Ranolazine combined with enalapril or metoprolol prevents progressive LV dysfunction and remodeling in dogs with moderate heart failure

Acute intravenous infusion of ranolazine (Ran), an anti-ischemic/antiangina drug, was previously shown to improve left ventricular (LV) ejection fraction (EF) without a concomitant increase in myocardial oxygen consumption in dogs with chronic heart failure (HF). This study examined the effects of treatment with Ran alone and in combination with metoprolol (Met) or enalapril (Ena) on LV function and remodeling in dogs with HF. Dogs (n = 28) with microembolization-induced HF were randomized to 3 mo oral treatment with Ran alone [375 mg twice daily (bid); n = 7], Ran (375 mg bid) in combination with Met tartrate (25 mg bid; n = 7), Ran (375 mg bid) in combination with Ena (10 mg bid; n = 7), or placebo (PL; Ran vehicle bid; n = 7). Ventriculographic measurements of LV end-diastolic volume (EDV) and end-systolic volume (ESV) and LV EF were obtained before treatment and after 3 mo of treatment. In PL-treated dogs, EDV and ESV increased significantly. Ran alone prevented the increase in EDV and ESV seen in the PL group and significantly increased EF, albeit modestly, from 35 +/- 1% to 37 +/- 2%. When combined with either Ena or Met, Ran prevented the increase in EDV, significantly decreased ESV, and markedly increased EF compared with those of PL. EF increased from 35 +/- 1% to 40 +/- 1% with Ran + Ena and from 34 +/- 1% to 41 +/- 1% with Ran + Met. Ran alone or in combination with Ena or Met was also associated with beneficial effects at the cellular level on histomorphometric parameters such as hypertrophy, fibrosis, and capillary density as well as the expression for pathological hypertrophy and Ca2+ cycling genes. In conclusion, Ran prevented progressive LV dysfunction and global and cellular myocardial remodeling, and Ran in combination with Ena or Met improved LV function beyond that observed with Ran alone.     

正常人左心室功能指标的参考值及其预计公式的初步研究报告*

目的: 当前评估左心室容量和功能仍常用正常值范围,个体化分析也仅使用体表面积进行校正。尚缺少个体化因素相关的大样本参考值和预计公式。方法: 本研究纳入美国加州洛杉矶县南湾地区1200名健康志愿者,其中男807女393,年龄20岁-94岁,心脏CT造影（CTA）,经过高精度三维成像技术处理,计算左心室容积在收缩和舒张过程中的连续动态变化,测定左心室（LV）容量和功能指标：舒张末期容积（EDV)、收缩末期容积(ESV)、每搏输出量(SV)、射血分数(EF)和心输出量(CO)。将以上指标与一般特征指标进行多因素相关分析,以探索正常人预计值计算公式。结果: 男性除LVEF小于女性外（P<0.001）,其余各指标均大于女性（P<0.001）。多元线性回归分析提示, 性别、年龄、身高和体质量均为EDV、ESV、SV的独立影响因子(P<0.001); 而CO仅受年龄、性别、体质量显著影响(P<0.001),但与身高无关(P>0.05)。CO的预测公式CO (L·min^-1)= 6.963+0.446(Male) -0.037×年龄(yr)+0.013×体质量(kg)。结论: 性别、年龄、身高、体质量均影响左心室容量和功能,建立预测值计算公式,对心血管疾病的无创评估和个体化精准医疗具有重要参考价值。     

Determination of the ejection fraction and cardiac volumes using magnetic resonance tomography

The results of NMR-tomography and radiocontrast ventriculography (VG) were compared in 20 CHD patients to determine ejection fraction (EF), and left ventricular (LV) end-diastolic and end-systolic volumes (EDV and ESV). NMR-tomography of the heart was performed at the field power of 0.23 T using the synchronization with ECG. Two methods of orientation of NMP-section on the LV long axis were employed. A sufficiently high correlation of NMR-tomography and VG findings in the determination of EF (r = 0.9) was obtained, low and insignificant--in the determination of EDV and ESV. Possible causes of differences between the results of both methods are under discussion.     

Left ventricular mechanical limitations to stroke volume in healthy humans during incremental exercise

During incremental exercise, stroke volume (SV) plateaus at 40-50% of maximal exercise capacity. In healthy individuals, left ventricular (LV) twist and untwisting ("LV twist mechanics") contribute to the generation of SV at rest, but whether the plateau in SV during incremental exercise is related to a blunting in LV twist mechanics remains unknown. To test this hypothesis, nine healthy young males performed continuous and discontinuous incremental supine cycling exercise up to 90% peak power in a randomized order. During both exercise protocols, end-diastolic volume (EDV), end-systolic volume (ESV), and SV reached a plateau at submaximal exercise intensities while heart rate increased continuously. Similar to LV volumes, two-dimensional speckle tracking-derived LV twist and untwisting velocity increased gradually from rest (all P < 0.001) and then leveled off at submaximal intensities. During continuous exercise, LV twist mechanics were linearly related to ESV, SV, heart rate, and cardiac output (all P < 0.01) while the relationship with EDV was exponential. In diastole, the increase in apical untwisting was significantly larger than that of basal untwisting (P < 0.01), emphasizing the importance of dynamic apical function. In conclusion, during incremental exercise, the plateau in LV twist mechanics and their close relationship with SV and cardiac output indicate a mechanical limitation in maximizing LV output during high exercise intensities. However, LV twist mechanics do not appear to be the sole factor limiting LV output, since EDV reaches its maximum before the plateau in LV twist mechanics, suggesting additional limitations in diastolic filling to the heart.     

Left ventricular volume and function in cynomolgus monkeys using real-time three-dimensional echocardiography

BACKGROUND: The purpose of this study was to investigate the feasibility of evaluating cardiac function by real time three-dimensional (RT3D) echocardiography in isoflurane-anesthetized male cynomolgus monkeys. Additionally differences between inhibitory effects of beta-blockers and a Ca channel blocker on left ventricular (LV) function were examined. METHODS AND RESULTS: End-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) in the control (without any drug effect) were not significantly changed by repetitive measurement at a 30-day interval. Propranolol and metoprolol (0.1 and 0.3 mg/kg/10 minutes, i.v.) caused a dose-dependent increase in ESV, but little effect on EDV, resulting in a decrease in EF. Verapamil (0.1 and 0.3 mg/kg/10 minutes, i.v.) increased both EDV and ESV, but decreased EF was noted at 0.3 mg/kg. CONCLUSIONS: These results demonstrate the feasibility of RT3D echocardiography in providing reproducible estimations of LV volume and EF in monkeys when evaluating drugs that may affect cardiac function.     

Darbepoetin-alpha prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure

In anemic patients with heart failure (HF), erythropoietin-type drugs can elicit clinical improvement. This study examined the effects of chronic monotherapy with darbepoetin-alpha (DARB) on left ventricular (LV) function and remodeling in nonanemic dogs with advanced HF. HF [LV ejection fraction (EF) approximately 25%] was produced in 14 dogs by intracoronary microembolizations. Dogs were randomized to once a week subcutaneous injection of DARB (1.0 microg/kg, n=7) or to no therapy (HF, n=7). All procedures were performed during cardiac catheterization under general anesthesia and under sterile conditions. LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were measured before the initiation of therapy and at the end of 3 mo of therapy. mRNA and protein expression of caspase-3, hypoxia inducible factor-1alpha, and the bone marrow-derived stem cell marker c-Kit were determined in LV tissue. In HF dogs, EDV and ESV increased and EF decreased after 3 mo of followup. Treatment with DARB prevented the increase in EDV, decreased ESV, and increased EF. DARB therapy also normalized the expression of HIF-1alpha and active caspase-3 and enhanced the expression of c-Kit. We conclude that chronic monotherapy with DARB prevents progressive LV dysfunction and dilation in nonanemic dogs with advanced HF. These results suggest that DARB elicits beneficial effects in HF that are independent of the presence of anemia.     

Effect of acute high-intensity interval exercise on postexercise biventricular function in mild heart failure

We studied the acute effect of high-intensity interval exercise on biventricular function using cardiac magnetic resonance imaging in nine patients [age: 49 ± 16 yr; left ventricular (LV) ejection fraction (EF): 35.8 ± 7.2%] with nonischemic mild heart failure (HF). We hypothesized that a significant impairment in the immediate postexercise end-systolic volume (ESV) and end-diastolic volume (EDV) would contribute to a reduction in EF. We found that immediately following acute high-intensity interval exercise, LV ESV decreased by 6% and LV systolic annular velocity increased by 21% (both P < 0.05). Thirty minutes following exercise (+30 min), there was an absolute increase in LV EF of 2.4% (P < 0.05). Measures of preload, left atrial volume and LV EDV, were reduced immediately following exercise. Similar responses were observed for right ventricular volumes. Early filling velocity, filling rate, and diastolic annular velocity remained unchanged, while LV untwisting rate increased 24% immediately following exercise (P < 0.05) and remained 18% above baseline at +30 min (P < 0.05). The major novel findings of this investigation are 1) that acute high-intensity interval exercise decreases the immediate postexercise LV ESV and increases LV EF at +30 min in patients with mild HF, and this is associated with a reduction in LV afterload and maintenance of contractility, and 2) that despite a reduction in left atrial volume and LV EDV immediately postexercise, diastolic function is preserved and may be modulated by enhanced LV peak untwisting rate. Acute high-intensity interval exercise does not impair postexercise biventricular function in patients with nonischemic mild HF.     

Gated F-18 FDG PET for Assessment of Left Ventricular Volumes and Ejection Fraction Using QGS and 4D-MSPECT in Patients with Heart Failure: A Comparison with Cardiac MRI

Purpose

Ventricular function is a powerful predictor of survival in patients with heart failure (HF). However, studies characterizing gated F-18 FDG PET for the assessment of the cardiac function are rare. The aim of this study was to prospectively compare gated F-18 FDG PET and cardiac MRI for the assessment of ventricular volume and ejection fraction (EF) in patients with HF.

Methods

Eighty-nine patients with diagnosed HF who underwent both gated F-18 FDG PET/CT and cardiac MRI within 3 days were included in the analysis. Left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), and EF were obtained from gated F-18 FDG PET/CT using the Quantitative Gated SPECT (QGS) and 4D-MSPECT software.

Results

LV EDV and LV ESV measured by QGS were significantly lower than those measured by cardiac MRI (both P<0.0001). In contrast, the corresponding values for LV EDV for 4D-MSPECT were comparable, and LV ESV was underestimated with borderline significance compared with cardiac MRI (P = 0.047). LV EF measured by QGS and cardiac MRI showed no significant differences, whereas the corresponding values for 4D-MSPECT were lower than for cardiac MRI (P<0.0001). The correlations of LV EDV, LV ESV, and LV EF between gated F-18 FDG PET/CT and cardiac MRI were excellent for both QGS (r = 0.92, 0.92, and 0.76, respectively) and 4D-MSPECT (r = 0.93, 0.94, and 0.75, respectively). However, Bland-Altman analysis revealed a significant systemic error, where LV EDV (−27.9±37.0 mL) and ESV (−18.6±33.8 mL) were underestimated by QGS.

Conclusion

Despite the observation that gated F-18 FDG PET/CT were well correlated with cardiac MRI for assessing LV function, variation was observed between the two imaging modalities, and so these imaging techniques should not be used interchangeably.     

Selective matrix metalloproteinase inhibition attenuates progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure

Matrix metalloproteinases (MMPs) contribute to the progression of left ventricular (LV) dysfunction and remodeling associated with heart failure (HF). The present study examined the long-term effects of a selective MMP inhibitor PG-530742 (PG) on the progression of LV dysfunction and remodeling in dogs with HF. Chronic HF [LV ejection fraction (LVEF), 相似文献   

Dynamic effects of positive-pressure ventilation on canine left ventricular pressure-volume relations.

Positive-pressure ventilation (PPV) may affect left ventricular (LV) performance by altering both LV diastolic compliance and pericardial pressure (Ppc). We measured the effect of PPV on LV intraluminal pressure, Ppc, LV volume, and LV cross-sectional area in 17 acute anesthetized dogs. To account for changes in lung volume independent of changes in Ppc and differences in contractility, measures were made during both open- and closed-chest conditions, during closed chest with and without chest wall binding, and after propranolol-induced acute ventricular failure (AVF). Apneic end-systolic pressure-volume relations (ESPVR) were generated by inferior vena caval occlusions. With the open chest, PPV had no effects. With the chest closed, PPV inspiration decreased LV end-diastolic volume (EDV) along its diastolic compliance curve and decreased end-systolic volume (ESV) such that the end-systolic pressure-volume domain was shifted to a point left of the LV ESPVR, even when referenced to Ppc. The decrease in EDV was greater in control than in AVF conditions, whereas the shift of the ESV to the left of the ESPVR was greater with AVF than in control conditions. We conclude that the hemodynamic effects of PPV inspiration are due primarily to changes in intrathoracic pressure and that the inspiration-induced decreases of LV EDV reflect direct effects of intrathoracic pressure on LV filling. The decreases in LV ESV exceed the amount explained solely by a reduction in LV ejection pressure.     

Altered high-energy phosphate metabolism predicts contractile dysfunction and subsequent ventricular remodeling in pressure-overload hypertrophy mice

To study the role of early energetic abnormalities in the subsequent development of heart failure, we performed serial in vivo combined magnetic resonance imaging (MRI) and (31)P magnetic resonance spectroscopy (MRS) studies in mice that underwent pressure-overload following transverse aorta constriction (TAC). After 3 wk of TAC, a significant increase in left ventricular (LV) mass (74 +/- 4 vs. 140 +/- 26 mg, control vs. TAC, respectively; P < 0.000005), size [end-diastolic volume (EDV): 48 +/- 3 vs. 61 +/- 8 microl; P < 0.005], and contractile dysfunction [ejection fraction (EF): 62 +/- 4 vs. 38 +/- 10%; P < 0.000005] was observed, as well as depressed cardiac energetics (PCr/ATP: 2.0 +/- 0.1 vs. 1.3 +/- 0.4, P < 0.0005) measured by combined MRI/MRS. After an additional 3 wk, LV mass (140 +/- 26 vs. 167 +/- 36 mg; P < 0.01) and cavity size (EDV: 61 +/- 8 vs. 76 +/- 8 microl; P < 0.001) increased further, but there was no additional decline in PCr/ATP or EF. Cardiac PCr/ATP correlated inversely with end-systolic volume and directly with EF at 6 wk but not at 3 wk, suggesting a role of sustained energetic abnormalities in evolving chamber dysfunction and remodeling. Indeed, reduced cardiac PCr/ATP observed at 3 wk strongly correlated with changes in EDV that developed over the ensuing 3 wk. These data suggest that abnormal energetics due to pressure overload predict subsequent LV remodeling and dysfunction.     

Assessing Right Ventricular Function in Patients with Hypertrophic Cardiomyopathy with Cardiac MRI: Correlation with the New York Heart Function Assessment (NYHA) Classification

Purpose

To determine whether 3.0-T magnetic resonance imaging (MRI) could assess right ventricular (RV) function in patients with hypertrophic cardiomyopathy (HCM), and if this assessment is correlated with the New York Heart Function Assessment (NYHA) classification.

Materials and Methods

Forty-six patients with HCM and 23 normal individuals were recruited. Left and right ventricular function parameters including end-diastolic and end-systolic volumes (EDV, ESV), stroke volume (SV) and ejection fraction (EF) and dimensions were measured and compared using 3.0-T MRI. RV function parameters between HCM patients and controls were compared using independent sample t tests. A one way ANOVA test with Bonferroni correction was used to determine significant differences among different NYHA groups. Receiver operating characteristic analyses calculated the sensitivity and specificity of RV dysfunction on MRI for the prediction of HCM severity.

Results

Statistical analysis revealed significant differences of left ventricular (LV) and RV volumetric values and masses between the HCM patients and controls (all p<0.05). Within the HCM group, the simultaneously decreased maximum RVEDD correlated well with the LVEDD (r = 0.53; p<0.001). The function and dimension parameters among Class I to III were not determined to be significantly different (all p>0.05). However, significant differences between the Class IV and I-III groups (all P<0.0167) indicated that the diastolic and systolic function in both the RV and LV were impaired in Class IV patients. ROC analyses identified the EDV, ESV and EDD of both the LV and RV with a high sensitivity cutoff value to predict the HCM patients with severe heart failure (Class IV) with high sensitivity and specificity.

Conclusions

RV involvements were comparable to those of LV global function impairments in patients with HCM. The presence of RV dysfunction and decreased dimension on the MRI helped to predict the severe symptomatic HCM with high sensitivity and specificity.     

Xanthine oxidase inhibitors improve energetics and function after infarction in failing mouse hearts

After myocardial infarction, ventricular geometry and function, as well as energy metabolism, change markedly. In nonischemic heart failure, inhibition of xanthine oxidase (XO) improves mechanoenergetic coupling by improving contractile performance relative to a reduced energetic demand. However, the metabolic and contractile effects of XO inhibitors (XOIs) have not been characterized in failing hearts after infarction. After undergoing permanent coronary ligation, mice received a XOI (allopurinol or oxypurinol) or matching placebo in the daily drinking water. Four weeks later, 1H MRI and 31P magnetic resonance spectroscopy (MRS) were used to quantify in vivo functional and metabolic changes in postinfarction remodeled mouse myocardium and the effects of XOIs on that process. End-systolic (ESV) and end-diastolic volumes (EDV) were increased by more than sixfold after infarction, left ventricle (LV) mass doubled (P < 0.005), and the LV ejection fraction (EF) decreased (14 +/- 9%) compared with control hearts (59 +/- 8%, P < 0.005) at 1 mo. The myocardial phosphocreatine (PCr)-to-ATP ratio (PCr/ATP) was also significantly decreased in infarct remodeled hearts (1.4 +/- 0.6) compared with control animals (2.1 +/- 0.5, P < 0.02), in agreement with prior studies in larger animals. The XOIs allopurinol and oxypurinol did not change LV mass but limited the increase in ESV and EDV of infarct hearts by 50%, increased EF (23 +/- 9%, P = 0.01), and normalized cardiac PCr/ATP (2.0 +/- 0.5, P < 0.04). We conclude that XOIs improve ventricular function after infarction and normalize high-energy phosphate ratio in heart failure. Thus XOI therapy offers a new and potentially complementary approach to limit the adverse contractile and metabolic consequences after infarction.     

Echocardiographic and cardiac single photon emission computed tomography predictors of left ventricle reverse remodeling after surgical revascularization in patients with ischemic cardiomyopathy and left ventricle systolic dysfunction

Background: The extent of scar or viable hypocontractile myocardial tissue determines postinfarction left ventricle remodeling. The aim of this pilot study was to evaluate the revascularization effect in a group of patients with ischemic cardiomyopathy and LV systolic dysfunction indicated for surgical revascularization, based on evidence for multivessel disease on coronarography and viable myocardium (CMR, SPECT). Aims: To evaluate the revascularization effect in patients with ischemic LV systolic dysfunction and to find preoperative predictors of revascularization effect. Methods: 33 patients (64+/-11 years) with baseline LVEF 34.9+/-9.3 % were included in the study. After a follow-up of 10.7+/-1.2 months, ECHO and SPECT were performed again. The whole group of patients was divided according to revascularization effect (postoperative increase LVEF > 5 % and postoperative decrease LVESV > 5 % compared with baseline) into revascularization responders (R, n = 22) and nonresponders (NR, n = 11). Results: At baseline there was no difference between the subgroups in LVEF (R = 35.7+/-11.0 % vs. NR = 34.3+/-8.2 %), EDV (R = 183.6+/-43.2 vs. NR = 180.2+/-80.5 ml), ESV (R = 118.5+/-40.4 vs. NR = 119.7+/-55.2 ml). The responders showed in a revascularization effect subanalysis differences in the values of LVEF (+9.8+/-8.1 %, p < 0.009), reduction of EDV (-39.9+/-50.9 ml, p = 0.05) and ESV (-35.4+/-42.6 ml, p = 0,002) compared with baseline. The only preoperative parameters predicting LV reverse remodeling were the T(E-Em) (R = -10.6+/-44.1 vs. NR = 29.7+/-43.7 ms, p = 0.037) and the size of fixed perfusion defect (FPD) (R = 11.9+/-13.5 vs. NR = 22.9+/-15.3 % of LV, p = 0.044). Conclusions: Patients with ischemic LV systolic dysfunction with a preoperatively determined myocardial viability develop LV reverse remodeling. The only preoperative parameters predicting LV reverse remodeling were echocardiographic T(E-Em) and FPD on SPECT.     

Left Ventricular Function during Acute High-Altitude Exposure in a Large Group of Healthy Young Chinese Men

Objective

The purpose of this study was to observe left ventricular function during acute high-altitude exposure in a large group of healthy young males.

Methods

A prospective trial was conducted in Szechwan and Tibet from June to August, 2012. By Doppler echocardiography, left ventricular function was examined in 139 healthy young Chinese men at sea level; within 24 hours after arrival in Lhasa, Tibet, at 3700 m; and on day 7 following an ascent to Yangbajing at 4400 m after 7 days of acclimatization at 3700 m. The resting oxygen saturation (SaO2), heart rate (HR) and blood pressure (BP) were also measured at the above mentioned three time points.

Results

Within 24 hours of arrival at 3700 m, the HR, ejection fraction (EF), fractional shortening (FS), stroke volume (SV), cardiac output (CO), and left ventricular (LV) Tei index were significantly increased, but the LV end-systolic dimension (ESD), end-systolic volume (ESV), SaO2, E/A ratio, and ejection time (ET) were significantly decreased compared to the baseline levels in all subjects. On day 7 at 4400 m, the SV and CO were significantly decreased; the EF and FS Tei were not decreased compared with the values at 3700 m; the HR was further elevated; and the SaO2, ESV, ESD, and ET were further reduced. Additionally, the E/A ratio was significantly increased on day 7 but was still lower than it was at low altitude.

Conclusion

Upon acute high-altitude exposure, left ventricular systolic function was elevated with increased stroke volume, but diastolic function was decreased in healthy young males. With higher altitude exposure and prolonged acclimatization, the left ventricular systolic function was preserved with reduced stroke volume and improved diastolic function.     

Myocardial transfection with naked DNA plasmid encoding hepatocyte growth factor prevents the progression of heart failure in dogs

This study examined the effects of localized intramyocardial injections of hepatocyte growth factor (HGF) naked DNA plasmid on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure (HF). Twenty-one dogs with intracoronary microembolization-induced HF [LV ejection fraction (EF) = 35-40%] were randomized into three treatment groups, namely, high-dose HGF plasmid (4.0 mg, n = 7), low-dose HGF plasmid (0.4 mg, n = 7), and sham-operated controls treated with normal saline (n = 7). A total of 10-15 injections of HGF plasmid or saline were made directly into the anterior wall of LV. LV EF and end-systolic volume (ESV) were measured before randomization (pretreatment) and at the end of 3 mo of follow-up (posttreatment). Treatment effect (Δ) was calculated as the change from pre- to posttreatment. Protein expression of sarcoplasmic reticulum (SR) Ca(2+)-cycling proteins was determined in LV tissue obtained from the sites of HGF injection and remote areas. Low-dose HGF attenuated the decline in EF (ΔEF: -3 ± 1 vs. -8 ± 1%, P < 0.05) and the increase in ESV (ΔESV: 6 ± 2 vs. 10 ± 1 ml, P < 0.05) seen in control sham-operated dogs, whereas high-dose HGF significantly increased EF (ΔEF: 4 ± 1 vs. -8 ± 1%, P < 0.05) and prevented the increase in ΔESV (ESV: -1 ± 1 vs. 10 ± 1 ml, P < 0.05) compared with control dogs. Treatment with high- and low-dose HGF improved the expression of the SR Ca(2+)-cycling proteins compared with controls. In conclusion, regional intramyocardial injections of HGF naked DNA plasmid improve regional and global LV function and prevent progressive LV remodeling.     

Does fitness level modulate the cardiovascular hemodynamic response to exercise?

Subjects with greater aerobic fitness demonstrate better diastolic compliance at rest, but whether fitness modulates exercise cardiac compliance and cardiac filling pressures remains to be determined. On the basis of maximal oxygen consumption (VO2max), healthy male subjects were categorized into either low (LO: VO2max=43+/-6 ml.kg-1.min-1; n=3) or high (HI: VO2max=60+/-3 ml.kg-1.min-1; n=5) aerobic power. Subjects performed incremental cycle exercise to 90% Vo(2max). Right atrial (RAP) and pulmonary artery wedge (PAWP) pressures were measured, and left ventricular (LV) transmural filling pressure (TMFP=PAWP-RAP) was calculated. Cardiac output (CO) and stroke volume (SV) were determined by direct Fick, and LV end-diastolic volume (EDV) was estimated from echocardiographic fractional area change and Fick SV. There were no between-group differences for any measure at rest. At a submaximal workload of 150 W, PAWP and TMFP were higher (P<0.05) in LO compared with HI (12 vs. 8 mmHg, and 9 vs. 4 mmHg, respectively). At peak exercise, CO, SV, and EDV were lower in LO (P<0.05). RAP was not different at peak exercise, but PAWP (23 vs. 15 mmHg) and TMFP (12 vs. 6 mmHg) were higher in LO (P<0.05). Compared with less fit subjects, subjects with greater aerobic fitness demonstrated lower LV filling pressures during exercise, whereas SV and EDV were either similar (submaximal exercise) or higher (peak exercise), suggesting superior diastolic function and compliance.     

Hemodynamic effects of periodic obstructive apneas in sedated pigs with congestive heart failure.

Because of similar physiological changes such as increased left ventricular (LV) afterload and sympathetic tone, an exaggerated depression in cardiac output (CO) could be expected in patients with coexisting obstructive sleep apnea and congestive heart failure (CHF). To determine cardiovascular effects and mechanisms of periodic obstructive apnea in the presence of CHF, 11 sedated and chronically instrumented pigs with CHF (rapid pacing) were tested with upper airway occlusion under room air breathing (RA), O(2) breathing (O2), and room air breathing after hexamethonium (Hex). All conditions led to large negative swings in intrathoracic pressure (-30 to -39 Torr) and hypercapnia (PCO(2) approximately 60 Torr), and RA and Hex also caused hypoxia (to approximately 42 Torr). Relative to baseline, RA increased mean arterial pressure (from 97.5 +/- 5.0 to 107.3 +/- 5.7 Torr, P < 0.01), systemic vascular resistance, LV end-diastolic pressure, and LV end-systolic length while it decreased CO (from 2.17 +/- 0.27 to 1.52 +/- 0.31 l/min, P < 0.01), stroke volume (SV; from 23.5 +/- 2.4 to 16.0 +/- 4.0 ml, P < 0.01), and LV end-diastolic length (LVEDL). O2 and Hex decreased mean arterial pressure [from 102.3 +/- 4.1 to 16.0 +/- 4.0 Torr (P < 0.01) with O2 and from 86.0 +/- 8.5 to 78.1 +/- 8.7 Torr (P < 0.05) with Hex] and blunted the reduction in CO [from 2.09 +/- 0.15 to 1.78 +/- 0.18 l/ml for O2 and from 2.91 +/- 0.43 to 2.50 +/- 0.35 l/ml for Hex (both P < 0.05)] and SV. However, the reduction in LVEDL and LV end-diastolic pressure was the same as with RA. There was no change in systemic vascular resistance and LVEDL during O2 and Hex relative to baseline. In the CHF pigs during apnea, there was an exaggerated reduction in CO and SV relative to our previously published data from normal sedated pigs under similar conditions. The primary difference between CHF (present study) and the normal animals is that, in addition to increased LV afterload, there was a decrease in LV preload in CHF contributing to SV depression not seen in normal animals. The decrease in LV preload during apneas in CHF may be related to effects of ventricular interdependence.     

Radionuclide determination of absolute LV volumes: Interstudy,interobserver and intraobserver variances

The results of 22 absolute left ventricular volume (LVV) determinations by a radionuclide (RN) method are compared to the results obtained by contrast ventriculography (CV). Another 10 patients were analysed in order to evaluate the interstudy, interobserver and intraobserver variances. Good correlation was shown between the RN and CV measurements of the end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV) and ejection fraction (EF), but the RN method overestimates the EDV and ESV. The EF was underestimated, but no difference could be shown for the SV. On the inter- and intraobserver levels, regression analysis yielded excellent correlation (r > 0.99 in all cases) with no statistically significant difference (P < 0.05). The interstudy variance was minimal as indicated by regression analysis (r > 0.87) and no statistically significant difference (P < 0.05) could be shown between studies. The results indicate that the RN method of LVV determination can be used in intervention studies over a limited period.     

Atrioventricular plane displacement is the major contributor to left ventricular pumping in healthy adults, athletes, and patients with dilated cardiomyopathy

Previous studies using echocardiography in healthy subjects have reported conflicting data regarding the percentage of the stroke volume (SV) of the left ventricle (LV) resulting from longitudinal and radial function, respectively. Therefore, the aim was to quantify the percentage of SV explained by longitudinal atrioventricular plane displacement (AVPD) in controls, athletes, and patients with decreased LV function due to dilated cardiomyopathy (DCM). Twelve healthy subjects, 12 elite triathletes, and 12 patients with DCM and ejection fraction below 30% were examined by cine magnetic resonance imaging. AVPD and SV were measured in long- and short-axis images, respectively. The percentage of the SV explained by longitudinal function (SV(AVPD%)) was calculated as the mean epicardial area of the largest short-axis slices in end diastole multiplied by the AVPD and divided by the SV. SV was higher in athletes [140 +/- 4 ml (mean +/- SE), P = 0.009] and lower in patients (72 +/- 7 ml, P < 0.001) when compared with controls (116 +/- 6 ml). AVPD was similar in athletes (17 +/- 1 mm, P = 0.45) and lower in patients (7 +/- 1 mm, P < 0.001) when compared with controls (16 +/- 0 mm). SV(AVPD%) was similar both in athletes (57 +/- 2%, P = 0.51) and in patients (67 +/- 4%, P = 0.24) when compared with controls (60 +/- 2%). In conclusion, longitudinal AVPD is the primary contributor to LV pumping and accounts for approximately 60% of the SV. Although AVPD is less than half in patients with DCM when compared with controls and athletes, the contribution of AVPD to LV function is maintained, which can be explained by the larger short-axis area in DCM.