Normovolemic Animals Research Articles

Abstract 08: Computed Tomography Perfusion Of Cerebral Blood Flow During Open Cardiac Massage For Hypovolemic And Normovolemic Cardiac Arrest In Swine

Introduction: Adequate cerebral blood flow (CBF) during open cardiac massage (OCM) in cardiac arrest is critical for survivors to be neurologically intact. Cerebral perfusion is known to be poor during OCM but has not been quantified using a brain perfusion technique. The aim of this study is to measure CBF in swine undergoing OCM in hypovolemia and normovolemia using computed tomography perfusion (CTP) scanning. Methods: Anesthetized swine underwent instrumentation with right atrial and aortic pressure catheters. A pigtail catheter placed in the ascending aorta was used to administer iodinated contrast and CTP imaging acquired. Brain parenchymal attenuation was measured over time from which CBF (mL/100g of brain) and time to peak (TTP; secs) were derived. Animals were then euthanized exsanguination (hypovolemic group) or potassium chloride injection (normovolemic group). Animals were subject to a clamshell thoracotomy, OCM and repeated CTP. Data pertaining to peak coronary perfusion pressure (pCPP; mmHg) was collected and % CPP >15mmHg (% CPP; secs) calculated post hoc. Results: Normovolemic animals achieved superior pCPP compared to the hypovolemic animals (pCPP: 39.3 vs 12.3, p<0.001; % CPP: 14.5 ± 1.9 vs 30.9 ± 6.5, p<0.001). CTP was successfully performed during OCM generating an attenuation curve (figure). The TTP elongated from spontaneous circulation, normovolemia to hypovolemia (5.7 vs 10.8 vs 14.8, p=0.01). CBF during OCM was similar between hypovolemic and normovolemic groups (7.5 ± 8.1 vs 4.9 ± 6.0, p =0.73) which was lower than baseline values (51.9 ± 12.1, p<0.001). Conclusions: OCM in normovolemia generates superior coronary hemodynamics compared to hypovolemia. Despite this, neither generates adequate CBF as measured by CTP, compared to baseline. To improve the rate of neurologically intact survivors, novel resuscitative techniques need to be investigated that specifically target cerebral perfusion as existing techniques are inadequate.

Characterization of cerebral blood flow during open cardiac massage in swine: Effect of volume status.

Introduction: Patients in cardiac arrest treated with resuscitative thoracotomy and open cardiac massage (OCM) have high rates of mortality with poor neurological outcomes. The aim of this study is to quantitate cerebral perfusion during OCM using computed tomography perfusion (CTP) imaging in a swine model of normo- and hypovolemia. Methods: Anesthetized swine underwent instrumentation with right atrial and aortic pressure catheters. A catheter placed in the ascending aorta was used to administer iodinated contrast and CTP imaging acquired. Cerebral blood flow (CBF; ml/100 g of brain) and time to peak (TTP; s) were measured. Animals were then euthanized by exsanguination (hypovolemic group) or potassium chloride injection (normovolemic group) and subjected to a clamshell thoracotomy, aortic cross clamping, OCM, and repeated CTP. Data pertaining to peak coronary perfusion pressure (pCoPP; mmHg) were collected and % CoPP > 15 mmHg (% CoPP; s) calculated post hoc. Results: Normovolemic animals (n = 5) achieved superior pCoPP compared to the hypovolemic animals (n = 5) pCoPP (39.3 vs. 12.3, p < 0.001) and % CoPP (14.5 ± 1.9 vs. 30.9 ± 6.5, p < 0.001). CTP acquisition was successful and TTP elongated from spontaneous circulation, normovolemia to hypovolemia (5.7 vs. 10.8 vs. 14.8, p = 0.01). CBF during OCM was similar between hypovolemic and normovolemic groups (7.5 ± 8.1 vs. 4.9 ± 6.0, p = 0.73) which was significantly lower than baseline values (51.9 ± 12.1, p < 0.001). Conclusion: OCM in normovolemia generates superior coronary hemodynamics compared to hypovolemia. Despite this, neither generates adequate CBF as measured by CTP, compared to baseline. To improve the rate of neurologically intact survivors, novel resuscitative techniques need to be investigated that specifically target cerebral perfusion as existing techniques are inadequate.

Fluid Resuscitation for Refractory Hypotension.

Hypotension is a common occurrence, especially in anesthetized patients and in critical patients suffering from hypovolemia due to shock and sepsis. Hypotension can also occur in normovolemic animals, anesthetized or conscious, under conditions of vasodilation or decreased cardiac function. The main consequence of hypotension is decreased organ perfusion and tissue injury/dysfunction. In the human literature there is no consensus on what is the threshold value for hypotension, and ranges from < 80 to < 100 mmHg for systolic blood pressure and from < 50 to < 70 mmHg for mean arterial blood pressure have been referenced for intraoperative hypotension. In veterinary medicine, similar values are referenced, despite marked differences in normal arterial blood pressure between species and with respect to humans. Therapeutic intervention involves fluid therapy to normalize volemia and use of sympathomimetics to enhance cardiac function and regulate peripheral vascular resistance. Despite these therapeutic measures, there is a subset of patients that are seemingly refractory and exhibit persistent hypotension. This review covers the physiological aspects that govern arterial blood pressure control and blood flow to tissues/organs, the pathophysiological mechanisms involved in hypotension and refractory hypotension, and therapeutic considerations and expectations that include proper interpretation of cardiovascular parameters, fluid recommendations and therapy rates, use of sympathomimetics and vasopressors, and newer approaches derived from the human literature.

Total resuscitative endovascular balloon occlusion of the aorta causes inflammatory activation and organ damage within 30 minutes of occlusion in normovolemic pigs

BackgroundResuscitative endovascular balloon occlusion of the aorta (REBOA) causes physiological, metabolic, end-organ and inflammatory changes that need to be addressed for better management of severely injured patients. The aim of this study was to investigate occlusion time-dependent metabolic, end-organ and inflammatory effects of total REBOA in Zone I in a normovolemic animal model.MethodsTwenty-four pigs (25-35 kg) were randomized to total occlusion REBOA in Zone I for either 15, 30, 60 min (REBOA15, REBOA30, and REBOA60, respectively) or to a control group, followed by 3-h reperfusion. Hemodynamic variables, metabolic and inflammatory response, intraperitoneal and intrahepatic microdialysis, and plasma markers of end-organ injuries were measured during intervention and reperfusion. Intestinal histopathology was performed.ResultsMean arterial pressure and cardiac output increased significantly in all REBOA groups during occlusion and blood flow in the superior mesenteric artery and urinary production subsided during intervention. Metabolic acidosis with increased intraperitoneal and intrahepatic concentrations of lactate and glycerol was most pronounced in REBOA30 and REBOA60 during reperfusion and did not normalize at the end of reperfusion in REBOA60. Inflammatory response showed a significant and persistent increase of pro- and anti-inflammatory cytokines during reperfusion in REBOA30 and was most pronounced in REBOA60. Plasma concentrations of liver, kidney, pancreatic and skeletal muscle enzymes were significantly increased at the end of reperfusion in REBOA30 and REBOA60. Significant intestinal mucosal damage was present in REBOA30 and REBOA60.ConclusionTotal REBOA caused severe systemic and intra-abdominal metabolic disturbances, organ damage and inflammatory activation already at 30 min of occlusion.

Refrigerated platelets stored in whole blood up to 5 days adhere to thrombi formed during hemorrhagic hypotension in rats

Background There is renewed interest in the therapeutic use of cold-stored platelets for bleeding patients. However, critical information is absent or partially available in vitro. Therefore, thrombus formation and platelet adhesion were studied in vivo, in situ, using bleeding and thrombosis models in instrumented rats, and confocal intravital videomicroscopy. Objectives We tested the hypothesis that refrigerated (4 °C) platelets (stored for 24 h or 5 days) participated in thrombus formation as well as platelets stored at room temperature (RT, 22 °C). This hypothesis was tested in normovolemia and hemorrhagic hypotension. Methods & Results After fluorescently-labeled platelet infusion, endothelial injury and vessel rupture were laser-induced in cremaster microvessels and platelet adhesion in > 230 developing thrombi was evaluated. Blood samples were collected for biochemistry and coagulation assays while multiple systemic physiologic parameters were recorded. Hemorrhagic hypotension study animals were subjected to 40% hemorrhage, leading to hypotension and hemodilution, during in vivo platelet adhesion assessments. The fluorescence intensity associated with labeled platelet adherence provided a quantitative index of adhesion. Cold-stored platelets performed as well as those stored at RT in normovolemic animals. During hypotension, cold-stored platelets still performed as well as RT-stored platelets, whereas platelet adhesion and thrombus formation were increased relative to normovolemic animals, in bleeding model experiments. Conclusions We found the methodology suitable for evaluating platelet function in vivo after different storage conditions in fully monitored animals. Refrigerated platelets (stored up to 5 days) participated as well as RT-stored platelets in thrombi formed after hemorrhage, suggesting that refrigerated platelets are effective during hypotensive situations.

The impact of inspired oxygen concentration on tissue oxygenation during progressive haemorrhage

Standard resuscitation practice for shock states mandates use of high flow, high concentration oxygen. However, this may induce microvascular constriction and potentially impair regional oxygen delivery. We thus investigated the impact of varying inspired oxygen concentrations in a rat model of progressive haemorrhage. Tissue oxygen tension (the balance between local O2 supply and demand) was measured in four different organ beds (liver, renal cortex, muscle, bladder), with concurrent assessment of cardiorespiratory function and organ perfusion in a spontaneously breathing, anaesthetised rat model. 10% aliquots of circulating blood volume were removed at 15 min intervals until death. Different oxygen fractions in the gas mixture (0.15-1.0) were administered following 20% blood removal. A control group consisted of normovolaemic animals breathing varying oxygen fractions. Survival times following progressive haemorrhage were similar in animals breathing room air (98 +/- 10 min), 60% O2 (102 +/- 6 min) or 100% O2 (90 +/- 4 min), but significantly worse in those breathing 15% O2 (52 +/- 8 min, P < 0.01). Significant derangements of blood pressure, aortic blood flow and lactataemia were observed in both hypoxaemic and hyperoxaemic groups compared to normoxaemic animals. Breathing 100% O2 increased arterial PO2 sevenfold and tPO2 approximately threefold over baseline values during normovolaemia and mild haemorrhage (20% blood volume removal). However, with progressive haemorrhage, and despite maintained PaO2 values, tissue PO2 fell in line with the decrease in global oxygen delivery. Hypoxaemia and hyperoxaemia both compromised haemodynamics and biochemical markers of organ perfusion during severe, progressive haemorrhage. This may carry implications for resuscitation practice.

Pro: Aprotinin Has a Good Efficacy and Safety Profile Relative to Other Alternatives for Prevention of Bleeding in Cardiac Surgery

Pro: Aprotinin Has a Good Efficacy and Safety Profile Relative to Other Alternatives for Prevention of Bleeding in Cardiac Surgery

Increased intra-abdominal pressure affects respiratory variations in arterial pressure in normovolaemic and hypovolaemic mechanically ventilated healthy pigs

To evaluate the effect of increased intra-abdominal pressure (IAP) on the systolic and pulse pressure variations induced by positive pressure ventilation in a porcine model. Experimental study in a research laboratory. Seven mechanically ventilated and instrumented pigs prone to normovolaemia and hypovolaemia by blood withdrawal. Abdominal banding gradually increased IAP in 5-mmHg steps up to 30 mmHg. Variations in systolic pressure, pulse pressure, inferior vena cava flow, and pleural and transmural (LVEDPtm) left-ventricular end-diastolic pressure were recorded at each step. Systolic pressure variations were 6.1+/-3.1%, 8.5+/-3.6% and 16.0+/-5.0% at 0, 10, and 30 mmHg IAP in normovolaemic animals (mean+/-SD; p<0.01 for IAP effect). They were 12.7+/-4.6%, 13.4+/-6.7%, and 23.4+/-6.3% in hypovolaemic animals (p<0.01 vs normovolaemic group) for the same IAP. Fluctuations of the inferior vena cava flow disappeared as the IAP increased. Breath cycle did not induce any variations of LVEDPtm for 0 and 30 mmHg IAP. In this model, the systolic pressure and pulse pressure variations, and inferior vena cava flow fluctuations were dependent on IAP values which caused changes in pleural pressure swing, and this dependency was more marked during hypovolaemia. The present study suggests that dynamic indices are not exclusively related to volaemia in the presence of increased IAP. However, their fluid responsiveness predictive value could not be ascertained as no fluid challenge was performed.

Effects of increased intra-abdominal pressure on central circulation

In an experimental model we investigated the effects of a gradual increase in intra-abdominal pressure (IAP) on the central circulation. Seven pigs were anaesthetized, mechanically ventilated and instrumented. IAP was gradually increased by 5 mm Hg up to 30 mm Hg by abdominal banding in normovolaemic animals, and then they were made hypovolaemic after blood withdrawal. Right atrial pressure (RAP) and left ventricular end-diastolic pressure (LVEDP) at each step and aortic, femoral and inferior vena cava blood flows were measured. Left ventricular end-diastolic area (LVEDA) was determined using epicardial echocardiography. Cardiac output maintained at mild IAP was reduced to 76 (24)% of the initial value at 30 mm Hg IAP [mean (sd)] in normovolaemic animals, and 72 (22)% (P<0.001) in hypovolaemic animals. In normovolaemic animals the LVEDA and LVEDP were significantly increased at an IAP of 10 and 15 mm Hg by 26 (24)% and 38 (23)%, respectively. At these IAP values, the difference between the RAP and IAP was positive. When this gradient became negative, that is beyond 15 mm Hg in normovolaemia and for all IAP values in hypovolaemic animals, the LVEDA declined, reaching 78 (16)% and 62 (22)% (P<0.05) of the initial values in normovolaemic and hypovolaemic groups at the highest IAP value. These results showed that a gradual increase in IAP led to a redistribution of abdominal blood volume towards the thoracic compartment, at IAP lower than 15 mm Hg in normovolaemia, and at its expense at higher values of IAP. In hypovolaemia there was no thoracic compartment gain. Whereas the absolute or transmural RAPs were not informative of the direction of this blood shift, an RAP greater than IAP was associated with an intrathoracic compartment gain.

Organ-specific extravasation of albumin-bound Evans blue during nonresuscitated hemorrhagic shock in rats.

Shock-induced enhanced capillary permeability is associated with alterations in the interstitial matrix composition and contributes to organ damage. This study was designed to evaluate albumin extravasation in various organ tissues during severe, hemorrhagic shock without fluid resuscitation and reperfusion. Target value of hemorrhagic shock was a reduction of cardiac output (CO) by 50% induced by removal of blood. Twelve anesthetized Sprague-Dawley rats (260-325 g) kept under continuous hemodynamic monitoring were randomly assigned to a group of hemorrhagic shock (n = 6) and a control group of normovolemic animals (n = 6). After 30 min of shock 50 mg/kg b.w. Evans blue (EB) was injected intravenously followed by an incubation period of 20 min. Exsanguination and wash out of the intravascular space was performed by a pressure-controlled perfusion with heparinized saline before harvesting organs to quantify albumin-bound EB extravasation. We found that withdrawal of 4.7 +/- 0.4 mL (mean, +/-SEM) blood, which accounts for 21.1% of the calculated total blood volume, resulted in a reduction of CO from 36.1 +/- 3.1 to 19.4 +/- 2.7 mL/min. Simultaneously, MAP decreased from 98 +/- 6 to 40 +/- 1 mmHg. In hemorrhaged rats, the interstitial concentration of EB in lung and kidney was significantly higher than observed in intact animals, whereas heart, spleen, liver, ileum, skeletal muscle, and skin showed no significant microvascular damage. We conclude that despite the absence of fluid resuscitation and reperfusion, microvascular damage in lung and kidney is evident within the first thirty minutes of hemorrhagic shock.

Efficiency of small-volume resuscitation in restoration of disturbed skeletal muscle microcirculation after soft-tissue trauma and haemorrhagic shock.

Despite advances in primary care, trauma in conjunction with shock remains the leading cause for morbidity and mortality of young adults in western countries. Herein, we report on the efficiency of small-volume resuscitation to improve compromised perfusion of traumatised skeletal muscle tissue in shock. In pentobarbital anaesthetised, mechanically ventilated rats, closed soft-tissue trauma of the right hind limb was induced, followed by induction of haemorrhagic shock [mean arterial blood pressure (MAP) 40 mmHg for 1 h]. For resuscitation, animals received saline (four-times the shed blood volume/20 min), 10% hydroxyethyl starch (HES) 200/0.5 (equal to shed blood volume/5 min) or 7.2% sodium chloride/6% hydroxyethyl starch 200/0.5 (HyperHES; 10% of shed blood volume/2 min). At 2 h of resuscitation, traumatised skeletal muscle tissue was analysed by in vivo microscopy. Non-resuscitated animals served as shock controls. Despite incomplete restoration of systemic blood pressure, HyperHES was superior to saline, but not to HES, with respect to amelioration of nutritive perfusion. Inflammatory cell response within the traumatised skeletal muscle tissue escaped from the anti-adhesive properties of HyperHES when applied for resuscitation from hypovolaemic shock, and did not differ from values in HES-treated and saline-treated animals. Resuscitation with HyperHES is as effective as HES in improving capillary perfusion in traumatised skeletal muscle during haemorrhagic shock. However, because values of functional capillary density in the HyperHES-treated and HES-treated animals were still markedly below those reported in traumatised skeletal muscle of normovolaemic animals, further tools are needed to enhance efficiency in treatment of local skeletal muscle tissue injury during haemorrhagic shock.

Endogenous central histamine-induced reversal of critical haemorrhagic hypotension in rats--studies with histamine N-methyltransferase inhibitor SKF 91488.

Activation of the histaminergic system is associated with mobilisation of compensatory mechanisms in response to the action of stimuli which disturb homeostasis. Therefore, the effects of endogenous histamine in central cardiovascular regulation were studied in a rat model of irreversible haemorrhagic hypotension. Cardiovascular parameters were measured in 66 and central histamine concentrations in 12 male Wistar rats anaesthetised with ketamine/xylazine. Haemorrhage-shocked rats with mean arterial pressure (MAP) 20-25 mmHg were injected intracerebroventricularly (icv) with histamine N-methyltransferase inhibitor SKF 91488 after icv pre-treatment with H, H2 and H3 histamine receptor antagonists--chlorpheniramine (100 nmol), ranitidine (200 nmol) and thioperamide (100 nmol), respectively, or saline. Arterial pressure and heart rate (HR) changes were monitored within 2 h after icv treatment, or to death if it occurred earlier. Histamine concentrations were measured using enzyme immunoassay. ANOVA followed by a test of Neuman-Keules, and Fisher's exact test were used to compare the results. SKF 91488 produced dose-dependent, significantly higher compared to normovolaemic animals, increases in MAP and HR with the improvement in survival rates. The action of SKF 91488 (100 microg) was associated with an increase in endogenous histamine concentrations in the cerebral cortex (1.19 +/- 0.09 vs. 0.77 +/- 0.21 nmol/g; p < 0.05), hypothalamus (5.62 +/- 0.68 vs. 4.18 +/- 0.45 nmol/g; p < 0.01) and medulla oblongata (0.53 +/- 0.17 vs. 0.29 +/- 0.05 nmol/g; p < 0.05) in comparison to saline-treated animals. SKF 91488-induced effects were inhibited by chlorpheniramine, whereas neither ranitidine nor thioperamide influenced the action. Endogenous central histamine, after SKF 91488 treatment, via activation of H, receptors produces reversal of hypotension, with improvement in the survival rate at 2 h after treatment, in rats subjected to critical haemorrhagic hypovolaemia.

Variations in gastric compliance induced by acute blood volume changes in anesthetized rats.

The impact of acute volume imbalances on gastric volume (GV) was studied in anesthetized rats (250-300 g). After cervical and femoral vessel cannulation, a balloon catheter was positioned in the proximal stomach. The opposite end of the catheter was connected to a barostat with an electronic sensor coupled to a plethysmometer. A standard ionic solution was used to fill the balloon (about 3.0 ml) and the communicating vessel system, and to raise the reservoir liquid level 4 cm above the animals' xiphoid appendix. Due to constant barostat pressure, GV values were considered to represent the gastric compliance index. All animals were monitored for 90 min. After a basal interval, they were randomly assigned to normovolemic, hypervolemic, hypovolemic or restored protocols. Data were compared by ANOVA followed by Bonferroni's test. Mean arterial pressure (MAP), central venous pressure (CVP) and GV values did not change in normovolemic animals (N = 5). Hypervolemic animals (N = 12) were transfused at 0.5 ml/min with a suspension of red blood cells in Ringer-lactate solution with albumin (12.5 ml/kg), which reduced GV values by 11.3% (P<0.05). Hypovolemic rats (N = 12) were bled up to 10 ml/kg, a procedure that increased GV values by 15.8% (P<0.05). In the restored group (N = 12), shed blood replacement brought GV values back to basal levels in bled animals (P>0.05). MAP and CVP values increased (P<0.05) after hypervolemia but decreased (P<0.05) with hypovolemia. In conclusion, blood volume level modulates gastric compliance, turning the stomach into an adjustable reservoir, which could be part of the homeostatic process to balance blood volume.

Effects of hypertonic saline solution on mesenteric microcirculation.

We evaluated systemic and microvascular effects of hypertonic NaCl solution on normovolemic and hemorrhaged animals. Forty-three Wistar rats (186 +/- 4 g, mean +/- SEM) were anesthetized with pentobarbital and cannulated for mean arterial pressure (MAP), heart rate (HR), and mean pulse pressure (MPP) monitoring and blood withdrawal. Diameters of 126 arterioles and 88 venules of the exteriorized mesentery were studied by using intravital microscopy. Microvascular blood flow was calculated from diameter and red blood cell velocity measurements. The protocol consisted of 15 min control, 30 min hypotension (MAP = 52.9 +/- 0.9 mmHg, hemorrhaged vol. = 17.1 +/- 0.7 mL/kg) and 60 min post-infusion of either normal (0.9%) or hypertonic saline (7.5%, 4 mL/kg). Normovolemic animals showed no systemic or microvascular effects of hypertonic saline. Hemorrhagic hypotension resulted in HR fall that was not changed after infusions. Hypertonic infusion reversed MPP decrease during hypotension but only partially restored MAP and microvascular blood flow. Venules did not change diameter during protocols. During hypotension, 24% of arterioles displayed vasomotion (38% of the rats) with low- and high-frequency components present in 74% and 87% of arterioles, respectively. Arterioles with vasomotion during hypotension had larger control diameters (28.9 +/- 2.0 microm) and contracted more (30.8 +/- 4.1%) than arterioles without vasomotion (18.7 +/- 1.2 microm and 8.1 +/- 1.5%, respectively). Mean arteriolar diameter did not change after infusions. After hypertonic solution, the number of vessels showing vasomotion increased 80%, frequency of vasomotion was unchanged, and amplitude increased. These findings may help to explain some of the mechanisms underlying resuscitation effects of hypertonic infusions during hemorrhagic hypotension.

Effects of Extradural Anesthesia on Microcirculatory Blood Flow in Free Latissimus Dorsi Musculocutaneous Flaps in Pigs

Free musculocutaneous flaps are used frequently in plastic surgery to reconstruct soft-tissue defects after radical cancer surgery and trauma. Despite improved surgical techniques, some of these flaps fail due to insufficient blood supply. Extradural anesthesia causes both sensory (pain relief) and sympathetic (vasodilatation) block that may be advantageous in free-flap surgery. This hypothesis, however, has not yet been studied. An experimental model in pigs was developed in which clinical conditions for anesthesia and microvascular surgery on the lower extremity were simulated as closely as possible. The effects of extradural anesthesia as well as phenylephrine infusion, combined with general anesthesia, on central hemodynamics and on microcirculatory blood flow in skin and muscle of the latissimus dorsi free flap were studied. After surgery, seven animals received extradural anesthesia during stable normovolemic conditions and another seven during mild hypovolemia (10 percent blood loss). The extradural block was objectively evaluated using the temporal summation test. Thirty minutes after induction of extradural anesthesia, the animals received an intravenous infusion of phenylephrine 1 microgram/kg per minute over a period of 15 minutes. Multichannel laser-Doppler flowmetry was used to measure microcirculatory blood flow in skin and muscle of the free flap as well as in control skin and muscle on the same extremity simultaneously. In normovolemic animals, extradural block caused a 10 percent decrease in mean arterial pressure and cardiac output and an approximately 20 percent decrease in microcirculatory blood flow in both the skin and muscle of the flap (all changes were nonsignificant). In slightly hypovolemic animals, however, extradural anesthesia caused a significant decrease in cardiac output (31 percent, p < 0.01), mean arterial pressure (24 percent, p < 0.01), and in mean blood flow in the flap muscle (22 percent, p < 0.05) and skin (20 percent, p < 0.05). During phenylephrine infusion, mean arterial pressure increased significantly (p < 0.05) in both hypovolemic and normovolemic animals, while cardiac output and microcirculatory blood flow in the flap remained almost unchanged. Extradural anesthesia does not improve microcirculatory blood flow in free musculocutaneous flaps in pigs. It causes a significant decrease in cardiac output, mean arterial pressure, and microcirculatory blood flow in slightly hypovolemic animals. During phenylephrine infusion, the microcirculatory blood flow in free flaps slightly improves due to the increase in mean arterial pressure. We suggest that extradural anesthesia for microvascular surgery should be used with great caution until human data are available.

Phagocytic reticuloendothelial function after hemorrhage and resuscitation: modulation by different fluids.

Although the efficacy of colloid resuscitation fluids in restoring cardiovascular status in hemorrhagic shock is accepted, the effect they have on the activity of the reticuloendothelial system (RES) is less clear. As interaction with the RES may be important in determining susceptibility to infections after resuscitation the effects of three such fluids, hydroxyethyl starch, Haemaccel, and fresh autologous blood on RES function after a 40% hemorrhage have been investigated in BALB/C mice. The mice, anesthetized with isoflurane, were bled over a 10 min period, left hypovolemic for 30 min, and then resuscitated with their shed blood or the same volume of asanguineous fluid. Normothermia was maintained throughout the experiments. Whole body phagocytic activity was assessed at 1, 6, 24, 48, and 72 h after the end of hemorrhage by measuring the clearance rate (K) of intravenously injected 51Cr-labeled sheep red blood cells. No significant change in K was found at any time in animals resuscitated with shed blood. However, significant increases in K were found 48 h after resuscitation with Haemaccel. Hepatic uptake of sheep red blood cells was significantly increased at 48 and 72 h in Haemaccel-resuscitated animals compared with hydroxyethyl starch or shed blood resuscitation, whereas spleen uptake decreased at 72 h. Lung uptake was not affected at any time with any fluid. The same volume of Haemaccel had no significant effect either on K or on organ uptake when given to normovolemic animals. The changes in organ uptake after hemorrhage and resuscitation with Haemaccel were partially prevented if animals were resuscitated with Haemaccel plus autologous red cells.

Volume Expansion Increases Right Ventricular Infarct Size in Dogs by Reducing Collateral Perfusion

Plasma volume expansion is frequently recommended to correct the low output state resulting from right ventricular (RV) infarction. However, any subsequent increase in pericardial and RV filling pressures from volume expansion could impair RV collateral blood flow. We examined whether volume expansion in dogs before right coronary ligation reduced collateral perfusion and worsened the extent of RV necrosis. Randomized experimental study. Animal research laboratory in university medical center. Forty anesthetized, closed-chest dogs were randomly assigned to normovolemic, pericardium opened (n = 10) or intact (n = 10) groups, and hypervolemic, pericardium opened (n = 10) or intact (n = 10) groups. Hypervolemic animals received 24 mL/kg of 6% hetastarch. All animals underwent 90 min right coronary ligation, followed by 120 min reperfusion. Collateral coronary blood flow (radioactive microspheres) and area of necrosis (An) were determined in the area at risk (Ar). Stroke volume decreased in all groups with ischemia but remained 25 to 40% greater in both hypervolemic groups than in normovolemic animals (p < 0.05). In hypervolemic animals with intact pericardium, RV end-diastolic pressure increased to 10.4 +/- 2.1 mm Hg (mean +/- SD), a value that significantly exceeded those of the other three groups. During RV ischemia, collateral perfusion in the Ar was similar in both normovolemic groups and in hypervolemic animals with opened pericardium (mean range, 12.9 +/- 8.8 to 13.8 +/- 7.6 mL/min/100 g; p = NS), and the An/Ar varied from 11.8 +/- 6.3 to 18.6 +/- 17.4% (p = NS). In contrast, in hypervolemic animals with intact pericardium, collateral perfusion decreased to 7.2 +/- 3.5 mL/min/100 g and the An/Ar was increased to 38.2 +/- 18.6% (p < 0.05 compared with other groups, respectively). Overall, An/Ar was inversely related to collateral blood flow in the Ar (r = -0.46; p < 0.05) and correlated positively with RV end-diastolic pressure (r = 0.61; p < 0.05). Volume expansion preserved stroke volume during RV ischemia, independent of pericardial integrity. However, volume expansion in animals with an intact pericardium increased RV infarct size by twofold to threefold secondary to reduced periischemic collateral perfusion. This detrimental effect of volume expansion on infarct size was prevented by opening the pericardium.

Pharmacokinetics from multiple intraosseous and peripheral intravenous site injections in normovolemic and hypovolemic pigs

To examine: a) the rate and extent of delivery of radioactive tracers to the central circulation from the tibial, medial malleolar, distal femoral, and humeral intraosseous sites, as well as from a peripheral intravenous site; and b) the end-tidal CO2 response to injected sodium bicarbonate at these sites. Prospective, descriptive study. Animal laboratory at a university medical center. Twenty anesthetized and mechanically ventilated piglets were cannulated with 18-gauge bone marrow needles at intraosseous sites and 22-gauge Teflon catheters in peripheral veins. A 22-gauge angiocath was placed in the right carotid artery of each subject. Drug kinetics were studied in the normovolemic and hypovolemic (acute bleeding of 25 mL/kg) states. Sodium bicarbonate (1 mEq/kg) was injected into each of the three intraosseous and one intravenous sites with simultaneous monitoring of end-tidal CO2. A 10-min period for stabilization was allowed between injections. Aliquots of 99mtechnetium were injected at randomly selected sites and blood samples were obtained at 1.5-sec intervals via carotid artery for radioactive counts. Experiments were repeated after withdrawal of 25 mL/kg of blood. Assessment by end-tidal CO2 monitoring after 1-mEq/kg injections of bicarbonate demonstrated a mean initial end-tidal CO2 increase at 12.8 secs and a mean maximal end-tidal CO2 increase of 8 torr (1.06 kPa), with no significant site differences noted. Radioactive tracer injections were detected in the carotid artery after 15.4 secs in normovolemic animals and after 21.4 secs in hypovolemic animals, with no significant site differences detected. The proportion of injected tracer at 2, 5, 10, 20, 30, and 40 mins identified no significant differences between various intraosseous and intravenous sites. Our study demonstrated similar rapid transit and proportion of bicarbonate and radioactive tracers, reaching the central circulation from multiple intraosseous sites and a peripheral intravenous site. This finding suggests that adjustments in drug dosage may not be required, using various intraosseous locations as an alternative to peripheral intravenous drug therapy.

Therapy of hemorrhagic shock using small volumes of hypertonic-hyperoncotic NaCl-dextran solution--effects on the brain

Infusion of small volumes of hypertonic/hyperoncotic solution (HHL: 7.2% NaCl/10% dextran 60) is highly effective in haemorrhagic shock. Cardiovascular function is restored in a matter of minutes by rapid mobilisation of extravasal fluid. However, little experience has been collected to date on the side effects on the brain by this new form of shock therapy. The present studies on HHL were conducted with particular reference to cerebral blood flow, cerebral oxygen supply, and intracranial pressure. Haemorrhagic shock with a drop in arterial blood pressure to 40 mmHg over a period of 30 min was induced in rabbits under alpha-chloralose anaesthesia by means of bloodletting. Subsequently, the hypertonic/hyperoncotic solution (HHL) was infused into the experimental animals within two minutes. The regional cerebral blood flow (H2-clearance) and the cerebral O2 supply were studied by determining the pO2 of the cerebral cortex in experimental animals without haemorrhagic shock but with infusion of HHL. Finally, separate single tests were conducted to analyse the effect of the infusion of HHL on the intracranial pressure after induction of a focal cold lesion of the brain in combination with the implantation of a rubber balloon in the epidural space as an intracranial space-occupying growth. Infusion of HHL during shock produced rapid normalisation of cardiac output, whereas in normovolaemic animals without shock it produced a temporary increase of this parameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of hemorrhagic hypotension with hypertonic/hyperoncotic solutions: effects on regional cerebral blood flow and brain surface oxygen tension.

Hypertonic/hyperoncotic solutions (e.g. HHS: 7.2% NaCl/10% dextran-60) are highly effective to normalize cardiovascular function in hemorrhagic shock due to rapid mobilization of fluid from the extravascular compartment. Since experiences are limited with regard to potential side effects of this treatment on the central nervous system, the present studies were carried out under particular consideration of the cerebral blood flow and O2 supply. HHS was administered in albino rabbits subjected to alpha-chloralose anesthesia and artificial ventilation with and without hemorrhagic hypovolemia. Hemorrhagic hypovolemia of 30 min duration was induced by withdrawal of approximately one third of the circulating blood volume resulting in a decrease in arterial blood pressure to 40 mm Hg. HHS was studied in addition to normovolemic animals. Cardiac output was rapidly normalized by infusion of HHS in animals with hypovolemia, while it increased intermittently in normovolemic animals. In animals with hemorrhagic shock arterial blood pressure recovered by treatment to approximately 70% of normal, whereas blood pressure remained unchanged after infusion of HHS in normovolemic controls. Cerebral blood flow, which was assessed by H2 clearance at the brain surface, had a range of 43.0-50.3 ml/100 g/min under control conditions. It remained virtually unchanged during hemorrhagic hypovolemia and also after infusion of HHS in normovolemic animals. Treatment of shock by HHS was followed 90 or 120 min later by a moderate increase in regional cerebral blood flow to 61 ml/100 g/min. Local tissue PO2 at the brain surface was obtained by an O2 multiwire electrode in the vicinity of the H2 clearance measurements using a weightless suspension system to avoid compression of the brain surface. Infusion of HHS in normovolemic animals did not affect the O2 supply of the brain. Hemorrhagic hypovolemia which led to a left shift of the cerebral PO2 histogram was followed by gradual normalization after fluid resuscitation. The current findings taken together do not indicate adverse side effects of this efficient method of fluid resuscitation with regard to the cerebral blood and O2 supply. The results make worthwhile further investigations on HHS in the presence of a focal brain lesion causing brain edema to find out whether the HHS are useful also for the treatment of intracranial hypertension.