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Three cases of right ventricular outflow tract obstruction caused by 3 distinct tumors-myxoma, sarcoma, and presumed metastatic tumor-diagnosed by transthoracic and transesophageal echocardiography are presented. The differences among these 3 types of tumors with similar clinical and echocardiographic findings are highlighted, and a review of the pertinent literature is discussed. By applying the approximate frequencies of cardiac tumors categorized by type and site, statistically, an intracavitary right ventricular outflow tract tumor is 70 to 140 times more likely to be malignant than benign; furthermore, if it is a primary cardiac tumor, it is approximately 2 times more likely to be a sarcoma than a myxoma.

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This case illustrates the complementary value of transesophageal echocardiography to routine transthoracic echocardiography in an asymptomatic adult patient with Turner's syndrome. The combined findings of bicuspid aortic valve, severe aortic dilation, coarctation of the aorta, and type A aortic dissection were clearly delineated by transesophageal echocardiography.

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OBJECTIVE: To determine the short-term safety and tolerability of the addition of ecadotril to conventional therapy in patients with mild to moderate heart failure. METHODS: Fifty ambulatory patients, 18 to 75 years of age, with mild to moderate heart failure, left ventricular ejection fraction

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The purpose of this study was to determine whether exercise technetium-99m sestamibi gated single-photon emission computed tomography (SPECT) accurately distinguishes between patients with ischemic cardiomyopathy and patients with nonischemic left ventricular systolic dysfunction. Noninvasive tests have previously failed to accurately separate patients with ischemic cardiomyopathy from those with nonischemic cardiomyopathy. Technetium-99m gated SPECT imaging offers advantages that have the potential to overcome the limitations of previous studies. Thirty-seven adults with a left ventricular ejection fraction < or = 35%, including 24 patients with nonischemic cardiomyopathy and 13 patients with ischemic cardiomyopathy, were prospectively evaluated using symptom-limited metabolic exercise treadmill testing with technetium-99m sestamibi gated SPECT imaging. Interpretation of myocardial perfusion and regional wall motion was performed, using a 17-segment model. Summed stress, rest, and reversibility perfusion defect scores were determined, and the variance of segmental wall motion scores was computed. Summed stress, rest, and reversibility perfusion defect scores were significantly lower in nonischemic cardiomyopathy patients, compared with those with ischemic cardiomyopathy (summed stress defect score: 6.9 +/- 3.8 vs 32.9 +/- 7.7, respectively, p <0.001). Variability in segmental wall motion was also significantly lower in patients with nonischemic cardiomyopathy compared with those with ischemic cardiomyopathy (variance: 0.3 +/- 0.3 vs 1.2 +/- 0.8, respectively, p <0.001). Thus, assessment of myocardial perfusion and regional ventricular function with exercise technetium-99m sestamibi gated SPECT imaging can reliably distinguish between patients with ischemic cardiomyopathy and patients with nonischemic dilated cardiomyopathy.

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BACKGROUND: The mechanism for early improvement in cardiac function after cardioversion from atrial fibrillation is unknown. METHODS: We measured ventricular volumes and load-independent contractility during atrial fibrillation and within 24 hours after cardioversion to sinus rhythm in 15 adult patients (10 men, 5 women; mean age 63+/-4 years, range 31 to 81 years). Duration of atrial fibrillation ranged from <1 day to 6 months. RESULTS: After cardioversion, left ventricular ejection fraction increased from 51%+/-4% to 61%+/-4% (P=.001, 95% confidence intervals for the difference, 7% to 15%), stroke volume increased from 57+/-4 mL to 76+/-6 mL (P < .001, 95% confidence intervals 8 to 32 mL), and mean cycle length increased from 0.77+/-.04 seconds in atrial fibrillation to 1.02+/-.04 seconds in sinus rhythm (P=.002, 95% confidence intervals, 0.1 to 0.4 seconds). Cardiac contractility, as expressed by the slope and the intercept of the relation between rate-corrected circumferential velocity of fiber shortening and end-systolic wall stress (Vcfc/ESWS) remained unaltered in 13 of 15 patients, suggesting that intrinsic inotropic state was unchanged immediately after return of normal sinus rhythm. Finally, a significant correlation was observed between improvement in stroke volume and peak A-wave velocity (r=0.79, P=.035). CONCLUSION: Both left ventricular stroke volume and ejection fraction increase immediately after cardioversion, whereas intrinsic cardiac contractility is largely unchanged. These data suggest that the mechanism of this increase is enhanced left ventricular diastolic filling due mostly to increased cycle length and return of left atrial mechanical function.

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OBJECTIVE: The aim was to examine the role of neutrophil activation in the genesis of oxidative stress during the early phases of reperfusion after ischaemia in patients subjected to aortocoronary bypass grafting. METHODS: Ten selected patients were studied. All had normal ejection fraction and normal left ventricular end diastolic pressures before operation. Each patient required at least three grafts, so that the duration of aortic crossclamping exceeded 30 min, the minimum ischaemic period required to detect oxidative stress upon reperfusion. Oxidative stress was assessed by measuring the formation and release of oxidised glutathione (GSSG) in the coronary sinus 1 min before and 3 min after the start of the cardiopulmonary bypass, and then 1, 5, 10, and 20 min after removal of the aortic clamp, and again 5 and 10 min after the end of the cardiopulmonary bypass. The arterial-coronary sinus difference for neutrophils, elastase-alpha 1 protease complex (elastase), and creatine phosphokinase was also monitored at the same intervals. RESULTS: Before clamping GSSG was undetectable in arterial and coronary sinus blood. There was no significant arterial-coronary sinus difference for neutrophils or elastase [53(SEM 66) cell.ml-1 and 1.10(2.49) micrograms.litre-1, respectively[. Five minutes after re-establishment of coronary blood flow, there was both a release of GSSG into the coronary sinus [arterial-coronary sinus difference: 11(2.6) nmol.dl-1] and an accumulation of neutrophils in the heart [arterial-coronary sinus difference: 262(33), P < 0.01 cell.ml-1], whereas no elastase release from the heart was measured [arterial-coronary sinus difference 7.6(4.46) microgram.litre-1, NS]. The arterial levels of elastase increased progressively during the operation from 48(5) microgram.litre-1 (preclamping) to 405(62) microgram.litre-1, P < 0.01 (end of the cardiopulmonary bypass). CONCLUSIONS: These data indicate that, in man, neutrophils do accumulate in the myocardium during early reperfusion. However, they are not activated when oxidative stress occurs. It is unlikely that the neutrophil localisation in the heart has pathological significance in the production of oxygen free radicals during early reperfusion. Free radical accumulation in the coronary vessels may contribute to disorders of coronary flow associated with reperfusion.

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Activation of phospholipases during prolonged myocardial ischemia could contribute to the functional derangement of myocardial cells by altering the phospholipid environment of a number of membrane bound proteins including receptors. The present study examined the kinetics of muscarinic receptor antagonist [3H]quinuclidinyl benzilate binding ([3H]QNB) to muscarinic receptors of highly purified sarcolemmal membranes under control conditions and after treatment with phospholipase A2 (PLA2; EC 3.1.1.4). Initial binding rates of QNB exhibited saturation kinetics, when plotted against the ligand concentration in control and PLA2 treated sarcolemmal membranes. This kinetic behaviour of QNB-binding is consistent with at least a two step binding mechanism. According to this two step binding hypothesis an unstable intermediate receptor-QNB complex (R*QNB) forms rapidly, and this form undergoes a slow conversion to the high affinity ligand-receptor complex R-QNB. The Michaelis constant Km of R-QNB formation was 1.8 nM, whereas the dissociation constant Kd obtained from equilibrium measurements was 0.062 nM. After 5 min exposure of sarcolemmal membranes to PLA2QNB binding capacity (Bmax) was reduced by 62%, and the affinity of the remaining receptor sites was decreased by 47% (Kd = 0.116 nM). This PLA2-induced increase of Kd was accompanied by a corresponding increase of Km, whereas the rate constants k2 and k-2 of the hypothetical slow conversion step (second reaction step) remained unchanged. These results suggest that binding of QNB to cardiac muscarinic receptors induces a transition in the receptor-ligand configuration, which is necessary for the formation of the final high affinity R-QNB complex. PLA2-induced changes of the lipid environment result in the inability of a part of the receptor population to undergo this transition, thereby inhibiting high affinity QNB-binding.

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Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)

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The binding of [3H]digoxin to purified canine cardiac sarcolemmal vesicles was characterized. Scatchard analysis of saturation isotherms yielded linear plots with a maximal binding capacity of 174 +/- 31.9 pmol/mg, a dissociation constant of 31.7 +/- 4.59 nM, and a Hill coefficient of 0.947 +/- 0.02 (mean +/- SEM), suggesting that [3H]digoxin bound to a single class of sites. In contrast to their marked effect on steady-state serum digoxin levels when administered in combination, quinidine, verapamil, and amiodarone were without effect on equilibrium binding of [3H]digoxin. Thus, increased steady-state serum concentrations of digoxin resulting from combination therapy with these particular drugs probably will have cardiac effects that may increase the risk of digitoxicity to the patient.

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To identify a rapid, uninhibited rate of exchange activity, we investigated in canine sarcolemmal vesicles the rapid kinetics of Na(+)-Ca2+ exchange. Sarcolemmal vesicles were incubated in 160 mM NaCl and 20 mM HEPES at 25 degrees C (pH 7.4) and actively loaded with 45Ca2+ for 2 minutes by Na(+)-Ca2+ exchange. After further uptake was inhibited by dilution into 0.15 mM Na(+)-free EGTA, sarcolemmal vesicles were immobilized on a rapid filtration apparatus that allowed millisecond resolution of 45Ca2+ fluxes. In the presence of external NaCl (Na+o) but not other monovalent cations (i.e., K+, Li+), a biphasic pattern of Ca2+ release was observed--an initial brief and rapid rate of Ca2+ release followed by a second slower, prolonged phase of Ca2+ release. Semilogarithmic plots of sarcolemmal Ca2+ content versus time were not linear but were consistent with a biexponential rate of Na+o-induced Ca2+ release during the first several seconds of the exchange reaction. The fast phase of Na+o-stimulated Ca2+ release was several thousand-fold more rapid than that in the absence of Na+o. Both phases of Ca2+ release showed a similar Na+o dependence (Km, approximately 12 mM) with evidence of a positive cooperative effect of Na+. Vmax of the fast and slow phases were approximately 37.0 and approximately 0.76 nmol/mg/sec, respectively. Using rapid-reaction techniques, we demonstrated in the present study that the initial velocity of sarcolemmal Na(+)-Ca2+ exchange activity is greater than previously reported in sarcolemmal vesicles and that this exchange process exhibits complex rate behavior with a biphasic pre-steady state kinetic pattern.

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Ambulatory electrocardiographic monitoring and the frequent use of stress electrocardiography have been important tools in characterizing the prevalence and prognostic importance of ventricular ectopic activity in both healthy persons and patients with organic heart disease. These studies have demonstrated that ventricular ectopy is not uncommon in persons with no evidence of heart disease. However, it is rarely of high density or repetitive, and even when frequent or repetitive, or both, carries little, if any, risk of sudden death in patients without syncope. However, in patients with organic heart disease and in certain clinical settings, frequent and repetitive ventricular ectopy identifies a population at high risk for arrhythmia-induced syncope or sudden death. These rhythm disturbances have particular prognostic importance in ischemic heart disease with depressed left ventricular function and hypertrophic cardiomyopathy. Patients with presyncope or syncope and structural heart disease who demonstrate frequent and repetitive ventricular ectopy are also a high-risk group. Therefore, individual risk stratification is important in deciding whether and how to treat patients with ventricular ectopy.

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These complications can be broken down into three major categories: the direct effects of ischemia, the effects of myocardial rupture or similar structural loss secondary to ischemic insult, and the effects of inhibitory autonomic reflexes triggered by infarction. It is critical to correlate the hemodynamic problem with its etiology in order to choose the appropriate treatment.

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Phospholipase A2 (PLA2) inhibits ligand binding to sarcolemmal muscarinic receptors in heart. To determine whether this effect of PLA2 is mediated by membrane accumulation of non-esterified fatty acids (FFA), the effect of selected fatty acids on the binding of 3H-quinuclidinyl benzylate (3H-QNB) to purified canine sarcolemmal membranes before and after PLA2 treatment was examined. Equilibrium 3H-QNB binding was inhibited by 5 min exposure of membrane vesicles to oleic, linoleic or arachidonic acid (IC50 = 6.3 +/- 0.9, 9.9 +/- 1.1, and 6.8 +/- 0.4 microM, respectively); the saturated fatty acids, stearic and palmitic acid (10 microM) had no effect. Scatchard analysis of equilibrium binding isotherms showed that the effect of the unsaturated fatty acids to inhibit 3H-QNB binding reflected a decrease of Bmax and a reduction of the affinity of the remaining receptors. The effect of unsaturated fatty acids was dependent on the mole ratio of fatty acid to membrane phospholipid present (FFA/PL ratio). Washing of fatty acid-treated membranes with bovine serum albumin (BSA) resulted in partial recovery of both maximal binding (Bmax) and affinity. The fatty acid-induced reduction of Bmax was also attenuated if binding was started by simultaneous addition of 3H-QNB and FFA. Similarity of the FFA induced effects on 3H-QNB binding to sarcolemmal muscarinic receptors to those induced by PLA2 suggest that membrane accumulation of unsaturated fatty acids underlies in part the effect of PLA2. Furthermore, modification of the receptor-ligand interaction by changes in the membrane lipid composition may be prevented by ligand occupation of the receptor.

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Verapamil, in addition to blocking calcium channels, exhibits such "non-specific" effects on myocardium as inhibition of sodium and potassium conductances and modifications of muscarinic receptor-ligand interactions. To characterize further the effects of verapamil on the cardiac muscarinic receptor, we examined the abilities of the enantiomers of verapamil to modify the binding of the muscarinic antagonist [3H]quinuclidinyl benzilate ([3H]QNB) to purified canine sarcolemmal vesicles. Membranes were incubated with [3H]QNB and various concentrations of racemic, (+)-, or (-)- verapamil (25 or 37 degrees, pH 7.4), and reactions were terminated by rapid filtration. (-)-Verapamil (Ki of 5.3 +/- 0.2 microM) was twice as potent an inhibitor of equilibrium binding as (+)-verapamil (Ki of 11.4 +/- 0.6 microM), and this effect resulted from the ability of each enantiomer to slow [3H]QNB-receptor association. This degree of stereoselectivity, albeit at nanomolar concentrations, was similar to that observed for each enantiomer to compete for the specific phenylalkylamine site in this preparation. Verapamil also inhibited [3H]QNB-receptor dissociation, but this effect required high concentrations and demonstrated stereoselectivity opposite to that observed for association. These findings support the view that verapamil interacts with two distinct sites, possibly within membrane lipid, each with a different affinity and preference for (+)- and (-)-verapamil, to modify the muscarinic receptor.

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Effects of phospholipase A2 (PLA2)-catalyzed hydrolysis of sarcolemmal phospholipids on ventricular muscarinic receptors were examined by measuring specific binding of 3H-quinuclidinyl benzilate (3H-QNB) to purified canine sarcolemmal vesicles. Scatchard analysis of 3H-QNB saturation isotherms (25 degrees C, pH 7.4) yielded a dissociation constant (Kd) of 58 +/- 10 pM and maximal binding capacity (Bmax) of 5.7 +/- 1.3 pmol/mg. Pretreatment of the sarcolemmal membranes with PLA2 (1 U/ml) for 5 and 30 mins reduced Bmax to 38% and 7% of control, and increased Kd to 109 +/- 21 and 129 +/- 12 pM, respectively. Washing of PLA2-treated sarcolemmal vesicles with defatted albumin resulted in a partial recovery of Bmax, presumably by removing hydrolysis products. PLA2 also reduced equilibrium binding of 3H-QNB to 43% of control when reactions were started by simultaneous addition of 3H-QNB and 1 U/ml PLA2; however, under these conditions the inhibitory effect of PLA2 could be overcome by increasing 3H-QNB from 30 to 600 pM. PLA2 added at equilibrium (59 mins after reaction start) had no effect on 3H-QNB binding. Lipid hydrolysis by PLA2 was unaffected by the presence of bound 3H-QNB. The ability of ligand occupation and removal of hydrolysis products to attenuate the effects of PLA2-treatment on muscarinic receptor sites may be explained if modification of the membrane lipid bilayer leads to transitions between different states of the receptor.

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Calcium has a central role in regulating both cardiac automaticity and myocardial contractility. The ability of calcium to increase tension in normal myocardium is well known. These properties of calcium have led to its use in the setting of cardiopulmonary resuscitation, especially in the presence of electromechanical dissociation or asystole, but evidence of benefit from this therapy is lacking. During cardiac arrest, disturbances in the control of calcium movement in myocardium would likely result in elevations in cytosolic calcium and the disturbances in myocardial function that occur with calcium overload. Administration of calcium and the subsequent elevation in serum calcium concentrations under these conditions may have further detrimental effects on the heart and vascular smooth muscle. The routine use of calcium in cardiac arrest is not recommended.

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