Factors Determining Periprocedural and Long-term Complications of High Risk Carotid Artery Stenting.

BACKGROUND AND PURPOSE: Carotid artery stenting (CAS) has been, historically, an alternative to open endarterectomy (CEA) for stroke prevention in high risk patients with carotid atherosclerosis. We sought to determine the rates of periprocedural and long-term stroke or death and the risk factors for complications after CAS in our high risk patient population. METHODS: Clinical and treatment variables of consecutive CAS procedures performed between 2002 and 2011 were analyzed. Using univariate and multivariate logistic regression analyses we examined how patient characteristics influenced outcomes and changes in modified Rankin Score (mRS). RESULTS: In 152 patients, the composite total of periprocedural death, stroke, transient ischemic attack (TIA) and myocardial infarction (MI) rate was 3.95% (6/152). Chronic kidney disease (CKD) was strongly associated with periprocedural complications (p<0.001). Coronary artery disease/peripheral vascular disease (CAD/PVD) (p=0.03), dyslipidemia (p=0.02), CKD (p=0.01), and contralateral internal carotid artery stenosis (p=0.02) were non-modifiable risk factors for mRS increase. There were 25 deaths, 8 strokes, 11 TIAs, and 1 MI (mean follow-up 38.4 months, range 0-116 months). The presence of CAD/PVD (p=0.009) and dyslipidemia (p=0.002) were significantly associated with long-term complications. CONCLUSION: CAS was performed with low periprocedural complications in high-risk patients. Our rates compare very favorably to large-scale trials that have ideal patients. This data encourages the consideration of CAS in patients considered high risk for CEA and provides possible patient characteristics (CKD) to help with periprocedural risk stratification.

Cerebral blood flow and ventilatory sensitivity to CO2 measured with the modified rebreathing method.

The ventilatory response to carbon dioxide (CO2) measured by modified rebreathing (SrVE) is closer to that measured by the steady-state method (SsVE) than is the response measured by Read's rebreathing method. Furthermore, the value estimated by the steady-state method depends upon the number of data points used to measure it. We planned to assess if these observations were also true for cerebral blood flow (CBF), as measured by steady-state (SsCBF) and modified rebreathing (SrCBF) tests. Six subjects undertook two protocols, one in the steady-state and one with modified rebreathing. SsVE depended upon the number of data points used to calculate it, and SsVE and SrVE were similar. However, this was not the case with SsCBF, and SsCBF was much higher than SrCBF. These findings are consistent with the notions that the specific CO2 stimulus differs for CBF control as compared with ventilation (VE) control, and that prior hypocapnia has an effect on CBF and VE for longer than the duration of the hypocapnia.

Cerebral blood flow sensitivities to CO2 measured with steady-state and modified rebreathing methods.

It is well established that the ventilatory response to carbon dioxide (CO(2)) measured by modified rebreathing (Sr(VE)) is closer to that measured by the steady-state method (Ss(VE)) than is the response measured by Read's rebreathing method. It is also known that the value estimated by the steady-state method depends upon the combination of data points used to measure it. The aim of this study was to investigate if these observations were also true for cerebral blood flow (CBF), as measured by steady-state (Ss(CBF)) and modified rebreathing (Sr(CBF)) tests. Six subjects undertook two protocols: (a) steady state: PET(CO2) was held at 1.5 mm Hg above normal (isocapnia) for 10 min, then raised to three levels of hypercapnia, (8 min each; 6.5, 11.5 and 16.5 mm Hg above normal, separated by 4 min isocapnia). End-tidal PO2 was held at 300 mm Hg; (b) modified rebreathing: subjects underwent 6 min of voluntary hyperventilation to PET(CO2) approximately 20 mm Hg, and then rebreathed via a 6l bag filled with 6.5% CO(2) in O(2). We confirmed that the value for Ss(VE) depended upon the combination of data points used to calculate it, and also confirmed that Ss(VE) and Sr(VE) were similar. However, this was not the case with CBF. Estimates of Ss(CBF) were the same, regardless of the data points used in calculation, and Ss(CBF) was 89% greater than Sr(CBF) (P<0.05). We interpret these findings as consistent with the notion that the specific CO(2) stimulus differs for CBF and ventilatory control. The data also indicate that prior hypocapnia in the modified rebreathing protocol may have a persistent effect on both cerebral vessels and central ventilatory control.

Cerebral blood flow sensitivity to CO2 measured with steady-state and Read's rebreathing methods.

The ventilatory response to carbon dioxide (CO2) measured by the steady-state method is lower than that measured by Read's rebreathing method. A change in end-tidal P CO2 (PET CO2) results in a lower increment change in brain tissue P CO2 (Pt CO2) in the steady-state than with rebreathing: since Pt(CO2) determines the ventilatory response to CO2, the response is lower in the steady-state. If cerebral blood flow (CBF) responds to Pt CO2, the CBF-CO2 response should be lower in the steady-state than with rebreathing. Six subjects undertook two protocols, (a) steady-state: PET CO2 was held at 1.5 mmHg above normal (isocapnia) for 10 min, then raised to three levels of hypercapnia, (8 min each; 6.5, 11.5 and 16.5 mmHg above normal, separated by 4 min isocapnia). End-tidal P O2 was held at 300 mmHg; (b) rebreathing: subjects rebreathed via a 6 L bag filled with 6.5% CO2 in O2. Transcranial Doppler-derived CBF yielded a higher CBF-CO2 sensitivity in the steady-state than with rebreathing, suggesting that CBF does not respond to Pt CO2.

Remodeling of the cardiac pacemaker L-type calcium current and its beta-adrenergic responsiveness in hypertension after neuronal NO synthase gene transfer.

Hypertension is associated with abnormal neurohumoral activation. We tested the hypothesis that beta-adrenergic hyperresponsiveness in the sinoatrial node (SAN) of the spontaneously hypertensive rat occurs at the level of the L-type calcium current because of altered cyclic nucleotide-dependent signaling. Furthermore, we hypothesized that NO, a modulator of cGMP and cAMP, would normalize the beta-adrenergic phenotype in the hypertensive rat. Chronotropic responsiveness to norepinephrine (NE), together with production of cAMP and cGMP, was assessed in isolated atrial preparations from age-matched hypertensive and normotensive rats. Right atrial/SAN pacemaking tissue was injected with adenovirus encoding enhanced green fluorescent protein (control vector) or neuronal NO synthase (nNOS). In addition, L-type calcium current was measured in cells isolated from the SAN of transfected animals. Basal levels of cGMP were lower in hypertensive rat atria. These atria were hyperresponsive to NE at all of the concentrations tested, with elevated production of cAMP. This was accompanied by increased basal and norepinephrine-stimulated L-type calcium current. Using enhanced green fluorescent protein, we observed transgene expression within both tissue sections and isolated pacemaking cells. Adenoviral nNOS increased right atrial nNOS protein expression and cGMP content. NE-stimulated cAMP concentration and L-type calcium current were also attenuated by adenoviral nNOS, along with the chronotropic responsiveness to NE in hypertensive rat atria. Decreased calcium current after cardiac nNOS gene transfer contributes to the normalization of beta-adrenergic hyperresponsiveness in the SAN from hypertensive rats by modulating cyclic nucleotide signaling.