Biomarkers of PAH exposure in an intertidal fish species from Prince William Sound, Alaska: 2004-2005.

Polycyclic aromatic hydrocarbon (PAH) exposure biomarkers were measured in high cockscomb prickleback (Anoplarchus purpurescens) fish collected from both previously oiled and unoiled shore in Prince William Sound (PWS), Alaska, to test the hypothesis that fish living in the nearshore environment of the sound were no longer being exposed to PAH from the Exxon Valdez oil spill. Pricklebacks spend their entire lives in the intertidal zone of rocky shores with short-term movements during feeding and breeding restricted to an area of about 15 meters in diameter. Fish were assayed for the PAH exposure biomarkers, bile fluorescent aromatic compounds (FAC), and liver ethoxyresorufin O-deethylase (EROD) activity (a measure of cytochrome P450 1A (CYP1A) monooxygenase activity). Bile FAC concentrations and EROD activities were low and not significantly different in fish from previously oiled and unoiled sites. The similar low EROD activity and bile FAC concentrations in fish from oiled and unoiled shores, supports the hypothesis that these low-level biomarker responses were not caused by exposure of the fish to residues of the spilled oil.

Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension.

Hypertension is a major cardiovascular risk factor in the metabolic syndrome (MS) in which the presence of insulin resistance, glucose intolerance, abnormal lipoprotein metabolism, and central obesity all confer an increased risk. Because essential hypertension (EHT), insulinemia, and visceral fat are associated with sympathetic hyperactivity, which is itself known to increase cardiovascular risk, the aim of this study was to see if MS is a state of sympathetic nerve hyperactivity and if the additional presence of EHT intensifies this hyperactivity. In 69 closely matched subjects, comprising hypertensive MS (MS+EHT, 18), normotensive MS (MS-EHT, 17), hypertensives without MS (EHT, 16), and normotensive controls without MS (NC, 18), we measured resting muscle sympathetic nerve activity (MSNA) as assessed from multiunit discharges and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in MS+EHT (76+/-3.1 impulses/100 beats) was greater (at least P<0.01) than in MS-EHT (62+/-3.2 impulses/100 beats) and in EHT (60+/-2.3 impulses/100 beats), and all these were significantly greater (at least P<0.01) than in NC (46+/-2.7 impulse/100 beats). The multi-unit MSNA followed a similar trend. These findings suggest that MS is a state of sympathetic nerve hyperactivity and that the additional presence of hypertension further intensifies this hyperactivity. The degree of sympathetic hyperactivity seen in this study could be argued at least partly to contribute to the higher cardiovascular risk and metabolic abnormalities seen in MS+EHT patients.

Polycyclic aromatic hydrocarbon sources related to biomarker levels in fish from Prince William Sound and the Gulf of Alaska.

Seafloor sediments in Prince William Sound (PWS) and the eastern Gulf of Alaska (GOA) have a substantial regional hydrocarbon background from natural sources including oil seeps and eroding sedimentary rocks along the eastern GOA coast. Polycyclic aromatic hydrocarbons (PAH) from that background appear to be bioavailable to fish. Fish collected from PWS and the GOA in a 1999--2000 biomarker study (bile fluorescent aromatic contaminants and liver ethoxyresorufin O-deethylase) show evidence of exposure to low levels of PAH at all categories of sites sampled. Seafloor sediments at fish sampling sites in the GOA east of PWS and at three PWS site categories (nonspill path, spill path oiled, and spill path not oiled) contain hydrocarbons from four principal sources: regional background, combustion products, residues from the 1989 Exxon Valdez oil spill (EVOS), and Monterey (CA) petroleum residues. GOA sediments between PWS and Yakutat Bay, approximately 350 km to the east, are dominated by regional petrogenic background hydrocarbons (total PAH (TPAH) range approximately 60-3400 ng/g) that are the probable cause of low biomarker levels measured in halibut from this area. PWS sediments contain varying proportions of regional background, combustion products, Monterey residues, and EVOS residues at some spill path sites. Rockfish caught in PWS embayments in 1999 have liver EROD activities that correlate positively with the pyrogenic PAH indicator ratio (FI+Py)/C24Ph. Although traces (<5-100 ng/g TPAH) of EVOS residues were detected in seafloor sediments at some nearshore spill path sites, biomarker levels in fish from those sites are not elevated relative to other sites in PWS.

Sympathetic drive in anterior and inferior uncomplicated acute myocardial infarction.

BACKGROUND: The sympathetic activation that follows acute myocardial infarction (AMI) has been associated with increased morbidity and mortality. Because the prognosis after anterior AMI (ant-AMI) is worse than that after inferior AMI (inf-AMI), we planned to determine whether the magnitude of sympathetic hyperactivity differs between the two. METHODS AND RESULTS: Thirty-nine patients with uncomplicated AMI, comprising 2 matched groups of 17 patients with ant-AMI, and 22 patients with inf-AMI were examined. Measurements were obtained 2 to 4 days after AMI and compared with 20 normal subjects (NC) who were matched in terms of age and body weight to the AMI groups. Resting muscle sympathetic nerve activity was quantified from multiunit bursts (MSNA) and from single units (s-MSNA). Both groups of AMI patients were matched with regard to hemodynamic variables, left ventricular function, and infarct size. Both groups had greater (at least P<0.01) sympathetic nerve activity than NC (60+/-4.3 bursts/100 cardiac beats and 68+/-4.9 impulses/100 cardiac beats), but the magnitude of sympathetic nerve hyperactivity in ant-AMI (81+/-4.0 bursts/100 cardiac beats and 91+/-4.9 impulses/100 cardiac beats) was similar (P>0.05) to that in inf-AMI (80+/-3.2 bursts/100 cardiac beats and 90+/-4.0 impulses/100 cardiac beats) CONCLUSIONS: Both ant-AMI and inf-AMI resulted primarily in a similar magnitude of sympathetic nerve hyperactivity. These findings suggest that the worse prognosis after ant-AMI compared with after inf-AMI would not be related primarily to the degree of sympathetic hyperactivity.

Impact of type 2 diabetes mellitus on sympathetic neural mechanisms in hypertension.

BACKGROUND: Essential hypertension (EHT) is a major cardiovascular risk factor, and the additional presence of type 2 diabetes mellitus (DM2) increases this risk. However, although the sympathetic nerve hyperactivity of EHT is known to play a role in cardiovascular risk, the level of sympathetic nerve activity is known neither in DM2 nor in hypertensive type 2 diabetic patients (EHT+DM2). Therefore, we planned to quantify the vasoconstrictor sympathetic nerve activity in patients with EHT+DM2 and with DM2 relative to that in matched groups with EHT and normal blood pressure (NT). METHODS AND RESULTS: In 68 closely matched subjects with EHT+DM2 (n=17), DM2 (n=17), EHT (n=17), and NT (n=17), we measured resting muscle sympathetic nerve activity as the mean frequency of multiunit bursts (MSNA) and of single units (s-MSNA) with defined vasoconstrictor properties. The s-MSNA in EHT+DM2 (97+/-3.8 impulses/100 beats) was greater (at least P<0.001) than in EHT (69+/-3.4 impulses/100 beats) and DM2 (78+/-4.1 impulses/100 beats), and all these were significantly greater (at least P<0.01) than in NT (53+/-3.3 impulses/100 beats) despite similar age and body mass index. The MSNA followed a similar trend. In addition, the level of insulin was also raised in EHT+DM2 (20.4+/-3.6 microU/mL) and DM2 (18.1+/-3.1 microU/mL; at least P<0.05) compared with HT or NT. CONCLUSIONS: Patients with EHT+DM2, EHT, or DM2 had central sympathetic hyperactivity, although plasma insulin levels were raised only in EHT+DM2 and DM2. The combination of EHT and DM2 resulted in the greatest sympathetic hyperactivity and level of plasma insulin, and this hyperactivity could constitute a mechanism for the increased risks of this condition.

Biomarkers in fish from Prince William Sound and the Gulf of Alaska: 1999-2000.

To test the hypothesis that biomarker levels in fish collected at Prince William Sound (PWS) sites impacted by the 1989 Exxon Valdez oil spill were higher than those collected at unimpacted sites, a 1999-2000 study collected five fish species and associated benthic sediments from 21 sites in PWS and the eastern Gulf of Alaska (GOA). PWS sites were divided in three oiling categories based upon 1989 shoreline assessments: nonspill path (NSP), spill path oiled (SPO), and spill path not oiled (SPNO). Rockfish (N = 177), rock sole (N = 30), and kelp greenling (N = 49) were collected at near-shore locations (approximately 50-500 m from shore); Pacific halibut (N = 131) and Pacific cod (N = 81) were collected further offshore (approximately 500-7000 m). Fish were assayed for bile fluorescent aromatic contaminants (FAC) and cytochrome P4501A (CYP1A) levels measured as liver ethoxyresorufin O-deethylase (EROD) activity and by immunohistochemistry (IHC) of various tissues. For all species studied at all sites, bile FAC concentrations and CYP1A levels were low and in the same range for fish collected at PWS SPO and SPNO sites relative to NSP sites in PWS and the GOA. Consequently, the hypothesis is rejected for the species studied. The bile FAC results further indicate a pervasive exposure of fish at all sites, including those in the GOA far removed from the effects of the spill, to low levels of polycyclic aromatic hydrocarbons. Analysis of the benthic sediments indicates that the probable sources of this exposure are petrogenic hydrocarbons derived from natural oil seeps and eroding sedimentary rocks in the eastern GOA.