Veerle Leunens

Changes in organ perfusion after brain death in the rat and its relation to circulating catecholamines.

Brain death can have an impact on donor organ function. This is often attributed to an altered hormonal, mainly thyroidal, status after brain death. A second possible explanation is that during the brain death process, blood flow is redistributed, causing ischemic damage in underperfused organs or regions. We investigated blood flow redistribution with colored microspheres in the rat early and late after brain death, induced by inflation of an intracranial balloon, and correlated this with the global hemodynamic situation and plasma catecholamine concentrations. Brain death was proven by the demonstration of lasting absence of brain perfusion in all animals. Myocardial blood flow closely followed the myocardial oxygen need as estimated by the rate-pressure product. The abdominal organs showed intense vasoconstriction early after brain death, which led to significantly decreased perfusion of these organs despite the highly increased perfusion pressure, followed by significant vasodilation. Total plasma catecholamine concentration was 57 times higher at 30 sec after brain death as compared with basal levels. Plasma noradrenaline concentration fell significantly below basal levels late after brain death. We conclude that brain death importantly alters regional perfusion, with possible implications for donor organ function. These changes are probably due to the tremendous alterations in the activity of the sympathetic nervous system.

Use of Tissue Oxygenation Index and Fractional Tissue Oxygen Extraction as Non-Invasive Parameters for Cerebral Oxygenation

Objective: To evaluate the relation between cerebral tissue oxygenation index (TOI), measured with spatially resolved spectroscopy (SRS), and the different oxygenation parameters. To evaluate the relation between a new parameter named fractional tissue oxygen extraction (FTOE) and the cerebral fractional oxygen extraction (FOE). Methods: Six newborn piglets were measured at 33, 35, and 37°C and in hypocapnia. Mean arterial blood pressure (MABP), haemoglobin (Hb), peripheral oxygen saturation (S_aO₂) and P_aCO₂ were measured at each step. Cerebral blood flow (CBF) was measured by injection of coloured microspheres into the left atrium. Jugular bulb oxygen saturation (JVS), cerebral arterial and venous oxygen content (C_aO₂ and C_vO₂) and FOE were calculated. TOI of the brain was calculated and FTOE was introduced as (S_aO₂ – TOI)/S_aO₂. The correlation was calculated with an ANCOVA test. Results: There was a positive correlation (R = 0.4 and p = 0.011) between TOI and JVS. No correlation was found with CBF, MABP or Hb. There was a positive correlation between P_aCO₂ and cerebral TOI (R = 0.24 and p = 0.03). FTOE correlated well with FOE (R = 0.4 and p = 0.016) and there was a negative correlation between FTOE and P_aCO₂ (R = 0.24, p = 0.03). Conclusion: The measurement of TOI and FTOE by SRS correlated well with the cerebral venous saturation and FOE, respectively.

Ischemic preconditioning reduces unloaded myocardial oxygen consumption in an in-vivo sheep model*

OBJECTIVE Ischemic preconditioning (IP) describes the adaptation of the myocardium to ischemic stress preceded by short periods of ischemia and reperfusion. However, its cardioprotective mechanisms are not completely understood. We assessed the effect of IP on ventricular energetics in an in-vivo sheep model. METHODS IP was performed in six sheep by three 5 min aortic cross-clamping periods interspersed with 5 min of reperfusion during cardiopulmonary bypass and with six sheep as time-matched controls. Global myocardial ischemia was subsequently achieved by 30 min aortic cross-clamping with left ventricular unloading during normothermic cardiopulmonary bypass. Weaning from cardiopulmonary bypass was performed 40 min after reperfusion. At baseline, after treatment (IP or time-matched cardiopulmonary bypass), and up to 100 min after reperfusion, left ventricular pressure-volume loops were measured using a conductance catheter during a right heart bypass preparation. Contractility, diastolic function, and ventriculo-arterial coupling were evaluated. Ventricular energetics [the relation between myocardial oxygen consumption (MVO(2)) and systolic pressure-volume area (PVA)] was also evaluated. A right heart bypass was instituted to control the preload and to decompress the right ventricle completely, thereby eliminating parallel conductance variation and minimizing the contribution of the right ventricle to MVO(2). RESULTS IP reduced unloaded MVO(2) (PVA-independent MVO(2)). Contractility, diastolic function, and ventriculo-arterial coupling in the IP group were better preserved than in the control group after ischemia-reperfusion. CONCLUSIONS IP reduces unloaded MVO(2), and preserves contractility, diastolic function, and ventriculo-arterial coupling after 30 min global myocardial ischemia in an in-vivo sheep model.

Measurement of the liver tissue oxygenation by near-infrared spectroscopy

ObjectiveTo study the relation between the liver tissue oxygenation index (TOI), transcutaneously measured with spatially resolved spectroscopy (a new method of near-infrared spectroscopy or NIRS), the mixed venous oxygen saturation and the blood flow in the different parts of the splanchnic circulation in newborn piglets.DesignTissue oxygenation index of the liver was measured in six newborn piglets at 33°C, 35°C, 37°C and after a decrease in arterial carbon dioxide pressure (PaCO2).MeasurementsMixed venous oxygen saturation, blood gas analysis and peripheral oxygen saturation were measured at each step. Gastric, proximal jejunal, midgut, distal ileal, splenic and hepatic arterial blood flow were measured by injection of coloured microspheres into the left atrium. NIRS optodes were attached to the skin over the liver and TOI was calculated.ResultsNo significant changes of TOI of the liver were seen during the increase in temperature or change in PaCO2. TOI correlated well with mixed venous oxygen saturation (r=0.85), the mid-ileal blood flow (r=0.57) and the distal ileal blood flow (r=0.72).ConclusionsMeasurement of the TOI of the liver might be a non-invasive way to measure the distal ileal blood flow.

Effect of transmyocardial laser revascularization on chronic ischemic hearts in sheep.

BACKGROUND We investigated the effect of transmyocardial laser revascularization (TMR) on myocardial function and regional blood flow in an animal model of ischemic heart disease. METHODS Chronic ischemia was induced in 11 sheep by the application of coronary stenosis on the left anterior descending (LAD) and circumflex coronary artery (LCX). Ten weeks later, in six of them, transmyocardial channels were created in the anterior free wall and in the posterior wall of the left ventricle. Five animals served as controls. The myocardial function was assessed by echocardiography taken at baseline and every 2 weeks after coronary stenosis and after TMR. Myocardial perfusion was measured by colored microspheres, injected at baseline, immediately after coronary stenosis, before and after TMR, and at 20 weeks after coronary stenosis. The hearts were retrieved at 20 weeks for light microscopic examination. RESULTS The left ventricular end-diastolic and end-systolic cavity area was elevated 20 weeks after coronary stenosis in the control and TMR groups. There was no difference between groups (analysis of variance; ANOVA, non-significant). The wall thickening fraction (WTF) decreased progressively and significantly after coronary stenosis in both groups. The WTF was further acutely reduced by TMR, and recovered gradually to the pre-TMR level. No significant difference in WTF was observed between the TMR and control groups. The resting myocardial blood flow was significantly increased by TMR at 20 weeks (P=0.03). Light microscopic examination revealed channel patency in 49% of the laser scars at 10 weeks post-TMR. A dense capillary network was observed at the edges of the surrounding scar. CONCLUSIONS In an experimental model of ischemic heart disease, TMR developed angiogenesis in the lased channels, but, however, failed to improve myocardial function.

Calcium uptake by the sarcoplasmic reticulum, high energy content and histological changes in ischemic cardiomyopathy

OBJECTIVES Sarcoplasmic reticulum (SR) Ca2+ uptake, myocardial high energy content and histology were examined in different zones of hearts from patients with ischemic cardiomyopathy. METHODS AND RESULTS Unfractionated homogenates were prepared from left ventricular samples obtained in three zones of each heart: an infarct-remote zone, an outer peri-infarct zone, and an inner peri-infarct zone. Oxalate-supported 45Ca2+ uptake was measured at 37 degrees C using a filtration method. Maximum rate (Vmax) of uptake in absence or in presence of ryanodine was lower in inner peri-infarct (7.4 +/- 0.7 and 9.5 +/- 0.8 nmol min-1 mg-1 of protein, respectively; mean +/- SEM) and outer peri-infarct tissues (8.8 +/- 0.8 and 12.0 +/- 0.8 nmol min-1 mg-1) than in infarct-remote myocardium (12.7 +/- 2.1 and 15.8 +/- 2.2 nmol min-1 mg-1). The apparent affinity constants for Ca2+ (KCa) as well as the Hill coefficients were not different. Homogenate DNA (1.6 +/- 0.1, 1.6 +/- 0.1 and 1.7 +/- 0.1 mg/g of remote, inner peri-infarct and outer peri-infarct myocardium, respectively) and adenine nucleotides contents (ATP: 15 +/- 1.3, 14 +/- 0.8 and 15 +/- 1.0 mumol/g dry weight, respectively) were similar in all tissues. Fibrosis was increased in inner peri-infarct tissue (37 +/- 6%; vs. 13 +/- 2% and 12 +/- 2% in both remote and outer peri-infarct tissues, respectively), but the number of abnormal cells was not significantly different. CONCLUSION The decrease of Ca2+ uptake in ischemic cardiomyopathy is not homogeneous in the ventricular wall, and reflects a decreased number/activity of SR Ca(2+)-ATPase, without altered Ca(2+)-affinity or increased Ca2+ leakage through ryanodine receptors.

Pediatric heart support with a newly developed catheter based pulsatile 12F rotary blood pump: an animal study §,§§

BACKGROUND To evaluate mechanical and hematological compatibility of a pediatric, temporary left heart support system in a lamb model as a less traumatic alternative to the widely used ECMO. METHODS A small, pulsatile rotary blood pump (target flow 0.5l/m at 80 mm Hg pressure head at 120 pulses per min) was inserted in six lambs (15.1+/-1 kg) via a left thoracotomy, through a purse string in the arcus aortae. With fluoroscopy the tip (=inflow) of the catheter was positioned in the outflow tract of the left ventricle. The outflow part was positioned immediately above the aortic valve. Animals were extubated at the end of the procedure. Mechanical and hematological parameters were followed for 14 days. RESULTS Five animals survived a 2-week follow-up. One animal died because of empyema on day 6. Flow maintained stable (0.8+/-0.2l/m) in all animals during the evaluation period. Free hemoglobin as a parameter of hemolysis and hematocrit remained also stable. Necropsy revealed minimal fibrous reaction on one aortic valve leaflet in one animal and small hematoma formation in three. All animals showed mild signs of endothelial damage on the aortic arch at the level of the motor housing. One animal showed signs of old kidney infarction suggesting possible embolization during placement. CONCLUSION This newly developed, catheter based, pediatric heart support system generates a stable flow for 14 days without compromising hematological stability and with acceptable tissue damage due to positioning of the catheter.

Cardioprotective effect of ischemic preconditioning on global myocardial ischemia in a sheep right heart bypass model

OBJECTIVES Ischemic preconditioning has been used to induce the myocardium to adapt to ischemic stress preceded by short periods of ischemia and reperfusion. We used a sheep right heart bypass model with a conductance catheter to assess the cardioprotective effect of ischemic preconditioning on 30-minute normothermic global myocardial ischemia. METHODS Ischemic preconditioning was conducted in 6 sheep in 35-minute aortic cross-clampings interspersed with 5 minutes of reperfusion during cardiopulmonary bypass, with 6 sheep as time-matched controls. Global myocardial ischemia was subsequently achieved in 30-minute aortic cross-clamping with left ventricular unloading during normothermic cardiopulmonary bypass. Weaning from cardiopulmonary bypass was conducted 40 minutes after reperfusion. Before ischemia and 40, 70, and 100 minutes after reperfusion, left ventricular pressure-volume loops were measured using a conductance catheter during right heart bypass preparation. Left ventricular contractility, diastolic function, and mechanical efficiency were then evaluated. Right heart bypass was instituted to control the preload and to decompress the right ventricle completely, thereby eliminating parallel conductance variation. RESULTS No differences in the studied parameters were seen between ischemic-preconditioning and control groups before ischemia. Left ventricular contractility, diastolic function, and mechanical efficiency in the ischemic-preconditioning group were significantly superior to those in the control group after reperfusion. CONCLUSIONS Ischemic preconditioning attenuates postischemic myocardial dysfunction in a sheep model using 30-minute unloaded normothermic global myocardial ischemia. Ischemic preconditioning would thus be clinically significant when the ischemic damage is severe.