Effect of Hetastarch, Mannitol, and Phenylephrine on Spinal Cord Blood Flow Following Experimental Spinal Injury

Abstract

Anesthetized lambs were subjected to epidural cord compression at T13 by means of an epidural balloon distended to 200 mmHg for 80 minutes. Determinations of spinal cord blood flow (SCBF) were made by labelled microspheres prior to and during compression, and then 1/2, 1 1/2, and 2 1/2 hours after compression. Twelve control animals received saline (80 ml/h). Nine animals received hetastarch (a 20 ml/kg bolus followed by an 80 ml/h infusion) and 8 animals received mannitol (a 1 g/kg bolus followed by 1 g/kg/hr). An additional 10 animals received phenylephrine to raise mean arterial pressure by 20 to 40%. Somatosensory evoked potentials (SEPs) were recorded following each determination of SCBF. Animals were killed following determination of the 2 1/2 hour postcompressive flow. The animals treated with either hetastarch or phenylephrine had a postcompressive mean arterial pressure that was significantly greater than that of the controls (P less than 0.01). During treatment, cardiac output in the hetastarch and mannitol animals was significantly greater and hematocrit significantly less than in the controls (P less than 0.05). In spite of these changes, postcompressive SCBF was significantly increased only in those animals treated with phenylephrine (P less than 0.05). Statistical analysis of the relationship between mean arterial pressure and postcompressive SCBF revealed that autoregulation is indeed lost with this experimental model of spinal cord injury. Histological examination of the injured site failed to demonstrate any difference in the area of hemorrhagic necrosis among the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Changes in Systemic Hemodynamics and Serum Vasopressin After Complete Cervical Spinal Cord Injury in Piglets

“…Our main findings were that complete cervical SCI caused an immediate tachycardia which lasted for approximately 1 h, immediate hypotension which was sustained for the 4-h duration of the study, decreases in both systemic and pulmonary vascular resistance, and a compensatory increase in cardiac output, which resulted initially from an increase in HR but was later sustained after resolution of tachycardia by an increase in cardiac stroke volume. These data are consistent with previously published findings in adult small and large animal models as well as in humans, which consistently demonstrate reductions in HR, MAP, and systemic vascular resistance over the first few hours and in clinical studies for up to 2 weeks after SCI [3][4][5][6][7][8][9][17][18][19][20][21][22][23]. Levi et al invasively measured hemodynamics beginning 11 ± 6 h after complete and incomplete cervical SCI in adults and found that 82% required vasopressors for an average of 5.7 days after injury to maintain MAP >90 mmHg [8].…”

“…* P < 0.05 for comparisons to baseline; # P < 0.05 for comparisons between groups much of which can be attributed to differences in anesthesia, characteristics of the SCI (level, severity, and mechanism) as well as species [25][26][27][28]. Studies employing anesthetics with cardiac depressant and vasodilatory effects, such as pentobarbital, halothane, and ether have reported lower cardiac output and blood pressure after SCI [22,23,25] compared to those using ketamine or chloralose [20,29]. The relatively mild hypotension seen in our study did not require treatment and may have been due, in part, to the use of fentanyl as the main anesthetic, which is devoid of effects on cardiac contractility and systemic vascular resistance [30].…”

“…Although our study is the first to examine hemodynamics after cervical SCI in an immature animal, Hitchon et al have performed a series of experiments in 3-monthold lambs weighing 20 ± 5 kg (approximately 1/3 of mature adult weight) in which they measured systemic hemodynamics and spinal cord blood flow following lower thoracic (T13) compressional SCI induced by inflating an epidural balloon for 40 (incomplete) or 80 (complete) min [22,23]. This injury mechanism differs from classical traumatic SCI in that blood flow falls to near zero during compression and is followed by hyperemia, suggestive more of an ischemic mechanism, whereas after traumatic contusional SCI hyperemia does not occur.…”

“…Experimental studies of the acute hemodynamic effects of SCI have been performed primarily in adult animal models [17][18][19][20][21][22][23]. These studies have demonstrated an immediate increase in blood pressure, heart rate (HR), and cardiac output usually lasting for 5-15 min, followed by prolonged periods of hypotension, bradycardia, escape rhythms, and variable changes in cardiac output.…”

Actual Aspects of Treatment Strategies in Spinal Cord Injury

“…The trauma-induced reduction of SCBF was attenuated in different animal models with various drugs including barbiturates [96], suloctidil [155], opiate antagonists such as naloxone [68,165], the calcium antagonist nimodipine [64,84], adrenoceptor agonists such as isoproterenol [45] and phenylephrine [47], as well as WEB 2170, a selective receptor antagonist of platelet-activating factor receptor [52] and MP [164].…”