Demonstration of exercise-induced painless myocardial ischemia in survivors of out-of-hospital ventricular fibrillation

To ascertain if myocardial ischemia is the mechanism of out-of-hospital ventricular fibrillation (VF), left ventricular (LV) function was assessed at rest and during submaximal exercise in 15 patients who survived out-of-hospital VF. They were separated into asymptomatic (9 patients, group A) and symptomatic (6 patients, group S) groups for a history of angina or myocardial infarction. Both groups had significant (at least 70% diameter stenosis) coronary artery disease. At catheterization no patient had angina during exercise, but 12 of 15 had ST depression or increased ST depression (group A, 1.9 +/- 1.4 mm; group S, 1.1 +/- 1.2 mm) and 11 had abnormal wall motion. From rest to exercise, patients in group S had increased LV end-diastolic pressure (from 21 +/- 9 to 37 +/- 11 mm Hg, p = 0.009) and volume (from 100 +/- 25 to 107 +/- 26 ml/m2, p = 0.006), with no significant change in LV ejection fraction (from 40 +/- 13 to 42 +/- 12%). In group A LV end-diastolic pressure increased from 19 +/- 4 to 31 +/- 8 mm Hg (p = 0.001), but neither end-diastolic volume nor ejection fraction changed significantly (from 83 +/- 13 to 92 +/- 23 ml/m2 and from 55 +/- 13% to 46 +/- 13%, respectively). Thus, patients with coronary artery disease who survive out-of-hospital VF may have evidence of myocardial ischemia during exercise without pain. Painless ischemia may have a role in out-of-hospital VF.     

Persistent ST segment depression in precordial leads V5-V6 after Q-wave anterior wall myocardial infarction is associated with restrictive physiology of the left ventricle

OBJECTIVES: To examine the relationship between the persistence of ST segment depression in leads V5-V6 after Q-wave anterior wall myocardial infarction (MI) and the filling pattern of the left ventricle (LV). BACKGROUND: Precordial ST segment depression predominantly in leads V5-V6 is associated with increased in-hospital morbidity and mortality after acute myocardial ischemia, perhaps due to reduced diastolic distensibility of the LV. METHODS: We prospectively studied 19 patients after Q-wave anterior wall MI (>6 months). All patients underwent 12-lead ECG recording, symptom-limited treadmill exercise testing with single photon emission computed tomography thallium-201 imaging, transthoracic Doppler echocardiography, cardiac catheterization and measurement of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels. Patients were classified based on the presence of ST segment depression in leads V5-V6: Group I = ST segment depression <0.1 mV (n = 10); Group II = ST segment depression > or =0.1 mV (n = 9). RESULTS: Patients in Group II had greater LV end diastolic pressures (32.4 +/- 6.5 mm Hg vs. 14.8 +/- 6.1 mm Hg; p = 0.0001), higher plasma ANP (44.4 +/- 47.1 pg/ml vs. 10.7 +/- 14 pg/ml; p = 0.04) and BNP levels (89.4 +/- 62.7 pg/ml vs. 23.6 +/- 33.1 pg/ml; p = 0.01), greater left atrium area (20.6 +/- 3.1 cm2 vs. 17.8 +/- 2.4 cm2; p = 0.05), lower peak atrial (A), higher early (E) mitral inflow velocities, a higher E/A ratio and a lower deceleration time (167 +/- 44 ms vs. 220 +/- 40 ms; p = 0.05). Lung thallium uptake during exercise was more common in Group II (78% vs. 10%, p = 0.04). CONCLUSIONS: Persistent ST segment depression in leads V5-V6 in survivors of Q-wave anterior wall MI is associated with increased LV filling pressure and a restrictive LV filling pattern.     

Evaluation of left ventricular contractility indexes for the detection of symptomatic and silent myocardial ischemia

This study evaluated the role of left ventricular (LV) ejection fraction and systolic blood pressure (BP) to end-systolic volume ratio to detect symptomatic and silent myocardial ischemia. The sensitivity and diagnostic accuracy of these contractility indexes were compared with angina and ST depression during exercise. Thirty consecutive patients referred for chest pain performed symptom-limited bicycle exercise and had coronary angiography within 3 months. Twenty-two had angiographically significant coronary artery disease and 8 had normal coronary anatomy. Systolic BP was measured by sphygmomanometry; LV ejection fraction and end-systolic volume were obtained by nuclear ventriculography. Normal values for contractility indexes were defined as LV ejection fraction greater than 52% at rest and increment of greater than or equal to 5% during exercise, and systolic BP to end-systolic volume ratio greater than 2.2 mm Hg/ml at rest and greater than 3.0 mm Hg/ml during exercise. The sensitivity of systolic BP to end-systolic volume ratio to identify patients with coronary artery disease at rest was 71 vs 33% for LV ejection fraction. During exercise, each contractility index had a sensitivity of 95% and there was a combined sensitivity of 100%. This compares with 71% for ST depression and 48% for exercise-induced angina. Thus, 52% had no angina and 36% of them were also silent by electrocardiography. Among the patients with symptomatic ischemia, 20% had no ST-segment depression. Measurement of contractility indexes enhanced the detection of silent myocardial ischemia and provided information on LV function vital to prognosis and management of patients with coronary artery disease.     

Effects of acute K-strophantidin administration on left ventricular relaxation and filling phase in coronary artery disease.

In 10 patients with coronary artery disease, preserved left ventricular (LV) performance and absence of previous myocardial infarction, the effects of an acute intravenous administration of k-strophantidin (0.005 mg/kg over 10 minutes) on selected parameters of both LV systolic and diastolic function, including relaxation, were evaluated. An increase in positive first derivative of LV pressure (dP/dt) and in the ratio between dP/dt and the pressure developed (dP/dt/P) (1,530 +/- 287) 1,600 +/- 329 mm Hg/s [p less than 0.05], and 30 +/- 6 to 34 +/- 8 s-1 [p less than 0.05], respectively) demonstrated the inotropic effect of k-strophantidin, whereas volumetric parameters of systolic function (end-systolic and stroke volume indexes, and ejection fraction) did not show any significant change. However, LV relaxation was impaired by k-strophantidin injection; in fact, mean values of T constant were significantly increased from 50 +/- 12 to 55 +/- 13 ms (p less than 0.01). Lowest LV and end-diastolic pressures increased from 8 +/- 4 to 11 +/- 4 mm Hg (p less than 0.05) and from 17 +/- 6 to 20 +/- 8 mm Hg (p less than 0.05), respectively. The end-diastolic volume and maximal rate of volumetric increase during the early and late filling phases were not modified by k-strophantidin. Mean aortic pressure increased from 110 +/- 10 to 120 +/- 12 mm Hg (p less than 0.001). Therefore, in patients with coronary artery disease and LV preserved performance, an acute intravenous administration of k-strophantidin appears to stimulate contractility and to worsen relaxation, and minimal LV and end-diastolic pressures.     

Effects of sublingual nitrate in patients receiving sustained therapy of isosorbide dinitrate for coronary artery disease

To examine the effects of sublingual isosorbide dinitrate (ISDN) in patients receiving sustained ISDN therapy, 24 patients with coronary artery disease were divided into 2 groups. Group C comprised 12 patients without sustained ISDN therapy and group N included 12 patients with sustained ISDN therapy. Before and during administration of sublingual ISDN in both groups, aortic systolic pressure, left ventricular end-diastolic pressure and coronary artery diameter were examined at cardiac catheterization. During sublingual ISDN, the aortic systolic pressure decreased by 20 +/- 6% (138 +/- 26 to 112 +/- 27 mm Hg, p less than 0.01) in group C and 10 +/- 6% (127 +/- 26 to 113 +/- 23 mm Hg, p less than 0.01) in group N (p less than 0.01, group C vs group N). The left ventricular end-diastolic pressure decreased by 65 +/- 16% (11 +/- 5 to 4 +/- 3 mm Hg, p less than 0.01) in group C and 43 +/- 14% (12 +/- 5 to 7 +/- 3 mm Hg, p less than 0.01) in group N (p less than 0.01, group C vs group N). During sublingual ISDN, the diameters of the proximal and distal segments of the left anterior descending and circumflex coronary arteries increased more significantly in group C than in group N (p less than 0.01, group C vs group N). Thus, sublingual ISDN produced less reduction of aortic systolic pressure and left ventricular end-diastolic pressure, and less dilation of coronary artery diameter in patients receiving sustained therapy with ISDN than in those without sustained therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variability of results during repeat exercise stress testing in patients with stable angina pectoris: role of dynamic coronary flow reserve

In some patients with stable angina, the variability of results during repeated exercise tests is higher than in others with similar symptoms. The aim of the study was to assess whether this difference can be explained by a different susceptibility of the coronary arteries to vasoconstrictor stimuli. Ten patients (group A) with stable angina, who developed myocardial ischemia (angina and ST segment depression greater than 0.1 mV) following ergonovine-induced coronary constriction, and 10 other patients (group B) with stable angina, but a negative ergonovine test result, were subjected to two treadmill exercise tests. The variability of heart rate and heart rate-blood pressure product at 0.1 mV ST segment depression was significantly higher in group A than in group B (12 +/- 4 vs 4 +/- 4 bpm, respectively, p less than 0.001 and 3366 +/- 1900 vs 930 +/- 960 bpm X mm Hg, respectively, p less than 0.005), such as the variability of heart rate-blood pressure product at the onset of angina (3887 +/- 2400 vs 1428 +/- 1800 bpm X mm Hg, respectively, p less than 0.04). The remaining exercise parameters were always more variable in group A than in group B, but these differences did not achieve statistical significance. Thus patients with stable angina who develop myocardial ischemia in response to ergonovine have a larger variability of results during repeat exercise testing. Such findings could be explained by an enhanced susceptibility to the coronary constrictor effects of exercise resulting in dynamic changes in coronary flow reserve.     

Left ventricular diastolic function in patients with left ventricular systolic dysfunction due to coronary artery disease and effect of nicardipine

To assess the effect of nicardipine on left ventricular (LV) diastolic function independent of concurrent effects on loading conditions in patients with LV systolic dysfunction due to coronary artery disease, equihypotensive doses of intravenous nitroprusside and nicardipine were administered to 12 patients with congestive heart failure due to previous myocardial infarction (LV ejection fraction less than 0.40). LV micromanometer pressure and simultaneous radionuclide volume were obtained during a baseline period, during nitroprusside infusion, during a second baseline period and during nicardipine infusion. Mean systemic arterial pressure decreased an average of 21 mm Hg with nitroprusside and 19 mm Hg with nicardipine. A greater decrease in LV end-diastolic pressure was observed with nitroprusside (29 +/- 2 to 15 +/- 2 mm Hg, p less than 0.01) than with nicardipine (29 +/- 2 to 25 +/- 3 mm Hg, p less than 0.05). There was a decrease in the time constant of relaxation during nitroprusside but not during nicardipine infusion. There was enough overlap in LV volumes in the baseline and nitroprusside periods to compare diastolic pressure-volume relations over a common range of volumes in 4 patients, and enough overlap in the baseline and nicardipine periods in 11 patients. The relation was shifted downward in 3 of 4 patients taking nitroprusside and in 6 of 11 patients taking nicardipine. The relation between end-diastolic pressure and volume was not shifted with nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular inotropic effect of atrial pacing after coronary artery bypass grafting

The effect of atrial pacing on left ventricular (LV) performance was studied in 19 patients, 24 hours after coronary artery bypass grafting (CABG). LV volumes were calculated from simultaneous radionuclide-thermodilution measurements at rest (heart rate 82 +/- 12 beats/min), 10 minutes after the start of atrial pacing (100 beats/min), and with atrial pacing plus volume loading to return preload toward baseline. Atrial pacing reduced preload as reflected by LV end-diastolic volume index (69 +/- 14 vs 60 +/- 14 ml/m2, mean +/- standard deviation) (p less than 0.0001), but returned to baseline with volume loading. Afterload, as reflected by arterial end-systolic pressure, did not change with atrial pacing (63 +/- 9 at baseline vs 64 +/- 8 mm Hg with pacing, difference not significant). Afterload increased with volume loading (68 +/- 10 mm Hg, p less than 0.025 vs baseline and pacing). LV stroke volume decreased with atrial pacing due to reduced preload, but returned to baseline with volume loading. Cardiac index increased with atrial pacing and increased further with volume loading. Compared with baseline, LV end-systolic volume index was reduced during atrial pacing both before and after volume loading, despite unchanged or augmented afterload. The combination of atrial pacing and volume loading resulted in augmentation of LV stroke work, despite no increase in preload compared with baseline. Thus, after CABG, increased (paced) heart rate augments inotropic state, as indicated by reduced LV end-systolic volume under conditions of unchanged or increased afterload, and elevated LV stroke work without an increase in preload or a decrease in afterload.     

Clinical and hemodynamic significance of left ventricular diastolic volume changes by exercise radionuclide ventriculography in coronary artery disease

Recent studies have suggested that left ventricular (LV) dilatation during exercise radionuclide ventriculography may identify coronary artery disease (CAD). Coronary anatomy and LV end-diastolic pressure at catheterization were compared with results of supine exercise radionuclide ventriculography in 66 patients evaluated for chest pain. Forty-six patients had significant CAD (greater than 75% diameter stenosis) and 20 patients were normal. Radionuclide ventriculography was performed within 18 hours of catheterization, at rest and at peak exercise. Relative LV end-diastolic volumes were extrapolated from end-diastolic counts. LV end-diastolic counts increased during exercise in 19 of 20 normal subjects. In patients with CAD, LV end-diastolic counts increased in 35 (group A) and decreased in 11 (group B). The percent change in LV end-diastolic counts from rest to exercise, rest ejection fraction, exercise ejection fraction and rest LV end-diastolic pressure for each group were 20 +/- 23%, 60 +/- 13%, 67 +/- 13% and 8 +/- 3 mm Hg in normal subjects; 20 +/- 20%, 50 +/- 12%, 47 +/- 13% and 12 +/- 4 mm Hg in group A; and -9 +/- 8%, 54 +/- 21%, 49 +/- 18% and 21 +/- 7 mm Hg in group B (mean +/- standard deviation). An increase in LV end-diastolic counts was unrelated to ejection fraction response or presence of underlying CAD but only correlated to rest LV end-diastolic pressure (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intracoronary contrast medium on left ventricular diastolic pressure-volume relationships

The purpose of this study was to investigate the effect of intracoronary injection of the contrast medium sodium-meglumine diatrizoate (CM) on left ventricular (LV) diastolic pressure-volume relationships. Seven closed-chest dogs were instrumented with pressure catheters in the left ventricle and aorta, a balloon transducer to measure pericardial pressure, and an aortic flow meter to determine stroke volume. We estimated LV volume from two diameters by sonomicrometry. Six milliliters of CM was injected into the left main coronary artery. Transmural LV end-diastolic pressure increased from 3.3 +/- 1.1 to 7.2 +/- 0.9 mm Hg and LV end-diastolic volume index from 40.8 +/- 6.8 to 44.7 +/- 7.4 ml. There was only a minor increase in pericardial pressure. Stroke volume decreased by 31 +/- 7%. There was no change in the intracavitary or transmural diastolic pressure-volume relationship, indicating unchanged LV "compliance." Increased LV filling pressure by CM reflected reduced systolic function.     

Effect of intravenous metoprolol on left ventricular performance in Q-wave acute myocardial infarction

To determine the effects of intravenous metoprolol on left ventricular (LV) function in acute myocardial infarction (AMI), 16 patients were studied within 48 hours of Q-wave AMI (mean ejection fraction 47 +/- 6%, mean pulmonary artery wedge pressure 22 +/- 6 mm Hg) with high fidelity pressure and biplane cineventriculography before and after intravenous metoprolol (dose 12 +/- 4 mg). Heart rate decreased from 90 +/- 13 to 74 +/- 11 beats/min (p less than 0.001), pulmonary arterial wedge pressure and LV end-diastolic pressure were unchanged (22 +/- 6 to 21 +/- 6 and 27 +/- 8 to 26 +/- 8 mm Hg, respectively), despite impaired LV relaxation (P = Poe-t/T) after intravenous metoprolol (T from 59 +/- 13 to 72 +/- 12 ms, p less than 0.001). Peak systolic circumferential LV wall stress decreased after beta-adrenergic blockade (330 +/- 93 to 268 +/- 89 g/cm2, p less than 0.05) and LV contractility decreased (dP/dtmax from 1,480 +/- 450 to 1,061 +/- 340 mm Hg/s, p less than 0.001). The ejection fraction decreased (48 +/- 7 to 43 +/- 7%, p less than 0.05) due to an increase in LV end-systolic volume (85 +/- 19 to 93 +/- 19 ml, p less than 0.05) since LV end-diastolic volume was unchanged (161 +/- 30 to 163 +/- 30 ml, difference not significant). In patients with Q-wave AMI, intravenous metoprolol reduces the major determinants of myocardial oxygen demand including heart rate, contractility and peak systolic wall stress. Further, despite decreased heart rate, (+)dP/dtmax, ejection fraction, isovolumic relaxation, LV end-diastolic pressure and end-diastolic volume remain unchanged.     

Influence of calcium administration on the short-term hemodynamic and anti-ischemic effects of nifedipine

This prospective study investigated whether pretreatment with intravenously administered calcium would influence the effect of nifedipine on rest hemodynamics and treadmill performance in patients with ischemic heart disease. Seventeen patients were studied after undergoing a qualifying treadmill exercise test that revealed ST segment depression indicative of ischemic heart disease. Study subjects performed three additional treadmill tests as part of the protocol. One treadmill test was obtained from each patient to provide baseline measurements without a preceding intravenous infusion and in the absence of all antianginal drugs including nifedipine; two additional exercise tests were preceded by an infusion and 10 mg of bite-and-swallow nifedipine. The infusions, administered in a randomized, double-blind, crossover fashion, consisted of either 10 ml of 10% calcium chloride (13.6 mEq) in 50 ml of 5% dextrose in water or 5% dextrose in water alone. Rest systolic blood pressure (134 +/- 4.6 mm Hg) was unchanged after placebo infusion (135 +/- 4.6 mm Hg) but decreased to 124 +/- 4.1 mm Hg (p less than 0.01) 25 min after nifedipine administration. Rest systolic blood pressure increased after calcium infusion (from 139 +/- 4.3 to 148 +/- 4.8 mm Hg, p less than 0.01) and then decreased significantly 25 min after nifedipine administration to 135 +/- 4.2 mm Hg (p less than 0.01). Despite a decrease at the time of peak nifedipine effect after either infusion, systolic blood pressure was significantly lower after administration of nifedipine alone than after administration of calcium and nifedipine (124 +/- 4.1 vs. 135 +/- 4.2 mm Hg, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Load dependence of left ventricular diastolic pressure-volume relations during short-term coronary artery occlusion.

We evaluated the effect of altered loading conditions on left ventricular (LV) diastolic pressure-volume relations during acute coronary artery occlusion that was produced by inflation of an intracoronary balloon. Open-chest anesthetized dogs (n = 18) were instrumented so that LV pressure (micromanometer) and LV volume (conductance) could be measured without disturbing the pericardium. The effects of brief periods of occlusion (1-2 minutes) were assessed under steady-state conditions before and after dextran infusion with the pericardium present and absent and during vena caval occlusion. Under steady-state conditions before dextran infusion with the pericardium removed, at an LV end-diastolic pressure (EDP) of 8.4 +/- 1.4 mm Hg, occlusion resulted in a rightward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 2.7 +/- 2.3 mm Hg; delta LVEDV, 6.3 +/- 4.7 ml, both p less than 0.05 versus control). After dextran infusion (LVEDP, 20.9 +/- 6.0 mm Hg), occlusion resulted in a rightward and upward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 5.8 +/- 4.4 mm Hg; delta LVEDV, 4.2 +/- 3.0 ml, both p less than 0.05 versus control). At low cardiac volumes before dextran infusion, the intact pericardium did not affect the response to occlusion. By contrast, after dextran infusion in the presence of an intact pericardium, LVEDP significantly increased (delta, 6.4 +/- 3.6 mm Hg, p less than 0.05) but LVDEV did not (delta, 0.7 +/- 1.5 ml, p = NS). There was a parallel upward shift in the diastolic portion of the LV pressure-volume loop that was eliminated by removal of the pericardium. Thus, the change in LV diastolic pressure and volume during occlusion varied and depended on the baseline cardiac volume and presence of the pericardium. Before dextran infusion with the pericardium present and absent, coronary artery occlusion did not alter the LV diastolic chamber stiffness parameter, which was calculated from the diastolic interval of an averaged steady-state beat (0.040 +/- 0.019 versus 0.036 +/- 0.015 mm Hg/ml, p = NS). After dextran infusion with the pericardium present and absent, coronary artery occlusion increased the LV diastolic chamber stiffness parameter (0.057 +/- 0.034 and 0.074 +/- 0.034 mm Hg/ml, both p less than 0.05 versus controls, respectively). Vena caval occlusion eliminated the shifts in the diastolic portion of the LV pressure-volume loop with the pericardium present and absent.(ABSTRACT TRUNCATED AT 400 WORDS)     

Preventive administration of intravenous N-acetylcysteine and development of tolerance to isosorbide dinitrate in patients with angina pectoris.

BACKGROUND. Development of tolerance to organic nitrates may be related to depletion of sulfhydryl groups in vascular smooth muscle. N-Acetylcysteine (NAC), a sulfhydryl donor, has been reported to potentiate the effect of nitroglycerin and reverse tolerance in humans. However, its ability to prevent or delay the development of nitrate tolerance in patients with angina pectoris has not been established. METHODS AND RESULTS. Ten patients with stable angina pectoris were treated with intravenous isosorbide dinitrate (ISDN; 5 mg/hr) combined with NAC (2 g i.v. over 15 minutes followed by 5 mg/kg/hr) or matching placebo for 30 hours in a double-blind, randomized, crossover study with a washout interval of 8 days. Bicycle exercise tests were performed before and at 1 1/2, 8, 20, 24, and 30 hours after start of treatment. After 24 hours of infusion, exercise parameters were not significantly different from pretreatment values (p greater than 0.05) during ISDN plus placebo, indicating development of tolerance to ISDN. In contrast, time to onset of angina, time to 1-mm ST segment depression, and total amount of ST segment depression were still significantly improved after 24-hour infusion of ISDN plus NAC (p less than 0.05). In addition, compared with placebo, a significant difference (p less than 0.05) in favor of NAC was observed regarding time to angina (507 +/- 63 versus 445 +/- 69 seconds, mean +/- SEM), time to 1-mm ST segment depression (435 +/- 43 versus 407 +/- 45 seconds), and total ST segment depression (1.8 +/- 0.9 versus 3.1 +/- 0.4 mm). CONCLUSIONS. These results suggest that infusion of high doses of NAC in combination with ISDN for 30 hours affects and partially prevents the development of tolerance to antianginal effects normally observed during infusion with ISDN.     

Effects of coronary venous pressure on left ventricular diastolic distensibility

Coronary arterial pressure and flow are known to influence left ventricular (LV) diastolic distensibility, but the influence of coronary venous pressure is unknown. To test the hypothesis that increased coronary venous pressure leads to an increase in LV wall volume and a decrease in LV diastolic distensibility, we studied excised, blood-perfused LV isovolumic dog hearts without the pericardium. In protocol I (n = 8), to raise coronary venous pressure the pressure of right atrium (RA) and right ventricle (RV) was increased by the height of a blood reservoir connected with a cannula that opened in both the RA and RV. In protocol II (n = 7), to isolate the effect of RV enlargement on LV diastolic distensibility (direct ventricular interaction), an isovolumic RV balloon was used with coronary venous pressure held constant at 0 mm Hg. Changes in LV diastolic distensibility were assessed by shifts of the LV end-diastolic pressure-volume relation. Changes in LV wall volume were detected by subepicardial segment length at end-diastole. The mean pressures of RA and RV (protocol I) and RV balloon only (protocol II) were increased from 0 to 15 and 30 mm Hg over a range of LV volume. In protocol I, when RA.RV pressure was increased from 0 to 30 mm Hg at three levels of LV volume (22 +/- 2, 31 +/- 3, and 40 +/- 3 ml), LV end-diastolic pressures increased significantly from 5.2 +/- 0.3 to 11.2 +/- 1.5, from 10.4 +/- 0.3 to 18.2 +/- 1.2, and from 20.2 +/- 1.0 to 28.8 +/- 1.2 mm Hg, respectively. In protocol II, when RV balloon pressure was increased from 0 to 30 mm Hg at the three LV volumes (21 +/- 3, 31 +/- 3, and 41 +/- 4 ml), LV end-diastolic pressures showed smaller increases from 5.2 +/- 0.2 to 6.6 +/- 0.2, from 9.8 +/- 0.3 to 11.6 +/- 0.6, and from 19.0 +/- 0.5 to 21.4 +/- 0.8 mm Hg, respectively. In both protocols, the LV end-diastolic pressure-volume relation shifted upward in a nearly parallel fashion, but the shift was much greater in protocol I than in protocol II. Despite constant LV volume, an increase in LV wall dimension in protocol I was significant and much greater than that in protocol II. From these results, we conclude that increased coronary venous pressure decreases LV diastolic distensibility with increasing LV wall volume, and this mechanism appears to act independently of diastolic ventricular interaction caused by RV enlargement.     

Preservation of left ventricular performance with reduced ischemic dysfunction by intravenous nisoldipine

The effect of intravenous nisoldipine on cardiac performance was examined during pacing-induced ischemia in 14 patients with coronary artery disease. The relative contributions of afterload reduction or prevention of myocardial ischemia were assessed using load-independent global (peak-systolic pressure/end-systolic volume) and regional (peak-systolic pressure/end-systolic radial length) "contractile" indexes. Nisoldipine decreased aortic pressure (predrug, 109 +/- 14 vs postdrug, 88 +/- 13 mm Hg, p less than 0.01) and prevented elevation of left ventricular end-diastolic pressure during rapid atrial pacing (predrug, 7.9 +/- 5.7 vs postdrug, -0.5 +/- 4.9 mm Hg, p less than 0.001). Resting cardiac index (predrug, 3.3 +/- 0.6 vs postdrug, 4.2 +/- 0.7 liters/min/m2, p less than 0.05), and left ventricular ejection fraction (predrug, 68.1 +/- 9.0 vs postdrug, 74.2 +/- 9.4%, p less than 0.05) increased after nisoldipine, which also prevented the deterioration in left ventricular ejection fraction (predrug, -8.1 +/- 7.9 vs postdrug, -1.0 +/- 3.7%, p less than 0.05) and fractional radial shortening (predrug, -8.7 +/- 13.1 vs postdrug, 3.7 +/- 16.4%, p less than 0.01) during rapid atrial pacing. Under these conditions, nisoldipine preserved myocardial function, as determined by global peak-systolic pressure/end-systolic volume (predrug, -0.82 +/- 0.39 vs postdrug, 0.17 +/- 1.54 mm Hg/ml, p less than 0.05) and regional (peak-systolic pressure/end-systolic radial length, predrug, -23.8 +/- 36.1 vs postdrug, 12.7 +/- 36.3 mm Hg/cm, p less than 0.01) "contractile" indexes. Intravenous nisoldipine maintains ventricular performance during rapid atrial pacing via a combination of systemic vasodilation and amelioration of ischemic myocardial dysfunction.     

Left ventricular response to submaximal exercise in endurance-trained athletes and sedentary adults.

This investigation examines the hypothesis that athletes increase stroke volume with submaximal exercise through an augmentation of left ventricular (LV) end-diastolic volume and a reduction of LV end-systolic volume, whereas sedentary adults only increase stroke volume modestly, because LV end-diastolic volume does not increase. Upright bicycle exercise was performed by 17 endurance-trained male athletes and 15 sedentary men. M-mode echocardiograms were obtained during submaximal exercise at predetermined heart rates. Athletes, at a heart rate of 130 beats/min, increased their stroke volume 67% from 72 +/- 18 ml to 120 +/- 26 ml (p less than 0.001). This resulted from an increase of LV end-diastolic volume from 119 +/- 23 to 152 +/- 28 ml (p less than 0.001) and a reduction in LV end-systolic volume from 46 +/- 14 to 31 +/- 9 ml (p less than 0.001). Sedentary men at the same heart rate increased stroke volume 22% from 63 +/- 15 to 77 +/- 21 ml (p less than 0.05). LV end-diastolic volume did not change (96 +/- 20 vs 97 +/- 28 ml) (p = not significant), but LV end-systolic volume decreased (33 +/- 11 vs 20 +/- 9 ml) (p less than 0.001). In conclusion, athletes increased cardiac output through a more prominent augmentation of stroke volume than sedentary subjects at submaximal exercise. This was accomplished through an augmentation of LV end-diastolic volume. This may have a conserving effect on myocardial oxygen consumption at these levels of exercise.     

Relationship of the electrocardiographic response to exercise to geometric and functional findings in aortic regurgitation

The exercise ECGs of 30 patients with pure aortic regurgitation (AR) were compared with functional and geometric variables measured by echocardiography and radionuclide cineangiography. The 10 patients with positive ECG responses to exercise (greater than or equal to 0.1 mV additional downsloping or horizontal ST segment depression) were similar to the 20 patients with negative tests with respect to mean age, exercise duration, peak work load achieved, symptoms, and resting ECG findings. Patients with positive exercise tests had significantly reduced left ventricular (LV) ejection fractions at rest (44 +/- 4% vs 52 +/- 2%) and during peak exercise (38 +/- 3% vs 48 +/- 2%), lower fractional shortening at rest (27 +/- 1% vs 34 +/- 2%), higher end-systolic wall stress (150 +/- 18 vs 99 +/- 8 dynes/cm2 X 10(3], lower left ventricular relative wall thickness (0.26 +/- 0.01 vs 0.30 +/- 0.01), and greater end-systolic diameter (5.7 +/- 0.3 vs 4.5 +/- 0.2 cm) than patients with negative tests (p less than 0.05 for all comparisons). Among the 18 asymptomatic patients, positive tests were associated with lower resting fractional shortening, lower exercise ejection fraction, higher wall stress, and greater end-systolic diameter. These data demonstrate that a positive exercise ECG in aortic regurgitation identifies patients, even when asymptomatic, who have developed markedly abnormal left ventricular functional and geometric responses to volume load, while a negative exercise ECG identifies a subset of asymptomatic patients who are unlikely to have severe ventricular dysfunction.     

ST-segment re-elevation unrelated to left ventricular ejection fraction or volume after anterior wall acute myocardial infarction treated with successful reperfusion

Ventricular remodeling is a major determinant of the long-term prognosis of patients with acute myocardial infarction (AMI). No previous study examined the relation of ST-segment re-elevation to left ventricular (LV) volume and function in patients with successful reperfusion. We examined the relation of ST-segment re-elevation to LV function and volume indices in 51 patients with anterior wall AMI who underwent successful reperfusion by direct coronary angioplasty. A 12-lead electrocardiogram was recorded once a day until 7 days after the onset of AMI. ST-segment shift was measured and Sigma ST was defined as the sum of ST-segment elevation obtained from leads V2, V3, and V4. ST-segment re-elevation was defined as present when the difference between maximal and minimal Sigma ST (Delta ST) was >0.3mV. LV indices were obtained from left ventriculography performed approximately 1 month after the onset of AMI. ST-segment re-elevation was observed in 15 patients (29%). No significant differences were observed between the ST- re-elevation group and non-ST-re-elevation group in LV ejection fraction (49.4+/-14.0 vs. 51.2+/-11.5%), LV end-systolic volume index (35.8+/-13.1 vs. 33.8+/-12.5 mL/m(2)) or LV end-diastolic volume index (69.7+/-12.8 vs. 68.3+/-14.4 mL/m(2)). The difference between maximal and minimal Sigma ST (Delta ST) was not significantly correlated with any LV index examined. In conclusion, the present study revealed that ST-segment re-elevation after successful reperfusion in anterior wall AMI patients was not related to LV volume or function, indicating that ST-re-elevation is not a clinically meaningful indicator of LV remodeling.     

Comparative effects of pacing-induced and balloon coronary occlusion ischemia on left ventricular diastolic function in man

BACKGROUND. Effects of pacing-induced and coronary occlusion myocardial ischemia on left ventricular (LV) function have been compared only in anesthetized dogs. Diastolic properties of the same LV anterior wall segment were therefore compared in 12 patients with single-vessel proximal left anterior descending coronary artery stenosis at rest, immediately after 7 +/- 1.2 minutes of pacing, and at the end of a 1-minute balloon occlusion of coronary angioplasty (CO). METHODS AND RESULTS. Shifts of the diastolic LV pressure-length relation, derived from simultaneous tip-micromanometer LV pressure recordings and digital subtraction LV angiograms, were used as an index of regional diastolic LV distensibility of the anterior wall segment. Immediately after pacing, LV end-diastolic pressure rose from 13.5 +/- 3.5 to 23.8 +/- 7.0 mm Hg (p less than 0.01 versus at rest) without a significant change of the LV end-diastolic volume index (83.1 +/- 18.9 versus 88.4 +/- 16.5 ml/m2), percentage systolic shortening (%SS) of the ischemic segment fell from 40.1 +/- 10.6% to 25.2 +/- 8.6% (p less than 0.01), and the diastolic LV pressure-radial length (P-RL) plot of the ischemic segment was shifted upward by 7.1 +/- 5.0 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. At the end of CO, LV end-diastolic pressure rose to 20.8 +/- 7.8 mm Hg (p less than 0.01 versus at rest) and the LV end-diastolic volume index rose to 95.6 +/- 16.3 ml/m2 (p less than 0.05 versus at rest, p less than 0.05 versus after pacing). Ejection fraction and %SS of the ischemic segment fell respectively from 76.6 +/- 6.8% to 46.6 +/- 11.4% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing) and from 40.1 +/- 10.6% to 6.4 +/- 8.6% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing). The diastolic LV P-RL plot of the ischemic segment was shifted upward by 3.1 +/- 2.3 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. This upward shift at the end of CO was significantly smaller (p less than 0.05) than that immediately after pacing. At the end of CO, a correlation (p less than 0.03) was observed for the ischemic segment between %SS and upward shift of the diastolic LV P-RL plot. CONCLUSIONS. The upward shift of the diastolic LV P-RL plot, which was used as an index of decreased regional diastolic LV distensibility, was larger immediately after pacing than at the end of CO. Persistent systolic shortening of ischemic myocardium seems to be a prerequisite for a decrease in diastolic distensibility of the ischemic segment because of the higher %SS of the ischemic segment immediately after pacing, and because of the correlation at the end of CO between the upward shift of the diastolic LV P-RL plot and %SS of the ischemic segment.