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Biomedical subjects

Christof Stamm

Publications and source records attributed to Christof Stamm.

At least 19 recordsLinked to original sources
PubMed2006

Intramyocardial delivery of human CD133+ cells in a SCID mouse cryoinjury model: Bone marrow vs. cord blood-derived cells.

OBJECTIVE: The regenerative potential of endothelial and hematopoietic progenitor cells in the heart may vary according to their origin. This study was designed to compare the functional effects of CD133+ cells from human cord blood and bone marrow in a mouse model of myocardial injury. METHODS: 5 x 10(5) CD133+ cells from bone marrow (BM(CD133)) or cord blood (UCB(CD133)) were injected in the necrosis border zone of NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice with left ventricular cryoinjury (CI+). Transplanted cells were tracked by immunostaining for hNuclear antigen and by PCR for hDNA. Echocardiography was used to measure contractility. Scar size, capillary density, and cardiomyocyte apoptosis were evaluated by histology. In addition, the myogenic and endothelial differentiation capacity of BM(CD133) and UCB(CD133) was compared in vitro. RESULTS: DNA was detected 4 weeks after cell injection by PCR, but hNuc+ cells were found by immunostaining only after 48 h. Capillary density in both BM(CD133) and UCB(CD133) cell-treated CI+ mice was higher than in control CI+ mice, but not different between BM(CD133) and UCB(CD133) cell-treated hearts. There were no differences in scar size and myocardial mass among BM(CD133), UCB(CD133) and control CI+ mice, but cardiomyocyte apoptosis was reduced by both BM(CD133) and UCB(CD133) cells. The post-injury deterioration of shortening fraction (46.2+/-1% in sham-operated mice and 41.3+/-0.8% in control CI+ mice) was prevented by BM(CD133) cells (45.4+/-0.9%), but not by UCB(CD133) cells (40.8+/-0.7%). On the other hand, both BM(CD133) and UCB(CD133) cells abolished post-injury mortality. In vitro, neither cultivated BM(CD133) or UCB(CD133) cells developed into myocytes, but both readily differentiated towards an endothelial cell phenotype. CONCLUSIONS: While both cord blood and marrow CD133+ cells have some beneficial effects on post-injury angiogenesis and survival, only marrow cells appear to improve myocardial contractility.

AC133 Antigen↗
PubMed2006

Cell-based therapies after myocardial injury.

Recent translational research into the emerging field of cardiac cell therapy has paved the way for novel clinical treatment strategies. However, neither the ideal source and type of cell nor the critical quantity and mode of application have yet been defined. In patients who have undergone acute myocardial infarction, several cell-based approaches are currently being evaluated, such as intracoronary delivery of autologous mononuclear bone marrow cells or enriched hematopoietic progenitor cell products; systemic cytokine stimulation with release of bone marrow progenitor cells into the systemic circulation; and both intravenous and intracoronary delivery of allogenic marrow stroma cell-derived cells. There are potentially encouraging data for each of these strategies, based to date on small cohorts with conflicting or equivocal recovery of function. Taken together, it is too early to consider cell therapy for heart disease to be effective. Future setbacks are likely, but both clinicians and basic scientists will eventually introduce more potent cell-based strategies into the clinical arena.

Journal Article↗
PubMed2006

Importance of endothelial nitric oxide synthase for the hypothermic protection of lungs against ischemia-reperfusion injury.

OBJECTIVES: The hypothesis that the protective effects of mild hypothermia against the pulmonary ischemia-reperfusion injury are mediated by endothelial nitric oxide synthase was tested. METHODS: Endothelial nitric oxide synthase knock-out and wild-type mice were sham operated or underwent a 1-hour occlusion of the left pulmonary hilum, followed by 5 hours of reperfusion. Temperature in the left pleural cavity during ischemia was maintained at either 36 degrees C (normothermia) or 32 degrees C (hypothermia). Inflammatory response (myeloperoxidase activity), endothelial barrier function (extravasation of Evans blue-labeled albumin), and endothelial nitric oxide synthase expression and phosphorylation were determined at the end of reperfusion. RESULTS: After normothermic ischemia both strains had a similar mortality (wild-type, 22.9%; knock-out, 15.4%), which was completely abolished by hypothermia. Endothelial barrier function was disturbed after normothermic ischemia in both wild-type and knock-out mice. Mild hypothermia significantly reduced pulmonary Evans blue extravasation in wild-type mice, but not in knock-out mice. Myeloperoxidase activity increased after normothermic ischemia to the same degree in both strains. This response was significantly attenuated by hypothermia in wild-type mice, but not in knock-out mice. In wild-type mice, endothelial nitric oxide synthase expression and phosphorylation were higher after hypothermic ischemia than after normothermic ischemia. No effect of ischemia on expression of inducible nitric oxide synthase was found in wild-type or knock-out mice. CONCLUSION: Hypothermic protection against pulmonary ischemia-reperfusion injury is dependent on endothelial nitric oxide synthase and is associated with increased expression and phosphorylation of endothelial nitric oxide synthase.

Animals↗
PubMed2006

Cardiac conduction through engineered tissue.

In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal muscle-derived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal's natural life. Perfusion of hearts with fluorescently labeled lec-tin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding re-cipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses, we provide evidence of permanent AV conduction through the implant in one-third of recipient animals. Our experiments provide a proof-of-principle that engineered tissue constructs can function as an electrical conduit and, ultimately, may offer a substitute treatment to conventional pacing therapy.

Animals↗
PubMed2006

Stem cell therapy for ischemic heart disease: beginning or end of the road?

Despite improvements in emergency treatment, myocardial infarction is often the beginning of a downward spiral leading to congestive heart failure. Other than heart transplantation, current therapeutic means aim at enabling the organism to survive with a heart that is working at a fraction of its original capacity. It is therefore no surprise that cardiac stem cell therapy has raised many hopes. However, neither the ideal source and type of stem cell nor the critical cell number and mode of application have been defined so far. Early reports on myocardial repair by adult bone marrow stem cells from rodent models promoted an unparalleled boost of clinical and experimental cell therapy studies. The phenomenon of stem/progenitor cell-induced angiogenesis in ischemic myocardium has ever since been reproduced by numerous groups in a variety of small and large animal models. Myogenesis, however, is an altogether different matter. Many of the initial clinical studies were fueled by the suggestion that early hematopoietic stem cells have a plasticity high enough to enable cross-lineage differentiation into cells of cardiomyocyte phenotype, but the initial enthusiasm has largely faded. The myogenic potential of stroma cell-derived mesenchymal stem cells is much better documented in animal models, but transfer to the clinical setting faces a variety of obstacles. In clinical pilot trials, we and others have demonstrated the feasibility and safety of administering progenitor cells derived from autologous bone marrow to the myocardium of patients with ischemic heart disease. Clinical efficacy data are still rare, but the few controlled trials that have been completed uniformly show a tendency towards better heart function in cell-treated patients. This review is an attempt to describe the scientific basis for cardiac cell therapy from the point of view of the clinician, focusing on problems that arise with beginning translation into the clinical setting.

Cell Survival↗
PubMed2005

Human cord blood cells induce angiogenesis following myocardial infarction in NOD/scid-mice.

OBJECTIVE: We tested the hypothesis that intravenously administered human umbilical cord blood (hUCB) cells contribute to repair processes following myocardial infarction. METHODS: hUCB mononuclear cells containing 0.11% to 1.1% CD34(+) cells were injected in the tail vein of NOD/scid mice that had (MI+) or had not (MI-) previously undergone ligation of the left anterior coronary artery (LAD). Homing to bone marrow and solid organs was determined by polymerase chain reaction (PCR) for human DNA (hDNA) using human-specific primers of Locus D7Z1. Immunostaining was used for phenotypic analysis, and capillary density as well as myocardial scar formation was assessed. Moreover, expression of stromal cell-derived factor-1 (SDF-1) was studied in infarcted and in normal hearts. RESULTS: hDNA was detected in marrow, spleen, and liver of both MI+ and MI- mice 24 h, 1 week, and 3 weeks after cell injection. In the heart, however, hDNA was detected in 10 of 19 MI+ mice but in none of the MI- mice (p=0.002). Infarct size was smaller in cell-treated MI+ mice than in untreated MI+ hearts (38.7 versus 47.8%, P<0.05), and there was also less collagen deposition. In cell-treated MI+ mice, capillary density in the infarct border zone was approximately 20% higher (p=0.03), and clusters of hUCB-derived cells were detected in the perivascular interstitium. Occasionally, chimeric capillaries composed of human and mouse endothelial cells were found, but the vast majority of neo-vessels appeared to consist of mouse cells only. Up to 70% of the cord blood-derived cells in the heart were CD45(+). There was no evidence of cardiomyocyte differentiation as determined by co-localization of HNA or HLA-I with GATA-4 or Connexin 43. In infarcted myocardium, expression of SDF-1 mRNA was approximately 7-fold higher than in normal hearts. CONCLUSIONS: hUCB cells migrate to infarcted, not to normal myocardium, where they engraft, participate in neoangiogenesis, and beneficially influence remodelling processes. Cord blood cells may hence be useful for cell therapy of ischemic heart disease.

Animals↗
PubMed2004

Promoting angiogenesis protects severely hypertrophied hearts from ischemic injury.

BACKGROUND: Myocardial hypertrophy is associated with progressive contractile dysfunction, increased vulnerability to ischemia-reperfusion injury, and is, therefore, a risk factor in cardiac surgery. During the progression of hypertrophy, a mismatch develops between the number of capillaries and cardiomyocytes per unit area, suggesting an increase in diffusion distance and the potential for limited supply of oxygen and nutrients. We hypothesized that promoting angiogenesis in hypertrophied hearts increases microvascular density, thereby improves tissue perfusion and substrate availability, maintains myocardial function, and improves postischemic recovery. METHODS: Left ventricular hypertrophy was created in 10-day-old rabbits by aortic banding and progression was monitored by echocardiography. At 4 weeks (compensated hypertrophy), 2 microg of vascular endothelial growth factor (VEGF) or placebo was administered intrapericardially. After 2 weeks, microvascular density, coronary flow (CF), and glucose uptake (GU) were measured. Tolerance to ischemia was determined by cardiac function measurements before and after ischemia-reperfusion using an isolated heart preparation. RESULTS: Microvascular density increased significantly following VEGF treatment (1.43 +/- 0.08/nuclei/field vs 1.04 +/- 0.06/nuclei/field untreated hypertrophy). Concomitantly, there was an increase in CF (7 +/- 0.5 vs 5 +/- 0.4 mL/min/g) and GU (1.24 +/- 0.2 vs 0.69 +/- 0.2 micromoles/g/30 minutes; p <or= 0.05). In vivo contractile function (-0.08 +/- 0.48 vs -1.39 +/- 0.35 untreated hypertrophy; p <or= 0.05) and postischemic myocardial recovery (% recovery: 93 +/- 2.0 vs 73 +/- 6.8 untreated hypertrophy; p <or= 0.05) were significantly improved in VEGF-treated hearts compared to untreated hypertrophied hearts. CONCLUSIONS: Treatment of hypertrophied hearts with VEGF resulted in an increase of microvascular density, improved tissue perfusion, and glucose delivery. Promoting angiogenesis proved useful in preserving myocardial function in late hypertrophy and improving postischemic recovery of contractile function.

Angiogenesis Inducing Agents↗
PubMed2004

Biomatrix/polymer composite material for heart valve tissue engineering.

BACKGROUND: Decellularized extracellular matrix has been suggested as a scaffold for heart valve tissue engineering or direct implantation. However, cell removal impairs the physical properties of the valve structure and exposes bare collagen fibers that are highly thrombogenic. Matrix/polymer hybrid valves with improved biological and mechanical characteristics may be advantageous. METHODS: Porcine aortic valves were decellularized enzymatically and impregnated with biodegradable poly(hydroxybutyrate) by a stepwise solvent exchange process. Biocompatibility was tested in vitro using cell proliferation and coagulation assays. Proinflammatory activity was assessed in vivo by implantation of matrix/polymer patches in the rabbit aorta. Biomechanic valve properties and fluid dynamics were tested in a pressure/flow-controlled pulse duplicating system. Matrix/polymer hybrid valves were implanted in pulmonary and aortic position in sheep. RESULTS: Biocompatibility assays indicated that human blood vessel cells survive and proliferate on matrix/polymer hybrid tissue. In vitro activation of cellular and plasmatic coagulation cascades was lower than with uncoated control tissue. After implantation in the rabbit aorta, matrix/polymer hybrid patches healed well, with complete endothelialization, mild leukocyte infiltration, and less calcification than control tissue. Matrix/polymer hybrid tissue had superior tensile strength and suture retention strength, and hybrid valves showed good fluid dynamic performance. The two valves in aortic position performed well, with complete endothelialization and limited inflammatory cell invasion after 12 weeks. Of the two valves in pulmonary position, one failed. CONCLUSIONS: Matrix/polymer hybrid tissue valves have good biological and biomechanic characteristics and may provide superior replacement valves.

Absorbable Implants↗
PubMed2004

Up-regulation of endothelial nitric oxide synthase inhibits pulmonary leukocyte migration following lung ischemia-reperfusion in mice.

Endogenous nitric oxide (NO) is known to modulate post-ischemic inflammatory response in various organs. However, the role of nitric oxide synthase isoforms (NOS) in mediating pulmonary post-ischemic inflammatory response is poorly understood. We therefore studied post-ischemic endothelial adhesion molecule expression and leukocyte migration in endothelial NOS knockout (eNOS-KO) mice subjected to pulmonary ischemia and reperfusion in vivo. Under anesthesia and mechanical ventilation, the left pulmonary hilum in wild-type (WT) and eNOS-KO mice was clamped for 1 hour, followed by reperfusion for up to 24 hours. In WT mice, we observed a selective up-regulation of both eNOS mRNA and protein in lung tissue, while inducible NOS (iNOS) and neuronal NOS (nNOS) remained unchanged. Survival in eNOS-KO mice was reduced due to severe pulmonary edema, underlining an increased susceptibility to ischemia-reperfusion (I/R) injury. Interstitial tissue infiltration by CD18- and CD11a-positive white blood cells as well as lung tissue water content peaked at 5 hours of reperfusion and were found significantly higher than in WT mice. Enhanced leukocyte-endothelial interaction was associated with pronounced up-regulation of vascular cell adhesion molecule (VCAM) in eNOS-KO mice during post-ischemic reperfusion. We conclude that eNOS attenuates post-ischemic inflammatory injury to the lung most probably via inhibition of endothelial adhesion molecule expression.

Animals↗
PubMed2004

Effects of hemodilution and phenylephrine on cerebral blood flow and metabolism during cardiopulmonary bypass.

OBJECTIVE: Hypotension resulting from hemodilution on cardiopulmonary bypass is often treated by pressor (eg, phenylephrine) infusion. The effect of phenylephrine on cerebral blood flow (CBF) in this setting is not clear. It was hypothesized that phenylephrine might decrease CBF. MEASUREMENTS AND MAIN RESULTS: Six different radioactively labeled microspheres (15 microm) were used to measure CBF at 6 time points (T) in 9 pigs (mean body weight 11.3 +/- 1.2 kg): T1 baseline before bypass (mean arterial pressure [MAP] 76 +/- 5 mmHg), T2 on mildly hypothermic CPB (34 degrees C, pump flow 100 mL/kg/min, hematocrit 30%, MAP 79 +/- 7 mmHg), T3 after moderate hemodilution with crystalloid (hematocrit 20%, resulting MAP 62 +/- 6 mmHg), T4 after phenylephrine administration to increase MAP to baseline values (hematocrit 20%), T5 after severe hemodilution (hematocrit 10%, resulting MAP 41 +/- 4 mmHg), and T6 after phenylephrine administration to normalize MAP (hematocrit 10%). In addition, blood flow to liver, small bowel and skeletal muscle, and pH of jugular venous blood were measured at each time point. After institution of CPB, the CBF (mL/min/100 g tissue) increased significantly to 53 +/- 9 (baseline levels 44 +/- 8, T1 v T2, p = 0.03). Hemodilution resulted in significant increases in CBF on CPB to 65 +/- 9 and 90 +/- 9 at hematocrit 20% and hematocrit 10%, respectively (T2 v T3, p = 0.03; T3 v T5, p = 0.01) and a progressive fall in jugular venous pH. At each level of hemodilution, phenylephrine resulted in an additional increase in CBF (T4, 74 +/- 8; T6, 108 +/- 12; T3 v T4, p = 0.04; T5 v T6, p = 0.01) but did not improve jugular venous pH. Changes in liver blood flow after hemodilution and vasopressor injection showed a similar pattern to CBF. However, the blood flow to small bowel and skeletal muscle increased with hemodilution but decreased significantly with phenylephrine administration. CONCLUSIONS: Phenylephrine redirects blood flow from the bowel and muscle to the brain and liver. Hemodilution increases CBF and pressor administration further increases CBF by elevating perfusion pressure. Maintenance of a higher hematocrit on CPB increases MAP and should decrease the need for vasopressor administration.

Animals↗
PubMed2004

Mechanical and structural properties of a novel hybrid heart valve scaffold for tissue engineering.

Hybrid heart valve scaffolds were fabricated from decellularized porcine aortic heart valve matrices and enhanced with bioresorbable polymers using different protocols: (i) dip coating of lyophilized decellularized matrices, and (ii) impregnation of wet decellularized matrices. The following polymers were evaluated: poly(4-hydroxybutyrate) and poly(3-hydroxybutyrate-co4-hydroxybutyrate). Tensile tests were conducted to assess the biomechanical behavior of valve leaflet strips. Suture retention strength was evaluated for the adjacent conduit. A pulse duplicator system was used for functional testing of the valves under physiological systemic load conditions. The properties of the hybrid structures were compared with native, decellularized, and glutaraldehyde-fixed specimens. Mechanisms of the polymer impregnation process were studied with IR spectroscopy, fluorescent microscopic imaging, and SEM. Altogether this study demonstrates the feasibility and improved biomechanical function of a novel hybrid heart valve scaffold for an application in tissue engineering.

Animals↗
PubMed2003

Cytosolic calcium in the ischemic rabbit heart: assessment by pH- and temperature-adjusted rhod-2 spectrofluorometry.

OBJECTIVES: Cytosolic calcium ([Ca(2+)](i)) mediates ischemia-reperfusion (I/R) injury, but magnitude and time course of I/R-induced [Ca(2+)](i) overload remain unclear. Fluorescent indicators are commonly used to measure [Ca(2+)](i), and have a dissociation constant (K(d)) that depends on pH and temperature. We hypothesized that changes of K(d) during I/R lead to misleading interpretations of [Ca(2+)](i) recordings. METHODS: (1) In isolated rabbit hearts (n=4 each), intracellular pH was measured during I/R at 37 degrees C, 20 degrees C, and 4 degrees C with and without cardioplegic arrest by (31)P-NMR-spectroscopy. (2) K(d) for rhod-2 and calcium was determined at varying pH and temperature in in vitro experiments. (3) Isolated rabbit hearts were subjected to I/R, and [Ca(2+)](i) was recorded by surface rhod-2 spectrofluorometry. Finally, [Ca(2+)](i) was computed using either the conventional K(d), or the pH- and temperature-adjusted K(d). RESULTS: K(d)(Ca(2+)Rhod-2) remained stable between pH 7.1 and 6.8, but increased exponentially with lower pH and/or temperature. Calculations using a static K(d) indicated that [Ca(2+)](i) rose only mildly during warm ischemia and did not rise during cardioplegic arrest, while a large Ca(2+) influx appeared to occur during early reperfusion. When the pH and temperature-adjusted K(d) was used for calculation, [Ca(2+)](i) rose significantly during ischemia (431+/-37% during 20 min 37 degrees C ischemia, and 78+/-19% during 20 min cardioplegic arrest at 20 degrees C). During early reperfusion, [Ca(2+)](i) decreased rapidly, without significant further [Ca(2+)](i) elevation. CONCLUSIONS: In contrast to previous reports, [Ca(2+)](i) accumulation occurs during unprotected ischemia as well as hypothermic ischemia with cardioplegic arrest, without further net Ca(2+) influx on reperfusion. This finding has important implications for timing of protective strategies during myocardial ischemia.

Animals↗
PubMed2003

Autologous bone-marrow stem-cell transplantation for myocardial regeneration.

Implantation of bone-marrow stem cells in the heart might be a new method to restore tissue viability after myocardial infarction. We injected up to 1.5x10(6) autologous AC133+ bone-marrow cells into the infarct border zone in six patients who had had a myocardial infarction and undergone coronary artery bypass grafting. 3-9 months after surgery, all patients were alive and well, global left-ventricular function was enhanced in four patients, and infarct tissue perfusion had improved strikingly in five patients. We believe that implantation of AC133+ stem cells to the heart is safe and might induce angiogenesis, thus improving perfusion of the infarcted myocardium. See Commentary page 11

Aged↗
PubMed2003

Noninvasive serial evaluation of myocardial mechanics in pressure overload hypertrophy of rabbit myocardium.

BACKGROUND: The determination of progression from afterload mismatch to myocardial failure in small animals requires invasive monitoring to assess ventricular pressure. OBJECTIVE: We sought to (1) validate the noninvasive determination of blood pressure using optical plethysmography, and (2) determine the time course and progression from afterload mismatch to myocyte failure in neonatal rabbits with coarctation (aortic banding at 7-10 days of life) compared to normal rabbits. METHODS AND RESULTS: Comparison of continuous arterial pressure determined by optical plethysmography with high-fidelity intraarterial recording was performed in nine animals. An accuracy of 5.9 +/- 4.7 and 9.2 +/- 6.9 mm Hg for systolic and diastolic blood pressure was noted. Fourier analysis confirmed similar frequency components. Simultaneous transthoracic echocardiography and optical plethysmography were serially performed in 33 banded and 13 control animals. Load-dependent and -independent measures of myocardial function were obtained. Midwall contractility, initially normal, showed a gradual significant deterioration (0.22 +/- 1.68 [week 3] to -1.36 +/- 1.24 [week 6]; Z-scores). CONCLUSIONS: This novel noninvasive method for determination of myocardial mechanics allows for serial evaluation of cardiac function and the determination of the time course from compensated hypertrophy to myocyte failure.

Analysis of Variance↗
PubMed2003

Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion: an intravital fluorescence microscopy study in pigs.

BACKGROUND: Retrograde cerebral perfusion (RCP) is used in some centers during aortic arch surgery for brain protection during hypothermic circulatory arrest. It is still unclear however whether RCP provides adequate microcirculatory blood flow at a capillary level. We used intravital microscopy to directly visualize the cerebral capillary blood flow in a piglet model of RCP. METHODS: Twelve pigs (weight 9.7 +/- 0.9 kg) were divided into two groups (n = 6 each): deep hypothermic circulatory arrest (DHCA) and RCP. After the creation of a window over the parietal cerebral cortex, pigs underwent 10 minutes of normothermic bypass and 40 minutes of cooling to 15 degrees C on cardiopulmonary bypass ([CPB] pH-stat, hemocrit 30%, pump flow 100 mL x kg(-1) x min(-1)). This was followed by 45 minutes of DHCA and rewarming on CPB to 37 degrees C. In the RCP group the brain was retrogradely perfused (pump flow 30 mL x kg(-1) x min(-1)) during DHCA through the superior vena cava after inferior vena cava occlusion. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD), defined as total length of erythrocyte-perfused capillaries per observation area. Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia. RESULTS: During normothermic and hypothermic antegrade cerebral perfusion the FCD did not significantly change from base line (97% +/- 14% and 96% +/- 12%, respectively). During retrograde cerebral perfusion the FCD decreased highly significantly to 2% +/- 2% of base line values (p < 0.001). Thus there was no evidence of significant capillary blood flow during retrograde cerebral perfusion. The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP. NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue oxygenation. At the end of retrograde cerebral perfusion there was macroscopic evidence of significant brain edema. CONCLUSIONS: RCP does not provide adequate cerebral capillary blood flow and does not prevent cerebral ischemia. Prolonged RCP induces brain edema. However, there might be a role for a short period of RCP to remove air and debris from the cerebral circulation after DHCA because retrograde flow could be detected in cerebral arterioles.

Animals↗