Evolution of a papillary fibroelastoma.

Papillary fibroelastoma is a rare primary tumor of the heart usually found incidentally at autopsy. Little is known about the natural history of this tumor, but an aggressive surgical approach is recommended because of the high incidence of embolization. We describe a patient whose tumor was found during transthoracic echocardiography and who had had a normal echo 10 years previously. This finding suggests that papillary fibroelastoma may be an acquired rather than a congenital lesion.

Safety and accuracy of dobutamine-atropine stress echocardiography for the detection of residual stenosis of the infarct-related artery and multivessel disease during the first week after acute myocardial infarction.

BACKGROUND: The safety of dobutamine-atropine echocardiography early after acute myocardial infarction is unknown. Its accuracy for the early detection of infarct artery stenosis and multivessel coronary artery disease is also unclear. The objective of the present study was to document its safety and accuracy during the first week after acute myocardial infarction. METHODS AND RESULTS: Multistage dobutamine-atropine stress echocardiography was performed in 232 patients (age, 58 +/- 13 years; 58 women) at 5 +/- 2 days after acute myocardial infarction. The peak heart rate was 116 +/- 20 bpm. There were no episodes of sustained ventricular tachycardia, myocardial infarction, or death. Atropine with dobutamine was tolerated well. Coronary angiography was performed in 206 patients (89%). There were 171 patients (83%) with infarct artery stenosis of > or = 50% and 114 patients (55%) with multivessel disease. Ischemic or biphasic responses in the infarction zone were 82% (140 of 171) sensitive and 80% (28 of 35) specific for residual stenosis. Sensitivity was similar for occluded arteries (77%, 36 of 47) and patent but stenotic arteries (84%, 104 of 124). Wall motion abnormalities outside the infarction zone were specific (97%, 89 of 92) and moderately sensitive (68%, 77 of 114) for multivessel disease. The only determinant of sensitivity for residual infarct artery stenosis was improved wall motion at low dose (P < .01). The determinants of sensitivity for multivessel disease were peak heart rate and infarct size (P < .01). CONCLUSIONS: Dobutamine-atropine stress echocardiography was safely used to detect residual infarct artery stenosis and multivessel disease during the first week after acute myocardial infarction. The test may be very effective for evaluating patients with acute myocardial infarction because sensitivity for residual stenosis and multivessel disease was maximal in the high-risk subsets of patients with viable, jeopardized myocardium and large infarct size.

Dobutamine stress echocardiography for risk stratification after myocardial infarction.

BACKGROUND: Because dobutamine stress echocardiography (DSE) provides assessment of left ventricular function and ischemia at a distance, the major determinants of adverse outcome after acute myocardial infarction (AMI), we undertook this study to determine the role of DSE in risk stratification after AMI. METHODS AND RESULTS: A graded DSE in 5-minute stages was performed in 214 patients (age, 57 +/- 13 years [mean +/- SD]) at 2 to 7 days after AMI. Coronary angiography was performed in 193 patients. Follow-up data regarding major cardiac events were obtained through telephone interviews and chart reviews. All patients were followed for > or = 500 days or until a hard cardiac event occurred. The mean follow-up interval was 494 +/- 182 days after AMI. Peak heart rate and systolic blood pressure were 115 +/- 21 bpm and 135 +/- 29 mm Hg, respectively. An adverse outcome occurred in 80 of 214 patients; cardiac death occurred in 15, nonfatal AMI occurred in 15, sustained or symptomatic ventricular arrhythmia occurred in 5, congestive heart failure occurred in 14, and unstable angina occurred in 31. Significant predictors of adverse outcome by univariate analysis were prior myocardial infarction (P = .005), anterior infarction (P = .006), multivessel coronary artery disease (P < .0001), global resting left ventricular wall motion score index (P < .0001), infarction zone nonviability based on akinesis unresponsive to low-dose dobutamine (P < .0001), and ischemia/infarction at a distance (P < .0001). Furthermore, the extent of infarct zone and nonviability correlated with the severity of the cardiac event. Multivariate analysis of clinical, angiographic, and DSE variables revealed that the only independent predictors of adverse outcome were ischemia/infarction at a distance (P < .0001) and infarction zone nonviability (P < .0001). Multivessel disease identified through DSE was more predictive of adverse outcome than was angiographically determined multivessel disease. CONCLUSIONS: DSE can be used to predict adverse outcomes after AMI.

Differential hemodynamic effects of the nitric oxide donor pirsidomine in comparison to SIN-1, nitroprusside and nitroglycerin.

The systemic and coronary hemodynamic effects of the nitrovasodilator, pirsidomine, were compared with SIN-1, nitroprusside, and nitroglycerin. Four groups consisting of 32 experiments were performed in 17 conscious dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dtmax, diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experimental days, systemic and coronary hemodynamics were recorded during control conditions and after intravenous administration of pirsidomine (1.0, 2.0, and 4.0 mg.kg-1), SIN-1, (50, 100, and 200 micrograms.kg-1), nitroprusside (0.5, 1.0, and 2.0 micrograms.kg-1.min-1), or nitroglycerin (1.0, 2.0, and 4.0 micrograms.kg-1.min-1). Pirsidomine decreased mean arterial, left ventricular systolic and end-diastolic pressures, stroke volume and systemic vascular resistance. Diastolic coronary blood flow velocity and heart rate were increased and coronary vascular resistance decreased by pirsidomine. SIN-1, nitroprusside and nitroglycerin caused similar decreases in preload (evaluated by left ventricular end-diastolic pressure) and afterload (indirectly assessed by mean arterial pressure and systemic vascular resistance) as compared to pirsidomine. However, equihypotensive doses of SIN-1, nitroprusside, and nitroglycerin improved ventricular performance as assessed by increases in left ventricular dP/dtmax, cardiac output and segment shortening, in contrast to those findings during comparable doses of pirsidomine (4 mg.kg-1). Despite similar loading conditions, high doses of pirsidomine did not enhance left ventricular function, suggesting that pirsidomine may have direct negative inotropic effects.

Zatebradine, a specific bradycardic agent, enhances the positive inotropic actions of dobutamine in ischemic myocardium.

OBJECTIVES: This investigation determined whether attenuation of the tachycardia produced by dobutamine administration would improve perfusion and function distal to a severe coronary artery stenosis. BACKGROUND: Tachycardia adversely affects perfusion and function distal to a coronary artery stenosis. It is not known whether a specific bradycardic agent can improve blood flow and function in an ischemic zone during administration of dobutamine. METHODS: The effects of dobutamine (2, 5 and 10 micrograms/kg body weight per min) alone and in combination with zatebradine (0.5 mg/kg), a specific bradycardic agent, on hemodynamic status, segment shortening (ultrasound length transducers) and myocardial perfusion (microspheres) were studied in anesthetized dogs with severe left circumflex coronary artery stenosis. RESULTS: A 50% reduction in left circumflex coronary artery blood flow (58 +/- 4 to 29 +/- 2 ml/min [mean value +/- SEM]) produced a decrease in systolic shortening in the ischemic zone. Only a dose of dobutamine that did not elevate heart rate (2 micrograms/kg per min) produced an increase in segment shortening in the ischemic zone. High doses of dobutamine (10 micrograms/kg per min) caused an increase in heart rate without improvement in function and a reduction in the subendocardial/subepicardial flow ratio (0.74 +/- 0.06 to 0.48 +/- 0.05). Zatebradine administered in the presence of dobutamine caused a decrease in heart rate, an increase in subendocardial/subepicardial blood flow ratio (0.48 +/- 0.05 to 0.78 +/- 0.09) and allowed an increase in ischemic zone segment shortening. When normalized for changes in heart rate, ischemic zone subendocardial flow increased by 123 +/- 41% (0.39 +/- 0.09 to 0.71 +/- 0.12 ml/100 g per beat). Atrial pacing abolished the effects of zatebradine. CONCLUSIONS: The present data suggest that the perfusion-contraction matching that accompanies a decrease in heart rate results in enhancement of inotropic stimulation of an ischemic zone. The actions of zatebradine are related to an increase in subendocardial blood flow per beat that allows improvement of regional contractile function.

Right aortic arch: demonstration by first-pass and multigated radionuclide ventriculography.

Right aortic arch is a rare congenital anomaly associated with abnormal development of the paired embryological aortic arches. While various abnormalities of the great vessels have been described using both first-pass and multigated radionuclide ventriculographic studies, diagnosis of a right-sided aortic arch has typically required a radiographic contrast technique. We present a case of a patient with a suspected right-sided aortic arch diagnosed by radionuclide methods.

Regional myocardial function after repetitive brief episodes of ischemia: effect of altering the duration of the reperfusion period.

How recovery of regional contractile function in myocardium is influenced by alterations in the duration of reperfusion after repetitive brief coronary artery occlusions was investigated in chronically instrumented, conscious dogs. All animals underwent five 5 minute left anterior descending coronary artery occlusions with a final 5-hour reperfusion period. Dogs were randomly assigned to one of three groups determined by the duration of reperfusion (5, 10, or 15 minutes) between successive 5-minute occlusion periods. A shortening of the duration of the reperfusion period between occlusions led to reduced recovery and progressive deterioration in systolic shortening after multiple occlusion-reperfusion sequences. With 15-minute reperfusion periods, the percentage of segment shortening (%SS) during the first through fourth reperfusion periods ranged from 17.1 +/- 2.6% to 18.2 +/- 1.8% and did not differ from the preocclusion control value (18.8 +/- 1.7%) by the end of the final reperfusion period. In contrast, in those dogs with 5-minute reperfusion periods, %SS was significantly reduced from the preocclusion control value (20.2 +/- 2.2%) at the completion of the final 5-hour reperfusion period (11.4 +/- 1.5%). Results of the present study indicate that after only a few brief periods of coronary artery occlusion, rapid and cumulative deterioration in regional contractile function can occur when the duration of intermittent reperfusion is sufficiently brief.

Dipyridamole-induced decrement of functional recovery of postischemic reperfused myocardium in conscious dogs with well-developed coronary collateral circulation.

The effects of dipyridamole (20 and 40 micrograms/kg/min intravenously) on the time course of functional recovery of myocardium after five 5-minute coronary artery occlusions and four 5-minute reperfusions and a subsequent 5-hour reperfusion period were studied in chronically instrumented, conscious dogs with well-developed coronary collateral circulation. In comparison with vehicle-treated control dogs, those given dipyridamole (20 and 40 micrograms/kg/min, respectively) 15 minutes before and during coronary occlusion had a greater depression of regional segment shortening (38 +/- 7% and 19 +/- 4%, respectively, vs control levels of 69 +/- 10% of preocclusion values) during acute coronary artery occlusion. After a 5-hour reperfusion period, segment shortening returned to preocclusion values in the control group but remained decreased in the dipyridamole groups (87 +/- 4% and 75%, respectively). These results suggest that dipyridamole in a dose-dependent manner exacerbates recovery of contractility of postischemic reperfused myocardium in dogs with well-developed coronary collateral circulation.

Steroid-induced enhancement of functional recovery of postischemic, reperfused myocardium in conscious dogs.

The effects of methylprednisolone sodium succinate (20 mg/kg, intravenously administered) on the time course of functional recovery of myocardium following a 15-minute coronary artery occlusion period and subsequent 5 hour reperfusion period were studied in chronically instrumented, conscious dogs. In comparison to a control group, animals receiving methylprednisolone 90 minutes prior to coronary occlusion demonstrated less depression of regional segment shortening following 15 minutes of reperfusion (52 +/- 13% vs control levels of 23 +/- 7% of preocclusion values) and improved recovery at 5 hours postreperfusion (106 +/- 6% vs control levels of 54 +/- 4% of preocclusion values). In animals receiving methylprednisolone immediately prior to reperfusion, there was also similar recovery of segment shortening at 5 hours (97 +/- 3%). In contrast, dogs receiving methylprednisolone 15 minutes after the onset of reperfusion or sodium succinate (5.5 mg/kg, intravenously administered) 90 minutes prior to occlusion demonstrated no improvement in recovery of function. Experiments in dogs not subjected to coronary occlusion documented that methylprednisolone sodium succinate lacked inotropic and vasodilator properties. The results suggest that methylprednisolone administered prior to or during coronary artery occlusion but not after reperfusion enhances the functional recovery of hypokinetic, postischemic, reperfused myocardium. These effects are unrelated to any direct hemodynamic action of steroids or to the sodium succinate salt.

Comparative effects of inotropic agents on coronary and systemic hemodynamics of conscious dogs: actions of milrinone, dopamine, ouabain and MCI-154.

The hemodynamic actions of a new inotropic agent, MCI-154, were compared to dopamine, ouabain and milrinone in conscious, chronically instrumented dogs. MCI-154 and milrinone produced similar hemodynamic changes: increases in heart rate, diastolic coronary blood flow velocity and peak positive dP/dt. Neither agent had significant effects on arterial pressure while both drugs reduced left ventricular end-diastolic pressure in a dose-related fashion and myocardial segment length, indicating a decrease in diastolic left-ventricular size. MCI-154 was found to be approximately twice as potent as milrinone. In contrast, dopamine and ouabain produced little change in left ventricular end-diastolic pressure or myocardial segment length during diastole, while both drugs produced increases in arterial and left ventricular systolic pressures. An increase in left ventricular afterload was not observed with either MCI-154 or milrinone, highlighting an important advantage of the latter compounds.

Changes in adrenergic pressor responses by calcium channel modulation in conscious dogs.

The influence of the slow channel calcium entry blocker, nifedipine, and the slow channel calcium entry promoter, BAY-K 8644, on receptor-mediated hemodynamic responses was studied in chronically instrumented, conscious dogs. Following ganglionic, cholinergic, and beta-adrenergic blockade, equipressor doses of phenylephrine (0.6 microgram/kg iv), a selective alpha 1-adrenoceptor agonist, and B-HT 933 (20 micrograms/kg iv), a selective alpha 2-adrenoceptor agonist, as well as a nonadrenergic vasoconstrictor, vasopressin (0.003 IU/kg) were administered before and after infusions of nifedipine or BAY-K 8644 (0.25, 0.5, 1.0, and 2.0 micrograms X kg-1 X min-1). In doses producing minimal or no haemodynamic effects, nifedipine caused dose-related attenuation from control of phenylephrine- (from 26 +/- 3 to 8 +/- 1 mmHg), B-HT 933- (from 30 +/- 2 to 5 +/- 2 mmHg), and vasopressin- (24 +/- 1 to 2 +/- 2 mmHg) mediated changes in mean arterial pressure. In contrast, BAY-K 8644 produced dose-related potentiation from control of the same pressor responses (phenylephrine, 24 +/- 2 to 41 +/- 3 mmHg; B-HT 933, 28 +/- 3 to 46 +/- 2 mmHg; vasopressin, 25 +/- 3 to 45 +/- 5 mmHg). In addition, BAY-K 8644 produced a marked increase in the duration of the pressor response produced by all three agonists. Thus, in conscious dogs, alpha 1-, alpha 2-, and vasopressin-mediated pressor responses are strongly modulated by transmembrane calcium flux and can be influenced by dihydropyridine slow channel calcium agonists and antagonists.

Cardiovascular actions of a new dihydropyridine calcium antagonist, 8363-S: comparison with nifedipine and nicardipine in awake, unsedated dogs.

The systemic and coronary hemodynamic actions of a new dihydropyridine, 8363-S, were compared with nifedipine and nicardipine in conscious, instrumented dogs following intravenous and oral administration. All agents produced similar reductions in arterial and ventricular pressures and increases in heart rate, dP/dt, and coronary blood flow velocity, following intravenous infusion. Following oral administration, all agents had qualitatively similar actions; however, there was a marked difference in potency. 8363-S was found to be most potent in that 0.25 mg/kg produced equivalent or larger changes from control than 0.5 mg/kg nifedipine or 1.0 mg/kg nicardipine. Furthermore, 8363-S had a longer duration of action following oral administration. The results suggest that important differences in bioavailability exist amongst dihydropyridines which may have important therapeutic implications.

Differential effects of nifedipine, nicorandil and nitroglycerin on the pressor responses elicited by selective alpha-1 and alpha-adrenoceptor agonists in conscious dogs.

The influence of vasodilators with varying mechanisms of action on pressor responses mediated by alpha-1 and alpha-2 adrenoceptors was investigated in chronically instrumented, conscious dogs. After ganglionic, cholinergic and beta adrenergic blockade, equipressor doses of phenylephrine (0.6 microgram/kg i.v.), a selective alpha-1 adrenoceptor agonist, and B-HT 933 (20 micrograms/kg i.v.) a selective alpha-2 adrenoceptor agonist, were administered before and in the presence of infusions of nifedipine (0.25-2.0 micrograms/kg/min), nicorandil (4.0-32.0 micrograms/kg/min) or nitroglycerin (1.0-8.0 micrograms/kg/min). Nifedipine produced a dose-related attenuation of the increase in mean arterial pressure after bolus administration of phenylephrine (from 26 +/- 1 to 7 +/- 1 mm Hg) and B-HT 933 (from 29 +/- 2 to 5 +/- 1 mm Hg). Nicorandil did not affect phenylephrine-mediated pressor responses but significantly attenuated those to B-HT 933 (28 +/- 2 to 10 +/- 1 mm Hg). In contrast, nitroglycerin had no effect on either phenylephrine or B-HT 933-mediated responses. In additional experiments after autonomic nervous system blockade, multiple doses of phenylephrine (0.6, 1.25 and 2.5 micrograms/kg i.v.) and B-HT 933 (10, 20 and 40 micrograms/kg i.v.) were administered before and after i.v. infusions of nifedipine (1.0 microgram/kg/min) or nicorandil (16.0 micrograms/kg/min). Nifedipine significantly decreased the pressor responses to all doses of phenylephrine and B-HT 933. In contrast, the attenuation from control of alpha-2-mediated increases in arterial pressure by nicorandil was partially overcome at higher doses (40 micrograms/kg) of B-HT 933.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulation of myocardium during reperfusion injury by a new inotrope-vasodilator agent, MCI-154.

The systemic and coronary hemodynamic actions of a newly synthesized inotropic agent structurally related to milrinone and amrinone, MCI-154 (0.5-4.0 micrograms/kg/min IV), were studied in 2 groups of conscious, chronically instrumented dogs with normal or depressed postischemic, reperfused myocardium after a 15-min coronary artery occlusion. In an additional group of control experiments, the time course of recovery of postischemic, reperfused myocardium was studied to verify the constancy of regional segment shortening in the previously ischemic zone during the time corresponding to drug infusion. Similar inotropic actions of MCI-154 were observed in both normal and postischemic, reperfused hearts, indicating significant contractile reserve to be present in 'stunned' myocardium. Global contractility as measured by peak positive dP/dt was significantly increased in both groups. In postischemic, reperfused myocardium 90 min after initiation of reflow, regional segment function remained depressed at 44% of control but improved to 93% of control after administration of MCI-154. In addition, MCI-154 produced significant dose-related decreases in mean arterial pressure, left ventricular end-diastolic pressure, end-diastolic segment length, and diastolic coronary vascular resistance. The data demonstrate that in addition to producing beneficial hemodynamic changes, MCI-154, a new non-sympathomimetic inotropic agent, markedly enhances regional contractility of postischemic, reperfused myocardium.