Small-volume resuscitation from hemorrhagic shock in dogs: effects on systemic hemodynamics and systemic blood flow.

BACKGROUND AND METHODS: This study compared canine systemic hemodynamics and organ blood flow (radioactive microsphere technique) after resuscitation with 0.8% saline (Na+ 137 mEq/L), 7.2% hypertonic saline (Na+ 1233 mEq/L), 20% hydroxyethyl starch in 0.8% saline, or 20% hydroxyethyl starch in 7.2% saline, each in a volume approximating 15% of shed blood volume. Twenty-four endotracheally intubated mongrel dogs (18 to 24 kg) underwent a 30-min period of hemorrhagic shock, from time 0 to 30 min into the shock period, followed by fluid resuscitation. Data were collected at baseline, 15 min into the shock period, immediately after fluid infusion, 5 min after the beginning of resuscitation, and at 60-min intervals for 2 hr, (65 min after the beginning of resuscitation, and 125 min after the beginning of resuscitation). The animals received one of four randomly assigned iv resuscitation fluids: saline (54 mL/kg), hypertonic saline (6.0 mL/kg), hydroxyethel starch (6.0 mL/kg) or hypertonic saline/hydroxyethyl starch (6.0 mL/kg). RESULTS: Mean arterial pressure increased in all groups after resuscitation. Cardiac output increased with resuscitation in all groups, exceeding baseline in the saline and hypertonic saline/hydroxyethyl starch groups (p less than .05 compared with hypertonic saline or hydroxyethyl starch). Sixty-five minutes after the beginning of resuscitation, cardiac output was significantly (p less than .05) greater in either of the two colloid-containing groups than in the hypertonic saline group. After resuscitation, hypertonic saline and hydroxyethyl starch produced minimal improvements in hepatic arterial flow, hypertonic saline/hydroxyethyl starch increased hepatic arterial flow to near baseline levels, and saline markedly increased hepatic arterial flow to levels exceeding baseline (p less than .05, saline vs. hydroxyethyl starch). One hundred twenty-five minutes after the beginning of resuscitation, hepatic arterial flow had decreased in all groups; hepatic arterial flow in the hypertonic saline group had decreased to levels comparable with those during shock. Myocardial, renal, and brain blood flow were not significantly different between groups. CONCLUSIONS: Small-volume resuscitation with the combination of hypertonic saline/hydroxyethyl starch is comparable with much larger volumes of 0.8% saline, and is equal to hypertonic saline or hydroxyethyl starch in the ability to restore and sustain BP and improve organ blood flow after resuscitation from hemorrhagic shock.     

Resuscitation with 7.5% NaCl in 6% dextran-70 during hemorrhagic shock in swine: effects on organ blood flow

We previously reported that small volume infusions of 7.5% NaCl in 6% dextran-70 (HSD) are superior to equal volumes of normal saline (NS) or 7.5% NaCl in the ability to resuscitate animals from an otherwise lethal hemorrhage. In the present experiment, we evaluated organ blood flow in unanesthetized swine bled 46 ml/kg in 15 min and subsequently infused with a volume of HSD (n = 5) or NS (n = 5) equal to 25% of the shed blood. Radiomicrospheres were injected before hemorrhage, immediately after hemorrhage, and 5 and 30 min after treatment. At the end of hemorrhage, cardiac output had fallen to one-third of baseline values. Five minutes after the infusion of HSD, cardiac output had returned to baseline levels, while cardiac output in the NS-treated controls had increased to only one-half of prehemorrhage values. Blood flows to the brain, diaphragm, skin, muscle, and fat were not different between the two groups. Infusion with HSD, however, produced flows to the myocardium, kidneys, liver, small intestine, and pancreas that were significantly greater than post-hemorrhage and NS-treated control values. NS was unable to increase these flows significantly above post-hemorrhage levels. We conclude that small volumes of HSD can significantly improve organ blood flow after hemorrhagic shock. This improvement in flow may explain the increased survival observed with this solution and may attenuate some of the later complications of hemorrhagic shock.     

TSC for hemorrhagic shock: effects on cytokines and blood pressure

Previous studies have shown that administering trans-sodium crocetinate (TSC) as a treatment of hemorrhagic shock leads to increased whole-body oxygen consumption and survival as well as protection of the liver and kidney. It has been suggested that TSC increases oxygen delivery by increasing the diffusivity of oxygen through plasma. However, as with any novel mechanism of action, there are always questions about whether the results could also be ascribed to other, previously described mechanisms of action. This study was designed to look at some aspects of that by examining the effect of different TSC dosing regimens on the blood pressure and the production of cytokines after hemorrhage because both responses have been reported with compounds that act via other mechanisms. In a constant-pressure rat model of hemorrhagic shock, it was seen that a singe bolus injection of TSC results in an immediate but transient increase in the arterial blood pressure. This is similar to the effect reported previously for using 100% oxygen. It was also found that if the TSC injections were repeated periodically over an hour, a sustained increase in the blood pressure would occur. Because inflammatory cytokines have been implicated in mortality and tissue damage, it has been suggested that TSC may affect the production of cytokines. Thus, the effect of TSC on the production of TNF-alpha and IL-10 was also examined. The data show that treatment with TSC results in lower concentrations of TNF-alpha in the liver and spleen as well as lower concentrations of IL-10 in the spleen. Again, similar effects on other cytokines have been seen with 100% oxygen. These results support the hypothesis that the effects of TSC on hemorrhagic shock are mediated via an effect on oxygen.     

Enalaprilat improves systemic and mesenteric blood flow during resuscitation from hemorrhagic shock in dogs

We investigated the systemic and mesenteric cardiovascular effects of administering enalaprilat during resuscitation from hemorrhage. Dogs were hemorrhaged (mean arterial pressure [MAP] 40-45 mmHg for 30 min, then 30-35 mmHg for 30 min) and were then resuscitated with intermittent lactated Ringer's solution (200 mL/kg/h during first 40 min, and 60 mL/kg/h during the following 130 min, MAP 75-80 mmHg). A constant-rate infusion of saline with or without enalaprilat (0.02 mg/kg/h) was initiated after 40 min of resuscitation. Blood flows declined with hemorrhage, increased with resuscitation, and then declined during the initial 40 min of resuscitation. Enalaprilat administration resulted in blood flow increases not seen in the controls (ending values for cardiac index: 2.8 +/- 0.4 L/min/m2 vs. 1.6 +/- 0.3 L/min/m2; celiac arterial flow 314 +/- 66 L/min/m2 vs. 139 +/- 13 mL/min/m2; and portal venous flow 596 +/- 172 L/min/m2 vs. 414 +/- 81 mL/min/m2 for enalaprilat versus controls, respectively). The greater flows with enalaprilat appeared to be due to prevention of the increases in afterload noted in the controls (ending arterial elastance values 3.73 +/- 0.97 mmHg/m2/mL vs. 7.74 +/- 1.80 mmHg/m2/mL for enalaprilat versus controls, respectively). We conclude that administration of a constant-rate infusion of enalaprilat during resuscitation can be used to improve systemic and mesenteric blood flow.     

Hemodynamic effects of combined treatment with oxygen and hypertonic saline in hemorrhagic shock

OBJECTIVE: In hemorrhagic shock, small volume resuscitation with hypertonic saline transiently increases mean arterial blood pressure (MABP) and cardiac output and augments organ perfusion. Inhalation of 100% oxygen after hemorrhage also increases MABP and redistributes blood flow to the splanchnic and renal vascular beds. We evaluated hemodynamic effects of combined resuscitation with hypertonic saline and oxygen in shock induced by controlled bleeding in rats. DESIGN: Animal study. SETTING: Research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Animals were assigned to four hemorrhage groups that received posttreatment with a) normal saline; b) normal saline + 100% oxygen; c) hypertonic saline; d) hypertonic saline + oxygen, and a fifth sham-shock group that received hypertonic saline + oxygen. MEASUREMENTS AND MAIN RESULTS: Bolus infusion of small volume hypertonic saline markedly increased MABP (p < .001), hindquarter vascular resistance (p < .05), and distal aorta blood flow (p < .01). Hypertonic saline transiently increased superior (cranial) mesenteric artery (SMA) blood flow (p < .001) and small bowel perfusion (p < .01). Inhalation of oxygen after normal saline rapidly increased MABP (p < .01) and hindquarter vascular resistance (p < .02) and decreased distal aorta blood flow (p < .02) and perfusion of the gracilis muscle (p < .05). When given after normal saline, oxygen did not change SMA resistance and increased SMA flow (p < .05). The supplementation of oxygen after hypertonic saline did not exert additional effects on vascular resistance and blood flows in the two vascular beds. However, the combined treatment prevented the oxygen-induced decrease in distal aorta blood flow and gracilis muscle perfusion and maintained MABP at slightly higher values and SMA flow at significantly higher values than hypertonic saline alone until the end of the protocol (p < .01). The two hemorrhaged groups treated with oxygen exhibited the lowest final plasma lactate concentrations (p < .05 from normal saline and hypertonic saline groups). CONCLUSIONS: We suggest that early combined use of hypertonic saline and oxygen exerts a favorable extended profile of hemodynamic effects that amends shortcomings of each treatment alone in hemorrhagic shock.     

Resuscitation with polyethylene glycol-modified human hemoglobin improves microcirculatory blood flow and tissue oxygenation after hemorrhagic shock in awake hamsters

OBJECTIVE: To determine whether resuscitation with polyethylene glycol-modified human hemoglobin (MalPEG-Hb), an oxygen-carrying blood replacement fluid with 4 g/dL Hb, viscosity of 2.5 cP, colloid osmotic pressure of 49 mm Hg, and p50 of 5.5 mm Hg, improves systemic and microvascular variables after hemorrhage compared with shed blood (SB) and 5% hydroxyethyl starch (HES). SETTING: Laboratory. SUBJECTS: Golden Syrian hamsters. DESIGN: Prospective study. INTERVENTIONS: Hamsters implemented with a skin fold chamber were hemorrhaged 50% of blood volume and resuscitated with 50% shed blood volume (SB, HES, or MalPEG-Hb). MEASUREMENTS AND MAIN RESULTS: Shock and resuscitation were monitored for 1 hr each. Microvascular events were characterized in terms of vessel diameter, flow velocity, functional capillary density, and Po(2) in arterioles, venules, and extravascular tissue. Systemic variables include mean arterial pressure, heart rate, Po(2), Pco(2), pH, and base excess. MalPEG-Hb resuscitation increased functional capillary density to 64% vs. 44% for SB and 32% for HES relative to baseline before shock. Microvascular flow increased 16% for MalPEG-Hb relative to baseline and remained decreased by 44% for SB and 80% for HES. Hemoglobin concentration was 10.4 g/dL with SB, 7.5 (6.8 g/dL in red blood cells and 0.9 g/dL in plasma) with MalPEG-Hb, and 7.5 g/dL with HES, leading to tissue Po(2) of 19, 8, and 5 mm Hg respectively. Calculations of oxygen extraction show that 0.9 g/dL of MalPEG-Hb increased oxygen extraction per gram of red cell hemoglobin in the tissue analyzed compared with SB. These measurements correlate well with a systemic indicator of recovery, base excess, 5.4 +/- 4.7 (MalPEG-Hb), 1.7 +/- 3.8 (SB), and -0.3 +/- 5.7 (HES). CONCLUSION: The presence of 0.9 g/dL of high oxygen affinity MalPEG-Hb improves microvascular blood flow and oxygen transport during shock to a significantly greater extent than that attainable with blood or HES.     

Enalaprilat improves systemic cardiovascular parameters and mesenteric blood flow during hypotensive resuscitation from hemorrhagic shock in dogs

Resuscitative interventions that improve mesenteric perfusion without causing instability in systemic arterial pressures may be helpful for improving trauma patient outcomes. Blocking angiotensin II formation with enalaprilat may be such an intervention. Two questions were addressed in this two-part study investigating resuscitation from hemorrhagic shock in dogs: Can systemic arterial pressures be maintained while administering a constant rate infusion of enalaprilat during resuscitation, and can enalaprilat improve cardiovascular status during resuscitation? Animals were hemorrhaged to a mean arterial pressure (MAP) of 40 to 45 mmHg for 30 min and then 30 to 35 mmHg for 30 min. Group I (n = 5) was resuscitated to a MAP 60 to 65 mmHg with enalaprilat (0.02 mg/kg/h). Group II was resuscitated to a MAP 40 to 45 mmHg with (n = 5) or without (n = 5) enalaprilat. Resuscitation in both groups consisted of intermittent intravenous lactated Ringer's solution (60 mL/kg/h) to reach and maintain the target MAPs. Systemic arterial pressures were unaffected by enalaprilat during resuscitation in Group I, allowing us to proceed to the second study. During severely hypotensive resuscitation (Group II), systemic arterial pressures were also stable and enalaprilat administration was associated with increases (P < or = 0.02) in cardiac index (+1.2 L/min/m2), stroke volume index (SVI) (+14.5 mL/m2), superior mesenteric artery flow (+80 mL/min), stroke work (+561 mmHg/mL/m2), and left ventricular power output (+55.7 mmHg/L/min/m2). Corresponding increases were not observed in controls. We conclude that administration of a constant rate infusion of enalaprilat during resuscitation can be accomplished without causing a hypotensive crisis. Since enalaprilat significantly improved cardiovascular status including mesenteric perfusion even during intentional hypotension, it has potential value for improving the treatment of trauma patients.     

Tissue blood flow and oxygen transport in critically ill patients.

The theoretical and practical solutions to the problems of increasing oxygen transport are well understood. Unfortunately the quantitation of hypoxia, both as an absolute deficit and as a precise method of prognosis is not yet available. This may well be because regional hypoxia in a vital tissue cannot be mirrored in a total body measurement. In the low-flow state, oxygen delivery can be maintained by redistribution of cardiac output, reduction of oxygen uptake by ischemic tissue by reducing work load, by increasing oxygenation of the blood, or by decreasing the affinity of oxygen for hemoglobin. The latter provides for more oxygen to be delivered by a given amount of oxyhemoglobin before the tension falls to deleterious regions (about 20 torr). There is some evidence that pharmacologic doses of methylprednisolone may be beneficial in this respect.     

Adrenaline in treatment of septic shock: Effects on haemodynamics and oxygen transport

The effects of adrenaline on haemodynamics and oxygen transport were studied in 13 patients with septic shock persisting after optimal fluid loading. adrenaline was administered by intravenous infusion at an increasing dose until no further benefit was seen. There were significant increases in mean arterial pressure, cardiac index, left ventricular stroke work index and oxygen delivery index. There was no significant change in oxygen consumption although the trend was towards an increase. There was a significant reduction in oxygen extraction ratio, but no change in shunt fraction. Adrenaline would appear to have beneficial haemodynamic effects in septic shock.     

Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs.

A comparison study of several vasoconstrictor and vasodilator agents was conducted measuring changes in intestinal blood flow and oxygen consumption during 10-min periods of intra-arterial infusion. Blood flow was measured in a branch of the superior mesenteric artery of anesthetized dogs with an electromagnetic blood flow meter, and the arteriovenous oxygen content difference across the gut segment was determined photometrically. Vasopressin (4 x 10(-3) and 7x 10(-4) U/kg-min) diminished blood flow 60 and 28% and reduced oxygen consumption 54 and 22%, respectively (all P less than 0.001). In a dose which did not lower blood flow, vasopressin still caused a decline in oxygen consumption (P less than 0.01). Epinephrine (5 x 10(-2) mug/kg-min) decreased blood flow 19% (P less than 0.001) but did not reduce oxygen consumption. After beta-adrenergic blockade, however, the same dose of epinephrine decreased blood flow 41% and oxygen consumption 33% (both P less than 0.001). Responses to angiotension II, calcium chloride, and prostaglandin F2alpha resembled effects of vasopressin rather than those of epinephrine, namely decreased blood flow and decreased oxygen consumption. The vasodilator agents, prostaglandin E1, is isoproterenol, and histamine, increased (P less than 0.001) both blood flow (130, 80, and 98%, respectively) and oxygen consumption (98, 64, and 70%, respectively). Vasopressin, angiotensin II, calcium chloride, and prostaglandin F2alpha appear to contract arteriolar and precapillary sphincteric smooth muscle indiscriminately to evoke both intestinal ischemia and hypoxia. Epinephrine is the exceptional constrictor in this case, producing diminished blood flow without a reduction in oxygen uptake.     

异氟烷麻醉对失血性休克血液循环和氧代谢的影响

目的 研究异氟烷麻醉对失血性休克(HS)血液循环和氧代谢的影响.方法 巴马小型猪16只,随机分为两组(n=8):清醒对照组(C组)和麻醉实验组(A组).两组猪分别于清醒和异氟烷麻醉两种状态下在15 min内按全身血容量的40%(即按30 mL/kg计算)匀速放血制备休克模型,监测放血前和放血后4 h内不同时间点的肺动脉温度(TP)、心率(HR)、平均动脉压(MAP)、中心静脉压(CVP)、平均肺动脉压(MPAP)、肺动脉楔压(PAWP)、心输出量(CO)、混合静脉血氧饱和度(SmvO2)及血气指标;计算每搏输出量(SV)、体循环阻力(SVR)、氧摄取量(Ca-vO2)、氧供(DO2)、氧耗(VO2)和氧摄取率(O2ER);记录每头猪的生存时间.结果 HS发生后,C组和A组HR分别增快至(193±19)次/min和(126±16)次/min,其后C组逐渐下降,A组变化较小;C组MAP和CO下降后回升较快、幅度较大,于HS 90 min分别回升至80 mm Hg和1.5 L/min以上,而A组回升不明显;但两组SVR增加较一致,且A组MPAP降低后回升较明显.HS导致两组DO2和VO2均分别降低至200 mL/min和150 mL/min以下,但A组下降并维持在更低水平,其O2ER、Ca-vO2和乳酸(LA)依然较低,SmvO2较高;两组猪在4 h内均存活.结论 异氟烷麻醉下,HS机体血流动力学应激代偿反应明显减弱,心血管系统受抑明显,氧供减少,但氧耗降低更显著,氧动力学失衡明显减轻.     

Microcirculatory effects of changing blood hemoglobin oxygen affinity during hemorrhagic shock resuscitation in an experimental model

Microvascular responses to blood volume restitution using red blood cells (RBCs) with modified hemoglobin (Hb) oxygen affinity were studied in the hamster window chamber model during resuscitation from hemorrhagic shock. Allosteric effectors inositol hexaphosphate and 5-hydroxymethyl-2-furfural were introduced into the RBCs by electroporation to decrease and increase Hb-oxygen affinity. In vitro P50s (partial pressure of oxygen at 50% Hb saturation) were modified to 10 and 50 mmHg (normal P50, 32 mmHg). Awake hamsters were subjected to hemorrhage of 50% of blood volume, followed by a shock period of 1 h, and then resuscitated with 25% blood volume with high or low P50 RBCs (hematocrit, 50%). After resuscitation, base excess was significantly lower than baseline in the high-P50 RBC group (HP50; 0.3 +/- 2 vs. 5.0 +/- 1.7 mM) and MAP was lower than baseline in the low-P50 RBC group (LP50; 93 +/- 6 vs. 109 +/- 6 mM). Arteriolar diameter and flow were significantly lower in the HP50. Functional capillary density in the HP50 was significantly lower than LP50 at 60 and 90 min after resuscitation. There was no significantly difference in arteriolar PO2. Tissue PO2, venular PO2, and oxygen delivery were higher in LP50 than in HP50. There was no significant difference in oxygen extraction. Oxygen extraction ratio (oxygen extraction/oxygen delivery) x 100 was significantly higher in HP50 than in LP50. These results suggest that lowering blood P50 in resuscitation provides improved microvascular function in comparison with higher P50.     

Effect of hemorrhagic shock on cefazolin and gentamicin pharmacokinetics in dogs.

The physiologic response to traumatic injury may alter the disposition of drugs and thereby affect their therapeutic or toxic potential. A study was conducted in 10 mongrel dogs to determine the effect of experimental hemorrhagic shock with resuscitation on the pharmacokinetics of gentamicin and cefazolin. Single simultaneous intravenous doses of gentamicin (3 mg/kg) and cefazolin (25 mg/kg) were administered to each animal on an initial study day, after which serial blood and urine collections were performed. After 1 week, a standard hemorrhagic shock model was applied to each animal. Shock was continued for 1 h, after which the animal was resuscitated with either whole blood or saline. After stabilization for 20 min, a second dose of gentamicin and cefazolin was administered, and blood and urine were again collected. Drug clearance was not significantly altered, except for that of cefazolin after saline resuscitation, for which there was a significant increase in drug clearance. After both methods of resuscitation an increase in the volume of distribution was noted for cefazolin and gentamicin. Drug half-life was noted to be increased after shock for cefazolin by both resuscitation methods and for gentamicin after shock by saline resuscitation. Although alterations of pharmacokinetic parameters were noted, mean concentrations of gentamicin and cefazolin in serum were similar for pre- and postshock phases.     

The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock

Objective: To assess the effects of low-dose dopamine on splanchnic blood flow and splanchnic oxygen uptake in patients with septic shock. Design: Prospective, controlled trial. Setting: University hospital intensive care unit Patients: 11 patients with septic shock, diagnosed according the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference, who required treatment with norepinephrine. Measurements and main results: Systemic and splanchnic hemodynamics and oxygen transport were measured before and during addition of low-dose dopamine (3 μg/kg per min). Low-dose dopamine had a marked effect on total body hemodynamics and oxygen transport. The fractional splanchnic flow at baseline ranged from 0.15 to 0.57. In 7 patients with a fractional splanchnic flow less than 0.30, low-dose dopamine increased splanchnic flow and splanchnic oxygen delivery and oxygen consumption. In 4 patients with a fractional splanchnic flow above 0.30, low-dose dopamine did not appear to change splanchnic blood flow. Conclusion: Low-dose dopamine has a potential beneficial effect on splanchnic blood flow and oxygen consumption in patients with septic shock, provided the fractional splanchnic flow is not already high before treatment. Received: 19 September 1995 Accepted: 21 September 1996     

Peripheral and liver tissue oxygen tensions in hemorrhagic shock.

BACKGROUND AND METHODS: Hepatic dysfunction after severe hemorrhagic shock is common and may be a consequence of visceral tissue hypoxia. Peripheral tissue PO2 has been suggested to correlate with the development of visceral hypoxia. To test the hypothesis that changes in peripheral tissue PO2 reflect changes in hepatic PO2, we measured subcutaneous PO2, transcutaneous PO2, transconjunctival PO2, and liver tissue PO2, and their relationship with changes in mean arterial blood pressure (MAP) and systemic oxygen transport (DO2), during progressive bleeding in pigs (n = 23). In addition to the tissue PO2, portal vein PO2 and circulating lactate concentrations were also measured in six of the animals. The animals were anesthetized and bled to an MAP of 50 mm Hg within 1 hr. RESULTS: After an induced 10% reduction of MAP, only the DO2 decreased significantly (p less than .05). After a 20% reduction of MAP, the DO2 decreased further and was associated with a significant (p less than .05) reduction of all peripheral tissue PO2 values. A significant (p less than .05) reduction of liver tissue PO2 was observed later during bleeding, after induction of a 30% reduction in MAP. In the subgroup with portal venous PO2 and lactate measurements, reductions of all peripheral tissue PO2 and portal venous PO2 values occurred after a 20% reduction (p less than .05) of MAP. An increase (p less than .05) in the portal venous lactate concentration was observed after a 50% reduction of MAP, and a decrease (p less than .05) in liver tissue PO2 was noted after a 60% reduction of MAP. CONCLUSIONS: Reductions of both peripheral and portal venous PO2 values occur early during hemorrhage. The liver tissue PO2, though initially low, appears to be better defended, suggesting either redistribution of splanchnic blood flow or adaptation in hepatic oxygen demand.     

Effects of exerimental right ventricular hypertrophy on myocardial blood flow in conscious dogs.

The effects of right ventricular hypertrophy on the overall and regional distribution of myocardial blood flow in the absence of an elevated coronary arterial driving pressure were evaluated in 18 concscious dogs subjected to a chronic pressure overload of the right ventricle induced by pulmonary artery constriction. The sustained pressure overload for duration of 4--6 wk or 4--5 mo resulted in significant increases in right ventricular mass (45 and 110%, respectively) and right ventricular fiber diameter (22 and 60%, respectively). Moreover, the presence of moderate and severe hypertrophy was associated with marked increases in transmural blood flow per gram to the right ventricle proportional to the observed increases in mass, i.e., of 36 and 109%, respectively, from a normal value of 0.67 +/- 0.04 ml/min per g, whereas left ventricular blood flow remained unaltered from a normal value of 1.00 +/- 0.06 ml/min per g. Despite the large increase in blood flow per gram to moderately and severely hypertrophied right ventricle, no significant changes in the ratio of capillary:muscle fiber number were observe. These data suggest that the development of right ventricular hypertroph is characterized by a sustained compensatory response of the coronary circulation to the augmented work load and mass, and that is not associated with a proliferative response of the vasculature supplying the enlarged ventricle.     

Divergent effects of oxygen therapy in four models of uncontrolled hemorrhagic shock

Treatment with oxygen exerts beneficial effects and prolongs survival in hemorrhagic shock induced by controlled bleeding. We evaluated the effects of inhalation of 100% oxygen in four models of uncontrolled bleeding in rats: amputation of the tail, laceration of two branches of the ileocolic artery, incision of the spleen, and laceration of the lateral lobe of the liver. After tail amputation, oxygen caused a short and transient increase in mean arterial blood pressure (MABP; P < 0.01), decreased distal aorta (DA) blood flow by 27% (P < 0.01), and induced transient redistribution of blood flow to the superior mesenteric artery (SMA; P < 0.01). Later on, MABP in the oxygen group decreased gradually and was significantly lower than in air controls (P < 0.01). Oxygen therapy increased the mean blood loss by 40% (P < 0.01), increased blood lactate (P < 0.01), and shortened the survival time (P < 0.01). After laceration of two branches of the ileocolic artery, oxygen treatment caused a transient increase in MABP and redistribution of blood flow to the SMA that was followed by a comparable decrease in MABP, increase in vascular resistance, and decreased blood flow in the DA and SMA. In this model, oxygen did not affect bleeding volume, blood lactate, or survival. A similar transient regional hemodynamic effect was found when oxygen was administered after spleen or liver injury; however, in both models, oxygen maintained MABP at significantly higher values (P < 0.05). The results point to differential effects of oxygen in uncontrolled bleeding with benefits in bleeding from small parenchymal vessels and possible detrimental effect in bleeding from large size vessels.