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George A Porter

Publications and source records attributed to George A Porter.

5 recordsLinked to original sources
PubMed2003

Intracellular calcium plays an essential role in cardiac development.

Intracellular calcium signaling plays an essential role in cardiac physiology and modulates cardiac gene expression. However, the role that intracellular calcium signaling plays during cardiac development is not known. To address this issue, we examined the effects of altered intracellular calcium levels on cardiac morphogenesis. In acutely cultured mouse embryos, L-type calcium channel blockade decreased resting intracellular calcium levels and inhibited calcium transients. Embryos cultured at embryonic day (E) 7.5-8.5 in the presence of the L-type calcium channel blockers nifedipine and verapamil developed hearts that had a large left ventricle, lacked a right ventricle and had a long, thin outflow tract. If embryos were cultured at E7.5, calcium channel blockade also induced an abnormal, anterior cardiac loop. These alterations in development were not due to altered cardiac function, as heart rates at the end of the culture period were not affected by calcium channel blockade and blood flow was observed. Treatment with nifedipine altered the mRNA expression of the transcription factor Gata4, which was absent in the developing ventricles, and the sarcomeric protein Mylpc (myosin light chain 2V), which was decreased distal to the left ventricle and was absent at the site of the developing right ventricle. In contrast, the expression pattern of other cardiac transcription factor (Hand1, Hand2, Mef2c, Nkx2-5) and cytoskeletal protein (Myhca, Tagln) mRNA did not change with calcium channel blockade. These data demonstrate that proper intracellular calcium signaling is essential for normal cardiac looping, gene expression, and organ development.

Animals↗
PubMed2003

Relationship between elevated serum troponin values in end-stage renal disease patients and abnormal isotopic cardiac scans following stress.

One hundred asymptomatic high-risk renal transplant candidates were screened for asymptomatic coronary artery disease using stress cardiac isotopic imaging. The cardiac markers, serum cTnT, cTnI, and CKMB, were collected pre and post stress testing. Of the 99 patients whose cardiac scans were technically satisfactory, 32 were normal, 49 had a definite imaging abnormality and the scan was indeterminate in the remaining 18 patients. Based on these results, patients were stratified into either normal, indeterminate or abnormal scan groups. They then were analyzed to detect any correlations between cardiac perfusion defects and either elevated pre-stress cardiac markers or consistent changes 24h after stress testing. While the mean pre-stress serum values for both cardiac troponin T (0.117 +/- 0.12 microgram/L) and cardiac troponin I (0.235 +/- 0.89 microgram/L) were increased in the abnormal cardiac scan group, only the cTnT value proved to differ significantly from the normal group (p < 0.01). For the indeterminate group neither marker was different from the normal scan group. Only an elevated serum cTnT > 0.1 microgram/L (OR 3.042, p = 0.030) proved to discriminate an abnormal scan in this population. It is concluded that the increase in pre-stress serum cTnT encountered in patients with chronic renal failure, with or without evidence of overt, symptomatic coronary artery disease, may represent a combination of subclinical myocardial damage and a prolonged half-life of the marker in the serum. Because of the frequency of elevated serum concentrations of cTnT and, to a lesser degree cTnI, the physician should exercise caution when interpreting a single elevated Troponin value during the evaluation of chest pain in patients with end-stage renal disease. A cTnT > 0.1 microgram/L increases the likelihood of finding significant coronary artery disease three fold in high-risk ESRD patients being evaluated for renal transplantation.

Adult↗
PubMed2002

Reduction in intracellular calcium levels inhibits myoblast differentiation.

In myocytes, calcium plays an important role in intracellular signaling and contraction. However, the ability of calcium to modulate the differentiation of striated muscle cells is poorly understood. To examine this issue we studied C2C12 cells, which is a myoblast cell line that differentiates in vitro. First, we observed that the L-type calcium channel blockers nifedipine and verapamil effectively inhibited electrically induced calcium transients. Next, C2C12 cells were exposed to these agents during conditions that induce myocyte differentiation. In the presence of nifedipine and verapamil, myoblasts failed to form myotubes. Dantrolene and thapsigargin, which decrease intracellular calcium by different mechanisms, also inhibited differentiation. In addition, nifedipine and verapamil inhibited the expression of myosin heavy chain and myogenin, two markers of skeletal myoblast differentiation. In contrast, levels of the transcriptional factor Myf5, which is expressed in undifferentiated myoblasts, did not decline. Calcium channel blockade also prevented the expression of a reporter driven by the skeletal muscle alpha-actin promoter. These data demonstrate that lowering intracellular calcium levels inhibits the differentiation of skeletal myoblasts into mature myotubes.

Actins↗
PubMed2002

Sinus node dysfunction associated with lithium therapy in a child.

Lithium salts have been used extensively in both adults and children during the last 30 years, for the treatment of a variety of psychiatric conditions, including bipolar disorder The cardiac side effects of lithium in adult patients have been well described. However, to the best of our knowledge, there are no reports of lithium-induced cardiac side effects in pediatric patients. We describe the case of a 9-year-old boy who developed cardiac toxicity while receiving long-term lithium therapy.

Child↗