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The clinical role of radionuclide imaging in cardiac transplantation.

Cardiac transplantation is developing into a routine therapy with widespread availability. Nuclear medicine studies play an important role in evaluating potential transplant recipients and in providing documentation of the severity of ventricular dysfunction and the presence of ischemic but viable myocardium. Nuclear cardiology has increased our knowledge of the physiology of cardiac transplants and is now playing an increasing adjunctive role in management. Radionuclide ventriculography performed early after transplantation can identify patients both with abnormal biventricular function resulting from preservation injury and with isolated right ventricular dysfunction. It also provides important functional data that complements the cardiac biopsy in allograft rejection. New techniques such as 111In antimyosin antibodies and 111In lymphocytes have potential value for the accurate, noninvasive diagnosis of rejection. PET promises to improve the ability to diagnose coronary atherosclerosis of the allograft.

Coronary Disease↗

Characterization of right ventricular function after monocrotaline-induced pulmonary hypertension in the intact rat.

We characterized hemodynamics and systolic and diastolic right ventricular (RV) function in relation to structural changes in the rat model of monocrotaline (MCT)-induced pulmonary hypertension. Rats were treated with MCT at 30 mg/kg body wt (MCT30, n = 15) and 80 mg/kg body wt (MCT80, n = 16) to induce compensated RV hypertrophy and RV failure, respectively. Saline-treated rats served as control (Cont, n = 13). After 4 wk, a pressure-conductance catheter was introduced into the RV to assess pressure-volume relations. Subsequently, rats were killed, hearts and lungs were rapidly dissected, and RV, left ventricle (LV), and interventricular septum (IVS) were weighed and analyzed histochemically. RV-to-(LV + IVS) weight ratio was 0.29 +/- 0.05 in Cont, 0.35 +/- 0.05 in MCT30, and 0.49 +/- 0.10 in MCT80 (P < 0.001 vs. Cont and MCT30) rats, confirming MCT-induced RV hypertrophy. RV ejection fraction was 49 +/- 6% in Cont, 40 +/- 12% in MCT30 (P < 0.05 vs. Cont), and 26 +/- 6% in MCT80 (P < 0.05 vs. Cont and MCT30) rats. In MCT30 rats, cardiac output was maintained, but RV volumes and filling pressures were significantly increased compared with Cont (all P < 0.05), indicating RV remodeling. In MCT80 rats, RV systolic pressure, volumes, and peak wall stress were further increased, and cardiac output was significantly decreased (all P < 0.05). However, RV end-systolic and end-diastolic stiffness were unchanged, consistent with the absence of interstitial fibrosis. MCT-induced pressure overload was associated with a dose-dependent development of RV hypertrophy. The most pronounced response to MCT was an overload-dependent increase of RV end-systolic and end-diastolic volumes, even under nonfailing conditions.

Animals↗

Improvement of ventricular function after atrioventricular junction ablation in a patient with atrial flutter after Mustard's operation.

Arrhythmias are common problems following Mustard's operation for D-transposition of the great arteries. A 19-year-old male is presented who was diagnosed at birth with D-transposition of the great arteries and a right aortic arch and underwent a Mustard procedure at 12 months of age. He developed sinus node dysfunction and atrial flutter unresponsive to antiarrhythmic drugs and dual chamber pacing. Following complete heart block with radiofrequency catheter ablation of the atrioventricular junction, the patient's heart was paced in VVIR mode. Ventricular function improved after the ablation and persisted in two years' follow-up.

Adult↗

[Septal rupture repaired in the acute stage of myocardial infarction. Clinical, hemodynamic and angio-coronarography findings in the evaluation of surgical risk].

Between 1977 and 1987, 27 consecutive patients (16 men, 11 women, mean age 66 years, range 54 to 75 years) with ventricular septal rupture complicating acute myocardial infarction underwent surgical repair. The purpose of this retrospective study was to analyse the post-operative mortality factors from clinical, haemodynamic and operative data in all patients and also from coronary angiographic data in 23/27 patients whose haemodynamic status allowed this type of exploration. Seventeen patients (63 p. 100) died during the first post-operative month, 10 survived and were discharged. Factors that influenced the prognosis were: (1) inferiorly-located necrosis associated with a 75 p. 100 mortality rate (9 out of 12 patients), as opposed to 53 p. 100 (8 out of 15 patients) with anterior necrosis; (2) right ventricular dysfunction, observed in 83 p. 100 of patients with inferior necrosis and 53 p. 100 with anterior necrosis, which was responsible for 7 out of 9 deaths in the inferior necrosis subgroup and contributed to 3 out of 8 deaths in the anterior necrosis subgroup; this established a cause-effect relationship between right ventricular function and the overmortality of patients with inferior necrosis; (3) independently of the haemodynamic status, two- and three-vessel lesions (56 p. 100 of all lesions) which had an 84 p. 100 mortality rate as opposed to 40 p. 100 with one-vessel lesions; (4) the presence of a state of shock which was associated with a 78 p. 100 mortality rate as opposed to 55 p. 100 in patients without shock. We conclude that when permitted by the patient's haemodynamic status coronary angiography should be part of the pre-operative evaluation to assess the operative risk and guide the surgical procedure.

Acute Disease↗

Arterial switch operation after left ventricular retraining in the adult.

Retraining the morphological left ventricle in transposition of the great arteries has been successfully reported in infancy, while older age seems to be a contraindication. A 23-year-old woman with ¿S,D,D¿ transposition of the great arteries and ventricular septal defect developed severe right systemic ventricular dysfunction 22 years after Mustard procedure and ventricular septal defect closure. Hemodynamic investigation revealed moderate pulmonary hypertension and preserved left ventricular function. A pulmonary artery band was applied to obtain a left-right ventricular pressure ratio of 0.91. Her postoperative course was characterized by biventricular failure, treated effectively with inotropic support. Six months later, she underwent a Mustard baffle takedown and arterial switch procedure. Her postoperative course was uneventful. She was discharged home on postoperative day 15. At 24-months follow-up, she is in excellent clinical condition; echocardiographic evaluation shows good left ventricular function (ejection fraction: 0.69) with left ventricular volume within normal limits (70 ml/m2). Our experience demonstrates that, despite adult age, a staged arterial switch operation can be performed successfully in selected patients when left ventricular function is preserved.

Adult↗

Right ventricular expression of extracellular matrix proteins, matrix-metalloproteinases, and their inhibitors over a period of 3 years after heart transplantation.

Fibrillar collagens I and III, nonfibrillar collagen IV, and the glycoproteins fibronectin and laminin, are elements of the myocardial extracellular matrix (ECM). Alterations in the normal concentrations and ratios of these elements may reflect remodeling in response to physiologic stress. In the case of patients' post-heart transplantation (HTx), specific patterns of alteration may herald myocardial dysfunction. Right ventricular biopsies were taken from the same 28 HTx patients before implantation and 1 week, 2 weeks, and 1, 2, and 3 years after HTx. The above-noted five ECM proteins, six matrix metalloproteinases (MMPs) and two of their tissue inhibitors (TIMPs) were detected by immunohistochemistry and scored as cells per square millimeter or semiquantitatively. The total connective tissue fibers were detected by connective tissue stain and morphometry. Variations in these ECM components were followed in the same patient cohort over 3 years. In summary, during the first 2 weeks after HTx, a predominant increase in connective tissue occurred. Increases in MMP-8 and MMP-9 were found. By 3 years after transplantation, there was a decrease of connective tissue fibers and a significant reduction of all ECM components and an increase in MMPs and TIMPs. These findings may reflect a pattern of remodeling specific to the transplanted heart.

Adolescent↗

[Right ventricular function: physiological and physiopathological features].

Sinus and conus constitute the two cavities of the right ventricle. They are anatomically and functionally different. The sinus is a flow-generator and the conus a pressure-regulator. The coronary circulation of the right ventricle is provided by the right coronary artery and the left anterior descending artery. The right ventricle is perfused during systole and diastole. When oxygen demand increases, coronary arteries dilate and oxygen extraction rises. As for the left ventricle, right ventricular performance depends upon heart rate, rhythm, contractility and loading conditions. Ventricular interactions are very important for right ventricular function. Loading conditions and contractility of the left ventricle are of major significance for right ventricular performance. For the right ventricle, the end of the ejection is different from the end of the active contraction. The time between them allows to achieve ventricular emptying. This duration is linked to afterload. Presently, it is impossible to accurately and simply assess these conditions. Pressure and volume overloadings result in right ventricular failure. They are responsible for ventricular dilation and ischaemia with a decrease in cardiac output, generating a vicious circle. Treatment includes the removal of the cause, and the maintenance of systemic arterial pressure and biventricular contractility. It is difficult to assess the effects of intravenous vasodilators on right ventricular afterload.

Coronary Circulation↗

Instructive ECG series in massive bilateral pulmonary embolism.

The ECG is abnormal in over 70% of patients with pulmonary embolism. Certain ECG abnormalities have been observed to return to normal after treatment. This case report describes an instructive ECG series in a patient with massive bilateral pulmonary embolism as shown by spiral computed tomography. The initial ECG showed sinus tachycardia with P pulmonale, although atrial tachycardia could not definitively be excluded. The patient had an increased troponin I concentration and echocardiographic evidence of right ventricular dysfunction and underwent thrombolysis with alteplase and anticoagulation with warfarin. P wave amplitude gradually decreased throughout admission and her tachycardia resolved. This may reflect a reduction in right atrial strain after treatment. This phenomenon has apparently not been described in this setting. The significance of ECG changes and the role of thrombolysis in pulmonary embolism are briefly discussed.

Anticoagulants↗

Significance of inducible nitric oxide synthase in acute myocarditis caused by Trypanosoma cruzi (Tulahuen strain).

Chagas' disease, caused by Trypanosoma cruzi, is associated with myocarditis and expression of myocardial cytokines and inducible nitric oxide synthase (NOS2). To assess the functional significance of NOS2 in murine Chagas' disease, we infected NOS2 knockout (NOS2(-/-)) and C57BL/6x129sv (wild type) mice with the Tulahuen strain of T. cruzi. Serial transthoracic echocardiography was performed to assess the progression of left and right ventricular dysfunction in infected mice. Uninfected wild type and NOS2(-/-) mice served as controls. At day 10 post-infection (p.i.), infected wild type mice had larger left ventricular end-diastolic diameter (2.52+/-0.14-vs-2.11+/-0.06 mm, P<0.02) and right ventricle (0.6+/-0.2-vs-0 visual grade, P<0.02) as compared with uninfected wild type mice. At day 19 p.i., compared with uninfected controls, infected wild type mice had larger left ventricular end-diastolic diameter (3.30+/-0.29-vs-2.11+/-0.07 mm), left ventricular end-systolic diameter (1.86+/-0.29-vs-0.88+/-0.05 mm), right ventricle (1.6+/-0.2-vs-0 visual grade), lower heart rate (413+/-27-vs-557+/-25 beats per min), left ventricular relative wall thickness (0.44+/-0.05-vs-0.64+/-0.03) and fractional shortening (45+/-4-vs-57+/-2%) [P<0.05 for all]. In contrast, no differences in left ventricular end-diastolic diameter or fractional shortening were noted among infected and uninfected NOS2(-/-) mice at day 19 p.i. Compared with uninfected controls, infected NOS2(-/-) mice had significantly lower heart rate (272+/-23-vs-512+/-31 beats per min, P<0.01) and larger right ventricle (0.6+/-0.2-vs-0, P<0.05 visual grade). The magnitude of right ventricular dilation in NOS2(-/-) mice was less than that observed in infected wild type mice. At necropsy, the heart weight was greater (129+/-16-vs-109+/-7 mg, P=0.02) and myocardial inflammation more severe in infected wild type compared with infected NOS2(-/-) mice. Myocardial interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha, and interferon-gamma were induced in all infected mice. These data indicate that nitric oxide derived from NOS2 plays an important role in the development and progression of ventricular dilation and systolic dysfunction in acute murine chagasic myocarditis caused by infection with the Tulahuen strain.

Animals↗

Alterations in angiotensin II receptor mediated signal transduction shortly after coronary artery constriction in the rat.

OBJECTIVE: The aim of the study was to determine the effect of coronary artery constriction on the density of angiotensin II receptors and on the effector responses coupled with these receptors on myocytes one week after surgical induction of coronary artery stenosis in rats. METHODS: After induction of coronary artery stenosis and following the estimation of global cardiac performance, myocytes were enzymatically dissociated and radioligand binding studies were performed. In addition, the isotonic contractile performance, cytosolic calcium transients, and angiotensin II stimulated inositol phosphate generation in myocytes were measured in the presence and absence of the angiotensin II receptor subtype antagonist losartan. RESULTS: After documenting left ventricular failure and right ventricular dysfunction, the expression and density of angiotensin II receptors in left ventricular myocytes were evaluated and found to be increased 3.1-fold and 4.1-fold, respectively. Corresponding increases in right ventricular myocytes were 3.6-fold and 4.5-fold. In contrast, the quantity of the regulatory protein Gq alpha was not altered in either ventricle. Angiotensin II did not increase the generation of total inositol phosphates in left and right ventricular myocytes at maximum stimulation. However, the threshold for the formation of inositol phosphates was lowered in left ventricular myocytes of coronary narrowed rats. Measurements of single cell mechanics indicated that angiotensin II stimulation markedly improved the depression in myocyte function biventricularly. This inotropic effect was coupled with the restoration of cytosolic calcium. CONCLUSIONS: The upregulation of angiotensin II receptors on myocytes in this model of global ischaemia may be a compensatory mechanism ameliorating myocyte contractility in an attempt to sustain ventricular pump function.

Angiotensin II↗

Dilated right ventricular cardiomyopathy: Uhl's disease.

Uhl's disease is a rare disorder originally described in 1952 in an infant with severe diffuse right ventricular dysfunction with total absence of the myocardium. Uhl considered the disease to be congenital in origin. We report a patient with severe dilated congestive cardiomyopathy limited to the right ventricle but apparently developing in adulthood.

Adult↗

Assessment of the right ventricle with radionuclide techniques.

The right ventricle has a prominent role in determining overall cardiac function. Thus an accurate measurement of right ventricular (RV) function is important. Radionuclide angiography has advanced our ability to measure RV function. In this way, it has furthered our understanding of the pathophysiology of disease states involving the right ventricle. This article reviews the current methods of measuring RV function by radionuclide angiography. The physiology of normal RV function is discussed. Then several common disease states in which RV dysfunction is prominent are addressed.

Animals↗

Prinzmetal's angina, normal coronary arteries and pericarditis.

A woman with Prinzmetal's variant angina had spontaneous attacks of myocardial ischemia characterized by severe chest pain, hypotension, inferior ST-segment elevation, transient complete heart block and selective right ventricular dysfunction. Despite initial improvement following intravenous administration of atropine and sublingual administration of nitroglycerin she died of cardiogenic shock. Autopsy showed normal coronary arteries and acute pericarditis, more pronounced over the right side of the heart. It is postulated that the pericardial inflammation elicited severe spasm of the subjacent right coronary artery.

Aged↗

Postcardiopulmonary bypass lung edema. A preventable complication?

Potential etiologic factors of postcardiopulmonary bypass (post-CPB) lung edema (LE) were investigated (phase 1 study). Further patient treatment was modified according to the results of phase 1 study and the influence that these changes had on the incidence of the complication was assessed (phase 2 study). In phase 1 study, among 100 patients who underwent coronary bypass graft surgery, prolonged assisted ventilation was required for severe LE in 7 cases, and 6 patients had a moderate form of LE. Patients who suffered from severe LE had left and right ventricular dysfunction and normal pulmonary vascular resistance. Three predictors of LE were evidenced by logistic regression analysis: number of bypass grafts completed with internal mammary arteries (p = 0.013), transfusions of blood collected in mobile units (p = 0.014), and the combination of a significant lesion of the left main stem and the right coronary artery at preoperative angiography (p = 0.040). In phase 2 study, a further group of 100 patients was treated differently by improving myocardial protection during surgery, achieving a higher rectal temperature at the end of CPB, and reducing the amount of transfusions. This resulted in only one case of LE (p < 0.001). In conclusion, the cases of post-CPB LE evidenced in our study were related to postoperative ventricular dysfunction and blood transfusions. Any means of improving postoperative hemodynamic stability and reducing the need for transfusions could thus prevent the latter complication.

Blood Transfusion↗

Acute right ventricular failure is caused by inadequate right ventricular hypothermia.

The hypothesis of this study was that inadequate right ventricular hypothermia contributes to the right ventricular dysfunction occasionally observed after cardiac operations. Dogs were placed on cardiopulmonary bypass, and 60 minute periods of hypothermic myocardial ischemia were imposed. Left ventricular temperature was always maintained at 15 degrees C and right ventricular temperatures were maintained at 15 degrees C (Group I, n = 8), 25 degrees C (Group II, n = 8), and 35 degrees C (Group III, n = 8). These temperatures were produced by infusion of hypothermic crystalloid cardioplegic solution and appropriate topical cooling and heating of the left and right ventricles, respectively. Multiple indices of ventricular function were obtained 15, 30, 45, and 60 minutes after bypass and compared to prebypass control values. In all Group I animals (left ventricular temperature = 15 degrees C, right ventricular temperature = 15 degrees C), postischemic indices of right ventricular function were not different from control values (p = NS). In Group II (left ventricular temperature = 15 degrees C, right ventricular temperature = 25 degrees C), two animals died 30 and 45 minutes after bypass, respectively, of right ventricular failure. In the other six animals in Group II, all indices of right ventricular function were significantly reduced (p less than 0.05) except for right ventricular systolic pressure. In Group III (left ventricular temperature = 15 degrees C, right ventricular temperature = 35 degrees C), two animals could not be weaned from cardiopulmonary bypass because of right ventricular akinesia. Six animals were weaned from bypass, but two died 15 minutes, one died 30 minutes, and one 45 minutes after bypass. Two animals lived 60 minutes, but all indices of right ventricular function were decreased. Failure to maintain right ventricular temperatures below 25 degrees C during 1 hour of cardiac ischemia in the dog can result in fatal right ventricular failure.

Animals↗