Atrial pacing lead location alters the hemodynamic effects of atrial-ventricular delay in dogs with pacing induced cardiomyopathy.

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.

Reactive oxygen species modulate coronary wall shear stress and endothelial function during hyperglycemia.

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 = 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.

Stent implantation alters coronary artery hemodynamics and wall shear stress during maximal vasodilation.

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.

Propofol alters left atrial function evaluated with pressure-volume relations in vivo.

UNLABELLED: The effects of IV anesthetics on left atrial (LA) function in vivo are unknown. We tested the hypothesis that propofol alters LA mechanics evaluated with pressure-volume relations in barbiturate-anesthetized dogs (n = 9) instrumented for measurement of aortic, LA, and left ventricular (LV) pressures (micromanometers) and LA volume (epicardial orthogonal sonomicrometers). LA myocardial contractility (E(es)) and dynamic chamber stiffness were assessed with end-systolic and end-reservoir pressure-volume relations, respectively. Relaxation was determined from the slope of LA pressure decline after contraction corrected for peak LA pressure. LA stroke work and reservoir function were assessed by A and V loop area, respectively, from the steady-state pressure-volume diagram. LA-LV coupling was determined by the ratio of E(es) to LV elastance. Dogs received propofol (5, 10, 20, or 40 mg. kg(-1). h(-1)) in a random manner, and LA function was determined after a 15-min equilibration at each dose. Propofol decreased heart rate, mean arterial blood pressure, and the maximal rate of increase of LV pressure. Propofol caused dose-related reductions in E(es), dynamic chamber stiffness, and E(es)/LV elastance. An increase in V loop area and declines in LA stroke work, emptying fraction, and the active LA contribution to LV filling also occurred. Relaxation was unchanged. The results indicate that propofol depresses LA myocardial contractility, reduces dynamic chamber stiffness, maintains reservoir function, and impairs LA-LV coupling but does not alter LA relaxation in vivo. IMPLICATIONS: Propofol depresses contractile function of left atrial (LA) myocardium, impairs mechanical matching between the LA and the left ventricular (LV), and reduces the active LA contribution to LV filling in vivo. Compensatory decreases in chamber stiffness contribute to relative maintenance of LA reservoir function during the administration of propofol.