PubMed Health⌕ Search

Biomedical subjects

A W Sielenkämper

Publications and source records attributed to A W Sielenkämper.

10 recordsLinked to original sources
PubMed2005

[Vasopressin and terlipressin in sepsis and systemic inflammatory response syndrome. Effects on microcirculation, oxygen transport, metabolism and organ function].

Vasopressin and terlipressin are increasingly used as alternative non-adrenergic vasopressors for hemodynamic support of septic patients with arterial hypotension. Despite excellent vasopressive effects, vasopressin analogues may potentially impair macro-hemodynamics, oxygen transport and microvascular blood flow. Due to those unwanted side-effects, vasopressin and terlipressin may potentially compromise organ function and possibly foster the development of multiple organ failure. This review article discusses the results of clinical and experimental studies to judge the effects of vasopressin and terlipressin on microcirculation, oxygen supply, metabolism and organ function in patients with sepsis or systemic inflammatory response syndrome (SIRS). Although vasopressin analogues are emerging as promising alternatives to treat catecholamine-refractory hypotension, there is no evidence that vasopressin receptor agonists improve outcome. To date, vasopressin and terlipressin can, therefore, not be recommended for routine clinical use.

Animals↗
PubMed2004

Modulation of hypoxic pulmonary vasoconstriction is time and nitric oxide dependent in a peritonitis model of sepsis.

OBJECTIVE: This study assessed modulation of hypoxic pulmonary vasoconstriction (HPV) in isolated perfused rat lungs during sepsis induced by cecal ligation and perforation (CLP) at different times and its relationship to nitric oxide synthases (NOS). DESIGN AND SETTING: Prospective controlled trial in a university research laboratory. SUBJECTS: 102 male Sprague-Dawley rats. INTERVENTIONS: Groups 1-3 received sham laparotomy 6 h before lung isolation: group 1, only laparotomy; group 2, concurrently L- N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg); group 3, concurrently N(Omega)-nitro-L-arginine methylester (L-NAME, 5 mg/kg). Groups 4-6 received CLP 6 h before lung isolation: group 4, only CLP; group 5, concurrently L-NIL; group 6, concurrently L-NAME. The same experiments were carried out with sham and CLP treatment for 24 h (groups 7-12). Exhaled NO from rats' lungs was measured after anesthesia and tracheostomy. After the pulmonary circuit was isolated and perfused, angiotensin II (0.1 microg) was injected into the inflow tract. The lungs were ventilated with the hypoxic mixture (HPV, 3% O2) for 10 min and then again with the normoxic mixture (21% O2) for an equal period. Changes in perfusion pressure were measured. Endothelial (eNOS) and inducible NOS (iNOS) expression of the lungs was determined. MEASUREMENTS AND RESULTS: Treatment with L-NAME but not L-NIL increased HPV in sham lungs. HPV was unaltered after CLP 6 h and decreased after CLP 24 h compared to sham. In CLP animals eNOS protein expression was reduced whereas iNOS expression was increased compared to sham animals. Exhaled NO, reflecting NOS activity was twice as high in the CLP 24 h group than in the CLP 6 h group. CONCLUSIONS: In the CLP sepsis model modulation of HPV was time-dependent. In addition, vasoconstriction to hypoxic stimuli was dependent on NOS activity.

Angiotensin II↗
PubMed2001

The effects of sepsis on gut mucosal blood flow in rats.

BACKGROUND AND OBJECTIVE: The effects of sepsis on gut mucosal blood flow have not been fully clarified. We designed an experiment to explicitly describe the effects of sepsis on gut mucosal blood flow in rats using an advanced intravital microscopy technique. METHODS: This work was performed as a prospective, controlled laboratory experiment. Twenty-four hours after sham laparotomy or laparotomy and caecal ligation and perforation to create sepsis, rats were anaesthetized and their lungs mechanically ventilated (n=7 per group). Intravital videomicroscopy was performed on 6-12 villi of ileum mucosa. Video recordings were analysed off-line using computerized image analysis. RESULTS: Intercapillary area size (inversely related to capillary density) was increased in sepsis as compared with the control group (941 +/- 92 vs. 669 +/- 79 microm(2), P < 0.05). In the central villus arteriole, blood flow was similar between groups (control: 3.5 +/- 0.4 nL min(-1); caecal ligation and perforation group: 3.6 +/- 0.5 nL min(-1)). There were no relevant changes in arteriolar red cell velocity and diameter. CONCLUSIONS: In the gut mucosa of rats, sepsis resulting from caecal ligation and perforation depressed the perfused capillary density without affecting blood flow in the central villus arteriole. Mucosal hypoperfusion at the level of the capillary networks may occur in the presence of precapillary shunting in the villus microcirculation.

Animals↗
PubMed2001

Anaesthesia and the elderly.

As a result of age-related physiological changes and multi-comorbidity, which both result in reduced functional reserve of the organ systems, old patients are more vulnerable to surgical stress and perioperative impairment in organ functions. Therefore, the incidence of severe complications during the perioperative course is increased in the elderly. Regional anaesthesia or a combination of regional and general anaesthesia is considered to be beneficial in elderly patients, because neuraxial blockade may reduce sympathetic activation, and has been demonstrated to reduce postoperative mortality. Other protective strategies to maintain organ functions in elderly patients include medication with beta-blockers in patients with cardiovascular risks, the avoidance of hypothermia, the maintenance of systemic oxygen delivery, and patient-controlled pain therapy.

Journal Article↗
PubMed2000

Thoracic epidural anesthesia increases mucosal perfusion in ileum of rats.

BACKGROUND: Previous studies reported that thoracic epidural anesthesia (TEA) protected against a decrease in gastric intramucosal pH, suggesting that TEA increased gut mucosal perfusion. The current study examines the effects of TEA on ileal mucosa using intravital microscopy in anesthetized rats. METHODS: Nineteen rats were equipped with epidural catheters, with the tip placed at T7 through T9. Rats were anesthetized and mechanically ventilated. After midline abdominal incision, the ileum was prepared for intravital microscopy. Videomicroscopy on the ileal mucosa was performed before and after epidural infusion of 20 microliter of bupivacaine 0.4% (TEA group, n = 11 rats) or normal saline (control group, n = 8 rats). Microvascular blood flow in ileum mucosa was assessed offline using computerized image analysis. RESULTS: Control rats exhibited unchanged mean arterial pressure and microvascular perfusion. During TEA, mean arterial pressure was decreased compared with the control group (93 +/- 10 vs. 105 +/- 9 mmHg; P < 0.05). Epidural bupivacaine increased red cell velocity in terminal arterioles from 888 +/- 202 to 1,215 +/- 268 micrometer/s (control, 793 +/- 250 to 741 +/- 195 micrometer/s; P < 0.001 between groups). Because arteriolar diameter was not affected, this increase in red cell velocity may represent an increase in arteriolar blood flow. Total intercapillary area (inversely related to perfused capillary density) was unchanged, but for the TEA group the difference between total intercapillary area and the intercapillary area calculated for continuously perfused capillaries was decreased compared with the control group (16 +/- 12 vs. 40 +/- 19%; P < 0.001), indicating a decrease in intermittent (stop-and-go) blood flow in the villus microcirculation. CONCLUSION: Thoracic epidural anesthesia increased gut mucosal blood flow and reduced intermittent flow in the villus microcirculation in the presence of a decreased perfusion pressure.

Anesthesia, Epidural↗
PubMed2000

Diaspirin cross-linked hemoglobin improves mucosal perfusion in the ileum of septic rats.

OBJECTIVE: To determine the effect of a bolus infusion of diaspirin cross-linked hemoglobin (DCLHb or hemoglobin crosfumaril) on the ileal mucosal microcirculation in septic rats. DESIGN: Prospective, randomized, single-blinded study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Twenty-four male Sprague-Dawley rats, weighing 320-380 g. INTERVENTIONS: Under inhalational anesthesia, arterial and venous catheters were inserted and sepsis was created by cecal ligation and perforation (CLP). Twenty-four hours later, animals were reanesthetized and ventilated. Via midline abdominal incision, the ileum was mobilized and prepared for intravital microscopy. Post-CLP hemodynamic values were obtained, and videomicroscopy was performed on four to ten villi. Animals were then randomized to receive 2 mL of DCLHb solution (100 mg/mL; n = 12) or pentastarch (n = 12) intravenously, and measurements were repeated after 20 mins. Rats treated with DCLHb then received nitroprusside to restore mean arterial pressure to post-CLP levels, and final measurements were obtained 15 mins later. MEASUREMENTS AND MAIN RESULTS: Cardiac index increased with both treatments (p < .001), whereas systemic vascular resistance index and mean arterial blood pressure were augmented only with DCLHb (p < .0001 compared with pentastarch). Intercapillary areas (ICA; inversely related to capillary density) were determined using computerized image analysis. ICA size decreased after treatment, from 974 +/- 79 to 791 +/- 106 microm2 with DCLHb and from 1044 +/- 90 to 840 +/- 82 microm2 with pentastarch (both p < .05). Red blood cell velocity in terminal arterioles, as assessed by velocimetry from the recorded images, increased by 15% with both treatments (p < .05). Restoration of mean arterial pressure to post-CLP levels in DCLHb animals by nitroprusside infusion abolished the effects of the hemoglobin solution on ICA size and red blood cell velocity. CONCLUSION: Both DCLHb and pentastarch infusion improved microcirculatory perfusion in the ileum of septic rats. In addition, DCLHb also exhibited vasopressor properties, which in combination with improved perfusion may be particularly useful in the treatment of sepsis.

Animals↗
PubMed2000

Diaspirin cross-linked Hb and norepinephrine prevent the sepsis-induced increase in critical O(2) delivery.

We hypothesized that support of arterial perfusion pressure with diaspirin cross-linked Hb (DCLHb) would prevent the sepsis-induced attenuation in the systemic O(2) delivery-O(2) uptake relationship. Awake septic rats were treated with a chronic infusion of DCLHb or a reference treatment [norepinephrine (NE)] to increase mean arterial pressure by 10-20% over 18 h. Septic and sham control groups received normal saline. Isovolemic hemodilution to create anemic hypoxia was then performed in a metabolic box during continuous measurement of systemic O(2) uptake. O(2) delivery was calculated from hemodynamic variables, and the critical point of O(2) delivery (DO(2 crit)) was determined using piecewise regression analysis of the O(2) delivery-O(2) uptake relationship. Sepsis increased DO(2 crit) from 4.99 +/- 0.17 to 6.69 +/- 0.42 ml x min(-1) x 100 g(-1) (P < 0.01), while O(2) extraction capacity was decreased (P < 0.05). DCLHb and NE infusion prevented the sepsis-induced increase in DO(2 crit) [4.56 +/- 0.42 ml x min(-1) x 100 g(-1) (P < 0.01) and 5.04 +/- 0.56 ml x min(-1) x 100 g(-1) (P < 0.05), respectively]. This was explained by a 59% increase in O(2) extraction capacity in the DCLHb group compared with septic controls (P < 0.05), whereas NE treatment decreased systemic O(2) uptake in anemic hypoxia (1.51 +/- 0.08 vs. 1.87 +/- 0.1 ml x min(-1) x 100 g(-1) in septic controls, P < 0.05). We conclude that DCLHb ameliorated O(2) extraction capacity in the septic microcirculation, whereas NE decreased the metabolic demands of the tissues.

Animals↗
PubMed1998

Thoracoscopic interruption of patent ductus arteriosus compromises cardiopulmonary function in newborn pigs.

UNLABELLED: Interruption of patent ductus arteriosus (PDA) using video-assisted thoracoscopic surgery (VATS) has recently been introduced into clinical practice. To study cardiovascular and pulmonary function during VATS, we treated 16 newborn pigs (weight 1421+/-44 g) with PDA with conventional surgical interruption (CSI; n = 7) or interruption via VATS (n = 9). Measurements of hemodynamics and gas exchange were performed before, during, and after surgery. Systemic perfusion was calculated using Fick's equation. Stress hormones (ACTH, epinephrine, and norepinephrine) were determined before and after surgery. The duration of the surgical procedure was 41+/-8 min for CSI and 49+/-9 min for VATS (mean+/-SEM). With VATS, PaO2 decreased during and after surgery (P < 0.05), whereas alveolar-arterial PO2 difference (PA-aO2) and PaCO2 were increased (P < 0.05). Compared with CSI after surgery, PaO2 with VATS was decreased (130+/-10 vs 171+/-12 mm Hg; P < 0.05). Systemic perfusion was lower during VATS (76.7% of baseline) than during CSI (107% of baseline; P < 0.05). Heart rate, mean arterial pressure, and right ventricular end-diastolic pressure remained unchanged with both treatments. Stress hormones were comparable between groups. We conclude that systemic perfusion and oxygenation were impaired during VATS compared with CSI. Therefore, VATS may be contraindicated in pediatric patients with minor cardiopulmonary reserve. IMPLICATIONS: We studied the cardiopulmonary effects of endoscopic interruption of the patent ductus arteriosus in an animal model of newborn pigs. Gas exchange and systemic perfusion were impaired compared with conventional interruption of the patent ductus arteriosus after thoracotomy.

Animals↗
PubMed1997

Diaspirin crosslinked hemoglobin improves systemic oxygen uptake in oxygen supply-dependent septic rats.

Diaspirin crosslinked hemoglobin (DCLHb) is a cell-free hemoglobin derived from human erythrocytes. DCLHb has been shown to improve blood flow to vital organs in healthy and septic animals. In this study, we determined the efficacy of DCLHb by comparing its effect on systemic O2 uptake to freshly stored and aged red blood cells (RBCs) in septic rats. Twenty-four hours after induction of sepsis by cecal ligation and perforation, O2 supply dependency was created by isovolemic hemodilution with rat plasma. In O2 supply dependency, rats were randomized to receive an exchange transfusion of 7.5 ml "fresh" RBCs (stored < 6 d; Hct: 70%), "fresh" diluted RBCs (stored < 6 d; Hct: 30%), "old" RBCs (stored 28 to 35 d; Hct: 70%), or DCLHb (Hb: 100 g/L). We found, that survival following O2 supply dependency and transfusion with old RBCs was poor (33% versus 91.7% in the other groups; p < 0.01), precluding further analysis of post-transfusion data from this group. Systemic O2 uptake increased in all remaining groups (p < 0.001), while systemic O2 delivery increased with "fresh" RBCs (p < 0.0001) and "fresh" diluted RBCs (p < 0.05) but not with DCLHb. Systemic O2 extraction increased with DCLHb as compared to baseline (p < 0.05) and to the other groups (p < 0.0001). Improved tissue oxygenation was associated with an increase in blood pressure and a fall in arterial lactate in all groups. We conclude that transfusion of DCLHb or "fresh" RBCs was efficacious at increasing systemic O2 uptake in O2 supply-dependent, septic rats.

Animals↗