SUMMARY Paradoxical septal motion is considered to be a characteristic feature of total anomalous pulmonary venous drainage, reflecting the right ventricular volume overload in this condition. Patients with additional pulmonary venous obstruction have reduced pulmonary blood flow, and would be expected to show normal septal motion. We have studied the haemodynamic and echocardiographic findings in 21 patients with proven total anomalous pulmonary venous drainage and found paradoxical septal motion in only 11 instances. Paradoxic-al septal motion was present in all nine patients over the age of 1 month. Of the 12 neonates, 10 showed normal septal motion.Patients with normal septal motion had clinical features of pulmonary venous obstruction, with significantly higher pulmonary artery pressures and lower pulmonary artery saturations than patients with paradoxical septal motion.It is concluded that in total anomalous pulmonary venous drainage, septal motion reflects pulmonary blood flow, allowing separation of patients into those with or those without pulmonary venous obstruction.Septal motion on the M-mode echocardiograms of children with total anomalous pulmonary venous drainage has been reported as typically paradoxical,1" reflecting the right ventricular volume overload in this condition. Normal septal motion, however, has been reported, particularly in very young infants.5 6 Since most other M-mode echocardiographic features of total anomalous pulmonary venous drainage are non-specific,3 4 we feel the diagnostic value of septal motion in these patients might be important. We reviewed the presenting echocardiographic and haemodynamic findings in 21 cases of proved total anomalous pulmonary venous drainage. Septal motion was classified and the clinical and haemodynamic features were compared between patients with normal septal motion and those with paradoxical septal motion. The effect of pulmonary venous obstruction on echocardiographic septal motion was noted. Patients and methodsBetween June 1975 and September 1980, 25 patients with total anomalous pulmonary venous drainage were diagnosed by cardiac catheterisation at the Received for publication 5 February 1981 Birmingham Children's Hospital. Twenty-one patients had preoperative echocardiograms of adequate standard and these formed the subjects of this study. All patients underwent operative correction and the site of drainage was verified at operation. The patients' age at presentation, weight, and relevant clinical, echocardiographic, and haemodynamic data are listed in the
Introduction: More that 10% of human proteins can be S-palmitoylated, a post-translational modification (PTM) whereby palmitoyl chains are covalently linked to cysteine thiol groups. S-palmitoylation influences protein trafficking, distribution and function. There is no information on the scope of protein S-palmitoylation in the heart, or how this enzyme-mediated reversible PTM is regulated. Hypothesis: S-palmitoylation occurs to a wide spectrum of proteins in cardiomyocytes, and is coordinated by membrane-embedded palmitoylating (DHHC) enzymes. DHHC enzymes are subject to remodeling during chronic hypertension. Methods: We used resin-assisted capture to purify S-palmitoylated proteins from ventricular myocardium of 3 species: human, dog, and rat. We used global unbiased proteomic search to identify S-palmitoylated proteins. We validated DHHC antibodies and used them to monitor protein level and subcellular distribution of native DHHC enzymes in ventricular myocytes. Results: We built a 'composite' cardiac palmitome composed of 462 S-palmitoylatable proteins identified in ≥ 2 species-specific cardiac palmitomes. Enrichment analysis based on GO term 'cellular component' indicated that they are mainly involved in cell-cell and cell-substrate associations, sarcolemma and sarcomere organization, vesicular trafficking, G-protein function, ATP-dependent transmembrane transport, and mitochondria inner and outer membrane organization. Among the 23 DHHC enzymes, we detected ten in hearts across species. In ventricular myocytes with well-defined subcellular compartments, DHHC enzymes exhibited distinct distribution patterns: peripheral sarcolemma (DHHC1), M-lines (DHHC2), Z-lines (DHHC5), vesicles (DHHC7) and intercalated disc (DHHC9). In aging spontaneously hypertensive rats (a model of chronic hypertension, some in heart failure), seven DHHC enzymes were upregulated in the heart, accompanied by a higher degree of S-palmitoylation of CaMK II, caveolin3, Na/Ca exchanger, and Na/K pump α-subunit. Conclusion: S-palmitoylation is involved in most, if not all, aspects of cardiomyocyte function. Palmitoylation dysregulation may contribute to pathological progression in hypertrophy leading to heart failure.
pre-diabetic cardiomyopathy (pre-DC). Cytosolic Ca measurements were performed in ventricular myocytes derived from mice affected by CPVT (CASQ2 Knockout or Cnull) or pre-DC (chronic fructose diet, FDT). The effects of pharmacological modulators of mitochondrial Ca (mCa) on arrhythmogenic Ca waves were examined. Kaempferol, an activator of the mitochondrial Ca uniporter (MCU) complex, abolished Ca waves in Cnull cells but exacerbated Ca waves in FDT cells. Moreover, the MCU inhibitor Ru360 increased Ca wave frequency in Cnull cells but inhibited Ca waves in FDT cells. Cyclosporine A (CsA), an inhibitor of mitochondrial permeability transition pore, increased Ca wave frequency in Cnull cells but failed to do so in FDT cells. CGP37157, a mitochondrial Na-Ca exchanger inhibitor, increased Ca wave frequency in both Cnull and FDT cells. MCa content was increased in Cnull vs WT cells, as measured by examining the FCCP induced increase in diastolic Ca after blocking SR Ca uptake and sarcolemmal Ca fluxes. Additionally, increased mitochondrial ROS generation was detected in Cnull cells treated with CsA or CGP37157. Moreover, CaMKII inhibition by KN93 reversed the exacerbation of Ca waves by kaempferol or CsA in FDT or Cnull cells, respectively. Collectively, our results suggest that mitochondria differentially influence myocyte Ca handling, acting either as a source of ROS or a Ca buffer, in different cardiac disease settings.
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