Detection of left atrial thrombus by intracardiac echocardiography in patients undergoing ablation of atrial fibrillation.

BACKGROUND: The role of intracardiac echocardiography (ICE) to detect thrombus within left atrium (LA) before atrial fibrillation (AF) ablation despite a recent transesophageal echocardiogram (TEE) is not well defined. We examined the prevalence of LA/left atrial appendage (LAA) thrombus using ICE immediately prior to AF ablation in patients in whom anticoagulation was not withheld. METHODS: We analyzed 122 consecutive patients (62.6 ± 10.8 years, 90 males, CHA(2)DS(2) -VASc score 2.4 ± 1.5, persistent AF 29.5 %) who underwent an ICE-guided AF ablation 1 day after a negative (n = 120) or inconclusive (n = 2) TEE for LA thrombus. LA was imaged with ICE from the right atrium, coronary sinus, and right ventricular inflow tract (RVIT). ICE and TEE images were compared for LAA area, thrombus, and spontaneous echo contrast (SEC). RESULTS: LAA was adequately visualized in 99 and 100 % of patients with TEE and ICE, respectively. RVIT was the best ICE view for LAA visualization. The LAA 2-D-area measured by TEE was 4.9 ± 0.5 vs. 5 ± 0.5 cm(2) by ICE (P = NS). ICE identified a thrombus in seven patients with a previous negative TEE, leading to cancellation of ablation. It ruled out a thrombus in two patients with an inconclusive TEE. Thrombi were found in the LAA (n = 4), atrial septum (n = 2), and left superior pulmonary vein (n = 1). SEC during TEE was more frequent in patients with thrombus on ICE than those without (85.7 vs. 17.4 %; p = 0.03; positive predictive value 23.1 %, negative predictive value 98.9 %). CONCLUSIONS: The results of our staged imaging approach suggest that ICE has a complimentary value in re-screening the LA/LAA for thrombus after a recent negative or equivocal TEE. The presence of SEC during TEE increases the probability of finding a thrombus with ICE, which could potentially be dislodged during catheter manipulation.

Revisiting the role of oxygen therapy in cardiac patients.

Over the past century, multiple studies lacking the precision of today's advanced technology provided conflicting data on the effects of oxygen therapy in normoxic cardiac patients. More importantly, no randomized, blinded, controlled studies have shown a benefit of such treatment. Yet the use of supplemental oxygen is widespread in cardiac patients. In these conditions, inadvertent hyperoxia commonly occurs because of concerns to ensure sufficient oxygenation and because hyperoxia is not perceived to be detrimental. In recent years, there has been mounting evidence demonstrating the potential adverse effects of hyperoxia on the cardiovascular system. In this report, we review data examining the effects of supplemental oxygen in normoxic patients with acute presentations of coronary artery disease. It is also the aim of this report to emphasize the point that oxygen therapy might have major adverse physiologic effects that must be considered when it is employed.

Hypoxia-induced vasodilation and effects of regional phentolamine in awake patients with sleep apnea.

Obstructive sleep apnea (OSA) is associated with increased sympathetic nerve activity, endothelial dysfunction, and premature cardiovascular disease. To determine whether hypoxia is associated with impaired skeletal muscle vasodilation, we compared femoral artery blood flow (ultrasound) and muscle sympathetic nerve activity (peroneal microneurography) during exposure to acute systemic hypoxia (fraction of inspired oxygen 0.1) in awake patients with OSA (n=10) and controls (n=8). To assess the role of elevated sympathetic nerve activity, in a separate group of patients with OSA (n=10) and controls (n=10) we measured brachial artery blood flow during hypoxia before and after regional alpha-adrenergic block with phentolamine. Despite elevated sympathetic activity, in OSA the vascular responses to hypoxia in the leg did not differ significantly from those in controls [P=not significant (NS)]. Following regional phentolamine, in both groups the hypoxia-induced increase in brachial blood flow was markedly enhanced (OSA pre vs. post, 84+/-13 vs. 201+/-34 ml/min, P<0.002; controls pre vs. post 62+/-8 vs. 140+/-26 ml/min, P<0.01). At end hypoxia after phentolamine, the increase of brachial blood flow above baseline was similar (OSA vs. controls +61+/-16 vs. +48+/-6%; P=NS). We conclude that despite high sympathetic vasoconstrictor tone and prominent sympathetic responses to acute hypoxia, hypoxia-induced limb vasodilation is preserved in OSA.

Sympathetic responses during saline infusion into the veins of an occluded limb.

Animal studies have shown that the increased intravenous pressure stimulates the group III and IV muscle afferent fibres, and in turn induce cardiovascular responses. However, this pathway of autonomic regulation has not been examined in humans. The aim of this study was to examine the hypothesis that infusion of saline into the venous circulation of an arterially occluded vascular bed evokes sympathetic activation in healthy individuals. Blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) responses were assessed in 19 young healthy subjects during local infusion of 40 ml saline into a forearm vein in the circulatory arrested condition. From baseline (11.8 +/- 1.2 bursts min(-1)), MSNA increased significantly during the saline infusion (22.5 +/- 2.6 bursts min(-1), P < 0.001). Blood pressure also increased significantly during the saline infusion. Three control trials were performed during separate visits. The results from the control trial show that the observed MSNA and blood pressure responses were not due to muscle ischaemia. The present data show that saline infusion into the venous circulation of an arterially occluded vascular bed induces sympathetic activation and an increase in blood pressure. We speculate that the infusion under such conditions stimulates the afferent endings near the vessels, and evokes the sympathetic activation.

Coronary blood flow responses to physiological stress in humans.

Animal reports suggest that reflex activation of cardiac sympathetic nerves can evoke coronary vasoconstriction. Conversely, physiological stress may induce coronary vasodilation to meet an increased metabolic demand. Whether the sympathetic nervous system can modulate coronary vasomotor tone in response to stress in humans is unclear. Coronary blood velocity (CBV), an index of coronary blood flow, can be measured in humans by noninvasive duplex ultrasound. We studied 11 healthy volunteers and measured beat-by-beat changes in CBV, blood pressure, and heart rate during 1) static handgrip for 20 s at 10% and 70% of maximal voluntary contraction; 2) lower body negative pressure at -10 and -30 mmHg for 3 min each; 3) cold pressor test for 90 s; and 4) hypoxia (10% O(2)), hyperoxia (100% O(2)), and hypercapnia (5% CO(2)) for 5 min each. At the higher level of handgrip, mean blood pressure increased (P < 0.001), whereas CBV did not change [P = not significant (NS)]. In addition, during lower body negative pressure, CBV decreased (P < 0.02; and P < 0.01, for -10 and -30 mmHg, respectively), whereas blood pressure did not change (P = NS). The dissociation between the responses of CBV and blood pressure to handgrip and lower body negative pressure is consistent with coronary vasoconstriction. During hypoxia, CBV increased (P < 0.02) and decreased during hyperoxia (P < 0.01), although blood pressure did not change (P = NS), suggesting coronary vasodilation during hypoxia and vasoconstriction during hyperoxia. In contrast, concordant increases in CBV and blood pressure were noted during the cold pressor test, and hypercapnia had no effects on either parameter. Thus the physiological stress known to be associated with sympathetic activation can produce coronary vasoconstriction in humans. Contrasting responses were noted during systemic hypoxia and hyperoxia where mechanisms independent of autonomic influences appear to dominate the vascular end-organ effects.

Cyclooxygenase inhibition attenuates sympathetic responses to muscle stretch in humans.

Passive muscle stretch performed during a period of post-exercise muscle ischemia (PEMI) increases muscle sympathetic nerve activity (MSNA), and this suggests that the muscle metabolites may sensitize mechanoreceptors in healthy humans. However, the responsible substance(s) has not been studied thoroughly in humans. Human and animal studies suggest that cyclooxygenase products sensitize muscle mechanoreceptors. Thus we hypothesized that local cyclooxygenase inhibition in exercising muscles could attenuate MSNA responses to passive muscle stretch during PEMI. Blood pressure (Finapres), heart rate, and MSNA (microneurography) responses to passive muscle stretch were assessed in 13 young healthy subjects during PEMI before and after cyclooxygenase inhibition, which was accomplished by a local infusion of 6 mg ketorolac tromethamine in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased prostaglandin synthesis to approximately 34% of the baseline. Before ketorolac Bier block, passive muscle stretch evoked significant increases in MSNA (P < 0.005) and mean arterial blood pressure (P < 0.02). After ketorolac Bier block, passive muscle stretch did not evoke significant responses in MSNA (P = 0.11) or mean arterial blood pressure (P = 0.83). Saline Bier block had no effect on the MSNA or blood pressure response to ischemic stretch. These observations indicate that cyclooxygenase inhibition attenuates MSNA responses seen during PEMI and suggest that cyclooxygenase products sensitize the muscle mechanoreceptors.

Effects of muscle metabolites on responses of muscle sympathetic nerve activity to mechanoreceptor(s) stimulation in healthy humans.

Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors and increase mechanoreceptor-mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this study, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean MSNA when muscle metabolite concentrations were increased. In 12 young healthy subjects, MSNA, ECG, and blood pressure were recorded. Subjects performed static fatiguing isometric handgrip at 30% maximum voluntary contraction followed by 4 min of postexercise muscle ischemia (PEMI). After 2 min of PEMI, wrist extension (i.e., wrist dorsiflexion) was performed. The static stretch protocol was also performed during 1) a freely perfused condition, 2) ischemia alone, and 3) PEMI after nonfatiguing exercise. Finally, repetitive short bouts of wrist extension were also performed under freely perfused conditions. This last paradigm evoked transient increases in MSNA but had no significant effect on mean MSNA over the whole protocol. During the PEMI after fatiguing handgrip, static stretch induced significant increases in MSNA (552 +/- 74 to 673 +/- 90 U/min, P < 0.01) and mean blood pressure (102 +/- 2 to 106 +/- 2 mmHg, P < 0.001). Static stretch performed under the other three conditions had no significant effects on mean MSNA and blood pressure. The present data verified that in healthy humans mechanoreceptor(s) stimulation evokes significant increases in mean MSNA and blood pressure when muscle metabolite concentrations are increased above a certain threshold.

Metabolic forearm vasodilation is enhanced following Bier block with phentolamine.

The extent to which sympathetic nerve activity restrains metabolic vasodilation in skeletal muscle remains unclear. We determined forearm blood flow (FBF; ultrasound/Doppler) and vascular conductance (FVC) responses to 10 min of ischemia [reactive hyperemic blood flow (RHBF)] and 10 min of systemic hypoxia (inspired O(2) fraction = 0.1) before and after regional sympathetic blockade with the alpha-receptor antagonist phentolamine via Bier block in healthy humans. In a control group, we performed sham Bier block with saline. Consistent with alpha- receptor inhibition, post-phentolamine, basal FVC (FBF/mean arterial pressure) increased (pre vs. post: 0.42 +/- 0.05 vs. 1.03 +/- 0.21 units; P < 0.01; n = 12) but did not change in the saline controls (pre vs. post: 0.56 +/- 0.14 vs. 0.53 +/- 0.08 units; P = not significant; n = 5). Post-phentolamine, total RHBF (over 3 min) increased substantially (pre vs. post: 628 +/- 75 vs. 826 +/- 92 ml/min; P < 0.01) but did not change in the controls (pre vs. post: 618 +/- 66 vs. 661 +/- 35 ml/min; P = not significant). In all conditions, compared with peak RHBF, peak skin reactive hyperemia was markedly delayed. Furthermore, post-phentolamine (pre vs. post: 0.43 +/- 0.06 vs. 1.16 +/- 0.17 units; P < 0.01; n = 8) but not post-saline (pre vs. post: 0.93 +/- 0.16 vs. 0.87 +/- 0.19 ml/min; P = not significant; n = 5), the FVC response to hypoxia (arterial O(2) saturation = 77 +/- 1%) was markedly enhanced. These data suggest that sympathetic vasoconstrictor nerve activity markedly restrains skeletal muscle vasodilation induced by local (forearm ischemia) and systemic (hypoxia) vasodilator stimuli.

The role of the cyclooxygenase products in evoking sympathetic activation in exercise.

Animal studies suggest that prostaglandins in skeletal muscles stimulate afferents and contribute to the exercise pressor reflex. However, human data regarding a role for prostaglandins in this reflex are varied, in part because of systemic effects of pharmacological agents used to block prostaglandin synthesis. We hypothesized that local blockade of prostaglandin synthesis in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing exercise. Blood pressure (Finapres), heart rate, and MSNA (microneurography) were assessed in 12 young healthy subjects during static handgrip and postexercise muscle ischemia (PEMI) before and after local infusion of 6 mg of ketorolac tromethamine in saline via Bier block (regional intravenous anesthesia). In the second experiment (n = 10), the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased the prostaglandins synthesis to approximately 33% of the baseline. After ketorolac Bier block, the increases in MSNA from the baseline during the fatiguing handgrip was significantly lower than that before the Bier block (before ketorolac: Delta502 +/- 111; post ketorolac: Delta348 +/- 62%, P = 0.016). Moreover, the increase in total MSNA during PEMI after ketorolac was significantly lower than that before the Bier block (P = 0.014). Saline Bier block had no similar effect. The observations indicate that blockade of prostaglandin synthesis attenuates MSNA responses seen during fatiguing handgrip and suggest that prostaglandins contribute to the exercise pressor reflex.

Muscle sympathetic nerve activity responses to dynamic passive muscle stretch in humans.

It is suggested that mechanoreceptors in muscle play an important role in the exercise pressor reflex. However, it has not been verified whether isolated stimulation of the mechanoreceptors can induce responses in muscle sympathetic nerve activity (MSNA) in young healthy individuals. We tested the hypothesis that passive stretch of muscle can evoke an increase in MSNA in healthy individuals. In 12 young subjects, leg calf muscles were passively stretched, or actively contracted for 5 s followed by a 15-25 s (random length) relaxation period. Stretch and contraction were each repeated 25 times. MSNA, heart rate and blood pressure were analysed, and averaged according to the onset of the force on a beat-by-beat basis. At the 1st to the 3rd heart beat from the onset of stretch, MSNA (199 +/- 30%, P < 0.05) as well as heart rate (102.5 +/- 0.7%, P < 0.05) increased transiently but significantly from the prior stretch baseline (100%), followed (from 3rd to 7th beat from the onset of stretch) by a transient increase in mean blood pressure (101.9 +/- 0.3%, P < 0.05) from the baseline. Similar response patterns were observed during active muscle contractions. The present data show that MSNA responses to isolated stimulation of mechanoreceptors are measurable. Because of baroreflex engagement, the magnitude of the response is small and transient, and the haemodynamic consequences using this protocol may be limited.