Loss Of Left Ventricular Mass Research Articles

Cardiac Magnetic Resonance Studies in a Large Animal Model That Simulates the Cardiac Abnormalities of Human Septic Shock.

Septic shock is associated with increases in end-diastolic volume (EDV) and decreases in ejection fraction that reverse within 10 days. Nonsurvivors do not develop EDV increases. The mechanism is unknown. Purpose-bred beagles (n=33) were randomized to receive intrabronchial Staphylococcus aureus or saline. Over 96 hours, cardiac magnetic resonance imaging and echocardiograms were performed. Tissue was obtained at 66 hours. From 0 to 96 hours after bacterial challenge, septic animals versus controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%). On histology, the major finding was nonocclusive microvascular injury with edema in myocytes, the interstitium, and endothelial cells. Edema was associated with significant worsening of biventricular ejection fractions, ventricular-arterial coupling, and circumferential strain. Early during sepsis, (0-24 hours), the EDV decreased; significantly more in nonsurvivors (ie, greater diastolic dysfunction). From 24 to 48 hours, septic animals' biventricular chamber sizes increased; in survivors significantly greater than baseline and nonsurvivors, whose EDVs were not different from baseline. Preload, afterload, or heart rate differences did not explain these differential changes. The cardiac dysfunction of sepsis is associated with wall edema. In nonsurvivors, at 0 to 24 hours, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part, explain the EDV increases from 24 to 48 hours because of a potentially reparative process removing damaged wall tissue. Septic cardiomyopathy is most consistent with a nonocclusive microvascular injury resulting in edema causing reversible systolic and diastolic dysfunction with more severe diastolic dysfunction being associated with a decreased EDV and death.

Cardiac Magnetic Resonance Studies in a Large Animal Model that Simulates the Cardiac Abnormalities of Human Septic Shock.

Septic shock, in humans and in our well-established animal model, is associated with increases in biventricular end diastolic volume (EDV) and decreases in ejection fraction (EF). These abnormalities occur over 2 days and reverse within 10 days. Septic non-survivors do not develop an increase in EDV. The mechanism for this cardiac dysfunction and EDV differences is unknown. Purpose-bred beagles randomized to receive intrabronchial Staphylococcus aureus (n=27) or saline (n=6) were provided standard ICU care including sedation, mechanical ventilation, and fluid resuscitation to a pulmonary arterial occlusion pressure of over 10mmHg. No catecholamines were administered. Over 96h, cardiac magnetic resonance imaging, echocardiograms, and invasive hemodynamics were serially performed, and laboratory data was collected. Tissue was obtained at 66h from six septic animals. From 0-96h after bacterial challenge, septic animals vs. controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%) which was more pronounced at 48h in non-survivors than survivors. On histology, edema was located predominantly in myocytes, the interstitium, and endothelial cells. Edema was associated with significantly worse biventricular function (lower EFs), ventricular-arterial coupling, and circumferential strain. In septic animals, from 0-24h, the EDV decreased from baseline and, despite cardiac filling pressures being similar, decreased significantly more in non-survivors. From 24-48h, all septic animals had increases in biventricular chamber sizes. Survivors biventricular EDVs were significantly greater than baseline and in non-survivors, where biventricular EDVs were not different from baseline. Preload, afterload, or HR differences did not explain these differential serial changes in chamber size. Systolic and diastolic cardiac dysfunction during sepsis is associated with ventricular wall edema. Rather than differences in preload, afterload, or heart rate, structural alterations to the ventricular wall best account for the volume changes associated with outcome during sepsis. In non-survivors, from 0-24h, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part explain, the EDV increases from 24-48h. However, these changes continued and even accelerated into the recovery phase consistent with a reparative process rather than ongoing injury.

Rapid atrophy of cardiac left ventricular mass in patients with non-small cell carcinoma of the lung.

BackgroundCancer is a systemic catabolic condition affecting skeletal muscle and fat. We aimed to determine whether cardiac atrophy occurs in this condition and assess its association with cardiac function, symptoms, and clinical outcomes.MethodsTreatment naïve metastatic non‐small cell lung cancer patients (n = 50) were assessed prior to and 4 months after commencement of carboplatin‐based palliative chemotherapy. Methods included echocardiography for left ventricular mass (LVM) and LV function [LV ejection fraction, global longitudinal strain (GLS), diastolic function], computed tomography to quantify skeletal muscle and total adipose tissue, Eastern Cooperative Oncology Group Performance Status (ECOG‐PS), validated questionnaires for dyspnoea and fatigue, plasma biomarkers, tumour response to therapy, and overall survival.ResultsDuring 112 ± 6 days, the median change in LVM was −8.9% [95% confidence interval (95% CI) −10.8 to −4.8, P < 0.001]. Quartiles of LVM loss were −20.1%, −12.9%, −4.8%, and +5.5%. Losses of muscle, adipose tissue, and LVM were frequently concurrent; LVM loss > median value was associated with loss of skeletal muscle [odds ratio (OR) = 4.5, 95% CI: 1.4–14.8, P=0.01] and loss of total adipose tissue (OR = 10.0, 95% CI: 2.7–36.7, P < 0.001). LVM loss was associated with decreased GLS (OR = 6.6, 95% CI: 1.9–22.7, P=0.003) but not with LV ejection fraction or diastolic function. In the population overall, plasma levels of C‐reactive protein (P=0.008), high sensitivity troponin T (hs‐TnT) (P=0.03), and galectin‐3 (P=0.02) increased over time, while N‐terminal pro B‐type natriuretic peptide and hs‐cTnI did not change over time. C‐reactive protein was the only biomarker associated with LVM loss but at the univariate level only. Independent predictors of LVM loss were prior weight loss (adjusted OR = 10.2, 95% CI: 2.2–46.9, P=0.003) and tumour progression (adjusted OR = 14.6, 95% CI: 1.4–153.9, P=0.02). LVM loss was associated with exacerbations of fatigue (OR = 6.6, 95% CI: 1.9–22.7, P=0.003), dyspnoea (OR = 9.3, 95% CI: 2.4–35.8, P<0.001), and deterioration of performance status (OR = 4.8, 95% CI: 1.3–18.3,P=0.02). Patients with concurrent loss of LVM, skeletal muscle, and fat were more likely to deteriorate in all three symptom domains and to have reduced survival (P=0.05).ConclusionsIntense LVM atrophy is associated with non‐small cell lung cancer‐induced cachexia. Loss of LVM was associated with emerging alterations of GLS, indicating subtle changes in left ventricular function. Longer term studies are needed to assess the full scope of cardiac atrophy and its impact. LVM atrophy arises in conjunction with losses of fat and skeletal muscle and is temporally associated with meaningful declines in performance status, worsening of fatigue, and dyspnoea, as well as poorer tumour response and decreased survival. The specific contribution of LVM atrophy to these outcomes requires further study.

Myocardial CKIP-1 Overexpression Protects from Simulated Microgravity-Induced Cardiac Remodeling.

Human cardiovascular system has adapted to Earth's gravity of 1G. The microgravity during space flight can induce cardiac remodeling and decline of cardiac function. At present, the mechanism of cardiac remodeling induced by microgravity remains to be disclosed. Casein kinase-2 interacting protein-1 (CKIP-1) is an important inhibitor of pressure-overload induced cardiac remodeling by decreasing the phosphorylation level of HDAC4. However, the role of CKIP-1 in the cardiac remodeling induced by microgravity is unknown. The purpose of this study was to determine whether CKIP-1 was also involved in the regulation of cardiac remodeling induced by microgravity. We first detected the expression of CKIP-1 in the heart from mice and monkey after simulated microgravity using Q-PCR and western blotting. Then, myocardial specific CKIP-1 transgenic (TG) and wild type mice were hindlimb-suspended (HU) to simulate microgravity effect. We estimated the cardiac remodeling in morphology and function by histological analysis and echocardiography. Finally, we detected the phosphorylation of AMPK, ERK1/2, and HDAC4 in the heart from wild type and CKIP-1 transgenic mice after HU. The results revealed the reduced expression of CKIP-1 in the heart both from mice and monkey after simulated microgravity. Myocardial CKIP-1 overexpression protected from simulated microgravity-induced decline of cardiac function and loss of left ventricular mass. Histological analysis demonstrated CKIP-1 TG inhibited the decreases in the size of individual cardiomyocytes of mice after hindlimb unloading. CKIP-1 TG can inhibit the activation of HDAC4 and ERK1/2 and the inactivation of AMPK in heart of mice induced by simulated microgravity. These results demonstrated CKIP-1 was a suppressor of cardiac remodeling induced by simulated microgravity.

Pay attention to cardiac remodeling in cancer cachexia.

Cancer cachexia is a complex and multifaceted disease state characterized by fatigue, weakness, and loss of skeletal muscle and adipose tissue. Recently, the profound negative effects of cancer cachexia on cardiac tissue draw much attention, which is likely to contribute to mortality in tumor-bearing animals. The mechanism of cardiac remodeling is not so clear and involved with a series of molecular alterations. In cancer cachexia model, progressive loss of left ventricular mass and decrease in myocardial function is observed and cardiac autonomic functions are altered. Levels of several emerging cardiovascular neurohormones are found elevating in patients with cancer, but it is still controversial whether the changes could reflect the heart injury accurately. The remedy for cardiac remodeling has been explored. It is showed that exercise can modulate signaling pathways activated by wasting cytokines and impact on the resulting outcomes on heart adaptation. Some drugs, such as bisoprolol, spironolactone, perindopril, tandospirone, and simvastatin, can mitigate adverse effects of the tumor on the heart and prolong survival.

Oral Coenzyme Q10 Supplementation Does Not Prevent Cardiac Alterations During a High Altitude Trek to Everest Base Camp

Exposure to high altitude is associated with sustained, but reversible, changes in cardiac mass, diastolic function, and high-energy phosphate metabolism. Whilst the underlying mechanisms remain elusive, tissue hypoxia increases generation of reactive oxygen species (ROS), which can stabilize hypoxia-inducible factor (HIF) transcription factors, bringing about transcriptional changes that suppress oxidative phosphorylation and activate autophagy. We therefore investigated whether oral supplementation with an antioxidant, Coenzyme Q10, prevented the cardiac perturbations associated with altitude exposure. Twenty-three volunteers (10 male, 13 female, 46±3 years) were recruited from the 2009 Caudwell Xtreme Everest Research Treks and studied before, and within 48 h of return from, a 17-day trek to Everest Base Camp, with subjects receiving either no intervention (controls) or 300 mg Coenzyme Q10 per day throughout altitude exposure. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac morphology and function. Following altitude exposure, body mass fell by 3 kg in all subjects (p<0.001), associated with a loss of body fat and a fall in BMI. Post-trek, left ventricular mass had decreased by 11% in controls (p<0.05) and by 16% in Coenzyme Q10-treated subjects (p<0.001), whereas mitral inflow E/A had decreased by 18% in controls (p<0.05) and by 21% in Coenzyme Q10-treated subjects (p<0.05). Coenzyme Q10 supplementation did not, therefore, prevent the loss of left ventricular mass or change in diastolic function that occurred following a trek to Everest Base Camp.

Cardiovascular and urological dysfunction in spinal cord injury

A spinal cord injury (SCI) above the sixth thoracic vertebra interrupts the supraspinal control of the sympathetic nervous system causing an imbalance between the sympathetic and the parasympathetic nervous system. This article focuses on the symptoms, treatment and examination of autonomic disturbances of the cardiovascular and the urinary system after a SCI. A non-systematic literature search in the PubMed database. Frequent complications in the acute phase of cervical and high thoracic SCI are bradyarrhythmias, hypotension, hypothermia/hyperthermia, increased neurogenic shock, vagovagal reflex, supraventricular/ventricular ectopic beats, vasodilatation and congestion. Serious complications in the chronic phase of SCI are orthostatic hypotension, impaired cardiovascular reflexes, autonomic dysreflexia (AD), reduced sensation of cardiac pain, loss of reflex cardiac acceleration, quadriplegic cardiac atrophy due to loss of left ventricular mass and pseudo-myocardial infarction. AD is associated with a sudden, uncontrolled sympathetic response, triggered by stimuli below the injury. It may cause mild symptoms like skin rash or slight headache, but also severe hypertension, cerebral haemorrhage and death. Early recognition and prompt treatment are important. Urinary autonomic dysfunctions include hyperreflexia or areflexia of detrusor and/or sphincter of the bladder. Patients with SCI have a high risk of cardiovascular complications, AD and urinary autonomic dysfunction both in the acute phase and later, affecting their prognosis and quality of life. Knowledge of cardiovascular and urological complications after SCI is important for proper diagnosis and treatment.

A study of presbycardia, with gender differences favoring ageing women

Background The impact of ageing on the human cardiovascular system has been the subject of several studies in recent years, but with insufficient emphasis on defining sex-specific differences. To rectify this, gender-specific differences in structure and function in the human cardiovascular system were studied in a European population during natural ageing. Methods Cardiac power output (CPO) was measured and integrated with changes in left ventricular (LV) mass, diastolic, systolic and limb blood flow, blood pressure and exercise capacity in 93 health-screened men and 122 women, aged 20 to 75 years. Results Correlating with a 21% loss of LV mass, maximum cardiac pumping (i.e. CPO max = Q̇ max x MAP max) and reserve (CR = CPO max − CPO rest) capacities decreased 20–25% with age in male hearts. In contrast, CPO max, CR and LV mass were all preserved in ageing women. Maximum cardiac output (Q̇ max; 26–32%), peak forearm blood flow (FBF peak; 61%) and exercise capacity (40–50%) all decreased, but more so in men than women. In contrast, systemic vascular resistance (68–75%) and mean arterial pressure (MAP max; 14–26%) increased in both sexes. CPO rest decreased 27% in men, but was unchanged in women, despite lower early:late diastolic filling (48–51%), Q̇ rest (19–23%) and FBF rest (56%) in both sexes. Conclusions Understanding sex-specific differences in cardiovascular ageing is important for public health and biomedical research, given increasingly larger older populations and the need to prevent and treat cardiovascular disease.

What's Good for the Marrow Is Bad for the Heart: Improving Anemia in a Cardiac Iron Overload Model of Hbbth1/th1 Mice.

β-thalassemia is a β-globin gene mutation that leads to ineffective erythropoiesis, increased apoptosis, shortened red blood cell (RBC) survival, and anemia. The severity of anemia is variable, ranging from β-thalassemia major patients requiring transfusion therapy to β-thalassemia intermedia patients who are transfusion independent but absorb more iron from the gastrointestinal tract. Both types develop iron overload, with cardiac complications accounting for the majority of deaths. We hypothesized that cardiac iron overload in β-thalassemia intermedia occurs as a consequence of increased iron demand in the hematopoietic organs which, when not met, unexpectedly leads to relative iron deficiency and increased iron absorption. Iron is not present in the hearts of Hbbth1/th1 mice at baseline. However, abnormal echocardiogram results were observed in our mice relative to wild type, with lower ejection fractions (P=0.004, n=6) and a proportionally larger left ventricular mass (P=0.005, n=6) at baseline. We also developed a mouse model of cardiac iron overload in Hbbth1/th1 mice using iron dextran injections. After iron dextran, we demonstrated a significant decrease in left ventricular mass (P=0.008, n=4) compared to baseline and in a pilot experiment, observed a 150-fold increase in non-heme iron in heart as measured by spectrophotometry,. Furthermore, 130 mg of iron dextran injected over four weeks increases the reticulocyte count (P=0.03, n=5) as well as the hematocrit (P=0.01, n=5). Transferrin saturation with this method of iron loading increased from 35% to 100% (P=6x10−9 relative to baseline, n=6). Extramedullary hematopoiesis in the liver increased proportionally to the amount of iron administered and could be visualized near iron-laden Kupffer cells. Due to the increased iron demand in β-thalassemia and improved reticulocyte count and hemoglobin with the administration of iron, we postulated that Hbbth1/th1 mice are relatively iron deficient and set out to analyze the physiological mechanism of improved hematopoiesis after iron. With ter-119 and CD-71 to identify RBC precursors, and Annexin-V to identify apoptotic cells, we used flow cytometry to show that iron dextran administration decreases the degree of apoptosis in RBC precursors (from 21% to 8.5%) in Hbbth1/th1 mice to levels measured in wildtype mice at baseline. Preliminary results on RBC lifespan show that there is a shortened RBC survival in Hbbth1/th1 mice, with 50% of Hbbth1/th1 RBCs destroyed at 10.1 days relative to 21.8 days in C57 controls (P<0.0001, n=5). This analysis confirms the utility of this method for measuring the effects of iron on RBC survival in Hbbth1/th1 mice. In conclusion, the administration of iron dextran leads to clear improvement in erythropoiesis in Hbbth1/th1 mice and is in part due to increased extramedullary hematopoiesis, decreased apoptosis of RBC precursors, and possibly improved RBC survival. The loss of left ventricular mass after iron dextran administration implies myocyte death and supports our use of Hbbth1/th1 mice as a model of cardiac iron overload in β-thalassemia intermedia.

An unusual cause for reintervention after coronary artery bypass grafting

A CUTE myocardial infarction (MI) may be followed by severe complications leading to rapid hemodynamic deterioration. Well-known examples are pump failure secondary to loss of left ventricular mass, ventricular fibrillation, ventricular septal rupture, and papillary muscle rupture. Any patient with a recent MI who has to undergo coronary artery bypass grafting (CABG) because of postinfarction angina can sustain these complications in the postoperative period. This case describes a patient who developed cardiovascular collapse in the early postoperative period of a CABG, probably as a sequela of the recent myocardial infarction.

Cardiac function in adolescents and young adults with anorexia nervosa

Twelve patients with anorexia nervosa (mean age 17.6 years) underwent noninvasive cardiac evaluation. All patients had normal sinus rhythm at rest, during exercise, and following 24-hr electrocardiographic monitoring. The chest roentgenograms demonstrated a small heart secondary to a loss of left ventricular mass. Three of four patients studied had left ventricular mass measurements less than 100 g (normal is 90-360 g). Most patients had an elevated heart rate response to exercise with a slightly blunted systolic and a normal diastolic blood pressure response. Eleven of the 12 patients had reduced overall maximal working capacity. All but one had normal left ventricular ejection fraction at rest. There was no evidence of arrhythmias at rest, during exercise, or with continuous electrocardiographic recording. Young patients with anorexia nervosa appeared to have essentially normal cardiac function with a reduction in left ventricular muscle mass.