Cerebral perfusion and metabolism with mild hypercapnia vs. normocapnia in a porcine post cardiac arrest model with and without targeted temperature management.

Aim: To determine whether targeting mild hypercapnia (PaCO2 7 kPa) would yield improved cerebral blood flow and metabolism compared to normocapnia (PaCO2 5 kPa) with and without targeted temperature management to 33 °C (TTM33) in a porcine post-cardiac arrest model. Methods: 39 pigs were resuscitated after 10 minutes of cardiac arrest using cardiopulmonary bypass and randomised to TTM33 or no-TTM, and hypercapnia or normocapnia. TTM33 was managed with intravasal cooling. Animals were stabilized for 30 minutes followed by a two-hour intervention period. Hemodynamic parameters were measured continuously, and neuromonitoring included intracranial pressure (ICP), pressure reactivity index, cerebral blood flow, brain-tissue pCO2 and microdialysis. Measurements are reported as proportion of baseline, and areas under the curve during the 120 min intervention period were compared. Results: Hypercapnia increased cerebral flow in both TTM33 and no-TTM groups, but also increased ICP (199% vs. 183% of baseline, p = 0.018) and reduced cerebral perfusion pressure (70% vs. 84% of baseline, p < 0.001) in no-TTM animals. Cerebral lactate (196% vs. 297% of baseline, p < 0.001), pyruvate (118% vs. 152% of baseline, p < 0.001), glycerol and lactate/pyruvate ratios were lower with hypercapnia in the TTM33 group, but only pyruvate (133% vs. 150% of baseline, p = 0.002) was lower with hypercapnia among no-TTM animals. Conclusion: In this porcine post-arrest model, hypercapnia led to increased cerebral flow both with and without hypothermia, but also increased ICP and reduced cerebral perfusion pressure in no-TTM animals. The effects of hypercapnia were different with and without TTM.(Institutional protocol number: FOTS, id 14931).

The effects of geometry on stiffness measurements in high-field magnetic resonance elastography: A study on rodent cardiac phantoms.

PURPOSE: Cardiac magnetic resonance elastography (MRE) can be used to assess myocardial stiffness in vivo. Rodents play an important role in modern cardiovascular research, and small animal cardiac MRE may reveal important aspects of myocardial stiffness. The aim of this study was to explore the feasibility of small animal cardiac MRE through investigation of stiffness measurements of small cardiac phantoms that have known underlying stiffness. METHODS: Agarose gel phantoms of three different geometrical designs were used: homogeneous gels, solid hearts, and biventricular phantoms. The size of the heart phantoms was comparable with that of an end-diastolic rat heart. All phantoms were made with different underlying stiffnesses agarose concentration, (7.5, 10.0,15.0)g/l, and MRE acquisition was performed with three different frequencies (360, 380, 400)Hz. Two different post-processing methods were applied to the MRE wave images: local frequency estimate (LFE) and direct inversion (DI). RESULTS: The stiffness associated with the different agarose concentrations (7.5, 10.0, 15.0)g/l in the homogenous gels at 400 Hz were (1.80 ± 0.18, 3.13 ± 0.20, 4.13 ± 0.37)kPa for LFE and (2.25 ± 0.24, 4.35 ± 0.45, 6.54 ± 0.44)kPa for DI, respectively. Significant differences in MRE-derived stiffness were observed among phantoms with different agarose concentrations for all geometries. However, biases in the stiffness measurements among the different geometries were observed and could not be explained by the measurement variability. The relative stiffness uncertainty was smallest for the LFE inversion algorithm. CONCLUSIONS: The stiffness measurements validate the use of the MRE technique to differentiate between various underlying stiffnesses in small cardiac phantoms. The stiffness measurements seemed to be dominated by geometrical effects when the cardiac MRE wavelength was longer than half the size of the heart. LFE was the inversion algorithm that was most sensitive to the changes in underlying stiffness.

Cerebral perfusion and metabolism with mean arterial pressure 90 vs. 60 mmHg in a porcine post cardiac arrest model with and without targeted temperature management.

AIM: To determine whether targeting a mean arterial pressure of 90 mmHg (MAP90) would yield improved cerebral blood flow and less ischaemia compared to MAP 60 mmHg (MAP60) with and without targeted temperature management at 33 °C (TTM33) in a porcine post-cardiac arrest model. METHODS: After 10 min of cardiac arrest, 41 swine of either sex were resuscitated until return of spontaneous circulation (ROSC). They were randomised to TTM33 or no-TTM, and MAP60 or MAP90; yielding four groups. Temperatures were managed with intravasal cooling and blood pressure targets with noradrenaline, vasopressin and nitroprusside, as appropriate. After 30 min of stabilisation, animals were observed for two hours. Cerebral perfusion pressure (CPP), cerebral blood flow (CBF), pressure reactivity index (PRx), brain tissue pCO2 (PbtCO2) and tissue intermediary metabolites were measured continuously and compared using mixed models. RESULTS: Animals randomised to MAP90 had higher CPP (p < 0.001 for both no-TTM and TTM33) and CBF (no-TTM, p < 0.03; TH, p < 0.001) compared to MAP60 during the 150 min observational period post-ROSC. We also observed higher lactate and pyruvate in MAP60 irrespective of temperature, but no significant differences in PbtCO2 and lactate/pyruvate-ratio. We found lower PRx (indicating more intact autoregulation) in MAP90 vs. MAP60 (no-TTM, p = 0.04; TTM33, p = 0.03). CONCLUSION: In this porcine cardiac arrest model, targeting MAP90 led to better cerebral perfusion and more intact autoregulation, but without clear differences in ischaemic markers, compared to MAP60. INSTITUTIONAL PROTOCOL NUMBER: FOTS, id 8442.

Absence of NLRP3 Inflammasome in Hematopoietic Cells Reduces Adverse Remodeling After Experimental Myocardial Infarction.

An inflammatory response is required for tissue healing after a myocardial infarction (MI), but the process must be balanced to prevent maladaptive remodeling. This study shows that improved survival and cardiac function following MI, in mice deficient for the NLRP3 inflammasome, can be recapitulated in wild-type mice receiving bone marrow from Nlrp3 -/- mice. This suggests that NLRP3 activation in hematopoietic cells infiltrating in the myocardium increases mortality and late ventricular remodeling. Our data should encourage performing clinical trials directly targeting NLRP3 inflammasome and their inflammatory cytokines (interleukin-1ß and -18) in MI patients.

Improved MR phase-contrast velocimetry using a novel nine-point balanced motion-encoding scheme with increased robustness to eddy current effects.

Phase-contrast MRI (PC-MRI) velocimetry is a noninvasive, high-resolution motion assessment tool. However, high motion sensitivity requires strong motion-encoding magnetic gradients, making phase-contrast-MRI prone to baseline shift artifacts due to the generation of eddy currents. In this study, we propose a novel nine-point balanced velocity-encoding strategy, designed to be more accurate in the presence of strong and rapidly changing gradients. The proposed method was validated using a rotating phantom, and its robustness and precision were explored and compared with established approaches through computer simulations and in vivo experiments. Computer simulations yielded a 39-57% improvement in velocity-noise ratio (corresponding to a 27-33% reduction in measurement error), depending on which method was used for comparison. Moreover, in vivo experiments confirmed this by demonstrating a 26-53% reduction in accumulated velocity error over the R-R interval. The nine-point balanced phase-contrast-MRI-encoding strategy is likely useful for settings where high spatial and temporal resolution and/or high motion sensitivity is required, such as in high-resolution rodent myocardial tissue phase mapping.