Atrial contractile dysfunction after short-term atrial fibrillation is reduced by the calcium antagonist verapamil, which suggests that transsarcolemmal calcium influx contributed to this dysfunction. The calcium agonist BAY K8644 increased postfibrillation atrial contractile dysfunction. Atrial ischemia was not observed during fibrillation.

Background-Stimulation of 5-HT 4 receptors increases atrial chronotropic and inotropic responses. Whether other electrophysiological effects are produced is unknown. In humans and swine, 5-HT 4 receptors are present only in atrium. Therefore, the effects of a novel 5-HT 4 receptor antagonist, RS-100302, and the partial agonist cisapride on atrial flutter and fibrillation induced in swine were studied to delineate the role of the 5-HT 4 receptor in modulating atrial electrophysiological properties and the antiarrhythmic potential of RS-100302. Methods and Results-In 17 anesthetized, open-chest, juvenile pigs, atrial flutter or fibrillation was induced by rapid right atrial pacing with or without a right atrial free wall crush injury, respectively. Atrial effective refractory period (ERP), conduction velocity, wavelength, and dispersion of refractoriness were determined during programmed stimulation via a 56-electrode mapping plaque sutured to the right atrial free wall. Ventricular electrophysiological parameters were also measured. All electrophysiological parameters were measured at baseline and after infusion of RS-100302 and cisapride.In the atrium, RS-100302 prolonged mean ERP (115Ϯ8 versus 146Ϯ7 ms, PϽ0.01) and wavelength (8.3Ϯ0.9 versus 9.9Ϯ0.8 cm, PϽ0.01), reduced dispersion of ERP (15Ϯ5 versus 8Ϯ1 ms, PϽ0.01), and minimally slowed conduction velocity (72Ϯ4 versus 67Ϯ5 cm/s, PϽ0.01). These effects were all partially reversed by cisapride. RS-100302 produced no ventricular electrophysiological effects. RS-100302 terminated atrial flutter in 6 of 8 animals and atrial fibrillation in 8 of 9 animals and prevented reinduction of sustained tachycardia in all animals. Conclusions-The electrophysiological profile of RS-100302 suggests that it may have atrial antiarrhythmic potential without producing ventricular proarrhythmic effects.

The degree of blood flow mismatch between ischemic and normal myocardial regions during graded coronary stenoses can be estimated in the dog by quantitative assessment of myocardial perfusion produced by IV myocardial contrast echocardiography.

Atrial fibrillation is associated with a fall in cardiac output, and cardioversion to sinus rhythm is frequently attempted. After cardioversion, atrial contractile performance might be depressed. It is, however, unclear whether or not atrial contractile performance is altered following atrial fibrillation periods lasting < 1 wk. Atrial contractile performance after short-term paroxysmal atrial fibrillation was examined in seven barbiturate-anesthetized, open-chest pigs paced at constant ventricular rate after complete atrioventricular block. Percent left atrial systolic shortening (systolic shortening of left atrial diameter in percent of atrial diameter at onset of atrial contraction, %LASS) increased from 100 to 116.2% (107.7-121.8) (median and 95% confidence interval) immediately after cessation of a fibrillation period of 1 min. A brief phase of atrial hypercontractility (%LASS significantly above control) was also demonstrated after fibrillation periods of 5 and 15 min. A subsequent phase of atrial hypocontractility (%LASS significantly below control) was recorded after atrial fibrillation periods of 5, 15, and 30 min. After the 30-min fibrillation period, atrial hypocontractility was most pronounced and reached a nadir of 86.8% (75.1-93.3).

The effects of atrial fibrillation on left and right atrial dimensions, pressures, and compliances were examined in two groups of seven barbiturate-anesthetized open-chest pigs. Atrial diameters and pressures were recorded during atrioventricular (AV) pace and thereafter during atrial fibrillation. Both rhythms were studied with constant ventricular rate after complete AV block. Left atrial maximal diameter, which appeared at the end of the atrial filling phase, decreased from 32.4 (28.9-36.7; median and 95% confidence interval) to 31.3 (28.4-35.7) mm after induction of atrial fibrillation. The right atrial maximal diameter also decreased, although not significantly. Atrial pressure at the peak of the v wave rose from 7.0 (5.5-8.5) to 9.6 (8.3-11.2) mmHg in the left atrium and from 5.0 (4.3-5.6) to 7.3 (6.2-8.7) mmHg in the right atrium. Left and right atrial chamber stiffness constants increased from 0.25 (0.19-0.48) to 0.41 (0.28-0.66) mm-1 and from 0.21 (0.11-0.31) to 0.33 (0.30-0.39) mm-1, respectively. Instantaneous diastolic atrial compliance decreased in both atria after induction of atrial fibrillation. Thus, during atrial fibrillation with regular ventricular rate, changes in atrial diameter, pressure, and compliance take place.

The mechanism for increased secretion of atrial natriuretic factor (ANF) during tachycardia and atrial fibrillation has remained unsettled. In seven open-chest pigs, the plasma concentration of ANF increased from 49.8 +/- 12.4 to 131.8 +/- 15.7 pg/ml when heart rate was increased from 133 +/- 13 to 212 +/- 4 beats/min by atrial pacing. Right atrial maximal diameter, recorded by ultrasonic technique at the maximal atrial filling, did not increase. During pacing tachycardia, the atrial contraction (a wave) occurs during atrial filling, and the a wave becomes superimposed on the v wave. In the present study the systolic atrial pressure (a wave) increased from 5.8 +/- 0.8 to 9.6 +/- 0.5 mmHg. The significance of this pressure rise was subsequently examined. After complete atrioventricular (AV) block, the AV delay was progressively increased, without altering heart rate, until the a wave was similar to the the a wave during the preceding tachycardia. Plasma ANF increased to 113.8 +/- 14.7 pg/ml, which showed that the increase in atrial pressure during atrial systole is a stimulus for ANF release. In the second part of the study, atrial fibrillation was induced in six open-chest pigs by rapid atrial pacing after complete AV block. Plasma ANF increased from 83.5 +/- 7.2 to 269.0 +/- 45.4 pg/ml during atrial fibrillation. No increase in atrial dimensions occurred during atrial fibrillation, but atrial pressure was substantially elevated. Thus, although passive atrial stretch stimulates ANF release during blood volume expansion, the present study shows that the increase in atrial pressure during atrial contraction is a stimulus for release of ANF during tachycardia and atrial fibrillation.

Background-Although defects on intracoronary myocardial contrast echocardiography (MCE) indicate loss of viability after reperfusion, opacified segments may also exhibit persistent dyssynergy. Therefore, we related the intensity and texture of opacification produced by an intravenous contrast agent to histological findings to determine the characteristics of necrotic tissue by postreperfusion MCE. Methods and Results-MCE was performed by intravenous injection of 0.15 mL/kg QW7437 in 14 dogs who underwent 3-hour coronary occlusion followed by 3-hour reperfusion. At baseline and 3 hours after reperfusion, midventricular short-axis images were digitized and segmented. Infarction fraction (IF) for each segment was determined by triphenyltetrazolium chloride stain. Of 224 segments, 140 showed no or small infarction and served as a control group. Of 84 segments with significant infarction (IFϾ30%), 52 exhibited a defect on MCE, and 32 exhibited no defect. Echo texture was quantified by computing entropy based on the co-occurrence matrix analysis of gray-level pairs within each segment. Three hours after reperfusion, average and maximal entropies in the infarct segments without opacification defects were significantly higher than control levels. Histologically, the degree of intracapillary erythrocyte stasis was less in this group than in the infarcted segments with MCE defects with similar magnitude of tissue injuries. Conclusions-Opacification defects by MCE may be present or absent in myocardium with histologically confirmed infarction. The texture of MCE from opacified but infarcted myocardium differed significantly from control segments and may assist in determination of segmental viability after reperfusion.

During atrial fibrillation synchronized atrial contraction is lost and cardiac output declines. Concomitantly, atrial pressure increases. The significance of the increase in atrial pressure on stroke volume was examined before and after blood volume expansion. Atrial fibrillation was induced by rapid atrial pacing in seven anaesthetized, open-chest pigs. The increase in right atrial pressure subsequently was counteracted by an appropriate constriction of the inferior vena cava. To avoid the confounding effect of a rapid and irregular heart rate, ventricular rate was kept constant by separate His bundle pacing after complete atrioventricular block. When atrial fibrillation was induced, right and left atrial pressure at the top of the v-wave increased both during normovolaemia and during hypervolaemia. Concomitantly, stroke volume declined. When the increase in atrial pressure was prevented during atrial fibrillation, stroke volume declined further: by 35 (21-50) and 9 (2-17)% (difference: P = 0.01), during normo- and hypervolaemia, respectively. Thus, the increase in atrial pressure counteracts the decline in stroke volume after induction of atrial fibrillation and thereby represents an important compensatory mechanism. This mechanism is more important with normal blood volume than during hypervolaemia.