could not be reinitiated by the thromboxane A2 analogue U46619. Continuous infusion of epinephrine (0.4 micrograms/kg/min) caused CFRs to return; however, 3.7 mg/kg additional aurintricarboxylic acid again induced total inhibition of CFRs. In addition, five animals received a bolus infusion of 10 mg/kg aurintricarboxylic acid, which caused total inhibition of CFRs. The average area of stenosis in the constricted vessels was 83%, and shear stress at the site of constriction averaged 350 dynes/cm2. Aurintricarboxylic acid did not alter hemodynamics, thrombin time, platelet count, or ADP/epinephrine-induced platelet aggregation. These data indicate that platelet glycoprotein Ib-von Willebrand factor interactions are important during coronary occlusion and that aurintricarboxylic acid can inhibit coronary thrombosis associated with coronary constriction.
Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy.
Authors: Treasure C B , Vita J A , Cox D A , Fish R D , Gordon J B , Mudge G H , Colucci W S , Sutton M G , Selwyn A P , Alexander R W
Published: June 2011

Dilator reserve of the coronary microvasculature is diminished in patients with dilated cardiomyopathy. Although increased extravascular compressive forces, tachycardia, and increased myocardial mass can explain some impairment, recent evidence suggests the possibility of intrinsic microvascular disease. We tested the hypothesis that impairment of endothelium-dependent dilation of the microvasculature could be a contributing mechanism. We infused the endothelium-dependent dilator acetylcholine (Ach) (10(-8) to 10(-6) M) and the smooth muscle vasodilator adenosine (AD) (10(-6) to 10(-4) M) into the left anterior descending coronary artery in eight patients with dilated cardiomyopathy (mean ejection fraction, 28%) and seven controls (atypical chest pain). Small vessel resistance was assessed by measuring coronary blood flow (CBF) at constant arterial pressure with a Doppler velocity catheter (corrected for cross-sectional area by angiography). With Ach, control patients increased CBF 232 +/- 40% (mean +/- SEM), whereas CBF did not significantly change in cardiomyopathy patients (41 +/- 24%) (p less than 0.0001, control vs. cardiomyopathy). With AD, control patients increased CBF 422 +/- 56% and cardiomyopathy patients increased CBF 268 +/- 43% (p = 0.13). An index of the proportion of coronary flow reserve attributable to endothelium-dependent vasodilation was obtained by standardizing each patient's Ach dose response to his maximal AD flow response. In seven control patients receiving both Ach and AD, 56 +/- 9% of the maximal AD flow response was attained with the endothelium-dependent vasodilator Ach, whereas in seven cardiomyopathy patients receiving both Ach and AD, only 23 +/- 14% of the maximal AD response was attained (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Serial measurement of integrated ultrasonic backscatter in human cardiac allografts for the recognition of acute rejection.
Authors: Masuyama T , Valantine H A , Gibbons R , Schnittger I , Popp R L
Published: June 2011

Cyclic variation of integrated ultrasonic backscatter (IB) was noninvasively measured in the septum and left ventricular posterior wall using a quantitative IB imaging system to assess the alterations in the acoustic properties of myocardium associated with acute cardiac allograft rejection. The study population consisted of 23 cardiac allograft recipients and 18 normal subjects. In each cardiac allograft recipient, one to eight (mean, four) IB studies were performed, each within 24 hours of right ventricular endomyocardial biopsy performed for rejection surveillance. The magnitude of the cyclic variation of IB in the posterior wall was 5.9 +/- 0.9 dB in normal subjects and 6.2 +/- 1.3 dB in the cardiac allograft recipients without previous or current histological evidence of acute rejection (n = 17, p = NS vs. normal subjects). The magnitude of cyclic variation of IB in the septum was 4.8 +/- 1.1 dB in normal subjects and 3.8 +/- 2.0 dB in the cardiac allograft recipients (n = 15, p = NS vs. normal subjects). A significant decrease in the septal IB measure was observed in cardiac allograft recipients with left ventricular hypertrophy (wall thickness of at least 13 mm) (2.6 +/- 1.7 dB, n = 8, p less than 0.05 vs. normal subjects). IB studies were done before and during moderate acute rejection in 11 recipients (14 episodes). During moderate acute cardiac rejection, the magnitude of the cyclic variation in IB decreased from 6.7 +/- 1.3 to 5.1 +/- 1.4 dB in the posterior wall (n = 14, p less than 0.05) and from 4.2 +/- 2.1 dB to 2.9 +/- 1.8 dB in the septum (n = 12, p less than 0.05). These data suggest 1) the magnitude of the cyclic variation in IB of the septum is different in cardiac allografts with cardiac hypertrophy and normal subjects, possibly reflecting regionally depressed myocardial contractile performance and 2) acute cardiac rejection in humans is accompanied by an alteration in the acoustic properties of the myocardium. This change is detectable by serial measurement of the magnitude of the cyclic variation in IB, both in the septum and in the posterior wall.
Body surface mapping during percutaneous transluminal coronary angioplasty. QRS changes indicating regional myocardial conduction delay.
Authors: Spekhorst H , SippensGroenewegen A , David G K , Janse M J , Dunning A J
Published: June 2011

Using a radiotransparent electrode array, body surface maps (BSMs) were constructed based on simultaneous recordings from 62 leads on the entire thorax before, during, and after balloon inflation during percutaneous transluminal coronary angioplasty (PTCA). Twenty-five patients were studied, and 30 angioplasties were performed; 20 patients had one-vessel disease, and five patients had two-vessel disease. In total, 15 dilations in the left anterior descending artery (LAD), seven in the right coronary artery (RCA), and eight in the left circumflex artery (LCx) were studied. For each patient, the BSM and the QRS integral map before, during, and after the inflation was compared by subtraction of recordings "during-minus-before" inflation and "before-minus-after" inflation. The subtraction was performed on the results of the QRS integral maps. The conclusions derived from the inspection of the BSMs and the difference maps show specific changes in the QRS complex during ischemia related to the corresponding ischemic segment in 21 of 25 patients in the three groups. An area of positive potentials remained present on the BSM during dilation, indicating a depolarization wave front. For the LAD group, positive potentials were seen on the anterior thorax and, for the RCA group, on the lower part of the thorax. By subtraction analysis, these changes were extracted and presented as difference maps. For the LCx group, the BSM revealed no changes in pattern but the difference map showed a difference vector pointing in a anteroposterior direction. A regional myocardial conduction delay was hypothesized as the most likely cause for the results.
Do changes in pulmonary capillary wedge pressure adequately reflect myocardial ischemia during anesthesia? A correlative preoperative hemodynamic, electrocardiographic, and transesophageal echocardiographic study.
Authors: van Daele M E , Sutherland G R , Mitchell M M , Fraser A G , Prakash O , Rulf E N , Roelandt J R
Published: June 2011

Pulmonary capillary wedge pressure (PCWP) is monitored during anesthesia in an attempt to detect changes in myocardial function in patients at risk of preoperative cardiac complications. Because the sensitivity with which preoperative PCWP monitoring indicates myocardial ischemia is uncertain, we monitored PCWP, 12-lead electrocardiogram, and left ventricular wall motion abnormalities as defined by transesophageal echocardiography (TEE) in 98 anesthetized patients before coronary artery bypass grafting. Measurements were made five times in each patient, before and after induction of anesthesia. Myocardial ischemia was identified by TEE in 14 patients; in 10 of these, it was associated with concomitant ST segment depression of at least 1 mm. The onset of ischemia, as defined by TEE, was accompanied by a mean increase in PCWP of 3.5 +/- 4.8 mm Hg, as compared with a mean change of 0 +/- 2.2 mm Hg between observations not associated with the onset of ischemia (p less than 0.01). An increase in PCWP of at least 3 mm Hg, tested as an indicator of ischemia, had a sensitivity of 25% and a positive predictive value of 15%; after correction for background changes associated with anesthetic induction, the sensitivity of this indicator was 33%, and its positive predictive value was 16%. These figures were not improved by selecting cutoff points higher or lower than 3 mm Hg. In this study, the onset of myocardial ischemia was associated with a small yet significant increase in mean PCWP at group level.(ABSTRACT TRUNCATED AT 250 WORDS)
Agonist-induced desensitization of beta-adrenoceptor function in humans. Subtype-selective reduction in beta 1- or beta 2-adrenoceptor-mediated physiological effects by xamoterol or procaterol.
Authors: Brodde O E , Daul A , Michel-Reher M , Boomsma F , Man in 't Veld A J , Schlieper P , Michel M C
Published: June 2011

We investigated the effects of beta 2- (procaterol 2 x 50 micrograms/day for 9 days) and beta 1- (xamoterol 2 x 200 mg/day for 14 days) adrenoceptor agonists on lymphocyte beta 2-adrenoceptor density and beta 1- and beta 2-adrenoceptor in vivo function (assessed as isoprenaline-infusion-evoked hemodynamic effects and exercise-induced tachycardia) in healthy volunteers. Procaterol decreased lymphocyte beta 2-adrenoceptor density and all beta 2-adrenoceptor-mediated in vivo effects but did not affect beta 1-adrenoceptor-mediated in vivo effects. In contrast, xamoterol neither affected lymphocyte beta 2-adrenoceptors nor beta 2-adrenoceptor-mediated in vivo effects but decreased beta 1-adrenoceptor-mediated in vivo effects. It is concluded that in humans, generally long-term application of beta 1- or beta 2-adrenoceptor agonists causes desensitization of beta-adrenoceptor function but in a beta-adrenoceptor subtype-selective fashion.
Noninvasive quantification of left ventricular rotational deformation in normal humans using magnetic resonance imaging myocardial tagging.
Authors: Buchalter M B , Weiss J L , Rogers W J , Zerhouni E A , Weisfeldt M L , Beyar R , Shapiro E P
Published: June 2011

It has been postulated that rotation of the left ventricular apex with respect to the base is a component of normal systolic function in humans, but it has been difficult to measure it noninvasively. Tagging is a new magnetic resonance imaging technique that labels specific areas of myocardium by selective radio-frequency excitation of narrow planes orthogonal to the imaging plane before acquiring an image. Tags appear as black lines and persist in myocardium for 400-500 msec and, if applied at end diastole, will move with the myocardium through systole. Tagging was used to noninvasively quantify left ventricular torsion and circumferential-longitudinal shear (shearCL) in humans. Eight normal volunteers, aged 24-38 years, were imaged in a 0.38-T iron-core resistive magnet. Five short-axis left ventricular images, positioned to encompass the entire left ventricle (LV), were obtained separately at end systole. Four equiangular radial tags had been applied at end diastole, intersecting the myocardium at eight locations. We calculated the difference in angular displacement of each epicardial and endocardial tag point (a tag point being where the tag crossed the epicardium or endocardium) at end systole from the systolic position of the corresponding tag point on the basal plane. This value was called the torsion angle. From this, shearCL, the angle inscribed on the epicardial or endocardial surface between the systolic tag position, the corresponding basal tag position, and its projection onto the slice of interest could be calculated at 32 points in the left ventricular wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Premature ventricular complex morphology. A marker for left ventricular structure and function.
Authors: Moulton K P , Medcalf T , Lazzara R
Published: June 2011

The shape of a premature ventricular complex (PVC) might reflect the presence or absence of myocardial disease. To test this, 100 patients with a PVC on a 12-lead electrocardiogram at cardiac catheterization or nuclear angiography were classified according to PVC morphology. Group 1 (n = 50) had PVC QRS complexes with either smooth and uninterrupted contour or with narrow (less than 40 msec) notching. Group 2 (n = 50) demonstrated PVC with broad (greater than or equal to 40 msec) notching or shelves. Clinical, electrocardiographic and angiographic variables were assessed to define group differences. All patients had one or more etiological forms of heart disease none of which distinguished either group. Groups 1 and 2 differed with respect to a history of congestive heart failure (12% vs. 66%, p = 0.0004), dilated cardiomyopathy (2% vs. 38%, p = 0.0005), and the presence of mitral regurgitation (13% vs. 58%, p = 0.001), respectively. In group 1, 45 of 50 (90%) patients with a PVC had no notching. Patients in group 2 had greater PVC QRS duration as compared with patients in group 1 (181 +/- 6 vs. 134 +/- 3 msec, p = 0.0001). End-diastolic volume index (EDVI) (78 +/- 3 vs. 139 +/- 11 ml/m2, p = 0.0000) and ejection fraction (EF) (0.59 +/- 0.02 vs. 0.34 +/- 0.03, p = 0.0000) significantly discriminated between group 1 and 2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Interstudy variability of coronary flow reserve. Influence of heart rate, arterial pressure, and ventricular preload.
Authors: McGinn A L , White C W , Wilson R F
Published: June 2011

To define the long-term variability of serial coronary flow reserve (CFR) measurements in humans and to evaluate the influence of changes in heart rate, mean arterial pressure, and left ventricular preload on CFR, 45 patients with normal left ventricular function (38 cardiac allograft recipients, five patients with normal coronary arteries, and two patients with minimal coronary artery disease [less than 50% diameter stenosis]) were studied. CFR (ratio of peak hyperemic [h] to resting [r] coronary blood flow velocity [CBFV]) was measured with a 3F coronary Doppler catheter and intracoronary papaverine. Initial CFR measurements were highly correlated with repeat measurements obtained 11 +/- 0.6 months later (r = 0.95; mean absolute difference, 0.3 +/- 0.1; n = 17). Differences in CFR between studies were related to changes in heart rate (r = 0.61, p = 0.01) but not to changes in mean arterial pressure (r = 0.25, p = 0.33). To define the effects of rapid changes in heart rate, mean arterial pressure, and preload on CFR, these variables were altered by atrial pacing, handgrip exercise, and volume expansion, respectively. Atrial pacing produced a rate-related increase in rCBFV but did not change hCBFV. Consequently, CFR was significantly reduced as heart rate was increased progressively from 76 +/- 2 in sinus rhythm (4.5 +/- 0.2) to 100 (3.8 +/- 0.2, p less than 0.05, n = 32) to 120 beats/min (3.2 +/- 0.1, p less than 0.05, n = 7). Despite a 19 +/- 2 mm Hg rise in mean arterial pressure during handgrip exercise, CFR was unchanged from baseline (3.7 +/- 0.3 vs. 3.7 +/- 0.4, p = NS, n = 7) because rCBFV rose proportionally with hCBFV. When pulmonary capillary wedge pressure was increased from 9 +/- 1 to 16 +/- 1 mm Hg after volume expansion, CFR was significantly decreased (from 3.8 +/- 0.2 to 2.9 +/- 0.2, p less than 0.05, n = 9) because rCBFV was increased while hCBFV remained unchanged. Hence, serial CFR measurements in humans are highly reproducible in the absence of conditions known to affect resting or hyperemic coronary blood flow. Increases in heart rate or preload reduced CFR because rCBFV was increased while hCBFV was unchanged. In contrast, changes in mean arterial pressure did not alter CFR. Proper interpretation of CFR measurements should take into account the hemodynamic conditions at which they are obtained.
Diminished beta-adrenergic receptor responsiveness and cardiac dilation in hearts of myopathic Syrian hamsters (BIO 53.58) are associated with a functional abnormality of the G stimulatory protein.
Authors: Feldman A M , Tena R G , Kessler P D , Weisman H F , Schulman S P , Blumenthal R S , Jackson D G , Van Dop C
Published: June 2011

Previous studies have demonstrated a diminution in the bioactivity of the guanine nucleotide-binding regulatory protein that stimulates adenylyl cyclase (Gs) in hearts of the hypertrophic BIO 14.6 Syrian hamster. In this study, we measured functional activity and immunodetectable levels of Gs in a mutant strain of hamsters (BIO 53.58) that develop a dilated cardiomyopathy. Pathological studies demonstrated that 100-day-old BIO 53.58 hamsters had substantial ventricular dilation when compared with age-matched F1B controls. Additionally, these 100-day-old hamsters demonstrated diminished contractile response to beta-adrenergic receptor stimulation. The pathological and hemodynamic changes were associated with defective coupling of Gs to adenylyl cyclase as adenylyl cyclase activation was distinctly decreased in the presence of isoproterenol, fluoride ion, guanine nucleotides, and forskolin. Additionally, the ability of the alpha-subunit of Gs to reconstitute isoproterenol-stimulated adenylyl cyclase activity in S49 cyc- membranes was reduced approximately 65%. By contrast, cyc- complementation assays did not reveal a difference between the functional activity of Gs in hearts from 30-day-old BIO 53.58 hamsters and F1B controls. Furthermore, beta-adrenergic receptor stimulation of adenylyl cyclase in the membranes of the young BIO 53.58 hamsters was not significantly different from controls. The substantial alterations in Gs bioactivity in hearts of the 100-day-old BIO 53.58 hamsters was not associated with alterations in the immunodetectable levels of either alpha Gs or alpha Gi on Western Blots. These results suggest that G protein changes are associated with ventricular dilation in BIO 53.58 hamsters and that G protein levels are not always reflective of G protein bioactivity.
Augmented and sustained plasma concentrations after intramuscular injections of molecular variants and deglycosylated forms of tissue-type plasminogen activators.
Authors: Sobel B E , Sarnoff S J , Nachowiak D A
Published: June 2011

We have previously explored induction of coronary thrombolysis with tissue-type plasminogen activator (t-PA) administered intramuscularly. Absorption-enhancing agents that rendered the approach feasible were identified, but large amounts of activator were required and initial elevations of concentrations in plasma could not be sustained. The present study was designed to determine whether more therapeutically favorable plasma concentrations could be induced by genetically engineering or chemically modifying t-PA to prolong its half-life based on the hypothesis that the ratio of absorption to clearance would be increased. Each of four genetically engineered variants (one variant with growth factor and kringle 1 domains deleted and kringle 2 duplicated, a second variant with a cysteine for Arg substitution in the growth factor domain, a third variant with an additional urokinase kringle inserted, and a fourth variant with the growth factor domain deleted) and enzymatically deglycosylated t-PA exhibited prolonged half-life after bolus intravenous injection in rabbits. Each elicited substantially higher and more sustained elevations in plasma after intramuscular injection in rabbits or dogs with absorption-enhancing agents as compared with wild-type t-PA that were not accompanied by a systemic lytic state. Thus, use of molecular variants of t-PA with prolonged half-lives in the circulation permits induction of augmented and sustained elevations of plasma concentrations after intramuscular injection with absorption-enhancing agents as compared with wild-type t-PA, rendering potentially therapeutic blood levels more attainable with relatively modest amounts of material.
Effect of duration of ventricular fibrillation on defibrillation efficacy in humans.
Authors: Winkle R A , Mead R H , Ruder M A , Smith N A , Buch W S , Gaudiani V A
Published: June 2011

The currently available automatic implantable cardioverter-defibrillator has proven highly successful for termination of ventricular tachycardia and fibrillation. Newer devices, however, permit lower energy shocks to be delivered initially and longer episodes of arrhythmia to occur before shocks are delivered. These changes may result in longer durations of arrhythmia before successful termination. Little is known about the effects of the duration of ventricular fibrillation on the efficacy of defibrillating shocks. In this study, we examined the efficacy of defibrillating shocks in 22 patients undergoing automatic implantable cardioverter-defibrillator implantation or generator change. Defibrillating shocks ranging from 300 to 600 V (5.9-24.2 J) were delivered in matched pairs after 5 and 15 seconds of ventricular fibrillation. For the 300-V shocks (5.9 J), defibrillation was accomplished in 82% of patients when the shocks were given after 5 seconds of ventricular fibrillation and in only 45% of patients when the shocks were delivered after 15 seconds (p less than 0.01). At higher energies, there was no difference in the efficacy of defibrillation shocks delivered after 5 compared with 15 seconds of ventricular fibrillation. The postshock aortic, systolic, and diastolic blood pressures were significantly lower when the shocks were given after 15 seconds of ventricular fibrillation than after only 5 seconds. We conclude that the duration of ventricular fibrillation affects defibrillation efficacy especially at energies that are relatively low compared with maximal device outputs and that longer episodes of ventricular fibrillation cause more postshock hemodynamic depression. These observations have implications for defibrillation threshold testing at the time of device implantation and for the design and programming of future automatic implantable antitachycardia devices.
Evolving concepts in the management of congenital junctional ectopic tachycardia. A multicenter study.
Authors: Villain E , Vetter V L , Garcia J M , Herre J , Cifarelli A , Garson A
Published: June 2011

We reviewed the records of 26 infants with congenital junctional ectopic tachycardia (JET) from seven institutions to examine the evolution in the management of this tachycardia that is difficult to treat. JET was defined electrocardiographically as an incessant tachycardia with normal QRS morphology and atrioventricular (AV) dissociation. The ventricular rate ranged from 140 to 370 beats/min (mean, 230 beats/min); 16 of 26 patients had cardiac failure. Treatment success was defined as a stable decrease in the rate of JET, below 150 beats/min; partial success was a significant decrease of JET rate with alleviation of symptoms. All patients received digoxin with no significant effect. Propranolol was given to 16 patients, with two successes and one partial success. Combinations of other conventional agents were used in 11 patients with two successes; 14 patients were treated with amiodarone, which resulted in eight successes and three partial successes; three patients died suddenly on medical treatment (amiodarone, one patient; propranolol, one patient; or amiodarone plus propranolol, one patient); sudden AV block was a possible cause and consequently, two later patients had pacemaker implantation as well as medical treatment. His catheter ablation was successfully performed twice but contributed to death in a newborn; three surgical His ablations were performed for intractable JET with two successes and one death. The overall mortality was 35%. Among survivors, treatment has been stopped without any complications in five patients ranging in age from 10 months to 8 years (mean, 3.5 years). It seems that amiodarone alone is the best drug for treatment of congenital JET; necessity for permanent pacing remains unsettled. His ablation should be reserved only for intractable JET.
Controlled trial of aerobic exercise in hypertension.
Authors: Martin J E , Dubbert P M , Cushman W C
Published: June 2011

To determine the antihypertensive efficacy of aerobic exercise training in mild essential hypertension, a prospective randomized controlled trial was conducted comparing an aerobic exercise regimen to a placebo exercise regimen, with a crossover replication of the aerobic regimen in the placebo exercise group. The study took place in an outpatient research clinic in a university-affiliated Veterans Administration medical center. Twenty-seven men with untreated diastolic blood pressure (DBP) of 90-104 mm Hg were randomized to the two exercise regimens. Ten patients completed the aerobic regimen. Nine patients completed the control regimen, seven of whom subsequently entered and completed the aerobic regimen. The aerobic regimen consisted of walking, jogging, stationary bicycling, or any combination of these activities for 30 minutes, four times a week, at 65-80% maximal heart rate. The control regimen consisted of slow calisthenics and stretching for the same duration and frequency but maintaining less than 60% maximal heart rate. DBP decreased 9.6 +/- 4.7 mm Hg in the aerobic exercise group but increased 0.8 +/- 6.2 mm Hg in the placebo control exercise group (p = 0.02). Systolic blood pressure (SBP) decreased 6.4 +/- 9.1 mm Hg in the aerobic group and increased 0.9 +/- 9.7 mm Hg in the control group (p = 0.11). Subsequently, seven of the nine controls entered a treatment crossover and completed the aerobic regimen with significant reductions in both DBP (-6.1 +/- 3.2 mm Hg, p less than 0.01) and SBP (-8.1 +/- 5.7 mm Hg, p less than 0.01). BP changes were not associated with any significant changes in weight, body fat, urinary electrolytes, or resting heart rate. This randomized controlled trial provides evidence for the independent BP lowering effect of aerobic exercise in unmedicated mildly hypertensive men.
Buffer agents do not reverse intramyocardial acidosis during cardiac resuscitation.
Authors: Kette F , Weil M H , von Planta M , Gazmuri R J , Rackow E C
Published: June 2011

We investigated the effects of carbon dioxide-producing and carbon dioxide-consuming buffers on intramyocardial pH and on cardiac resuscitability. In 29 pigs, intramyocardial pH was continuously measured with a glass electrode advanced into the midmyocardium of the posterior left ventricle through a diaphragmatic window. Ventricular fibrillation (VF) was electrically induced by alternating current applied to the epicardium of the left ventricle. After 3 minutes of VF, precordial compression was begun and continued for an interval of 8 minutes. Sodium bicarbonate (a carbon dioxide-generating buffer), Carbicarb (a carbon dioxide-consuming buffer), and hypertonic sodium chloride (control solution) were infused into the right atrium during cardiac resuscitation. Defibrillation was attempted by transthoracic direct-current shock after 11 minutes of VF. Intramyocardial pH progressively decreased from an average value of 7.26 before VF to 6.87 before infusion of buffers. Systemic circulation and great cardiac vein pH significantly increased after administration of the two buffer agents. However, intramyocardial pH continued to decline to an average of 6.62 after 11 minutes of VF, and this decline was not altered by either buffer solution or by the saline control. As in previous studies, resuscitability was closely related to coronary perfusion pressure at the time of direct-current countershock but not to pH. Accordingly, the rationale of reversing acidosis by the administration of these buffer agents is not supported. Even more important, neither carbon dioxide-consuming nor carbon dioxide-producing buffers altered myocardial acidosis or improved myocardial resuscitability under controlled experimental conditions of cardiac arrest.