bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of pacing on triggered activity induced by early afterdepolarizations.
Authors: Damiano B P , Rosen M R
Published: June 2011

Early afterdepolarizations (EADs) are depolarizing potentials that occur during phase 2 or phase 3 of repolarization. They can induce triggered activity and have been proposed as a cause for arrhythmias in the heart in situ. To determine the response of EADs and triggered activity to interventions analogous to those used in the clinic for identifying arrhythmogenic mechanisms, we used a pacing protocol to study the response of EADs to sustained drive and extrastimuli. Cesium chloride (5 to 20 mM), which induces triggered arrhythmias in the intact dog, was used to induce EADs in isolated canine Purkinje fibers, and these were studied by microelectrode techniques. Cesium prolonged action potential duration and induced two types of EADs. At a potassium concentration of 4 mM, EADs occurred at membrane potentials of -3 to -30 mV. They were initiated 240 to 680 msec after the action potential upstroke and were 2 to 30 mV in amplitude. Their amplitude increased as drive cycle length increased, but their coupling interval to the action potential did not change with drive cycle length. These EADs did not induce triggered action potentials. At a potassium concentration of 2 mM, EADs usually occurred at higher membrane potentials (-50 to -70 mV) and longer coupling intervals (470 to 1360 msec) and were manifested as a delay of phase 3 repolarization. These EADs induced triggered action potentials. When the triggered rhythms became sustained, premature stimuli either reset or terminated them, depending on the maximum diastolic potential. Termination occurred more frequently as the maximum diastolic potential increased. The extent of overdrive suppression induced by pacing for 15 sec to 3 min also increased as the maximum diastolic potential increased. In summary, cesium induced EADs at low or high membrane potentials. The former did not induce triggered activity, but the latter did. The triggered rhythms that occurred were similar to abnormal automatic mechanisms in their response to overdrive pacing and extrastimuli.
Mechanism of decreased left ventricular stroke volume during inspiration in man.
Authors: Karam M , Wise R A , Natarajan T K , Permutt S , Wagner H N
Published: June 2011

Radionuclide ventriculography was performed in 15 healthy subjects during quiet breathing and during inspiration against a 24 cm H2O threshold load with a respiratory gating technique. Inspiratory threshold loading caused an inspiratory decrease in ejection fraction from 64% to 59% (p less than .001). Stroke counts proportional to stroke volume decreased by 9.6% (p less than .02) due to an increase in end-systolic counts of 15.9% (p less than .05). End-diastolic counts decreased in four subjects and increased in three subjects, but the mean counts did not change significantly. These findings suggest that negative pleural pressure causes an impediment to left ventricular ejection comparable to an increase in arterial pressure. Respiratory gating of radionuclide ventriculography during loaded breathing is suggested as a controlled stress on the ventricle for diagnostic purposes.
Effects of spontaneous respiration on left ventricular function assessed by echocardiography.
Authors: Andersen K , Vik-Mo H
Published: June 2011

The effects of quiet respiration on assessment of left ventricular function by two-dimensional echocardiography were investigated in 12 healthy men. End-diastolic area in the parasternal short-axis view decreased with inspiration (from 17.3 +/- 2.1 [mean +/- SD] to 16.0 +/- 2.1 cm2, p less than .01), while end-systolic area did not change (from 7.6 +/- 1.4 to 7.7 +/- 1.5 cm2; NS). A fixed cursor that was located through the center of the left ventricular area at end-expiration made a tangential cut of the area at end-inspiration were smaller along the cursor than through the center of the short-axis area both at end-diastole (1.9 +/- 1.7 mm; p less than .01) and end-systole (3.8 +/- 4.0 mm; p less than .01). Our results suggest a need for standardization with regard to respiratory phases in assessment of left ventricular function by two-dimensional echocardiography and indicate the occurrence of inspiratory reduction of left ventricular stroke volume associated with decreased diastolic filling. Motion of the heart relative to the echo beam may play a part in the respiratory variations in left ventricular dimensions assessed by M mode echocardiography.
Clinical characteristics and long-term survival of patients with variant angina.
Authors: Mark D B , Califf R M , Morris K G , Harrell F E , Pryor D B , Hlatky M A , Lee K L , Rosati R A
Published: June 2011

We studied 109 consecutive patients with variant angina who underwent cardiac catheterization over an 11 year period. All patients were followed for at least 6 months or until death, and 46 patients (22 treated medically and 24 treated surgically) were followed for 5 years or more. Of the 62 patients initially treated medically, 14 had nonfatal myocardial infarctions (12 within 1 month of catheterization) and 12 died (six within 6 months). Survival probabilities at 1, 3, and 5 years were 0.88, 0.84, and 0.77, respectively. Of the 48 surgically treated patients (including four patients initially treated medically and one initially treated with coronary angioplasty), four had nonfatal infarctions (three in the perioperative period) and three died (all in the perioperative period). The survival probability in these patients at 1 year was 0.94 and remained unchanged at 3 and 5 years. Only one nonfatal infarction and no deaths have occurred in the group of surgically treated patients subsequent to hospital discharge. Three additional patients were treated with coronary angioplasty. The single most important prognostic factor in medically treated patients was the presence or absence of fixed obstructive coronary artery disease. Infarction-free survival probabilities at 1 and 3 years in the 23 patients without significant coronary artery disease were 1.0 and 0.89, compared with 0.51 and 0.46 in the 39 patients with significant coronary disease. Analysis by the Cox model showed that variant angina patients had a higher probability of death and nonfatal infarction than did those with nonvariant angina coronary disease if other important prognostic variables were held constant.(ABSTRACT TRUNCATED AT 250 WORDS)
Improvement of regional myocardial metabolism after coronary thrombolysis induced with tissue-type plasminogen activator or streptokinase.
Authors: Sobel B E , Geltman E M , Tiefenbrunn A J , Jaffe A S , Spadaro J J , Ter-Pogossian M M , Collen D , Ludbrook P A
Published: June 2011

To assess the effects on the heart itself of coronary thrombolysis induced with either tissue-type plasminogen activator (t-PA) or streptokinase (SK), we performed positron emission tomography with 11C-palmitate in 19 patients with initial transmural myocardial infarction immediately after admission and again within 48 to 72 hr after intracoronary administration of t-PA (n = 2) or SK (n = 17). Clots were persistent in eight patients treated with SK despite an average dose of 336,000 IU, sufficient to markedly deplete fibrinogen. In the absence of lysis, favorable tomographic changes did not occur. In contrast, in each of the 11 patients in whom lysis was induced (two with t-PA and nine with SK) myocardial accumulation of 11C-palmitate improved by an average of 29% in late compared with early studies (p less than .001). Results were comparable in patients with anterior and those with inferior infarction. Thus clot lysis induced with either t-PA or SK led to improved regional myocardial metabolism.
Exercise intolerance in patients with chronic heart failure: role of impaired nutritive flow to skeletal muscle.
Authors: Wilson J R , Martin J L , Schwartz D , Ferraro N
Published: June 2011

The maximal exercise capacity of patients with chronic heart failure is frequently reduced. To investigate whether this exercise intolerance is caused by inadequate nutritive flow to skeletal muscle, we compared cardiac outputs, leg blood flow, and leg metabolism during maximal bicycle exercise in seven patients with normal maximal oxygen uptake (VO2) (greater than 20 ml/min/kg; group A), eight patients with heart failure and moderately reduced maximal VO2 (15 to 18 ml/min/kg; group B), and eight patients with heart failure and markedly reduced maximal VO2 (less than 14 ml/min/kg; group C). As the severity of exercise intolerance increased from group A to group C there was a progressive decline in cardiac output and leg blood flow at any given workload accompanied by a progressive decline in maximal cardiac output (liters/min) (A, 12.4 +/- 1.0; B, 8.7 +/- 0.9; C, 5.5 +/- 0.7), maximal leg flow (liters/min) (A, 4.0 +/- 0.3; B, 2.6 +/- 0.4; C, 1.4 +/- 0.2), and maximal leg VO2 (ml/min) (A, 564 +/- 49; B, 403 +/- 41; C, 213 +/- 35 ml/min). All patients terminated exercise because of severe leg fatigue. At termination of exercise, all three groups exhibited similar marked levels of leg O2 extraction (%) (A, 80 +/- 2; B, 83 +/- 3; C, 89 +/- 1) and high femoral-arterial lactate gradients (mg/dl) (A, 15.4 +/- 2.6; B, 18.3 +/- 3.5; C, 19.2 +/- 3.6), suggesting that exercise was limited when a critical level of muscle underperfusion was reached. These data suggest that the reduced maximal exercise capacity of patients with chronic heart failure is primarily due to impaired nutritive flow to skeletal muscle and resultant muscular fatigue.
Postextrasystolic alterations in refractoriness of the His-Purkinje system and ventricular myocardium in man.
Authors: Lehmann M H , Denker S , Mahmud R , Akhtar M
Published: June 2011

The changes in refractoriness of the His-Purkinje system (HPS) and ventricular myocardium (VM) that are associated with the occurrence of postextrasystolic beats in man are unknown. Accordingly, using a pacing model of the cycle length changes created by a ventricular extrasystole-postextrasystole sequence, we measured retrograde HPS and VM relative and effective refractory periods (RRP and ERP) in 15 patients with the use of ventricular test extrastimuli during preextrasystolic basic control drive (method I) and after programmed extrasystolic (method II) and postextrasystolic (method III) beats. The basic cycle length (same for all three methods) ranged from 500 to 700 msec (mean 613 +/- 74 msec) and the extrasystolic coupling interval (identical for methods II and III) comprised 68 +/- 4% of the basic cycle length. In method III the postextrasystolic pause was programmed to equal the basic cycle length (i.e., noncompensatory) so that method I could serve as control for method III. RRP-HPS decreased from 331 +/- 37 msec in method I to 245 +/- 37 msec or less during the extrasystolic beat (p less than .001). A less dramatic corresponding shortening of ERP-VM and RRP-VM was observed, i.e., from 245 +/- 21 and 264 +/- 23 msec (method I) to 233 +/- 23 and 251 +/- 22 msec (method II), respectively (p less than .001). With the postextrasystolic beat, however, RRP-HPS increased to exceed the control value of method I by 23 +/- 11 msec (p less than .001). This greater-than-expected RP prolongation was also associated with significantly increased retrograde HPS conduction times (in method III vs method I) at both long and short test stimulus coupling intervals.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of the selective thromboxane synthetase inhibitor dazoxiben on variations in cyclic blood flow in stenosed canine coronary arteries.
Authors: Bush L R , Campbell W B , Buja L M , Tilton G D , Willerson J T
Published: June 2011

Recent studies suggest that platelet activation and subsequent thromboxane (TX) A2 release play important roles in certain coronary syndromes. To further test this possibility, we examined the ability of a selective TXA2-synthetase inhibitor, dazoxiben (UK-37-248), to abolish cyclic flow reductions (CFRs) that occur in experimentally stenosed canine coronary arteries. CFRs, which are characterized by progressive declines in coronary blood flow and interrupted by sudden and usually spontaneous restorations of flow, were produced by placing hard plastic cylindrical constrictors (5 mm long X 4.5 mm outer diameter) on the proximal left anterior descending or circumflex coronary artery in open-chest, anesthetized dogs. Coronary blood flow was measured with pulsed Doppler flow probes placed proximal to the constrictors and regional myocardial blood flow with 15 micron radiolabeled microspheres. CFRs were observed for 1 hr, during which coronary blood flow was monitored continuously. Regional myocardial blood flow was measured before constriction, when coronary blood flow appeared to be at its nadir, and after spontaneous restorations of flow. After 1 hr dazoxiben (2.5 mg/kg iv) or an equal volume of saline was given and coronary blood flow was monitored for another hour. Dazoxiben abolished CFRs completely in 18 of 28 dogs and significantly reduced their frequency in the dogs receiving the drug (10.1 +/- 0.8 vs 3.2 +/- 1.0 per hour [+/- SE]; p less than .001, n = 28). The frequency and magnitude of variations in cyclic blood flow were unchanged after saline (8.8 +/- 0.8 vs 9.0 +/- 1.0 per hour; p = NS, n = 13). The lowest levels of coronary blood flow before and after dazoxiben were 8.6 +/- 2.2% and 48.8 +/- 5.4% of control, respectively (p less than .001, n = 28), whereas this parameter remained unchanged after saline (18.7 +/- 5.7% vs 13.4 +/- 4.1%, respectively; n = 13). The levels of TXB2 and 6-keto-prostaglandin (PG) F1 alpha (stable breakdown products of TXA2 and prostacyclin, respectively) were measured in blood collected from aortic and distal coronary arterial catheters before coronary constriction (control), during CFRs, and after administration of dazoxiben. TXB2 levels measured distal to the stenosis were increased fivefold during CFRs (352 +/- 126 vs 71 +/- 18 pg/ml plasma; p less than .03) and were reduced to preconstriction (control) levels by dazoxiben (57 +/- 12 pg/ml). Aortic TXB2 levels almost doubled with CFRs and also returned to control levels after dazoxiben.(ABSTRACT TRUNCATED AT 400 WORDS)
Left ventricular performance, regional blood flow, wall motion, and lactate metabolism during transluminal angioplasty.
Authors: Serruys P W , Wijns W , van den Brand M , Meij S , Slager C , Schuurbiers J C , Hugenholtz P G , Brower R W
Published: June 2011

The response of left ventricular function, coronary blood flow, and myocardial lactate metabolism during percutaneous transluminal coronary angioplasty (PTCA) was studied in a series of patients undergoing the procedure. From four to six balloon inflation procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD) and a total occlusion time of 252 +/- 140 sec. Analysis of left ventricular hemodynamics in 19 patients showed that the relaxation parameters, peak negative rate of change in pressure, and early time constants of relaxation, responded earliest to short-term coronary occlusion (peak effect at 17 +/- 7 sec) while other parameters, such as peak pressure, left ventricular end-diastolic pressure, and peak positive rate of change in pressure, responded more gradually, suggesting a progressive depression of myocardial mechanics throughout the procedure. Left ventricular angiograms, available for 14 patients, indicated an early onset of asynchronous relaxation concurrent with the early response in peak negative dP/dt and the time constant of early relaxation. All hemodynamic functions fully recovered within minutes after the end of PTCA. Mean blood flow in the great cardiac vein and proximal coronary sinus and the hyperemic response were measured in 20 patients. Before PTCA mean flow in the great cardiac vein was 69 +/- 17 ml/min and in the coronary sinus it was 129 +/- 34 ml/min. Reactive hyperemia (great cardiac vein) was 55% after the first PTCA and 91% after the third. A more pronounced reaction was observed when the residual functional coronary stenosis was reduced in subsequent dilatations. Arteriovenous lactate difference appeared constant during the first two occlusions (control +0.11 mmol/liter, first PTCA -0.87 mmol/liter, and second PTCA -0.82 mmol/liter) and did not increase during subsequent occlusions. Within minutes after the procedure lactate balance was again positive, demonstrating the reversibility of the metabolic disturbances after repeated ischemia. The results of this study indicate that there is no permanent dysfunction of global or regional myocardial mechanics, myocardial blood flow, or lactate metabolism after PTCA with four to six coronary occlusions of 40 to 60 sec.
Endocardial mapping in humans in sinus rhythm with normal left ventricles: activation patterns and characteristics of electrograms.
Authors: Cassidy D M , Vassallo J A , Marchlinski F E , Buxton A E , Untereker W J , Josephson M E
Published: June 2011

Endocardial catheter mapping was performed in 15 patients in sinus rhythm who had no evidence of structural heart disease and normal left ventricles. Mapping was performed with the use of 10 mm interelectrode distance from various left ventricular endocardial sites. In 10 patients a quantitative analysis of electrographic amplitude, duration, and amplitude/duration ratio was performed. The normal left ventricular bipolar electrograms had an amplitude of greater than 3 mV, a duration of less than 70 msec, and an amplitude/duration ratio of greater than 0.045. Local activation times were also assessed in the 15 patients. This analysis revealed two endocardial breakthrough sites, one on the midinferior septum and a second on the anterior wall near the insertion of the anterior papillary muscle. We therefore have defined normal quantitative characteristics of left ventricular bipolar electrograms and the normal left ventricular activation sequence in the intact normal human left ventricle.
Effects of physical conditioning on left ventricular ejection fraction in patients with coronary artery disease.
Authors: Williams R S , McKinnis R A , Cobb F R , Higginbotham M B , Wallace A G , Coleman R E , Califf R M
Published: June 2011

To address the hypothesis that physical conditioning may improve left ventricular function in patients with coronary artery disease, we performed first-pass radionuclide ventriculography in 53 patients at rest and during upright bicycle exercise before and after 6 to 12 months of exercise training. The peak bicycle workload achieved before the onset of fatigue, dyspnea, or angina increased by an average of 22% (p = .0001) after training, and mean heart rate at a workload equal to the pretraining maximum workload was decreased by 10 beats/min after training (p = .0002). Of 21 subjects with angina or exertional ST segment depression before training, 15 (71%) were able to exercise to the same workload without these manifestations of ischemia after training. Whereas neither mean resting left ventricular ejection fraction (LVEF) nor LVEF at peak exertion was significantly altered, mean LVEF at the pretraining maximum workload was increased from 0.50 to 0.54 (p = .002) after training. There was a significant correlation between the magnitude of training bradycardia and the increment in LVEF at the pretraining maximum workload (p = .009). We conclude that the relative bradycardia at comparable exercise workloads produced by exercise conditioning is associated with improvements in left ventricular performance as assessed by the LVEF. This observation is compatible with the hypothesis that training bradycardia in conditioned subjects with ischemic heart disease is associated with lower myocardial oxygen demand and lesser degrees of ischemia at comparable workloads. However, training effects on ventricular afterload or on ischemia contractile performance of the heart cannot be excluded.
Safety of maximal exercise testing in patients at high risk for ventricular arrhythmia.
Authors: Young D Z , Lampert S , Graboys T B , Lown B
Published: June 2011

While maximal exercise testing is useful for detection of arrhythmias and assessment of antiarrhythmic drug efficacy, few reports have documented the safety of this procedure in patients with malignant ventricular arrhythmias. We reviewed the complications of symptom-limited exercise in 263 patients with such arrhythmias who underwent a total of 1377 maximal treadmill tests. Seventy-four percent of the population studied had a history of ventricular fibrillation or hemodynamically compromising ventricular tachycardia and the remainder had experienced ventricular tachycardia in the setting of either recent myocardial infarction or poor left ventricular function. A complication was defined as the occurrence of arrhythmia during exercise testing--ventricular fibrillation, ventricular tachycardia, or bradycardia--that mandated immediate medical treatment (cardioversion, use of intravenous drugs, or closed-chest compression). Complications were noted in 24 patients (9.1%) during 32 tests (2.3%), whereas 239 patients (90.9%) were free of complication during 1345 tests (97.7%). There were no deaths, myocardial infarctions, or lasting morbid events. Clinical descriptors associated with complications included male sex, presence of coronary artery disease, and a history of exertional arrhythmia (p less than .05). Clinical variables previously considered to confer increased risk during exercise, such as poor left ventricular function, high-grade ventricular arrhythmias (Lown grade 4A or 4B) before or during exercise, exertional hypotension, and ST depression, were not predictive of complications (p greater than .05). Occurrence of a complication was also unaffected by the use of antiarrhythmic drugs at the time of exercise (chi square = 0.19, p greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Noninvasive prediction of the angiographic extent of coronary artery disease after myocardial infarction: comparison of clinical, bicycle exercise electrocardiographic, and ventriculographic parameters.
Authors: Morris D D , Rozanski A , Berman D S , Diamond G A , Swan H J
Published: June 2011

To assess alternative criteria for the prediction of multivessel coronary artery disease after myocardial infarction, we compared the clinical, bicycle electrocardiographic, and radionuclide ventriculographic (ejection fraction and wall motion) responses in 110 patients undergoing coronary angiography after myocardial infarction. Ninety-seven of the 110 patients had multivessel coronary artery disease (two or more diseased vessels). Clinical or electrocardiographic abnormalities were observed in 41 of 97 (sensitivity = 43%) patients with multivessel disease, and in only two of 13 (specificity = 85%) patients without multivessel disease. The average information content of these combined clinical and electrocardiographic variables relative to perfect discrimination was 5%. Among the scintigraphic parameters, the conventional criterion for ejection fraction abnormality, a rise of less than 5% had a sensitivity of 72% and a specificity of 62% for multivessel coronary artery disease, while a fall in ejection fraction of 5% or more had a sensitivity of 39% and specificity of 92% for multivessel coronary artery disease. The presence of an exercise wall motion abnormality in the nonadjacent noninfarcted (remote) region had a sensitivity of 82% and specificity of 55% for multivessel coronary artery disease. A more stringent criterion, worsening of remote wall motion with exercise, had a sensitivity of 52% and specificity of 75%. When this latter criterion was combined with a fall in ejection fraction, the sensitivity for multivessel coronary artery disease increased to 62%, specificity remained 75%, and information content increased from 5% to 10%. We conclude that conventional diagnostic criteria for abnormal clinical, bicycle electrocardiographic, or scintigraphic results do not identify patients with additional coronary artery disease after infarction with high accuracy. Two alternative ventriculographic parameters--a fall in ejection fraction and wall motion worsening--are similar to clinical parameters in specificity, but have a higher sensitivity and information content.
Validity of echocardiographic determination of left ventricular systolic wall thickening.
Authors: Feneley M P , Hickie J B
Published: June 2011

Previous direct measurements of left ventricular systolic wall thickening (SWT) in animal studies have yielded values approximately one-half those found echocardiographically in humans, suggesting a possible overestimation of SWT by echocardiographic techniques. To test the validity of echocardiographic SWT measurements, the relationship between echocardiographically determined end-diastolic and end-systolic left ventricular short-axis myocardial cross-sectional areas (ED Myo CSA and ES Myo CSA, respectively) was assessed in 18 normal subjects. Since Myo CSA is a function of wall thickness and wall circumference, overestimation of SWT by echocardiography would be expected to produce an overestimation of ES Myo CSA relative to ED Myo CSA. SWT, as determined by both M mode (52%) and two-dimensional echocardiography (48%), was consistent with previously reported echocardiographic values, but exceeded that reported in animal studies. By least squares linear regression analysis, ES Myo CSA was 1.078 X ED Myo CSA - 0.385 cm2 (r = .947 SEE = 1.183 cm2) when assessed by one observer and was 1.042 X ED Myo CSA - 0.142 cm2 (r = .906, SEE = 1.831 cm2) when assessed independently by another. The close relationship observed between echocardiographically determined ES Myo CSA and ED Myo CSA was consistent with constant left ventricular myocardial mass throughout the cardiac cycle and thus did not suggest an overestimation of SWT by echocardiographic techniques.
Quantitative two-dimensional echocardiographic analysis of regional wall motion in patients with perioperative myocardial infarction.
Authors: Force T , Bloomfield P , O'Boyle J E , Khuri S F , Josa M , Parisi A F
Published: June 2011

Regional left ventricular wall motion was evaluated by two-dimensional echocardiographic techniques with fixed- and floating-axis analytical algorithms in three groups of subjects: normal subjects (n = 15), patients undergoing uncomplicated coronary artery bypass graft surgery (CABG) (n = 10), and patients suffering perioperative myocardial infarction (n = 27). In patients undergoing uncomplicated CABG, fixed-axis analysis in the apical four-chamber view produced septal hypokinesis indistinguishable from the septal hypokinesis seen in patients with anterior myocardial infarction. In addition, fixed-axis analysis enhanced lateral wall motion so that patients with lateral myocardial infarction were classified as normal. Floating-axis analysis corrected these limitations by (1) producing regional left ventricular wall motion in the patients undergoing uncomplicated CABG, which was identical to that in normal subjects, and (2) producing regional left ventricular wall motion in patients with myocardial infarction that was hypokinetic in segments corresponding to the electrocardiographic area of involvement. In patients with new Q waves, fixed-axis analysis detected abnormalities of regional left ventricular wall motion in 24 of 34 (71%) electrocardiographically involved regions but also classified 44 of 100 segments in uncomplicated patients as abnormal. Floating-axis analysis detected regional left ventricular wall motion abnormalities in 30 of 34 patients (88%; p less than .05 vs fixed-axis analysis) and only 15 of 100 segments in patients undergoing uncomplicated CABG were classified as abnormal (p less than .001 vs fixed-axis analysis). We conclude that floating-axis analysis is a more accurate and clinically relevant method of evaluating regional left ventricular wall motion in patients undergoing CABG who suffer myocardial infarction as a perioperative complication.
The effects of organic nitrates on prostacyclin biosynthesis and platelet function in humans.
Authors: Fitzgerald D J , Roy L , Robertson R M , FitzGerald G A
Published: June 2011

The results of prior studies indicate that nitroglycerin stimulates prostacyclin release by cultured endothelium and by the coronary vasculature in vivo. However, the accuracy of these findings in coronary vasculature relies on plasma samples obtained from the circulation via cardiac catheters, a procedure we have shown to stimulate prostacyclin release, thereby confounding interpretation of drug action. We studied the effects of short-acting (nitroglycerin) and long-acting (isosorbide dinitrate) nitrates on a noninvasive index of prostacyclin synthesis, excretion of urinary 2,3-dinor-6-keto-PGF1 alpha. Nitroglycerin was infused into six subjects to either a maximum of 480 micrograms/min or until mean arterial pressure fell by 20 mm Hg. Urine was collected for negative ion chemical ionization gas chromatographic, mass spectrometric analysis before and during the nitroglycerin infusion and for two 2 hr periods after nitroglycerin. The peak nitroglycerin infusion rate was 387 +/- 67 micrograms/min, which caused a fall in supine blood pressure (systolic/diastolic) of 11 +/- 5/14 +/- 4 mm Hg and a 12 +/- 3 beats/min increase in heart rate. Excretion of 2,3-dinor-6-keto-PGF1 alpha (pg/mg creatinine) was unchanged from control infusion values (106 +/- 19.5) either during (123 +/- 21) or after (134 +/- 14.6; 139 +/- 36) nitroglycerin infusion. Platelet aggregation to arachidonic acid (0.33 to 1.33 microM) and epinephrine (1 to 10 microM) ex vivo was inhibited in only one subject in whom excretion of 2,3-dinor-6-keto-PGF1 alpha was unaltered. Serum thromboxane B2 was not changed by nitroglycerin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Hydrogen peroxide contrast echocardiography: quantification in vivo of myocardial risk area during coronary occlusion and of the necrotic area remaining after myocardial reperfusion.
Authors: Kemper A J , O'Boyle J E , Cohen C A , Taylor A , Parisi A F
Published: June 2011

During sustained coronary occlusion in canine preparations, the extent of regions that fail to show contrast enhancement when imaged by supra-aortic hydrogen peroxide contrast echocardiography (SHPCE) has been shown to correlate well for single cross sections with the extent of malperfused myocardium "at risk" of infarction. In the present study, SHPCE was investigated as a means of determining the fraction of total left ventricular mass at risk during occlusion. Since necrotic tissue has low blood flow even when reperfused, we also investigated the potential of quantitating the extent of infarcted myocardium by measuring the extent of contrast defects seen with SHPCE performed during reperfusion. In 20 dogs the fraction of the left ventricle showing a contrast defect during coronary occlusion correlated well with the fraction of the left ventricular mass "at risk" by an autoradiographic technique (autoradiography = 0.83 echocardiography + 8.6%; r = .89, SEE = 4.5%). SHPCE was also performed after 3 hr of reperfusion following occlusions varying in duration from 60 to 150 min. The fraction of the ventricle showing a contrast defect during reperfusion predicted the infarcted portion of the left ventricle as shown by triphenyl tetrazolium chloride staining (% left ventricle infarcted = 0.81 echocardiography + 3.3%; r = .84, SEE = 5.3%). Observer variability for the fraction of the ventricle showing a contrast defect was excellent during both occlusion and reperfusion. The ratio of the left ventricular extent of contrast-negative regions during reperfusion and occlusion was used to calculate a necrosis-to-risk index in vivo that correlated relatively well with the myocardial necrosis-to-risk ratio determined morphologically (r = .77, SEE = 16%).(ABSTRACT TRUNCATED AT 250 WORDS)
Failure of nifedipine and reperfusion to reduce infarct size relative to region at risk as measured by NADH fluorophotography.
Authors: Foster E , DeJong D , Connelly C , Apstein C S
Published: June 2011

In this report we describe a new technique for the measurement of region at risk after coronary artery ligation in the rabbit by NADH fluorophotography. We also describe the application of this technique to a study of nifedipine combined with reperfusion in experimental myocardial infarction. In 16 untreated rabbits the epicardial surface area of NADH fluorescence immediately after coronary ligation correlated with infarct size at 24 hr after coronary occlusion, as measured by nitro blue tetrazolium staining (r = .84, p less than .001). In 24 rabbits we studied the effect of nifedipine administered immediately after coronary ligation and combined with reperfusion at 1 hr after occlusion. Nifedipine had no significant effect on region at risk or infarct size.
Reversal of left ventricular dysfunction after aortic valve replacement for chronic aortic regurgitation: influence of duration of preoperative left ventricular dysfunction.
Authors: Bonow R O , Rosing D R , Maron B J , McIntosh C L , Jones M , Bacharach S L , Green M V , Clark R E , Epstein S E
Published: June 2011

Preoperative left ventricular systolic function is an important predictor of postoperative prognosis in patients with aortic regurgitation. Although left ventricular dysfunction is reversible after aortic valve replacement to a greater extent in patients with good preoperative exercise capacity compared with patients with impaired exercise capacity, not all patients with preserved exercise capacity demonstrate improved left ventricular function after aortic valve replacement. To determine the influence of duration of preoperative left ventricular dysfunction on postoperative reversal of left ventricular dysfunction, we studied 37 patients with aortic regurgitation who preoperatively had left ventricular dysfunction, defined as subnormal echocardiographic fractional shortening (less than 29%), and good preoperative exercise capacity, defined as completion of stage I of the NIH treadmill protocol without limiting symptoms. Eight patients were asymptomatic. In 11 patients left ventricular dysfunction was documented 18 to 57 months preoperatively (prolonged); in 10 patients left ventricular dysfunction developed in an interval of 14 months or less preoperatively (brief); in 16 patients duration of left ventricular dysfunction was unknown. Patients with brief vs those with prolonged left ventricular dysfunction did not differ with respect to severity of preoperative symptoms or exercise tolerance, echocardiographically determined left ventricular dimensions or fractional shortening (25 +/- 3% [SD] vs 25 +/- 3%), or radionuclide angiographic ejection fraction (42 +/- 5% vs 42 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)
New application of direct sinus node recordings in man: assessment of sinus node recovery time.
Authors: Gomes J A , Hariman R I , Chowdry I A
Published: June 2011

Sinus node recovery time (SNRT) is frequently used to assess sinus node function in patients with suspected sick sinus syndrome (SSS). Although SNRT is assumed to reflect sinus node automaticity, this assumption remains unproven. The purpose of this study was (1) to test the hypothesis that SNRT in patients with and without SSS reflects sinus node automaticity, and (2) to assess the role of sinoatrial conduction time in the measurement of SNRT. A total of 16 patients (mean +/- SD age 63 +/- 9 years), seven of which had SSS, form the basis of this report. An electrogram of the sinus node was obtained for each of the 16 patients, and overdrive pacing was performed in each at cycle lengths of 1000 to 300 msec. SNRT was measured (1) on the sinus node electrogram (direct method, measuring SNRTd) as the interval from the last pacing stimulus artifact to the onset of the upstroke slope of first postpacing sinus beat and (2) on the high right atrial electrogram (indirect method, measuring SNRTi). Results were as follows: (1) The longest SNRTd was significantly shorter than the longest SNRTi (989 +/- 304 vs 1309 +/- 356 msec, p less than .001). (2) For the first postpacing sinus beat there was a significant prolongation of sinoatrial conduction time as compared with that for sinus beats before pacing (319 +/- 152 vs 99 +/- 35 msec, p less than .001). Sinoatrial conduction time normalized within 3.6 +/- 0.96 postpacing sinus beats. (3) At the pacing cycle length that resulted in the longest recovery time, sinus node depression was seen in 56% of patients, sinus node acceleration was noted in 26%, and no appreciable change in sinus node automaticity was observed in 19%. (4) Sinoatrial conduction time for the sinus beat before pacing and that for the first postpacing beat was longer in patients with SSS when compared with in patients without SSS. (5) In patients with SSS the abnormal SNRTi, when corrected for the degree of prolongation of sinoatrial conduction time for the first postpacing beat, became normal in five of six patients. We conclude that (1) SNRTi reflects both sinus node automaticity and sinoatrial conduction time, whereas SNRTd reflects sinus node automaticity, (2) overdrive atrial pacing results in marked prolongation of sinoatrial conduction time for the first postpacing beat, which is longer in patients with SSS when compared with in those without SSS, and (3) in patients with SSS the inference of abnormal sinus node automaticity on the basis of a prolonged corrected SNRTi is usually incorrect.
Preservation of high-energy phosphates by verapamil in reperfused myocardium.
Authors: Lange R , Ingwall J , Hale S L , Alker K J , Braunwald E , Kloner R A
Published: June 2011

To determine whether verapamil prevents depletion of adenine nucleotides during and after severe myocardial ischemia, dogs were subjected to 15 min occlusions of the left anterior descending coronary artery followed by 240 min of reperfusion. One hour before occlusion, dogs were randomly assigned to a treatment group (n = 10) to which an infusion of intravenous verapamil was given until the onset of reperfusion or to an untreated saline group (n = 9). Verapamil reduced mean aortic pressure and heart rate. After 15 min of ischemia, endocardial adenosine triphosphate (ATP) level, determined by needle biopsy, decreased in the untreated group from 34.7 +/- 2.0 to 24.4 +/- 2.7 nmol X mg protein-1 (p less than .005 vs preocclusion) and in the verapamil group from 32.8 +/- 1.5 to 30.3 +/- 1.5 nmol X mg protein-1 (NS vs preocclusion). Dogs receiving verapamil had significantly higher ATP levels than untreated animals after 90 and 240 min of reperfusion. In untreated animals the sum of inosine and hypoxanthine levels increased during occlusion from very low levels to 4.6 +/- 1.1 nmol X mg protein-1 in the epicardium and to 6.8 +/- 1.5 nmol X mg protein-1 in the endocardium (p less than .05 compared with preocclusion values). In verapamil-treated dogs inosine and hypoxanthine levels increased to only 1.2 +/- 0.3 (epicardium) and 1.9 +/- 0.6 nmol X mg protein-1 (endocardium) (both NS compared with preocclusion values). After 90 min of reperfusion the sum of ATP, adenosine diphosphate, adenosine monophosphate, inosine, and hypoxanthine levels was decreased in the endocardium by 10.2 nmol X mg protein-1 in the untreated group, but no change was observed in verapamil-treated animals. We conclude that breakdown of ATP to inosine and hypoxanthine during severe ischemia is reduced by verapamil, resulting in higher ATP concentrations during occlusion and reperfusion and decreased washout of the diffusible purines inosine and hypoxanthine during reperfusion.
Continuous measurement of left ventricular volume in animals and humans by conductance catheter.
Authors: Baan J , van der Velde E T , de Bruin H G , Smeenk G J , Koops J , van Dijk A D , Temmerman D , Senden J , Buis B
Published: June 2011

An eight-electrode conductance catheter previously developed by us and used to determine stroke volume in dogs was applied in human beings and dogs to measure absolute left ventricular volume quantitatively. For calibration we developed the formula V(t) = (1/alpha)(L2/sigma b)G(t) - Vc, where V(t) is time-varying left ventricular volume, alpha is a dimensionless constant, L is the electrode separation, sigma b is the conductivity of blood obtained by a sampling cuvette, and G(t) is the measured conductance within the left ventricular cavity. Vc is a correction term caused by the parallel conductance of structures surrounding the cavity and is measured in two ways. The first method, applicable in the anesthetized animal, consists of temporary reduction of volume to zero by suction. The second method uses a transient change in sigma b by injection of a small bolus of hypertonic saline (dogs) or 10 ml of cold glucose (humans) into the pulmonary artery. The validity of the formula was previously established for the isolated postmortem canine heart. The predicted linearity, slope constant alpha, and accuracy of Vc for the left ventricle in vivo were investigated by comparing the conductance volume data with results from independent methods: electromagnetic blood flow measurement for stroke volume and indicator dilution technique for ejection fraction (dogs), thermal dilution for cardiac output (12 patients), and single-plane cineventriculography for V(t) (five patients). In all comparisons, linear regression showed high correlation (from r = .82 [n = 46] to r = .988 [n = 20]) while alpha, with one exception, ranged from 0.75 to 1.07 and the error in Vc ranged from 0.5% to 16.5% (mean 7%). After positioning of the catheter, no arrhythmias were observed. It is concluded that the conductance catheter provides a reliable and simple method to measure left ventricular volume, giving an on-line, time-varying signal that is easily calibrated. Together with left ventricular pressure obtained through the catheter lumen, the instrument may be used for instantaneous display of pressure-volume loops to facilitate assessment of left ventricular pump performance.
Effect of heparin bonding on catheter-induced fibrin formation and platelet activation.
Authors: Nichols A B , Owen J , Grossman B A , Marcella J J , Fleisher L N , Lee M M
Published: June 2011

Pathologic and experimental evidence indicates that platelet activation and fibrin formation contribute to the pathogenesis of angina pectoris, coronary vasospasm and myocardial infarction. Detection of localized intravascular platelet activation and fibrin formation in vivo by selective blood sampling requires catheters that do not induce coagulation ex vivo. We studied the effect of heparin bonding of catheter surfaces on activation of the coagulation system by cardiovascular catheters. Woven Dacron, polyvinylchloride, and polyurethane catheters were tested and compared with identical catheters with heparin-bonded surfaces in 47 patients undergoing percutaneous cardiac catheterization. Platelet activation was measured by radioimmunoassay of plasma platelet factor 4 (PF4), beta-thromboglobulin (BTG), and thromboxane B2 (TXB2) in blood samples withdrawn through catheters, and fibrin formation was assessed by determination of fibrinopeptide A (FPA) levels. In blood samples collected through conventional catheters, FPA, PF4, BTG, and TXB2 levels were markedly elevated; blood sampling through heparin-bonded catheters had no significant effect on FPA, PF4, BTG, or TXB2 levels. Scanning electron microscopy disclosed extensive platelet aggregates and fibrin strands adherent to the surface of conventional catheters but not to heparin-bonded catheter surfaces. This study demonstrates that (1) collection of blood samples through cardiovascular catheters causes artifactual elevation of FPA, PF4, BTG, and TXB2 levels, and (2) heparin-bonded catheter surfaces effectively prevent catheter-induced platelet alpha-granule release and fibrin formation on catheter surfaces. Heparin-bonded catheters will facilitate investigation of the role of intravascular coagulation in coronary artery disease by eliminating catheter-induced fibrin formation and platelet activation.
Balloon dilatation angioplasty: nonsurgical management of coarctation of the aorta.
Authors: Cooper R S , Ritter S B , Golinko R J
Published: June 2011

Balloon dilatation angioplasty was successfully performed in five patients (ages 18 months to 17 years) with discrete aortic coarctation. The catheter size was No. 8F or 9F. Selection of balloon diameter was based on angiographic measurements of the aorta determined proximal and distal to the coarctation site. A 10 sec inflation-deflation cycle at 6 to 8 atmospheres (90 to 120 psi) was performed. The systolic pressure gradients across the coarctation before balloon dilatation angioplasty ranged from 35 to 70 mm Hg. Systolic pressure gradients after balloon dilatation angioplasty ranged from 0 to 10 mm Hg. All patients had normalized blood pressure immediately. Abnormal pulsed Doppler echocardiograms were observed in all patients before balloon dilatation angioplasty; four patients had normal echocardiograms after balloon dilatation angioplasty. No serious intraprocedural complications occurred. One patient required femoral artery thrombectomy 36 hr after balloon dilatation angioplasty. One to 6 months after balloon dilatation angioplasty no patients have evidence of restenosis of coarctation. Early results suggest that balloon dilatation angioplasty may offer a safe and effective nonsurgical alternative for the treatment of discrete coarctation in older infants and children. Long-term follow-up for the incidence of restenosis and formation of aneurysms will ultimately determine the efficacy and safety of this procedure.
The use of left ventricular end-ejection pressure and peak pressure in the estimation of the end-systolic pressure-volume relationship.
Authors: Kono A , Maughan W L , Sunagawa K , Hamilton K , Sagawa K , Weisfeldt M L
Published: June 2011

The end-systolic pressure-volume relationship (ESPVR) as derived from left ventricular pressure-volume loops has gained increasing acceptance as an index of ventricular contractile function. In animal experiments the ESPVR has been defined as a line connecting the upper left corners of several differently loaded pressure-volume (P-V) loops with a slope parameter Ees and a volume axis intercept parameter Vo. In the clinical setting, several variants of the ESPVR have been determined with use of peak left ventricular pressure, end-ejection pressure, and end-ejection volume. The maximum P-V ratio has also frequently been measured. We attempted to determine which of these alternatives resulted in good approximations of the reference ESPVR in eight isolated canine ventricles that ejected into a simulated arterial impedance system with resistance, compliance, and characteristic impedance. We determined various versions of the ESPVR from the same set of beats quickly obtained with little change in inotropic background. To vary ventricular pressure wave forms, each of the arterial impedance parameters was independently controlled at 50%, 100%, and 200% of normal. Against each of the nine combinations of the impedance parameters four P-V loops were obtained under four preloads and from each of the sets of four P-V loops, the reference ESPVR, linear regression of the peak pressure on end-ejection volume (ESPVRPP-EEV), and linear regression of end-ejection pressure on end-ejection volume (ESPVREEPV) were determined. In addition, the maximum P-V ratio (MPVR) was calculated for each P-V loop.(ABSTRACT TRUNCATED AT 250 WORDS)