Biomedical subjects

D S DeWitt

Publications and source records attributed to D S DeWitt.

At least 37 records · Page 2Linked to original sources

PubMed1997

L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion after fluid-percussion traumatic brain injury.

To determine whether treatment with L-arginine or superoxide dismutase (SOD) would prove effective in reducing cerebral hypoperfusion after traumatic brain injury (TBI), we measured cerebral blood flow (CBF) using laser Doppler flowmetry (LDF) in rats treated before or after moderate (2.2 atm) fluid-percussion (FP) TBI. Rats were anesthetized with isoflurane and prepared for midline FP TBI and then for LDF by thinning the calvaria using an air-cooled drill. Rats were then randomly assigned to receive sham injury, sham injury plus L-arginine (100 mg/kg, 5 min after sham TBI), TBI plus 0.9% NaCl, TBI plus L-arginine (100 mg/kg, 5 min post-TBI), TBI plus SOD (24,000 U/kg pre-TBI + 1600 units/kg/min for 15 min after TBI), or TBI plus SOD and L-arginine. A second group of rats received TBI plus saline, L-, or D-arginine (100 mg/kg, 5 min after-TBI). After treatment and TBI or sham injury, CBF was measured continuously using LDF for 2 h and CBF was expressed as a percent of the preinjury baseline for 2 h after TBI. Rats treated with saline or D-arginine exhibited significant reductions in CBF that persisted throughout the monitoring period. Rats treated with L-arginine alone or in combination with SOD exhibited no decreases in CBF after TBI. CBF in the SOD-treated group decreased significantly within 15 min after TBI but returned to baseline levels by 45 min after TBI. These studies indicate that L-arginine but not D-arginine administered after TBI prevents posttraumatic hypoperfusion and that pretreatment with SOD will restore CBF after a brief period of hypoperfusion.

Animals↗

PubMed1997

Traumatic brain injury does not alter cerebral artery contractility.

Previous studies have shown that traumatic brain injury (TBI) significantly reduces cerebral blood flow determined in vivo and reduces vascular reactivity in the pial circulation measured with cranial window preparations. We have now tested the hypothesis that TBI induces these changes by impairing intrinsic contractile activity of cerebral arteries. Anesthetized rats underwent moderate (2.2 atm) and severe (3.0 atm) midline fluid percussion TBI or sham injury following which posterior cerebral or middle cerebral arteries were isolated and isometric force generation was measured. Moderate (n = 5) and severe (n = 3) trauma had no effect on the magnitude of serotonin- or K+-induced force generation or sensitivity to serotonin in arteries isolated within 10 min of TBI. Functional disruption of the endothelium of posterior cerebral arteries isolated 10 min after moderate trauma or sham injury caused a reduction in the active tension response to serotonin that was similar in both groups. Blockade of cyclooxygenase with 5 microM indomethacin had no effect on serotonin-induced force generated by vessels with moderate trauma or in sham-treated rats. Acetylcholine induced an endothelium-dependent relaxation of posterior and middle cerebral arteries; the magnitude of the response was unaffected by moderate TBI. To determine whether prolonged in situ exposure of vessels to the traumatized cerebral milieu could reveal an alteration in intrinsic contractility, posterior cerebral arteries were isolated 30 min after TBI; again, no differences in the tension or relaxation responses were observed. It is concluded that midline fluid percussion TBI did not affect contraction or relaxation of proximal middle or posterior cerebral arteries in rats.

Acetylcholine↗

PubMed1996

Hypertonic saline does not improve cerebral oxygen delivery after head injury and mild hemorrhage in cats.

OBJECTIVES: To investigate the effects of hypertonic saline for resuscitation after mild hemorrhagic hypotension combined with fluid-percussion traumatic brain injury. Specifically, the effects of hypertonic saline on intracranial pressure, cerebral blood flow (radioactive microsphere method), cerebral oxygen delivery (cerebral oxygen delivery = cerebral blood flow x arterial oxygen content), and electroencephalographic activity were studied. DESIGN: Randomized, controlled, intervention trial. SETTING: University laboratory. SUBJECTS: Thirty-four mongrel cats of either sex, anesthetized with 1.0% to 1.5% isoflurane in nitrous oxide/oxygen (70:30). INTERVENTIONS: Anesthetized (isoflurane) cats were prepared for traumatic brain injury, and then randomly assigned to the following groups: moderate traumatic brain injury only (2.7 +/- 0.2 atmospheres [atm], group 1); mild hemorrhage (18 mL/kg) only, followed immediately by resuscitation with 10% hydroxyethyl starch in 0.9% saline in a volume equal to shed blood (group 2); or both traumatic brain injury (2.7 +/- 0.1 atm) and mild hemorrhage, followed immediately by replacement of a volume equal to shed blood of 10% hydroxyethyl starch in 0.9% saline (group 3); or 3.0% saline (group 4). MEASUREMENTS AND MAIN RESULTS: Data were collected at baseline, at the end of hemorrhage, and at 0, 60, and 120 mins after resuscitation (or at comparable time points in group 1). Intracranial pressure in group 1 was significantly increased by traumatic brain injury at the end of hemorrhage, immediately after resuscitation, and 60 mins after resuscitation (p < .02 vs. baseline). In group 2, intracranial pressure increased significantly only immediately after resuscitation (p < .0001 vs. baseline). Groups 3 and 4 exhibited higher, although statistically insignificant, intracranial pressure increases at 60 and 120 mins after resuscitation. During resuscitation, cerebral blood flow increased significantly (p < .02 vs. baseline) in the uninjured cats. In contrast, cerebral blood flow failed to increase during resuscitation in the cats subjected to traumatic brain injury before hemorrhage and resuscitation. Although cerebral oxygen delivery in group 2 decreased significantly immediately, 60 mins, and 120 mins after resuscitation (p < .001 vs. baseline) both groups 3 and 4 had significantly lower cerebral oxygen delivery at 60 and 120 mins after resuscitation (p < .01 and p < .005, respectively, vs. group 1 at 60 mins after resuscitation, and p < .01 and p < .01, respectively, vs. group 1 at 120 mins after resuscitation). CONCLUSIONS: After a combination of hemorrhage and traumatic brain injury, neither 10% hydroxyethyl starch nor 3.0% hypertonic saline restored cerebral oxygen delivery. Although neither trauma alone nor hemorrhage alone altered electroencephalographic activity, the combination produced significant decreases in electroencephalographic activity at 60 and 120 mins after resuscitation in groups 3 and 4, suggesting that cerebral oxygen delivery is inadequately restored by either resuscitation fluid. Therefore, traumatic brain injury abolished compensatory cerebral blood flow increases to hemodilution, and neither hydroxyethyl starch nor 3.0% hypertonic saline restored cerebral blood flow, cerebral oxygen delivery, or electroencephalographic activity after hemorrhagic hypotension after traumatic brain injury.

Animals↗

PubMed1995

In vivo detection of superoxide anion production by the brain using a cytochrome c electrode.

A cytochrome c-coated platinized carbon electrode was utilized to detect superoxide generated by the brain during hypoxia/hypercarbia, focal ischemia, and reperfusion and following fluid percussion brain injury with and without hemorrhagic hypotension and reperfusion in the rat. All three of these forms of brain injury were associated with an increase in the superoxide signal. The cytochrome c electrode proved to be sensitive and responsive enough for minute-by-minute measurement of superoxide generation by brain tissue.

Animals↗

PubMed1995

Cerebral metabolic consequences of hypotensive challenges in hemodiluted pigs with and without cardiopulmonary bypass.

We tested the hypothesis that progressive aortic hypotension with bicarotid occlusion produces greater reductions in cerebral blood flow (CBF) and more flow-metabolism mismatching with hemodilution during cardiopulmonary bypass (CPB) than with hemodilution alone. In Yorkshire pigs randomized to hemodilution with CPB (n = 10) or hemodilution without CPB (control; n = 9), the effects of bicarotid ligation and graded hypotension on CBF (microspheres), the electroencephalogram (EEG), and cortical energy metabolites were examined. After bicarotid ligation, systemic flow was reduced for 15-min intervals of 80, 60, and 40 mm Hg aortic pressure, followed by a cortical brain biopsy. At baseline, CBF was lower in CPB (58 +/- 3 mL.100g-1.min-1) than control (90 +/- 3 mL.100 g-1.min-1., P < 0.05) animals, as was cerebral oxygen metabolism (3.1 +/- 0.1 vs 4.2 +/- 0.2 mL.min-1.100g-1; P < 0.05). Although CBF remained 40% lower at each level of hypotension in CPB than control animals (P < 0.05), EEG scores showed no intergroup differences, indicating similar flow-metabolism matching. Brain metabolites were similar between CPB and control groups (adenosine triphosphate, 9.6 +/- 2.4 vs 12.4 +/- 1.9 mumol/g; adenosine diphosphate, 6.0 +/- 0.7 vs 6.3 +/- 0.4 mumol/g; adenosine monophosphate, 4.8 +/- 0.9 vs 3.8 +/- 0.8 mumol/g; creatine phosphate, 8.3 +/- 1.8 vs 7.9 +/- 1.0 mumol/g; and lactate, 178.4 +/- 20.2 vs 150.8 +/- 13.9 mumol/g). Thus, despite significantly lower CBF during hypotension with bicarotid occlusion in hemodiluted animals during normothermic CPB, cortical electrical activity and the balance between flow and metabolism did not differ from those in control animals without CPB.

Adenine Nucleotides↗

PubMed1995

Enhanced vulnerability to secondary ischemic insults after experimental traumatic brain injury.

Both experimental traumatic brain injury and clinical traumatic brain injury appear to render the brain more vulnerable to a second ischemic insult. The mechanisms of enhanced vulnerability to subsequent ischemia appear to include a reduced ability to increase cerebral blood flow in response to hypotension, hypoxemia, or acute anemia and increased tissue sensitivity to ischemia. Although numerous mediators may be involved in increased tissue sensitivity, those that particularly merit investigation include oxygen free radicals, glutamate, arachidonate metabolites, calcium ions, and protein kinase C.

Animals↗

PubMed1994

Arterial microsphere concentrations in cats are not affected by changes in hematocrit.

BACKGROUND AND PURPOSE: Acute anemia may lead to erroneously low arterial reference sample concentrations of radioactive microspheres, depending on the sampling rate and the size of the artery from which the reference samples are withdrawn. Because this error would lead to falsely high cerebral blood flow values in studies involving hemodilution caused by hemorrhage and fluid resuscitation, we studied the effects of hematocrit, withdrawal rate, and vessel location and size on arterial microsphere concentrations in anesthetized adult cats. METHODS: Cats were anesthetized with ketamine, isoflurane, and nitrous oxide; both brachial arteries were cannulated with polyethylene tubing, as was the abdominal aorta through the femoral artery. Sequential left atrial microsphere injections were made using several doses of each of five isotopes. The rate of reference sample withdrawal from the three sampling catheters was randomized to 1.03 mL.min-1 or 2.06 mL.min-1. We analyzed the ratio of the number of microspheres in paired reference samples using the factors hematocrit, rate of withdrawal, and site. A ratio less than 1 indicates an underestimation of arterial microsphere concentration, which would lead to erroneously high cerebral blood flow values. The procedure was repeated after isovolemic hemodilution with 10% hetastarch to hemoglobin levels approximating 85%, 70%, 55%, and 40% of baseline. RESULTS: No significant effects of hematocrit on ratios of microsphere concentrations existed at any withdrawal rate or site. Ratios of microsphere concentrations in reference samples withdrawn slowly (1.03 mL.min-1) from the aorta and ratios of microsphere concentrations withdrawn either rapidly (2.06 mL.min-1) or slowly from the brachial arteries were significantly (P < .001) less than 1. CONCLUSIONS: Hemodilution did not affect microsphere concentrations in arterial reference samples at any withdrawal site or rate and therefore does not affect the accuracy of microsphere blood flow determinations. However, slow withdrawal from a large vessel may underestimate actual microsphere concentrations.

Animals↗

PubMed1994

Phenylephrine does not reduce cerebral perfusion during canine cardiopulmonary bypass.

Gaseous microemboli during cardiopulmonary bypass (CPB) could injure the blood-brain barrier so that cerebral vasoconstriction would result from infusing alpha-agonist drugs, such as phenylephrine. Cerebral blood flow (radioactive microspheres) and metabolism were measured in seven dogs after rewarming from 150 min hypothermic CPB with bubble oxygenators used to produce gaseous microemboli. Phenylephrine (40 micrograms/min) was infused directly into the brachiocephalic artery so that aortic pressure before (80 +/- 2 mm Hg) and during (79 +/- 3 mm Hg) the infusion did not change. Neither blood flow to the cerebral hemispheres (P = 0.960), cerebellum (P = 0.854), and brainstem (P = 0.694) nor the cerebral metabolic rate for oxygen (P = 0.862) differed when values obtained before and after 30 min of phenylephrine infusion were compared. Cerebral vascular resistance was also unchanged by phenylephrine, being 1.22 +/- 0.10 mm Hg.mL-1.min-1 x 100 g-1 before infusion and 1.25 +/- 0.17 mm Hg.mL-1.min-1 x 100 g-1 during infusion (P = 0.849). Phenylephrine does not cause cerebral vasoconstriction after rewarming from hypothermic CPB, a finding which suggests that the blood-brain barrier is preserved during bypass.

Animals↗

PubMed1993

Significance of gaseous microemboli in the cerebral circulation during cardiopulmonary bypass in dogs.

BACKGROUND: Gaseous microemboli during cardiac surgery may damage the brain by reducing cerebral blood flow (CBF). We examined whether the incidence of gaseous microemboli during 150-minute hypothermic (28 degrees C) cardiopulmonary bypass (CPB) adversely affects CBF (radioactive microspheres). METHODS AND RESULTS: Thirty anesthetized dogs were placed on CPB using bubble oxygenators with 50% O2 (n = 10) or 100% O2 (n = 10) to produce a wide range in the number of gaseous microemboli or membrane oxygenators with 50% O2 (n = 10) to avoid microemboli. The number of carotid artery microemboli occurring in a 1-minute interval was counted using a 5-MHz Doppler probe every 15 minutes for the duration of CPB, which lasted 258 +/- 5 minutes. With bubbled 100% O2, the number of microemboli averaged 4.1 +/- 1.7 emboli per minute on normothermic bypass and increased with cooling to 18.3 +/- 4.9 emboli per minute (P < .001). With bubbled 50% O2, the microemboli number was greater on normothermic bypass (19.8 +/- 9.8 emboli per minute, P = .0653 compared with bubbled 100% O2) and increased with cooling (100.3 +/- 18.7 emboli per minute, P < .001) to a greater extent than with bubbled 100% O2 (P < .001). In contrast, with membrane 50% O2, the emboli number was small (0.6 +/- 0.1 emboli per minute) and did not change with CPB temperature. CBF values were not reduced after termination of CPB, even when compared with prebypass values, being 48.3 +/- 7.5 mL/min per 100 g (bubbled 50% O2), 49.6 +/- 4.1 mL/min per 100 g (bubble 100% O2), and 44.5 +/- 2.8 mL/min per 100 g (membrane 50% O2, P = .7581). Similarly, regional perfusion to the cerebellum, hippocampus, and caudal brainstem was not adversely affected by microemboli. After CPB, cortical biopsies demonstrated no difference among groups with respect to lactate (P = .1753), energy charge (P = .5179), and brain water content (P = .939). Retinal histopathology indicated no differences among groups. CONCLUSIONS: These results indicate that: (1) the incidence of gaseous microemboli during hypothermia increases when a bubble oxygenator is used, and (2) global CBF and regional brain perfusion are not adversely affected by numerous gaseous microemboli.

Animals↗

PubMed1992

Enduring suppression of hippocampal long-term potentiation following traumatic brain injury in rat.

This study investigated changes in synaptic responses (population spike and population EPSP) of CA1 pyramidal cells of the rat hippocampus to stimulation of the Schaffer collateral/commissural pathways 2-3 h after traumatic brain injury (TBI). TBI was induced by a fluid percussion pulse delivered to the parietal epidural space resulting in loss of righting responses for 4.90-8.98 min. Prior to tetanic stimulation, changes observed after the injury included: (1) decreases in population spikes threshold but not EPSP thresholds; (2) decreases in maximal amplitude of population spikes as well as EPSPs. TBI also suppressed long-term potentiation (LTP), as evidenced by reductions in post-tetanic increases in population spikes as well as EPSPs. Since LTP may reflect processes involved in memory formation, the observed suppression of LTP may be an electrophysiological correlate of enduring memory deficits previously demonstrated in the same injury model.

Animals↗

PubMed1992

Regional cerebrovascular responses to progressive hypotension after traumatic brain injury in cats.

We investigated the effects of hypotension on cerebral blood flow (CBF) after traumatic brain injury (TBI) in cats. Isoflurane-anesthetized cats were prepared for TBI and for microsphere measurements of total (T) and regional (r) CBF. Four groups were studied: sham injury (group I, n = 6); TBI (group II, n = 6); isoflurane anesthesia, no TBI or hypotension (group III, n = 4); and isoflurane and TBI, no hypotension (group IV, n = 8). After TBI or sham trauma, mean arterial pressure (MAP) was reduced to 80, 60, and 40 mmHg by hemorrhage. Group I TCBF did not change significantly from baseline until MAP reached 40 mmHg, but rCBF was more dependent on MAP in anterior hemispheric than in brain stem regions. Group II TCBF was significantly lower than baseline, and group I TCBF at all levels of hypotension and autoregulation was impaired at higher MAP levels in anterior than in posterior brain regions. Groups III and IV indicated that decreases in TCBF were not due to duration of the preparation or to TBI in the absence of hemorrhagic hypotension. We conclude that global and regional autoregulation are absent in response to hemorrhagic hypotension after TBI.

Anesthesia↗

PubMed1992

Reduced cerebral blood flow, oxygen delivery, and electroencephalographic activity after traumatic brain injury and mild hemorrhage in cats.

The authors investigated the effects of transient, mild hemorrhagic hypotension after fluid-percussion traumatic brain injury on intracranial pressure, cerebral blood flow (CBF), cerebral oxygen delivery (CBF x arterial O2 content), and electroencephalographic (EEG) activity. Adult mongrel cats were anesthetized with 1.6% isoflurane in N2O:O2 (70:30) and prepared for trauma and for radioactive microsphere CBF measurement. Isoflurane concentration was decreased to 0.8%, and the cats were randomly assigned to one of four control groups or to an experimental group. Animals in the four control groups underwent either mild hemorrhage (18 ml.kg-1) immediately followed by resuscitation with equal volumes of 10% Hetastarch (eight cats), mild hemorrhage followed by replacement of shed blood (six cats), isovolemic hemodilution with 18 ml.kg-1 of Hetastarch (six cats), or moderate (2.2 atm) trauma alone (eight cats). The experimental group received a combination of trauma and mild hemorrhage followed by resuscitation with Hetastarch (eight cats). Mild hemorrhage produced no significant changes in CBF, renal blood flow, or cardiac output. Following resuscitation from mild hemorrhage, mean arterial blood pressure, cardiac output, renal blood flow, and CBF were not significantly different from baseline; cardiac output and renal blood flow did not differ significantly from baseline 2 hours after Hetastarch resuscitation. Neither hemorrhage nor trauma alone produced significant decreases in CBF or in EEG activity, but trauma followed by hemorrhage and resuscitation produced significant (p less than 0.01) decreases in CBF, cerebral oxygen delivery, and EEG score. These data demonstrate that, following traumatic brain injury, even mild hemorrhagic hypotension is associated with significant deficits in cerebral oxygen availability and neurological function.

Animals↗

PubMed1991

Cerebral perfusion during canine hypothermic cardiopulmonary bypass: effect of arterial carbon dioxide tension.

Cerebral blood flow (radioactive microspheres), intracranial pressure (subdural bolt), and retinal histopathology were examined in 20 dogs undergoing 150 minutes of hypothermic (28 degrees C) cardiopulmonary bypass to compare alpha-stat (arterial carbon dioxide tension, 40 +/- 1 mm Hg; n = 10) and pH-stat (arterial carbon dioxide tension, 61 +/- 1 mm Hg; n = 10) techniques of arterial carbon dioxide tension management. Pump flow (80 mL.kg-1.min-1), mean aortic pressure (78 +/- 2 mm Hg), and hemoglobin level (87 +/- 3 g/L [8.7 +/- 0.3 g/dL]) were maintained constant. During bypass, intracranial pressure progressively increased in the alpha-stat group from 6.0 +/- 1.0 to 13.9 +/- 1.8 mm Hg (p less than 0.05) and in the pH-stat group from 7.7 +/- 1.1 to 14.7 +/- 1.4 mm Hg (p less than 0.05), although there was no evidence of loss of intracranial compliance or intracranial edema formation as assessed by brain water content. With cooling, cerebral blood flow decreased by 56% to 62% in the alpha-stat group (p less than 0.05) and by 48% to 56% in the pH-stat group (p less than 0.05). However, 30 minutes after rewarming to 37 degrees C, cerebral blood flow in both groups failed to increase and remained significantly depressed compared with baseline values. Both groups showed similar amounts of ischemic retinal damage, with degeneration of bipolar cells found in the inner nuclear layer in 67% of animals. We conclude that, independent of the arterial carbon dioxide tension management technique, (1) cerebral perfusion decreased comparably during prolonged hypothermic bypass, (2) intracranial pressure increases progressively, (3) ischemic damage to retinal cells occurs despite maintenance of aortic pressure and flow, and (4) a significant reduction in cerebral perfusion persists after rewarming.

Animals↗

PubMed1991

Regional cerebral blood flow following resuscitation from hemorrhagic shock with hypertonic saline. Influence of a subdural mass.

After severe hemorrhage, hypertonic saline restores systemic hemodynamics and decreases intracranial pressure (ICP), but its effects on regional cerebral blood flow (rCBF) when used for resuscitation of experimental animals with combined shock and intracranial hypertension have not been reported. We compared rCBF changes (by radiolabeled microsphere technique) after resuscitation from hemorrhage with either 0.8 or 7.2% saline in animals with and without a right hemispheric subdural mass. We studied 24 mongrel dogs anesthetized with 0.5% halothane and 60% nitrous oxide. In group 1 (n = 12), hemorrhage reduced mean arterial pressure (MAP) to 45 mmHg for 30 min. In group 2 (n = 12), ICP was increased and maintained constant at 15 mmHg, whereas hemorrhage reduced MAP to 55 mmHg for 30 min (cerebral perfusion pressure [CPP] approximately 40 mmHg in each group). After the 30-min shock period, 6 animals in each group received one of two randomly assigned resuscitation fluids over a 5-min interval: 1) 7.2% hypertonic saline (HS; sodium 1,232 mEq.l-1, volume 6.0 ml.kg-1); or 2) 0.8% isotonic saline (SAL; sodium 137 mEq.l-1, volume 54 ml.kg-1). Once fluid resuscitation began, ICP was permitted to vary independently in both groups. Data were collected at baseline (before subdural balloon inflation in group 2), midway through the shock interval (T15), immediately after fluid infusion (T35), and 60 and 90 min later (T95, T155). In groups 1 and 2, ICP was significantly less in animals resuscitated with HS compared to those receiving SAL (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

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.

Animals↗

PubMed1991

Hemorrhage and intracranial hypertension in combination increase cerebral production of thromboxane A2.

BACKGROUND AND METHODS: To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period. RESULTS: Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2. CONCLUSIONS: Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock.

Animals↗

PubMed1991

Cerebrovascular effects of small volume resuscitation from hemorrhagic shock: comparison of hypertonic saline and concentrated hydroxyethyl starch in dogs.

To determine if hypertonic and hyperoncotic resuscitation solutions exerted comparable effects on cerebral hemodynamics following hemorrhagic shock, we compared randomly assigned, equal volumes (6.0 ml/kg) of hypertonic (7.2%) saline (HS) and hyperoncotic (20%) hydroxyethyl starch (HES) for resuscitation from acute experimental hemorrhage in 12 anesthetized dogs. Regional cerebral blood flow (radiolabeled microspheres), intracranial pressure (cisternal catheter), and systemic hemodynamics were recorded. Rapid hemorrhage reduced the mean arterial pressure to 45 mm Hg for 30 min. Resuscitation fluids were infused over 5 min. Both fluids restored mean arterial pressure and cardiac output equally. However, at 60 min following resuscitation, cardiac output decreased in the HS group in comparison to the HES group (1.7 +/- 0.1 vs. 3.1 +/- 0.2 L/min, p <0.05). Cardiac output rapidly declined, however, in the HS group in comparison to the HES group (p <0.05 60 min following resuscitation). Intracranial pressure and cerebral perfusion pressure were similar at all intervals. Regional cerebral blood flow was similar following both fluids. Neither fluid restored cerebral oxygen transport to baseline values. Based on these data, the authors conclude that, following severe hemorrhagic shock of brief duration, systemic and cerebral hemodynamic values are restored equally well by highly concentrated colloid or by hypertonic saline, although hypertonic saline only transiently improves cardiac output.

Journal Article↗

PubMed1991

Hypertonic/hyperoncotic fluid resuscitation after hemorrhagic shock in dogs.

We compared canine systemic and cerebral hemodynamics after resuscitation from hemorrhagic shock with 4 mL/kg (a volume approximating 12% of shed blood volume) of 7.2% saline (HS; 1233 mEq/L sodium), 20% hydroxyethyl starch (HES) in 0.8% saline, or a combination fluid consisting of 20% hydroxyethyl starch in 7.2% saline (HS/HES). Eighteen endotracheally intubated mongrel dogs (18-24 kg) were ventilated to maintain normocarbia with 0.5% halothane in nitrous oxide and oxygen (60:40). After a 30-min period of hemorrhagic shock (mean arterial blood pressure = 40 mm Hg), extending from time T0 to T30, animals received one of three randomly assigned intravenous resuscitation fluids: HS, HES, or HS/HES. Data were collected at baseline, at the beginning and end of the shock period (T0 and T30), immediately after fluid infusion (T35), and at 60-min intervals for 2 h (T95, T155). After resuscitation, mean arterial blood pressure and cardiac output increased similarly in all groups, but failed to return to baseline. Intracranial pressure decreased during shock and increased slightly, immediately after resuscitation in all groups. During shock, cerebral blood flow (cerebral venous outflow method) declined in all groups. After resuscitation, cerebral blood flow increased, exceeding baseline in the HS and HS/HES groups but remaining low in the HES group (P less than 0.05 HS vs HES at T35). We conclude that small-volume resuscitation (4 mL/kg) with HS, HS/HES, or HES does not effectively restore or sustain systemic hemodynamics in hemorrhaged dogs. In dogs without intracranial pathology, the effects on cerebral hemodynamics are also comparable, except for transiently greater cerebral blood flow in the HS group in comparison with the HES group.

Animals↗