ABSTRACT
Aging is a progressive decline of body function, during which many tissues accumulate few cells with high levels of deleted mitochondrial DNA (mtDNA), leading to a defect of mitochondrial functions. Whether this mosaic mitochondrial deficiency contributes to organ dysfunction is unknown. To investigate this, we generated mice with an accelerated accumulation of mtDNA deletions in the myocardium, by expressing a dominant-negative mutant mitochondrial helicase. These animals accumulated few randomly distributed cardiomyocytes with compromised mitochondrial function, which led to spontaneous ventricular premature contractions and AV blocks at 18 months. These symptoms were not caused by a general mitochondrial dysfunction in the entire myocardium, and were not observed in mice at 12 months with significantly lower numbers of dysfunctional cells. Therefore, our results suggest that the disposition to arrhythmia typically found in the aged human heart might be due to the random accumulation of mtDNA deletions and the subsequent mosaic respiratory chain deficiency.
Subject(s)
Aging , Arrhythmias, Cardiac/etiology , DNA, Mitochondrial/genetics , Mitochondria/genetics , Mitochondrial Diseases/complications , Mitochondrial Diseases/genetics , Oxygen/metabolism , Animals , Arrhythmias, Cardiac/genetics , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/pathology , Cell Respiration , Electron Transport Complex IV/genetics , Electron Transport Complex IV/metabolism , Gene Deletion , Mice , Mitochondria/metabolism , Mitochondria/pathology , Mitochondrial Diseases/metabolism , Mitochondrial Diseases/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathologySubject(s)
Aortic Valve Stenosis/complications , Endocarditis/complications , Heart Failure/diagnosis , Kidney Failure, Chronic/diagnosis , Nails/pathology , Aged , Aortic Valve Stenosis/pathology , Early Diagnosis , Endocarditis/etiology , Endocarditis/pathology , Fingers , Heart Failure/complications , Heart Failure/pathology , Heart Valve Prosthesis/adverse effects , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/pathology , Male , Middle AgedABSTRACT
Intracardiac myxomas are the most common benign cardiac tumors in adults. They are a rare source of cardiogenic embolisms and sudden death, especially in young patients. This report describes the case of a male adolescent who presented with right-sided paresis and aphasia. Magnetic resonance imaging of the brain revealed an ischemic stroke without evidence of acute bleeding. Intra-arterial local thrombolysis was immediately started. An echocardiographic screening after successful thrombolysis with a remarkable recovery of symptoms detected a thrombotic-like mass in the left atrium. The mass was excised surgically, confirmed as a benign atrial myxoma, and the patient was discharged with restitution ad integrum. Thus, contrary to some critical reports, thrombolytic therapy for acute ischemic strokes due to atrial myxomas may be safe and highly effective.
Subject(s)
Fibrinolytic Agents/therapeutic use , Heart Neoplasms/complications , Myxoma/complications , Stroke/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Adolescent , Heart Atria/pathology , Heart Neoplasms/diagnostic imaging , Heart Neoplasms/surgery , Humans , Male , Myxoma/diagnostic imaging , Myxoma/surgery , Stroke/pathology , Stroke/surgery , UltrasonographyABSTRACT
BACKGROUND: The validity of Doppler echocardiographic (DE) measurement of systolic pulmonary artery pressure (sPAP) has been questioned. Recent studies suggest that mean pulmonary artery pressure (mPAP) might reflect more accurately the invasive pressures. METHODOLOGY/PRINCIPAL FINDINGS: 241 patients were prospectively studied to evaluate the diagnostic accuracy of mPAP for the diagnosis of PH. Right heart catheterization (RHC) and DE were performed in 164 patients mainly for preoperative evaluation of heart valve dysfunction. The correlation between DE and RHC was better when mPAP (r=0.93) and not sPAP (r=0.81) was assessed. Bland-Altman analysis revealed a smaller variation of mPAP than sPAP. The following ROC analysis identified that a mPAP≥25.5 mmHg is useful for the diagnosis of PH. This value was validated in an independent cohort of patients (n=50) with the suspicion of chronic-thromboembolic pulmonary hypertension. The calculated diagnostic accuracy was 98%, based on excellent sensitivity of 98% and specificity of 100%. The corresponding positive and negative predictive values were 100%, respectively 88%. CONCLUSION: mPAP has been found to be highly accurate for the initial diagnosis of PH. A cut-off value of 25.5 mmHg might be helpful to avoid unnecessary RHC and select patients in whom RHC might be beneficial.