First Report of Extraspinal Lead Migration Along a Thoracic Spinal Nerve After Spinal Cord Stimulation.

BACKGROUND: Spinal cord stimulation for failed back surgery syndrome and chronic pain is a well-established treatment regimen today. Lead migration is the most common complication; mainly epidural caudal more than cranial electrode migration from the primary position is described repeatedly throughout the literature. CASE DESCRIPTION: A 60-year-old male patient with failed back surgery syndrome was eligible for spinal cord stimulation. Surgery had been performed 4 weeks before readmission with proper lead positioning of both electrodes in the midline of the epidural space. The electrode fixation mechanism at L2/3 had to be revised and was replaced with multiple ligature fixations due to the patient's slim build. He presented to our outpatient clinic with thoracic right-sided pain matching T5 with signs of overstimulation of the paravertebral muscles. X-ray imaging revealed cranial migration of 1 lead to T4 and a right-sided extraspinal migration of the other lead along a spinal nerve in T5 exiting the neuroforamen and following beneath the corresponding rib dorsally. Revision surgery was performed using a thoracic paddle electrode. CONCLUSIONS: Lead migration remains a challenge in spinal cord stimulation regardless of the fixation method. Rare unusual migration patterns in addition to simple caudal or cranial migration might pose a challenge for revision surgery and thus might reduce overall treatment efficacy.

Long-term Outcome and Adverse Events of Intrathecal Opioid Therapy for Nonmalignant Pain Syndrome.

OBJECTIVE: Intrathecal (IT) opioid pumps are one therapeutic cornerstone of refractory nonmalignant pain syndromes. The aim of this study was to evaluate the efficacy of and surgical and pharmacological complications of IT pumps beyond a time span of 10 years. METHODS: In this retrospective single-center cohort study, 27 patients (14 female, 13 male, age 64.0 ± 8.9 [median, 1 SD] years) were identified. Pain intensity using the numeric rating scale (NRS), pain and IT pump characteristics, and complications were analyzed. The German Pain Questionnaire was used to investigate the physical and mental health status. RESULTS: Overall time of IT therapy from first implantation to last follow-up was 20.4 ± 6.0 years. Time to implantation of the second pump (n = 18) was 10.0 ± 5.3 years, and between the second and third pump (n = 6) 6.5 ± 2.7 years; 2 patients received their fourth pump 6 years later. The NRS score was 9.0 ± 0.9 before implantation, 7.0 ± 1.8 1 year after implantation, and 4.0 ± 2.3 at the last follow-up. IT drug dose remained stable after 3 years. Opioid intoxications occurred in 3 patients (10%). One patient (3%) underwent revision surgery due to a catheter infection. Drug side effects occurred in 4 patients (14%). Our patient group had pain-related restrictions in physical activities with menial impact regarding mental and emotional stress. CONCLUSION: Even after a time span of over 15 years and several exchanges of pump systems, pain intensity was still reduced. After 3 years, IT drug dose remained unchanged with low side-effect and complication rates.

Effects of inhaled aerosolized iloprost and inhaled NO on pulmonary circulation and edema formation in ovine lung injury.

Although inhaled NO (iNO) has been shown to lower pulmonary pressures and edema accumulation in experimental acute lung injury, its clinical use has been questioned because of a lack of improvement in outcome, rebound phenomena, and potential toxicity. We investigated the effects of aerosolized iloprost, a stable prostacyclin analogue, compared with iNO on pulmonary pressures and lung edema in 20 female sheep with oleic acid lung injury. The most effective dose of iloprost was determined in healthy animals before the experiment. Anesthetized and ventilated sheep received a central venous oleic acid infusion and were continuously infused with Ringer lactate to achieve a positive fluid balance (5 mL.kg(-1).h(-1)). In the iNO group (n = 6), iNO (20 ppm) was administered continuously for 8 h. Animals in the iloprost group (n = 6) received aerosolized iloprost (40 microg 2 h(-1)). Animals in the control group (n = 6) had no further intervention. Oleic acid infusion was associated with impaired oxygenation, pulmonary hypertension, and lung edema in all groups. Although iNO significantly decreased pulmonary vascular resistance index, effective pulmonary capillary pressure, and extravascular lung water index, these parameters were unaffected by iloprost. Oxygenation index (Pao2/Fio2) increased significantly both during NO and iloprost inhalation but also tended to improve in the control group over time. In contrast to iNO, the investigated dose of iloprost was ineffective to attenuate acute lung injury-induced changes in pulmonary hemodynamics and lung edema in this experimental model.

Somatostatin infusion increases intestinal ischemia and does not improve vasoconstrictor response to norepinephrine in ovine endotoxemia.

Hemodynamic support of patients with septic shock is often complicated by a tachyphylaxis against exogenous catecholamines. Because an increase in somatotropic hormones may play a pivotal role in the regulation of the inflammatory response to endotoxin, intravenous supplementation of the neuroendocrine hormone somatostatin (SOMA) may attenuate hemodynamic dysfunction resulting from endotoxemia. The objective of the present study was to assess the short-term effects of SOMA alone and in combination with norepinephrine (NE) on cardiopulmonary hemodynamics, global oxygen transport, plasma nitrate/nitrite levels, and intestinal integrity compared with single NE therapy in ovine endotoxemia. After a baseline measurement in healthy sheep (n = 16) had been performed, Salmonella typhosa endotoxin was centrally infused (10 ng x kg(-1) x min(-1)) to induce a hypotensive-hyperdynamic circulation using an established protocol. Animals surviving 16 h of endotoxemia were randomly assigned to one of the two groups (each n = 6). Sheep allocated to the SOMA + NE group received SOMA as a loading dose of 10.5 microg x kg(-1) x min(-1) for 1 h, followed by a continuous infusion of 3.5 microg x kg(-1) x min(-1) for the next 2 h. After the SOMA loading dose had been given, NE was concurrently infused (0.3 microg x kg(-1) x min(-1)) for 2 h. In the NE group (control), NE (0.3 microg x kg(-1) x min(-1)) was continuously infused for 3 h. Endotoxemia caused a decrease in MAP and systemic vascular resistance index in both groups, but to a greater extent in the NE group. Arterial hypotension persisted despite administration of the study drugs. Infusion of SOMA alone and in combination with NE did not significantly increase systemic vascular resistance index. Neither SOMA nor NE infusion alone affected pulmonary vasoregulation. Plasma nitrate/nitrite levels did not differ between groups. However, combined infusion of SOMA and NE significantly increased arterial lactate concentrations, oxygen consumption index, and oxygen extraction rate (P < 0.05) and aggravated ileal mucosal injury. In conclusion, short-term treatment with SOMA failed to attenuate cardiocirculatory shock resulting from endotoxemia and did not improve vasopressor response to NE. In addition, combined SOMA and NE therapy resulted in intestinal injury. Therefore, SOMA does not seem to represent a therapeutic option to treat arterial hypotension resulting from sepsis and systemic inflammatory response syndrome.

Hemodynamic effects of thoracic epidural analgesia in ovine hyperdynamic endotoxemia.

BACKGROUND AND OBJECTIVES: Thoracic epidural analgesia (TEA) is increasingly used for perioperative analgesia. If patients with TEA develop sepsis or systemic inflammatory response subsequent to extended surgery the question arises if it would be safe to continue TEA with its beneficial effects of improving gastrointestinal perfusion and augmenting tissue oxygenation. A major concern in this regard is hemodynamic instability that might ensue from TEA-induced vasodilation. The objective of the present study was to assess the effects of TEA on systemic and pulmonary hemodynamics in a sepsis model of hyperdynamic endotoxemia. METHODS: After a baseline measurement in healthy sheep (n = 14), Salmonella thyphosa endotoxin was continuously infused at a rate of 10 ngxkg(-1)xmin(-1) over 16 hours. The surviving animals (n = 12) were then randomly assigned to 1 of 2 study groups. In the treatment group (n = 6), continuous TEA was initiated with 0.1 mLxkg(-1) bupivacaine 0.125% and maintained with 0.1 mLxkg(-1)xh(-1). In the control group (n = 6) the same amount of isotonic sodium saline solution was injected at the same rate through the epidural catheter. RESULTS: In both experimental groups cardiac index increased and systemic vascular resistance decreased concurrently (each P < .05). Functional epidural blockade in the TEA group was confirmed by sustained suppression of the cutaneous (or panniculus) reflex. During the observational period of 6 hours neither systemic nor pulmonary circulatory variables were impaired by TEA. CONCLUSIONS: From a hemodynamic point of view, TEA presents as a safe treatment option in sepsis or systemic inflammatory response syndrome.

Continuous thoracic epidural anesthesia improves gut mucosal microcirculation in rats with sepsis.

Microcirculatory dysfunction contributes significantly to tissue hypoxia and multiple organ failure in sepsis. Ischemia of the gut and intestinal hypoxia are especially relevant for the evolution of sepsis because the mucosal barrier function may be impaired, leading to translocation of bacteria and toxins. Because sympathetic blockade enhances intestinal perfusion under physiologic conditions, we hypothesized that thoracic epidural anesthesia (TEA) may attenuate microcirculatory perturbations during sepsis. The present study was designed as a prospective and controlled laboratory experiment to assess the effects of continuous TEA on the mucosal microcirculation in a cecal ligation and perforation model of sepsis in rats. Anesthetized Sprague-Dawley rats underwent laparotomy and cecal ligation and perforation to induce sepsis. Subsequently, either bupivacaine 0.125% (n = 10) or isotonic sodium chloride solution (n = 9) was continuously infused via the thoracic epidural catheter for 24 h. In addition, a sham laparotomy was carried out in eight animals. Intravital videomicroscopy was then performed on six to ten villi of ileum mucosa. The capillary density was measured as areas encircled by perfused capillaries, that is, intercapillary areas. The TEA accomplished recruitment of microcirculatory units in the intestinal mucosa by decreasing total intercapillary areas (1,317 +/- 403 vs. 1,001 +/- 236 microm2) and continuously perfused intercapillary areas (1,937 +/- 512 vs. 1,311 +/- 678 microm2, each P < 0.05). Notably, TEA did not impair systemic hemodynamic variables beyond the changes caused by sepsis itself. Therefore, sympathetic blockade may represent a therapeutic option to treat impaired microcirculation in the gut mucosa resulting from sepsis. Additional studies are warranted to assess the microcirculatory effects of sympathetic blockade on other splanchnic organs in systemic inflammation.

Continuously infused glipizide reverses the hyperdynamic circulation in ovine endotoxemia.

In advanced sepsis, hemodynamic support is often complicated by a tachyphylaxis against exogenous catecholamines. Although activation of adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels plays a pivotal role in the pathogenesis of hyperdynamic vasodilatory shock, previous studies demonstrated only a transient increase in mean arterial pressure (MAP) after bolus administration of K(ATP) channel inhibitors. We hypothesized that a continuous infusion of the sulfonylurea glipizide, a K(ATP) channel inhibitor, may reverse cardiovascular dysfunctions in sepsis permanently. Eighteen adult sheep were instrumented for chronic study. After a baseline measurement in healthy ewes, endotoxin (Salmonella typhosa, 10 ng kg(-1) min(-1)) was continuously infused for 19 h. After 16 h of endotoxemia, the surviving sheep (n = 14) were randomly assigned to be treated with either glipizide (5 mg/kg, followed by a continuous infusion of 8 mg kg(-1) h(-1)) or placebo (normal saline; each n = 7). Measurements of cardiopulmonary hemodynamics, global oxygen transport, acid-base status, and urine output were performed in the healthy state, after 16 h of endotoxemia, and during 3 h of glipizide infusion. Continuous infusion of glipizide reversed the endotoxin-induced hyperdynamic circulation, as indicated by significant increases in MAP and systemic vascular resistance index, as well as decreases in cardiac index and heart rate (P < 0.001 each). In addition, glipizide increased urine output as compared with untreated controls (P < 0.001). The anticipated decrease in glucose plasma levels was prevented by infusion of glucose 5%. From these results, we conclude that continuous glipizide infusion may represent a useful therapeutic option in the treatment of arterial hypotension related to sepsis and systemic inflammatory response syndrome.

Effects of thoracic epidural anesthesia on hemodynamics and global oxygen transport in ovine endotoxemia.

Besides providing effective analgesia, thoracic epidural anesthesia (TEA) has been shown to decrease perioperative morbidity and mortality. Because of its vasodilatory properties in association with the sympathetic blockade, however, TEA may potentially aggravate cardiovascular dysfunctions resulting from sepsis and systemic inflammatory response syndrome. The objective of the present study was to assess the effects of TEA on hemodynamics, global oxygen transport, and renal function in ovine endotoxemia. After a baseline measurement in healthy sheep (n = 18), Salmonella typhosa endotoxin was centrally infused at incremental doses to induce and maintain a hypotensive-hypodynamic circulation using an established protocol. The animals were then randomly assigned to one of two groups. In the treatment group, continuous TEA was initiated with 0.1 mL.kg of 0.125% bupivacaine at the onset of endotoxemia and maintained with 0.1 mL.kg.h. In the control group, the same amount of isotonic sodium chloride solution was injected through the epidural catheter. In the animals surviving the entire experiment (n = 7 per group), cardiac index and mean arterial pressure decreased in a dose-dependent manner during endotoxin infusion. In the TEA group, neither systemic hemodynamics nor global oxygen transport were impaired beyond the changes caused by endotoxemia itself. Urinary output was increased in the TEA group as compared with the control group (P < 0.05). In this model of endotoxic shock, TEA improved renal perfusion without affecting cardiopulmonary hemodynamics and global oxygen transport.

Dobutamine reverses the vasopressin-associated impairment in cardiac index and systemic oxygen supply in ovine endotoxemia.

INTRODUCTION: Arginine vasopressin (AVP) is increasingly used to treat sepsis-related vasodilation and to decrease catecholamine requirements. However, AVP infusion may be associated with a marked decrease in systemic blood flow and oxygen transport. The purpose of the present study was to evaluate whether dobutamine may be titrated to reverse the AVP-related decrease in cardiac index (CI) and systemic oxygen delivery index (DO2I) in an established model of ovine endotoxemia. METHODS: Twenty-four adult ewes were chronically instrumented to determine cardiopulmonary hemodynamics and global oxygen transport. All ewes received a continuous endotoxin infusion that contributed to a hypotensive-hyperdynamic circulation and death of five sheep. After 16 hours of endotoxemia, the surviving ewes (n = 19; weight 35.6 +/- 1.5 kg (mean +/- SEM)) were randomized to receive either AVP (0.04 Umin-1) and dobutamine (n = 8) or the vehicle (normal saline; n = 6) and compared with a third group treated with AVP infusion alone (n = 5). Dobutamine infusion was started at an initial rate of 2 microg kg-1min-1 and was increased to 5 and 10 microg kg-1 min-1 after 30 and 60 minutes, respectively. RESULTS: AVP infusion increased mean arterial pressure (MAP) and systemic vascular resistance index at the expense of a markedly decreased CI (4.1 +/- 0.5 versus 8.2 +/- 0.3 l min-1 m-2), DO2I (577 +/- 68 versus 1,150 +/- 50 ml min-1 m-2) and mixed-venous oxygen saturation (SvO2; 54.5 +/- 1.8% versus 69.4 +/- 1.0%; all p < 0.001 versus control). Dobutamine dose-dependently reversed the decrease in CI (8.8 +/- 0.7 l min-1 m-2 versus 4.4 +/- 0.5 l min-1 m-2), DO2I (1323 +/- 102 versus 633 +/- 61 ml min-1 m-2) and SvO2 (72.2 +/- 1.7% versus 56.5 +/- 2.0%, all p < 0.001 at dobutamine 10 microg kg-1 min-1 versus AVP group) and further increased MAP. CONCLUSION: This study provides evidence that dobutamine is a useful agent for reversing the AVP-associated impairment in systemic blood flow and global oxygen transport.

[Invasive cardiovascular monitoring--four methods compared]. / Invasives Kreislaufmonitoring--Vier Methoden im Vergleich.

The impact of invasive hemodynamic monitoring on patient safety and outcome in perioperative medicine remains inadequately tested and unproven. The indications for the use of these tools should, therefore, be evaluated according to an individual risk-benefit analysis. The measurement of central venous oxygen saturation (ScvO2) is of little invasiveness as most high-risk patients are instrumented with central venous catheters, and ScvO2 has been shown to improve outcome in patients with septic shock. Transpulmonary thermodilution (e.g. PiCCO-system) delivers information not only on global cardiac function and intravascular volume status but also helps to define the pulmonary consequences of cardiovascular therapy. Transesophageal echocardiography (TEE) is a valuable tool in patients undergoing cardiac surgery and represents the beside-method of choice for rapid assessment of acute life-threatening cardiovascular instability. Apart from special indications, these tools tend to replace the pulmonary artery catheter (PAC) which has been shown to be of little value in various patient populations.

Cerebral response to norepinephrine compared with fluid resuscitation in ovine traumatic brain injury and systemic inflammation.

OBJECTIVE: Traumatic brain injury is frequently accompanied by a systemic inflammatory response. Systemic inflammation was associated with cerebral hyperperfusion uncoupled to global oxygen metabolism in ovine head trauma. The present study investigated the cerebral effects of cerebral perfusion pressure (CPP) management performed by either fluid resuscitation or vasopressor treatment of low CPP induced by systemic inflammation. DESIGN: Nonrandomized experimental study. SETTING: University hospital laboratory. SUBJECTS: A total of 12 adult sheep. INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS: Sheep were anesthetized and ventilated throughout the experimental period (13 hrs). After baseline measurements (hour 0), blunt head trauma was induced by a nonpenetrating stunner. After postinjury measurements (hour 2), all animals received continuous endotoxin infusion. At hour 10, one group (n = 6) was infused with hydroxyethyl starch until CPP reached 60-70 mm Hg. A second group (n = 6) received norepinephrine for CPP elevation. In the norepinephrine group, blood was isovolemically exchanged by hydroxyethyl starch to achieve comparable hematocrit levels. Head trauma increased intracranial pressure and decreased brain tissue oxygen tension. Endotoxemia induced a hyperdynamic cardiovascular response with increased internal carotid blood flow in the presence of systemic hypotension and decreased CPP. Hydroxyethyl starch infusion further increased internal carotid blood flow from (mean +/- sd) 247 +/- 26 (hour 10) to 342 +/- 42 mL/min (hour 13) and intracranial pressure from 20 +/- 4 (hour 10) to a maximum of 25 +/- 3 mm Hg (hour 12) but did not significantly affect brain tissue oxygen tension, sinus venous oxygen saturation and oxygen extraction fraction. Norepinephrine increased internal carotid blood flow from 268 +/- 19 to 342 +/- 58 mL/min and intracranial pressure from 22 +/- 11 to 24 +/- 11 mm Hg (hour 10 vs. hour 13) but significantly increased sinus venous oxygen saturation from 49 +/- 4 (hour 10) to a maximum of 59 +/- 6 mm Hg (hour 12) and decreased oxygen extraction fraction. The increase in brain tissue oxygen tension during norepinephrine treatment was not significant. CONCLUSION: We conclude that despite identical carotid blood flows, only CPP management with norepinephrine reduced the cerebral oxygen deficit in this model.

Roles of MMP-2/-9 in cardiac dysfunction during early multiple organ failure in an ovine animal model.

Biventricular dilation and severe cardiac dysfunction are observed during septic shock. However, when endotoxemia and vasoconstrictor-masked hypovolemia work in concert in the pathogenesis of shock, the clinical scenario is more adverse compared to one of the insults acting alone. Matrix metalloproteinases (MMPs) are involved in chronic and acute heart failure by degrading the mechanical scaffold of the heart and several intracellular proteins. Therefore, the roles of MMP-2, MMP-9, MT1-MMP, focal adhesion kinase (FAK), and Paxillin in hearts of early multiple organ failure induced by norfenefrine-masked hypovolemia and endotoxemia were investigated in an ovine model. Experimental groups included (1) norfenefrine-masked hypovolemia plus endotoxemia (NMH+ENDO) (n=6), (2) norfenefrine-masked hypovolemia without endotoxemia (NMH) (n=6), (3) recurrent endotoxemia during normovolemia (ENDO) (n=6), and (4) healthy untreated controls (CON) (n=3). Apoptosis was determined by TUNEL-staining. Gel zymography revealed significantly increased MMP-2 activity in NMH+ENDO compared to ENDO and controls. MMP-9 activity was significantly elevated in all experimental groups. MMP-2 was significantly increased at the protein level, while MMP-9 was unaltered. MT1-MMP was not significantly changed in any group. Increased MMP activities were associated with cardiac deterioration. MMP-2/-9 activity and phosphorylated Paxillin (p-Paxillin) expression correlated positively with cardiomyocyte apoptosis. This study underscores the pivotal roles of MMP in acute cardiac dysfunction during early multiple organ failure in combined vasoconstrictor-masked hypovolemic and endotoxemia shock.

Role of atrial natriuretic peptide in pulmonary permeability and vasoregulation in ovine sepsis.

OBJECTIVE: Atrial natriuretic peptide is regarded as an important regulator of pulmonary vasomotor tone and permeability. This study investigated the role of atrial natriuretic peptide in sepsis-associated pulmonary pathophysiology. DESIGN: Prospective experimental investigation. SETTING: Laboratory at a university hospital. SUBJECTS: Twelve awake, chronically instrumented sheep. INTERVENTIONS: The sheep were instrumented with lung lymph fistulas and received a continuous infusion with live Pseudomonas aeruginosa for 48 hrs. After 40 hrs, the atrial natriuretic peptide-receptor antagonist HS-142-1 was continuously infused in the HS-124-1 group (3 mg/kg/hr, n = 6) for 8 hrs, whereas the control group received the carrier (n = 6). MEASUREMENTS AND MAIN RESULTS: Lung lymph flow was markedly elevated in response to sepsis after 40 hrs in both groups. Atrial natriuretic peptide-receptor blockade further increased lymph flows by 41 +/- 17% (41 hrs) up to 64 +/- 20% (44 hrs, p < .05) in the presence of normal permeability to protein. Although mean pulmonary artery pressure increased (p < .05 vs. 40 hrs), capillary pressure remained unaffected. Despite identical fluid balances in both groups, cardiovascular filling variables significantly increased in the HS-142-1 group. This was associated with increasing cardiac index and mean arterial pressure (p < .05 vs. 40 hrs). In the control group, all variables remained constant between 41 and 48 hrs. CONCLUSION: Blockade of atrial natriuretic peptide receptors increases pulmonary transvascular fluid flux independent of changes in permeability to protein in chronic ovine sepsis. Atrial natriuretic peptide may therefore play a protective role for the alveolar-capillary barrier during sepsis.

Cerebral vascular and metabolic response to sustained systemic inflammation in ovine traumatic brain injury.

Traumatic brain injury (TBI) is frequently accompanied by a systemic inflammatory response secondary to multiple trauma, shock, or infections. This study investigated the impact of sustained systemic inflammation on cerebral hemodynamics and metabolism in ovine traumatic brain injury. Fifteen sheep were investigated for 14 hours. Head injury was induced with a nonpenetrating stunner in anesthetized, ventilated animals. One group (TBI/Endo, n = 6) subsequently received a continuous endotoxin infusion for 12 hours, whereas a second group (TBI, n = 6) received the carrier. Three instrumented animals served as sham controls. Head impact significantly increased intracranial pressure from 9 +/- 4 mm Hg to 21 +/- 15 mm Hg (TBI/Endo) and from 10 +/- 3 mm Hg to 24 +/- 19 mm Hg (TBI) (means +/- SD). Internal carotid blood flow increased and cerebral vascular resistance decreased (P < 0.05) during the hyperdynamic inflammatory response between 10 and 14 hours in the TBI/Endo group, whereas these parameters were at baseline level in the TBI group. Intracranial pressure remained unchanged during this period, but increased during hypercapnia. The CMRO2, PaCO2, and arterial hematocrit values were identical among the groups between 10 and 14 hours. It is concluded that chronic endotoxemia in ovine traumatic brain injury was associated with cerebral vasodilation uncoupled from global brain metabolism. Different mechanisms appear to induce cerebral vasodilation in response to inflammation and hypercapnia.

Arteriovenous carboxyhemoglobin difference is not correlated to TNF-alpha, IL-6, PCT, CRP and leukocytes in critically ill patients.

BACKGROUND: It is still unclear as to whether the paradoxical arteriovenous carboxyhemoglobin (COHb) difference found in critical illness may represent a novel marker of the acute inflammatory response. We determined whether the arterial and central venous COHb concentration or their difference may be correlated to classical pro-inflammatory markers. METHODS: Arterial and matched central venous blood gases were obtained from non-smoking intensive care patients undergoing gastrointestinal surgery, and were correlated with plasma concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and leukocytes. RESULTS: No correlation was found between arteriovenous COHb difference and the investigated pro-inflammatory mediators. While arterial and central venous COHb concentrations were positively correlated to plasma concentrations of TNF-alpha (P< or =0.01), IL-6 (P<0.05) and PCT (P< or =0.01), they were neither interrelated with PCT nor with leukocytes. CONCLUSIONS: Arteriovenous COHb difference does not appear to be a marker of the acute inflammatory response. Future studies are needed to investigate whether arterial and central venous COHb concentrations by themselves may serve as indicators of systemic inflammation.

Dopexamine reverses the vasopressin-associated impairment in tissue oxygen supply but decreases systemic blood pressure in ovine endotoxemia.

Since arginine vasopressin (AVP) may reduce cardiac output and, in proportion, oxygen delivery, we studied the efficacy of dopexamine (DPX) as an adjunct to AVP infusion. After 1 h of continuous AVP infusion (0.04 U/min) in healthy sheep (n = 7), DPX was additionally administered in incremental doses (1, 5, and 10 microg. kg(-1). min(-1); each dose for 30 min). After a 24-h period of recovery, endotoxin was continuously infused in the same sheep to induce and maintain a hypotensive/hyperdynamic circulation. After 16 h of endotoxemia, AVP and DPX were given as described previously. AVP infusion increased systemic vascular resistance index and decreased cardiac index in both healthy and endotoxemic conditions (P < 0.001 each). This was accompanied by an augmented pulmonary vascular resistance index in endotoxemia (159 +/- 13 dynes. cm(-5). m(-2) versus 202 +/- 16 dynes. cm(-5). m(-2)) and a decrease in oxygen delivery index (health: 842 +/- 66 mL. min(-2). m(-2) versus 475 +/- 38 mL. min(-2). m(-2); endotoxemia: 1073 +/- 49 mL. min(-2). m(-2) versus 613 +/- 44 mL. min(-2). m(-2)) and mixed venous oxygen content (health: 63% +/- 2% versus 47% +/- 2%; endotoxemia: 68% +/- 2% versus 51% +/- 3%; P < 0.001 each). Small doses of DPX (1 and 5 microg. kg(-1). min(-1)) improved not only the AVP-associated depressions in cardiac index, oxygen delivery index, and mixed venous oxygen content, but also the pulmonary vasopressive effect in both groups. While large-dose DPX (10 microg. kg(-1). min(-1)) also reduced mean pulmonary arterial pressure in endotoxemia (27 +/- 1 mm Hg versus 23 +/- 1 mm Hg; P < 0.05 versus baseline), mean arterial blood pressure decreased (105 +/- 4 mm Hg versus 80 +/- 3 mm Hg) and heart rate increased (84 +/- 4 bpm versus 136 +/- 9 bpm; P < 0.001 versus AVP alone), thereby limiting its therapeutic use.

Heat shock protein 72 and apoptosis indicate cardiac decompensation during early multiple organ failure in sheep.

OBJECTIVE: Inducible heat shock protein 72 (HSP 72) preserves myocardial function and prevents apoptosis. We investigated the expression and localization of HSP 72 and apoptosis in our previously described new model of multiple organ failure. DESIGN: Eighteen adult-instrumented sheep and three healthy controls were randomly assigned to one of three groups: (a) norfenefrine-masked hypovolemia plus endotoxemia (NMH+ENDO); (b) norfenefrine-masked hypovolemia without endotoxemia (NMH); (c) recurrent endotoxemia during normovolemia (ENDO); and (d) normovolemia without endotoxemia (CONTROLS). MEASUREMENTS AND RESULTS: Hearts were analyzed by light microscopy, Western blots, immunohistochemistry, and TUNEL staining. HSP 72 expression was approximately threefold increased in NMH+ENDO compared with the other groups ( p<0.05) and was localized mainly in left ventricular cardiomyocytes. HSP 72 was elevated in animals with norfenefrine-refractory shock compared to survivors ( p=0.015). TUNEL-positive cells in the left ventricle were significantly elevated in the NMH+ENDO group ( p=0.05) and correlated with HSP 72 expression (r=0.51, p=0.018). HSP 72 correlated positively with heart rate (r=0.76, p<0.0001), the prefinal hourly dose of norfenefrine (r=0.88, p<0.0001), and negatively with left ventricular stroke work index (r=-0.52, p=0.028). Double staining revealed TUNEL-positive cells with and without HSP 72 expression. Micronecroses were only detectable in NMH and NMH+ENDO without intergroup difference or correlations with hemodynamics. CONCLUSION: HSP 72 overexpression and apoptosis, but not necrosis, indicate cardiovascular decompensation and poor outcome during early multiple organ failure.