Pulmonary vein isolation by radiosurgery: implications for non-invasive treatment of atrial fibrillation.

AIMS: Electrical isolation of the pulmonary veins (PVs) has been established in clinical routine as a curative treatment for atrial fibrillation (AF). While catheter ablation carries procedural risks, radiosurgery might be able to non-invasively induce lesions at the PV ostia to block veno-atrial electrical conduction. This porcine feasibility and dose escalation study determined the effect of radiosurgery on electrophysiologic properties of the left atrial-PV junction. METHODS AND RESULTS: Eight adult Goettingen mini-pigs underwent electrophysiological voltage mapping in the left atrium and the upper right PV. Radiation was delivered with a conventional linear accelerator. A single homogeneous dose ranging from 22.5 to 40 Gy was applied circumferentially to the target vein antrum. Six months after radiosurgery, electrophysiological mapping was repeated and a histological examination performed. Voltage mapping consistently showed electrical potentials in the upper right PV at baseline. Pacing the target vein prompted atrial excitation, thus proving veno-atrial electrical conduction. After 6 months, radiation had reduced PV electrogram amplitudes. This was dose dependent with a mean interaction effect of -5.8%/Gy. Complete block of atrio-venous electrical conduction occurred after 40 Gy dose application. Histology revealed transmural scarring of the targeted PV musculature with doses >30 Gy. After 40 Gy, it spanned the entire circumference in accordance with pulmonary vein isolation. CONCLUSION: Pulmonary vein isolation to treat AF can be achieved by radiosurgery with a conventional linear accelerator. Yet, it requires a high radiation dose which might limit clinical applicability.

Dose-escalation study for cardiac radiosurgery in a porcine model.

PURPOSE: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. METHODS AND MATERIALS: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. RESULTS: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. CONCLUSIONS: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

Propofol in bronchoalveolar lavage during anaesthesia.

BACKGROUND: The lung protecting effect of propofol requires methods to measure the propofol concentration of the epithelial line fluid covering the alveolar surface. We hypothesized that (1) propofol can be determined in bronchoalveolar lavage (BAL) by reversed phase high performance liquid chromatography with fluorescence detection. (2) Positive end-expiratory pressure (PEEP) ventilation may have an effect on propofol concentration in BAL (cpB). METHODS: 76 surgical patients were investigated after institutional review board approval. After criteria-based exclusion 45 samples were included. For group I (n=15) BAL was performed directly after induction, for group Z (n=15, PEEP=0 cm H2O) and P (n=15, PEEP=10 cm H2O) at the end of anaesthesia. BAL and plasma samples were analysed for propofol by reversed phase high performance liquid chromatography with fluorescence detection. Data from all groups were compared by non-parametric Mann-Whitney U-test. RESULTS: Propofol can be detected in BAL. CpB varied between 23 and 167 µg l⁻¹ in all groups. Patients ventilated with PEEP (group P) showed significantly higher cpB (median 74.5 µg l⁻¹) compared to those immediately after induction of anaesthesia (median 42.0 µg l⁻¹) (group I), but not to those ventilated without PEEP in group Z (median 52.5 µg l⁻¹). CONCLUSION: Epithelial line fluid, sampled by BAL, can be used to determine cpB by reversed phase high performance liquid chromatography with fluorescence detection. Continuous propofol infusion and PEEP ventilation may have an effect on cpB.

Time course of ethanol and propofol exhalation after bolus injection using ion molecule reaction-mass spectrometry.

The transit of ethanol from blood to breath gas is well characterised. It is used for intraoperative monitoring and in forensic investigations. A further substance, which can be measured in breath gas, is the phenol propofol. After a simultaneous bolus injection, the signals (time course and amplitude) of ethanol and propofol in breath gas were detected by ion molecule reaction-mass spectrometry (IMR-MS) and compared. After approval by the regional authorities, eight pigs were endotracheally intubated after a propofol-free induction with etomidate. Boluses of ethanol (16 µg/kg) and propofol (4 or 2 mg/kg) were infused alone and in combination. For both substances, breath gas concentrations were continuously measured by IMR-MS; the delay time, time to peak and amplitude were determined and compared using non-parametric statistic tests. IMR-MS allows a simultaneous continuous measurement of both substances in breath gas. Ethanol appeared (median delay time, 12 vs 29.5 s) and reached its peak concentration (median time to peak, 45.5 vs 112 s) significantly earlier than propofol. Time courses of ethanol and propofol in breath gas can be simultaneously described with IMR-MS. Differing pharmacological and physicochemical properties of the two substances can explain the earlier appearance and time to peak of ethanol in breath gas compared with propofol.

Impact of valves in a biomechanical heart model assisting failing hearts.

Experimental valveless muscular blood pumps (biomechanical hearts) in goats can pump more than 1 L.min(-1), but due to a high pendulum volume, no significant flow contribution to the circulation is gained. Thus valved and valveless biomechanical hearts were compared for efficacy. Heart failure was induced in 5 adult Bore goats by repeated intracoronary embolization. A valved and balloon-equipped pumping chamber was integrated into the descending aorta, simulating standard biomechanical circulatory support. The valveless biomechanical heart supported a failing heart with a baseline cardiac output of 2,670 +/- 710 mL.min(-1) by contributing additional flow of 113 +/- 37 mL.min(-1). The biomechanical heart model incorporating an outlet valve offered an additional 304 +/- 126 mL.min(-1), and the use of 2 valves significantly enhanced pulmonary blood flow by 1,235 +/- 526 mL.min(-1). The use of 2 valves in biomechanical hearts seems to be essential to achieve adequate circulatory support. Double-valved biomechanical hearts driven by an appropriate skeletal muscle ventricle may contribute to the therapy of heart failure.

Bio-technologies for a glandular stem cell cardiomyopexy.

The glandular stem cell cardiomyopexy should become a treatment option for end-stage heart failure. It combines an expected regenerative potential of transformed adult glandular stem cells into cardiomyocytes within the myocardium or onto the myocardium of the recipient and the potential of a hypercapillarized latissimus dorsi muscle (LDM) wrapped around the heart for stem cell nutrition and girdling.

Assessment of regional lung recruitment and derecruitment during a PEEP trial based on electrical impedance tomography.

OBJECTIVE: To investigate whether electrical impedance tomography (EIT) is capable of monitoring regional lung recruitment and lung collapse during a positive end-expiratory pressure (PEEP) trial. DESIGN: Experimental animal study of acute lung injury. SUBJECT: Six pigs with saline-lavage-induced acute lung injury. INTERVENTIONS: An incremental and decremental PEEP trial at ten pressure levels was performed. Ventilatory, gas exchange, and hemodynamic parameters were automatically recorded. EIT and computed tomography (CT) scans of the same slice were simultaneously taken at each PEEP level. MEASUREMENTS AND RESULTS: A significant correlation between EIT and CT analyses of end-expiratory gas volumes (r=0.98 up to 0.99) and tidal volumes (r=0.55 up to r=0.88) could be demonstrated. Changes in global and regional tidal volumes and arterial oxygenation (PaO2/FiO2) demonstrated recruitment/derecruitment during the trial, but at different onsets. During the decremental trial, derecruitment first occurred in dependent lung areas. This was indicated by lowered regional tidal volumes measured in this area and by a decrease of PaO2/FiO2. At the same time, the global tidal volume still continued to increase, because the increase of ventilation of the non-dependent areas was higher than the loss in the dependent areas. This indicates that opposing regional changes might cancel each other out when combined in a global parameter. CONCLUSIONS: EIT is suitable for monitoring the dynamic effects of PEEP variations on the regional change of tidal volume. It is superior to global ventilation parameters in assessing the beginning of alveolar recruitment and lung collapse.

Differences of propofol concentrations in mammalian whole blood and in corresponding plasma samples analyzed by high performance liquid chromatography.

BACKGROUND: In preparation for a study of the pharmacokinetics and elimination of propofol, a frequently used intravenous narcotic, we sought for a simple but accurate method for determining the drug in biological fluids from various mammalian species. MATERIALS AND METHODS: We established an isocratic high performance liquid chromatography (HPLC) assay with fluorimetric detection for quantification of propofol, studied the analytical characteristics of the method, and measured the narcotic in heparinized whole blood and corresponding plasma samples drawn from 5 subjects each of humans, pigs, sheep and goats prior to and after 10 minutes of constant infusion of propofol. RESULTS: Following protein precipitation with methanol, propofol was quantified in the alcoholic phase. With 30 microl extract, lower limits of detection and quantification of propofol were 2 and 10 microg I(-1), the measurable range extended to 8000 microg I(-1). Intra- and inter-assay CVs tested at propofol concentrations between 40 and 3000 microg I(-1) were < 3% and < 8%, respectively. Propofol levels ranged from 900 to 10,000 microg I(-1) after 10 minutes of drug infusion; among the animals treated with identical doses, pigs exhibited the highest and sheep the lowest circulating propofol concentrations. CONCLUSIONS: Analysis of propofol by the HPLC method described is highly practicable, sensitive and specific. Propofol concentrations measured in heparinized blood and corresponding plasma samples differ slightly; in addition to inter-individual variations, species-specific differences in the drug's disposition between plasma and blood cells were observed.

Changes in corneal hysteresis after clear corneal cataract surgery.

PURPOSE: To assess the changes in corneal hysteresis (CH) as measured by the Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments, Buffalo, New York, USA) to describe the influence of clear corneal cataract surgery on corneal viscoelastic properties and intraocular pressure (IOP) measured by noncontact tonometry (NCT) and Goldmann applanation tonometry (GAT). DESIGN: Retrospective, interventional, comparative study. METHODS: One hundred and one eyes of 101 consecutive patients who underwent routine clear corneal cataract surgery were evaluated. CH, NCT, and central corneal thickness (CCT) were measured by ORA before surgery and at postoperative day 1. A control group of 48 pseudophakic eyes (surgery >3 months previously) was included. RESULTS: CCT increased from 556.82 +/- 32.5 microm before surgery to 580.26 +/- 45.5 microm after surgery (P < .001; control, 555.16 +/- 42.33 microm). Mean CH decreased from 10.35 +/- 2.5 mm Hg before surgery to 9.20 +/- 1.9 mm Hg after surgery (P < .001; control, 10.47 +/- 1.63 mm Hg). NCT values rose from 17.85 +/- 3.8 mm Hg before surgery to 20.10 +/- 6.3 mm Hg after surgery. GAT values were 14.85 +/- 2.8 mm Hg before surgery and 15.24 +/- 4.1 mm Hg after surgery (P = .52). There was no significant difference of CCT or CH between the preoperative values and the values of the control group (CCT, P = .986; CH, P = .166), in contrast to the difference between postoperative values and the values of the control group (CCT, P = .005; CH, P = .031). CONCLUSIONS: At day 1 after clear corneal cataract surgery, CH is diminished, whereas CCT is increased significantly. Postoperative corneal edema leads to a change of corneal viscoelastic properties, resulting in a lower damping capacity of the cornea. It is supposed that GAT and NCT measurements are significantly different because of postoperative changes in viscoelastic properties of the cornea.

Discontinuous monitoring of propofol concentrations in expired alveolar gas and in arterial and venous plasma during artificial ventilation.

BACKGROUND: Analyzing propofol concentration in expired alveolar gas (cPA) may be considered as a convenient, noninvasive method to follow the propofol concentration in plasma (cPPL). In the current study, the authors established procedures to measure cPA and cPPL for the assessment of their relation in two animal models during anesthesia. METHODS: Expired alveolar gas and mixed venous and arterial blood were simultaneously sampled during continuous application of propofol for general anesthesia to three goats and three pigs. Propofol infusion rates were varied to modify plasma concentrations. cPA, sampled cumulatively over several respiratory cycles, was quantified by thermal desorption gas chromatography-mass spectrometry. cPPL was determined using reversed phase high-performance liquid chromatography with fluorescence detection. RESULTS: cPA ranged from 0 to 1.4 and from 0 to 22 parts per billion in goats and pigs, respectively, at cPPL of 0-8 microg/ml. The relation between cPA and cPPL was linear; however, the slopes of the regression lines varied between animals. CONCLUSION: Propofol can be quantified in expired alveolar gas. The results stress the role of marked species-specific variability.

Strategies for the reduction of cerebral microembolism during transmyocardial laser revascularization.

BACKGROUND AND OBJECTIVES: During transmyocardial laser revascularization (TMLR), multiple microembolic signals (MES) can be detected in cerebral arteries. We sought to characterize composition and clinical relevance of these MES and to evaluate strategies to reduce cerebral microembolization during TMLR. STUDY DESIGN/MATERIALS AND METHODS: TMLR was performed in pigs. Laser energy was set to 4-10 J (group A) or 80 J (group B). Oxygen concentration was varied between 21 and 100%. MES were recorded in the ophthalmic artery. Brain and spinal cord were investigated histologically after 10 days. RESULTS: More MES could be detected during high- compared to low-energy laser procedures. Ventilation with 100% oxygen reduced the number of MES. No lesions were found on histology. CONCLUSIONS: The number of MES depends on the laser energy. Laser-induces cavitation-effects lead to an additional release of nitrogen bubbles. Thus, the microembolic load can be reduced by ventilation with 100% oxygen and by decreasing the laser energy.

Development of muscular blood pumps performed in a one-step operation.

Up to now, the employment of skeletal muscle ventricles (SMVs) has required a two-step operation, that is, first, the construction followed by a vascular delay and electrical conditioning, and second, the integration into circulation by a second operation. As shown previously, clenbuterol increased the power of electrically conditioned SMVs wrapped around a mock system. These clenbuterol-supported SMVs pumped successfully from construction to several months against a pressure of 60-70 mm Hg. Due to these successful former experiments, a muscular blood pump has been employed via a one-step procedure, trained within the circulation under the support of clenbuterol. It appeared to be hemodynamically relevant and is expected to become clinically practicable for the treatment of end-stage heart failure.