Depressed Myocardial Function Research Articles

Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats

Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant to treat partial seizures and neuropathic pain. While a majority of the side effects are associated with the nervous system, emerging evidence suggests a high risk for heart disease in the patients taking GBP. Given GBP can bind with high affnity to the α2δ subunits of voltage-gated Ca2+ channels (VGCCs) to block Ca2+ influx of cardiomyocytes, we hypothesize GBP suppresses cardiac function by evoking calcium signaling dysfunction. By using a preclinical rat model treated with GBP, we investigated (1) the acute cardiovascular responses to GBP (bolus i.v. injection; 50 mg/kg, 100 mg/ml x 0.1 ml in 3 min) and (2) the effects of chronic GBP treatment (i.p. 100 mg/kg/day x 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane-anesthesia, blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics of the rats were measured using two Millar pressure transducers; one was implanted in abdominal aorta via right femoral artery, and the another was implanted in the LV chamber via right carotid artery. The LV myocardium was analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction, with the brain cortex used as a control tissue. In experiment (1), we found that i.v. GBP treatment significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (*p < 0.05 and **p < 0.01 vs baseline; n = 4/group). This cardiovascular inhibition started at the injection time point and lasted at least 60 min, with a maximal effect appearing at 30 min post injection. In experiment (2), we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium of these rats, we used mass spectra to identify 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Particularly, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain, suggesting a myocardium-specific dysregulation of calcium signaling pathway, which may play a critical role in GBP-induced cardiac inhibition. Subsequent bioinformatics assays revealed a reduced Ca2+ release of sarcoplasmic reticulum (SR) and increased electrophoretic Ca2+ uptake into the matrix of mitochondria in the hearts of GBP-treated rats. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes where GBP binds to VGCCs to reduce extracellular Ca2+ influx and cytosolic Ca2+ release from SR, resulting in blockage of excitation-contraction coupling. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function. This project is funded by NIH R01 HL 160820. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute cardiovascular manifestations with multisystem inflammatory syndrome in children due to COVID-19 infection: A single-center prospective observational study

Abstract Background: Cardiac involvement is common in children with multisystem inflammatory syndrome associated with the COVID-19 pandemic. A majority of children have significantly raised levels of NT pro-BNP, ferritin, D-dimers, and cardiac troponin in addition to high C-reactive protein and procalcitonin levels. Cardiac involvement may include rhythm disturbance, depressed myocardial function, valvar regurgitation, and/or coronary artery inflammation. This hospital-based prospective study was aimed to evaluate cardiovascular manifestations in cases of multisystem inflammatory syndrome in children (MIS-C). Subjects and Methods: The current study was a prospective observational study that included 100 children admitted to the pediatric intensive care unit after getting the requisite clearance from the institutional ethics committee; informed written consent of parents was taken before the start of the study. Results: The mean age of the study participants was 8.9 ± 3.9 years with 62% male children. Ninety-four percentage had MIS-C with KD phenotype while only 6% of kids developed shock. Abnormal electrocardiography (ECG) was found in 41%, pericardial effusion in 16%, left ventricular dysfunction (LVD) in 42%, and coronary lesions found in 30% of patients. Abnormal NT-proBNP (>125 pg/ml) was noted in 90% of children. Abnormal cTnT was seen in 89%, and 91% of children had abnormal BNP. The present study found a mortality of 6%. Conclusions: MIS-C with KD phenotype is the most common presentation with raised cardiac injury markers. Abnormal ECG LVD and coronary lesions are transient common cardiac abnormalities which get resolved within 3 months of treatment.

Effects of Acute and Chronic Gabapentin Treatment on Cardiovascular Function of Rats.

Gabapentin (GBP), a GABA analogue, is primarily used as an anticonvulsant for the treatment of partial seizures and neuropathic pain. Whereas a majority of the side effects are associated with the nervous system, emerging evidence suggests there is a high risk of heart diseases in patients taking GBP. In the present study, we first used a preclinical model of rats to investigate, firstly, the acute cardiovascular responses to GBP (bolus i.v. injection, 50 mg/kg) and secondly the effects of chronic GBP treatment (i.p. 100 mg/kg/day × 7 days) on cardiovascular function and the myocardial proteome. Under isoflurane anesthesia, rat blood pressure (BP), heart rate (HR), and left ventricular (LV) hemodynamics were measured using Millar pressure transducers. The LV myocardium and brain cortex were analyzed by proteomics, bioinformatics, and western blot to explore the molecular mechanisms underlying GBP-induced cardiac dysfunction. In the first experiment, we found that i.v. GBP significantly decreased BP, HR, maximal LV pressure, and maximal and minimal dP/dt, whereas it increased IRP-AdP/dt, Tau, systolic, diastolic, and cycle durations (* p < 0.05 and ** p < 0.01 vs. baseline; n = 4). In the second experiment, we found that chronic GBP treatment resulted in hypotension, bradycardia, and LV systolic dysfunction, with no change in plasma norepinephrine. In the myocardium, we identified 109 differentially expressed proteins involved in calcium pathways, cholesterol metabolism, and galactose metabolism. Notably, we found that calmodulin, a key protein of intracellular calcium signaling, was significantly upregulated by GBP in the heart but not in the brain. In summary, we found that acute and chronic GBP treatments suppressed cardiovascular function in rats, which is attributed to abnormal calcium signaling in cardiomyocytes. These data reveal a novel side effect of GBP independent of the nervous system, providing important translational evidence to suggest that GBP can evoke adverse cardiovascular events by depression of myocardial function.

Negative Effects Of Protamine On Myocardium In Paediatrics Patients Undergoing Cardiac Surgery Using A Cardiopulmonary Bypass Machine

The administration of protamine, a heparin reversal agent, is an integral part of cardiovascular bypass protocols, particularly in the post-bypass phase. In paediatric cases, protamine is administered in a titration dose. The use of protamine is associated with various adverse events, including myocardial impairment. Proper dosage adjustment is crucial during protamine administration, as excessive doses may result in the depression of myocardial function. Experimental studies examining protamine usage have revealed myocyte impairments, such as reduced myocyte contractility, dysfunction in signaling pathways, and alterations in cardiac receptors. Despite these findings, research on the impact of pediatric protamine on the myocardium remains limited and necessitates further investigation.

Factors associated with the need for inotropic support following pulmonary artery banding surgery for CHD.

We aimed to identify factors independently associated with the need for inotropic support for low cardiac output or haemodynamic instability after pulmonary artery banding surgery for CHD. We performed a retrospective chart review of all neonates and infants who underwent pulmonary banding between January 2016 and June 2019 at our institution. Bivariate and multivariable analyses were performed to identify factors independently associated with the use of post-operative inotropic support, defined as the initiation of inotropic infusion(s) for depressed myocardial function, hypotension, or compromised perfusion within 24 hours of pulmonary artery banding. We reviewed 61 patients. Median age at surgery was 10 days (25%,75%:7,30). Cardiac anatomy was biventricular in 38 patients (62%), hypoplastic right ventricle in 14 patients (23%), and hypoplastic left ventricle in 9 patients (15%). Inotropic support was implemented in 30 patients (49%). Baseline characteristics of patients who received inotropic support, including ventricular anatomy and pre-operative ventricular function, were not statistically different from the rest of the cohort. Patients who received inotropic support, however, were exposed to larger cumulative doses of ketamine intraoperatively - median 4.0 mg/kg (25%,75%:2.8,5.9) versus 1.8 mg/kg (25%,75%:0.9,4.5), p < 0.001. In a multivariable model, cumulative ketamine dose greater than 2.5mg/kg was associated with post-operative inotropic support(odds ratio 5.5; 95% confidence interval: 1.7,17.8), independent of total surgery time. Inotropic support was administered in approximately half of patients who underwent pulmonary artery banding and more commonly occurred in patients who received higher cumulative doses of ketamine intraoperatively, independent of the duration of surgery.

Abstract 15293: Predictive Value of Thyroid Hormone Levels in Patients Suffering From Cardiogenic Shock Complicating Acute Myocardial Infarction

Hypothesis: Introduction. Acute critically ill patients experience a rapid decline in plasma free thyroid hormone levels (free triiodothyronine (FT3) and free levothyroxine (FT4)), with a marked elevation of reverse T3, recognized as the euthyroid sick syndrome (ESS) or low-T3 syndrome. The ESS is also often associated with depressed myocardial function, sometimes referred to as the 'stunned myocardium. The role of thyroid hormone levels in patients with cardiogenic shock complicated myocardial infarction has not been shown Methods: The purpose of the study was to assess the impact of thyroid hormone levels on hospital mortality in patients with infarction related cardiogenic shock. Thyroid hormone levels were measured from routine blood specimens and analyzed initial and up to 96 hours. Results: We identified 40 patients with infarction related cardiogenic shock treated at our university hospital. Majority of the CS-patients had on admission reduced TSH levels of 1,42 ± 0,22mU/l. Nevertheless, in-hospital mortality rate was higher in patients with lower admission TSH levels and levels over time. In addition, FT3 in CS-survivors showed a flat slope from normal levels. Non-survivor had a trend towards lower levels after 72 and 96 hours. When we analyzed for low T3 syndrome (i.e. FT3 &gt;3,1pmol/l) we saw a 3x times higher mortality rate compared to CS patients with normal levels. In contrast, FT4 levels of non survivors were significantly elevated compared to surviving CS patients. After 96 hours both groups had similar levels. Predictors of hospital death in CS patients were low TSH levels, low T3 syndrome and elevated FT4. Conclusions: Thyroid hormone level on admission and over time (i.e. low TSH, low T3 and elevated FT4) are predictors of in-hospital death in patients with infarction related cardiogenic shock. Interestingly TSH stays almost stable over time whereas FT3 and FT4 declines over time. Further studies have to show if administration of thyroid hormone might be beneficial in patients with infarction related cardiogenic shock.

Detection of Congestive Heart Failure and Myocardial Dysfunction in Cats With Cardiomyopathy by Using Two-Dimensional Speckle-Tracking Echocardiography.

Congestive heart failure (CHF) is a life-threatening condition in cats with cardiomyopathy. We hypothesized that myocardial dysfunction may induce progression to CHF pathophysiology in cats with cardiomyopathy. However, no previous studies have evaluated the involvement of myocardial dysfunction in cats with CHF. In this study, we aimed to evaluate the relationship between CHF and myocardial function assessed using two-dimensional speckle-tracking echocardiography (2D-STE). Sixteen client-owned healthy cats and 32 cats with cardiomyopathy were enrolled in this study. Cats were classified into three groups: healthy cats, cardiomyopathy without CHF (CM group), and cardiomyopathy with CHF (CHF group). Left ventricular (LV) longitudinal and circumferential strains (SL and SC, respectively), and right ventricular (RV) SL were measured using 2D-STE. Logistic regression analysis was performed to assess the relationship between CHF and echocardiographic variables, including 2D-STE. Results comparing the healthy cats and CM vs. CHF groups showed that increased left atrial to aortic diameter ratio and decreased LV apical SC were significantly associated with the existence of CHF (odds ratio [95% confidence interval]: 1.40 [1.16–1.78] and 1.59 [1.06–2.36], respectively). Results comparing the CM vs. CHF group showed that increased end-diastolic RV internal dimension and decreased RV SL were significantly associated with the existence of CHF (odds ratio: 1.07 [1.00–1.13] and 1.34 [1.07–1.68], respectively). Left atrial enlargement and depressed LV apical myocardial function may be useful tools for predicting the progression to CHF in cats. Furthermore, RV enlargement and dysfunction may lead to the onset of CHF in asymptomatic cats with cardiomyopathy.

Bone marrow- or adipose-mesenchymal stromal cell secretome preserves myocardial transcriptome profile and ameliorates cardiac damage following ex vivo cold storage

BackgroundHeart transplantation, a life-saving approach for patients with end-stage heart disease, is limited by shortage of donor organs. While prolonged storage provides more organs, it increases the extent of ischemia. Therefore, we seek to understand molecular mechanisms underlying pathophysiological changes of donor hearts during prolonged storage. Additionally, considering mesenchymal stromal cell (MSC)-derived paracrine protection, we aim to test if MSC secretome preserves myocardial transcriptome profile and whether MSC secretome from a certain source provides the optimal protection in donor hearts during cold storage. Methods and resultsIsolated mouse hearts were divided into: no cold storage (control), 6 h cold storage (6 h-I), 6 h-I + conditioned media from bone marrow MSCs (BM-MSC CM), and 6 h-I + adipose-MSC CM (Ad-MSC CM). Deep RNA sequencing analysis revealed that compared to control, 6 h-I led to 266 differentially expressed genes, many of which were implicated in modulating mitochondrial performance, oxidative stress response, myocardial function, and apoptosis. BM-MSC CM and Ad-MSC CM restored these gene expression towards control. They also improved 6 h-I-induced myocardial functional depression, reduced inflammatory cytokine production, decreased apoptosis, and reduced myocardial H2O2. However, neither MSC-exosomes nor exosome-depleted CM recapitulated MSC CM-ameliorated apoptosis and CM-improved mitochondrial preservation during cold ischemia. Knockdown of Per2 by specific siRNA abolished MSC CM-mediated these protective effects in cardiomyocytes following 6 h cold storage. ConclusionsOur results demonstrated that using MSC secretome (BM-MSCs and Ad-MSCs) during prolonged cold storage confers preservation of the normal transcriptional “fingerprint”, and reduces donor heart damage. MSC-released soluble factors and exosomes may synergistically act for donor heart protection.

A Study on the Cardiac Manifestations and their Short-Term Outcome in Patients with Kawasaki Disease in an Indian Population

Objectives: This study aimed to assess the prevalence of cardiac manifestations and their short-term outcome in patients with Kawasaki disease (KD) in an Indian population. Methods: This single-center prospective study enrolled a total of 56 consecutive patients with classic and incomplete KD. Six months and 1-year clinical outcomes were analyzed. Results: Fifty-six consecutive patients were enrolled in the study and followed up for 1 year. About 87% completed 6 months follow-up. A diagnosis of complete KD was made in 41 (73%) patients and incomplete KD in 15 (27%). Cardiac manifestations were present in 25% of patients with KD. Coronary involvement was observed in 11 (20%) patients by either Japanese Ministry of Health Criteria or a z score of ≥2.5. Nonpurulent conjunctivitis was significantly higher among children with cardiac involvement (79% vs. 43% P= 0.04). The mean value of erythrocyte sedimentation rate (ESR) was significantly higher among patients with cardiac involvement (101.92 ± 22 vs. 74.26 ± 28.6; P= 0.002). An ESR value of &gt;100 mm/hr was predictive of cardiac involvement (P = 0.03). The mean serum glutamic-pyruvic transaminase value was higher among those with cardiac involvement (P = 0.008). Coronary dilatation got resolved in 3 months in 73% of patients. Valvular regurgitations, aortic root involvement, and depressed left ventricular myocardial function were not observed in the population studied. Conclusions: Cardiac manifestations were present in 25% of patients with KD, 20% of children had coronary involvement in the form of an aneurysm, or ectasia. About 73% of patients with coronary dilatation got resolved in 3 months. Significant valvular heart diseases, aortic root involvement, and myocardial contractile dysfunction were not seen in the studied population with KD.

Extracorporeal membrane oxygenation for multisystem inflammatory syndrome in children.

Early reports suggested that pediatric COVID-19 cases were less severe in children. Most children requiring intensive care admission in these reports had underlying medical conditions. Shortly after the surge of adult COVID-19 cases in Detroit, Michigan, previously healthy children began to present with shock with multiorgan dysfunction, elevated inflammatory markers, and physical exam findings with features of Kawasaki disease. This disease process was later called multisystem inflammatory syndrome in children (MIS-C.) In this case series, we describe three previously healthy children who presented with severe manifestations of MIS-C, including cardiogenic shock and profound systemic inflammation. These children developed severely depressed myocardial function with end-organ injury and were cannulated to veno-arterial extracorporeal membrane oxygenation (VA-ECMO) due to cardiogenic shock with arrhythmia. All three children improved with VA-ECMO support and anti-inflammatory treatment. All had complete recovery of myocardial function at discharge and 6-month follow-up with no significant morbidity.

Chrysin rescues rat myocardium from ischemia-reperfusion injury via PPAR-γ/Nrf2 activation

Pharmacological strategies aimed at co-activating peroxisome proliferator-activated receptor-gamma (PPAR-γ)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway have shown promising results in alleviating myocardial injury. The aim of the study was to evaluate the role of chrysin, a PPAR-γ agonist, in ischemia-reperfusion (IR)-induced myocardial infarction (MI) in rats and to explore the molecular mechanism driving this activity. To evaluate this hypothesis, chrysin (60 mg/kg, orally), PPAR-γ antagonist (GW9662, 1 mg/kg, intraperitoneally), or both were administered to rats for 28 days. On the 29th day, one-stage ligation of left anterior descending coronary artery for 45 min followed by 60 min of reperfusion was performed. Chrysin significantly decreased infarct size and improved cardiac functions following IR-induced MI. This improvement was corroborated by augmented PPAR-γ/Nrf2 expression as confirmed by immunohistochemistry and western blotting analysis. Chrysin exhibited strong anti-oxidant property as demonstrated by increased GSH and CAT levels and decreased 8-OHdG and TBARS levels. Our findings also imply that chrysin significantly inhibited inflammatory response as validated by decreased NF-κB, IKK-β, CRP, TNF-α and MPO levels. In addition, chrysin decreased TUNEL/DAPI positivity, a marker of apoptotic response and normalized cardiac injury markers. The histopathological and ultrastructural analysis further supported the functional and biochemical outcomes, showing preserved myocardial architecture. Intriguingly, co-administration with GW9662 significantly diminished the cardioprotective effect of chrysin as demonstrated by depressed myocardial function, decreased PPAR-γ/Nrf2 expression and increased oxidative stress. In conclusion, the present study demonstrates that co-activation of PPAR-γ/Nrf2 by chrysin may be crucial for its cardioprotective effect.

Assessment of Hemodynamic Status and Perfusion Markers in Critically Ill Children with Septic Shock

Abstract Background Severe sepsis causes release of inflammatory mediators and an associated redistribution of intravascular volume together with depression of myocardial function which manifests as hemodynamic pattern of low cardiac output, low systemic vascular resistance, hypotension, hyperlactatemia and signs of altered tissue perfusion such as oliguria and prolonged capillary refill time. Aim of the Work To assess hemodynamic status together with the perfusion markers (lactate) in critically ill children with septic shock. Patients and Methods This single cohort study was conducted on 40 patients recruited from the pediatric intensive care units (PICU) at: Ain Shams university hospital, Al-Galaa Military medical complex and Ghamra Military hospital From December 2017 to August 2018. Results Only four cases of cases with septic shock developed ejection fraction below 55% denoting myocardial dysfunction during the duration of assessment (first 24 hours of diagnosis). There was negative correlation between cardiac functions represented by hemodynamic measures on one side and SOFA score, PIM 2 score and serum lactate levels on the other side. However, by studying the performance of the parameters included in our study in predicting death; only lactate-24 ≥2.0 (mmoL/L) had statistically significant moderate diagnostic performance, other studied measurements had weak diagnostic performance. Conclusion Myocardial dysfunction was found to be common in children having septic shock. Close monitoring and hemodynamic assessment is important to avoid missing these cases. In addition, serum blood lactate level is an important biomarker that should be carefully monitored as it is a good prognostic tool that can predict outcome in pediatric sepsis and septic shock.

Dantrolene Attenuates Cardiotoxicity of Doxorubicin Without Reducing its Antitumor Efficacy in a Breast Cancer Model

Dysregulation of calcium homeostasis is a major mechanism of doxorubicin (DOX)-induced cardiotoxicity. Treatment with DOX causes activation of sarcoplasmic reticulum (SR) ryanodine receptor (RYR) and rapid release of Ca2+ in the cytoplasm resulting in depression of myocardial function. The aim of this study was to examine the effect of dantrolene (DNT) a RYR blocker on both the cardiotoxicity and antitumor activity of DOX in a rat model of breast cancer. Female F344 rats with implanted MAT B III breast cancer cells were randomized to receive intraperitoneal DOX twice per week (12 mg/kg total dose), 5 mg/kg/day oral DNT or a combination of DOX + DNT for 3 weeks. Echocardiography and blood troponin I levels were used to measure myocardial injury. Hearts and tumors were evaluated for histopathological alterations. Blood glutathione was assessed as a measure of oxidative stress. The results showed that DNT improved DOX-induced alterations in the echocardiographic parameters by 50%. Histopathologic analysis of hearts showed reduced DOX induced cardiotoxicity in the group treated with DOX + DNT as shown by reduced interstitial edema, cytoplasmic vacuolization, and myofibrillar disruption, compared with DOX-only–treated hearts. Rats treated with DNT lost less body weight, had higher blood GSH levels and lower troponin I levels than DOX-treated rats. These data indicate that DNT is able to provide protection against DOX cardiotoxicity without reducing its antitumor activity. Further studies are needed to determine the optimal dosing of DNT and DOX in a tumor-bearing host.

Changes of Left Ventricular Systolic Function in Patients Undergoing Coronary Artery Bypass Grafting.

AIM:This prospective study was designed to evaluate the changes in left ventricular (LV) systolic function after coronary artery bypass grafting (CABG) in patients with both normal and abnormal pre-operative systolic function.METHODS:During the period from October 2017 to October 2018, forty-seven consecutive patients undergoing CABG were enrolled in this prospective study. Transthoracic echocardiography was performed within 1 week before CABG as well as 4 to 6 months after surgery. All measurements were made by a single experienced investigator.RESULTS:While the mean LV ejection fraction (LVEF) showed neither improvement nor significant reduction in the whole group of patients following CABG (from 54.21 ± 15.36 to 53.66 ± 11.56%, p = 0.677), significant improvement in LVEF was detected in the subgroup of patients with pre-operative LV dysfunction (from 40.05 ± 8.65 to 45.85 ± 9.04%, p = 0.008). On the other hand, there was a significant decline in LEFT in the subgroup of patients with normal pre-operative LEFT (from 64.70 ± 9.72 to 59.44 ± 9.75%, p = 0.008). As for the other parameters of systolic function, significant decrease in LV end-diastolic volume index (LVEDVI) (p = 0.001), LV end-systolic volume index (LVESVI) (p = 0.0001), wall motion score index (WMSI) (p = 0.013) and LVmass index in male patients (p = 0.011) was shown only in patients with decreased LVEF after CABG. Patients with improved postoperative LVEF (53.2% of all patients) had significantly lower baseline LVEF (p = 0.0001), higher LVESVI (0.009) and higher WMSI (p = 0.006) vs patients with worsened postoperative LVEF (38.3% of all patients). Postoperative improvement of LVEF was correlated with stabile angina, lack of preoperative myocardial infarction and smoking, higher baseline WMSI, higher LV internal diameters and indexed volumes in diastole and systole and lower baseline LVEF. In stepwise linear regression analysis the value of baseline LVEF appeared as independent predictor of improved LVEF after CABG (B = 0,836%; 95% CI 0.655-1.017; p = 0.0001).CONCLUSION:Our study showed that LVEF, internal baseline diameters and indexed volumes of LV in diastole and systole are important determinants of postoperative change in LVEF. In patients with preoperative depressed myocardial function, there is an improvement in systolic function, whereas in patients with preserved preoperative myocardial function, the decline in postoperative LVEF was detected.

Transient depression of myocardial function after influenza virus infection: A study of echocardiographic tissue imaging.

BackgroundInfluenza virus infection (IVI) was reported to be associated with minor cardiac changes, mostly those detected on electrocardiogram with and without elevated blood markers of myocardial injury; however, the characteristics of myocardial involvement in association with IVI are poorly understood. This study used echocardiographic tissue imaging (tissue Doppler, strain, and strain rate) to evaluate changes in left atrial (LA) and left ventricular (LV) myocardial function after IVI.Methods and resultsWe examined 20 adult individuals (mean age, 43 years) at 2 and 4 weeks after diagnosis of IVI. For myocardial functional variables, we obtained LV global longitudinal strain (GLS), LV early diastolic strain rate (e'sr), LA strain, and LA stiffness (E/e’/LA strain), in addition to data on tissue Doppler (s’, e’, and a’) and myocardial performance index. Blood markers of myocardial injury were also examined. During follow-up, there were no significant changes in global chamber function such as LV ejection fraction, E/e’, and LA volume. However, significant changes in myocardial function were observed, namely, in s’ (8.0 ± 1.6 cm/s to 9.3 ± 1.5 cm/s; p = 0.01), e’ (10.2 ± 2.8 cm/s to 11.4 ± 3.0 cm/s; p < 0.001), e’sr (1.43 ± 0.44 1/s to 1.59 ± 0.43 1/s; p = 0.005), and LA strain (35 ± 8% to 40 ± 12%; p = 0.025), and the myocardial performance index (0.52 ± 0.20 to 0.38 ± 0.09; p = 0.009), but not in a’, LA stiffness, or GLS. Cardiac troponin T and creatinine kinase isoenzyme MB were not elevated significantly at any examination.ConclusionsMyocardial dysfunction during IVI recovery appeared to be transient particularly in the absence of myocardial injury. Echocardiographic tissue imaging may be useful to detect subclinical cardiac changes in association with IVI.

Energy Intake and Expenditure in Children With Heart Failure.

Up to one third of children with heart failure exhibit growth failure. Limited data exists reporting energy requirements in this population. A study was designed to characterize the energy intake and total daily energy expenditure of children with heart failure using the doubly labeled water method. Prospective study using doubly labeled water to measure total daily energy expenditure in children with heart failure. Doubly labeled water was administered orally and daily urine samples collected for 10 days. Total daily energy expenditure was compared with historic data from age- and gender-matched healthy population. Anthropometrics and 3-day calorie count were also done. The Cardiovascular Intensive Care Unit and Cardiology ward at Texas Children's Hospital. Children with new presentation of heart failure as defined by an ejection fraction less than 35% and requiring inotrope(s) at the time of enrollment. A total of five children with heart failure were enrolled from 2015 to 2016. All children showed weight-for-length less than mean-for-age. All had depressed myocardial function at enrollment, and all but one demonstrated improvement in ejection fraction at follow-up. Three had energy intake that met or surpassed their total daily energy expenditure, with total daily energy expenditure that measured below historic controls. One infant, despite supplementation, had an energy intake substantially below that of measured total daily energy expenditure and required cardiac transplantation. Growth failure in heart failure is likely multifactorial and may be related to suboptimal energy intake secondary to exercise intolerance, malabsorption, and/or end-organ dysfunction due to impaired cardiac output. Doubly labeled water is a feasible method to assess total daily energy expenditure in children with heart failure.

Cardiac recovery and outcome of neonates and infants presenting with severe aortic coarctation and depressed cardiac function.

ObjectivesCoarctation of the aorta represents 5–8% of all congenital heart diseases. Children with severe coarctation of the aorta may present with significant depression of myocardial function. The aim of this study is to identify short and midterm outcomes of neonates and infants with isolated coarctation of the aorta and depressed left ventricular systolic function with regard to recovery of their cardiac function.MethodsAll patients with isolated coarctation of the aorta who underwent surgical repair between December 2002 and December 2015 were retrospectively reviewed in a cohort study. The patients were divided into 2 groups: (1) Patients with depressed left ventricle systolic function who were found to have an ejection fraction and fractional shortening less than 55% and 25%, respectively, (2) Patients with coarctation of the aorta and normal left ventricle systolic function (Control Group). We reviewed both groups after surgery and compared them in terms of their cardiac function recovery.Results58 patients were included. 25 patients (43%) depressed left ventricle systolic function group, 33 patients (57%) Control Group. There were statistically significant differences in ejection fraction and fractional shortening (p < 0.0001) between the two groups before surgery. Follow-up demonstrated improvement and recovery of ventricular function in most of the patients, six months after surgery there was no more statistical difference between the groups in terms of cardiac function.ConclusionMajority of the patients with isolated coarctation of the aorta and depressed left ventricle systolic function showed improvement of ventricular function within 4 weeks after surgery, except for patients with residual coarctation of the aorta.

Acute Pediatric Colchicine Toxicity is Associated with Marked Bradydysrhythmias

BackgroundColchicine ingestion is rare but highly lethal. Patients usually die of multiorgan failure and cardiogenic shock. Colchicine is not only associated with depressed myocardial function but also with fatal heart rhythm disturbances, such as complete heart block, ventricular tachycardia, and asystole. While histologic changes of myocytes are well known, the mechanism by which colchicine affects cardiac impulse generation and conduction is not fully understood. Case ReportWe present a case of colchicine ingestion with sinus bradycardia, marked sinus arrhythmia, and first- and second-degree heart block. A 10-year-old previously healthy boy was brought to the emergency department for the sudden onset of dizziness, abdominal pain, and vomiting after ingesting his grandfather's colchicine and furosemide. His symptoms improved with ondansetron and intravenous normal saline. However, because of the colchicine ingestion, he was admitted to the pediatric intensive care unit for observation. He first developed PR prolongation (∼4–30 h postingestion) followed by marked sinus bradycardia and sinus arrhythmia along with second-degree heart block (∼48–60 hours postingestion). The minimum heart rate was 40 beats/min. Marked sinus arrhythmia was observed, suggesting an increase in parasympathetic activity. His heart rhythm improved initially with less sinus arrhythmia followed by resolution of heart block. He was discharged home without any sequelae. Holter monitoring 1 week after discharge showed normal heart rate variability for age. Why Should an Emergency Physician Be Aware of This?This case provides novel insights into how colchicine may affect the heart's electrophysiology. Colchicine may increase the parasympathetic tone enough to cause sinus bradycardia and different degrees of heart block.

Dexmedetomidine-Ketamine Sedation in a Patient With Dilated Cardiomyopathy

Sedative and analgesic medications may impact physiologic function resulting in adverse effects especially in patients with co-morbid diseases. We present the successful use of a combination of dexmedetomidine and ketamine to provide sedation and analgesia in a 9-month-old patient with dilated cardiomyopathy undergoing hemodynamic cardiac catheterization with angiography. Co-morbid conditions included depressed myocardial function, hypertension, right renal artery agenesis, and narrowing of the abdominal aorta. A combination of dexmedetomidine and ketamine was used to provide procedural sedation while maintaining spontaneous ventilation. A review of previously published reports of dexmedetomidine and ketamine for procedural sedation is reviewed and the potential efficacy of this combination for procedural sedation in patients with depressed myocardial function is presented. J Med Cases. 2017;8(10):293-296 doi: https://doi.org/10.14740/jmc2851w

AMPK activation by metformin inhibits local innate immune responses in the isolated rat heart by suppression of TLR 4-related pathway

Toll like receptors (TLRs) are key players in the innate immune responses. The energy sensing enzyme, AMPK, has been implicated in the modulation of immunity. The present study investigated whether AMPK activation by metformin could contribute to the regulation of immune responses in the isolated heart via suppression of TLR4 activity, independent of circulatory immunity. Isolated Wistar rat hearts were perfused with Krebs-Henseleit buffer in the absence or presence of lipopolysaccharide (LPS; 0.2μM), LPS+metformin (10mM), and LPS+metformin+compound C (10μM). Following measurement of hemodynamic parameters, TLR4-activation related changes and TLR4 mRNA level in the heart was examined by western blotting and real-time PCR. The activation of AMPK was evaluated by measuring the ratio of p-AMPKα and p-ACC to their non-phosphorylated forms. The effluent and cardiac levels of TNF-α and IL6 were assayed by ELISA. LPS profoundly increased the levels of TLR4 mRNA, MyD88 (TLR4 adaptor protein), and NF-κB and also the release of TNF-α and IL6 from the heart. The enhancement in the TLR4 activity was associated with a significant depression of myocardial function. Metformin clearly augmented the phosphorylation of both AMPKα and ACC and in addition to improvement of cardiac performance, markedly suppressed the TLR4 activity. Antagonizing AMPK by compound C which is a selective inhibitor of AMPK pathway, considerably reversed the protective effects of metformin against the TLR4-related activity. The results of the study demonstrated the importance of TLR4-involved local immune responses in the LPS-induced myocardial dysfunction and indicated a clear link between AMPK and TLR4.