bluuebunny/crossref_metadata_2025 huggingface dataset:
Summation and inhibition by ultrarapid train pacing in the human ventricle.
Authors: Swerdlow C D , Liem L B , Franz M R
Published: June 2011

Trains of ultrarapid stimuli that begin late in the refractory period have been reported both to produce early single captures to terminate tachyarrhythmias and to inhibit the response to subsequent threshold stimuli. To determine which characteristics of trains facilitate capture and which enhance inhibition, we compared the right ventricular strength interval relationship for single extrastimuli (S2) with that for 100 Hz trains with a duration of 100 msec in 29 patients. Pulse frequency was varied in 12 patients (50, 100, and 200 Hz) and train duration (50, 100, and 150 msec) was varied in 11 patients; the effect of procainamide (10.1 +/- 2.3 micrograms/ml) was assessed in 10 patients. Relative to S2, 100 Hz trains with a duration of 100 msec prolonged the effective refractory period (ERP) at low current strength (inhibition), but shortened the ERP at high-current strength (summation): at 0.5 mA, the train ERP was 47 +/- 6 (SEM) msec longer than the S2 ERP (p less than .001); at 16 mA it was 12 +/- 1 msec shorter (p less than .001). Trains prolonged the functional refractory period (FRP) slightly at low currents (13 +/- 3 msec, p = .001 at .05 mA), but did not shorten FRP significantly at high currents (2 +/- 2 msec, p = NS at 16 mA) because of increased stimulus-response latency. Inhibition increased with increasing pulse frequency (p less than .001), increasing train duration (p less than .001), and procainamide (p less than .01). Summation increased with increasing pulse frequency (p less than .001), but not increasing train duration or procainamide, suggesting that inhibition and summation depend on different electrophysiologic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Improved defibrillation thresholds with large contoured epicardial electrodes and biphasic waveforms.
Authors: Dixon E G , Tang A S , Wolf P D , Meador J T , Fine M J , Calfee R V , Ideker R E
Published: June 2011

A reduction in the shock strength required for defibrillation would allow use of a smaller automatic implantable cardioverter-defibrillator and would reduce the possibility of myocardial damage by the shock. Most internal defibrillation electrodes require 5 to 25 J for successful defibrillation in human beings and in dogs. In an attempt to lower the shock strength needed for defibrillation, we designed two large titanium defibrillation patch electrodes that were contoured to fit over the right and left ventricles of the dog heart, covering areas of approximately 33 and 39 cm2, respectively. In six anesthetized open-chest dogs, the electrodes were secured directly to the epicardium and ventricular fibrillation was induced by 60 Hz alternating current. Truncated exponential monophasic and biphasic shocks were given 10 sec later and defibrillation thresholds (DFTs) were determined. The DFT was 159 +/- 48 V, 3.2 +/- 1.9 J (mean +/- SD) for 10 msec monophasic shocks and 106 +/- 22 V, 1.3 +/- 0.4 J, for biphasic shocks with both phase durations equal to 5 msec (5-5 msec). The experiment was repeated in another six dogs in which the electrodes were secured to the pericardium. The mean DFT was not significantly higher than that for the electrodes on the epicardium: 165 +/- 27 V, 3.1 +/- 1.2 J for 10 msec monophasic shocks and 116 +/- 19 V, 1.6 +/- 0.5 J for 5-5 msec biphasic shocks. Low DFTs were also obtained with biphasic shocks in which the duration of the first phase was longer than that of the second.(ABSTRACT TRUNCATED AT 250 WORDS)
Myocardial perfusion abnormalities in patients with hypertrophic cardiomyopathy: assessment with thallium-201 emission computed tomography.
Authors: O'Gara P T , Bonow R O , Maron B J , Damske B A , Van Lingen A , Bacharach S L , Larson S M , Epstein S E
Published: June 2011

Myocardial ischemia may play a critical role in the symptomatic presentation and natural history of hypertrophic cardiomyopathy (HCM). To assess the relative prevalence and functional significance of myocardial perfusion abnormalities in patients comprising the broad clinical spectrum of HCM, we studied 72 patients (ages 12 to 69 years, mean 40) using thallium-201 emission computed tomography. Imaging was performed immediately after maximal exercise and again after a 3 hr delay. Regional perfusion defects were identified in 41 of the 72 patients (57%). Fixed or only partially reversible defects were evident in 17 patients, 14 of whom (82%) had left ventricular ejection fractions of less than 50% at rest. Twenty-four patients demonstrated perfusion defects during exercise that completely reversed at rest; all had normal or hyperdynamic left ventricular systolic function (ejection fraction greater than or equal to 50%). Perfusion abnormalities were present in all regions of the left ventricle. However, the fixed defects were observed predominantly in segments of the left ventricular wall that were of normal or only mildly increased (15 to 20 mm) thickness; in contrast, a substantial proportion (41%) of the completely reversible defects occurred in areas of moderate-to-marked wall thickness (greater than or equal to 20 mm, p less than .001). Neither a history of chest pain nor its provocation with treadmill exercise was predictive of an abnormal thallium study, since regional perfusion defects were present in 10 of 18 (56%) completely asymptomatic patients, compared with 31 of 54 (58%) symptomatic patients. These data indicate that myocardial perfusion abnormalities occur commonly among patients with HCM. Fixed or only partially reversible defects suggestive of myocardial scar and/or severe ischemia occur primarily in patients with impaired systolic performance. Completely reversible perfusion abnormalities occur predominantly in patients with normal or supranormal left ventricular systolic function. Such dynamic changes in regional thallium activity may reflect an ischemic process that contributes importantly to the clinical manifestations and natural history of HCM.
Seasonal cholesterol cycles: the Lipid Research Clinics Coronary Primary Prevention Trial placebo group.
Authors: Gordon D J , Trost D C , Hyde J , Whaley F S , Hannan P J , Jacobs D R , Ekelund L G
Published: June 2011

Seasonal variation of plasma cholesterol levels was studied in 1446 hypercholesterolemic 35- to 59-year-old male participants in the Lipid Research Clinics Coronary Primary Prevention Trial placebo group. Each man's serial cholesterol data, obtained at bimonthly intervals for 2.0 to 6.5 years, were analyzed as a separate periodic time series, and distributions of cycle zeniths and amplitudes were calculated. A highly significant (chi 2= 706, 2 degrees of freedom) seasonal effect, 7.4 mg/dl higher on December 30 than on June 30, was found. This effect was similar among the 12 LRC centers, including such disparate climates as those of Minneapolis and San Diego, and tended to be larger in the southern centers. Its magnitude was independent of baseline levels of plasma cholesterol and other baseline characteristics. Observed seasonal differences in weight and diet explained less than one-third of the seasonal variation in plasma cholesterol levels. Plasma low- and high-density lipoprotein cholesterol levels, analyzed similarly, also showed significant synchronous seasonal cycles. Plasma triglyceride levels showed a weaker irregular seasonal pattern, highest in midsummer and late autumn and lowest in spring. The etiologies and mechanisms for these seasonal patterns remain largely unknown.
Secular decline in death rates due to ischemic heart disease in Mexican Americans and non-Hispanic whites in Texas, 1970-1980.
Authors: Stern M P , Bradshaw B S , Eifler C W , Fong D S , Hazuda H P , Rosenthal M
Published: June 2011

Although the decline in ischemic heart disease mortality is now entering its third decade, there has been no definitive information on the experience of Mexican Americans, the nation's second largest minority group. Earlier studies carried out in the 1970s were hampered by the unavailability of satisfactory population data beyond 1970. In the present study we have used 1970 and 1980 census data to compute death rates in Mexican Americans and non-Hispanic whites from Texas for the periods 1969-1971 and 1979-1981. All four sex-ethnic groups showed statistically significant declines in death rates due to all causes, due to total ischemic heart disease, and due to acute myocardial infarction between 1969-1971 and 1979-1981. Declines in the latter two causes of death were least marked in Mexican American men. This sex-ethnic group was also the only one that failed to show a decline in death rates due to chronic ischemic heart diseases. The fact that Mexican Americans have been shown to be less well informed about and less likely to adopt lifestyle changes aimed at reducing heart disease risk than non-Hispanic whites may account for the less striking mortality decline observed in Mexican American men, but is harder to reconcile with the apparent equal decline in Mexican American women compared with non-Hispanic whites.
Measurement of myocardial blood flow by ultrafast computed tomography.
Authors: Wolfkiel C J , Ferguson J L , Chomka E V , Law W R , Labin I N , Tenzer M L , Booker M , Brundage B H
Published: June 2011

Myocardial blood flow was analyzed by radioisotope-labeled microspheres and ultrafast computed tomography (CT) in 16 closed-chest, anesthetized dogs. The first set of 10 dogs had CT and microsphere measurements before and after chromonar-induced increases in myocardial blood flow. A second set of six dogs had flows measured at control and during temporary reductions in regional flow produced by balloon cuff occlusion of the left anterior descending coronary artery. All dogs had four-slice, 20-instance CT scans after injection of a medium bolus (0.35 ml/kg) of contrast medium into a femoral vein simultaneous with injection of microspheres into the left atrium. CT myocardial flow was calculated as the change in myocardial CT numbers divided by the area from a blood pool time-density curve. A wide range of myocardial blood flows was produced as determined by microspheres (0 to 6.7 ml/min/g). Global flow of the first set of dogs was shown to have excellent correlation (r = .95, n = 17) for a limited range (.4 less than X less than 1.4 ml/min/g) of flows. Regional flows of these measurements demonstrated less correlation (r = .63, n = 110) but extended the range of flow to 1.7 ml/min/g. At higher flows (greater than 2.5 ml/min/g) the correlation for global and regional flows was not significantly different than zero. Regional ischemic flow correlation extended the linear range of flow to 0 ml/min/g (r = .62, n = 17). These results show that CT can measure myocardial blood flow over a limited but clinically relevant range of flows defined as slightly above normal to ischemic. These results indicate that another preparation of CT flow measurement must be sought for quantification of myocardial perfusion values significantly above normal.
Enhancement of procainamide-induced rate-dependent conduction slowing by elevated myocardial extracellular potassium concentration in vivo.
Authors: Cascio W E , Foster J R , Buchanan J W , Johnson T A , Gettes L S
Published: June 2011

Procainamide, a type 1A antiarrhythmic drug, blocks sodium channels and reduces the maximum rate of rise of the cardiac action potential (Vmax) in a rate-dependent fashion. In vitro, the magnitude of this rate-dependent reduction in Vmax is greater in tissue that is partially depolarized at rest than in tissue with a normal resting potential. Reductions in Vmax produced by drugs that block sodium channels are also directly related to the reductions in longitudinal conduction velocity of action potential propagation in papillary muscle preparations. We therefore sought to determine whether the rate-dependent conduction slowing induced by procainamide in the intact canine heart is enhanced in myocardial tissue abnormally depolarized by an elevated myocardial extracellular potassium concentration, [K+]o. QRS duration and epicardial activation times were measured as indexes of myocardial conduction. QRS duration and epicardial activation times were measured at control (4.0 mM) and at intermediate (6.5 mM) and high (9.2 mM) myocardial [K+]o in the presence or absence of a clinically relevant procainamide concentration (12.2 +/- 2.6 g/ml) at the longest obtainable interstimulus interval of 440 msec and at 330, 280, and 250 msec. Intermediate and high myocardial [K+]o alone induced rate-dependent conduction slowing as the frequency of stimulation increased (cycle length 440 msec to 330, 280, and 250 msec). In the presence of procainamide, rate-dependent conduction slowing was observed at all levels of myocardial [K+]o, and the amount of rate-dependent change in conduction time increased as the myocardial [K+]o was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of procainamide and N-acetylprocainamide on atrial flutter: studies in vivo and in vitro.
Authors: Wu K M , Hoffman B F
Published: June 2011

We studied the effects of procainamide and N-acetylprocainamide (NAPA) in a conscious dog preparation of atrial flutter resulting from circus movement around the tricuspid orifice. We also recorded transmembrane potentials of atrial tissues from the circus path in vitro. In 12 instrumented dogs, average flutter cycle length was 157 msec, the duration of the excitable gap was 73 msec, and conduction velocity was 0.75 m/sec. At 4 and 8 mg/kg, procainamide moderately prolonged cycle length, but did not terminate the flutter. At a cycle length of 300 msec procainamide increased effective refractory period (ERP) by 12% and 20% and conduction time by 8% and 19%. At 16 and 32 mg/kg procainamide prolonged cycle length, ERP, and conduction time by 60% to 80% and stopped the flutter in all trials. NAPA, at 16, 32, and 64 mg/kg, increased flutter cycle length by 16%, 16%, and 31%, ERP by 14%, 28%, and 41%, and conduction time by less than 15%. NAPA terminated the flutter in two of six dogs given 32 mg/kg, and three of five dogs given 64 mg/kg. The excitable gap was lengthened by both procainamide and NAPA. Transmembrane potentials showed that at a cycle length from 1000 to 300 msec procainamide (10 mg/liter) increased action potential duration and decreased the first time derivative of phase O of the action potential (Vmax), whereas NAPA (20 mg/liter) increased action potential duration without changing Vmax. These findings show the difficulty of relating drug effects on transmembrane potentials to efficacy in vivo since the former do not necessarily indicate which changes in cellular electrical activity are responsible for efficacy against a particular arrhythmogenic mechanism.
Effects of nifedipine on diastolic function during brief periods of flow-limiting ischemia in the conscious dog.
Authors: Applegate R J , Walsh R A , O'Rourke R A
Published: June 2011

To determine the contribution of transsarcolemmal calcium flux to abnormal diastolic function produced by brief periods of flow-limiting ischemia and reperfusion, we evaluated early and late diastolic function during transient coronary occlusion and reperfusion before and during administration of intravenous nifedipine (NIF) (10 +/- 1 microgram/kg/min) in nine preinstrumented conscious dogs. We also assessed the effects of nitroprusside (NTP) (2 +/- 0.2 micrograms/kg/min) during an identical period of ischemia and reperfusion to independently assess the consequences of altered loading alone on diastolic function. To minimize the effects of temporal dysynchrony and altered ventricular loading conditions on isovolumetric relaxation, we developed a conscious dog preparation of reversible transient (30 to 60 sec) bilateral coronary occlusion (BCO). BCO was characterized by significant systolic depression: maximum (+)dP/dt decreased (from 2617 +/- 600 to 1981 +/- 565 mm Hg/sec, p less than .05), left ventricular transverse dimension shortening diminished (from 20 +/- 5 to 9 +/- 5%, p less than .05), and the left ventricle dilated (42.4 +/- 6.4 to 43.8 +/- 6.3 mm, p less than .05). Concomitantly the time constants of isovolumetric relaxation prolonged (from 22 +/- 3 to 28 +/- 4 msec, p less than .05) and minimal diastolic left ventricular pressure increased (from -3 +/- 6 to 6 +/-6 mm Hg, p less than .05). The passive diastolic pressure-dimension relationship shifted upward and to the right and was associated with increased chamber stiffness (from 0.50 +/- 0.26 to 1.03 +/- 0.53 mm Hg/mm, p less than .05) and increased left ventricular end-diastolic pressure (from 7 +/- 7 to 19 +/- 7 mm Hg, p less than .05). Reperfusion immediately after BCO was characterized by prompt restoration of systolic contractile performance [maximum (+)dP/dt 3220 +/- 530 mm Hg/sec] but persistently abnormal early and late diastolic function (time constant of isovolumetric relaxation 30 +/- 6 msec, left ventricular end-diastolic pressure 20 +/- 7 mm Hg). The effects of drug administration on ventricular function during BCO were then evaluated under matched loading conditions. NTP improved time constant of isovolumetric relaxation (20 +/- 8 vs 28 +/- 4 msec, p less than .05) and minimal diastolic left ventricular pressure (2 +/- 5 vs 6 +/- mm Hg, p less than .05) during BCO, but NIF did not (time constant of isovolumetric relaxation 27 +/- 6 msec, minimal diastolic left ventricular pressure 7 +/- 5 mm Hg).(ABSTRACT TRUNCATED AT 400 WORDS)
Identification of patients with sustained ventricular tachycardia by frequency analysis of signal-averaged electrocardiograms despite the presence of bundle branch block.
Authors: Lindsay B D , Markham J , Schechtman K B , Ambos H D , Cain M E
Published: June 2011

Previously, we have demonstrated distinguishing features in the fast Fourier transform (FFT) of signal-averaged electrocardiograms (ECGs) obtained during sinus rhythm in the absence of bundle branch block that differentiate patients with from those without sustained ventricular tachycardia (VT). The ECGs during sinus rhythm from many patients with sustained VT, however, exhibit intraventricular conduction abnormalities. Accordingly, this study was performed to determine whether the presence of bundle branch block during sinus rhythm precluded accurate identification of patients with sustained VT. Studies were performed in 28 normal subjects (group I) and 141 patients with organic heart disease grouped according to clinical characteristics. Group II comprised 40 patients without VT in whom the QRS duration during sinus rhythm was less than 120 msec. Group III included 21 patients without VT in whom the QRS duration during sinus rhythm was 120 msec or greater. Group IV comprised 43 patients with sustained VT having ECGs during sinus rhythm with QRS durations less than 120 msec. Group V included 37 patients with sustained VT in whom the QRS duration during sinus rhythm was 120 msec or greater. FFTs of the terminal QRS and ST segment of signal-averaged X, Y, and Z ECGs were computed. Transformed data were expressed as an FFT magnitude and the relative contribution and peak magnitudes of 20 to 50 Hz frequencies determined after first demonstrating that this FFT method was more appropriate, when compared with the energy spectrum, for analyzing ECG signals having a broad range of ST segment durations.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of changes in afterload on systolic bulging.
Authors: Noma S , Askenase A D , Agarwal J B , Helfant R H
Published: June 2011

It has been previously shown that after acute coronary occlusion, the extent of systolic bulging is dependent on preload and the function of the remote nonischemic myocardium is influenced by the motion of the ischemic myocardium as well as by the loading conditions. To examine the isolated effects of changing afterload on the movement of acutely ischemic and nonischemic myocardium, seven open-chest, anesthetized dogs were paced from the left atrium at a rate of 100 beats/min after crushing of the sinus node. The pulmonary artery was perfused artificially and the left ventricular end-diastolic pressure (LVEDP) was carefully controlled with a right heart bypass system. Twenty minutes after occlusion of the left anterior descending artery, the peak left ventricular pressure (LVP) was adjusted to three levels (70, 90, and 110 mm Hg) by blood withdrawal or aortic constriction, while the LVEDP was kept constant (8.3 +/- 2.3 mm Hg). Segment length in the ischemic (IZ) and nonischemic zones (NZ) were measured with sonomicrometers and total, isovolumetric, and ejection systolic shortening (% delta L) were calculated. Changes in left ventricular minor-axis diameter were measured with diameter crystals. Increasing the peak LVP increased the LVP both at aortic valve opening and closing. To keep the LVEDP constant as peak LVP was increased, the cardiac output had to be decreased (p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Improved hemodynamic function during hypoxia with Carbicarb, a new agent for the management of acidosis.
Authors: Bersin R M , Arieff A I
Published: June 2011

Carbicarb is a mixture of Na2CO3/NaHCO3 that buffers similarly to NaHCO3, but without net generation of CO2. We studied the effects of carbicarb in an animal preparation of hypoxic lactic acidosis (HLA). HLA was induced by ventilating dogs with an hypoxic gas mixture (8% O2/92% N2). Dogs with HLA (n = 28) were then treated with 2.5 meq/kg of either NaHCO3 or carbicarb over 1 hr. Measurements were made, after 1 hr of hypoxia and 1 hr of therapy, of: cardiac hemodynamics, blood gases, liver intracellular pH (pHi), oxygen consumption, and regional lactate production. After therapy, the arterial pH rose with carbicarb (7.22 to 7.27, p less than .01), and fell with NaHCO3 (7.18 to 7.13, p less than .01). Mixed venous PCO2 did not change with carbicarb but increased with NaHCO3 (p less than .05). Arterial lactates stabilized with carbicarb but rose with NaHCO3 (by 3.1 mmol/liter, p less than .005). Lactate use by muscle, gut, and liver all improved with carbicarb and decreased with NaHCO3. The liver pHi (normal = 6.99, hypoxia = 6.80) improved with carbicarb (to 6.92), but decreased further with NaHCO3 (to 6.40). Muscle O2 consumption rose with carbicarb, whereas it decreased with NaHCO3. Arterial pressure fell less with carbicarb (-12 vs -46 mm Hg, p less than .006) and the cardiac output was stable with carbicarb but decreased with NaHCO3 (from 143 to 98 ml/kg/min, p less than .004). Stroke volume also improved with carbicarb but there was no change in pulmonary capillary wedge pressure, suggesting that carbicarb had a beneficial effect on myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative analysis of right and left ventricular infarction in the presence of postinfarction ventricular septal defect.
Authors: Cummings R G , Reimer K A , Califf R , Hackel D , Boswick J , Lowe J E
Published: June 2011

To quantitate the amount of right and left ventricular infarction in patients dying with postinfarction ventricular septal defect (PIVSD), hearts from 54 patients with anterior or inferior myocardial infarction were studied at autopsy. Fifteen hearts had myocardial infarction with PIVSD and 39 hearts had infarction without PIVSD and were used as a comparison group. All infarcts were sized histologically and the percent of each ventricle infarcted was quantitated by computer-assisted planimetry. The pathologic substrate for PIVSD was diffuse coronary artery disease with acute thrombosis resulting in transmural confluent infarction. Within the PIVSD group, there was significantly more left ventricle involved in anterior infarctions than in inferior infarctions (p less than .04). Conversely, there was more right ventricular infarction in inferiorly located myocardial infarctions with resulting PIVSD (p = .059). When infarctions resulting in PIVSD were compared with infarctions not resulting in PIVSD, the PIVSD group was characterized by larger left and right ventricular infarcts irrespective of infarct location (p less than .003). The incidence of right ventricular infarction was 100% in the PIVSD group (p less than .0001). Twelve of the 15 patients with PIVSD (80%) developed cardiogenic shock within 48 hr of septal rupture. The high incidence of shock and the rapid deterioration may have been secondary to right ventricular infarction in these patients. Therefore, infarcts resulting in PIVSD and subsequent death are characterized by a high incidence of right ventricular infarction. Significantly more infarction of the right ventricle is seen in either anterior or inferior infarctions resulting in PIVSD compared with infarctions not resulting in PIVSD. PIVSD complicating inferior infarctions is associated with the greatest amount of right ventricular infarction.
The association between blood pressure, age, and dietary sodium and potassium: a population study.
Authors: Khaw K T , Barrett-Connor E
Published: June 2011

We examined the relationship between blood pressure and dietary sodium and potassium intake estimated from 24 hr diet recall in a population of 584 men and 718 women 30 to 79 years old in Southern California. In men, but not women, age-adjusted systolic and diastolic blood pressure correlated significantly with dietary sodium intake. In both men and women, age-adjusted diastolic blood pressure significantly inversely correlated with dietary potassium intake. Age-adjusted systolic and diastolic blood pressure correlated significantly with the dietary sodium/potassium ratio in each sex; correlations were better for the ratio than for either sodium or potassium alone. The relationship was apparent over the whole range of blood pressure and dietary intake. A marked age gradient was apparent in men, the regression slope for blood pressure vs sodium/potassium ratio increasing with increasing age, suggesting increasing sensitivity to dietary sodium/potassium ratio with age. Adjusting for intake of other dietary variables, including calories, protein, carbohydrate, saturated fat, alcohol, calcium, and fiber, did not alter the relationships; adjusting for body mass index reduced the strength of the association in women but not in men. These results support the hypothesis that dietary sodium and potassium are related to blood pressure within a population.
Carcinoid heart disease: relationship of circulating vasoactive substances to ultrasound-detectable cardiac abnormalities.
Authors: Lundin L , Norheim I , Landelius J , Oberg K , Theodorsson-Norheim E
Published: June 2011

Cardiac ultrasound investigation of 68 prospectively studied patients with histologically proven midgut carcinoid tumors showed right heart disease in 66%. The abnormal findings included morphologic and functional aberrations of the tricuspid valve in 52% and 83%, respectively, right atrial and ventricular enlargement in 53% and 30%, and paradoxical systolic septal contractions in 19%. The patients with the most pronounced right heart disease had significantly higher (p less than .01) plasma levels of the tachykinins neuropeptide K and substance P as well as higher (p less than .001) urinary excretion of the serotonin metabolite 5-hydroxyindoleacetic acid. These patients also had the most extensive tumor disease. The occurrence of echocardiographic abnormalities of the left heart was similar to that in healthy individuals of the same age, but abnormalities were less frequent among the patients with severe right heart disease. Electrocardiographic changes were nonspecific. Right heart disease thus seems to be present more often than previously reported in patients with malignant midgut carcinoid tumors. The severity of cardiac involvement does not seem to be related to the duration of carcinoid disease but more to the extent of the disease, i.e., higher plasma levels of serotonin and tachykinins.
Accentuated antagonism between beta-adrenergic and vagal effects on ventricular refractoriness in humans.
Authors: Morady F , Kou W H , Nelson S D , de Buitleir M , Schmaltz S , Kadish A H , Toivonen L K , Kushner J A
Published: June 2011

The purpose of this study was to determine whether there is accentuated antagonism between sympathetic and vagal effects on ventricular refractory periods (VRPs) in humans. The effects of 0.04 mg/kg of atropine on the right ventricular effective and functional refractory periods were determined in the setting of beta-adrenergic blockade by propranolol (0.15 mg/kg loading dose, then 0.1 mg/min continuous infusion, group 1) and in the setting of beta-adrenergic stimulation by 25 or 50 ng/kg/min isoproterenol (groups 2 and 3, respectively). Groups 4 to 6 served as control groups. In group 4, VRPs were determined on three occasions separated by 10 min each in the absence of drug. VRPs also were determined on two occasions after infusion of propranolol (group 5) or 25 ng/kg/min of isoproterenol (group 6). Groups 1 to 4 consisted of 10 subjects each, and groups 5 and 6 consisted of five subjects each. VRPs were determined with the use of basic drive cycle lengths of 600, 500, 400, and 350 msec. Because of sinus tachycardia, sufficient data for comparison of groups 1 to 3 were available only at drive cycle lengths of 400 and 350 msec. Atropine significantly shortened the VRPs in groups 1 to 3, but the magnitude of atropine's effects in group 3 (5.3% to 5.8% shortening at drive cycle length of 350 msec) was significantly greater than in group 1 (2.6% to 3.0% shortening, p less than .05) Data from the control groups demonstrated that there was no effect of time on measurement of VRPs either in the drug-free state or in the presence of propranolol or isoproterenol. The results of this study indicate that cholinergic tone lengthens VRPs in the absence of background sympathetic activity and that this lengthening of VRPs may become accentuated during beta-adrenergic stimulation.
Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism.
Authors: Verstraete M , Miller G A , Bounameaux H , Charbonnier B , Colle J P , Lecorf G , Marbet G A , Mombaerts P , Olsson C G
Published: June 2011

Eight centers participated in a study in which intrapulmonary and intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) were compared in 34 patients with acute massive pulmonary embolism. All patients received intravenous heparin in a bolus of 5,000 IU followed by 1,000 IU/hr. After 50 mg rt-PA given over 2 hr the severity of embolism, determined from pulmonary angiograms, declined by 12% in the intrapulmonary drug group (p less than .005) and 15% in the intravenous drug group (p less than .005); mean pulmonary arterial pressure fell from 31 +/- 7 to 22 +/- 6 mm Hg (p less than .005) and from 31 +/- 12 to 21 +/- 9 mm Hg (p less than .005) in the respective groups. After a further 50 mg given over 5 hr (22 patients), the angiographically determined severity of embolism had decreased by 38% from baseline in the intrapulmonary drug group and by 38% in the intravenous drug group. The mean pulmonary arterial pressure further declined to 18 +/- 7 and 12 +/- 5 mm Hg in the respective groups. Fibrinogen levels dropped to 48% of baseline after 50 mg and to 36% of baseline after 100 mg rt-PA. Some degree of bleeding at puncture and/or operation sites was noted in 16 patients, including four who required a transfusion of two or more units of blood and had been operated on an average of 7.5 days (range 2 to 13) before thrombolytic treatment was started.(ABSTRACT TRUNCATED AT 250 WORDS)
Reentrant ventricular rhythms in the late myocardial infarction period: prevention of reentry by dual stimulation during basic rhythm.
Authors: Restivo M , Gough W B , el-Sherif N
Published: June 2011

Stimulation at two ventricular sites during basic rhythm as a means of preventing the induction of ventricular arrhythmias in the postinfarction heart was investigated. Isochronal maps of ventricular epicardial activation from dogs were analyzed 4 days after ligation of the left anterior descending coronary artery. Activation patterns were obtained by use of a computerized data acquisition system recording from 62 sites. Effective refractoriness and conduction time during basic paced rhythm (S1) for each site were summed to construct isochronal maps of recovery time. The patterns of recovery time on the heart were eccentrically layered, with a narrow zone of differentially prolonged recovery time along one border of the infarct. The formation of an arc of functional conduction block after premature stimulation (S2) was correlated with regions of differentially prolonged recovery time (59 +/- 30 msec, mean +/- SD) between recording sites spaced 5 to 10 mm apart. The recovery time difference between sites that did not block (17 +/- 14 msec) was significantly shorter. The spatial distribution of recovery time on the heart could be modified by application of stimuli at two sites during the basic rhythm. Reentry was prevented by appropriate placement of the secondary site in the ischemic zone and the temporal sequencing of the paired stimuli. Stimulation at the secondary site "peeled back" refractoriness in the ischemic zone. Prevention of reentry was a result of either: (1) a shift in the arc of conduction block toward the ischemic zone, (2) a reduction in the extent of the continuous arc, (3) early activation of regions distal to the arc, or (4) a combination of the above. In two dogs, the arc of block was abolished entirely after dual stimulation. This report illustrates the criteria for effective prevention of reentry, applied to a well-described verifiable model of reentrant activation.
PQRST isoarea maps from patients with the Wolff-Parkinson-White syndrome: an index for global alterations of ventricular repolarization.
Authors: Nadeau R , Ackaoui A , Giorgi C , Savard P , Shenasa M , Pagé P
Published: June 2011

Isoarea maps during the PQRST sequence were computed in 22 healthy subjects and 48 patients with Wolff-Parkinson-White (WPW) syndrome. Thirty-eight patients with WPW were on no medication and 10 were treated with class I, II, or III antiarrhythmic drugs. Seventeen isoarea maps were recorded before and 17 were recorded after accessory pathway ablation. One patient had intermittent preexcitation. Body surface maps from all healthy subjects were similar, although the magnitudes of the maxima and minima showed significant variability. In all patients with WPW who were on no medication and in those on class I and II agents, PQRST maps were normal. Two patients taking amiodarone had abnormal PQRST maps, as did patients early after surgery. In the patient with intermittent preexcitation, PQRST maps were very similar during normal and preexcited beats. In conclusion, our results support the theory that the PQRST time integral reflects intrinsic recovery properties of the heart and is independent of the activation sequence.
Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities.
Authors: Sullivan M J , Higginbotham M B , Cobb F R
Published: June 2011

This study was designed to determine the pathophysiologic basis of increased exercise ventilation in the presence of chronic heart failure. Sixty-four ambulatory patients with chronic heart failure and 38 age-matched normal control subjects performed exercise according to identical staged, symptom-limited bicycle exercise protocols with measurement of hemodynamic, ventilatory, and metabolic responses. Compared with normal subjects, ventilation and the ratio of ventilation to CO2 production (Ve/VCO2), and pulmonary capillary wedge pressure were elevated in patients at rest and during exercise. The ratio of pulmonary dead space to tidal volume (Vd/Vt) also was elevated in the heart failure group at rest and during exercise and was closely related to Ve/VCO2 (all r greater than .72, p less than .001). Rest and exercise arterial PCO2 regulation was normal in patients. Peak exercise Ve/VCO2 did not correlate with pulmonary vascular pressures, but was inversely related to cardiac output (r = -.49, p less than .001). Thus, neurohumoral ventilatory control mechanisms are intact in patients with chronic heart failure and act to maintain normal PaCO2 levels in the face of increased pulmonary dead space. Activation of abnormal reflexes due to hemodynamic derangements during exercise are not important in determining ventilation in the presence of chronic heart failure. The demonstration of a correlation between decreased cardiac output and increased ventilation in the patient group suggests that attenuated pulmonary perfusion may play a role in causing exercise hyperpnea in the presence of chronic heart failure by producing ventilation perfusion abnormalities and thereby increasing physiologic pulmonary dead space.
Physiologic mechanisms governing hemodynamic responses to positive inotropic therapy in patients with dilated cardiomyopathy.
Authors: Borow K M , Lang R M , Neumann A , Carroll J D , Rajfer S I
Published: June 2011

Clinical trials in patients with dilated cardiomyopathy (DCM) have shown a wide disparity in the hemodynamic responses to positive inotropic therapy. In addition, the response of the failing left ventricle to positive inotropic agents reflects the net interaction of multiple factors, including the magnitude of contractile abnormality and compensatory mechanisms. In the current study, left ventricular geometry, loading conditions, and contractile state were assessed in 13 patients with nonischemic DCM with the use of simultaneous high-fidelity pressure measurements and echocardiographic recordings. Comparisons were made with echocardiographic and calibrated carotid pulse data acquired in nine age-matched normal subjects. The patients with DCM were divided according to the left ventricular end-diastolic wall thickness-to-dimension ratio into groups with "appropriate" hypertrophy (i.e., less than or equal to 2 SDs from mean normal; n = 5; group 1) and "inadequate" hypertrophy (i.e., greater than 2 SDs from mean normal; n = 8; group 2). Age, New York Heart Association functional class, left ventricular wall mass index, and left ventricular end-diastolic pressure and dimension were similar for the DCM groups. Baseline left ventricular afterload (defined as circumferential end-systolic wall stress, sigma es) was 168% and 203% greater than normal in groups 1 and 2, respectively. The administration of the beta-adrenoceptor agonist dobutamine decreased left ventricular afterload by 12% in the normal subjects and by 10% in group 1 patients, while augmenting afterload by 5% in group 2 patients. The latter response occurred despite a 17% fall in systemic vascular resistance. Overall left ventricular performance, as assessed by the rate-corrected mean velocity of fiber shortening (Vcfc), was related to left ventricular afterload (i.e., sigma es). The resultant sigma es -Vcfc relationship, a sensitive measure of left ventricular contractility, was determined over a wide range of afterload conditions generated by methoxamine (normal subjects) or nitroprusside (DCM). Baseline left ventricular contractile state was 61% of normal for group 1 and 44% of normal for group 2. The contractile response to dobutamine infusion was 52% of normal for group 1 and only 22% of normal for group 2. Thus, positive inotropic therapy with dobutamine in patients with DCM is limited by (1) an attenuated contractile response and (2) elevated left ventricular afterload, which may be augmented further during its administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Contractile dysfunction and ATP depletion after transient calcium overload in perfused ferret hearts.
Authors: Kitakaze M , Weisman H F , Marban E
Published: June 2011

Although a number of lines of evidence hint that an elevation of intracellular calcium leads to myocardial injury, the cellular consequences of transient Ca overload remain unclear. To determine the contractile, histologic, and metabolic sequelae of transient Ca overload, we measured developed pressure (DP) in isovolumetric Langendorff-perfused ferret hearts at 37 degrees C before and 20 min after three 5 min periods of perfusion with a 10 mM [Ca]o, 1 mM [Mg]o solution (high-Ca group, n = 8) without ischemia, and in control hearts (n = 5) exposed transiently to the same total divalent cation concentration without a change in [Ca]o (9 mM [Mg]o, 2mM [Ca]o). DP, measured at various [Ca]o (0.5 to 5 mM), was depressed in the high-Ca group relative to control (p less than .001). Representative hearts from the control group were histologically normal, whereas hearts from the high-Ca group exhibited rare foci of predominantly "reversible" injury (mitochondrial swelling, glycogen deposition, and clumping of nuclear chromatin). Maximal Ca++-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was also decreased in the high-Ca group (230 +/- 4 vs 262 +/- 6 mm Hg, p less than .001). Cao sensitivity, determined by normalization of the DP-[Ca]o relationship to the corresponding MCAP, was shifted to higher [Ca]o in the high-Ca group. Phosphorus nuclear magnetic resonance spectra were obtained in four high-Ca hearts. [ATP] declined by 30% to 40% after exposure to high [Ca]o, but inorganic phosphate, phosphocreatine, and pH remained unchanged. These results indicate that transient exposure to high [Ca]o without ischemia leaves behind distinctive contractile, metabolic, and histologic sequelae. The possible implications for the pathogenesis of postischemic contractile dysfunction are discussed.
Color Doppler flow mapping in patients with coarctation of the aorta: new observations and improved evaluation with color flow diameter and proximal acceleration as predictors of severity.
Authors: Simpson I A , Sahn D J , Valdes-Cruz L M , Chung K J , Sherman F S , Swensson R E
Published: June 2011

We performed color Doppler flow mapping in 15 patients, 1 week to 17 years old (mean 42 months), with coarctation of the aorta that was confirmed subsequently by angiography and/or surgery. Twelve patients had native coarctation and three had mild recoarctation after surgical repair. Color Doppler flow maps were analyzed with a digital analysis package and a Sony computer system. The diameter in the region of coarctation from the color Doppler flow map (mean = 2.0 +/- 0.8 mm [SD]) correlated well with the coarctation diameter measured at angiography (mean = 1.8 +/- 0.8 mm; r = .83, SEE 0.43 mm) in the 10 patients with native coarctation undergoing angiography, but the coarctation diameter measured by two-dimensional echocardiography (3.9 +/- 1.5 mm) was poorly predictive of the angiographic severity (r = .23). Additionally, spatial acceleration was seen in all patients proximal to the coarctation site, with an aliased and accelerating stream narrowing progressively as it proceeded toward the coarctation site, a pattern that is not seen in healthy subjects. Computer analysis of the color Doppler images provided pseudo three-dimensional and digital velocity maps for blue, red, and green (turbulent) flow velocities to allow an enhanced appreciation of the accelerating stream, easily separating this from normal descending aortic aliasing patterns. The narrowing of the acceleration area in the proximal descending aorta (distal/proximal acceleration zone ratio) was also predictive of the angiographic severity of coarctation (r = .83). The distribution of low-level turbulence seen proximally paralleled the distribution of the proximal accelerating stream.(ABSTRACT TRUNCATED AT 250 WORDS)
Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: a double-blind, cross-over study.
Authors: Brevetti G , Chiariello M , Ferulano G , Policicchio A , Nevola E , Rossini A , Attisano T , Ambrosio G , Siliprandi N , Angelini C
Published: June 2011

A double-blind, cross-over study was designed to evaluate the effects of L-carnitine in patients with peripheral vascular disease. After drug washout, 20 patients were randomly assigned to receive placebo or L-carnitine (2 g bid, orally) for a period of 3 weeks and were then crossed over to the other treatment for an additional 3 weeks. The effect on walking distance at the end of each treatment period was measured by treadmill test. Absolute walking distance rose from 174 +/- 63 m with placebo to 306 +/- 122 m (p less than .01) with carnitine. Biopsy of the ischemic muscle, carried out before and after 15 days of L-carnitine administration in four additional patients, showed that treatment significantly increased total carnitine levels. An additional goal of this study was to ascertain the effects of L-carnitine on the metabolic changes induced by exercise in the affected limb. In six patients under control conditions, arterial and popliteal venous lactate and pyruvate concentrations were determined at rest, when the maximal walking distance was reached, and 5 min after the walking test. Twenty-four hours later, L-carnitine was administered intravenously (3 g as a bolus followed by an infusion of 2 mg/kg/min for 30 min) and metabolic assessments were repeated. Five minutes after the walking test, popliteal venous lactate concentration increased by 107 +/- 16% before treatment and by only 54 +/- 32% (p less than .01) after carnitine. Furthermore, carnitine induced a more rapid recovery to the resting value of the lactate/pyruvate ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Atriofascicular connection or a nodoventricular Mahaim fiber? Electrophysiologic elucidation of the pathway and associated reentrant circuit.
Authors: Tchou P , Lehmann M H , Jazayeri M , Akhtar M
Published: June 2011

Accessory pathways showing decremental properties and inserting into the right ventricle have been frequently described as "nodoventricular" or Mahaim pathways. However, conclusive evidence for a nodal origination of such pathways is lacking. The patient in this study had characteristics typical of such a pathway. Antegradely, the pathway showed decremental, nodelike conduction properties. With the aid of right bundle branch recordings, the pathway was demonstrated to insert directly into the right bundle branch. Atrioventricular reciprocating tachycardia could be readily initiated by atrial or ventricular pacing. The QRS morphology was normal during sinus rhythm and demonstrated a left bundle branch block pattern with normal axis during tachycardia. The reentrant circuit involved antegrade conduction over the accessory pathway and retrograde conduction via the bundle branches, His bundle, and the atrioventricular node. More significantly, late atrial stimuli delivered during tachycardia could preexcite the ventricle via the accessory pathway despite their inability to enter the atrioventricular node. Thus, the upper "turn around" of the reentrant circuit involved atrial tissue and the accessory pathway originated directly from the right atrium independent of the atrioventricular node. In view of these new findings and other recent observations during surgical resection of similar pathways, a reassessment of previous descriptions of "nodoventricular" fibers may be necessary. Many of these pathways may actually represent atriofascicular or atrioventricular connections with decremental properties.