Hours Of Shock Research Articles

Beneficial effects of antioxidants in hemorrhagic shock: Angiology 1995; 46/4 (281–297)

The present study was undertaken to investigate the role of endogenous hydrogen peroxide (H 2 O 2 ) in cardiac depression and cytotoxicity during hemorrhagic shock and reinfusion. To achieve this objective, the changes in the cardiac function and contractility, plasma creatine kinase (CK) and CK-MB activity and lactate concentration, oxyradical-producing activity of polymorphonuclear leukocytes (PMNL-CL), and cardiac malondialdehyde (MDA) concentration in anesthetized dogs were determined before and during shock and reinfusion in the presence or absence of catalase (a metabolizer of H 2 O 2 ). The dogs were divided into three groups randomly. Group I: sham, four hour duration; group II: two hours of shock followed by two hours of reinfusion; group III: same as group II but pretreated with catalase. Hemorrhagic shock was produced in the dogs by lowering the mean arterial pressure to 50±5 mm Hg by bleeding into standard blood bank bags containing 63 mL of citrate, phosphate, dextrose, and adenine (CPDA) anticoagulant for 450 mL of blood. The shock was maintained for two hours by bleeding or reinfusing the shed blood as needed. Cardiac function and contractility were depressed while plasma CK, CK-MB, and lactate increased during shock. Reinfusion after two hours of shock tended to return hemodynamic parameters and plasma lactate levels toward control values. Plasma CK and CK-MB and PMNL-CL increased further. Cardiac MDA content also increased after shock and reinfusion, suggesting oxidative damage. Pretreatment with catalase attenuated the deleterious effects of shock and reinfusion on the cardiovascular function and contractility, and the rise in plasma CK, CK-MB, and lactate, PMNL-CL, and cardiac MDA. However, the protection with catalase was not complete. These results suggest that hydrogen peroxide (H 2 O 2 ) may partly be involved in the deterioration of cardiovascular function and cellular injury during hemorrhagic shock and reinfusion

Serial blood lactate levels can predict the development of multiple organ failure following septic shock

Despite successful initial resuscitation, septic shock frequently evolves into multiple system organ failure (MSOF) and death. Since blood lactate levels can reflect the degree of cellular derangements, we examined the relation between serial blood lactate levels and the development of MSOF, or mortality, in patients with septic shock. In 87 patients with a first episode of septic shock, we measured initial lactate (at onset of septic shock), final lactate (before recovery or death), "lactime" (time during which blood lactate was > 2.0 mmol/L, and the area under the curve (AUC) for abnormal values (above 2.0 mmol/L). These measurements were correlated with survival and organ failure and scored for four systems (ie, respiratory, renal, hepatic, and coagulation), adding to a maximal score of 8. Thirty-three (38%) patients survived. Of the 54 (62%) nonsurvivors, the 13 patients who died during the first 24 hours of septic shock had higher initial blood lactate levels than those who died later (mean +/- standard deviation 9.6 +/- 5.3 mmol/L versus 5.6 +/- 3.7 mmol/L, P< 0.05). The 74 patients who survived the first 24 hours of shock, were studied in more detail. On presentation, survivors had a significantly higher mean arterial pressure (76 +/- 12 mm Hg versus 63 +/- 20 mm Hg, P < 0.001) and arterial pH (7.40 +/- 0.07 versus 7.37 +/- 0.09, P< 0.05) than nonsurvivors. Although the differences in initial blood lactate levels between survivors and nonsurvivors did not reach statistical significance (4.7 +/- 2.5 mmol/L versus 5.6 +/- 3.7 mmol/L), only the survivors had a significant decrease during the first 24 hours of septic shock. The survivors had a significantly lower lactime and AUC than the nonsurvivors. The duration of lactic acidosis was the best predictor of survival (multiple regression analysis, R2 = 0.266, P <0.001), followed by age, heart rate, and mean arterial pressure. Patients with lower organ failure scores had lower initial blood lactate, lactime, and AUC. The duration of lactic acidosis was the only significant predictor of organ failure. In patients with septic shock, serial determinations of blood lactate levels are good predictors of the development of MSOF an death. In this respect, the duration of lactic acidosis is more important than the initial lactate value. Although a number of factors may contribute to hyperlactatemia, these observations are compatible with a direct role of prolonged tissue hypoxia in the development of complications following septic shock.

Traumatic Hypothermia Is Related to Hypotension, Not Resuscitation

Study objective: To determine whether posttraumatic hypothermia is associated with hemorrhage or with resuscitation. Methods: We used a sequential hemorrhage-resuscitation rat model. Rats were subjected to hemorrhage (30 mL/kg), then 1 hour of shock, followed by 2:1 crystalloid/blood resuscitation (60 mL/kg) at ambient temperature. A control group underwent neither hemorrhage nor resuscitation. Results: We recorded core temperature and blood pressure every 10 minutes. Temperature drop averaged 3.4°C and was fastest during hypotensive shock. Rate of temperature change correlated with blood pressure (β=.0102, P<.001), shock phase (β=.4504, P=.041), and blood pressure during shock phase (β=.0116, P<.001), but not with resuscitation phase or with duration of shock or resuscitation. Three of 14 rats died during shock, none during resuscitation. An increase in temperature was noted in 1 of 14 rats during shock and in 7 of 11 rats during resuscitation. Conclusion: Hemorrhage-associated hypothermia occurs during hypotensive shock, not during fluid resuscitation. [Bergstein JM, Slakey DP, Wallace JR, Gottlieb M: Traumatic hypothermia is related to hypotension, not resuscitation. Ann Emerg Med January 1996;27:39-42.]

Acute pulmonary injury in a model of ruptured abdominal aortic aneurysm.

The purpose of this study was to determine whether the combined insults of hemorrhagic shock and aortic clamping simulating ruptured abdominal aortic aneurysm repair had a synergistic effect on the production of pulmonary injury, indicating remote organ injury. Animals were randomized to one of three groups, infrarenal clamp plus 1 hour of shock, infrarenal clamp plus 2 hours of shock, and supramesenteric clamp plus 1 hour of shock. Each of these groups had four subgroups; sham, shock (mean arterial pressure of 50 mm Hg), clamp, or combined [shock plus clamp]). All animals had a laparotomy with aortic clamping in only the clamp and combined groups. Five hours after clamp removal lung permeability index and neutrophil sequestration were quantified. Lung permeability index (6.60 +/- 0.63, p < 0.05 vs all other groups) and neutrophil sequestration (3.72 +/- 0.45 vs sham and clamp, p < 0.05) were significantly increased when shock and supramesenteric clamp were combined. After 1 or 2 hours of shock and infrarenal clamping, no increase in lung permeability index was noted, although neutrophil sequestration was increased in the 2-hour shock group. These results demonstrate the additive effect of shock and supramesenteric clamping, which initiated a cascade of injurious events that resulted in a rapid pulmonary injury. The high mortality rate related to remote organ failure in ruptured abdominal aortic aneurysm may be related to the synergy of these two injurious processes.

Beneficial effects of antioxidants in hemorrhagic shock.

The present study was undertaken to investigate the role of endogenous hydrogen peroxide (H2O2) in cardiac depression and cytotoxicity during hemorrhagic shock and reinfusion. To achieve this objective, the changes in the cardiac function and contractility, plasma creatine kinase (CK) and CK-MB activity and lactate concentration, oxyradical-producing activity of polymorphonuclear leukocytes (PMNL-CL), and cardiac malondialdehyde (MDA) concentration in anesthetized dogs were determined before and during shock and reinfusion in the presence of absence of catalase (a metabolizer of H2O2). The dogs were divided into three groups randomly. Group I: sham, four hour duration; group II: two hours of shock followed by two hours of reinfusion; group III: same as group II but pretreated with catalase. Hemorrhage shock was produced in the dogs by lowering the mean arterial pressure to 50 +/- 5 mm Hg by bleeding into standard blood bank bags containing 63 mL of citrate, phosphate, dextrose, and adenine (CPDA) anticoagulant for 450 mL of blood. The shock was maintained for two hours by bleeding or reinfusing the shed blood as needed. Cardiac function and contractility were depressed while plasma CK, CK-MB, and lactate increased during shock. Reinfusion after two hours of shock tended to return hemodynamic parameters and plasma lactate levels toward control values. Plasma CK and CK-MB and PMNL-CL increased further. Cardiac MDA content also increased after shock and reinfusion, suggesting oxidative damage. Pretreatment with catalase attenuated the deleterious effects of shock and reinfusion on the cardiovascular function and contractility, and the rise in plasma CK, CK-MB, and lactate, PMNL-CL, and cardiac MDA. However, the protection with catalase was not complete. These results suggest that hydrogen peroxide (H2O2) may partly be involved in the deterioration of cardiovascular function and cellular injury during hemorrhagic shock and reinfusion.

Organ Distribution of Radiolabeled Enteric Escherichia Coli During and After Hemorrhagic Shock

Translocation of intestinal bacteria to the blood during hemorrhagic shock (HS) has been confirmed in rats and humans. The current study was designed to trace the path of translocated intestinal bacteria in a murine HS model. Thirty-one rats were gavaged with 1,000,000 counts of viable 14C oleic acid-labeled Escherichia coli. Forty-eight hours later the animals were bled to 30 mmHg until either 80% of their maximal shed blood was returned or 5 hours of shock had elapsed and they were resuscitated with Ringer's lactate as previously described. Control animals were cannulated but not shocked. Eight rats immediately after shock and resuscitation, 6 rats 24 hours after shock, 3 rats 48 hours after shock, and 4 animals that died in shock had their heart, lung, liver, spleen, kidney, and serum harvested, cultured, and radioactive content measured. Translocated enteric bacteria are found primarily in the lung immediately after shock with redistribution to the liver and kidney 24 hours later. Animals surviving to 48 hours were capable of eliminating the majority of the bacteria from their major organ systems. Positive cultures for E. coli were also found in the blood, lung, liver, and kidney. We speculate that the inflammatory response stimulated by the bacteria in these organs may contribute to the multiple-organ failure syndrome seen after HS.

Gastric Mucosal Perfusion and Injury

Acute erosions of the gastric mucosa occur in a variety of clinical settings characterized by a mismatch between mucosal blood supply and demand. Using a canine model incorporating the clinically important insults, we examined the relationship between the gastric mucosal injury measured by planimetry and the animal's regional gastric perfusion measured before, during, and after hemorrhagic shock. The proximal gastric mucosa developed lesions which were inversely related to the amount of gastric flow through 2 hours of shock. In later shock and after reperfusion the relationship reversed, coinciding with the appearance of visible ulcerations. This work demonstrates that early in shock gastric blood flow is inversely related to mucosal injury, but late in shock and after reperfusion increased blood flow is associated with increased mucosal damage.

Hypovolemic shock, pancreatic blood flow, and pancreatitis.

Electromagnetic blood flow determinations were carried out on the superior pancreatic duodena (SPDA), the splenic (SA) and the superior mesenteric (SMA) arteries and compared to cardiac output (CO, thermodilution technique) in 12 anesthetized dogs submitted to hypovolemic shock of various duration: 5 dogs underwent a one-hour and 7 a three-hour period of shock. A 50 mm Hg level of mean arterial blood pressure (MABP) was maintained throughout hypovolemia. Dogs were then reinfused. Control preshock values were 4.12 l/min for CO, 38.0 ml/min for SPDA, 405.9 ml/min for SA, and 963.6 ml/min for SMA. SPDA, SA and SMA flows expressed as % of CO amounted to 0.9, 9.8 and 23.4% respectively. No significant changes in SPDA and SMA flows were noted within the first hour of shock. However, from the end of the second hour on, both flows differed significantly (P less than 0.01), SMA increasing from -75.6% of its control value at the end of bleeding to -61.0%, and SPDA decreasing from -75.6 to -86.9%. Similar observations were made when respective flows were considered as % of CO. The SA behaved somewhat in an intermediate fashion. This relative spoliation in pancreatic blood supply as hypovolemia proceeds supports an ischemic etiology of acute pancreatitis (AP), which could account for some of the so-called idiopathic cases of AP.

The gut as source of sepsis after hemorrhagic shock

In a model of severe hemorrhagic shock in rats, blood culture findings became positive within 2 to 4 hours of shock. The organisms cultured were primarily gram-negative. To test the hypothesis that the gut was the source of the bacteria, E. coli labeled with carbon-14 oleic acid were fed to rats undergoing hemorrhagic shock. Their plasma was then assayed for carbon-14 activity. Seven of the 14 shocked animals demonstrated increased plasma carbon-14 activity during or after shock. The mortality rate was 100 percent 80 hours postshock, and all animals had E. coli on subsequent blood culture. The seven rats without increased plasma carbon-14 activity had a survival rate of 83 percent postshock. Sham-shocked animals did not exhibit plasma carbon-14 levels greater than the background levels. These data suggest that bacterial translocation occurs during hemorrhagic shock and that the gut is the source of the bacteremia seen during hemorrhagic shock.

OCCURRENCE OF BACTEREMIA DURING AND AFTER HEMORRHAGIC SHOCK

In recent research, hemorrhagic shock and septic shock have been studied as two separate entities. We have developed a treated model of hemorrhagic shock in which unrestrained and unanesthetized rats are bled to a mean arterial pressure of 30 torr until 80% of the maximum shed volume must be returned. Rats are maintained preshock and treated post shock with a 20% glucose-electrolyte solution. Survival of these animals is 62% at 24 hours post shock and all animals are dead at 72 hours post shock. Blood cultures obtained during shock become positive at 2 hours into the shock period and are significant compared to controls at 3 to 5 hours of shock (p less than 0.0001). Blood cultures obtained after the period of shock are significantly positive at 24 and 48 hours post shock (p less than 0.05) compared to controls. Intrashock cultures are monomicrobial; the majority of post-shock cultures are polymicrobial. All cultured organisms are normal rat enteric flora. Histologic changes of renal failure are also demonstrated post shock. We suggest that bacterial invasion, possibly from the gut, plays a role in the sepsis seen in patients following severe hemorrhagic shock. Sepsis may precede rather than follow the immune incompetence which accompanies shock.

Effect of enkephalins on function of calcium-regulating endocrine glands in shock

The experiments on white rats weighing 180-220 g have shown that in traumatic and hemorrhagic shock the initial increase in parathyroid hormone blood concentration is followed by the decrease of functional activity of parathyroid glands. Calcitonin concentration is found to increase during the first hours of shock. The changes in calcium-regulating gland function result in significant disturbances of calcium exchange during shock. The injection of synthetic leu-enkephalin analogs to rats with shock leads to normalization of calcium-regulating endocrine glands function.

Skeletal muscle metabolism and insulin resistance during endotoxin shock in the dog

The effect of locally infused endotoxin on gracilis muscle glucose uptake was determined in anesthetized mongrel dogs. The effects of infusion of small amounts of Escherichia coli endotoxin into the arteries of isolated, innervated, constant flow perfused gracilis muscles on glucose uptake and other metabolic variables were determined. Locally infused endotoxin consistently caused a significant and substantial increase in skeletal muscle glucose uptake with no alterations in muscle arteriovenous difference of insulin, oxygen, carbon dioxode, or pH, or in venous blood hematocrit or temperature. These data demonstrate that endotoxin can act locally to increase glucose uptake by skeletal muscle, independent of the action of insulin or other metabolic factors. During natural (free flow) conditions, glucose uptake by the muscle increased markedly during six hours of shock. Increased glucose uptake occurred concomitantly with muscle ischemia and hypoxia. However, when muscle blood flow was held constant, thereby preventing local muscle ischemia and hypoxia, glucose uptake by the gracilis muscle did not change during shock. These results implicate local muscle ischemia and/or hypoxia as the mediator(s) of the increased muscle glucose uptake during shock. Further studies demonstrated that local muscle hypoxia was the stimulus for increased glucose uptake by skeletal muscle during endotoxin shock, and muscle ischemia per se did not after muscle glucose uptake. Since approximately 50% of body mass is composed of skeletal muscle, the contribution of this organ system to the hypoglycemia of endotoxin shock in the dog may be substantial. The ability of insulin to promote glucose diffusion into skeletal muscle before and during gram-negative endotoxin shock was studied in mongrel dogs anesthetized with sodium pentobarbital. The in vivo, isolated, innervated, constant flow perfused gracilis muscle preparation was used. Prior to shock induction, close intra-arterial insulin infusion resulted in a 320% increase in muscle glucose uptake. However, at one, two, and three hours of endotoxin shock, gracilis muscle glucose uptake was unaltered by insulin infusion. This loss of responsiveness to insulin occurred with no alteration in gracilis muscle oxygen uptake, muscle venous P O 2 , or muscle blood flow. During control experiments, however, the muscle response to intra-arterial infusion of insulin (increased glucose uptake) was unaltered during the three-hour control period. These data demonstrate that skeletal muscle insulin resistance develops early and is maintained during three hours of endotoxin shock in the dog.

Hemodynamic effects of aortic occlusion during hemorrhagic shock

We investigated cardiac dynamics following temporary aortic occlusion during profound hypovolemia and abdominal distention. Control animals (N = 10) were bled from a femoral artery catheter to a systolic blood pressure of 60 mm Hg, while simultaneous abdominal distention was effected with intraperitoneal infusion of saline. After one hour of shock, thoracic aortic occlusion and immediate laparotomy were performed. The aorta was clamped for 20 minutes and then released over 5 minutes. The second group (N = 10) underwent the same procedure but received methylprednisolone sodium succinate intravenously at the time of aortic occlusion. During hypotension, mean arterial pressure, cardiac output, stroke volume, and stroke work decreased, while systemic vascular resistance increased. Aortic occlusion improved cardiac hemodynamics in the control group; in the steroid group these changes were even more pronounced. Measurement of dp/dt demonstrated ventricular contractility impaired during hypotension and improved during the period of aortic occlusion. Temporary thoracic aortic occlusion in the face of profound hypotension and massive abdominal distention improved cardiac function. The resulting increased afterload in this hypovolemic state was without deleterious effects. Furthermore, steroids appeared to enhance the cardiac response to aortic cross-clamping.

Pulmonary vascular effects of acetylsalicylic acid, chloroquine, dextran and methylprednisolone given after haemorrhagic shock in dogs.

We have described increases in lung water and pulmonary vascular resistance and reduced myocardial performance in both pigs and dogs after two hours of haemorrhagic shock followed by re-infusion of blood. In this experiment haemorrhagic shock was induced by removing blood to ACD blood packs in five groups of dogs. After two hours of shock, blood was re-infused and NaHCO3 was given to correct the metabolic acidosis of shock. One group of dogs remained as control and received no drugs. Experiments were carried out on three other groups of dogs with one of aspirin, dextran and methylprednisolone given intravenously at the end of the shock period and before blood was re-infused. To allow absorption, chloroquine was given intramuscularly before the period of shock in the fifth group of dogs. In the group with no drugs pulmonary vascular resistance (PVR) increased 95 per cent (significant) from the control period to the end of the experiment. PVR in the control period was not significantly different from PVR at the end of the experiment in any drug group. However, chloroquin was associated with the greatest increase in PVR between these times (77 per cent N.S.). PVR actually fell from control levels to the end of the experiment in both the aspirin (-3.4 per cent N.S.) and dextran (-2.9 per cent N.S.) groups. PVR rose (14 per cent N.S.) from the control period to the end of the experiment in the methylprednisolone group. The aspirin, dextran and methylprednisolone PVR results are all significantly different from the “no drug” group. In both the aspirin and dextran groups platelet aggregation was inhibited. Only the methylprednisolone group had a significant increase in lung water (21 per cent) and the smallest increase in lung water occurred in the aspirin group (9.8 per cent N.S.). We could not relate lung water changes to PVR changes. The lung water changes were compatible with interstitial pulmonary oedema and did not lead to serious gas exchange problems. Myocardial performance appeared improved with dextran and methylprednisolone after shock. We conclude that while dextran and methylprednisolone confer some benefit in preventing increases in PVR and lung water after haemorrhage shock, aspirin is the best drug of those studied in preventing these changes.

Use of chloroquine in shock.

One group of dogs received single doses of intramuscular chloroquine and another group served as a control. The dogs were subjected to haemorrhagic shock and then retransfused with their own blood after two hours of shock. The chloroquine-treated dogs had normal PA pressures after correction of acidosis and significantly smaller increases in the pulmonary vascular resistance. The results are similar but less marked than those obtained with aspirin. Chloroquine inhibited in vitro platelet aggregation by 50% and was not associated with any increased bleeding. This may be an advantage when used in patients with multiple trauma or increased bleeding tendency.

The role of bile in antral mucosal disruption during hemorrhagic shock.

The stress ulcers that occur in shocked dogs are averted by pyloric cross-clamping prior to shock. These experiments studied the role of bile reflux in the pathogenesis of stress ulcers in the shocked dog. Two and one-half hours of hemorrhagic shock in dogs with acute antral pouches isolated from the duodenum did not alter antral mucosal integrity as measured by gastric mucosal volume and ionic flux rates despite a fall in transgastric potential difference (PD) indicating mucosal injury (-33.5 +/- 1.7 m Volts vs -12.8 +/- 2.0, p < 0.01). Similarly 4(1/2) hours of shock did not alter mucosal integrity when the pylorus was cross-clamped during shock (PD -59.8 +/- 1.8 mV vs -42.5 +/- 7.0, p = 0.05). In contrast, 4(1/2) hours of shock in dogs in whom the pylorus was open resulted in increased hydrogen ion back diffusion (-106.3 +/- 21.5 microEq vs -300.5 +/- 63.1, p < 0.01, PD -56.8 +/- 3.6 mV vs -24.3 +/- 3.4, p < 0.01). The concentration of bile acids refluxed into the stomach during unmodified shock (8.45 +/- 3.92 mM) exceeds that necessary to disrupt the gastric mucosal barrier. These data suggest that increased hydrogen ion back diffusion initiated by refluxed bile plays an important role in the pathogenesis of gastric stress ulcers in the shocked dog.

Vasopressin clearance and secretion during haemorrhage in normal dogs and in dogs with experimental diabetes insipidus.

1. The secretion of vasopressin in response to haemorrhagic shock has been investigated in anaesthetized dogs.2. The changes in the plasma concentrations of vasopressin were followed over a period of 5 hr, during which the arterial blood pressure was kept constant at 40 mm Hg. It was found that vasopressin concentration in plasma rose to a high peak shortly after the onset of shock and gradually declined thereafter. Five hours later, it was still 3.5 times higher than control. Re-transfusion of blood was followed by a return to control levels.3. The clearance of vasopressin was calculated before and during shock in normal dogs and in dogs with experimental diabetes insipidus. Soon after the onset of shock, the clearance rate dropped to one quarter of its normal level but slowly recovered, returning to near control values at the fifth hour of shock. Clearance rates did not vary as a function of infusion rates, suggesting that there is no maximal transport rate for the removal of the hormone over the entire secretory range found in normal and hypotensive dogs.4. From the clearance rates and from the plasma concentrations of endogenously secreted vasopressin it has been possible to calculate the approximate secretory rates of the hormone in response to shock. Secretion rose to a very high level, some 40 times greater than control, at the onset of shock. This was followed by a fairly constant secretory plateau. At the fifth hour of shock secretion was 3.5 times higher than control.5. The half-life of vasopressin was measured in normal and hypotensive dogs. Control measurements confirm the generally accepted value of approximately 5 min. The half-life was significantly higher in the early stage of shock, but returned to control values in the later stage.6. Haemorrhage experiments performed in normal and diabetic dogs suggest that vasopressin may play a part in the development of irreversible haemorrhagic shock: all normal animals died within a few hours of retransfusion, whereas four out of eight diabetic dogs similarly treated survived a 24 hr observation period. In a separate set of experiments, eight diabetic dogs were subjected to the haemorrhage procedure while receiving a constant infusion of vasopressin: only two of these survived. Surviving dogs showed none of the characteristic lesions of irreversible haemorrhagic shock.

Serum insulin and growth hormone response to hemorrhagic shock.

Many metabolic abnormalities, including hyperglycemia and glucose intolerance, occur in hemorrhagic shock, which has been previously reported in dogs to be accompanied by elevations in plasma insulin levels. In this study, large primates (baboons) were subjected to hemorrhagic hypotension for 2 hr, during which time marked hyperglycemia occurred. Within 5 min of the onset of hemorrhage, insulin levels declined substantially in both fed and fasted animals and remained below preshock levels during the first hour of shock. During the second hour, insulin levels gradually rose, reaching levels slightly above base line values in approximately half the animals studied. Insulin response to intravenous tolbutamide was subnormal when administered after 1 hr of hypotension. Growth hormone levels remained suppressed in the majority of animals studied, and in the remaining animals changes in growth hormone levels did not correlate well with fluctuations in glucose concentration. These studies demonstrate that hemorrh...

Contributions of coronary perfusion pressure, metabolic acidosis and adrenergic factors to the reduction of myocardial contractility during hemorrhagic shock in the cat.

The contributions of metabolic acidosis, coronary perfusion pressure (CPP) and adrenergic support to left ventricular performance during hemorrhagic shock at aortic pressure (AP) of 30 ± 5 mm Hg were evaluated in cats in which AP, cardiac output (CO), and heart rate (HR) were controlled, and arterial pH, Po 2 and Pco 2 were continuously monitored. After 2 hours of shock, the stroke volume (SV), ejected at end-diastolic pressure of 10 cm H 2 O (SV 10 ), was irreversibly reduced to 46 ± 4% (P &lt; .001) of initial values (arterial pH 6.93 ± .05). In control animals SV 10 after 2 hours was 86 ± 6% (pH 7.32 ± .07). Eight animals were subject to shock, but their CPP was held at 100 mm Hg. These showed no difference in SV 10 from controls after 2 hours, although the pH had fallen to 6.90 ± .05. Reduction of CPP in these animals without correction of pH resulted in a rapid fall of SV 10 . In 10 animals subjected to shock for 2 hours, the arterial pH was maintained near 7.40 by infusion of Tris buffer. Five showed no greater reduction of SV 10 than the controls, and five became severely depressed. In five cats subjected to beta-receptor blockade, hemorrhagic shock (pH 7.40) produced a rapid fall of SV 10 which initially could be reversed by reelevation of AP. In less than 15 minutes, the SV 10 depression became irreversible. Thus, shock (2 hours) and associated metabolic acidosis is detrimental to ventricular contractility only if CPP is also reduced. The contribution of acidosis may be related to the amount of sympathetic support during shock. With beta-receptor blockade, shock results in a marked reduction in SV 10 , even in the absence of metabolic acidosis.

BIOCHEMICAL CHANGES DURING ACUTE PHYSIOLOGICAL FAILURE IN THE RAT: I. THE COENZYME A CONTENT OF THE COMPARTMENTS OF THE LIVER CELLS OF THE RAT DURING SHOCK

Shock was produced in the albino rat by means of a standardized method of blood removal. Coenzyme A (CoA) was extracted from the liver and estimated during the reversible and the irreversible phases of shock. The assay procedure was designed so that each animal served as its own "control".The CoA concentration in the liver fell rapidly during the first half hour of shock and thereafter at a progressively slower rate as the state of shock became more severe. Escape of the coenzyme from the mitochondria and the nucleus into the cytoplasm of the liver cells became evident during the reversible phase, and its breakdown in the cytoplasm began with the onset of the irreversible phase. Even at death, however, the CoA concentration of the liver was rarely lower than 35% of the original concentration. It is unlikely, therefore, that the decrease in the CoA content of the liver is a key factor in the initiation of the state of irreversibility in hemorrhagic shock.