Coronary stents improve resting blood flow and flow reserve in the presence of stenoses, but the impact of these devices on fluid dynamics during profound vasodilation is largely unknown. We tested the hypothesis that stent implantation affects adenosine-induced alterations in coronary hemodynamics and wall shear stress in anesthetized dogs (n = 6) instrumented for measurement of left anterior descending coronary artery (LAD) blood flow, velocity, diameter, and radius of curvature. Indexes of fluid dynamics and shear stress were determined before and after placement of a slotted-tube stent in the absence and presence of an adenosine infusion (1.0 mg/min). Adenosine increased blood flow, Reynolds (Re) and Dean numbers (De), and regional and oscillatory shear stress concomitant with reductions in LAD vascular resistance and segmental compliance before stent implantation. Increases in LAD blood flow, Re, De, and indexes of shear stress were observed after stent deployment (P < 0.05). Stent implantation reduced LAD segmental compliance to zero and potentiated increases in segmental and coronary vascular resistance during adenosine. Adenosine-induced increases in coronary blood flow and reserve, Re, De, and regional and oscillatory shear stress were attenuated after the stent was implanted. The results indicate that stent implantation blunts alterations in fluid dynamics during coronary vasodilation in vivo.

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Reactive oxygen species modulate coronary wall shear stress and endothelial function during hyperglycemia. Am J Physiol Heart Circ Physiol 284: H1552-H1559, 2003. First published January 23, 2003 10.1152/ajpheart.01013. 2002-Hyperglycemia is associated with generation of reactive oxygen species (ROS), and this action may contribute to accelerated atherogenesis. We tested the hypothesis that hyperglycemia produces alterations in left anterior descending coronary artery (LAD) wall shear stress concomitant with endothelial dysfunction and ROS production in dogs (n ϭ 12) instrumented for measurement of LAD blood flow, velocity, and diameter. Dogs were randomly assigned to receive vehicle (0.9% saline) or the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) and were administered intravenous infusions of D-glucose to achieve target blood glucose concentrations of 350 and 600 mg/dl (moderate and severe hyperglycemia, respectively). Endothelial function and ROS generation were assessed by coronary blood flow responses to acetylcholine (10, 30, and 100 ng/kg) and dihydroethidium fluorescence of myocardial biopsies, respectively. Indexes of wall shear stress were calculated with conventional fluid dynamics theory. Hyperglycemia produced dose-related endothelial dysfunction, increases in ROS production, and reductions in oscillatory shear stress that were normalized by tempol. The results suggest a direct association between hyperglycemia-induced ROS production, endothelial dysfunction, and decreases in oscillatory shear stress in vivo. coronary artery disease; diabetes; oscillatory shear stress; oxidant stress REACTIVE OXYGEN SPECIES (ROS) have been implicated in the pathogenesis of cardiovascular disease during diabetes mellitus and hyperglycemia. Several potential mechanisms have been identified that may account for increases in ROS generation during hyperglycemia including glucose autooxidation (2), mitochondrial superoxide anion overproduction by the electron transport chain (32), depletion of tetrahydrobiopterin (34), and synthesis of advanced glycation end-products (36). Hyperglycemia inhibits endothelium-dependent coronary vasodilation through oxidant-sensitive mechanisms (20,21,38). A disproportionate increase in superoxide anion compared with nitric oxide (NO) concentrations occurs during hyperglycemia that may account for endothelial dysfunction by altering the balance of oxidant stress (2,5,6), and this effect is attenuated by free radical scavengers that indirectly increase the availability of NO (2,29,35,38).Hyperglycemia has also been shown to adversely alter vascular fluid dynamics. An inverse relation between fasting blood glucose concentrations and wall shear stress has been observed in patients with diabetes compared with age-matched controls (15, 16), and endothelium-derived relaxing factors including NO are modulated by wall shear stress in a frequency-and amplitude-dependent manner (11,12). Regions of the arterial vasculature that are chronically exposed to low-ma...

Background. Nitric oxide (NO)-signal transduction plays an important role in renal ischemia/reperfusion (I/R) injury. NO produced by endothelial NO-synthase (eNOS) has protective functions whereas NO from inducible NO-synthase (iNOS) induces impairment. Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor (PPAR)-γ agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance. Methods. RGZ (5 mg/kg) was administered i.p. to SD-rats (f) subjected to bilateral renal ischemia (60 min). Following 24 h of reperfusion, inulin- and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3) was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue. Results. RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion) and reduces histomorphological injury. Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ. Conclusion. RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury.

The role of atrial lead location in cardiovascular function in the presence of impaired ventricular dysfunction is unknown. We tested the hypothesis that left atrial (LA) and left ventricular (LV) hemodynamics are affected by alterations in AV delay and are influenced by atrial pacing site in dogs with dilated cardiomyopathy. Dogs (n = 7) were chronically paced at 220 beats/min for 3 weeks to produce cardiomyopathy and then instrumented for measurement of LA, LV end diastolic pressure (LVEDP) and mean arterial pressure (MAP), LA volume, LV short-axis diameter, and aortic and pulmonary venous blood flow. Hemodynamics were measured after instrumentation and during atrial overdrive pacing from the right atrial appendage (RAA), coronary sinus ostium (CSO) and lower LA lateral wall (LAW). The AV node was then ablated, and hemodynamics were compared during dual chamber AV pacing (right ventricular apex) from each atrial lead location at several AV delays between 20 and 350 ms. Atrial overdrive pacing from different sites did not alter hemodynamics. Cardiac output (CO), stroke volume, LVEDP, MAP and +dLVP/dt demonstrated significant (P < 0.05) variation with AV delay during dual chamber pacing. CO was higher during LAW pacing than RAA and CSO pacing (2.3 +/- 0.4 vs 2.1 +/- 0.3 vs 2.0 +/- 0.3 l/min, respectively) at an AV delay of 120 ms. Also, MAP was higher in the LAW than RAA and CSO (65 +/- 9 vs 59 +/- 9 vs 54 +/- 11 mmHg, respectively) at an AV delay of 350 ms. Atrial lead location affects indices of LV performance independent of AV delay during dual chamber pacing in dogs with cardiomyopathy.