Hypoxia-Induced Kidney Injury in Newborn Rats.

Exposure to hypoxia during the early postnatal period can have adverse effects on vital organs. Neonatal Sprague-Dawley rats housed in a hypoxic chamber were compared to those in a normoxic chamber from postnatal days 0 to 7. Arterial blood was collected to evaluate renal function and hypoxia. Kidney morphology and fibrosis were evaluated using staining methods and immunoblotting. In the kidneys of the hypoxic group, protein expressions of hypoxia-inducible factor-1 were higher than those in the normoxic group. Hypoxic rats had higher levels of hematocrit, serum creatinine, and lactate than normoxic rats. Body weight was reduced, and protein loss of kidney tissue was observed in hypoxic rats compared to normoxic rats. Histologically, hypoxic rats showed glomerular atrophy and tubular injury. Renal fibrosis with collagen fiber deposition was observed in the hypoxic group. The expression of nicotinamide adenine dinucleotide phosphate oxidases was enhanced in the kidneys of hypoxic rats. Proteins involved in apoptosis were upregulated in the kidneys of hypoxic rats. An increase in the expression of pro-inflammatory cytokines was also observed in the kidneys of hypoxic rats. Hypoxic kidney injury in neonatal rats was associated with oxidative stress, inflammation, apoptosis, and fibrosis.

Low-Dose Propranolol Prevents Functional Decline in Catecholamine-Induced Acute Heart Failure in Rats.

Severe hyper-catecholaminergic states likely cause heart failure and cardiac fibrosis. While previous studies demonstrated the effects of beta-blockade in experimental models of single-catecholamine excess states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states are less clearly understood. In this study, we examined different therapeutic dosages and the effects of propranolol in rats with hyper-acute catecholamine-induced heart failure, and subsequent cardiopulmonary changes. Rats (n = 41) underwent a 6 h infusion of epinephrine and norepinephrine alone, with additional low-dose (1 mg/kg) or high-dose propranolol (10 mg/kg) at hour 1. Cardiac and pulmonary tissues were examined after 6 h. Catecholamine-only groups had the lowest survival rate. Higher doses of propranolol (15 mg/kg) caused similarly low survival rates and were not further analyzed. All low-dose propranolol rats survived, with a modest survival improvement in the high-dose propranolol groups. Left ventricular (LV) systolic pressure and LV end-diastolic pressure improved maximally with low-dose propranolol. Cardiac immunohistochemistry revealed an LV upregulation of FGF-23 in the catecholamine groups, and this improved in low-dose propranolol groups. These results suggest catecholamine-induced heart failure initiates early pre-fibrotic pathways through FGF-23 upregulation. Low-dose propranolol exerted cardio-preventative effects through FGF-23 downregulation and hemodynamic-parameter improvement in our model of hyper-acute catecholamine-induced heart failure.

Influence of Resveratrol on the Cardiovascular Health Effects of Chronic Kidney Disease.

Cardiovascular disease (CVD) is closely related to chronic kidney disease (CKD), and patients with CKD have a high risk of CVD-related mortality. Traditional CVD risk factors cannot account for the higher cardiovascular risk of patients with CKD, and standard CVD interventions cannot reduce the mortality rates among patients with CKD. Nontraditional factors related to mineral and vitamin-D metabolic disorders provide some explanation for the increased CVD risk. Non-dialyzable toxins, indoxyl sulfate (IS) and p-cresol sulfate (PCS)-produced in the liver by colonic microorganisms-cause kidney and vascular dysfunction. Plasma trimethylamine-N-oxide (TMAO)-a gut microbe-dependent metabolite of dietary L-carnitine and choline-is elevated in CKD and related to vascular disease, resulting in poorer long-term survival. Therefore, the modulation of colonic flora can improve prospects for patients with CKD. Managing metabolic syndrome, anemia, and abnormal mineral metabolism is recommended for the prevention of CVD in patients with CKD. Considering nontraditional risk factors, the use of resveratrol (RSV), a nutraceutical, can be helpful for patients with CVD and CKD. This paper discusses the beneficial effects of RSV on biologic, pathophysiological and clinical responses, including improvements in intestinal epithelial integrity, modulation of the intestinal microbiota and reduction in hepatic synthesis of IS, PCS and TMAO in patients with CVD and CKD.

Norepinephrine Leads to More Cardiopulmonary Toxicities than Epinephrine by Catecholamine Overdose in Rats.

While catecholamines like epinephrine (E) and norepinephrine (NE) are commonly used in emergency medicine, limited studies have discussed the harm of exogenously induced catecholamine overdose. We investigated the possible toxic effects of excessive catecholamine administration on cardiopulmonary function and structure via continuous 6 h intravenous injection of E and/or NE in rats. Heart rate, echocardiography, and ventricular pressure were measured throughout administration. Cardiopulmonary structure was also assessed by examining heart and lung tissue. Consecutive catecholamine injections induced severe tachycardia. Echocardiography results showed NE caused worse dysfunction than E. Simultaneously, both E and NE led to higher expression of Troponin T and connexin43 in the whole ventricles, which increased further with E+NE administration. The NE and E+NE groups showed severe pulmonary edema while all catecholamine-administering groups demonstrated reduced expression of receptor for advanced glycation end products and increased connexin43 levels in lung tissue. The right ventricle was more vulnerable to catecholamine overdose than the left. Rats injected with NE had a lower survival rate than those injected with E within 6 h. Catecholamine overdose induces acute lung injuries and ventricular cardiomyopathy, and E+NE is associated with a more severe outcome. The similarities of the results between the NE and E+NE groups may indicate a predominant role of NE in determining the overall cardiopulmonary damage. The results provide important clinical insights into the pathogenesis of catecholamine storm.

Hepatic pathology in patients after Fontan operation: A computed tomography imaging study.

BACKGROUND: Hepatic dysfunction is an important long-term complication in Fontan patients. The purpose of this study was to evaluate the hepatic computed tomography (CT) findings after Fontan surgery and identify their association with clinical parameters. METHODS: This study recruited 43 patients (23 male and 20 female patients aged 15.3 ± 6.8 years), who underwent Fontan surgery. Medical records were reviewed to collect their age, sex, congenital heart disease type, date of Fontan surgery, laboratory data, and hepatic CT findings. The relationship between hepatic findings and clinical parameters was analyzed. RESULTS: The follow-up duration was 6.8 ± 4.1 years. Abnormal hepatic parenchymal enhancement was observed in 77% of the patients, with mild degree in 18, moderate degree in 10, and severe degree in 5 patients. According to the univariate analysis, risk factors for hepatic parenchymal enhancement were follow-up duration (odds ratio [OR]: 1.354 [95% confidence interval (CI): 1.024-2.078]; p = 0.042), hypoplastic left heart syndrome (HLHS) (OR: 3.262 [95% CI: 1.145-5.628]; p = 0.002), mean pulmonary artery pressure (OR: 1.598 [95% CI: 1.089-2.132]; p = 0.026), pulmonary vascular resistance index (OR: 1.263 [95% CI: 1.068-1.245]; p = 0.032), and brain natriuretic peptide (OR: 1.956 [95% CI: 1.085-2.673]; p = 0.045). According to the multivariate analysis, only HLHS (OR: 3.856 [95% CI: 1.389-5.863]; p = 0.001), mean pulmonary artery pressure (OR: 1.846 [95% CI: 1.362-2.549]; p = 0.015), and pulmonary vascular resistance index (OR: 1.185 [95% CI: 1.042-1.736]; p = 0.047) were significant risk factors for abnormal parenchymal enhancement. CONCLUSION: Abnormal hepatic parenchymal enhancement detected through CT is common in Fontan patients. Regular liver function test in conjunction with imaging studies may be considered when following up Fontan patients.

Acute myocarditis complicated with permanent complete atrioventricular block caused by Escherichia coli bacteremia: A rare case report.

RATIONALE: Acute myocarditis complicated with complete atrioventricular block (CAVB) is rare in clinical scenario. We report an uncommon case of myocarditis complicated with permanent CAVB caused by Escherichia coli (E coli) bacteremia. PATIENT CONCERNS: A 77-year-old woman presented at the emergency department with chest pain, dizziness, nausea, and cold sweats of 1-day duration. She had histories of type 2 diabetes mellitus, hyperlipidemia, and chronic kidney disease with regular medical therapy. DIAGNOSIS: Both blood and urine cultures were positive for E coli. Regional inferior wall motion abnormalities on echocardiography, unexplained life-threatening arrhythmias, newly abnormal electrocardiogram, elevated cardiac troponins, and healthy coronary arteries on angiography were consistent with E coli-induced myocarditis. INTERVENTIONS: The patient received implantation of a dual-chamber pacemaker because of irreversible CAVB. OUTCOMES: The patient was discharged on day 8 and remained asymptomatic at 15 months of follow-up, with ST-segment normalization and normal left ventricular function. LESSONS: This extremely rare case of E coli-induced myocarditis masquerading as acute STEMI and with permanent CAVB sequelae, highlights the importance of sensitivity to non-ischemia etiologies of ST-segment elevation and the potential impact of E coli sepsis on the cardiac conduction system.

Traumatic Ventricular Septal Defect in a 1-Year-Old Boy After Accidental Chest Compression by an Adult.

We report a 1-year-old boy with a delayed diagnosis of traumatic ventricular septal defect (VSD) related to chest compression. His cardiac function was stable after adequate medical treatment. Spontaneous closure of traumatic VSD occurred to this patient at the age of 4 years. This is a rare case of traumatic VSD associated with accidental chest compression, which is similar to rupture of the ventricular septum after blunt chest trauma. It should be kept in mind that traumatic VSD and concomitant thoracic injuries can develop during chest compression. The clinician should pay attention to the potential risk of traumatic VSD in patients experiencing chest compression. Echocardiography is a convenient and effective tool for serial follow-up examination and avoiding the delayed diagnosis. Troponin I level can be a useful screening test. Conservative management of traumatic VSD with hemodynamic stability is recommended because of possible spontaneous closure.

PRKAG3 polymorphisms associated with sporadic Wolff-Parkinson-White syndrome among a Taiwanese population.

BACKGROUND: The aim of this study was to investigate whether mutation in AMP-activated protein kinase (AMPK) subunit genes (PRKAG3-230) is associated with sporadic, isolated Wolff-Parkinson-White (WPW) syndrome. METHODS: This study consisted of 87 patients with symptomatic WPW syndrome and 93 healthy controls. PRKAG3-230 genotypes were determined using real-time polymerase chain reaction assay. Genotype and allele frequencies of PRKAG3-230 between patients with WPW syndrome and healthy controls were ascertained using chi-square test or Fisher exact test when appropriate. RESULTS: PRKAG3-230 were genotyped in 87 patients (53 men and 34 women; age=24.4±18.0 years) with WPW syndrome and 93 healthy controls (57 men and 36 women; age=16.8±4.2 years). There were no significant differences between the two groups in terms of age and sex. The patients with CG and CG+CC genotypes had a significantly increased risk of WPW syndrome compared with those with GG genotype [odds ratio (OR)=1.99, 95% confidence interval (CI)=1.01-3.89, p=0.045; OR=1.99, 95% CI=1.04-3.78, p=0.037, respectively]. The allelic types were not associated with the risk of WPW syndrome. The patients with manifest type with CG and CG+CC genotypes had a significantly increased risk of WPW syndrome compared with those with GG genotype (OR=2.86, 95% CI=1.16-7.05, p=0.022; OR=2.84, 95% CI=1.19-6.80, p=0.019, respectively). The patients with right-side accessory pathways with CG and CG+CC genotypes had a significantly increased risk of WPW syndrome compared with those with GG genotype (OR=3.07, 95% CI=1.25-7.51, p=0.014; OR=2.84, 95% CI=1.19-6.80, p=0.019, respectively). The allelic types were not associated with the risk of WPW types and locations. CONCLUSION: This study shows that PRKAG3-230 may be associated with sporadic WPW syndrome among a Taiwanese population. Further studies are warranted to elucidate the role of mutations in AMPK subunit genes other than PRKAG3-230 in sporadic WPW syndrome.

Echocardiographic Diagnosis of Incidentally Found Left Coronary Artery to Pulmonary Artery Fistula in an 11-Year-Old Girl.

We report on a healthy 11-year-old girl who presented to our facility with sudden onset of fainting in a strenuous running course. Transthoracic echocardiography at short-axis view showed a diastolic flow into the main pulmonary artery (PA). The diagnosis of left anterior descending artery (LAD) to PA fistula was documented by cardiac computed tomography and catheterization. Interventional therapy of LAD to the main PA fistula was not performed because of no evidence of myocardial ischemia or significant hemodynamic change. Presently, the patient remains asymptomatic. Coronary fistula with an incidence of about 0.1-0.8% is very rare and may be undetected, particularly in pediatric patients without cardiac murmur. We herein describe the diagnostic approach and discuss the current treatment modalities.