bluuebunny/crossref_metadata_2025 huggingface dataset:
Right atrial pressure-volume relationships in tricuspid regurgitation.
Authors: Miller M J , McKay R G , Ferguson J J , Sahagian P , Nakao S , Come P C , Grossman W
Published: June 2011

Pressure-volume relationships in the right atrium were examined before and after the creation of acute experimental tricuspid regurgitation in pigs. A 1.3 kHz multielectrode impedance catheter with a measuring current of 4 mA was used to determine instantaneous right atrial pressure and relative blood volume; right atrial dimension was assessed simultaneously with ultrasonic crystals attached to the atrial walls. Impedance volume waveforms and ultrasonic crystal dimensions closely paralleled each other at baseline and after the induction of tricuspid regurgitation. The normal right atrial pressure-volume plot exhibited a figure-of-eight configuration, with an "a-loop" and a "v-loop" corresponding to the a-wave and v-wave of the right atrial pressure tracing. With severe tricuspid regurgitation, atrial pump function was abolished, and the pressure-volume plot exhibited a single clockwise loop, consistent with complete ventricularization of the right atrium. Intermediate degrees of tricuspid regurgitation preserved the figure-of-eight loop, but the size of both the a-loop and the v-loop were increased, consistent with a Starling-type load imposed on the atrium by the regurgitant blood volume. Increased right ventricular afterload mediated by constriction of the pulmonary artery and infusion of methoxamine reversibly converted the right atrial pressure-volume loop from that of mild to that of severe tricuspid regurgitation. Alternatively, constriction of the inferior vena cava and infusion of nitroprusside changed the right atrial pressure-volume loop from that of a severe pattern of tricuspid regurgitation to a less severe type of pattern. Infusion of dobutamine increased the size of the a-loop relative to the v-loop both at baseline and after induction of tricuspid regurgitation. We conclude that tricuspid regurgitation induces changes in right atrial mechanics that can be detected and quantified with an impedance catheter.
Effect of epinephrine on cerebral and myocardial perfusion in an infant animal preparation of cardiopulmonary resuscitation.
Authors: Schleien C L , Dean J M , Koehler R C , Michael J R , Chantarojanasiri T , Traystman R , Rogers M C
Published: June 2011

We assessed the efficacy of conventional cardiopulmonary resuscitation (CPR) in 2-week-old piglets. We determined intrathoracic vascular pressures, cerebral (CBF) and myocardial blood flows (MBF), and cerebral oxygen uptake during conventional CPR in this infant animal preparation and contrasted these results with those of previous work on adult animals. We further examined the effects of the infusion of epinephrine on these pressures and flows and on cerebral oxygen uptake, which has not been previously evaluated in adult preparations. Conventional CPR was performed on pentobarbital-anesthetized piglets with a 20% sternal displacement with the use of a pneumatic piston compressor. Chest recoil was incomplete, leading to an 18% to 27% reduction in anteroposterior diameter during the relaxation phase. Aortic and right atrial pressures in excess of 80 mm Hg were generated. These pressures are greater than those generally obtained in adult animals with similar percent pulsatile displacements. CBF and MBF were also initially greater than those reported in adult animals undergoing conventional CPR. However, when CPR was prolonged beyond 20 min, aortic pressure fell and CBF and MBF declined to the near-zero levels seen in adult preparations. At 5 min of CPR, CBF and MBF were 24 +/- 7 and 27 +/- 7 ml . min-1 x 100 g-1 (50% and 17% of the values during cardiac arrest), respectively. With the continuous infusion of epinephrine (4 micrograms/kg/min) in another group of animals, MBF was significantly greater at 20 min of CPR and CBF and cerebral O2 uptake were greater at 35 min of CPR as a result of higher perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of verapamil on ischemia-induced changes in extracellular K+, pH, and local activation in the pig.
Authors: Fleet W F , Johnson T A , Graebner C A , Engle C L , Gettes L S
Published: June 2011

In experimental animals, the calcium channel-blocking agents lessen the arrhythmogenic, ionic, metabolic, and electrical changes that occur during acute myocardial ischemia. To date, these effects have been studied separately, and the effects of these agents on local activation have not been correlated with ionic or metabolic effects. In open-chest, anesthetized swine, we used bipolar and ion-selective plunge electrodes to simultaneously measure ischemia-induced changes in left ventricular local activation, extracellular K+ ([K+]e), and extracellular pH (pHe). The effects of verapamil (0.2 mg/kg) on these variables were studied during a series of 10 min occlusions of the left anterior descending coronary artery. Compared with control occlusions, verapamil (1) slowed the rise in [K+]e at the center of the ischemic zone and at its lateral margin and decreased the peak [K+]e by 0.9 mM at the center (p less than .05) and by 0.1 mM at the margin (p = .10); (2) slowed the development of acidosis and decreased the peak level of acidosis beyond that expected solely as a result of serial occlusions by 0.19 pH units at the center (p less than .05) and by 0.07 pH units at the margin (p = .10); and (3) slowed the development of local activation delay and often prevented the local activation block that was observed during control occlusions. Effects on local activation became less marked at [K+]e levels greater than 9.0 mM, and the effects of verapamil on local activation were not explained solely by its effects on the local rise in [K+]e or fall in pHe. A possible mechanism for this additional effect on local activation is suggested by preliminary results showing a diminution by verapamil of ionic inhomogeneity.
Mechanical thrombolysis: a new rotational catheter approach for acute thrombi.
Authors: Ritchie J L , Hansen D D , Vracko R , Auth D C
Published: June 2011

We tested a new rotational thrombectomy catheter in acute thrombi formed both in vitro and in vivo. The catheter consisted of a rounded platinum tip, 0.025 inch diameter by 0.08 inch long, attached to a flexible steel guidewire supported by an external sheath. In vitro, the force required to penetrate thrombus was reduced fivefold by rotation of the catheter at 4000 rpm (0.75 +/- 1.2 g rotating vs 3.9 +/- 2.1 g static; p less than .001). Fibrin was extracted selectively from the thrombus and tightly wound about the shaft (3.8 +/- 1.5 mg rotating vs 0.75 +/- 0.4 mg static; p less than .001). In vivo, subtotal or complete thrombosis of the canine femoral artery was created. Thrombectomy by catheter rotation always produced tightly wound adherent fibrin on the catheter shaft. Angiographic patency was restored in 20 of 22 (91%) arteries, totally in seven of 22 (32%) and partially (greater than 20% increase in lumen diameter) in 13 of 22 (59%). There was one arterial perforation (5%). We conclude that this new mechanical catheter device reduces the force required to penetrate thrombus. Additionally, by winding fibrin about its shaft, the catheter is able to selectively remove the fibrin matrix of thrombus. Thus both the ease of initial thrombus recanalization as well as physical removal of thrombus are promoted by this new approach. Such an approach may be relevant to the treatment of recent thrombosis in acute myocardial infarction.
Hematologic effects of the high-energy endocardial ablation technique.
Authors: Holt P M , Boyd E G
Published: June 2011

Ablation of atrioventricular conduction is now widely accepted in the management of supraventricular arrhythmias. Reports of high temperatures, high pressures, and gas production suggest that there may be adverse effects on the blood, the electrode, and the cardiovascular system. In this investigation, using samples of fresh, heparinized pig blood, we measured hemolytic damage, the liberated gas volume and composition, and electrode erosion associated with high-energy electrical ablation. The blood was tested in a 10 liter tank at room temperature. Impulses of 10 to 400 J were applied to new USCI No. 6F bipolar pacing electrodes using both positive and negative polarities. Voltage and current waveforms were recorded. The volume of gas liberated with cathodal electrodes was 0.50 microliter/J up to 50 J and 0.29 microliter/J above 100 J. It was composed predominantly of hydrogen and nitrogen, with carbon dioxide and oxygen. With positive electrodes, the gas volume was linearly related to energy at 4.34 microliter/J up to 200 J and also contained carbon monoxide. The hemolysis was directly proportional to impulse energy for both cathodal and anodal electrodes, being 1.37 microliter/J and 4.48 microliters/J, respectively. Electrode erosion was substantial but clinically acceptable. We conclude that there are marked differences in the energy conversion processes and, where the same energy can achieve a comparable clinical effectiveness, there are advantages in using a cathodal electrode polarity. It is also advisable to use lower energies.
Protective effects of N-2-mercaptopropionyl glycine against myocardial reperfusion injury after neutrophil depletion in the dog: evidence for the role of intracellular-derived free radicals.
Authors: Mitsos S E , Askew T E , Fantone J C , Kunkel S L , Abrams G D , Schork A , Lucchesi B R
Published: June 2011

Reperfusion of the previously ischemic myocardium is associated with the production of oxygen free radicals and their metabolites, which contribute to the ultimate extent of irreversible myocardial injury. The relative importance of polymorphonuclear leukocytes vs intracellular-derived oxygen metabolites has remained uncertain. We evaluated the effectiveness of a free-radical scavenger, N-2-mercaptopropionyl glycine (MPG), in limiting infarct size after ischemia/reperfusion in dogs that were depleted of neutrophils with specific antisera. Twenty-four urethane-anesthetized open-chest dogs were subjected to 90 min of ischemia by occlusion of the left circumflex coronary artery followed by 6 hr of reperfusion. Dogs were randomly assigned to receive nonimmune serum, neutrophil antiserum, or neutrophil antiserum plus MPG (20 mg/kg intra-atrially 15 min before reperfusion was initiated and for 45 min after reperfusion). Infarct size, as a percent of the area at risk, was reduced by 33% in the neutrophil antiserum group as compared with the nonimmune group (30.7 +/- 2.7% vs 45.6 +/- 3.7%, p less than .01). The combined administration of neutrophil antiserum plus MPG reduced the size of infarction by 63% of the area at risk compared with that in the nonimmune group (17.0 +/- 2.7% vs 45.6 +/- 3.7%, p less than .01). The reduction in infarct size with neutrophil antiserum plus MPG was significantly greater than that with the neutrophil antiserum alone (p less than .01). The areas at risk did not differ among the groups. Myocardial protection could not be explained on the basis of hemodynamic differences. The observation that MPG enhances the protective effects of neutrophil depletion suggests that both extramyocardial- and intramyocardial-derived oxygen free radicals contribute significantly to reperfusion-induced myocardial injury.
Prognostic significance of electrocardiographic site of infarction after correction for enzymatic size of infarction.
Authors: Hands M E , Lloyd B L , Robinson J S , de Klerk N , Thompson P L
Published: June 2011

To assess whether the site of myocardial infarction is an independent prognostic indicator, the outcome of patients with anterior myocardial infarction was compared with that of patients with inferior infarction. A consecutive series of patients who had suffered their first myocardial infarction was analyzed (398 with anterior and 391 with inferior infarction). Patients with anterior myocardial infarction had a higher 1 year mortality than those with inferior infarction (18.3% vs 10.5%, p = .002). When patients were matched for infarct size determined by peak creatine kinase (CK) level expressed as a multiple of the upper limit of normal, those with anterior myocardial infarction tended to have a higher 1 year mortality than those with inferior infarction for all subgroups of peak CK. Early mortality (day 1 to 28 after myocardial infarction) was greater in the anterior than in the inferior myocardial infarction group (10% vs 6.4%, p = .03); this was most significant when peak CK was greater than four times normal (12.4% vs 7.0%, p = .04). Late mortality was also higher in the anterior (8.4% vs 4.1%, p = .04) than the inferior infarction group and this was most significant when peak CK was less than two times normal (15.2% vs 0%, p = .02) or greater than eight times normal (10.6% vs 4.1%, p = .04). Multivariate analysis with proportional-hazards regression confirmed the prognostic significance of location of infarction independent of peak CK level. Thus, infarct location was found to be a predictor of prognosis that is independent of infarct size based on peak CK levels.
Bayesian analysis versus discriminant function analysis: their relative utility in the diagnosis of coronary disease.
Authors: Detrano R , Leatherman J , Salcedo E E , Yiannikas J , Williams G
Published: June 2011

Both Bayesian analysis assuming independence and discriminant function analysis have been used to estimate probabilities of coronary disease. To compare their relative accuracy, we submitted 303 subjects referred for coronary angiography to stress electrocardiography, thallium scintigraphy, and cine fluoroscopy. Severe angiographic disease was defined as at least one greater than 50% occlusion of a major vessel. Four calculations were done: (1) Bayesian analysis using literature estimates of pretest probabilities, sensitivities, and specificities was applied to the clinical and test data of a randomly selected subgroup (group I, 151 patients) to calculate posttest probabilities. (2) Bayesian analysis using literature estimates of pretest probabilities (but with sensitivities and specificities derived from the remaining 152 subjects [group II]) was applied to group I data to estimate posttest probabilities. (3) A discriminant function with logistic regression coefficients derived from the clinical and test variables of group II was used to calculate posttest probabilities of group I. (4) A discriminant function derived with the use of test results from group II and pretest probabilities from the literature was used to calculate posttest probabilities of group I. Receiver operating characteristic curve analysis showed that all four calculations could equivalently rank the disease probabilities for our patients. A goodness-of-fit analysis suggested the following relationship between the accuracies of the four calculations: (1) less than (2) approximately equal to (4) less than (3). Our results suggest that data-based discriminant functions are more accurate than literature-based Bayesian analysis assuming independence in predicting severe coronary disease based on clinical and noninvasive test results.
Dynamics of oxygen uptake during exercise in adults with cyanotic congenital heart disease.
Authors: Sietsema K E , Cooper D M , Perloff J K , Rosove M H , Child J S , Canobbio M M , Whipp B J , Wasserman K
Published: June 2011

The dynamic increase in oxygen uptake (VO2) at the start of exercise reflects the circulatory adjustments to metabolic changes induced by the exercise. Because VO2 measured at the lungs is the product of pulmonary blood flow and arteriovenous oxygen difference, pathologic conditions affecting the capacity of these factors to change would be expected to alter VO2 kinetics. To determine whether measurement of VO2 kinetics can detect conditions in which the pulmonary blood flow response to exercise is abnormal, VO2 was measured, breath-by-breath, during the transition from rest to exercise in 13 adults with cyanotic congenital heart disease (central venoarterial shunting) and in nine normal subjects. The increase in VO2 above baseline during the first 20 sec of exercise (phase I), reflecting the immediate increase in pulmonary blood flow, was diminished in the patients compared with that in normal subjects (14.8 +/- 10.9 vs. 49.8 +/- 19.2 ml of oxygen) (p less than .001). The patients' phase I responses correlated with their reported physical activity tolerance (p less than .01). In addition, the second phase of the VO2 response kinetics was prolonged in patients compared with normal subjects (half-time = 63 +/- 13 vs 15 +/- 13 sec) (p less than .001). We conclude that striking disturbances in VO2 kinetics occur in patients with cyanotic congenital heart disease and that these measurements provide a useful noninvasive means of evaluating the degree to which the increase in pulmonary blood flow is constrained in response to exercise.
Effect of activation of the H1 receptor on coronary hemodynamics in man.
Authors: Vigorito C , Poto S , Picotti G B , Triggiani M , Marone G
Published: June 2011

We evaluated the effects of selective activation of H1 receptors on coronary hemodynamics in 16 patients divided into two groups: group A, 11 patients with atypical angina or valvular heart disease and normal coronary arteries, and group B, five patients with spontaneous angina, four of whom had significant (greater than 70% stenosis) coronary artery disease and one with normal coronaries. Selective H1 receptor stimulation was achieved by infusing 0.5 microgram/kg/min of histamine intravenously for 5 min after pretreatment with cimetidine (25 mg/kg). Heart rate was maintained constant (100 beats/min) by coronary sinus pacing and coronary blood flow (CBF) was measured by thermodilution. In group A, during histamine infusion mean aortic pressure fell from 99 +/- 5 to 77 +/- 4 mm Hg (mean +/- SEM, p less than .001), coronary vascular resistance (CVR) decreased from 1.07 +/- 0.17 to 0.82 +/- 0.14 mm Hg/ml/min (p less than .02), and CBF and myocardial oxygen consumption remained unchanged. None of the patients in this subgroup developed angina during histamine infusion. In group B, while no significant average changes in mean arterial pressure, CVR, or CBF were observed, two of the five patients (40%) developed angina during histamine infusion, accompanied by ST-T elevation, a decrease in CBF, and an increase in CVR. In one of these two patients circumflex coronary arterial spasm was angiographically demonstrated during histamine-induced angina. Our results suggest that stimulation of the H1 receptor induces a reduction of CVR, probably resulting from vasodilation of small coronary resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased thromboxane biosynthesis in a human preparation of platelet activation: biochemical and functional consequences of selective inhibition of thromboxane synthase.
Authors: Reilly I A , Doran J B , Smith B , FitzGerald G A
Published: June 2011

Although thromboxane A2 is a potent platelet agonist and vasoconstrictor in vitro, our knowledge of its pathophysiologic importance in human disease is limited. To facilitate the elucidation of its role in vivo, we sought to define a human syndrome in which pharmacologic interventions designed to inhibit the biosynthesis or biologic actions of thromboxane A2 might be appropriately assessed. Patients with severe peripheral vascular disease were selected on the basis of elevated plasma beta-thromboglobulin and circulating platelet aggregates and compared with healthy, age-matched control subjects. In addition to the platelet indexes, their bleeding time was shorter and excretion of 2,3-dinor-thromboxane B2, a noninvasive index of thromboxane formation in vivo, and 2,3-dinor-6-keto-prostaglandin F 1 alpha, the major urinary metabolite of prostacyclin, was markedly increased. A selective inhibitor of thromboxane synthase, imidazo (1,5-2) pyridine-5-hexanoic acid, was administered to these patients under randomized, double-blind, controlled conditions. Platelet aggregation ex vivo, the circulating platelet aggregate ratio, and the bleeding time were all unaltered, despite almost maximal inhibition of platelet thromboxane formation 1 hr after dosing. By contrast, pronounced inhibition of aggregation was observed when platelet cyclooxygenase was inhibited by aspirin. During long-term dosing with the synthetic inhibitor, inhibition of thromboxane biosynthesis was incomplete, which would permit continued thromboxane-dependent platelet aggregation to occur. However, the failure of enzyme blockade to influence platelet function at the time of maximal drug action, despite efficient inhibition of serum thromboxane B2, suggests that accumulation of proaggregatory endoperoxides is also likely to have contributed to the persistence of platelet activation. We have characterized a human preparation in which platelet activation coexists with increased thromboxane biosynthesis. In this setting, platelet activation persists despite long-term administration of a thromboxane synthase inhibitor in a dosing regimen representative of that employed in clinical trials. Prolongation of drug action and combination with antagonists of the shared endoperoxide/thromboxane A2 receptor may be necessary to assess the potential of selective inhibition of thromboxane synthase as a therapeutic strategy in man.
Valvular-ventricular interaction: importance of the mitral apparatus in canine left ventricular systolic performance.
Authors: Hansen D E , Cahill P D , DeCampli W M , Harrison D C , Derby G C , Mitchell R S , Miller D C
Published: June 2011

As the mitral valvular apparatus tenses during systole, forces transmitted along the chordae tendineae to the left ventricular chamber may influence left ventricular performance. To test this hypothesis, 10 dogs anesthetized with fentanyl were studied during cardiopulmonary bypass. The importance of the mitral apparatus in left ventricular systolic function was assessed independent of load by means of the slope of the contractile state-dependent left ventricular peak isovolumetric pressure-volume relationship (Emax), which was measured at constant heart rate and aortic pressure with a micromanometer inside a left ventricular intracavitary balloon before and immediately after all chordae tendineae were severed. Herniation of the balloon was prevented by a disk secured to the mitral anulus. Emax decreased from 11.97 +/- 3.35 (+/- SD) to 6.38 +/- 0.96 mm Hg/ml (p less than .001) with chordal severing. The volume intercept (Vo) was unchanged. Fluoroscopic studies of the balloon contour in eight additional dogs revealed dyskinesia in the area of the papillary muscle insertion and substantial alterations in chamber geometry during systole after the chordae were severed. Accordingly, we conclude that global left ventricular systolic performance is impaired when chordal attachments of the mitral valve are disrupted. Changes in left ventricular geometry or loss of inward force normally transmitted to the left ventricular wall as the valve tense may underlie these changes. These findings suggest that postoperative left ventricular dysfunction after mitral valve replacement may be attributable, in part, to excision of the native mitral apparatus at the time of surgery and support efforts to spare chordae during mitral valve surgery.
Mechanisms underlying the antiarrhythmic and arrhythmogenic actions of quinidine in a Purkinje fiber-ischemic gap preparation of reflected reentry.
Authors: Shen X T , Antzelevitch C
Published: June 2011

The effects of therapeutic levels of quinidine were studied in an ischemic gap preparation of reflected reentry. The preparation consisted of a Purkinje fiber mounted in a three-compartment chamber. A narrow central compartment was perfused with a solution prepared to mimic the extracellular milieu at a site of ischemia. Quinidine in concentrations that exert little effect on normal Purkinje tissue, 1 to 2 micrograms/ml, greatly impaired conduction and markedly prolonged refractoriness across the ischemic gap. The drug effected these changes by (1) extending the inexcitable zone within the depressed region, (2) decreasing the amplitude of the input signal entering this zone, and (3) decreasing the excitability of the tissue beyond the depressed zone (evaluated by current clamp techniques). These actions of the drug produced both antiarrhythmic and proarrhythmic effects. When the initial level of conduction impairment was high, quinidine totally suppressed reflected reentry at all frequencies by precipitating complete anterograde conduction block. At intermediate levels of block, the drug generally caused a prominent shift of the frequency dependence of reentrant activity to lower stimulation rates. Finally, when conduction was relatively less impaired, quinidine created the conditions for reflected reentry to occur. Our results suggest that the heart rate dependence of reentrant arrhythmias might be of prognostic value in the administration of antiarrhythmic drugs.
The influence of residual coronary stenosis on size of infarction after reperfusion in a canine preparation.
Authors: Schmidt S B , Varghese P J , Bloom S , Yackee J M , Ross A M
Published: June 2011

The effect of a residual coronary artery stenosis on size of myocardial infarction was studied in an open-chest canine preparation of coronary occlusion and reperfusion. Eighteen male mongrel dogs (16 to 26 kg) underwent left thoracotomy under general anesthesia; the circumflex artery was instrumented with a hydraulic cuff occluder, a screw clamp, and an electromagnetic flow probe. Animals were randomized to one of three groups: group I (n = 6) had a 6 hr circumflex occlusion, group II (n = 6) had a 2 hr occlusion followed by 4 hr of partial reperfusion through a residual stenosis adjusted to approximately 30% of baseline flow, and group III (n = 6) had full reperfusion for 4 hr after a 2 hr occlusion. Zones of risk, infarction, and no reflow were defined by staining with Evans blue, triphenyl tetrazolium chloride, and fluorescein, respectively. At 6 hr the hearts were excised and areas of risk, infarction, no reflow, and hemorrhage were determined by planimetry of serial transverse heart slices (5 mm thick). Infarction as a percent of the risk area was 96 +/- 1% in group I, 90 +/- 2% in group II, and 79 +/- 4% in group III (p less than .001), and the differences between each of the groups were significant. Gross hemorrhage was seen in none of the six dogs in group I, two of the six in group II, and five of the six in group III, but did not affect infarct size. We conclude that residual stenoses may exert a deleterious effect on the outcome of coronary reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanics of postextrasystolic potentiation in normal subjects and patients with valvular heart disease.
Authors: Wisenbaugh T , Nissen S , DeMaria A
Published: June 2011

To determine the relative influence of preload, afterload, and inotropic state on postextrasystolic potentiation (PESP) of ventricular performance in man, we computed angiographic left ventricular volume and wall stress frame by frame for a control and potentiated beat in each of 31 patients. In 10 normal subjects, PESP increased ejection fraction by 14%, while left ventricular end-diastolic volume increased by 8% (p less than .001) and end-systolic stress fell by 21% (p less than .005). Enhanced diastolic filling (+6%, p less than .005) with a small decline in end-systolic stress (-8%, p = NS) likewise contributed to potentiation of ejection fraction (+14%, p less than .001) in seven patients with aortic stenosis. Diastolic filling was not significantly augmented during the compensatory pause in six patients with isolated mitral regurgitation, nor in eight patients with aortic regurgitation (+2%, p = NS for both). Although afterload tended to fall for potentiated beats in patients with aortic (-11%, p = NS) and mitral regurgitation (-23%, p = NS), analysis of ejection fraction-end-systolic stress relationships demonstrated an independent effect of inotropic state on potentiated ejection performance. Thus, utilization of preload reserve contributed to PESP in normal subjects and patients with aortic stenosis, but not in those with volume overload imposed by chronic valvular regurgitation. Enhanced inotropic state independent of small changes in afterload was demonstrated in all subgroups.
Does prostacyclin enhance the selective pulmonary vasodilator effect of oxygen in children with congenital heart disease?
Authors: Bush A , Busst C , Booth K , Knight W B , Shinebourne E A
Published: June 2011

We have obtained dose-response curves for the effects of prostacyclin on the pulmonary and systemic circulations in 20 children (median age 3 years) with pulmonary hypertension complicating congenital heart disease. Results were obtained with the children breathing both air and 100% oxygen. Under both sets of conditions, remote respiratory mass spectrometry was used to measure oxygen consumption and hence cardiac output by the direct Fick principle. When the subjects breathed air, prostacyclin caused a dose-dependent fall in pulmonary vascular resistance (measured in mm Hg . liter-1 . min . m2) (11.12 to 8.07, standard error of difference [SED] = 0.5, p less than .01). The level of the pulmonary vascular resistance when the subjects breathed air during the infusion of 20 ng/kg/min prostacyclin was not significantly different from that found when they breathed 100% oxygen and did not receive the drug (8.67 vs 8.93, SED = 0.55, p = NS). When infused while the subjects breathed 100% oxygen, prostacyclin caused additional dose-dependent pulmonary vasodilation (pulmonary vascular resistance 8.93 to 7.23, SED = 0.3, p less than .01). Unlike 100% oxygen, prostacyclin was not selective, and caused tachycardia and systemic hypotension at the higher doses. These results suggest that in children with congenital heart disease 100% oxygen does not maximally vasodilate the pulmonary circulation, and further pulmonary vasodilatation can be obtained with a blood-borne agent.
Direct measurement of inner and outer wall thickening dynamics with epicardial echocardiography.
Authors: Myers J H , Stirling M C , Choy M , Buda A J , Gallagher K P
Published: June 2011

Simple geometric models of the left ventricle and indirect experimental measurements suggest that the inner myocardial wall contributes the largest fraction to total wall thickening. We measured transmural differences in regional wall thickening directly, using an epicardial M mode echocardiographic transducer (6 mm diameter, 5 MHz) placed on the anterior free wall of the left ventricle. Wall thickness was partitioned into inner and outer regions by inserting a waxed, 3-0 suture at different depths within the wall. The suture was used as an intramural echo target that was imaged simultaneously with the endocardium to determine inner and outer fractional contribution to total wall thickness. Data were collected in open-chest dogs at rest, during inotropic stimulation with isoproterenol, and during right heart bypass, which was used to vary cardiac output and preload. Results obtained with this method demonstrated that systolic wall thickness was nonuniform at rest and during each intervention. The fractional contributions to total wall thickening of the inner, middle, and outer thirds of the myocardial wall were estimated from the data to be 58%, 25%, and 17%, respectively. The experimental findings corresponded closely to theoretical predictions, supporting the conclusion that a gradient of thickening exists across the myocardial wall, with the inner portion of the wall contributing the largest fraction to total systolic thickening.
Interrelationship of mid-diastolic mitral valve motion, pulmonary venous flow, and transmitral flow.
Authors: Keren G , Meisner J S , Sherez J , Yellin E L , Laniado S
Published: June 2011

This study offers a unifying mechanism of left ventricular filling dynamics to link the unexplained mid-diastolic motion of the mitral valve with an associated increase in transmitral flow, with the phasic character of pulmonary vein flow, and with changes in the atrioventricular pressure difference. M mode echograms of mitral valve motion and Doppler echocardiograms of mitral and pulmonary vein flow velocities were recorded in 12 healthy volunteers (heart rate = 60 +/- 9 beats/min). All echocardiograms showed an undulation in the mitral valve (L motion) at a relatively constant delay from the peak of the diastolic phase of pulmonary vein flow (K phase). In six subjects, the L motion was also associated with a distinct wave of mitral flow (L wave). Measured from the onset of the QRS complex, Q-K was 577 +/- 39 msec; Q-L was 703 +/- 42 msec, and K-L was 125 +/- 16 msec. Multiple measurements within each subject during respiratory variations in RR interval indicated exceptionally small differences in the temporal relationships (mean coefficient of variation 2%). Early rapid flow deceleration is caused by a reversal of the atrioventricular pressure gradient, and the L wave arises from the subsequent reestablishment of a positive gradient due to left atrial filling via the pulmonary veins. The mitral valve moves passively in response to the flowing blood and the associated pressure difference. This interpretation is confirmed by (1) a computational model, and (2) a retrospective analysis of data from patients with mitral stenosis and from conscious dogs instrumented to measure transmitral pressure-flow relationships.
Clinical and prognostic importance of persistent precordial (V1-V4) electrocardiographic ST segment depression in patients with inferior transmural myocardial infarction.
Authors: Lembo N J , Starling M R , Dell'Italia L J , Crawford M H , Chaudhuri T K , O'Rourke R A
Published: June 2011

Forty-three consecutive patients with acute inferior transmural myocardial infarction but no history or electrocardiographic evidence of prior myocardial infarction were evaluated prospectively to assess the clinical and prognostic importance of persistent precordial (V1-V4) ST segment depression. Patients were evaluated within 24 hr of admission by history, physical examination, cardiac enzyme levels, right heart catheterization, and radionuclide angiography; all were followed for 1 year. Ten of the 43 patients (group I) had persistent anterior precordial ST segment depression, defined as 1 mm or greater in one or more precordial leads (V1-V4) 24 hr after admission to the coronary care unit, and 33 patients (group II) did not. Clinical variables that differed between groups I and II, respectively, included mean age (67 +/- 9 [+/- 1 SD] vs 59 +/- 8 years; p less than .01), incidence of Killip class II to IV (100% vs 33%; p less than .001), and average peak creatine kinase concentration (2878 +/- 1139 vs 1511 +/- 1034 IU/liter; p less than .001). Hemodynamic differences between groups I and II included a higher pulmonary arterial wedge pressure (19 +/- 4 vs 11 +/- 5 mm Hg; p less than .001) and a lower cardiac index (2.0 +/- 0.5 vs 2.6 +/- 0.7 liters/min/m2; p less than .05). An evaluation of left ventricular ejection fraction and wall motion index by radionuclide angiography showed that group I had a lower ejection fraction (44 +/- 11% vs 53 +/- 10%; p less than .05) and higher wall motion index (1.7 +/- 0.4 vs 1.4 +/- 0.3; p less than .05) compared with group II.(ABSTRACT TRUNCATED AT 250 WORDS)
The role of initial minimum potentials on body surface maps in predicting the site of accessory pathways in patients with Wolff-Parkinson-White syndrome.
Authors: Kamakura S , Shimomura K , Ohe T , Matsuhisa M , Toyoshima H
Published: June 2011

Forty-one patients (23 men and 18 women, ages 20 to 66 years) with Wolff-Parkinson-White syndrome were studied with isopotential body surface maps during sinus rhythm to find the most reliable index for predicting the sites of single accessory pathways. The sites predicted by surface maps were compared with those confirmed by multicatheter electrophysiologic study or in the course of surgical operation. Location of the initial minimum by a time criterion, 40 msec after onset of the QRS complex, was not reliable enough for prediction in patients with the small delta wave on their electrocardiograms, because ventricular activation via the normal conduction pathway significantly influenced the location of the minimum. Location of the minimum by an amplitude criterion, -0.15 mV or slightly deeper, was influenced minimally by fusion of ventricular activation, the patient's body size, or age and corresponded well to the site of the accessory pathway in 36 of 41 patients. Those minima appeared on circumscribed areas of the map in accordance with the anatomic subdivisions of the atrioventricular ring. Thus location of the minimum by the amplitude criterion was an excellent index for predicting the site of the accessory pathway, regardless of the degree of ventricular fusion. These amplitude-based map features suggest that nonstandard electrocardiograms recorded from selected positions on the body surface can be used as accurate predictors of the sites of accessory pathways.
Family history of heart attack: a modifiable risk factor?
Authors: Khaw K T , Barrett-Connor E
Published: June 2011

A family history of heart attack is reported to be an independent predictor of cardiovascular death in men. In a 9 year follow-up of 4014 adults from 40 to 79 years old in the Rancho Bernardo Study, men under 60 years of age with a family history of heart attack were at fivefold increased risk. In this study, we sought to determine whether modifiable risk factors, i.e., blood pressure, plasma cholesterol, obesity, and cigarette smoking, have a differential effect on cardiovascular risk in those with and without a family history of heart attack. For both sexes, cigarette smoking was a stronger predictor of cardiovascular disease in those with a family history of heart attack (relative risk of smokers vs nonsmokers was 2.5 for men and 4.0 for women) than in those with no such family history (relative risk of smokers vs nonsmokers was 1.1 for men and 1.7 for women). Conversely, an increased risk of cardiovascular mortality in men with a family history of heart attack was present predominantly in smokers (relative risk related to positive family history was 1.2 in nonsmokers, and 3.3 in smokers). An estimated 68% of the excess deaths in men with a family history of heart attack were attributable solely to the interaction of family history with smoking habit and were therefore potentially avoidable. The risk of cardiovascular disease associated with an apparently inherited predisposition appears to be profoundly affected by modifiable behavior.
Failure to augment maximal limb blood flow in response to one-leg versus two-leg exercise in patients with severe heart failure.
Authors: LeJemtel T H , Maskin C S , Lucido D , Chadwick B J
Published: June 2011

Lower limb blood flow, oxygen uptake, and femoral vein O2 content were measured at rest and during maximal bicycle exercise, performed with two legs and one leg, in four normal subjects and in five patients with severe congestive heart failure. While in normal subjects femoral vein blood flow and lower limb vascular conductance were significantly greater during one-leg exercise than during two-leg exercise (6084 +/- 745 vs 5370 +/- 803 ml/min, p less than .05, and 52.3 +/- 8.0 vs 45.1 +/- 8.2 U X 10(3), p less than .05, respectively), in patients with severe congestive heart failure these values were similar during the two forms of exercise (1082 +/- 459 vs 1053 +/- 479 ml/min and 9.6 +/- 3.7 vs 9.4 +/- 3.5 U X 10(3), respectively). In five additional patients, one-leg maximal bicycle exercise was performed before and after administration of phentolamine into the femoral artery of the active leg. Regional alpha-adrenergic blockade with phentolamine did not alter maximal oxygen uptake attained during one-leg bicycle exercise (9.8 +/- 1.5 vs 10.3 +/- 1.9 ml/kg). Lower limb blood flow and femoral vein O2 content attained during maximal one-leg exercise were also similar before and after phentolamine. Thus, in contrast with normal subjects, patients with severe congestive heart failure were unable to further increase limb blood flow during one-leg bicycle exercise. Moreover, local alpha-adrenergic blockade does not augment blood flow to the active limb during maximal one-leg bicycle exercise. This suggests that the ability of the muscular vasculature to vasodilate during exercise is impaired and may be a limiting factor to maximal exercise capacity in such patients.
Predictive value of the exercise tolerance test for mortality in North American men: the Lipid Research Clinics Mortality Follow-up Study.
Authors: Gordon D J , Ekelund L G , Karon J M , Probstfield J L , Rubenstein C , Sheffield L T , Weissfeld L
Published: June 2011

More than 3600 white men, from 30 to 79 years old and without a history of myocardial infarction, underwent submaximal treadmill exercise tolerance tests as part of their baseline evaluation for the Lipid Research Clinics Mortality Follow-up Study. The exercise test was conducted according to a common protocol and coded centrally; depression of the ST segment by at least 1 mm (visual coding) and/or 10 microV-sec (ST integral, computer coding) signified a positive test. Concurrent measurements of age, blood pressure, history of cigarette smoking, and plasma levels of lipids, lipoproteins, and glucose, as well as other coronary risk factors, were obtained. Cumulative mortality from cardiovascular disease was 11.9% (22/185) over 8.1 years mean follow-up among men with a positive exercise test vs 1.2% (36/2993) over 8.6 years mean follow-up among men with a negative test. Three-quarters (43) of these deaths were due to coronary heart disease. The relative risk for cardiovascular mortality associated with a positive exercise test was 9.3 before and 4.6 after age adjustment. Cardiovascular mortality rates were especially elevated (relative risk 15.6 before and 5.1 after age adjustment) among the 82 men whose exercise tests were adjusted "strongly" positive based on degree and timing of the ischemic electrocardiographic response. A positive exercise test was also moderately associated with noncardiovascular mortality; the relative risk for all-cause mortality was 7.2 before and 3.4 after age adjustment. The relative risk for cardiovascular mortality associated with a positive exercise test was not appreciably altered by covariance adjustment for known coronary risk factors other than age. A positive exercise test was a stronger predictor of cardiovascular death than were high plasma levels of low-density lipoprotein cholesterol, low plasma levels of high-density lipoprotein cholesterol, smoking, hyperglycemia, or hypertension. Its impact on risk of cardiovascular death was equivalent to that of a 17.4 year increment in age.
Provocation of coronary spasm by dopamine in patients with active variant angina pectoris.
Authors: Crea F , Chierchia S , Kaski J C , Davies G J , Margonato A , Miran D O , Maseri A
Published: June 2011

The effects of dopamine on arteries are different depending on the dose, route of administration, and receptor population. Its administration can cause vasodilation by stimulation of dopaminergic receptors, vasoconstriction by stimulation of alpha-adrenergic and serotonergic receptors, and even spasm of cerebral arteries when given intracisternally in dogs. The ability of dopamine to provoke coronary spasm was assessed in 18 patients with active vasospastic angina in whom this amine was infused at rates of 5, 10, and 15 micrograms/kg/min for periods of 5 min each. The 12-lead electrocardiogram and blood pressure (cuff) were monitored throughout the whole test. In nine patients dopamine caused angina and ischemic electrocardiographic changes suggestive of coronary spasm: ST segment elevation in six patients and ST segment depression in the absence of important coronary stenoses in the remaining three. Infusion of dopamine was repeated during coronary angiography in three patients with positive test results: this provoked occlusive coronary spasm with ST segment elevation in two patients and nonocclusive spasm with ST segment depression in the remainder. In conclusion, infusion of dopamine provokes coronary spasm in a sizeable proportion of patients with active vasospastic angina. Its administration may be detrimental in patients susceptible to coronary spasm, such as those with acute myocardial infarction.
Adenosine-sensitive ventricular tachycardia: evidence suggesting cyclic AMP-mediated triggered activity.
Authors: Lerman B B , Belardinelli L , West G A , Berne R M , DiMarco J P
Published: June 2011

Catecholamine-induced triggered activity is thought to be caused by intracellular calcium overload mediated by elevation of intracellular cyclic AMP (cAMP). Although shown to occur in isolated preparations, evidence supporting its clinical existence has been lacking. Electrophysiologic studies were performed in four patients with structurally normal hearts who had exertionally related sustained ventricular tachycardia (VT). Programmed stimulation reproducibly initiated and terminated VT in all patients. Induction of tachycardia was also facilitated by infusion of isoproterenol. Adenosine, an endogenous nucleoside, whose only known electrophysiologic effect on ventricular myocardium and Purkinje fibers is antagonism of catecholamine-induced stimulation of intracellular cAMP production, reproducibly terminated all episodes of VT. The tachycardia was also terminated by intravenous verapamil and by the Valsalva maneuver and/or carotid sinus massage. Beta-Adrenergic receptor blockade with propranolol either terminated or prevented induction of VT during programmed stimulation or catecholamine challenge. Adenosine was also administered during VT to 14 patients whose arrhythmias fulfilled standard criteria for reentry, two of whom also had exercise-induced VT. Adenosine, at a dose (112.5 to 225 micrograms/kg iv) sufficient to cause either sinus slowing/arrest or ventriculoatrial block during ventricular pacing, failed to slow or terminate any episode of VT in these patients. Verapamil and autonomic modulation were also ineffective in this group of patients. Adenosine, verapamil, vagal maneuvers (acetylcholine), and beta-adrenergic receptor blockade are all known to decrease the slow-inward calcium current either directly by modulating calcium channels or indirectly by inhibiting production of cellular cAMP. Therefore the observation in this study that interventions that lower intracellular cAMP either terminate or prevent induction of VT in patients with structurally normal hearts and exercise-induced VT suggests that the mechanism of tachycardia may be cAMP-mediated triggered activity.
Value of the intracoronary electrocardiogram to monitor myocardial ischemia during percutaneous transluminal coronary angioplasty.
Authors: Friedman P L , Shook T L , Kirshenbaum J M , Selwyn A P , Ganz P
Published: June 2011

To enhance detection of ischemia during percutaneous transluminal coronary angioplasty (PTCA), unipolar intracoronary electrocardiograms (ECGs) were recorded during PTCA in 25 patients from the tips of guidewires positioned distal to stenoses being dilated. Surface electrocardiographic leads chosen to reflect likely areas of reversible ischemia during PTCA were recorded simultaneously. In 21 of 29 stenoses dilated (72%), ST segment elevation and/or T wave peaking in intracoronary ECG appeared during balloon inflation and disappeared after deflation, accompanied by transient angina on 19 occasions. Two patients had transient ST segment elevation in intracoronary ECGs during PTCA without associated angina. ST changes in the surface ECG during PTCA were seen on only nine occasions (31%), always accompanied by ST segment elevation in the intracoronary ECG that appeared earlier and was of much greater magnitude. Five patients with prior myocardial infarction and aneurysm formation had fixed ST segment elevation in the intracoronary ECG unrelated to balloon inflation. Myocardial ischemia during PTCA can be detected easily with intracoronary ECGs and with greater sensitivity than that of the surface ECG. Furthermore, intracoronary ECGs may help to clarify the nature of chest pain during balloon inflation or during suspected complications.