Prejunctional control of pH 6-induced bronchoconstriction by NK1, NK2, mu-opioid, alpha2-adrenoceptor and glucocorticoid receptors in guinea-pig isolated perfused lung.

This study investigated the release of calcitonin-gene related peptide-like (CGRP) immunoreactivity and bronchoconstriction induced by pH 6 buffer in guinea-pig isolated perfused lung. Both pH 6-induced CGRP-like immunoreactivity and bronchoconstriction were completely abolished after systemic pretreatment with capsaicin. Pretreatment with the NK2 receptor antagonist SR 48968 (5 x 10(-7)M) completely inhibited bronchoconstriction and significantly reduced the immunoreactivity induced by the pH 6 buffer. The NK1 antagonist SR 140333 (5 x 10(-7)M) and, to a lesser extent the NK1 antagonist CP 96345, morphine (5 x 10(-6)M), the alpha2-adrenoceptor agonist UK 14304 (10(-7)M) and betamethasone (10(-6)M) significantly reduced both pH 6-induced bronchial response and CGRP-like immunoreactivity overflow. The effects of morphine and UK14304 were partially reversed by naloxone (5 x 10(-5)M) and idazoxan (5 x 10(-50M). Therefore, NK1, NK2, mu-opioid, alpha2-adrenoceptor and glucocorticoid receptors seemed to have a prejunctional action on pH 6 buffer-induced CGRP-like immunoreactivity and bronchoconstriction.

Cerebral arterial spasm after penetrating craniocerebral gunshot wounds: transcranial Doppler and cerebral blood flow findings.

OBJECTIVE: The goals of the study were to determine the incidence and time course of cerebral arterial spasm in patients with penetrating craniocerebral gunshot wounds, to study the relationship between vasospasm and subarachnoid hemorrhage (SAH) in these patients, and to evaluate the effects of vasospasm on outcome. METHODS: Thirty-three patients with craniocerebral gunshot wounds underwent computed tomography at admission and then underwent transcranial doppler ultrasonography (TCD). Velocities in the middle cerebral artery and the extracranial internal carotid artery were measured. Vasospasm was defined as a middle cerebral artery velocity greater than 120 cm per second and a hemispheric index (ratio of middle cerebral artery to internal carotid artery velocity) greater than 3. Intravenous xenon-133 cerebral blood flow (CBF) studies were performed for 10 patients. RESULTS: TCD was initiated, on average, 1.1 days after injury; 205 studies (mean, 6.3 studies/patient) were performed 0 to 33 days after injury. TCD showed vasospasm in 14 patients (42.4%). Xenon-133 studies performed within 24 hours of TCD measurements indicating spasm demonstrated normal or low CBF in three of five patients with spasm, ruling out hyperemia as the cause of elevated flow velocities in these three patients. Seven patients had unilateral vasospasm, and seven had bilateral spasm. Vasospasm was most prominent from Days 5 through 11. Vasospasm was distributed across all levels of injury severity, as defined by the Glasgow Coma Scale. Initial computed tomographic scans demonstrated SAH in all 14 patients with vasospasm but in only 9 of 19 without spasm (100 versus 47%, P < 0.0001, binomial distribution probability test). Outcomes for patients with vasospasm were slightly worse than for those without spasm (35.7 versus 47.4% good outcomes, respectively); however, this difference did not reach statistical significance (P = 0.12). CONCLUSION: These findings demonstrate that delayed cerebral arterial spasm is a frequent complication in patients with craniocerebral gunshot wounds and is strongly associated with SAH. The frequency, time course, and severity of spasm are comparable with those observed with aneurysmal SAH and traumatic SAH caused by closed head injury. This study offers new insights into the hemodynamic pathophysiology after gunshot wounds to the brain and suggests that increased vigilance for vasospasm may be of benefit.

Cerebral blood flow as a predictor of outcome following traumatic brain injury.

As part of a prospective study of the cerebrovascular effects of head injury, 54 moderate and severely injured patients underwent 184 133Xe-cerebral blood flow (CBF) studies to determine the relationship between the period of maximum blood flow and outcome. The lowest blood flows were observed on the day of injury (Day 0) and the highest CBFs were documented on postinjury Days 1 to 5. Patients were divided into three groups based on CBF values obtained during this period of maximum flow: Group 1 (seven patients), CBF less than 33 ml/100 g/minute on all determinations; Group 2 (13 patients), CBF both less than and greater than or equal to 33 ml/100 g/minute; and Group 3 (34 patients), CBF greater than or equal to 33 ml/100 g/minute on all measurements. For Groups 1, 2, and 3, mean CBF during Days 1 to 5 postinjury was 25.7 +/- 4, 36.5 +/- 4.2, and 49.4 +/- 9.3 ml/100 g/minute, respectively, and PaCO2 at the time of the CBF study was 31.4 +/- 6, 32.7 +/- 2.9, and 33.4 +/- 4.7 mm Hg, respectively. There were significant differences across Groups 1, 2, and 3 regarding mean age, percentage of individuals younger than 35 years of age (42.9%, 23.1%, and 76.5%, respectively), incidence of patients requiring evacuation of intradural hematomas (57.1%, 38.5%, and 17.6%, respectively) and incidence of abnormal pupils (57.1%, 61.5%, and 32.4%, respectively). Favorable neurological outcome at 6 months postinjury in Groups 1, 2, and 3 was 0%, 46.2%, and 58.8%, respectively (p < 0.05). Further analysis of patients in Group 3 revealed that of 14 with poor outcomes, six had one or more episodes of hyperemia-associated intracranial hypertension (simultaneous CBF > 55 ml/100 g/minute and ICP > 20 mm Hg). These six patients were unique in having the highest CBFs for postinjury Days 1 to 5 (mean 59.8 ml/100 g/minute) and the most severe degree of intracranial hypertension and reduced cerebral perfusion pressure (p < 0.0001). These results indicate that a phasic elevation in CBF acutely after head injury is a necessary condition for achieving functional recovery. It is postulated that for the majority of patients, this rise in blood flow results from an increase in metabolic demands in the setting of intact vasoreactivity. In a minority of individuals, however, the constellation of supranormal CBF, severe intracranial hypertension, and poor outcome indicates a state of grossly impaired vasoreactivity with uncoupling between blood flow and metabolism.

Hyperemia following traumatic brain injury: relationship to intracranial hypertension and outcome.

The role of posttraumatic hyperemia in the development of raised intracranial pressure (ICP) has important pathophysiological and therapeutic implications. To determine the relationship between hyperemia (cerebral blood flow (CBF) > 55 ml/100 g/minute), intracranial hypertension (ICP > 20 mm Hg), and neurological outcome, 193 simultaneous measurements of ICP and CBF (xenon-133 method) were obtained in 59 patients with moderate and severe head injury. Hyperemia was associated with an increased incidence of simultaneous intracranial hypertension compared to nonhyperemic CBF measurements (32.2% vs. 21.6%, respectively; p < 0.059). However, in 78% of blood flow studies in which ICP was greater than 20 mm Hg, CBF was less than or equal to 55 ml/100 g/minute. At least one episode of hyperemia was documented in 34% of patients, all of whom had a Glasgow Coma Scale (GCS) score of 9 or below. In 12 individuals with hyperemia without simultaneous intracranial hypertension, ICP was greater than 20 mm Hg for an average of 11 +/- 16 hours and favorable outcomes were seen in 75% of patients. In contrast, in eight individuals with hyperemia and at least one episode of hyperemia-associated intracranial hypertension, ICP was greater than 20 mm Hg for an average of 148 +/- 84 hours (p < 0.001), and a favorable outcome was seen in only one patient (p < 0.001). Compared to the remainder of the cohort, patients with hyperemia-associated intracranial hypertension were distinctive in being the youngest, exhibiting the lowest GCS scores (all < or = 6), and having the highest incidence of effaced basilar cisterns and intractable intracranial hypertension. In the majority of individuals with hyperemia-associated intracranial hypertension, their clinical profile suggests the occurrence of a severe initial insult with resultant gross impairment of metabolic vasoreactivity and pressure autoregulation. In a minority of these patients, however, high CBF may be coupled to a hypermetabolic state, given their responsiveness to metabolic suppressive therapy. In patients with hyperemia but without intracranial hypertension, elevated CBF is also likely to be a manifestation of appropriate coupling to increased metabolic demand consistent with a generally favorable outcome. This study supports the concept that there are multiple etiologies of both elevated blood flow and intracranial hypertension after head injury.

Cerebral hemodynamic disturbances following penetrating craniocerebral injury and their influence on outcome.

Available data on the subject of cerebrovascular dynamics after penetrating craniocerebral injury and their effect on outcome were reviewed. Following penetrating injury, CBF is depressed, as is cerebral metabolism. This decreased flow likely is associated with poor outcome as previously shown in closed head injuries. A phenomenon interrelated with a decreased blood flow is posttraumatic vasospasm. Vasospasm occurs in a significant percentage of patients as demonstrated both by TCD and angiography, and there is a strong relationship with SAH. Vasospasm following penetrating injury has an onset and time course similar to that seen in both closed head injury and aneurysmal SAH. Vasospasm following penetrating craniocerebral injury may be a cause of secondary ischemic injury, but further study is needed before the prognostic significance of this phenomenon is defined. For now, drawing a parallel with closed head injury and aneurysmal SAH, it can be inferred that vasospasm following cranial gunshot wound may be an important pathophysiologic factor. Because interventions are available to combat vasospasm, including medications (e.g., nimodipine), volume expansion, and elevation of blood pressure, the authors believe that identification and treatment of this potentially damaging condition are compelling, especially in patients whose CT scans demonstrate SAH.