Relationship of Laser-Doppler-Flow and coronary perfusion and a concise update on the importance of coronary microcirculation in donor heart machine perfusion

BACKGROUND: Machine perfusion (MP) is a novel method for donor heart preservation. The coronary microvascular function is important for the transplantation outcome. However, current research on MP in heart transplantation focuses mainly on contractile function. OBJECTIVE: We aim to present the application of Laser-Doppler-Flowmetry to investigate coronary microvascular function during MP. Furthermore, we will discuss the importance of microcirculation monitoring for perfusion-associated studies in HTx research. METHODS: Porcine hearts were cardioplegically arrested and harvested (Control group, N = 4). In an ischemia group (N = 5), we induced global ischemia of the animal by the termination of mechanical ventilation before harvesting. All hearts were mounted on an MP system for blood perfusion. After 90 minutes, we evaluated the effect of coronary perfusion pressures from 20 to 100 mmHg while coronary laser-doppler-flow (LDF) was measured. RESULTS: Ischemic hearts showed a significantly decreased relative LDF compared to control hearts (1.07±0.06 vs. 1.47±0.15; p = 0.034). In the control group, the coronary flow was significantly lower at 100 mmHg of perfusion pressure than in the ischemia group (895±66 ml vs. 1112±32 ml; p = 0.016). CONCLUSIONS: Laser-Doppler-Flowmetry is able to reveal coronary microvascular dysfunction during machine perfusion of hearts and is therefore of substantial interest for perfusion-associated research in heart transplantation.

CT-Guided Placement of a Neuromonitoring Suite in Swine for Trauma and Resuscitation Research

Background: This manuscript aims to describe a standardized method for placement of a neuromonitoring suite into the brain of a porcine model using CT guidance for use in trauma and resuscitation research. Methods: A baseline CT allowed for precise planning of the placement of the neuromonitoring suite including measurement of skull thickness at the location of the intended burr hole. After the burr hole was drilled, three neuromonitoring probes (pressure catheter, temperature probe, and laser doppler flow probe) were advanced into the brain parenchyma of the swine. A subsequent CT confirmed appropriate placement of the neuromonitoring suite. Results: Effective placement of the neuromonitoring suite was accomplished successfully and without complication in 6 Yorkshire swine. Mean duration of the procedure was 49.6 minutes ± 6.3. Representative data from one animal includes the following presented as mean ± standard deviation: intracranial pressure of 10 ± 0 mmHg, cerebral perfusion pressure of 61 ± 1 mmHg, intracranial temperature of 34.8 ± 0 °C, and brain perfusion of 704 ± 13 relative perfusion units. Conclusions: This CT-guided method facilitates placement of a neuromonitoring suite in a safe and reliable manner. The use of a neuromonitoring suite using CT may offer valuable insight into cerebral perfusion in the context of endovascular resuscitation.

P1094PULSE AMPLITUDE OF THE TOE MEASURED WITH A PORTABLE LASER DOPPLER FLOW METER IS USEFUL FOR SCREENING OF DIALYSIS PATIENTS FOR PERIPHERAL ARTERIAL DISEASE

Background and Aims Peripheral arterial disease (PAD) occurs at a high frequency in hemodialysis (HD) patients and is known to be associated with poor outcomes. Measurement of the ankle-brachial blood pressure index (ABI) or toe brachial index (TBI) has been used for screening, diagnosis and severity determination of PAD. However, the procedures for measurement of these indices are complicated and the measurements cannot be performed during dialysis sessions. The purpose of the present study was to clarify the ability of the toe blood flow and pulse amplitude measured with a portable laser Doppler flow meter (LDF) to detect PAD in dialysis patients, in comparison with the diagnostic abilities of ABI and TBI. Methods Fourteen patients on maintenance HD participated in this study. The mean age was 65.2 years old and the mean duration of HD was 9.1 years. We measured the ABI and TBI before HD, and the blood flow and pulse amplitude on the ventral side of the first toe with a portable LDF (pocket LDF®, JMS Co., Ltd., Tokyo, Japan) during the HD session on the same day. The correlations between the blood flow / pulse amplitude in the toe and the ABI / TBI were investigated. The sensitivity and specificity of the blood flow and pulse amplitude in the toe for PAD detection were determined by a receiver operating characteristic curve analysis. Statistical analysis was performed using the Fisher’s exact test. A p value of <5% was considered to indicate a significant difference. Results and Discussion No significant correlation was found between the blood flow and the pulse amplitude in the toe (p = 0.454). The blood flow was not correlated with either the ABI or the TBI (p = 0.286, p = 0.115, respectively). However, the pulse amplitude showed significant correlations with both the ABI and TBI (p < 0.001, p < 0.05). When we used the general reference cutoff values for ABI and TBI of 0.9 and 0.6, respectively, the sensitivity and specificity of ABI for the detection of PAD were 0.75 and 0.75, respectively, and those of TBI were 1.0 and 0.75, respectively. On the other hand, the sensitivity and specificity of blood flow in the toe were 0.50 and 1.0, respectively, when the cutoff value was set at 23.8 mL/min. The sensitivity and specificity of the pulse amplitude were 0.75 and 1.0, respectively, when the cutoff value was set at 7.6 mL/min. These results indicate that the pulse amplitude in the toe showed a high diagnostic ability, like ABI and TBI, for the detection of PAD. Although our results in this study were obtained from a small sample size and further investigation is warranted, the pulse amplitude measured with the portable LDF was correlated well with both the ABI and TBI, and its sensitivity and specificity for the detection of PAD were also high, indicating the high diagnostic ability of the pulse amplitude for PAD. As compared to the measurement of ABI or TBI, the pulse amplitude in the toe can be easily measured with a portable LDF, even during a dialysis session. Thus, we believe that the use of a portable LDF might be of great benefit as a screening tool for PAD. Conclusion The pulse amplitude in the toe measured with a portable LDF may have the potential to become a novel easily measurable index in the screening of dialysis patients for PAD.

Selective Thermal Stimulation Delays the Progression of Vasoconstriction During Body Cooling

The objective of this study was to test the feasibility of selective thermal stimulation (STS) as a method to upregulate glabrous skin blood flow. STS is accomplished by mild surface heating along the spinal cord. Four healthy subjects were tested in this study. Each participated in a control experiment and an intervention experiment (STS). Both experiments included establishing a maximum level of vasodilation, considered unique to a subject on a test day, and then cooling to a maximum level of vasoconstriction. Perfusion was measured by a laser Doppler flow probe on the index fingertip. The percent of perfusion in the range of minimum to maximum was the primary outcome variable. The data were fit to a linear mixed effects model to determine if STS had a significant influence on perfusion during whole body cooling. STS had a statistically significant effect on perfusion and increased glabrous skin blood flow by 16.3% (P < 0.001, CI (13.1%, 19.5%)) as skin temperature was decreased. This study supports the theory that STS improves the heat exchanger efficiency of palmar and plantar surfaces by increasing the blood flow.

Correlation of rheoencephalography and laser Doppler flow: a rat study

Measuring brain electrical impedance (rheoencephalography) is a potential technique for noninvasive, continuous neuro-monitoring of cerebral blood flow autoregulation in humans. In the present rat study, we compared changes in cerebral blood flow autoregulation during CO2 inhalation measured by rheoencephalography to changes measured by laser Doppler flowmetry, an invasive continuous monitoring modality. Our hypothesis was that both modalities would reflect cerebral blood flow autoregulation. Male Sprague-Dawley rats (n=28; 28 control and 82 CO2 challenges) were measured under anesthesia. The surgical preparation involved implantation of intracerebral REG electrodes and an LDF probe into the brain. Analog waveforms were stored in a computer. CO2 inhalation caused transient, simultaneous increases in the signals of both laser Doppler flow (171.99 ± 46.68 %) and rheoencephalography (329.88 ± 175.50%). These results showed a correlation between the two measured modalities; the area under the receiver operating characteristic curve was 0.8394. The similar results obtained by measurements made with laser Doppler flowmetry and rheoencephalography indicate that rheo-encephalography, like laser Doppler flowmetry, reflects cerebral blood flow autoregulation. Rheoencephalography therefore shows potential for use as a continuous neuro-monitoring technique.

Contribution of epoxyeicosatrienoic acids to the cerebral blood flow response to hypoxemia

Adenosine A2A receptors and ATP-activated K+ (KATP) channels contribute to part of the cerebral vasodilatory response to systemic hypoxia, but other mediators are likely involved. Epoxyeicosatrienoic acids (EETs) are cerebral vasodilators and are released from astrocytes exposed to hypoxia. Moreover, stimulation of metabotropic glutamate receptors (mGluR) produces vasodilation by an EET-dependent mechanism. Here, we tested the hypothesis that EET signaling and mGluR activation contribute to hypoxic vasodilation. Laser-Doppler flow was measured over cerebral cortex of anesthetized rats subjected to stepwise reductions in arterial oxygen saturation to 50-70%. Hypoxic reactivity was calculated as the slope of the change in laser-Doppler flow vs. the reciprocal of arterial oxygen content. Hypoxic reactivity significantly decreased from 9.2 ± 1.9 (±95% confidence interval) in controls with vehicle treatment to 2.6 ± 1.4 with the EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid, to 3.0 ± 1.5 with the EET synthesis inhibitor MS-PPOH, to 1.9 ± 2.3 with the combined mGluR subtype 1 and 5 antagonists 2-methyl-6-(phenylethynyl)pyridine and LY367385 , to 5.6 ± 1.2 with the KATP channel inhibitor glibenclamide, and to 5.8 ± 2.3 with the A2A receptor antagonist SCH58261. However, reactivity was not significantly altered by the A2B receptor antagonist MRS1754 (6.7 ± 1.8; P = 0.28 Dunnett's test) or by the 20-hydroxyeicosatetraenoic acid synthesis inhibitor HET0016 (7.5 ± 2.3; P = 0.6). These data indicate that, in addition to the known contributions of A2A receptors and KATP channels to the increase in cerebral blood flow during hypoxia, EETs and mGluRs make a major contribution, possibly by mGluR stimulation and hypoxia-induced release of EETs. In contrast, A2B receptors do not make a major contribution, and 20-hydroxyeicosatetraenoic acid does not significantly limit hypoxic vasodilation.