Shock In Dogs Research Articles

Normovolemic hemodilution improves oxygen extraction capabilities in endotoxic shock.

We studied the effects of normovolemic hemodilution on tissue oxygen extraction capabilities in a canine model of endotoxic shock. Eighteen anesthetized and mechanically ventilated dogs underwent normovolemic hemodilution with 6% hydroxyethyl starch solution to reach hematocrit (Hct) levels around 40, 30, or 20% before the administration of 2 mg/kg of Escherichia coli endotoxin. Cardiac tamponade was then induced by repeated injections of normal saline into the pericardial sac to reduce cardiac output and study whole body oxygen extraction capabilities. Whole body critical oxygen delivery was lower in the Hct 20% and 30% groups (8.4 +/- 0.4 and 10.4 +/- 0.7 ml. kg(-1). min(-1), respectively) than in the Hct 40% group (12.8 +/- 0.8 ml. kg(-1). min(-1)) (both P < 0.005). The whole body critical oxygen extraction ratio was higher in the Hct 30% and 20% groups (49.1 +/- 8.2 and 55.2 +/- 4.6%, respectively) than in the Hct 40% group (37.1 +/- 4.4 %) (both P < 0.05). Liver critical oxygen extraction ratio was also higher in the Hct 30% and 20% groups than in the Hct 40% group. The arterial lactate concentrations and the gradient between ileum mucosal PCO(2) and arterial PCO(2) were lower in the Hct 20% and 30% groups than in the Hct 40% group. We conclude that, during an acute reduction in blood flow during endotoxic shock in dogs, normovolemic hemodilution is associated with improved tissue perfusion and increased oxygen extraction capabilities.

Efficacy of prostaglandin E 1 in combination with volume replacement therapy in the treatment of hemorrhagic shock in dogs

Objective: The aim of the present study was to assess the effects of prostaglandin E 1 (PGE 1) on hemodynamic and splanchnic blood flow in a canine model of hemorrhagic shock and volume replacement therapy. Methods: Hemorrhagic shock was induced in 14 anesthetized dogs by withdrawing blood into a reservoir until the mean arterial pressure stabilized at 50 mm Hg for 30 minutes. During oligemia, the drawn blood was stored at room temperature in plastic bags containing citrate-phosphate-dextrose solution. The shock period was then terminated and the remainder of the drawn blood was reinfused within a 2-minute period. The dogs were divided into 2 equal groups. Group P received PGE 1 0.1 μg/kg per minute; group S received saline in an amount equal to the diluent in group P (0.6 mL/kg per hour). The efficacy of both therapies in maintaining hemodynamic variables and splanchnic blood flow (renal cortex, renal medulla, liver, and pancreas) was investigated over 180 minutes. Splanchnic blood flow was determined by the hydrogen gas clearance method. Results: Sixty to 180 minutes after resuscitation, the cardiac index and left ventricular stroke work index values in group P were significantly greater than those in group S ( P < 0.05), and systemic vascular resistance in group P was significantly lower than that in group S during the resuscitative period ( P < 0.05). Splanchnic organ blood flow decreased significantly with hemorrhagic shock. Splanchnic blood flow to all organs in group P returned to baseline values when resuscitative therapy was performed, but the values in group S were decreased significantly compared with baseline despite resuscitation ( P < 0.05). Moreover, all splanchnic blood flow values were significantly greater in group P than in group S. Conclusions: The results of this study in dogs demonstrate that PGE 1 added to volume replacement therapy is a useful adjuvant with respect to hemodynamic and splanchnic recovery in hemorrhagic shock.

Relaxing and contracting activities of heartworm extract on isolated canine abdominal aorta.

Effect of adult heartworm (HW) crude extract on isolated canine abdominal aortic strips precontracted with noradrenaline was examined by recording isometric changes in tension. HW extract caused contraction of the aortic strip at a low concentration (LC) and its relaxation at a high concentration (HC). In aortic strips without endothelium, LC extract elicited a contraction similar to that in the strips with endothelium, whereas HC extract failed to produce any relaxation but instead produced a contraction. The relaxing effect of HC extract was blocked after treatment with 300 microM NG-nitro-L-arginine methyl ester hydrochloride, with reversal by additional treatment with 3 mM L-arginine. It was also markedly reduced or abolished after treatment with 3 microM oxyhemoglobin or 1 microM methylene blue. Fractionation of HW extract by high-performance liquid chromatography revealed that the relaxing and contracting activities are due to different substances in the extract. The results indicate that HW extract contains 2 different vasoactive substances, 1 causing contraction of canine abdominal aorta via a direct action on the smooth muscle, and the other its relaxation indirectly by releasing nitric oxide from endothelial cells. These vasoactive substances might play a role in HW extract-induced shock in dogs, and in the pathogenesis of HW infection.

Role of histamine in heartworm extract-induced shock in dogs.

To determine whether heartworm (HW) extract-induced shock in dogs is consistent with anaphylactic shock by examining the role of histamine. 6 mixed-breed dogs (3 without and 3 with HW infections) and 4 specific pathogen-free (SPF) Beagles. Four experiments were performed as follows: 1) 6 mixed-breed dogs were treated IV with 2 ml of HW extract, and plasma histamine concentrations were determined; 2) 4 SPF dogs were treated IV with 2 ml of HW extract and examined for shock; 3) sera from 6 dogs of experiment 1 and from 4 SPF dogs of experiment 2 that were obtained before HW extract treatment were tested for heterologous passive cutaneous anaphylaxis (PCA), using rabbits during a sensitization period of 48 to 72 hours; and 4) mast cell degranulation by HW extract was tested, using rat mesentery and canine cultured mast cells. Experiment 1: 6 dogs developed shock, and plasma histamine concentrations increased significantly from 0.3 +/- 0.2 (mean +/- SD) ng/ml before HW extract treatment to 44.6 +/- 68.9 ng/ml at the onset of shock; experiment 2: all SPF dogs developed shock and had an increase in plasma histamine concentrations; experiment 3: sera from mixed-breed dogs without HW infection and from SPF dogs had negative PCA reactions; experiment 4: HW extract degranulated rat mesentery mast cells and released histamine directly from canine mast cells. Results of our study indicate that an unknown mast cell-degranulating substances contained in HW extract may degranulate mast cells directly, consequently releasing histamine that may participate in the onset of shock in HW extract-induced shock in dogs.

Time Course of Inducible Nitric Oxide Synthase Activity Following Endotoxin Administration in Dogs

An increased production of nitric oxide (NO) via the inducible isoform of NO synthase (iNOS) has been incriminated in the pathogenesis of septic shock. Since the time course of iNOS activity is not known during endotoxic shock in dogs, we measured iNOS activity, estimated by the rate of conversion of 14C-arginine to 14C-citrulline in the absence of calcium, in the heart, lung, liver, kidney, and gut at 1, 2, 3, 4, and 6 h after a bolus of Escherichia coli endotoxin (2 mg/kg, iv), in the dog. This model, including generous fluid administration, is associated with typical features of human septic shock, including low systemic vascular resistance, altered myocardial function and limited oxygen extraction capability. An increase in iNOS activity was observed at 4 h in the liver (0.24 vs 0.04 mU/mg/min) and at 6 h in the heart (0.26 vs 0.09 mU/mg/min). These findings may contribute to a better delineation of the involvement of NO in endotoxic shock, and to the evaluation of the therapeutic effects of NO inhibitors.

Diaspirin cross-linked hemoglobin improves oxygen extraction capabilities in endotoxic shock.

We studied the effects of diaspirin cross-linked hemoglobin (DCLHb), a cell-free hemoglobin derived from human erythrocytes, on blood flow distribution and tissue oxygen extraction capabilities in endotoxic shock. Eighteen pentobarbital sodium-anesthetized, mechanically ventilated dogs received 2 mg/kg of E. coli endotoxin, followed by saline resuscitation to restore cardiac filling pressures to baseline levels. The animals were randomly divided into three groups: six served as control, six received DCLHb at a dose of 500 mg/kg (group 1) and six DCLHb at a dose of 1,000 mg/kg (group 2). Cardiac tamponade was then induced by saline injection in the pericardial sac to progressively reduce cardiac index and thereby allow study of tissue oxygen extraction capabilities. DCLHb had a dose-dependent vasopressor effect but did not significantly alter cardiac index or regional blood flow. During cardiac tamponade, critical oxygen delivery was 12.8 +/- 0.7 ml. kg(-1). min(-1) in the control group, but 8.6 +/- 0.9 and 8.2 +/- 0.7 ml. kg(-1). min(-1) in groups 1 and 2, respectively (both P < 0.05 vs. control group). The critical oxygen extraction ratio was 39.1 +/- 3.1% in the control group but 58.7 +/- 12.8% and 60.2 +/- 9.0% in groups 1 and 2, respectively. We conclude that DCLHb can improve whole body oxygen extraction capabilities during endotoxic shock in dogs.

Heart rate variability during massive hemorrhage and progressive hemorrhagic shock in dogs.

To investigate the sequential changes in heart rate (HR), autonomic nervous activity presented by the spectral analysis of heart rate variability (HRV), hemodynamics and metabolism during massive hemorrhage and progressive hemorrhagic shock in dogs. Twelve dogs were subjected to acute massive hemorrhage until mean arterial pressure (MAP) reached 50 mm Hg. Then bleeding was stopped and they were allowed to reach a plateau phase. They were divided, post hoc, into bradycardic or tachycardic groups according to their HR response to the acute massive hemorrhage. After reaching a plateau phase, the dogs were further bled to keep their MAP around 50 mmHg (progressive hemorrhagic shock). Their heart rate power spectra were quantified into low-frequency (LF) (0.04-0.15 Hz) and high-frequency (HF) (0.15-0.4 Hz) components. In the bradycardic group, both LF and HF increased after massive hemorrhage, but during progressive hemorrhagic shock these components decreased while HR increased. In the tachycardic group, LF increased after massive hemorrhage, but during progressive hemorrhagic shock LF decreased with continuous suppression of HF CONCLUSION: Massive hemorrhage caused two types of HR response: bradycardia and tachycardia. The HRV profile showed differential autonomic characteristics, and could be a valuable tool in assessing various degrees of hemorrhagic shock.

Hyperthermic resuscitation is safe and effective after hemorrhagic shock in dogs.

To show that resuscitation from hypothermic, hemorrhagic shock using 65 degrees C intravenous fluid results in a more rapid return to euthermia compared with 40 degrees C intravenous fluid, without significant endothelial or hemolytic injury. Fourteen anesthetized beagles (10-12 kg) were cooled to a core temperature of 30 degrees C and hemorrhaged to a mean arterial pressure of 40 to 45 mm Hg for 30 minutes. The animals were randomized to receive either 65 degrees C or 40 degrees C intravenous fluid through a specially designed catheter at a rate of 80% of their blood volume per hour until euthermic (37 degrees C) or for 2 hours. Blood pressure, pulmonary artery pressure, heart rate, and core temperature were continuously monitored. Blood samples were collected at baseline, after hemorrhage, 2 hours of resuscitation, and at postmortem examination after 7 days of survival. Laboratory measurements included complete blood count, plasma-free hemoglobin, and osmotic fragility. Values were compared using the Student's paired or unpaired t test with p approximately 0.05 indicating significance. Postmortem examination included light microscopy of the proximal superior vena cava or right atrium. Animals receiving 65 degrees C intravenous fluid warmed 3.6 degrees C/hour, significantly faster than the 40 degrees C animals (1.9 degrees C/hour). There were no significant differences in plasma-free hemoglobin or osmotic fragility. Endothelial injuries were found in two animals in each group. These defects occurred along the path of catheter insertion and not at the infusion site. Central intravenous fluid at 65 degrees C is a more rapid means of treating hypothermia than standard 40 degrees C intravenous fluid. It is safe even in hypovolemic animals.

Vasopressin, renin, and adrenocorticotropic hormone levels during the resuscitation of hemorrhagic shock in dogs

Hemorrhage is a potent stimulus for the release of vasopressin (VP), renin, and adrenocorticotropic hormone (ACTH). The goal of this study was to analyze changes in plasma VP, renin, and ACTH levels during hemorrhagic shock and resuscitation with two different solutions: hypertonic acetate dextran (HAD) and lactated Ringer’s (LR) solution. Eight randomized dogs were shocked by removing 37 ± 9 mL/kg of blood while maintaining the mean arterial pressure (MAP) at 45 ± 5 mmHg for 1 h. Test solutions were randomized and infused as needed with the hemorrhaged blood to restore the MAP and cardiac index to baseline. Blood samples for hormone analyses were taken in baseline, shock, and resuscitation periods. For each experiment, all hormone levels increased in the postshock period and then returned to baseline values after resuscitation with both solutions. VP and renin levels rapidly returned to baseline values after resuscitation in the LR dogs compared with the HAD dogs ( p < 0.05). By contrast, there was no significant difference in ACTH levels between the two solutions. High-volume infusion with LR achieves more rapid restoration than small-volume infusion with HAD for VP and renin levels.

S-Nitroso-N-acetylpenicillamine (SNAP) during hemorrhagic shock improves mortality as a result of recovery from vascular hyporeactivity.

Nitric oxide donors are protective against hemorrhagic shock (HS). However, no detailed investigation has been performed. We investigated this mechanism using S-nitroso-N-acetylpenicillamine (SNAP). HS (mean arterial pressure: 40 mm Hg) was induced in 20 dogs. Sixty min after HS, the animals were treated with saline (Cont-Gr: n = 7) or SNAP; 5 microg. kg(-1). 10 min(-1) followed by 5 microg. kg(-1). h(-1) (SNAP-Gr: n = 7). After another 60 min, the shed blood was reinfused. Reactivities to noradrenalin (NA), changes in hemodynamics, the plasma catecholamines, and nitric oxide derivatives were determined. In Cont-Gr, 3 dogs died at 90, 98, and 102 min after HS. In Cont-Gr, % changes of systolic arterial blood pressure to 1 and 2.5 microg/kg of NA after the recovery from HS decreased from 23.7% +/- 4.1% (before HS) to 6.5% +/- 0.6% and from 50.1% +/- 7.7% (before HS) to 14.5% +/- 2.6%, respectively (P < 0. 01). In SNAP-Gr, reactivity to NA was maintained. At 120 min after HS, mean arterial pressure and cardiac output in SNAP-Gr increased but not in Cont-Gr. Plasma catecholamine levels in SNAP-Gr were suppressed compared with those of Cont-Gr. In conclusion, a small dose of SNAP during HS decreased the mortality of the dogs. This might have been caused in part by residual vascular hyporeactivity. The administration of a small dose of S-nitroso-N-acetylpenicillamine (a nitric oxide donor), a dose which did not exert a significant vasodilator effect, was administered during hemorrhagic shock in dogs. S-nitroso-N-acetylpenicillamine improved the vascular hyporeactivity to noradrenaline and decreased the mortality rate.

S-nitroso-N-acetylpenicillamine (SNAP) During Hemorrhagic Shock Improves Mortality as a Result of Recovery From Vascular Hyporeactivity

Nitric oxide donors are protective against hemorrhagic shock (HS). However, no detailed investigation has been performed. We investigated this mechanism using S-nitroso-N-acetylpenicillamine (SNAP). HS (mean arterial pressure: 40 mm Hg) was induced in 20 dogs. Sixty min after HS, the animals were treated with saline (Cont-Gr:n = 7) or SNAP; 5 μg · kg−1 · 10 min−1 fol- lowed by 5 μg · kg−1 · h−1 (SNAP-Gr:n = 7). After another 60 min, the shed blood was reinfused. Reactivities to noradrenalin (NA), changes in hemodynamics, the plasma catecholamines, and nitric oxide derivatives were determined. In Cont-Gr, 3 dogs died at 90, 98, and 102 min after HS. In Cont-Gr, % changes of systolic arterial blood pressure to 1 and 2.5 μg/kg of NA after the recovery from HS decreased from 23.7% ± 4.1% (before HS) to 6.5% ± 0.6% and from 50.1% ± 7.7% (before HS) to 14.5% ± 2.6%, respectively (P < 0.01). In SNAP-Gr, reactivity to NA was maintained. At 120 min after HS, mean arterial pressure and cardiac output in SNAP-Gr increased but not in Cont-Gr. Plasma catecholamine levels in SNAP-Gr were suppressed compared with those of Cont-Gr. In conclusion, a small dose of SNAP during HS decreased the mortality of the dogs. This might have been caused in part by residual vascular hyporeactivity. Implications The administration of a small dose of S-nitroso-N-acetylpenicillamine (a nitric oxide donor), a dose which did not exert a significant vasodilator effect, was administered during hemorrhagic shock in dogs. S-nitroso-N-acetylpenicillamine improved the vascular hyporeactivity to noradrenaline and decreased the mortality rate.

Intravenous administration of hypertonic sodium chloride solution with dextran or isotonic sodium chloride solution for treatment of septic shock secondary to pyometra in dogs

Objective To determine effects of IV administration of hypertonic saline (7.5% NaCl) solution with 6% dextran 70 (HSSD) or isotonic saline (0.9% NaCl) solution (ISS) to dogs with septic shock secondary to pyometra. Design Prospective, randomized, clinical study. Animals 14 client-owned dogs with septic shock secondary to pyometra. Procedure Prior to emergency ovariohysterectomy, catheters were placed in pulmonary and femoral arteries of each dog to evaluate hemodynamic and oxygenation status. Immediately prior to surgery, 7 dogs received HSSD (4 ml/kg [1.82 ml/lb] of body weight, IV) and 7 dogs received ISS (32 ml/kg [14.54 ml/lb], IV) during a 5-minute period. Measurements of hemodynamic and oxygenation variables were obtained before and 5 and 20 minutes after administration of fluids. Results Mean arterial pressure (MAP) increased significantly 5 and 20 minutes after administration of HSSD, whereas ISS did not affect MAP. However, cardiac output, cardiac index, and oxygen delivery increased and hematocrit decreased after both treatments. Oxygen consumption and extraction rate and degree of acidosis did not improve after either treatment. Conclusions and Clinical Relevance Intravenous administration of small volumes of HSSD to dogs with septic shock secondary to pyometra resulted in improvement of hemodynamic and oxygenation status. Although cardiac output, cardiac index, and oxygen delivery improved after administration of a volume of ISS equal to 8 times that of HSSD, MAP increased to &gt; 80 mm Hg only after treatment with HSSD. Administration of HSSD may be an effective treatment for septic shock in dogs. (J Am Vet Med Assoc 1999;215:1283–1287)

Continuous venovenous hemofiltration improves cardiac performance by mechanisms other than tumor necrosis factor-alpha attenuation during endotoxic shock.

To assess the effects of continuous venovenous hemofiltration (CWH) on global and regional hemodynamics, plasma lactate, and tumor necrosis factor-oa (TNF-a) levels during endotoxic shock in dogs. Thirty pentobarbital-anesthetized and mechanically ventilated dogs were divided into six groups of five dogs each. Group 1 served as a control, undergoing CWH at 3 Uhr without endotoxin. Group 2 served as the endotoxin-alone time-matching group. Group 3 received CWH 1 hr after endotoxin at 3 Uhr for 270 mins. Group 4 received CWH 1 hr after endotoxin at 3 Uhr for 150 mins and at 6 Uhr for an additional 120 mins. Group 5 and group 6 received the ultrafiltrate from group 1 and group 3, respectively. Three hours after endotoxin challenge, dogs treated with CWH at 3 Uhr had a higher cardiac output (4.9 + 0.6 vs. 2.9 + 0.6 Umin; p < .05) and stroke volume (35 + 7 vs. 20 + 4 mL; p < .05) and a lower pulmonary vascular resistance (116 26 vs. 331 + 126 dyne-sec/cm5; p < .05) than the endotoxin-alone group. Five hours after endotoxin, dogs treated with CWH at 6 Uhr also had higher hepatic (464 + 164 vs. 126 + 75 mUmin; p < .05) and femoral (95 + 46 vs. 30 + 34 mL/min; p < .05) blood flow. Moreover, dogs treated with CWH at 6 Uhr had higher mean arterial blood pressure (84 + 24 vs. 40 + 15 mm Hg; p < .05) and left ventricular stroke work index (1.1 + 0.6 vs. 0.2 + 0.2 g/kg; p < .05) than the endotoxin-alone group. Plasma lactate levels were lower in the CWH group at 6 Uhr (2.7 + 1.1 mmol/L) than in the endotoxin-alone group (4.4 + 0.6 mmol/L; p < .05). Plasma TNF-ao levels were unaffected, and only minor amounts of TNF-o were found in the ultrafiltrate. In this acute endotoxic shock model, CWH at 3 Uhr improved cardiac performance and decreased pulmonary vasoconstriction. Moreover, CWH at 6 LUhr also increased arterial blood pressure and left ventricular stroke work, increased hepatic and femoral arterial blood flow, and decreased blood lactate levels. These effects were not attributable to TNF-alpha removal.

Hepato-splanchnic Blood Flow and Oxygen Extraction Capabilities during Experimental Tamponade: Effects of Endotoxin

We studied the hepato-splanchnic vascular response and changes in O2extraction capabilities to a reduction in blood flow following endotoxemia. Fourteen anesthetized and mechanically ventilated dogs were divided into two groups of seven each. Group 1 received 2 mg/kg ofE. coliendotoxin, and group 2 served as a control. After initial fluid resuscitation following endotoxic shock, regional blood flow estimated by an ultrasonic technique increased similarly in the hepatic artery, portal vein, and mesenteric artery, but microvascular blood flow estimated by a laser Doppler technique was lower in the liver than in the intestinal mucosa. When blood flow was reduced by cardiac tamponade, endotoxin-treated animals had greater whole body and regional critical O2delivery (DO2crit) and lower whole body, liver, and intestinal critical O2extraction ratios (O2ERcrit). DO2critwas higher in the liver than in intestine but O2ERcritwas similar in the two organs. Whole bodyDO2critat the onset of organ O2supply dependency was similar under control (9.4 ± 1.9 mL/kg · min for whole body, 10.3 ± 4.7 mL/kg · min for liver, and 10.0 ± 2.6 mL/kg · min for intestine) and endotoxic conditions (13.6 ± 3.2 mL/kg · min for whole body, 15.6 ± 2.7 mL/kg · min for liver, and 15.4 ± 8.7 mL/kg · min for intestine). We conclude that fluid-resuscitated endotoxic shock in dogs is characterized by blood flow redistribution within the liver and intestine. Microvascular depression may be more severe in the liver than in the intestinal mucosa, although the whole body, the liver, and the intestine became O2supply-dependent simultaneously.

Plasma concentration of adrenomedullin is increased in hemorrhagic shock in dogs.

Plasma concentration of adrenomedullin is increased in hemorrhagic shock in dogs.

Plasma Concentration of Adrenomedullin Is Increased in Hemorrhagic Shock in Dogs

Plasma Concentration of Adrenomedullin Is Increased in Hemorrhagic Shock in Dogs

Effects of anaphylaxis mediators on partitioned pulmonary vascular resistance during ragweed shock in dogs.

We examined the effect of anaphylactic shock on the longitudinal distribution of pulmonary vascular resistance (PVR) in ragweed-sensitized dogs in which PVR was partitioned into an upstream arterial component (Rus) and a downstream venous and capillary component (Rds). We also assessed whether Rus and Rds would be reduced by pretreatment with histamine H1- and H2-receptor blocking agents and with cyclooxygenase and lipoxygenase pathway inhibitors. Anesthetized animals were examined on separate occasions 3 wk apart in which one of the treatments was randomly given. The pulmonary arterial occlusion technique was used to determine segmental pressure drops. During ragweed challenge, PVR increased approximately 4 times compared with the preshock value (3.04 vs. 12. 07 mmHg . l-1 . min; P < 0.05). Although both Rus and Rds increased postshock, the greatest relative increase occurred in Rds. None of the treatments reduced partitioned resistances compared with no treatment. Our results show that, under conditions of anaphylactic shock, increases in Rus and Rds could not be ascribed to release of histamine or products of the cyclooxygenase and lipoxygenase pathways.

Study of polymerized hemoglobin in experiment.

Lyophilized polymerized hemoglobin has no group specificity and does not damage the kidney after 2 days of storage; its T/2 is 14-16 hours. P50 of solution prepared on the hemoglobin basis is 24-28 torr at 37 degrees C and pCO2, 40 torr in 0.05 M Tris-buffer, pH 7.4. As was shown in models of hemorrhagic shock in dogs, the hemodynamic properties of the solutions is such that it is capable of increasing the cardiac output and maintains the arterial pressure at the level close to initial one. Analysis of the oxygen expenditure suggests the expediency of using the solution in doses of 1 gr/kg of body weight. The increase in oxygen capacity of the solutions administered in the said dose is the result of increase in the hemoglobin concentration in blood plasma. Contribution of the solution to blood oxygen capacity is 12-13%. The solution of lyophilized modified hemoglobin can be used for correction of both hemodynamic disorders and decreased oxygen delivery to tissues in hemorrhagic shock.

Intrahepatocellular erythrocyte inclusions and increased calcium precipitation in canine endotoxic shock

Aims: To investigate the electron microscopic lozalization of membrane-bound and exchangeable calcium with specific calcium precipitation techniques during endotoxic shock in the dog. Methods: Ten pentobarbital anesthetized, mechanically ventilated, and paralyzed dogs were studied. Six dogs received 2 mg/kg E.coli endotoxin i.v. followed by a continuous 0.9% saline infusion to restore and maintain baseline cardiac filling pressures. Four dogs served as time-matched controls. Each experiment lasted for 3 h. After the completion of study, the livers of four endotoxic and two control dogs were fixed by perfusion of 3% glutaraldehyde via the portal vein. Liver sections were then prepared for electron microscopy and calcium localization studies. Results: Hepatocytes of endotoxic animals completely lost their plasma membrane-bound calcium. The most severely damaged cells cells showed extensive “blebbing” of the plasma membrane and contained numerous cytoplasmic erythrocyte inclusions. Endotoxin administration also caused excessive calcium precipitation inside hepatocytes in areas with pronounced sinusoidal damage. Conclusions: In this acute model of fluid-resuscitated endotoxic shock in dogs, the use of specific calcium localization techniques enables the demonstration of disturbances in hepatocellular calcium handling, which appear to be closely related to structural alterations of the hepatocyte cell membrane. Erythrocyte uptake by hepatocytes is a previously undescribed phenomenon in canine endotoxic shock and may serve as an additional histologic marker of ultrastructural cell (membrane) damage.

Effects of norepinephrine on regional blood flow and oxygen extraction capabilities during endotoxic shock.

We explored the effects of norepinephrine on blood flow distribution and oxygen extraction capabilities during hyperdynamic endotoxic shock. Twelve anesthetized and mechanically ventilated dogs received 2 mg/kg of Escherichia coli endotoxin followed by a general saline infusion and were then randomly divided into two groups: six received norepinephrine (1 microg/kg/min), and six served as control subjects. The norepinephrine group maintained higher mean arterial pressure, cardiac index, left ventricular stroke work index, and hepatic arterial blood flow without altering blood flow to portal, mesenteric, and renal beds. When cardiac tamponade was induced to study tissue oxygen extraction capabilities, the norepinephrine group had a lower critical oxygen delivery in whole body (11.5 +/- 5.2 versus 14.3 +/- 1.4 ml/kg/min, p < 0.05) and in liver (25.0 +/- 11.3 versus 38.0 +/- 9.0 ml/min, p = NS) and a higher critical oxygen extraction ratio in whole body (53.8 +/- 17.7 versus 32.0 +/- 6.1%, p < 0.05), and in liver (57.0 +/- 11.9 versus 35.2 +/- 4.3%, p < 0.05). We conclude that during endotoxic shock in dogs, norepinephrine hardly influences blood flow distribution and could even increase hepatic artery blood flow, and it can also improve whole body and liver oxygen extraction capabilities.