bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical pharmacology of platelet cyclooxygenase inhibition.
Authors: Patrono C , Ciabattoni G , Patrignani P , Pugliese F , Filabozzi P , Catella F , Davì G , Forni L
Published: June 2011

Nonsteroidal anti-inflammatory drugs and sulfinpyrazone compete dose-dependently with arachidonate for binding to platelet cyclooxygenase. Such a process closely follows systemic plasma drug concentrations and is reversible as a function of drug elimination. Peak inhibition and extent of its reversibility at 24 hr varies consistently with individual pharmacokinetic profile. Inhibition of platelet cyclooxygenase activity by these agents is associated with variable effects on prostaglandin (PG) synthesis in the gastric mucosa and the kidney. Aspirin acetylates platelet cyclooxygenase and permanently inhibits thromboxane (TX) A2 production in a dose-dependent fashion when single doses of 0.1 to 2.0 mg/kg are given. Acetylation of the enzyme by low-dose aspirin is cumulative on repeated dosing. The fractional dose of aspirin necessary to achieve a given level of acetylation by virtue of cumulative effects approximately equals the fractional daily platelet turnover. Serum TXB2 measurements obtained during long-term dosing with 0.11, 0.22, and 0.44 mg/kg aspirin in four healthy subjects could be fitted by a theoretical model assuming identical acetylation of platelet (irreversible) and megakaryocyte (reversible) cyclooxygenase. For a given dose within this range, both the rate at which cumulative acetylation occurs and its maximal extent largely depend upon the rate of platelet turnover. Continuous administration of low-dose aspirin (20 to 40 mg/day) has no statistically significant effect on urinary excretion of either 6-keto-PGF1 alpha or 2,3-dinor-6-keto-PGF1 alpha, i.e., indexes of renal and extrarenal PGI2 biosynthesis in vivo. Whether a selective sparing of extraplatelet cyclooxygenase activity by low-dose aspirin will result in increased antithrombotic efficacy, fewer toxic reactions, or both remains to be established in prospective clinical trials.
Further observations on transient entrainment: importance of pacing site and properties of the components of the reentry circuit.
Authors: Okumura K , Henthorn R W , Epstein A E , Plumb V J , Waldo A L
Published: June 2011

Transient entrainment of circus-movement tachycardia utilizing an atrioventricular (AV) bypass pathway was studied in 13 patients (nine with the orthodromic form, two with the antidromic form, and two with both the orthodromic and antidromic forms). All patients had a left-sided AV bypass pathway. Pacing at selected rates faster than the spontaneous rate was performed during the tachycardia at a site proximal or distal to the AV node, an area of slow conduction within the reentry loop. Rapid pacing from a site proximal to the AV node (from the right atrium during the orthodromic form of the arrhythmia or the right ventricle during the antidromic form of the arrhythmia) always demonstrated at least one of the three entrainment criteria: constant fusion beats except for the last captured beat, which was entrained but not fused (first criterion); progressive fusion (second criterion); localized conduction block to a site(s) for 1 paced beat associated with interruption of the tachycardia followed by activation of that site(s) by the next paced beat from a different direction and with a shorter conduction time (third criterion). In contrast, rapid pacing from a site distal to the AV node (from the right ventricle during the orthodromic form of the arrhythmia, or the right atrium during the antidromic form of the arrhythmia) transiently entrained the tachycardia, but never demonstrated any entrainment criteria because the antidromic wave front from the pacing impulse always blocked in the AV node (concealed entrainment). We conclude that the location of the pacing site relative to the components of a reentry loop is critical to the demonstration of the criteria of transient entrainment; i.e., if it is proximal to an area of slow conduction and/or unidirectional block within a reentry loop, transient entrainment should be demonstrable, but if it is distal, it will not be demonstrable.
Prevention of coronary thrombosis with subthrombolytic doses of tissue-type plasminogen activator.
Authors: Fox K A , Robison A K , Knabb R M , Rosamond T L , Sobel B E , Bergmann S R
Published: June 2011

To determine whether tissue-type plasminogen activator (t-PA) may prevent coronary thrombosis or accelerate the lysis of clot formed under conditions in which increased concentration of the activator is present before thrombosis, clot lysis studies were undertaken in vitro and in vivo. In vitro, exogenous t-PA (6 to 100,000 ng/ml) accelerated the lysis of clot in a dose-dependent fashion when the clot was formed either from whole plasma or from euglobulin fractions (n = 316 determinations). Adding t-PA before clot formation shortened the time to lysis by at least threefold with euglobulin fractions and by at least 10-fold with whole plasma clots, which is consistent with the presence of inhibitors of fibrinolysis in whole plasma and with the binding of t-PA to nascent fibrin. In an intact dog preparation of coronary thrombosis (n = 25), occlusive thrombus formation was prevented when t-PA was present in subthrombolytic concentrations (430 to 1200 ng/ml, n = 5). Occlusive thrombus formation occurred after only discontinuation of the t-PA infusion and clearance of t-PA. Lower concentrations of t-PA (147 to 427 ng/ml, n = 6) significantly delayed occlusion (26 +/- 6.5 vs 7.8 +/- 2.8 min for controls). In animals with t-PA concentrations of less than 140 ng/ml (n = 4), the time to occlusion was unaltered (7.7 +/- 4.5 min). The present study demonstrates that t-PA present before clot formation inhibits thrombosis or accelerates thrombolysis depending on concentration, and that subthrombolytic doses of t-PA can prevent thrombus formation in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
Correlation between refractory periods and activation-recovery intervals from electrograms: effects of rate and adrenergic interventions.
Authors: Millar C K , Kralios F A , Lux R L
Published: June 2011

Unipolar electrograms from ventricular epicardium in dogs were analyzed for the timing of local excitation and repolarization with computer assistance. The most rapid decrease in voltage in the QRS (dV/dt min) was used to determine local excitation time, and the maximum rate of voltage increase (dV/dt max) near the peak of the T wave was used to time local repolarization. The difference between dV/dt min and dV/dt max, the activation-recovery interval, is theoretically related to the net effect of the durations of the action potentials at that site. Paired data for refractory periods and activation-recovery intervals obtained from the same electrodes during fixed activation orders were obtained before and during repolarization changes induced by changes in cycle length, infusion of norepinephrine, and cardiac sympathetic nerve stimulation. Correlation coefficients were close to 1.00 and standard errors were 2.0 to 4.3 msec for changes at individual sites. Pooling of data from multiple sites increased standard errors and reduced correlation coefficients. Results provide quantification of errors in the use of unipolar electrograms to time local repolarization changes induced by variations in rate and adrenergic tone. They should increase the practical usefulness of the unipolar electrogram as a tool for assessing the time course and spatial distribution of repolarization changes.
Electrocardiographic changes after cardioversion of ventricular arrhythmias.
Authors: Eysmann S B , Marchlinski F E , Buxton A E , Josephson M E
Published: June 2011

To evaluate rhythm and QRS-T changes after cardioversion of induced ventricular arrhythmias, 56 patients underwent continuous three-lead and serial 12-lead electrocardiographic monitoring for 15 min after 77 cardioversions. Fifty patients were cardioverted externally and nine internally with an implanted automatic cardioverter/defibrillator. Initial energy for external cardioversion was 200 Wsec in 57 of 64 arrhythmia episodes. Two hundred watt-seconds of energy effectively terminated 41 of 44 episodes of ventricular tachycardia and six of 13 episodes of ventricular fibrillation (p less than .001). Early bradycardia (mean cycle length greater than or equal to 1200 msec during the first 5 sec) occurred after 17 of 64 external and two of 13 internal cardioversions (p = NS) in a total of 16 patients. Bradycardia persisted at 10 sec after cardioversion in nine patients. Early bradycardia was associated with the need for multiple cardioversions to terminate the arrhythmia (six of 10 multiple cardioversions vs 13 of 67 single cardioversions, p less than .05) and the presence of inferior myocardial infarction (eight of 16 patients with vs eight of 40 patients without inferior infarction, p less than .05). Supraventricular tachycardia (cycle length less than or equal to 500 msec) occurred after 19 of 64 external and six of 13 internal cardioversions (p = NS). Nonsustained ventricular tachycardia (4 to 40 beats) was observed after seven external cardioversions, with three episodes lasting 3 sec or more.(ABSTRACT TRUNCATED AT 250 WORDS)
Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure.
Authors: Lee W H , Packer M
Published: June 2011

Although past reports have identified a variety of prognostic factors in patients with severe chronic heart failure, previous studies have not evaluated the interaction of prognostic variables and drug treatment. We analyzed the association of 30 clinical, hemodynamic, and biochemical variables with survival in 203 consecutive patients with severe heart failure; all variables were assessed just before initiation of treatment with a variety of vasodilator drugs, and all patients were subsequently followed for 6 to 94 months. By regression analysis, pretreatment serum sodium concentration was the most powerful predictor of cardiovascular mortality, with hyponatremic patients having a substantially shorter median survival than did patients with a normal serum sodium concentration (164 vs 373 days, p = .006). The unfavorable prognosis for hyponatremic patients appeared to be related to the marked elevation of plasma renin activity that we noted in these individuals (10.0 +/- 2.0 ng/ml/hr), since hyponatremic patients fared significantly better when treated with angiotensin converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin II biosynthesis (median survival 232 vs 108 days, p = .003). In contrast, there was no selective benefit of converting-enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low (1.9 +/- 0.3 ng/ml/hr). This interaction between serum sodium concentration, drug treatment, and long-term outcome suggests that the renin-angiotensin system may exert a deleterious effect on the survival of some patients with chronic heart failure, which can be antagonized by converting enzyme inhibition, and provides a clinical counterpart for the similar prognostic role that has been postulated for angiotensin II in experimental preparations of heart failure.
A theoretically and practically more effective method for interruption of ventricular tachycardia: self-adapting autodecremental overdrive pacing.
Authors: Charos G S , Haffajee C I , Gold R L , Bishop R L , Berkovits B V , Alpert J S
Published: June 2011

The efficacy and safety of a new antitachycardia pacing technique, self-adapting decremental overdrive pacing, was assessed in patients with clinical ventricular tachyarrhythmias who underwent programmed ventricular stimulation and serial drug testing. The three phases of this study involved a learning/experience phase, followed by intrapatient comparison of decremental overdrive pacing with conventional antitachycardia pacing modalities of overdrive burst ventricular pacing, and diastolic scanning with single (S2) and double (S2S3) ventricular extrastimuli. The final phase involved an intrapatient comparison of automated decremental overdrive pacing with overdrive burst ventricular pacing in patients with ventricular tachycardia (VT) cycle lengths of 280 msec or greater. Decremental overdrive pacing was superior to overdrive burst pacing and diastolic scanning (S2S3 and S2) (83% vs 38%, 50%, 9%) in patients with VT cycle lengths of 280 msec or greater. Automated decremental overdrive pacing as applied in the final phase was the most efficacious modality, terminating 92% of VT episodes compared with 56% for overdrive burst pacing in the same patients.
Effects of the size of lesions of the cardiac neural crest at various embryonic ages on incidence and type of cardiac defects.
Authors: Besson W T , Kirby M L , Van Mierop L H , Teabeaut J R
Published: June 2011

Removal of premigratory neural crest over somites 1 through 3 in chick embryos has been shown previously to result in a significant incidence of persistent truncus arteriosus. In the present study, single somite-length pieces of premigratory neural crest were removed unilaterally at slightly different embryonic ages. These lesions resulted in a number of different heart defects. Two defects, ventricular septal defect and double outlet right ventricle, were significantly correlated with the location of neural crest removed. The stage at which the ablation was performed was important in determining the incidence but not the type of defects.
Regional blood flow correlates of ST segment depression in tachycardia-induced myocardial ischemia.
Authors: Mirvis D M , Ramanathan K B , Wilson J L
Published: June 2011

Tachycardia produces subendocardial ischemia and ST segment abnormalities after coronary obstruction. To determine whether a quantitative relationship exists between these ST shifts and transmural blood flow, 19 dogs were studied. Coronary obstruction was produced by ameroid constriction of the left circumflex artery, and tachycardia was generated by atrial pacing at 90 to 210 beats/min. ST shifts were studied by body surface isopotential mapping with an 84-electrode torso grid, and blood flow was quantitated by serial radiolabeled microsphere injections. Isopotential maps at each paced rate, 40 msec into the ST segment, were classified as normal or ischemic based on spatial patterns of voltages. Pacing after 3 weeks of ameroid constriction reduced endocardial/epicardial flow ratios in 11 dogs from 1.16 +/- 0.22 at rest to 0.41 +/- 0.18 at 210 beats/min. Abnormal ST depression developed in these dogs at a rate of 184.0 +/- 16.5 beats/min. Endocardial/epicardial ratios with ST depression (0.45 +/- 0.15) were lower than at those without ST depression (1.05 +/- 0.19; p less than .01). Logistic regression analysis demonstrated that ST depression corresponded to an endocardial/epicardial ratio of 0.67 or less (p less than .01). With this model, 95.5% of data sets were correctly classified. Neither heart rate nor perfusion bed size were significant independent predictors of an ischemic electrocardiographic response. The magnitude of abnormal ST segment shift was significantly correlated (r = .87) with the transmural flow ratio. Thus development of electrocardiographic changes indicative of ischemia corresponds to a predictable degree of flow redistribution and the magnitude of the ST shift is correlated with the intensity of the flow abnormality.
Renal function and urate metabolism in late survivors with cyanotic congenital heart disease.
Authors: Ross E A , Perloff J K , Danovitch G M , Child J S , Canobbio M M
Published: June 2011

Diminished glomerular filtration rate, proteinuria, and large hypercellular congested glomeruli with segmental sclerosis are found in late survivors with cyanotic congenital heart disease (CCHD). Hyperuricemia is common, acute gouty arthritis is less common than uric acid levels would predict, and overt tophaceous deposits of uric acid are exceptional. The role of the kidney in causing the basic biochemical disturbances, and the relative importance of impaired urate excretion vs urate overproduction have not been established. Accordingly, we reviewed the courses of two index patients and prospectively studied eight additional CCHD patients from 28 years to 46 years old with mean hematocrits of (62 +/- 10%). Plasma creatinine concentration was normal (0.9 +/- 0.1 mg/dl) yet glomerular filtration rate was mildly reduced to 93 +/- 14 ml/min as measured by creatinine clearance and to 81 +/- 6 ml/min as measured by 111In DTPA. Three patients had significant proteinuria and one was nephrotic. Plasma uric acid concentration was high in all but one (8.2 +/- 2.1 mg/dl), mean 24 hr uric acid excretion was normal (564 +/- 221 mg), and fractional uric acid excretion was relatively low (6.3 +/- 2.6%). The two patients with highest plasma uric acid levels (12.0 and 10.2 mg/dl) had the lowest fractional excretions (2.8% and 4.0%). Both of these patients had diminished capacity to excrete a water load (38% and 27%/4 hr) and to maximally concentrate urine (520 and 635 mOsm/kg after water deprivation and vasopressin). In conclusion, high plasma uric acid levels in late survivors with CCHD are secondary to inappropriately low fractional uric acid excretion, not to urate overproduction.(ABSTRACT TRUNCATED AT 250 WORDS)
The relationship between pericardial pressure and right atrial pressure: an intraoperative study.
Authors: Tyberg J V , Taichman G C , Smith E R , Douglas N W , Smiseth O A , Keon W J
Published: June 2011

The objective of this study was to determine the constraining effect of the normal human pericardium. Accordingly, immediately after thoracotomy in nine patients undergoing elective cardiac surgery, we measured mean pericardial surface pressure over the lateral free wall of the left ventricle with a flat balloon as well as mean right atrial pressure while incrementally infusing up to 2.1 liters of Ringer's solution to increase right atrial pressure. In each case, the slope of the relationship between right atrial (range -4 to 20 mm Hg, overall) and pericardial pressures was near unity (1.16 +/- 0.20 mean +/- SD) and the intercept was approximately zero (0.71 +/- 2.48 mm Hg). Correlation coefficients ranged from .86 to .97. These observations suggest that right atrial pressure can be used as an estimate of pericardial surface pressure. If this is the case, true left ventricular preload (i.e., effective distending pressure or transmural diastolic pressure) might be estimated from the difference between left ventricular filling pressure and right atrial pressure, both conveniently measurable clinically by means of a triple-lumen, flow-directed catheter.
Comparison of bipolar and unipolar programmed electrical stimulation for the initiation of ventricular arrhythmias: significance of anodal excitation during bipolar stimulation.
Authors: Stevenson W G , Wiener I , Weiss J N
Published: June 2011

To determine if anodal excitation during bipolar stimulation facilitates the initiation of sustained monomorphic ventricular tachycardia, nonsustained polymorphic ventricular tachycardia, or repetitive ventricular responses, both bipolar and cathodal unipolar programmed ventricular stimulation with one to three extrastimuli delivered during ventricular pacing at two rates from the right ventricular apex were performed in 28 patients evaluated for spontaneous sustained ventricular tachycardia or ventricular fibrillation (11 patients), nonsustained tachycardia (eight patients), or syncope (nine patients). In 25 patients a hexapolar pacing catheter was used to record local endocardial activation times adjacent to the cathode and anode and ventricular excitation during bipolar stimulation was defined as predominantly anodal, cathodal, or simultaneous at both anode and cathode. When bipolar and unipolar stimulation were compared there was no difference in the incidence of initiating sustained monomorphic ventricular tachycardia (57% vs 57%), nonsustained polymorphic ventricular tachycardia (14% vs 14%), or repetitive ventricular responses (21% vs 21%), although the response to bipolar vs unipolar stimulation was not concordant in every patient. Evidence of anodal excitation was observed in 11 (44%) patients but did not indicate increased risk of initiation of any ventricular arrhythmia, despite the fact that it was associated with shortening of the ventricular effective refractory period by 5.2 +/- 8.7 msec (p less than .05) during bipolar as opposed to unipolar stimulation. We conclude that unipolar and bipolar stimulation produce a similar incidence of initiation of arrhythmia, despite the frequent occurrence of anodal excitation during bipolar stimulation. Thus, the risk of initiation of nonspecific ventricular arrhythmias during programmed stimulation is unlikely to be reduced by the use of unipolar stimulation.
Restenosis after successful coronary angioplasty in patients with single-vessel disease.
Authors: Leimgruber P P , Roubin G S , Hollman J , Cotsonis G A , Meier B , Douglas J S , King S B , Gruentzig A R
Published: June 2011

To determine risk factors for restenosis, we studied 998 patients who underwent elective coronary angioplasty (PTCA) to native coronary arteries between July 1980 and July 1984. Restenosis, defined as a luminal narrowing of greater than 50% at follow-up, was present in 302 patients (30.2%). Univariate analysis of 29 factors revealed seven factors related to restenosis: vessel dilated (circumflex coronary artery 18%, right coronary artery 27%, left anterior descending artery 34%; p less than .01), final gradient of 15 mm Hg or less compared with greater than 15 mm Hg (27% vs 38%, p less than .01), duration of angina greater than 2 months compared with angina of shorter duration (27% vs 35%, p = .01), post-PTCA stenosis of 30% or less compared with 31% to 50% (28% vs 36%, p less than .025), stable vs unstable angina (26% vs 34%, p less than .05), presence vs absence of intimal dissection (26% vs 32%, p = .07), and female gender vs male gender (25% vs 32%, p = .08). Multivariate analysis revealed five factors independently related to increased risk of restenosis in the following order of importance: PTCA in the left anterior descending artery, absence of intimal dissection immediately after PTCA, final gradient greater than 15 mm Hg, a large residual stenosis after PTCA, and unstable angina. Restenosis after PTCA is a multifactorial problem. The hemodynamic and angiographic result at the time of PTCA significantly influences long-term outcome, but additional measures aimed at reducing the rate of recurrence of atherosclerotic plaque are required.
Failure of superoxide dismutase and catalase to alter size of infarction in conscious dogs after 3 hours of occlusion followed by reperfusion.
Authors: Gallagher K P , Buda A J , Pace D , Gerren R A , Shlafer M
Published: June 2011

Superoxide dismutase (SOD) and catalase (CAT), enzymes that degrade superoxide anion and hydrogen peroxide, respectively, reduce size of infarction in anesthetized, open-chest dogs subjected to coronary occlusion followed by reperfusion. To evaluate potential protective effects of these enzymes in conscious animals, three groups of dogs were instrumented at sterile surgery with a hydraulic occluder on the left circumflex (LCX) coronary artery, sonomicrometers to measure regional wall thickness, and catheters to monitor arterial and left ventricular pressures. Ten to 14 days after surgery, the animals were sedated with morphine sulfate (0.5 mg/kg). The LCX artery was occluded for 3 hr by inflation of the hydraulic cuff. Infusions of SOD (n = 7), CAT (n = 6), or saline (control group, n = 7) were begun 15 min before reperfusion and lasted for 45 min of reperfusion. The doses of SOD and CAT were 5 mg/kg, dissolved in 60 ml of saline, and infused at a rate of 1 ml/min. Myocardial blood flow was measured with tracer-labeled microspheres (15 micron diameter) before occlusion, after 5 to 10 min of occlusion, after 150 min of occlusion, and 5 to 10 min after reperfusion. Size of infarction was measured 24 hr later by dual-perfusion staining with Evans blue and triphenyl tetrazolium. Size of infarction (expressed as a percentage of area at risk) did not differ significantly among the three groups: control, 32 +/- 17% (mean +/- SD); SOD, 38 +/- 17%; CAT, 27 +/- 17%. Hemodynamic parameters and myocardial blood flows (measured before infusion of any agents) were not significantly different among the three groups. Serum SOD levels in SOD-treated dogs were 19 +/- 2 micrograms/ml at the onset of reperfusion and 29 +/- 3 micrograms/ml at the end of the infusion. Blood assays collected after infusion showed a monoexponential decay of SOD levels with a half-life of 22 +/- 6 min. We conclude that myocardial protection by SOD or CAT is model dependent. In conscious dogs subjected to 3 hr of coronary occlusion followed by reperfusion, SOD and CAT failed to alter size of infarction.
The mechanism of disappearance of the physiologic third heart sound with age.
Authors: Van de Werf F , Geboers J , Kesteloot H , De Geest H , Barrios L
Published: June 2011

To study the mechanism of disappearance of the physiologic third heart sound (S3) with advancing age, combined phonoechocardiographic and phonomechanocardiographic recordings from 165 normal subjects between 6 and 62 years old were quantitatively analyzed. Nearly all individuals under 40 years old had a recordable S3. Although recordable in 38.6% of the 44 subjects over 40 years old, the physiologic S3 found in adults was less intense and occurred later in diastole when compared with that in children and adolescents. Marked changes in left ventricular filling hemodynamics were observed with aging, including an increase in left ventricular wall thickness and mass, a prolongation of the left ventricular isovolumetric relaxation period, a decrease in left ventricular early diastolic filling and wall thinning rates, and a reduction in the height and steepness of the rapid filling wave measured on the calibrated left apexcardiogram (linear correlation with age significant at p less than .001 for all parameters). Although less pronounced, these changes were very similar to the diastolic abnormalities found in patients with pressure overload left ventricular hypertrophy. Therefore, the higher pressure load imposed on the left ventricular wall due to the well-known gradual increase in blood pressure that occurs during normal growth and adulthood appears to be the most likely explanation for the observed changes in diastolic filling. It is concluded that the later occurrence, the diminishing amplitude, and the eventual complete disappearance of the physiologic S3 with age results from a decrease in early diastolic left ventricular filling and subsequent deceleration of inflow caused by the development of relative left ventricular hypertrophy in adulthood as compared with childhood.
Effect of sudden rate acceleration on the human His-Purkinje system: adaptation of refractoriness in a dampened oscillatory pattern.
Authors: Tchou P J , Lehmann M H , Dongas J , Mahmud R , Denker S T , Akhtar M
Published: June 2011

Although the refractoriness of the human His-Purkinje system (HPS) during constant-cycle length pacing appears to be closely related to the cycle length of the stimulation, the mode of adaptation of this refractoriness with sudden rate acceleration is not well understood. A systematic evaluation of this adaptation was performed in 14 patients with normal QRS durations and HV intervals referred for electrophysiologic evaluation. The relative refractory period of the HPS (HPS-RRP) was evaluated by the extrastimulus (S2) method during a constant ventricular drive (S1) having a cycle length as close to sinus rhythm as possible. An accelerated train of 6 ventricular beats (S1') was then added to the constant drive and the HPS-RRP of each successive beat of this train was similarly determined. Mean S1 cycle length was 750 +/- 164 msec (range 600 to 1000). Mean S1' cycle length was 475 +/- 55 msec (range 400 to 600). The HPS-RRP of each successive beat of the accelerated train was significantly shorter than that during the S1 drive and behaved in a dampened oscillatory fashion alternating from a lower value on the odd-numbered beats to a higher value on the even-numbered beats. In contrast, the effective and relative refractory periods of the ventricular myocardium during the accelerated train behaved in a cumulative manner, decreasing progressively with the first 2 beats of the train before reaching a plateau value. In conclusion, the data reported here present a new and intriguing picture of the mode of adaptation of the HPS refractoriness to sudden rate acceleration. At least in the range of the cycle lengths used in this study, the refractoriness of the HPS behaves in a dampened oscillatory manner that is radically different from the behavior of the ventricular myocardial refractoriness.
Abnormal skeletal muscle bioenergetics during exercise in patients with heart failure: role of reduced muscle blood flow.
Authors: Wiener D H , Fink L I , Maris J , Jones R A , Chance B , Wilson J R
Published: June 2011

Using phosphorous nuclear magnetic resonance, we have previously demonstrated that patients with heart failure often exhibit abnormal forearm muscle metabolism during forearm exercise. To determine if this altered metabolism is due to reduced muscle flow, we measured forearm blood flow with plethysmography and forearm muscle inorganic phosphate (Pi), phosphocreatine (PCr), and pH with 31P nuclear magnetic resonance spectroscopy at rest and during mild forearm exercise (0.2, 0.4, and 0.6 W) in 21 men with heart failure and in 12 age-matched normal male subjects. The Pi/PCr ratio was correlated with power output and the slope of this relationship was used as an index of forearm metabolism. At rest, both groups had similar Pi/PCr ratios (normal subjects 0.11 +/- 0.05; patients with heart failure 0.11 +/- 0.03; p = NS) and forearm blood flows (normal subjects 2.9 +/- 1.4 ml/min/100 ml; patients with heart failure 2.6 +/- 1.2 ml/min/100 ml; p = NS). In both groups, exercise resulted in a progressive increase in both Pi/PCr and forearm blood flow as power output increased. However, the patients exhibited a steeper slope of the Pi/PCr-to-power output relationship than did the normal subjects (normal subjects 1.4 +/- 0.6 Pi/PCr U/W; patients with heart failure 3.0 +/- 2.4 Pi/PCr U/W; p less than .03). In contrast, forearm blood flow was similar in both groups during exercise (at 0.2 W, 6.3 +/- 3.3 and 6.8 +/- 3.2 ml/min/100 ml in normal subjects and patients with heart failure, respectively; at 0.4 W, 8.7 +/- 6.5 and 8.3 +/- 3.3; at 0.6 W, 12.8 +/- 7.9 and 12.0 +/- 4.6; all p = NS). Nine of the 21 patients with heart failure had slopes of the Pi/PCr-to-power output relationship above the normal range. These nine patients also had forearm blood flows comparable to flows observed in the normal subjects. These data indicate that forearm muscle metabolism during forearm exercise is altered in a subpopulation of patients with heart failure. This metabolic alteration does not appear to be due to decreased muscle blood flow, suggesting that other mechanisms, such as alterations in mitochondrial population or substrate utilization, may be responsible.
Measurement of transstenotic pressure gradient during percutaneous transluminal coronary angioplasty.
Authors: Anderson H V , Roubin G S , Leimgruber P P , Cox W R , Douglas J S , King S B , Gruentzig A R
Published: June 2011

Obstruction to blood flow is accompanied by a pressure gradient across the obstructed site. In certain clinical settings, magnitude of pressure gradient has been used to judge severity of obstruction, and gradient reduction to judge success of an interventional procedure. In percutaneous transluminal coronary angioplasty (PTCA) the relationships between transstenotic pressure gradient, diameter stenosis, and lesion length are imprecisely known. We therefore examined 4263 sets of measurements in patients who underwent PTCA on single, discrete coronary arterial lesions. Multivariate regression analysis demonstrated that pressure gradient was artifactually elevated by about 12 mm Hg at low values of diameter stenosis but increased by the 4th power of stenosis as expected from fluid dynamics models. Pressure gradient was dampened and relatively constant at values of diameter stenosis of 60% or higher, probably because of total or near-total occlusion of the artery. Lesion length was not found to influence pressure gradient. Reductions in diameter stenosis (delta D) and pressure gradient (delta G) were related nonlinearly, with delta D proportional to the square root of delta G, suggesting that a reduction in gradient is directly proportional to an increase in cross-sectional area of the stenosis. The predictive value of final post-PTCA pressure gradients was found: a final gradient of 15 mm Hg or less predicted a final post-PTCA diameter stenosis of 30% or less, with 75% sensitivity and 29% specificity (p less than .01). The results of this study suggest that (1) pressure gradient as currently measured during PTCA is related to diameter stenosis but not to lesion length (2) reductions in pressure gradient and diameter stenosis are nonlinearly related.(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of surgery on the natural history of angiographically documented left ventricular aneurysm: the Coronary Artery Surgery Study.
Authors: Faxon D P , Myers W O , McCabe C H , Davis K B , Schaff H V , Wilson J W , Ryan T J
Published: June 2011

Coronary artery bypass surgery with or without aneurysmectomy has been used to treat patients with angiographically defined left ventricular aneurysm. To evaluate whether surgery benefits such patients, we analyzed the data from 1131 patients who were enrolled in the registry of the Coronary Artery Surgery Study. Four hundred sixty-seven patients underwent bypass surgery, of which 238 also had left ventricular resection, and 30 had resection alone. The overall operative mortality was 7.9%; the operative mortality was 7% for bypass alone compared with 9% for bypass surgery plus left ventricular resection (NS). Long-term survival by life-table analysis was similar for both medically and surgically treated patients (69% vs 67%, respectively). Cox survival analysis identified congestive heart failure score, duration of chest pain, extent of coronary disease, left ventricular end-diastolic pressure, age, and surgical therapy as important predictors of outcome. Patient subsets that showed improved survival with surgical therapy after adjustment for inequities in baseline characteristics were patients with three-vessel disease and those patients in moderate- and high-risk subgroups. Surgical therapy significantly reduced symptoms of angina and use of cardiac medications but the incidence of recurrent infarction was similar for both therapies.
Magnetic resonance imaging of cardiac transplants: the evaluation of rejection of cardiac allografts with and without immunosuppression.
Authors: Aherne T , Tscholakoff D , Finkbeiner W , Sechtem U , Derugin N , Yee E , Higgins C B
Published: June 2011

The purpose of this study was to evaluate the potential of magnetic resonance imaging (MRI) in vivo for the characterization of tissue changes associated with acute myocardial rejection after cardiac transplantation. Of 15 dogs that underwent heterotopic cardiac transplantation, six served as untreated controls, and nine received immunosuppressive therapy (25 mg/kg/day cyclosporine, 1 mg/kg/day prednisone). Serial electrocardiographically gated MRI (spin-echo technique) and histologic examinations of allograft biopsy samples were performed for each dog at 2 to 3, 7 to 10, 14 to 17, and 26 to 29 days after transplantation and immediately after animals were killed. Untreated allografts showed a significant increase (p less than .01) in T2 (spin-spin) relaxation time (T2 = 66 +/- 8 msec) and intensity values compared with values in the native hearts (T2 = 44 +/- 6 msec) as early as 1 week after transplantation. The significant difference in T2 values could be observed in vivo as well as on postmortem examination and corresponded to histologic progression of the rejection process. There was no significant difference in T1, T2, or intensity values in cyclosporine-treated allografts and native hearts except in two dogs in which T2 relaxation times and signal intensity in the transplanted hearts increased simultaneously with histologic evidence of rejection, indicating failure of immunosuppressive therapy. There was a significant correlation between histologic grading of severity of rejection and T2 relaxation times of the cardiac transplants (r = .72). Likewise, there was a significant linear relationship between T2 values in vivo and percent water content when the differences between native hearts and allografts were compared (r = .92, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
The shift in the relationship between intrapericardial fluid pressure and volume induced by acute left ventricular pressure overload during cardiac tamponade.
Authors: Cogswell T L , Bernath G A , Keelan M H , Wann L S , Klopfenstein H S
Published: June 2011

We hypothesized that a process leading to an acute increase in cardiac size would change the relationship between intrapericardial pressure and fluid volume during cardiac tamponade, resulting in a change in the time of onset of right ventricular diastolic collapse (RVDC) as seen on the two-dimensional echocardiogram. Five spontaneously breathing dogs were instrumented to measure ascending aortic and right atrial blood pressures and intrapericardial pressure (IPP). A hydraulic occluder was placed around the proximal descending thoracic aorta. Each animal underwent six consecutive episodes of cardiac tamponade, three in the presence alternating with three in the absence of aortic constriction. The onset of RVDC was recorded and the volume infused into the pericardial space was measured. In the presence of aortic constriction, the relationship between pericardial pressure and incremental pericardial fluid volume was shifted so that IPP was an average of 3.4 mm Hg higher at any given intrapericardial fluid volume (p less than .001). At the onset of RVDC, the mean IPP was higher and the intrapericardial fluid volume was lower during aortic constriction than under control conditions (p less than .001 for both comparisons). Thus, a rapid increase in left ventricular volume in the presence of an otherwise unimportant pericardial effusion may increase intrapericardial fluid pressure sufficiently to cause RVDC.
Postinfarction ventricular septal rupture: the importance of location of infarction and right ventricular function in determining survival.
Authors: Moore C A , Nygaard T W , Kaiser D L , Cooper A A , Gibson R S
Published: June 2011

Over a 5.5 year period, 1264 consecutive patients with acute myocardial infarction as confirmed by enzyme levels were prospectively identified. Of these, 25 (2%) suffered ventricular septal rupture (pulmonary/systemic flow range 1.5 to 6) 7 +/- 7 days after onset of myocardial infarction. Death occurred in 14 patients (56%) and was more common after inferior than anterior myocardial infarction (11 of 15 [73%] vs three of 10 [30%], p less than .05). Among 133 variables analyzed, survivors and nonsurvivors were similar with respect to all premorbid clinical characteristics, infarct size as assessed by peak creatine kinase values, shunt size, two-dimensional echocardiographic and hemodynamic indexes of left ventricular function, and extent of coronary disease. Compared with survivors, the nonsurvivors had greater impairment of right ventricular function as determined by a higher two-dimensional echocardiographically derived right ventricular wall motion index (RVWMI) (0.55 +/- 0.87 vs 1.70 +/- 0.45, p less than .001), greater elevation of right ventricular end-diastolic pressure (11 +/- 6 vs 17 +/- 6, p less than .02), and greater mean right atrial pressure (10 +/- 6 vs 16 +/- 3, p less than .01). Of interest, two of the three patients who presented with anterior myocardial infarction and who died had inferiorly extended infarcts and all had abnormal RVWMIs (greater than or equal to 1.0). As expected, cardiogenic shock shortly after onset of ventricular septal rupture was associated with a 91% mortality, but was more common after inferior than anterior myocardial infarction (60% vs 20%, p less than .05). The mean effective cardiac index was also higher in survivors than nonsurvivors (2.1 +/- 0.5 vs 1.2 +/- 0.5, p less than .001). Finally, multivariate analysis indicated that all nonsurvivors could be identified based on: an effective cardiac index of 1.75 liters/min/m2 or less, the presence of extensive right ventricular and septal dysfunction on the two-dimensional echocardiogram, a mean right atrial pressure of 12 mm Hg or more, and early onset of ventricular septal rupture. Thus, our data demonstrate that: mortality is higher when ventricular septal rupture complicates inferior than when it complicates anterior myocardial infarction, survivors can be distinguished from nonsurvivors and the prediction of outcome is highly accurate, and combined right ventricular and septal dysfunction has a substantial impact on prognosis.
Increased uptake of 18F-fluorodeoxyglucose in postischemic myocardium of patients with exercise-induced angina.
Authors: Camici P , Araujo L I , Spinks T , Lammertsma A A , Kaski J C , Shea M J , Selwyn A P , Jones T , Maseri A
Published: June 2011

Regional myocardial perfusion and exogenous glucose uptake were assessed with rubidium-82 (82Rb) and 18F-2-fluoro-2-deoxyglucose (FDG) in 10 normal volunteers and 12 patients with coronary artery disease and stable angina pectoris by means of positron emission tomography. In patients at rest, the myocardial uptake of 82Rb and FDG did not differ significantly from that measured in normal subjects. The exercise test performed within the positron camera in eight patients produced typical chest pain and ischemic electrocardiographic changes in all. In each of the eight patients a region of reduced cation uptake was demonstrated in the 82Rb scan recorded at peak exercise, after which uptake of 82Rb returned to the control value 5 to 14 min after the end of the exercise. In these patients, FDG was injected in the recovery phase when all the variables that were altered during exercise, including regional myocardial 82Rb uptake, had returned to control values. In all but one patient, FDG accumulation in the regions of reduced 82Rb uptake during exercise was significantly higher than that in the nonischemic regions, i.e., the ones with a normal increment of 82Rb uptake on exercise. In the nonischemic areas, FDG uptake was not significantly different from that found in normal subjects after exercise. In conclusion, myocardial glucose transport and phosphorylation seem to be enhanced in the postischemic myocardium of patients with exercise-induced ischemia.
Flow in the aorta and patent ductus arteriosus in infants with aortic atresia or aortic stenosis: a pulsed Doppler ultrasound study.
Authors: Bass J L , Berry J M , Einzig S
Published: June 2011

We used pulsed Doppler ultrasound to determine the flow dynamics of the aorta and patent ductus arteriosus (PDA) in 21 infants (ages 1 to 16 days) with PDA and aortic atresia (n = 15) or aortic stenosis (n = 6). The flow within the PDA was recorded in 19, and was right-to-left during systole in all. There was a diastolic left-to-right PDA shunt in 11 patients with aortic atresia and in three with aortic stenosis, and the shunt was associated with large (3 to 11 mm in diameter) interatrial communications. In two patients with aortic atresia and three with aortic stenosis, however, the diastolic PDA shunt was from right to left, and the interatrial communications were small (0 to 2 mm in diameter). The right-to-left diastolic PDA shunting may be best explained by the relative pulmonary (high with left-sided inflow obstruction and a small interatrial communication) and systemic resistances. All patients with aortic atresia and three with aortic stenosis had retrograde systolic flow in the transverse aortic arch, probably resulting from inadequate left ventricular output. Antegrade diastolic flow in the transverse aortic arch toward the PDA was observed in all infants with aortic atresia and a left-to-right PDA shunt. Ascending aortic flow was recorded in 11 patients with aortic atresia, and was retrograde during diastole in each, the result of coronary perfusion. Application of pulsed Doppler ultrasound can lead to a better understanding of the hemodynamics and physiology of patients with congenital cardiovascular disease.
Limitation of myocardial ischemia by collateral circulation during sudden controlled coronary artery occlusion in human subjects: a prospective study.
Authors: Cohen M , Rentrop K P
Published: June 2011

We have shown improvement in collateral filling immediately after sudden controlled coronary occlusion in human subjects undergoing elective coronary angioplasty. It has been suggested but not proved that collateral circulation can limit myocardial ischemia. We prospectively studied 23 patients with isolated left anterior descending (n = 14) or right coronary (n = 9) disease and normal left ventriculograms during elective coronary angioplasty. A second arterial catheter was used for injection of the contralateral artery to assess collateral filling before balloon placement and during coronary occlusion by balloon inflation. Left ventriculography was performed during another inflation. Grading of collateral filling was as follows: 0 = none, 1 = filling of side branches only, 2 = partial filling of the epicardial segment, 3 = complete filling of the epicardial segment. Indexes of myocardial ischemia included percent of the left ventricular perimeter showing new hypocontractility and the sum of ST segment elevation measured on a simultaneous 12-lead electrocardiogram recorded during each inflation. Collateral filling during balloon occlusion and indexes of ischemia were assessed at 30 to 40 sec into inflation. Aortic pressure and heart rate did not correlate with the percent hypocontractile perimeter nor the sum of ST segment elevation. There was a significant correlation between the grade of collateral filling during inflation and both percent hypocontractile perimeter (r = -.85) and the sum of ST segment elevation (r = -.87). Anginal pain occurred in all patients with grade 0 or 1 collateral filling but in only 36% of patients with grade 2 or 3 collaterals. In conclusion, collateral circulation limits myocardial ischemia as assessed by the extent of new ventricular asynergy and electrocardiographic changes during coronary occlusion in patients.
Scintigraphic quantification of myocardial necrosis in patients after intravenous injection of myosin-specific antibody.
Authors: Khaw B A , Gold H K , Yasuda T , Leinbach R C , Kanke M , Fallon J T , Barlai-Kovach M , Strauss H W , Sheehan F , Haber E
Published: June 2011

The Fab fragments of antimyosin antibodies, labeled with 99mTc, were used in the scintigraphic examination of 30 patients with myocardial infarction. The ability to detect necrosis and determine its extent from the antimyosin scan were compared with the results of quantitative regional wall motion analysis by contrast ventriculography at 10 to 14 days and 99mTc-pyrophosphate imaging. Antimyosin images recorded by planar and single photon-emission computed tomography (SPECT) delineated areas of myocardial necrosis in 27 of 30 patients (90%) compared with a 91% sensitivity of pyrophosphate in 21 of 23 patients. Infarct size was determined by both antimyosin and pyrophosphate SPECT images. Results by both techniques showed a significant correlation with computer-derived hypokinetic segment length (r = .79 for both, p = .002) and peak creatine kinase (r = .9 for both, p less than .01). Although sensitivity for and correlations with markers of necrosis were similar with both techniques, infarct size by pyrophosphate SPECT was 1.7 times larger than infarct size by antimyosin SPECT (p less than .01). Certain zones in the infarct area were differentially labeled; the nature and irreversibility of injury within these zones remains to be clarified.