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Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction.

BACKGROUND: Human umbilical cord blood contains an abundance of immature stem/progenitor cells, which may participate in the repair of hearts that have been damaged by myocardial infarction (MI). This study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (hUCBC) transplantation on cardiac function and left ventricular remodeling in rat model of MI. METHODS: Forty-five male Wistar rats were randomized into three groups: MI or control group (n = 15), MI plus cell transplantation (n = 15), and sham group (n = 15). Acute myocardial infarction (AMI) was established by ligating the left anterior descending artery, thereafter, hUCBC were implanted into the marginal area of infarcted myocardium. In MI/control group, DMEM was injected instead of hUCBC following the same protocol. Left ventricular function assessment was carried out by echocardiography and invasive hemodynamic measurements one month post MI. All rats were sacrificed for histological and immunochemical examinations. RESULTS: The transplanted hUCBC survived and engaged in the process of myocardial repair in the host heart. Echocardiography demonstrated that left ventricular function improved significantly in the rats that underwent cell transplantation. Hemodynamic studies found a significantly decreased left ventricular end-diastolic pressure (LVEDP) [(21.08 +/- 8.10) mmHg vs (30.82 +/- 9.59) mmHg, P < 0.05], increase in +dp/dt(max) [(4.29 +/- 1.27) mmHg/ms vs (3.24 +/- 0.75) mmHg/ms, P < 0.05), and increase in -dp/dt(max) [(3.71 +/- 0.79) mmHg/ms vs (3.00 +/- 0.49) mmHg/ms, P < 0.05] among MI group with hUCBC transplantation when compared with MI/control group. Masson's trichrome staining revealed that the collagen density in the left ventricle was significantly lower in rats of transplantation group than that in the MI control groups [(6.33 +/- 2.69)% vs (11.10 +/- 3.75)%, P < 0.01]. Based on immunostaining of alpha-actin, the numbers of microvessels were significantly (P < 0.01) increased at the boundary of infarction site. Similarly higher mRNA expression of vascular endothelial growth factor (VEGF) 164 and VEGF188 were found at 7- and 28-day post cell transplantation in MI group with hUCBC transplantation when compared with MI/control group. CONCLUSIONS: Transplanted hUCBC can survive in host myocardium without immunorejection, significantly improve left ventricular remodeling after AMI and promote a higher level of angiogenesis in the infarct zones. All these factors beneficially affect cardiac repair in the setting of MI. Therefore human umbilical cord blood may be potential source for cell-based therapy for AMI.

Actins↗

Prediction of outcome after revascularization in patients with poor left ventricular function.

BACKGROUND: In patients with poor left ventricular function, the determinants of outcome after revascularization are unknown. METHODS: We studied prospectively 57 patients with stable coronary artery disease and poor left ventricular function (left ventricular ejection fraction, 0.28 +/- 0.04) who underwent coronary artery bypass grafting. Clinical variables were assessed as predictors of outcome in all patients, and preoperative stress thallium-201 scintigraphic data were analysed in 37 patients. RESULTS: The operative mortality was 1.7%. At 12 months after operation, 46 of the 49 survivors were angina-free and 35 had fewer heart failure symptoms, but postoperative left ventricular ejection fraction (0.30 +/- 0.09) did not change significantly. Eighteen survivors had left ventricular ejection fraction improved by 0.05 or more (0.30 +/- 0.03 preoperatively, 0.40 +/- 0.05 postoperatively; p = 0.0001). The adjusted odds ratio of large reversible thallium-201 defects in predicting such outcome was 15 (95% confidence interval, 1.6 to 140), whereas other clinical variables had no predictive value. The transplantation-free 5-year survival was 73%. CONCLUSIONS: In patients with poor left ventricular function, surgical revascularization can be performed safely, with good symptomatic relief and long-term survival. One-year survival and improvement in left ventricular function is better in patients with large reversible defects on preoperative stress thallium-201 scintigraphy.

Aged↗

The ventricular septum: the lion of right ventricular function, and its impact on right ventricular restoration.

OBJECTIVE: To evaluate the structure-function relationships of the right ventricle (RV) and septum and determine if the helical ventricular band model would define fiber orientation for maximal force response. Implications were made for right ventricular function. METHODS: The right ventricular free wall and biventricular septum were studied by inserting sonomicrometer crystals at different angulations to determine the maximum response of fiber shortening. These reactions were compared to the lateral left ventricular (LV) wall and further tested by use of positive and negative inotropic drug infusions. RESULTS: The maximum contraction of the free wall was achieved by placing crystals in the transverse orientation angulations, whereas oblique orientation allowed the maximal septal response. Fiber orientation angulation was the same for the LV free wall and septum. These angulations correlate with the MRI-related twisting actions of septal motion needed for ejection and suction for rapid filling. These findings have important impact, because they imply that the septum is 'lion of right ventricular function,' since septal twisting is essential when pulmonary vascular resistance is increased. The incidence of postoperative right heart failure due to septal dyssyncrony, with loss of septal twisting action from inadequate myocardial protection, is explored relative to RV free wall and septum function. Furthermore, early studies of right ventricular restoration in patients with RV dysplasia and RV failure after chronic pulmonary insufficiency following repair of Tetralogy of Fallot are described, with predominant attention directed toward rebuilding normal septal architecture and function. CONCLUSIONS: This experimental and clinical overview indicates that the septum is 'the lion of right ventricular function,' and implies that the use of this knowledge can become an important guideline for planning novel surgical geometric interventions after RV failure.

Heart Septum↗

Left ventricular function in experimental volume overload hypertrophy.

Left ventricular function in volume overload hypertrophy is controversial. In humans, chronic severe volume overload eventually results in left ventricular dysfunction; paradoxically, experimental volume overload hypertrophy has nearly always been associated with normal left ventricular function. However, in most cases, experimental volume overload hypertrophy has either been mild or only present for a short duration. To help resolve the issue of contractile function in volume overload hypertrophy, we examined ventricular function in a recently described model of severe chronic experimental mitral regurgitation. Left ventricular function was measured before and 3 mo after the creation of severe mitral regurgitation (averaged regurgitant fraction 0.64 +/- 0.04). At 3 mo end-diastolic volume had increased from 78 +/- 5 to 114 +/- 7 ml (P less than 0.01). Significant left ventricular hypertrophy had occurred with an increase in the left ventricular weight-to-body weight ratio from 3.84 +/- 0.2 to 5.22 +/- 0.2 (P less than 0.01). All indicators of left ventricular function (ejection fraction, the end ejection stress-volume relationship, this relationship corrected for eccentric hypertrophy, and mean velocity of circumferential fiber shortening at a common stress) were reduced at 3 mo. Our study produced 64% volume overload which was maintained for 3 mo at which time there was a 36% increase in left ventricular mass. This amount of volume overload of this duration produced significant left ventricular dysfunction.

Animals↗

Nitroglycerin as a nitric oxide donor accelerates lipid peroxidation but preserves ventricular function in a canine model of orthotopic heart transplantation.

BACKGROUND: Nitric oxide has cardioprotective effects through several mechanisms. However, nitric oxide may have deleterious effects in the presence of superoxide because it is converted to peroxynitrite, which then initiates lipid peroxidation. Using a canine model of orthotopic heart transplantation, we examined whether adding an organic nitric oxide donor, nitroglycerin, to preservation solution elicits lipid peroxidation after reperfusion and causes deleterious effects on coronary endothelial function and left ventricular function. METHODS AND RESULTS: The donor heart was preserved for 24 hours in cold University of Wisconsin solution with nitroglycerin (0.1 mg/mL) supplementation (group NTG, n = 8) or in standard University of Wisconsin solution (group C, n = 8). After reperfusion, changes of coronary resistance were measured during the infusion of acetylcholine (0.1 mg/min) and of sodium nitroprusside (1 mg/min), and percent coronary relaxation was calculated. Left ventricular function was evaluated by pressure-volume relations with the use of a conductance catheter, thereby deriving the slopes of end-systolic pressure-volume relation, stroke work-end-diastolic volume relation, and maximum rate of change of left ventricular pressure-end-diastolic volume relation. Serum lipid peroxide level was measured. Percent coronary relaxation was similar for the 2 groups. The slopes of end-systolic pressure-volume relation, stroke work-end-diastolic volume relation, and maximum rate of change of left ventricular pressure-end-diastolic volume relation in group NTG were significantly higher than those in group C. On the other side, serum lipid peroxide level in group NTG was significantly higher than that in group C. CONCLUSIONS: Nitroglycerin may have detrimental effects evidenced by the increase in lipid peroxidation, which implied peroxynitrite formation. However, the overall effect of nitroglycerin was cardioprotective. Although the exact mechanism is yet to be clarified, the superb cardioprotective effect of nitroglycerin overwhelms the exaggeration of lipid peroxidation.

Animals↗

Coronary reserve and right ventricular function in awake newborn lambs with persistent right ventricular hypertension.

Right ventricular function curves as measured by right ventricular stroke work were normal in all control lambs, whereas three of five lambs with banded pulmonary arteries had relatively flat curves. Left ventricular function was similarly normal in the control group as compared to a near zero slope function curve in the banded group. Regional myocardial blood flow to the septum and right and left ventricles was similar in control and banded lambs. At rest right ventricular coronary vascular resistance was lower in the banded than in the control group and decreased in both groups during both isoproterenol and dextran stress states. In general, both groups had a similar ratio of right to left ventricular oxygen supply to demand ratio. These results show first that there is minimal, if any, biventricular functional reserve in lambs with persistent right ventricular hypertension, and second, that there is substantial coronary vascular reserve in both normal and banded groups.

Animals↗

The presence of contractile reserve has no predictive value for the evolution of left ventricular function following atrio-ventricular node ablation in patients with permanent atrial fibrillation.

AIMS: Transcatheter ablation of the atrio-ventricular (AV) node followed by ventricular pacing has been shown to improve symptoms and quality of life (QOL) of patients with permanent atrial fibrillation (AF). In a considerable number of patients, cardiac function deteriorates after AV node ablation. We aimed to determine whether the absence of contractile reserve assessed by low dose dobutamine stress echocardiography (LDDSE) could identify those patients whose left ventricular (LV) function deteriorates after AV node ablation. METHODS: All 25 patients studied had permanent AF for at least 12 months. LVEF was determined 6 days and 3 months after AV node ablation by radionuclide ventriculography (RNV), at a paced rate of 80 beats/min. Deterioration in cardiac function was defined as a decrease in LVEF>5%. LDSE was performed in all patients before and after ablation. The presence of contractile reserve was defined as an improvement in regional function of >or=1 grade at low dose dobutamine in at least 4 segments. QOL measurements were taken using Minnesota, NHBP and MPWB questionnaires. RESULTS: LVEF showed no improvement in the overall group (52.8+/-11.1% vs. 51.8+/-9.8%, p=NS). QOL showed significant improvement in all questionnaires (Minnesota: 4.1+/-2.1 vs. 2.5+/-2, p=0.001; NHBP: 54.8+/-43.3 vs. 34.2+/-34.3, p=0.002; MPWB: 22.2+/-4.6 vs. 19.4+/-6.2, p=0.03). There was no significant difference in change of LVEF between patients with and without contractile reserve (-0.4+/-8.7 vs. 1.6+/-11.3, p=NS). However, patients with a preserved LVEF at baseline showed more frequently a reduced LVEF after AV node ablation (62.2+/-10.4% vs. 47.5+/-7.6%, p=0.001). CONCLUSIONS: (1) The absence of contractile reserve does not predict deterioration of cardiac function after AV node ablation. (2) AV node ablation results in a significant improvement in QOL, which is not necessarily associated with improvement of LVEF. (3) Higher baseline LVEF predicts deterioration of cardiac function. These data suggest that although AV node ablation is an excellent way of controlling symptoms, it should be avoided in patients with normal LV function.

Adult↗

Left ventricular aneurysm as a coronary risk factor independent of overall left ventricular function.

Patients with left ventricular aneurysm (LVA) have been shown to have a higher mortality rate than those with normal left ventricular function. The purpose of this study was to determine whether or not LVA, in patients with coronary artery disease, is a risk factor independent of left ventricular function. Thirty-nine patients with angiographically demonstrated segmental dyskinesis (LVA group) were retrospectively compared to 28 patients with segmental akinesis and ejection fraction less than 60% (control group). There was no significant difference in age, ejection fraction, severity of coronary artery disease, cardiac index, or frequency of cardiac surgery between the two groups. Compared to control subjects, the LVA group had a significantly higher left ventricular end-diastolic pressure and greater tendency to have apical involvement. Although electrocardiography, echocardiography, and radioventriculography were each highly specific, their sensitivities were only 40% to 60%. Follow-up data were available for a mean of 33 months after catheterization. No significant benefit from aneurysmectomy could be demonstrated. There was an insignificant trend in the LVA group toward more severe congestive heart failure and less angina. There was no significant difference in the reinfarction rate, incidence of ventricular tachycardia, or embolism. Mortality rate was 38% in the LVA group and 32% in the control group (p = 0.59). We conclude that LVA is not an independent risk factor for congestive heart failure, angina, ventricular tachycardia, reinfarction, embolism, or death.

Aged↗

Effects of amlodipine on exercise tolerance, quality of life, and left ventricular function in patients with heart failure from left ventricular systolic dysfunction.

BACKGROUND: A preliminary study suggested that the long-acting late-generation calcium-channel blocker amlodipine has favorable effects on exercise tolerance and is safe to use in heart failure, in contrast to earlier generation agents. The goal of 2 multicenter studies was to assess the effect of adjunctive therapy with amlodipine in addition to standard therapy on exercise capacity, quality of life, left ventricular function, and safety parameters in patients with heart failure and left ventricular systolic dysfunction. METHODS: Two large multicenter trials examining the effects of amlodipine on these parameters over a 12-week period of therapy were undertaken in patients with mild to moderate heart failure and left ventricular systolic dysfunction. A total of 437 patients with stable heart failure were studied in a randomized, double-blind, placebo-controlled prospective design. RESULTS: Amlodipine at a dose of 10 mg/day in addition to standard therapy in such patients was associated with no significant difference in change in exercise tolerance on a Naughton protocol compared with placebo in each trial. Among all patients taking amlodipine, exercise time increased 53 +/- 9 (SE) seconds; exercise time for those taking placebo increased 66 +/- 9 seconds (P = not significant). There were no significant differences in changes of quality of life parameters between amlodipine- and placebo-treated patients, and there were no significant differences in symptom scores or New York Heart Association classification between groups. Left ventricular function (measured as ejection fraction) improved 3. 4% +/- 0.5% in amlodipine-treated patients and 1.5% +/- 0.5% in placebo-treated patients (P =.007). There was no statistically significant excess of important adverse events (episodes of worsening heart failure in 10% amlodipine-treated vs 6.3% of placebo-treated patients) or differences in need for changes in background medication between groups. CONCLUSIONS: The addition of 10 mg of amlodipine per day to standard therapy in patients with heart failure is associated with no significant improvement in exercise time compared with placebo therapy over a 12-week period, and there was no increased incidence of adverse events. These data suggest that the addition of amlodipine to standard therapy in heart failure will not result in additional efficacy per se beyond standard therapy.

Aged↗

Assessment of left ventricular function by 201Tl SPECT using left ventricular cavity-to-myocardium count ratio.

Equilibrium radionuclide angiography (ERNA) is the 'gold standard' for assessing left ventricular ejection fraction (LVEF). The aim of the study was to determine whether the left ventricular cavity-to-myocardium count ratio (LVCMR) from 201Tl myocardial single photon emission computed tomography (SPECT) correlated with LVEF assessed by ERNA. The study group included 159 consecutive patients (117 male, 42 female), aged 59+/-12 years, who underwent both 201Tl SPECT and ERNA at rest on the same day. The LVCMR was calculated from a mid-ventricular short axis slice on redistribution studies, using two regions of interest (ROIs). One ROI was placed in the centre of the left ventricular cavity (C) and the other was placed in the myocardium with maximum uptake (Mmax): LVCMR= (C/Mmax) x 100. The correlation between LVCMR and LVEF was r = 0.85 (y = 0.943x+5.002; P < 0.0001). The mean calculated values +/- 1 SD were LVCMR=54+/-16% and LVEF=52+/-15%. In conclusion, LVCMR from 201Tl SPECT studies was closely correlated with LVEF from ERNA studies and can be used to easily and rapidly estimate left ventricular function.

Adolescent↗

Optimization of ventricular function by improving the activation sequence during ventricular pacing.

Abnormal electrical activation occurring during ventricular pacing reduces left ventricular (LV) pump function. Two strategies were compared to optimize LV function using ventricular pacing, minimal asynchrony and optimal sequence of electrical activation. ECG and hemodynamics aortic flowprobe, thermodilution cardiac output, LV pressure and its maximal rates of rise (LVdP/dtpos) and fall (LVdP/dtneg) were measured in anesthetized open-chest dogs (n = 7) with healthy hearts. The QRS duration (a measure of asynchrony of activation) was 47 +/- 5 ms during sinus rhythm and increased to 110 +/- 12 ms during DDD pacing at the right ventricular (RV) apex with a short AV interval. During pacing at the LV apex and LV base, the QRS duration was 8% +/- 7% and 15% +/- 7% (P < 0.05) longer than during RV apex pacing, respectively. Stroke volumes, LVdP/dtpos and LVdP/dtneg, however, were higher during LV apex (15% +/- 16%, 10% +/- 12% [P < 0.05], and 15% +/- 10%, respectively) and LV base pacing (11% +/- 12% [P < 0.05], 3% +/- 12%, and 3% +/- 11%, respectively) than during RV apex pacing. Systolic LV pressure was not influenced significantly by the site of pacing. Biventricular pacing (RV apex together with one or two LV sites) decreased the QRS duration by approximately 20% as compared with RV apex pacing, however, it did not improve stroke volumes, LVdP/dtpos and LVdP/dtneg beyond those during pacing at the LV apex alone. In conclusion, the sequence of electrical activation is a stronger determinant of ventricular function than the synchrony of activation. For optimal LV function the selection of an optimal single pacing site, like the LV apex, is more important than pacing from multiple sites.

Animals↗

[Cardiac function during exercise in patients with coronary bypass surgery assessed by continuous ventricular function monitoring].

The response of left ventricular function during exercise and recovery after exercise was assessed in 52 patients with coronary artery bypass surgery by means of a radionuclide continuous ventricular function monitor. This system consists of 2 radionuclide detectors, recorder and a computer. After the equilibration of 20 mCi technetium 99m-labeled autologaous red blood cells into the intravascular space, the beat by beat radionuclide data were summed for 20-sec intervals to measure left ventricular ejection fraction (EF). Before surgery, the mean EF decreased with exercise from 51 +/- 9% to 45 +/- 11% (p less than 0.001). Cardiac response was divided into 4 types according to the profiles of the EFs during exercise. In 6 patients, EF continued to increase until maximal exercise (type A). In 10 patients, EF initially increased and then decreased in late exercise stages (type B). In 9 patients, EF did not change significantly during exercise (type C). In 27 patients, EF decreased throughout exercise (type D). After surgery, the mean EF increased with exercise from 53 +/- 10% to 60 +/- 13% (p less than 0.001). Thirty-five patients showed type A, 9 type B, 5 type C, and 3 type D. Two type D and 5 type B patients had occluded grafts or ungrafted coronary arteries. Four patients with complete revascularization including an internal thoracic artery and saphenous vein grafts showed type B. Three patients with extensive infarction and poor left ventricular function showed type C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The angiotensin infusion test as a method of evaluating left ventricular function.

Fifteen patients had left ventricular function measured by the angiotensin infusion method. Seven patients had no evidence of heart disease, and eight patients had angina pectoris and coronary arteriographic evidence of coronary disease without congestive heart failure. During angiotensin infusion, those patients without heart disease had a decrease in cardiac index (average, 0.63 L. per minute per square meter) and a decrease in heart rate (average, 12 beats per minute.) The ventricular function curve had a poor SWI response in four of the seven subjects. The patients with coronary artery disease also had a reduction in cardiac index during angiotensin (average, 0.44 L. per minute per square meter) and the heart rate was unchanged in four subjects, increased in two subjects, and decreased in two subjects. Six of the subjects had flat or descending slopes on the function curve, and in one subject there was only a very gradual ascending slope. Many of the curves of both groups looked similar so that the function curves did not differentiate between those patients with or without heart disease. The mechanism for production of bradycardia, reduction of cardiac output, and depressed function curves with angiotensin is multifactorial, but is probably due to the baroreceptor reflex response, the increase in coronary artery resistance, and possible to the direct effect of increased left ventricular afterload itself. The ventricular response to angiotensin is so variable that the angiotensin infusion method of evaluating ventricular function is not reliable.

Adolescent↗

Left ventricular function during strength testing and resistance exercise in patients with left ventricular dysfunction.

PURPOSE: Deterioration in left ventricular function is a more sensitive marker of myocardial ischemia during exercise than ST segment depression. The current study was designed to evaluate left ventricular function during one-repetition-maximum (1-RM) strength testing and resistance exercise in cardiac patients with moderate left ventricular dysfunction. METHODS: Using echocardiographic methods, left ventricular function was evaluated in 15 patients with left ventricular dysfunction (age, 65 +/- 6.5 years; ejection fraction, 42.1 +/- 5.8). Measurements were performed during 1-RM testing and resistance exercise (20%, 40%, and 60% of 1-RM using 10 to 15 repetitions) on the one-arm biceps curl (BIC) and bilateral knee extension exercises and compared with measurements of left ventricular function during the symptom-limited graded exercise test (SL-GXT). RESULTS: During the knee extension exercise, there was a slight but significant reduction (P< or =.05) in ejection fraction values at the end of 60% 1-RM, as compared with rest and previous workloads. Significant increases in systolic blood pressure and left ventricular end-systolic volume ratio values (P< or =.05) from rest to exercise were observed across test modes and for all workloads. The prevalence of new wall motion abnormalities during knee extension and BIC 1-RM strength testing was comparable with that observed during SL-GXT. The greatest increase in new wall motion abnormalities was seen during 60% 1-RM of knee extension exercise, as compared with prior workloads, BIC exercises, and SL-GXT. CONCLUSIONS: Despite an increase in occurrence of ischemic changes during the highest resistance exercise workloads and with larger muscle mass, the findings are small in magnitude and do not suggest reduced cardiac performance.

Aged↗

Effects of intrapleural pressure changes on canine left ventricular function.

Left ventricular diameter, pressure, and dP/dt, as well as aortic and intrapleural pressures, were recorded simultaneously from 10 acute anethetized mongrel dogs. Normal inspiration produced a significant decrease in end-diastolic diameter (46.9 +/- 1.2 to 43.1 +/- 1.0 mm) and end-systolic diameter (35.5 +/- 1.4 to 34.2 +/- 1.7 mm), reducing stroke diameter 2.5 mm. Airway occlusion (greater than or equal to 60%) produced a reduction in the decrease of end-diastolic diameter seen with normal inspiration and, to a lesser degree, in end-systolic diameter. Because only acute airway occlusion greater than or equal to 80% produced a significant increase in left ventricular afterload, the authors conclude that normal spontaneous inspiration results in a decrease in left ventricular preload due to pooling of blood in the pulmonary vasculature. The data suggest that this decrease in left ventricular preload is the predominant mechanism responsible for the inspiratory decrease in left ventricular stroke volume.

Airway Obstruction↗

Effect of sodium bicarbonate on canine left ventricular function.

Left ventricular performance was evaluated in seven canine right heart bypass preparations during and after the intraauricular administration of sodium bicarbonate (100 ml, 1100 Osm, 60 mEq). Under conditions of constant cardiac input and left ventricular volume, sodium bicarbonate produced mild and brief left ventricular depression, as manifested by a decline of left ventricular dp/dt with simultaneous rise of left ventricular end-diastrolic and left atrial pressures. These findings occurred as aortic impedance fell. Identical results accrued in paced and unpaced preparations. The data lends credence to the proposition that a sudden rise in blood pCO2 produces increased transport of CO2 across the cardiac membranes with intracellular acidosis. However, the data is also compatible with hyperosmolality induced contractile depression. Possible clinical implications are discussed.

Animals↗

Right ventricular function: methodologic and clinical considerations in noninvasive scintigraphic assessment.

Right ventricular function plays an important role in many cardiac disorders. Changes in left ventricular function, right ventricular afterload and preload, cardiac medications and ischemia may affect right ventricular function. Radionuclide ventriculography permits quantitative assessment of regional and global function of the right ventricle. This assessment can be made at rest, during exercise or after pharmacologic interventions. The overlap between right ventricle and right atrium is a major limitation for gated scintigraphic techniques. The use of imaging with newer short-lived radionuclides may permit more accurate and reproducible assessment of right ventricular function by means of the first pass method. Further work in areas related to improvement of techniques and the impact of right ventricular function on prognosis is needed.

Animals↗