REG can be used to detect cerebrovascular alteration caused by alcoholism.

Despite recent evidence of the beneficial effects of moderate alcohol consumption in arteriosclerosis prevention, the neurotoxic effects of alcohol abuse are well known. Our hypothesis was that uncontrolled alcohol consumption may cause cerebrovascular damage detectable by rheoencepholography (REG), a noninvasive bio-impedance technique for estimating cerebral blood flow. Test subjects were 48 alcoholic patients in Hungary; the control group consisted of 12 drug-addicted and depressed patients in Hungary and 13 healthy male subjects in the United States. Additional subgroups were formed according to smoking habits and average daily alcohol dose. REG was measured by a computer-based system, "Cerberus"; REG anacrotic time above 180 ms was considered pathological. ANOVA showed that daily alcohol consumption and smoking were significantly higher in alcoholics than in drug-addicted and depressed patients. Twelve alcoholics showed a pathological REG anacrotic time. Longer REG anacrotic time was correlated with higher daily alcohol consumption. In the alcoholic group, the steeper regression line of REG slope reflected the pathological impact of alcohol abuse. The healthy control sample showed a nearly identical slope for both REG and age. The correlation of increased REG anacrotic time and daily alcohol consumption supports the hypothesis that REG detects accelerated cerebrovascular aging (arteriosclerosis) in alcoholic subjects.

Changes in the intracranial rheoencephalogram at lower limit of cerebral blood flow autoregulation.

Cerebral blood flow (CBF) reactivity monitoring is an appropriate primary parameter to evaluate cerebral resuscitation due to a systemic or regional cerebral injury leading to possible irreversible brain injury. Use of the electrical impedance method to estimate CBF is rare, as the method's anatomical background is not well understood. Use of intracranial rheoencephalography (iREG) during hemorrhage and comparison of iREG to other CBF measurements have not been previously reported. Our hypothesis was that iREG would reflect early cerebrovascular alteration (CBF autoregulation). Studies comparing iREG, laser Doppler flowmetry and ultrasound were undertaken on anesthetized rats to define CBF changes during hemorrhage. Blood was removed at a rate required to achieve a mean arterial blood pressure (MABP) of 40 mm Hg over 15 min. Estimation of CBF was taken with intracranial, bipolar REG (REG I; n=14), laser Doppler flowmetry (LDF; n=3) and carotid flow by ultrasound (n=11). Data were processed off-line. During the initial phase of hemorrhage, when MABP was close to 40 mm Hg, intracranial REG amplitude transiently increased (80.94%); LDF (77.92%) and carotid flow (52.04%) decreased and changed with systemic arterial pressure. Intracranial REG amplitude change suggests classical CBF autoregulation, demonstrating its close relationship to arteriolar changes. The studies indicate that iREG might reflect cerebrovascular responses more accurately than changes in local CBF measured by LDF and carotid flow. REG may indicate promise as a continuous, non-invasive life-sign monitoring tool with potential advantages over ultrasound, the CBF measurement technique normally applied in clinical practice. REG has particular advantages in non-hospital settings such as military and emergency medicine.

Cerebrovascular reactivity: rat studies in rheoencephalography.

Here we describe a correlative study of cerebral blood flow (CBF) using global, local CBF and carotid flow measurements. The primary objective of this study was to establish a relationship between REG and CBF autoregulation. Rheoencephalography (REG), a rarely used method to measure CBF, is a potential tool of non-invasive continuous life sign monitoring and detection of early cerebrovascular alteration. However, the anatomical background of REG is not clearly understood. Two experimental studies were undertaken on anesthetized rats to define two CBF measurements: (1) CO2 inhalation, and, (2) clamping of common carotid arteries. Measurement of CBF was taken with REG, laser Doppler flowmetry (LDF) and carotid flow by Doppler ultrasound. Data were off-line processed. During CO2 inhalation, the increases in REG and LDF were significant (p = 0.0001), while carotid flow and systemic arterial pressure decreased. During carotid artery clamping, the decrease in REG and Doppler ultrasound was significant (p = 0.0001). REG showed cerebrovascular reactivity, indicating the relationship to arteriolar changes. Compared to LDF and carotid flow, only REG showed the classical CBF autoregulation.

Logistics of parenteral fluids in battlefield resuscitation.

The paper discusses the substantial reduction in weight and volume of the fluids of resuscitation that is possible and desirable on the basis of sound physiology and the vast experience of the U.S. Army in four major wars in this century. We note the major shift in emphasis from massive colloid and whole blood in World War II and Korea to massive crystalloid and packed cells in Vietnam and the serious complications with which this was associated. These complications were edematous in nature and best known as the Da Nang lung, or adult respiratory distress syndrome, multiorgan dysfunction syndrome, and systemic inflammatory response syndrome. The advantage of colloid in reducing the weight and volume of resuscitation fluids in forward areas by 60% to 90%, as well as in avoiding the edematous complications of crystalloid-, are emphasized.

The role of histamine in mediating the decompensatory phase of hemorrhagic shock in the rat.

Our laboratory has previously reported that plasma histamine levels rise significantly and coincidentally with the onset of the decompensatory phase of isobaric hemorrhagic shock in rats. The histamine levels seen in shock were comparable to those that induce profound vasodilatation in many vascular beds under normovolemic conditions. We, therefore, sought to determine whether the elevation in plasma histamine contributes to the cardiovascular collapse seen in the decompensatory phase of hemorrhagic shock. Sprague-Dawley rats were bled according to an isobaric bleeding protocol which maintained the mean arterial blood pressure (MAP) at 40 mmHg until death. Selected H1 (diphenhydramine) and/or H2 (cimetidine and famotidine) antagonists were administered at 75% of the estimated peak shed blood volume (PSBV), a point preceding the rise in plasma histamine. Plasma histamine levels in all groups were similar throughout the time course of hemorrhagic shock. None of the histamine receptor antagonists affected the time of onset or the rate of decompensation. Suspecting that hypotension may alter the animal's response to histamine, we investigated the effect of exogenous histamine administration on MAP before and after hemorrhage. In unbled animals, bolus histamine infusions (.6 mg/kg) dropped the MAP by 62.0 +/- 2.7 mmHg, however, in animals bled to 40 mmHg, histamine dropped the MAP by 7.2 +/- 2.7 mmHg (p = .002). On the basis of the results of these two interventions, we conclude that histamine is not an important mediator of the cardiovascular collapse seen in the decompensatory phase of hemorrhagic shock in the rat.

The effect of hypothermia on potassium and glucose changes in isobaric hemorrhagic shock in the rat.

Hypothermia has been shown to decrease oxygen consumption requirements and improve survival during hemorrhagic shock. however, hypothermia applied therapeutically does not prevent the development of a lactic acidosis during hemorrhage. We re-examined the development of a hemorrhage-induced lactic acidosis and other metabolic parameters (glucose, plasma electrolytes, and arterial blood gases) at various temperatures (29-37 degrees C) to better define the protective action of hypothermia in hemorrhagic shock. Five groups of male, Sprague-Dawley rats were bled to a mean arterial blood pressure (MABP) of 40 mmHg over a 15 min period and held there by further blood removal until death. The final level and rate of development of the lactic acidemia was the same in all groups. However, the rate of decline in plasma glucose and rate of rise in plasma potassium were temperature dependent. These results suggest that temperature-dependent changes in serum glucose and potassium may contribute to the protective effect of hypothermia during hemorrhagic shock.

Lifting and handling of patients by anaesthetists.

The process of transferring patients from the operating table was assessed in a district general hospital. The survey was conducted in two parts; a confidential questionnaire was sent to all members of the department and a month long assessment of three anaesthetists' caseload was undertaken. All the anaesthetists questioned had scanty knowledge of the relevant manual handling regulations. Although 70% of anaesthetists questioned lift and transfer patients on a regular basis, none had received any relevant training. Ninety-six percent of patient transfers were performed by two staff alone, even though there were five or more staff available to assist at 95% of transfers. Difficulty in transferring patients occurred in 32% of cases. Improvement of training anaesthetists in safe manual handling procedures is recommended.

Plasma and tissue histamine changes during hemorrhagic shock in the rat.

We investigated the phase-associated changes in plasma histamine levels in an isobaric model of hemorrhagic shock, in an attempt to determine whether histamine might be an etiologic factor in the onset of decompensation. Sprague-Dawley rats were bled according to an isobaric bleeding protocol which maintained the mean arterial blood pressure at 40 mmHg until death. The status of vascular compensation for the blood loss was tracked by measurement of the shed blood volume (SBV) required to maintain the target pressure. Blood samples for analysis were taken at the control period and at 25% intervals of the peak shed blood volume (PSBV) during the compensatory and decompensatory phases. Plasma and tissue histamine levels were measured using a radioimmunoassay method. In untreated animals, plasma histamine levels at control, 75 and 100% of the PSBV, and after return of 25 and 75% of the PSBV were 45 +/- 10, 48 +/- 9,134 +/- 48,693 +/- 351, and 994 +/- 371 nM, respectively. These results show that rises in plasma histamine occurred coincidentally with the onset of decompensation (p < .05), however, the subsequent rate of decompensation did not correlate with plasma histamine changes during decompensation. Organ histamine levels measured after hemorrhage were lower in the duodenum and colon than in unbled control animals, suggesting that parts of the intestinal tract may contribute to the elevated plasma histamine levels seen in severe hypotension (p < .05).

Glucose infusion arrests the decompensatory phase of hemorrhagic shock.

Waning of hyperglycemia has been shown to be closely associated with the deterioration of mechanisms supporting homeostasis during hemorrhagic shock. However, the mechanisms which link plasma glucose levels to maintenance of homeostasis during hemorrhagic shock are not clear. The goal of the present study was to evaluate the importance of glucose to maintenance of compensatory mechanisms. This was undertaken by maintaining plasma glucose levels through infusion of hypertonic glucose (2-3 M) starting at the onset of decompensation during persisting hypovolemia. Administration of glucose at a rate of between 60 and 80 mumoles/min X kg arrested the fall in glucose concentration and significantly slowed or arrested the decompensatory phase. All of the saline infused control animals (n = 6) died within 3 hours after reaching their maximum shed blood volume, averaging 145 +/- 25 minutes, while two of the eight animals in the glucose infusion group died less than 4 hours after reaching the maximum shed blood volume. The remaining six animals were sacrificed between 270 and 397 minutes (average, 340 +/- 22 minutes) after reaching the maximum shed blood volume since decompensation was arrested. Compared to the saline-infused control group, animals receiving glucose infusion exhibited a more moderate acidosis, and the hemoconcentration which normally accompanies decompensation was also prevented. Since the increase in plasma osmolality and the fraction of the total osmolality change accounted for by glucose was less in the glucose-infused animals, these results suggest that the effect is not mediated through a glucose-related maintenance of a transcapillary osmotic gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Verapamil crystalloid cardioplegia: an experimental evaluation of dose-response relationships.

Calcium channel blockers have been advocated as agents which enhance myocardial protection during ischemia and reperfusion. Unfortunately, while cellular integrity is preserved, myocardial function is depressed as a result of the negative inotropic effects of these agents. In order to assess the efficacy of verapamil cardioplegia, 25 isolated perfused rabbit hearts were studied. A model of normothermic ischemic arrest was utilized, employing either verapamil-free crystalloid cardioplegia or cardioplegia containing verapamil in concentrations of 0.5, 1.0, or 5.0 mg/liter. All three verapamil-treated groups demonstrated increased postischemic left ventricular developed pressure and improved postischemic compliance when compared with the untreated group (P less than 0.05). However, myocardial function was significantly depressed at 15 min of reperfusion in the 1.0 and 5.0 mg/liter verapamil-treated groups when compared with the 0.5 ml/liter group (P less than 0.05). These data suggest that the addition of verapamil to crystalloid cardioplegia results in enhanced myocardial function while minimizing the early reperfusion depression associated with higher dose therapy.

Failure of oxygen-free radical scavengers to improve postischemic liver function.

Previous investigations have demonstrated reduction of postischemic organ injury with improved flow rates following administration of superoxide dismutase (SOD) and catalase (CAT) just before reperfusion. Presumably these oxygen-free radical scavengers provide protection against oxygen-free radicals produced during reoxygenation, but the site of action remains unclear. The present study was designed to determine the effect of SOD/CAT on hepatic function following global ischemia independent of flow. Livers obtained from Sprague-Dawley rats fasted 24 hours were perfused with Krebs-Henseleit buffer containing 5 mM lactate for 130 minutes. Following a 30-minute control period, livers were subjected to 55 minutes of warm, global ischemia. The control group (N = 12) was reperfused under oxygenated conditions for an additional 45 minutes. Two other groups (N = 9; N = 4) were reperfused under identical conditions with administration of 150,000 U/L or 450,000 U/L of SOD/CAT 3 minutes before reperfusion. Hepatic flow returned to normal levels following ischemia, but gluconeogenic activity and bile production remained significantly depressed. No significant recovery of gluconeogenic activity or bile production was noted when SOD/CAT was administered before reperfusion. These results demonstrate that in the absence of flow augmentation SOD/CAT do not provide protection from oxygen-free radicals following global ischemia in the isolated rat liver. This implies that previously reported reductions of postischemic reperfusion injury, where blood flow improved as well, may be due to oxygen-free radical scavenging within the vascular network resulting in enhanced organ perfusion and, therefore, improved organ function.

Scaling of physiological responses: a new approach for hemorrhagic shock.

Standard protocols used to study hemorrhagic shock involve sampling at fixed time intervals and generating a time-based composite curve from each experiment. Although each animal may show the same sequence of responses, the time, rate, and size of the response varies from animal to animal. As a result, sampling times may be inappropriate to identify sharp transitions in the measured parameters, and the composite curves do not reflect the size and shape of the individual responses. This report evaluates several approaches to normalizing hematocrit and blood glucose data obtained from a constant-pressure model of hemorrhagic shock in fed and fasted and dehydrated animals to see if phase relationships and fractional responses from individual animals can be made coherent. Scaling for fractional blood loss on the x-axis and maximal response on the y-axis resulted in convergence of the results from individual animals and different experimental series. Data from a constant rate of hemorrhage model also converged after scaling. A method for prospectively defining the scale and adjusting sampling frequency for individual animals is given.

Phase-related changes in tissue energy reserves during hemorrhagic shock.

In view of the well-known fact that the liver is more sensitive to ischemia than skeletal muscle, it was the purpose of the present study to determine the relationship between the hemorrhage-induced changes in plasma glucose and lactate concentrations and the status of the energy reserves of these two tissues. Sprague-Dawley rats were bled to a constant mean arterial blood pressure of 40 mm Hg and held there by removal or reinfusion of blood. The stages of shock defined on the basis of the net blood loss were early compensatory, maximal compensatory, early decompensatory, and late decompensatory phases. The results showed a depletion of hepatic ATP levels which occurred between the early compensatory and maximal compensatory phases of shock, coincident with the most dramatic increases in plasma glucose and lactate seen during the shock protocol. Hepatic ATP levels fell no further through the decompensatory phases of shock while plasma glucose declined to hypoglycemic levels and plasma lactate was maintained at the same high level attained at the maximal compensatory phase. Since hepatic sources of glucose were exhausted by the maximal compensatory phase and hepatic energy stores were depleted to a point which precludes significant gluconeogenesis, the large increase in plasma lactate was probably largely due to loss of the hepatic "sink" for lactate during this phase of shock. In contrast to the liver, soleus muscle showed no change in the levels of glycogen, ATP, CrP, free creatine, or total creatine compared to time-matched controls in any phase of hemorrhagic shock suggesting the absence of significant muscle ischemia. The possibility that red skeletal muscle may act as a "sink" for lactate is considered.

Extracellular-intracellular lactate gradients in skeletal muscle during hemorrhagic shock in the rat.

Previous studies performed in our laboratory with a constant-pressure model of hemorrhagic shock in the anesthetized rat have failed to find any significant effect of shock on the glycogen or high-energy phosphate content of the soleus muscle that would be consistent with inadequate oxygen supply. The present study examined the extracellular-intracellular lactate concentration gradients under conditions identical to those of our previous studies to determine whether skeletal muscle lactate accumulation might occur under these conditions. Twenty-seven pentobarbital-anesthetized rats were bled to a mean arterial blood pressure of 40 mm Hg during a 10-minute period and maintained at that level by withdrawal or reinfusion of shed blood. Arterial blood samples were taken and soleus muscles rapidly frozen during four defined phases of hemorrhagic shock: the early compensatory (phase I), maximal compensatory (phase II), early decompensatory (phase III), and late decompensatory (phase IV) phases. The results showed that although the plasma lactate and intracellular lactate concentrations change in parallel during all phases of shock, the extracellular--intracellular concentration gradient for lactate was always positive, ranging from 0.64 +/- 0.61 mmol/L in phase I to 6.41 +/- 0.93 mmol/L in phase III. These findings, together with the previous failure to find significant high-energy phosphate or glycogen changes in the soleus muscle, suggest that this skeletal muscle is not metabolizing anaerobically and does not contribute to the observed lactic acidemia in this model of hemorrhagic shock.

Preservation of myocardial function with mannitol reperfusate.

Reperfusion of the globally ischemic myocardium with mannitol has been shown to preserve myocardial function. However, it remains unclear whether the mechanism of mannitol protection relates to its hyperosmolar or free radical scavenging properties. Three groups of isolated, perfused rabbit hearts underwent 45 min of normothermic ischemia without cardioplegia in an experimental paradigm analogous to the clinical situation of coronary artery thrombosis with subsequent reperfusion. Six hearts were reperfused with an isosmolar solution, eight hearts were reperfused with a mannitol-containing solution (20 mOsm/liter), and five hearts were reperfused with a solution containing additional sodium chloride (10 meq/liter, 20 mOsm/liter) to control for the hyperosmotic effects of mannitol. Left ventricular developed pressure, its derivative dP/dt, and diastolic compliance were all significantly improved in the mannitol-reperfused hearts when compared with the hypertonic saline and control groups (p less than .05). There were no intergroup differences in myocardial edema formation, oxygen consumption, or lactate production. These data indicate that mannitol reperfusion offers significant myocardial protection independent of hyperosmolar properties. Free radical scavenging activity appears to be the most credible explanation for these observations, although confirmation of this mechanism awaits further biochemical and cellular investigation.

Influences of fasting and water intake on plasma refill during hemorrhagic shock.

The hyperglycemic response to hypovolemia has been regarded as an essential osmotic force for promoting the early phase of the internal restoration of plasma volume. Our previous studies of rats fasted 24 hours revealed that they did not develop the hyperglycemic response to hemorrhage observed in fed animals but they had a similar hyperosmotic response. The solutes responsible for the hyperosmolality in the fasted animals were primarily products of anaerobic glycolysis, rather than glucose which accounted for most of the hyperosmolality in fed animals. Plasma refill as reflected by a fall in the hematocrit (Hct) and survival time was significantly reduced in the fasted animals. This study was undertaken to test the hypothesis that the failure of fasted rats to exhibit a normal restoration of plasma volume after hemorrhage may reflect the detrimental effects of fasting on the state of hydration and on the plasma oncotic pressure of the fasted animals rather than the absence of a hyperglycemic response. Four groups of anesthetized rats (280-380 gm) were bled acutely and maintained at an arterial pressure of 40 mm Hg. Before hemorrhage animals in Group A were well fed, those in Groups B, C, and D were fasted for 24 hours. Rats in Group B were induced to drink by addition of sodium chloride in their water, rats in Group C spontaneously had a normal fluid intake, and rats in Group D had a significant reduction in their 24-hour fluid intake. The results demonstrated that 24 hours of fasting led to a loss of body weight of 7 to 10% and a fall in the concentration of plasma total protein of 12 to 17% in all rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary response of the rat to gram-negative bacteremia.

Hemodynamic and respiratory effects of a continuous 5-h intravenous infusion of live Escherichia coli were studied in rats. Control animals were infused with saline. Rats infused with 1.8 +/- 0.4 X 10(10) bacteria/h did not survive a 5-h infusion. These animals developed early hypotension and reduced cardiac output (CO) measured by thermal dilution technique. Rats infused with 8.0 +/- 0.4 X 10(9) bacteria/h survived a 5-h infusion with hypotension and reduced CO occurring later in the course of bacteremia. Heart rate was markedly elevated in both septic groups. Arterial blood gas measurements revealed that partial pressure of O2 was not affected by bacteremia, but partial pressure of CO2 was significantly decreased. Arterial pH remained within the normal range indicating respiratory compensation of a metabolic acidosis. Since hypotension and reduced CO were accompanied by a fall in right atrial pressure (RAP) during bacteremia, a third septic group was studied to evaluate cardiac performance during volume loading. After 3-5 h of bacteremia, a 40% reduction in CO was associated with a significant drop in arterial pressure and RAP. Despite volume loading, ventricular stroke work and arterial pressure were significantly reduced compared with control animals. The results indicate that severe gram-negative bacteremia produces myocardial depression in the rat. This model can be useful for further studies of cardiac dysfunction during sepsis.

Effect of hemorrhage and anoxia on hepatic gluconeogenesis and potassium balance in the rat.

Previous investigations have demonstrated impairment of hepatic gluconeogenic activity during both hypovolemia and sepsis, but the mechanisms responsible remain unclear. The present study was designed to determine the influence of lack of oxygen on gluconeogenesis independent of humoral factors, products of ischemic peripheral tissues or pH changes. Livers obtained from Sprague-Dawley rats fasted 24 hours were perfused with Krebs-Henseleit buffer containing 5 mM lactate for 30 minutes. In the control group (n = 8) perfusion was continued; in others, anoxia was induced by perfusing with buffer equilibrated with 95% N2 and 5% CO2 for periods of 15, 30, or 60 minutes (n = 4, 5, and 5, respectively). The initial conditions were then reinstituted for an additional 45 minutes. Anoxia caused hepatic release of K+, indicative of disordered hepatic cellular ionic gradients and an abrupt cessation of gluconeogenesis. Reoxygenation partially reversed these alterations but some impairment of gluconeogenesis persisted and the degree of uptake of K+ from the perfusion media was decreased as the duration of anoxia increased. The degree of restoration of gluconeogenesis after a period of anoxia was closely associated with restoration of cellular uptake of K+. By comparison, livers taken from hypovolemic animals maintained at a mean arterial blood pressure of 40 mm Hg until the beginning of the decompensatory stage of shock exhibited a gluconeogenic capacity of only 41% of control animals and was comparable to the compromise induced by between 30 and 60 minutes of anoxia. These results suggest that the abilities to restore hepatic electrolyte balance and gluconeogenesis after oxygen deprivation are affected in parallel and may reflect a common dependence on the restoration of ATP stores after the insult.

Liver adenosine triphosphate (ATP) in hypoxia and hemorrhagic shock.

Reduction of liver ATP in proportion to the severity of shock and hypoxia is well known. We have studied the interrelationships among arterial oxygenation, arterial pH, and liver ATP in experimental hypoxia and in hemorrhagic shock in rats. No significant correlation was found between liver ATP and arterial pH in both hemorrhagic shock and hypoxia and between liver ATP and arterial PO2 in hypoxia. Induction of experimental observations suggest that in this form of hemorrhagic shock, arterial pH may be a sensitive indicator of decreased hepatic perfusion and impaired liver ATP production.