G. C. van den Bos

Changes in regional plasma extravasation in rats following endotoxin infusion

Regional differences in plasma extravasation during endotoxin shock in rats and a possible relationship with changes in regional blood flow were studied with radioactive isotopes (125I-HSA, 51Cr-labeled red blood cells, microspheres) in anesthetized rats (pentobarbital). Shock was induced by intravenous infusion of endotoxin (Eschericia coli; 10 mg X kg-1) for 60 min (starting at t = 0); at t = 120 min, the experiments were terminated. These rats (n = 8) were compared with time-matched control rats (n = 8). A third group (rats killed 7.5 min after injection of 125I-HSA, i.e., no extravasation; n = 8) served as baseline. The amount of plasma extravasated in 2 hr of endotoxin shock was significantly increased over control values in skin (by 67%), colon (88%), skeletal muscle (105%), stomach (230%), pancreas (300%), and diaphragm (1300%). Losses of 125I-HSA into intestinal lumen and peritoneal cavity had also increased over control values by 146 and 380%, respectively. Blood flow was compromised in most organs except heart and diaphragm. Extravasation when normalized for total plasma supply was correlated with total blood supply; the more the blood supply decreased, the higher the normalized extravasation. In the diaphragm, however, blood supply and plasma leakage increased together. Decreased blood supply and plasma extravasation may be related but they could also be simultaneously occurring independent phenomena with a common origin.

Effects of endotoxemia on systemic plasma loss and hematocrit in rats

Endotoxemia in rats increases plasma extravasation but does not result in continuously rising hematocrit. These contradictory observations led us to design a study in anesthetized rats (C, control rats, n = 10; E, endotoxin rats, n = 10) in which we continuously measured in blood hematocrit (conductivity cell) and changes in concentration of 125I-HSA (human serum albumin) and 51Cr-labeled red cell (51Cr-RBC; multichannel analyzer) in an extracorporeal circuit. In two additional series of experiments we measured in blood samples changes in protein concentration (series II, C: n = 7, E: n = 7) and uptake of intraperitoneally injected 125I-HSA and 51Cr-RBC (reflecting lymph flow rate; series III, C: n = 6, E: n = 7). Endotoxemia was induced by infusion (iv, 0.2 ml/100 g.hr) of Escherichia coli endotoxin (20 mg/kg) from t = 0 to t = 60 min; controls received saline. Experiments ended at t = 120 (series I and II) or 150 min (series III). The endotoxemia resulted in a marked rise of serum lactate (by ca 500% at t = 120); heart rate increased and central venous pressure decreased (by ca 20 and -95% at t = 120, respectively). All rats showed characteristic changes in hematocrit during endotoxemia: an increase from t = 20 to t = 45 (by ca 9%) followed by a decrease to preshock values or less at t = 120. The 51Cr activity per microliter blood cells did not change, indicating that there was no red cell mobilization. Protein concentration and 125I-HSA activity also showed a temporary increase during endotoxemia, but 125I-HSA activity per gram protein was decreased. Peritoneal uptake of 125I-HSA and 51Cr-RBC was significantly increased during endotoxemia (by 200%). We conclude that fluid extravasation during endotoxemia is temporary, mainly concerns plasma water, and is compensated by mechanisms like reabsorption and increased lymph flow, resulting in restoration of plasma volume.

Development of Renal Failure in Endotoxemic Rats: Can It Be Explained by Early Changes in Renal Energy Metabolism?

Endotoxin shock not only causes renal failure, endotoxemia also leads to metabolic impairment, resulting in energy shortage and loss of cellular integrity; therefore, we tested the hypothesis that early changes in renal metabolism contribute to the development of acute renal failure during endotoxin shock. Endotoxin (Escherichia coli 127B8; 8 mg/kg from t = 0 to 60 min) was infused in three groups of 8 rats, in which renal biopsies were taken at t = 30, 50 and 90 min, respectively; a fourth group (n = 8) served as control. In the biopsies, glucose, lactate, ATP, ADP, AMP and creatine phosphate concentrations were determined. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured from the clearances of 131I-hippurate and 125I-thalamate, respectively. We also assayed urine flow (V; catheter in the bladder), cardiac output (CO), blood pressure (MAP), heart rate (HR) and arterial lactate, glucose and creatinine concentrations. During the first 30 min of endotoxemia, we found no systemic hemodynamic or biochemical changes. From t = 30 to t = 90, CO and MAP decreased to 59 and 70%, respectively, while HR and serum levels rose to 110 and 800%, respectively (p < 0.05), indicating progression of shock. Renal function clearly deteriorated from t = 30; at t = 90 RPF, GFR and V had decreased by 86, 84 and 86%, respectively, plasma creatinine being 193% of the baseline value (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and renal actions of dopexamine and dobutamine during endotoxin shock in the rat

Abstract Acute renal failure is a complication of endotoxin shock caused by decreased renal blood flow and nephrotoxic effects of endotoxin. We hypothesized that dopexamine (DX), a new dopamine and β2 receptor agonist that lacks α-adrenergic vasoconstrictor action, might prevent acute renal failure during shock by its vasodilator action on the renal circulation and not as a result of a concomitant increase in cardiac output (CO). We thus compared the action of DX with that of dobutamine (DB; β1-agonist, no renal effects) administered in such a dose that it caused a similar increase in CO. Shock was induced in anesthetized (sodium pentobarbital) rats by infusion (2 mL/kg/h) of endotoxin ( Escherichia coli 0127138, 10 mg/kg) from t = 0 to t = 60 minutes; experiments ended at t = 135 minutes. Dopexamine (3.10 −8 mol/kg/min; DX group, n = 8) or DB (10 −8 to 10 −7 mol/kg/min; DB group, n = 8) was infused from t = −30 to t = 135 minutes; a third group only received endotoxin (ES group, n = 8). Glomerular filtration rate (GFR) and renal plasma flow (RPF) during shock were calculated from plasma double exponential disappearance rate from t = 90 to t = 135 minutes of 125 I thalamate and 131 I hippurate, respectively. In renal biopsies, we also measured lactate, glucose, ATP, phosphocreatine concentration (CrP), energy charge ([ATP + 0.5 ADP]/[ATP + ADP + AMP]) and the number of leukocytes per 50 glomeruli at t = 135 minutes. In the ES group, CO was low (approximately 55 mL/min) and serum lactate was high (approximately 5 mmol/L, indicative of shock); RPF and GFR were 1.28 ± 0.31 and 0.46 ± 0.07 mL/min/100 g body weight, respectively. Cardiac output in the DX and DB groups was higher (by approximately 45%) than in the ES group due to a greater stroke volume, but RPF and GFR were significantly higher only in the DX group (by 140% and 76%, respectively). Dopexamine and DB improved renal metabolism to the same extent; the accumulation of leukocytes during endotoxemia was not prevented in either group. The major action of DX thus seems to be an increase in RPF that cannot be attributed to restored CO alone, but also to decreased renal vascular resistance. Acute renal failure was prevented by DX in this way.

Literature of resuscitationAbdominal compressions increase vital organ perfusion during CPR in dogs: Relation with efficacy of thoracic compressions: Ann Emerg Med 1995; 25/3 (375–385)

STUDY OBJECTIVE Abdominal compressions can be interposed between the thoracic compressions of standard CPR (SCPR). The resulting interposed abdominal compression CPR (IAC-CPR) may increase blood pressures and patient survival, particularly if applied as a primary technique after in-hospital cardiac arrest. We used a predominant cardiac compression canine model to study the effects of IAC-CPR on blood pressures and total and vital organ perfusion as a function of time after cardiac arrest and efficacy of SCPR. DESIGN In a crossover design, we measured blood pressures and total and regional blood flow (radioactive microspheres) during 6-minute episodes of mechanical SCPR and IAC-CPR, both early (4 to 16 minutes) and late (18 to 30 minutes) after induction of ventricular fibrillation in eight dogs (weight, 25 to 33 kg) under neuroleptanalgesia/anesthesia. RESULTS During IAC-CPR, the ascending aortic-right atrial pressure gradient increased (P < .05), and retrograde pressure pulses contributed to the rise of ascending aortic pressure. Within 2 minutes after the start of IAC-CPR, end-tidal CO2 fraction increased by 0.6 +/- 0.4 vol% (P < .05), suggesting enhanced venous return. IAC-CPR enhanced (P < .05) total forward blood flow (574 +/- 406 versus 394 +/- 266 mL/minute during SCPR for the early phase) and vital organ perfusion (including myocardium), in both early and late phases. The IAC-CPR-induced augmentation of blood flow was greater if perfusion was relatively high during SCPR. CONCLUSION Compared with predominant cardiac compressions alone (SCPR), the addition of interposed abdominal compressions (IAC-CPR) improves total and vital organ oxygen delivery through enhanced venous return and perfusion pressures.

Abdominal compressions increase vital organ perfusion during CPR in dogs: Relation with efficacy of thoracic compressions: Ann Emerg Med 1995; 25/3 (375–385)

STUDY OBJECTIVE Abdominal compressions can be interposed between the thoracic compressions of standard CPR (SCPR). The resulting interposed abdominal compression CPR (IAC-CPR) may increase blood pressures and patient survival, particularly if applied as a primary technique after in-hospital cardiac arrest. We used a predominant cardiac compression canine model to study the effects of IAC-CPR on blood pressures and total and vital organ perfusion as a function of time after cardiac arrest and efficacy of SCPR. DESIGN In a crossover design, we measured blood pressures and total and regional blood flow (radioactive microspheres) during 6-minute episodes of mechanical SCPR and IAC-CPR, both early (4 to 16 minutes) and late (18 to 30 minutes) after induction of ventricular fibrillation in eight dogs (weight, 25 to 33 kg) under neuroleptanalgesia/anesthesia. RESULTS During IAC-CPR, the ascending aortic-right atrial pressure gradient increased (P < .05), and retrograde pressure pulses contributed to the rise of ascending aortic pressure. Within 2 minutes after the start of IAC-CPR, end-tidal CO2 fraction increased by 0.6 +/- 0.4 vol% (P < .05), suggesting enhanced venous return. IAC-CPR enhanced (P < .05) total forward blood flow (574 +/- 406 versus 394 +/- 266 mL/minute during SCPR for the early phase) and vital organ perfusion (including myocardium), in both early and late phases. The IAC-CPR-induced augmentation of blood flow was greater if perfusion was relatively high during SCPR. CONCLUSION Compared with predominant cardiac compressions alone (SCPR), the addition of interposed abdominal compressions (IAC-CPR) improves total and vital organ oxygen delivery through enhanced venous return and perfusion pressures.

Abdominal compressions increase vital organ perfusion during CPR in dogs: Relation with efficacy of thoracic compressions

STUDY OBJECTIVE Abdominal compressions can be interposed between the thoracic compressions of standard CPR (SCPR). The resulting interposed abdominal compression CPR (IAC-CPR) may increase blood pressures and patient survival, particularly if applied as a primary technique after in-hospital cardiac arrest. We used a predominant cardiac compression canine model to study the effects of IAC-CPR on blood pressures and total and vital organ perfusion as a function of time after cardiac arrest and efficacy of SCPR. DESIGN In a crossover design, we measured blood pressures and total and regional blood flow (radioactive microspheres) during 6-minute episodes of mechanical SCPR and IAC-CPR, both early (4 to 16 minutes) and late (18 to 30 minutes) after induction of ventricular fibrillation in eight dogs (weight, 25 to 33 kg) under neuroleptanalgesia/anesthesia. RESULTS During IAC-CPR, the ascending aortic-right atrial pressure gradient increased (P < .05), and retrograde pressure pulses contributed to the rise of ascending aortic pressure. Within 2 minutes after the start of IAC-CPR, end-tidal CO2 fraction increased by 0.6 +/- 0.4 vol% (P < .05), suggesting enhanced venous return. IAC-CPR enhanced (P < .05) total forward blood flow (574 +/- 406 versus 394 +/- 266 mL/minute during SCPR for the early phase) and vital organ perfusion (including myocardium), in both early and late phases. The IAC-CPR-induced augmentation of blood flow was greater if perfusion was relatively high during SCPR. CONCLUSION Compared with predominant cardiac compressions alone (SCPR), the addition of interposed abdominal compressions (IAC-CPR) improves total and vital organ oxygen delivery through enhanced venous return and perfusion pressures.

Changes in Systemic Microvascular Permeability in Sepsis and Septic Shock

Generalized soft tissue edema both in dependent and nondependent parts of the body is a remarkable feature of severe sepsis and septic shock. Usually, septic patients need substantial intravascular volume replacement, much greater than could be anticipated on the basis of measurable fluid losses [3]. Fluid balances are strongly positive in many cases to become negative when the patient recovers, a tendency which is often not observed in nonsurvivors [15]. Marked persistent peripheral edema may therefore be an ominous prognostic sign. Tissue edema may have a number of serious clinical sequelae like generalized organ dysfunction, interference with oxygen diffusion from the intravascular compartment to the cell (longer diffusion distances) and abnormalities in drug metabolism due to changes in the volume of distribution [3]. Several mechanisms can be involved in the formation of edema in septic patients. Microvascular fluid exchange is governed by the Starling forces [11, 13].