Detlef Russ

Fluorescent Cardiac Imaging A Novel Intraoperative Method for Quantitative Assessment of Myocardial Perfusion During Graded Coronary Artery Stenosis

Background— The purpose of the present study was to examine whether the effect of coronary stenoses of variable severity on myocardial perfusion can be quantitatively assessed in vivo by analysis of fluorescent cardiac imaging (FCI) compared with the gold standard, the fluorescent microsphere method. FCI is a novel technology to visualize coronary vessels and myocardial perfusion intraoperatively using the indocyanine green dye with an infrared-sensitive imaging device. Methods and Results— Graded stenoses and total vessel occlusion of the left anterior descending coronary artery were created in 11 open-chest pigs. Stenoses were graded to reduce resting left anterior descending coronary artery flow by 25%, 50%, 75%, and 100% of baseline flow measured by transit-time flowmeter. FCI images were analyzed with a digital image processing system. The impairment of myocardial perfusion was quantified by background-subtracted peak fluorescence intensity and slope of fluorescence intensity obtained with FCI and compared with myocardial blood flow assessed by fluorescent microsphere. All stenoses resulted in an impairment of myocardial perfusion visualized by FCI. Occlusion of the left anterior descending coronary artery resulted in a total perfusion defect (no fluorescence intensity) of the corresponding anterior myocardial wall. During graded stenosis and total vessel occlusion, normalized background-subtracted peak fluorescence intensity and slope of fluorescence intensity decreased significantly (P<0.0001). Both background-subtracted peak fluorescence intensity (r=0.92, P<0.0001) and slope of fluorescence intensity (r=0.93, P<0.0001) analyzed by FCI demonstrated good linear correlation with fluorescent microsphere–derived myocardial blood flow. Conclusions— The impairment of myocardial perfusion in response to increased coronary stenosis severity and total vessel occlusion can be quantitatively assessed by FCI and correlates well with results obtained by fluorescent microsphere.

Myeloperoxidase deficiency preserves vasomotor function in humans

Aims Observational studies have suggested a mechanistic link between the leucocyte-derived enzyme myeloperoxidase (MPO) and vasomotor function. Here, we tested whether MPO is systemically affecting vascular tone in humans. Methods and results A total of 12 135 patients were screened for leucocyte peroxidase activity. We identified 15 individuals with low MPO expression and activity (MPOlow), who were matched with 30 participants exhibiting normal MPO protein content and activity (control). Nicotine-dependent activation of leucocytes caused attenuation of endothelial nitric oxide (NO) bioavailability in the control group (P < 0.01), but not in MPOlow individuals (P = 0.12); here the MPO burden of leucocytes correlated with the degree of vasomotor dysfunction (P = 0.008). To directly test the vasoactive properties of free circulating MPO, the enzyme was injected into the left atrium of anaesthetized, open-chest pigs. Myeloperoxidase plasma levels peaked within minutes and rapidly declined thereafter, reflecting vascular binding of MPO. Blood flow in the left anterior descending artery and the internal mammary artery (IMA) as well as myocardial perfusion decreased following MPO injection when compared with albumin-treated animals (P < 0.001). Isolated IMA-rings from animals subjected to MPO revealed markedly diminished relaxation in response to acetylcholine (P < 0.01) and nitroglycerine as opposed to controls (P < 0.001). Conclusion Myeloperoxidase elicits profound effects on vascular tone of conductance and resistance vessels in vivo. These findings not only call for revisiting the biological functions of leucocytes as systemic and mobile effectors of vascular tone, but also identify MPO as a critical systemic regulator of vasomotion in humans and thus a potential therapeutic target.

Hemodynamic impact of transseptal access to the ascending aorta in a porcine model.

Purpose To evaluate the hemodynamic impact of transseptal sheath access to the ascending aorta using increasing sheath diameters. Methods Transseptal puncture was performed in 6 pigs (62 ± 9 kg) facilitating guidewire passage across the left heart to the descending aorta to establish transseptal through-and-through access into the ascending aorta. Hemodynamic parameters were evaluated during 6- to 16-F sheath deployments and after sheath retraction according to a standardized protocol. Fluorescent microspheres were injected for quantitative assessment of myocardial and cerebral perfusion and left-right shunting volume. Results Cardiac output, heart rate, and central venous pressure (CVP) were stable throughout the study in all animals. The ratio between pulmonary artery pressure and mean arterial pressure was significantly higher during sheath deployment compared to after retraction (p<0.01), indicating transient mitral valve insufficiency. The ratio between left atrial pressure and CVP was significantly higher with the sheath in place (p<0.01), signaling transient left-right shunting; the hemodynamic alteration disappeared after sheath retraction. Myocardial perfusion (p=0.224), cerebral perfusion (p=0.209), and left-right shunting volume (p=0.111) were not significantly affected by the transseptal access. Conclusion Transseptal access to the ascending aorta in a porcine model is feasible without persisting hemodynamic impairment or severe influence on myocardial or cerebral perfusion even with up to 16-F sheaths. Potential adverse effects need to be addressed before clinical use of this alternative access to the ascending aorta, aortic arch, and its side branches.

Imaging of Perfusion with Indocyanine Green Fluorescence a Promising Approach

Summary Intraoperative graft patency verification is of major clinical importance for quality control after coronary artery bypass grafting (CABG). The purpose of this study was assessment of graft patency and stenosis of variable severity by fluorescence angiography (FA) using indocyanine green (ICG). For this purpose 32 domestic pigs (40–70 kg) were examined by FA technique. ICG induced fluorescence imaging was performed on the native coronary vessels (n = 6) and stenosis (n = 8) of the left anterior descending coronary artery (LAD). In 18 pigs CABG was performed using left internal mammary artery or vein graft to LAD on the beating heart. Artificial obstructions of LAD or bypass anastomosis at various grade were created. FA was compared to coronary angiography (CA) and transit time flow measurement (TTFM) after each intervention. In all cases coronary flow and flow reduction could be determined by FA, in good correlation to TTFM. Additionally, FA could measure myocardial perfusion and functional impairment of coronary bypass during graded stenosis, determined by the reduction of myocardial fluorescence. FA and CA identified stenosis as well as total occlusion of the LAD and the bypass anastomosis in all cases. Furthermore, using FA the degree of blood flow reduction in ischemic versus normal myocardium during graded coronary and bypass stenosis could be determined. In conclusion, FA is a highly sensitive and reproducible technique for intraoperative quality control in CABG.

The potential of laser-induced interstitial thermotherapy to treat liver metastases

SummaryLaser-induced interstitial thermotherapy (LITT) is a method which has become a promising alternative for the palliative treatment of non-resectable metastases. At an early stage, a bare fibre was inserted, e.g. into liver metastases. Sophisticated applicators, with an integrated cooling system, are now used to increase the coagulated volume. The applicators can be introduced via laparotomy and laparoscopy under US-control, or percutaneously under CT- or MR-control. Most often, the Nd:YAG laser is used as the energy source, because of its good penetration properties in biological tissue. There is a simultaneous increase of the temperature in the whole volume reached by the laser radiation. This is a great advantage over cryotherapy and other thermal procedures, which are purely based on heat conduction. However, the maximal diameter treated is limited by the blood perfusion, that takes away a large amount of heat. Coagulation volumes of 35 mm in diameter can be reached. The coagulation zone can be c...

Qualitative angiographic and quantitative myocardial perfusion assessment using fluorescent cardiac imaging during graded coronary artery bypass stenosis

Intraoperative graft assessment in coronary artery bypass (CAB) grafting is important to avoid early graft failure. This study aimed to evaluate the accuracy of fluorescent cardiac imaging (FCI) for intraoperative qualitative angiographic and quantitative myocardial perfusion assessment during graded CAB stenosis compared to coronary angiography (CA). After CAB grafting to the left anterior descending coronary artery, graded distal bypass stenoses were created in ten pigs by 25, 50, 75, and 100% flow reduction assessed by transit-time flow measurement (TTFM). Visual angiographic assessment was performed by FCI and CA during baseline and graded bypass stenoses. Altered myocardial perfusion was assessed by quantitative intraoperative fluorescence intensity (QIFI) derived from FCI and correlated to TTFM. Patent bypass grafts and graft occlusion were visualized successfully by FCI and CA, while discrimination between various graded bypass stenosis was possible in 73.3%. The degree of CAB stenosis was overestimated in 16.7% and underestimated in 10.0% by FCI compared to CA. Graded CAB stenosis reduced regional myocardial perfusion quantified by decreased QIFI value (p < 0.001). Mean QIFI value was 76.8 (95% CI 67.2–86.3) during baseline, 55.6 (95% CI 45.3–65.9) during 25% flow-reduction, 30.6 (95% CI 22.3–39.0) during 50% flow-reduction, 20.3 (95% CI 15.4–25.3) during 75% flow-reduction, and 0 during CAB occlusion (p < 0.001) with a significant correlation to TTFM (r = 0.955; p < 0.0001). Solely visual assessment of CAB quality using FCI is limited as compared to CA. Additional QIFI assessment identified graded CAB stenosis and occlusion with a significant correlation to TTFM.

Initial experience with a new quantitative assessment tool for fluorescent imaging in peripheral artery disease

BACKGROUND Perioperative evaluation in peripheral artery disease (PAD) by common vascular diagnostic tools is limited by open wounds, medial calcinosis or an altered collateral supply of the foot. Indocyanine green fluorescent imaging (ICG-FI) has recently been introduced as an alternative tool, but so far a standardized quantitative assessment of tissue perfusion in vascular surgery has not been performed for this purpose. The aim of this feasibility study was to investigate a new software for quantitative assessment of tissue perfusion in patients with PAD using indocyanine green fluorescent imaging (ICG-FI) before and after peripheral bypass grafting. PATIENTS AND METHODS Indocyanine green fluorescent imaging was performed in seven patients using the SPY Elite system before and after peripheral bypass grafting for PAD (Rutherford III-VI). Visual and quantitative evaluation of tissue perfusion was assessed in an area of low perfusion (ALP) and high perfusion (AHP), each by three independent investigators. Data assessment was performed offline using a specially customized software package (Institute for Laser Technology, University Ulm, GmbH). Slope of fluorescent intensity (SFI) was measured as time-intensity curves. Values were compared to ankle-brachial index (ABI), slope of oscillation (SOO), and time to peak (TTP) obtained from photoplethysmography (PPG). RESULTS All measurements before and after surgery were successfully performed, showing that ABI, TTP, and SOO increased significantly compared to preoperative values, all being statistically significant (P < 0.05), except for TTP (p = 0.061). Further, SFI increased significantly in both ALP and AHP (P < 0.05) and correlated considerably with ABI, TTP, and SOO (P < 0.05). CONCLUSIONS In addition to ABI and slope of oscillation (SOO), the ICG-FI technique allows visual assessment in combination with quantitative assessment of tissue perfusion in patients with PAD. Ratios related to different perfusion patterns and SFI seem to be useful tools to reduce factors disturbing ICG-FI measurements.

Er:YAG laser for the surgical treatment of the carpal tunnel syndrome

We developed a new surgical procedure to improve the recurrence rate using an Er:YAG laser as dissection tool for the carpal ligament with the objective to ablate a small amount of the carpal ligament and to denaturate its ends. The Er:YAG Laser was transmitted to the applicator via a GeO fiber. With this system we proceeded 10 carpal ligament dissections without any complications in the follow-up period. All patients were free of pain and recurrence.

Simulation of the thermal effect of laser irradiation to optimize laser epilation

For hair removal commonly lasers are used with wavelengths being selectively absorbed by melanin .As a consequence, laser radiation leads to an increase of the temperature not only in melanin containing structures of the hair but also in the epidermis. Therefore, we simulated and studied the laser induced temperature development in tissue for various laser wavelengths and various pulse profiles. Modifying the beam parameters can improve the selectivity of the method. Monte- Carlo-Simulations were used to calculate light absorption in dermal structures, considering the tissue specific optical properties. The thermal diffusion in tissue was calculated by a finite difference method. The biological reaction due to the temperature rise was determined by an Arrhenius formalism and depends on temperature and time of laser-tissue interaction. The simulation program allows to calculate the temperature distribution and thermal damage for various temporal pulse profiles, fluence rates and irradiation geometries. Superficial cooling has an important influence and has been considered in the calculations. The results of our simulations for various laser types show differences in the thermal reaction which can be used to optimize the treatment modalities. The potential and limits of laser epilation can be estimated from these results. For example, a series of laser pulses has some advantages compared to a longer single pulse.

PRK by Er:YAG laser: in-vitro studies and first in-vivo experiences

Photorefractive keratectomy (PRK) is usually performed by an excimer laser at 193 nm wavelength. Ablatio of corneal tissue is, however, not only possible in the UV region of the optical spectrum but also in the IR where water is an excellent absorber. Therefore, an Er:YAG laser was used at 2.94 micrometer wavelength as an alternative laser light source to perform in vitro studies of corneal ablation and also first clinical experiments to correct myopia of patients with blind eyes.