Effect of iodixanol and ioxilan on QT interval and renal function in patients with systolic heart failure.

BACKGROUND: Contrast media (CM) exposure is associated with a substantial risk of arrhythmias and nephrotoxicity. These adverse effects may be exacerbated in high-risk conditions such as heart failure, although no studies have evaluated newer CM agents in this population. This study evaluated the electrophysiologic and renal effects of two newer CM agents, iodixanol and ioxilan, in heart failure patients undergoing angiography. METHODS: Eighty-seven consecutive systolic heart failure patients who received either iso-osmolar iodixanol (n=44) or low-osmolar ioxilan (n=43), stratified for concomitant amiodarone, were evaluated for QT interval and serum creatinine changes in comparison to baseline. QT values were corrected according to three formulae: Bazett's correction, Fridericia formula, and Framingham equation. RESULTS: Baseline patient characteristics were not significantly different in the iodixanol versus ioxilan groups, except for myocardial infarction and renal disease. No significant change in mean QTc was observed after exposure to either CM agent compared to baseline. These results were unaffected by amiodarone. A significant improvement in serum creatinine from baseline was observed in the iodixanol group compared to the ioxilan group (-0.121 ± 0.35 mg/dL vs. 0.033 ± 0.23 mg/dL, respectively; p=0.045). CONCLUSIONS: No significant change in QTc interval was observed in patients receiving either iodixanol or ioxilan during angiography. Iodixanol appeared to improve short-term renal function in patients with heart failure and should be further investigated.

Radiofrequency catheter ablation and nerve growth factor concentration in humans.

BACKGROUND: In animal models, expression of nerve growth factor (NGF) is increased after necrotic myocardial injury. Whether radiofrequency (RF) catheter ablation increases NGF expression in humans is unclear. OBJECTIVES: The purpose of this study was to determine NGF concentrations in the aorta, coronary sinus, and peripheral veins before and after RF ablation in patients. METHODS: We sampled blood from aorta and either great cardiac vein (group 1, N = 18) or proximal (group 2, N = 20) coronary sinus before and after RF ablation. In group 3 (N = 21), peripheral venous blood was sampled before and after RF ablation and then up to postoperative day 7. In group 4 (N = 10), we sampled peripheral venous blood during diagnostic electrophysiologic study. The NGF concentration was determined by enzyme-linked immunosorbent assay. Transcardiac NGF concentration was the difference in NGF concentrations between coronary sinus and aorta. RESULTS: There was no change in transcardiac NGF concentrations in groups 1 and 2. In group 3, the NGF level did not change significantly from before the procedure (17.10 +/- 15.80 ng/mL) to immediately after the procedure (14.46 +/- 10.36 ng/mL). However, NGF levels increased significantly to 31.24 +/- 19.82 ng/mL (N = 21, P <.0001) on postoperative day 1, 26.23 +/- 16.89 ng/mL (N = 20, P <.001) on postoperative day 2, and 22.01 +/- 11.35 ng/mL (N = 16, P = .003) on postoperative day 3. NGF concentrations did not change significantly in group 4. CONCLUSION: RF ablation did not result in a detectable increase of transcardiac NGF concentration immediately after the procedure. However, the systemic NGF concentration increased significantly on postoperative days 1 to 3, suggesting that RF ablation resulted in increased NGF expression.

Mechanisms of cardiac nerve sprouting after myocardial infarction in dogs.

Cardiac nerve sprouting and sympathetic hyperinnervation after myocardial infarction (MI) both contribute to arrhythmogenesis and sudden death. However, the mechanisms responsible for nerve sprouting after MI are unclear. The expression of nerve growth factor (NGF), growth associated protein 43 (GAP43), and other nerve markers were studied at the infarcted site, the noninfarcted left ventricle free wall (LVFW), and the left stellate ganglion (LSG) at several time points (30 minutes to 1 month) after MI. Transcardiac (difference between coronary sinus and aorta) NGF levels were also assayed. Acute MI resulted in the immediate elevation of the transcardiac NGF concentration within 3.5 hours after MI, followed by the upregulation of cardiac NGF and GAP43 expression, which was earlier and more pronounced at the infarcted site than the noninfarcted LVFW. However, cardiac nerve sprouting and sympathetic hyperinnervation were more pronounced in the noninfarcted than the infarcted LVFW site and peaked at 1 week after MI. The NGF and GAP43 protein levels significantly increased in the LSG from 3 days (P<0.01 for all) after MI, without a concomitant increase in mRNA. There was persistent elevation of NGF levels in aorta and coronary sinus within 1 month after MI. We conclude MI results in immediate local NGF release, followed by upregulation of NGF and GAP43 expression at the infarcted site. NGF and GAP43 are transported retrogradely to LSG, which triggers nerve sprouting at the noninfarcted LVFW. A rapid and persistent upregulation of NGF and GAP43 expression at the infarcted site underlies the mechanisms of cardiac nerve sprouting after MI.

Smoking increases inflammation and metalloproteinase expression in human carotid atherosclerotic plaques.

OBJECTIVES: To evaluate the effects of cigarette smoking on the composition of human carotid endarterectomy plaques. BACKGROUND: Smoking has been recognized as a major risk factor in atherogenesis. It is believed that smoking contributes to the atherosclerotic process and plaque instability in part by increasing the adherence of macrophages to the vessel wall and inducing the release of proteolytic enzymes. However, data are lacking in humans. METHODS: Carotid endarterectomy specimens of 21 smokers and 21 nonsmokers matched for age, gender, and symptoms were immunohistochemically stained with antibodies against CD68 (macrophages [MAC]), macrophage-derived metalloelastase (MMP-12), and tissue inhibitor of metalloproteinase 1 (TIMP-1). Sections were also evaluated for elastin content by van Gieson staining. The stained areas were planimetrically quantified as the percentage of immunopositive tissue area of the total tissue area. RESULTS: Smoking was associated with increased macrophage immunoreactivity (9.1% +/-7.4% vs 3.4% +/- 2.9%; P = .003) as well as increased expression of MMP-12 (13.4% +/- 6.7% vs 5.5% +/- 3.5%; P = .0004). However, plaques from smokers had decreased TIMP-1 expression (7.7% +/- 5.7% vs 13.1% +/- 8.5%; P = .04) and decreased elastin content (26.9% +/- 14.5% vs 38.9% +/- 18.4%; P = .02). CONCLUSIONS: This study demonstrates that cigarette smoking increases markers of inflammation and tissue destruction in atherosclerotic plaques. This change in plaque composition may at least in part explain the effect of smoking on the instability of human atherosclerotic plaques.