Prolonged Hypovolemia Research Articles

NHE1 inhibition improves tissue perfusion and resuscitation outcome after severe hemorrhage

IntroductionThis study tested the hypothesis that blockade of the pH-regulatory protein, Na+/H+ exchanger (NHE1) during prolonged hemorrhagic shock can protect against whole-body ischemia-reperfusion injury, resulting in improved neurological outcomes. MethodsWe used a total of 24 male pigs in this study. We excluded two animals: one because of cardiac arrest after the initial hemorrhage, and the second because of a catheter malfunction for color microspheres. In Series 1, anesthetized pigs underwent an initial hemorrhage of 40 mL/kg for 30 min, and then were given either 3 mg/kg of NHE1 selective inhibitor BIIB513 (n = 6) or vehicle (n = 6). At 1 h after treatment, all animals received fluid resuscitation. We assessed survival and neurologic outcomes 72 h postresuscitation. In Series 2, we measured organ blood flow in a separate group of control (n = 5) and BIIB513-treated pigs (n = 5) undergoing the same experimental paradigm. ResultsFive of six control animals failed to be weaned from mechanical ventilation. We killed another control animal the next day because of severe complications. In contrast, all six animals treated with BIIB513 were weaned off the ventilator, and all but one survived the 72-h experimental period with normal neurological outcome. Results showed that NHE1 inhibition with BIIB513 improved blood flow to the brain, heart, and kidney, and prevented the development of metabolic acidosis in the 1-h hypovolemic period. In addition, BIIB513 facilitated the hemodynamic response to fluid resuscitation, increased mixed venous blood oxygen saturation and oxygen delivery, and reduced proinflammatory cytokine release and multiorgan injury compared with vehicle controls. ConclusionsIn this study, NHE1 inhibition with BIIB513 improved vital organ blood flow, prevented the development of metabolic acidosis during prolonged hypovolemia, and facilitated the hemodynamic response to fluid resuscitation, resulting in increased survival and normal neurological outcomes.

Sodium depletion activates the aldosterone-sensitive neurons in the NTS independently of thirst

Thirst and sodium appetite are both critical for restoring blood volume. Because these two behavioral drives can arise under similar physiological conditions, some of the brain sensory sites that stimulate thirst may also drive sodium appetite. However, the physiological and temporal dynamics of these two appetites exhibit clear differences, suggesting that they involve separate brain circuits. Unlike thirst-associated sensory neurons in the hypothalamus, the 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2) neurons in the rat nucleus tractus solitarius (NTS) are activated in close association with sodium appetite (16). Here, we tested whether the HSD2 neurons are also activated in response to either of the two physiological stimuli for thirst: hyperosmolarity and hypovolemia. Hyperosmolarity, produced by intraperitoneal injection of hypertonic saline, stimulated a large increase in water intake and a substantial increase in immunoreactivity for the neuronal activity marker c-Fos within the medial NTS, but not in the HSD2 neurons. Hypovolemia, produced by subcutaneous injection of hyperoncotic polyethylene glycol (PEG), stimulated an increase in water intake within 1-4 h without elevating c-Fos expression in the HSD2 neurons. The HSD2 neurons were, however, activated by prolonged hypovolemia, which also stimulated sodium appetite. Twelve hours after PEG was injected in rats that had been sodium deprived for 4 days, the HSD2 neurons showed a consistent increase in c-Fos immunoreactivity. In summary, the HSD2 neurons are activated specifically in association with sodium appetite and appear not to function in thirst.

Effect of infusion of hypertonic-hyperoncotic solution on cardiovascular function in surgery of the abdominal aorta during the perioperative period

When blood flow is decreased, as in prolonged hypovolaemia and hypotension, or in the course of transversal clamping of the aorta during aortic reconstruction, nutritive tissue perfusion can also fall below the critical level. The objective of this study was to analyse the effects of hypertonic-hyperoncotic solution on cardiovascular function during reconstruction of the abdominal aorta. This prospective randomised study included 40 patients. All patients underwent surgery of the abdominal aorta under general endotracheal anaesthesia. Based on the type of solution infused from the time of clamping to the moment of the removal of the transversal aortic clamp, the patients were divided into two groups of 20. The study group was infused with a small volume of hypertonic-hyperoncotic solution, while the controls were administered infusions of isotonic solution. Patients with a preoperative creatinine level over 130 micromol L(-1) and an ejection fraction of less than 40% were excluded from the study. Cardiac output increased from 5.67 +/- 2.95 to 7.05 +/- 3.39 L min(-1) in the study group, in comparison to the controls, where it increased from 4.98 +/- 2.06 to 5.99 +/- 3.02 L min(-1) (p = 0.004). Central venous pressure increased from 8.75 +/- 3.67 to 9.30 +/- 2.77 mm Hg in the study group, in comparison to the controls, where the values decreased from 6.84 +/- 2.73 to 6.45 +/- 2.50 mm Hg (p = 0.022). Diastolic pulmonary artery pressure increased from 15.92 +/- 5.61 to 16.65 +/- 6.53 mm Hg in the study group, in comparison to the controls, where it decreased from 12.65 +/- 4.28 to 11.85 +/- 3.91 mm Hg (p = 0.021). The amount of given crystalloids 24 hours after the removal of the aortic clamp totalled 2562.5 +/- 485.82 mL in the study group, versus 3350 +/- 727.29 mL in the control group (p = 0.000). The amount of given human albumins 24 hours after the removal of the aortic clamp totalled 30 +/- 49.74 mL in the study group versus 100 +/- 4.34 mL in the control group (p = 0.001). CONCLUSION Haemodynamic stability of patients and adequate organ perfusion during surgery are achieved through the infusion of hypertonic-hyperoncotic solution, which maintains optimal values of: cardiac output, mixed venous oxygen saturation, and delivery of oxygen, while reducing alveolo-arterial oxygen difference. The balance of fluids, 24 hours after the removal of the aortic clamp, was maintained with the aid of hypertonic-hyperoncotic solution, while isotonic solution produced an excess of over 1000 mL of fluid in the control patients. Hypertonic-hyperoncotic solution increases cardiac output considerably more than does isotonic solution, and its application significantly reduces the accumulation of crystalloid solutions and human albumins.

Colonic perforation following prolonged hypovolaemia in a major burns injury

Perforation of the lower gastrointestinal tract is rare in burns patients. A 41-year-old male, who sustained 40% total body surface area burns and subsequently developed an acute abdomen on day 15 postburn, is presented. Emergency management included a subtotal colectomy and ileostomy formation performed to repair a perforated transverse colon found at laparotomy. The burns were debrided and grafted and the patient required cardiac, renal and respiratory support initially in the ITU setting before making a complete recovery. It is suggested that ischaemia caused the perforated transverse colon due to a prolonged low flow state. This was not detected until invasive cardiovascular catheterisation was performed and revealed a hypovolaemic state, which was corrected by fluids and noradrenaline. Both the previous cardiac history of the patient (Fallot's Tetralogy repair) and the noradrenaline may have exacerbated the low flow state within the mesenteric circulation leading to ultimate perforation. This case highlights the difficulties that may arise in resuscitating a patient who has previously had a cardiac defect repaired. Despite repair, abnormal physiology may persist resulting in misleading observations that produce undetected hypovolaemia with subsequent adverse events, as in this case. In such patients, early invasive cardiovascular monitoring should be considered.

Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients

Summary Upper gastrointestinal bleeding (GIB) is a major complication in cirrhotic patients. Endoscopy and oesophageal sclerosis are reference treatments and must be done as soon as possible. However, such treatment is not possible unless the patient is admitted to hospital. In a prospective, randomised, double-blind trial, we compared the efficacy of terlipressin combined with glyceryl trinitrate (TER-GTN), administered as early as possible to 76 patients with cirrhosis who had active GIB (84 bleeding episodes). Infusion was done at the patient's home by the physician on the emergency team (a mobile intensive care unit) if the patient had GIB and a history and clinical signs of cirrhosis. Patients received either an intravenous injection (1 to 2 mg) of TER-GTN or a double-placebo injection, and then another injection at 4 and 8 h. Control of bleeding, rebleeding, and mortality rate at days 15 and 42 were evaluated. In most patients, endoscopy confirmed the rupture of oesophageal varices (75·7%). Bleeding control was significantly better in the TER-GTN group (n=41) than in the double-placebo group (n=43) (p=0·034). Mortality due to bleeding episodes was significantly lower in the TER-GTN group than in the double-placebo group at day 15 (p=0·035) and at day 42 (p=0·06). There were no serious side-effects. Early administration of TER-GTN lowers the deleterious consequences of prolonged hypovolaemia on the hepatic function of these patients.

Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness

To evaluate the reliability of the vital signs to evaluate circulatory stability as reflected by cardiac index. Descriptive analysis based on data gathered prospectively, using a predetermined protocol. University-run county hospital, with a large trauma service. Sixty-one high-risk trauma patients with accidental injury who were studied immediately after admission to the Emergency Department, and subsequently, 163 critically ill postoperative ICU patients. Standard fluid therapy, usually crystalloids, but occasionally packed red cell transfusions and colloids, as indicated by clinical criteria. Arterial BP was measured by pressure transducer and arterial catheter; heart rate (HR) was measured by electrocardiograph signal, and cardiac output was measured by thermodilution. In sudden severe hypovolemic hypotension, the mean arterial pressure (MAP) nadir (lowest) roughly correlated (r2 = .25) with flow, but there was poor correlation (r2 = .0001) when all pressure and flow values were evaluated. The pressure and flow values were obtained throughout the course of the hypotensive episodes during the initial resuscitation in ICU patients and during terminal illnesses. Observations at the time of acute severe hypotensive crises that show rough correlation of MAP and cardiac index should not be extrapolated throughout the entire hypotensive period or to other less extreme clinical situations. The stress response to hypovolemia, with endogenous catecholamines and neural mechanisms, tends to maintain arterial pressure in the face of decreasing flow for a variable period of time. However, when these mechanisms are overwhelmed by prolonged hypovolemia, the pressure decreases precipitously, but not synchronously, with flow. We conclude that blood flow cannot reliably be inferred from arterial pressure and heart rate measurements until extreme hypotension occurs.

The morphological changes of the pancreas in hypovolemic shock and the effect of pretreatment with steroids

Previous reports from this laboratory have described the effect of hypovolemic shock of varying duration on the exocrine function of the pancreas, and the ability of steroids to reverse the inhibition of secretion observed. This report is a study of pancreatic morphology in prolonged hypovolemia, as well as the effect of steroid pretreatment on the pathology observed. Twelve mongrel dogs were divided into two groups, one with and one without steroid pretreatment. The animals were bled until at least 30-35% of their blood had been withdrawn, or until mean blood pressure (BP) dropped to around 60 mmHg. When BP dropped to 80-90% mmHg, six animals received intravenous (i.v.) prednisolone in 50 cc of 0.9% NaCl, at the rate of 10 cc/min, for a dosage of 30 mg/kg. Of the twelve dogs, six were exposed to 120 min of hypovolemia, and six to 180 min. At the end of the observed hypovolemic period, the blood withdrawn was quickly retransfused. After an hour of recovery, the animals were killed and their pancreases removed. The pancreases were weighed, fixed and examined by light microscopy. Three pancreases were obtained as control from animals not subjected to shock or steroids. The steroid-treated animals displayed an insignificant (5%) increase in pancreatic weight following prolonged hypovolemia. Untreated canine pancreases, on the other hand, showed a significant weight gain (37%, P less than 0.001) after 3 h of hypovolemia. Microscopically, the untreated group revealed marked interstitial edema, hemorrhage and inflammation, as well as focal acinar cell necrosis and fat necrosis, while in the steroid group only very mild edema and inflammatory changes were seen. This study indicates a beneficial effect of steroids on the morphological changes seen in shock-induced pancreatitis in canines and a possible use in the therapy of acute pancreatitis in man.

The effect of steroid administration on pancreatic secretion during and after hypovolemic shock

In a previous report from this laboratory, 1 h of hypovolemia induced a significant decrease in pancreatic flow, bicarbonate and enzyme secretion. These parameters recover after restoration of blood volume, but never return to pre-shock levels. Furthermore, increasing the period of hypovolemia produced further decreases in pancreatic flow and bicarbonate secretion only. Enzyme secretion, however, rose significantly, probably due to leakage of protein through damaged cell membranes. Prolonged hypovolemia was also accompanied by visible edema. This model of secretory changes induced by fixed periods of hypovolemic shock is ideal to study the effect of steroids on secretion and to assess its possible cytoprotective properties against early induced ischemia pancreatic pathology. Pancreatic secretion was collected by cannulation of the main pancreatic duct in 12 anesthetized dogs. Secretin was administered by continuous intravenous (i.v.) infusion at 4 U/kg/h. Four 15-min samples of pancreatic juice were collected. Then the dogs were bled, withdrawing 25-30% of total blood volume or until the mean blood pressure dropped to about 60 mmHg. At this point, 30 mg/kg of methyl prednisolone were given in 50 cm3 of NaCl i.v. to six animals. Blood samples for amylase and 15-min collections of pancreatic juice for volume, bicarbonate and enzymes were obtained during hypovolemia, as well as during and following the restoration of blood volume. The responses of the two groups differed as follows: (1) Instead of the increase in protein enzyme secretion seen in the non-steroid group with increased duration of hypovolemia, steroid-treated dogs displayed a significant decrease in protein output.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin effectiveness in hypovolemic dogs.

The question addressed in this study was whether exogenous insulin can enhance the rate of assimilation of blood glucose after prolonged hypovolemia when homeostasis is waning. Twenty-three well-fed mongrel dogs were maintained at a mean arterial blood pressure of 50 mm Hg by bleeding. Periodic analyses were made of arterial and venous plasma concentration of glucose, femoral blood flow, arterial plasma concentration of insulin, and hematocrit. At the onset of physiologic deterioration signaled by the need to reinfuse 50 ml of shed blood to maintain 50 mm Hg blood pressure, dogs received either 10 ml saline (control; n=15) or 10 ml saline containing 2 units insulin (treated; n=8). Administration of 2 units of insulin to eight of the dogs caused a significantly faster decline of blood glucose than that observed in saline-treated animals. Despite the more rapid decline in plasma concentration of glucose in animals that received insulin, there was no significant difference in glucose uptake between the two groups of animals. The hemoconcentration reflected by a rising hematocrit that develops when hypovolemia persists was accentuated by the administration of insulin without supplementary fluids. The absence of any effect of insulin on glucose uptake in the hindlimb in the late phase of hypovolemic shock suggests that the accelerated decline in arterial glucose levels may be due to inhibitory effects of insulin on hepatic glucose release. These results are not consistent with the resistance of plasma glucose to insulin in the late phases of hypovolemic shock.

Skin and muscle circulatory responses during prolonged hypovolemia.

ARTICLESSkin and muscle circulatory responses during prolonged hypovolemiaJM Schwinghamer, GJ Grega, and FJ HaddyJM Schwinghamer, GJ Grega, and FJ HaddyPublished Online:01 Aug 1970https://doi.org/10.1152/ajplegacy.1970.219.2.318MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByAutonomic neuropathy and transcutaneous oxymetry in diabetic lower extremitiesDiabetologia, Vol. 37, No. 10Impairment during marked hypotension of the plasma volume control in hemorrhageActa Physiologica Scandinavica, Vol. 114, No. 3Hormonal and neurogenic adrenergic control of the fluid transfer from skeletal muscle to blood during hemorrhageActa Physiologica Scandinavica, Vol. 112, No. 3Further studies on beta-adrenergic control of transcapillary fluid absorption from skeletal muscle to blood during hemorrhageActa Physiologica Scandinavica, Vol. 112, No. 3Circulatory Correlates: Vascular Impedance, Resistance, and Capacity1 January 2011The interplay of central and peripheral factors in irreversible hemorrhagic shockProgress in Cardiovascular Diseases, Vol. 18, No. 2Potassium and blood vesselsLife Sciences, Vol. 16, No. 10Transcapillary Fluid Movements in Sympathectomized Intestine and Skin during Hemorrhagic HypotensionActa Physiologica Scandinavica, Vol. 94, No. 1Osmotic Fluid Transfer from Tissue to Blood during Hemorrhagic HypotensionActa Physiologica Scandinavica, Vol. 89, No. 2Transvascular Fluid Fluxes During Severe, Prolonged Canine Hemorrhagic or Endotoxin HypotensionChanges in Forelimb Weight and Segmental Vascular Resistances Following Severe HemorrhageCirculation Research, Vol. 29, No. 6 More from this issue > Volume 219Issue 2August 1970Pages 318-326 Copyright & PermissionsCopyright © 1970 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1970.219.2.318PubMed5448060History Published online 1 August 1970 Published in print 1 August 1970 Metrics