Microvascular dysfunction after myocardial ischemia.

Endothelium-mediated relaxation and smooth muscle function in large coronary arteries are resistant to prolonged global ischemia. We used a small-vessel myograph to test the hypothesis that small intramyocardial artery endothelium and smooth muscle function have greater sensitivity to ischemic injury than large artery endothelium and smooth muscle. Normothermic global ischemia was induced in 15 porcine hearts. Intramyocardial arterial ring segments were assessed at 0, 30, 60, 90, and 120 minutes of ischemia in vitro with a small-vessel myograph. Potassium determined smooth muscle contraction, bradykinin endothelium-mediated relaxation, and sodium nitroprusside direct smooth muscle relaxation. Endothelium-mediated relaxation after 30 minutes of ischemia was similar to control (56% versus 66%) but was impaired at 60, 90, and 120 minutes of ischemia (32%, 11%, and 6%). Smooth muscle contraction was unchanged at 30 and 60 minutes compared with control (56 and 53 versus 63 mm Hg) but was significantly decreased at 90 and 120 minutes (33 and 13 mm Hg). Direct smooth muscle relaxation was significantly decreased at 120 minutes of ischemia compared with control (58% versus 95%). In a previous study, epicardial coronary artery endothelium-mediated smooth muscle vasodilation and direct smooth muscle vasodilation were preserved until 160 minutes of ischemia. After 160 minutes of ischemia, endothelium-mediated relaxation was lost and only direct smooth muscle vasodilation was preserved. In contrast to vasodilation, vasoconstriction was significantly reduced at 140 minutes of ischemia. These data indicate a greater and earlier adverse effect of ischemia on intramyocardial arterial endothelium-mediated relaxation than smooth muscle contraction or relaxation. These data support the hypothesis that there is an early functional endothelial cell injury associated with global ischemia. Relaxation that is endothelium-dependent in intramyocardial arteries is more sensitive to ischemic injury than in epicardial arteries. Unique to this study was the evaluation of small intramyocardial arteries (281 +/- 29 microns) that are the primary sites of coronary vascular resistance. Microvascular endothelial dysfunction after ischemia, therefore, may contribute to the "no-reflow phenomenon" seen during reperfusion injury.

The influence of age and sex on human internal mammary artery size and reactivity.

Internal mammary arteries (IMAs) from women and the elderly have been postulated to be smaller and more reactive than IMAs from men and younger patients and, therefore, not as reliable for coronary artery bypass grafting in the short term. This study tests the physiologic basis for that hypothesis. Trimmed IMA segments were obtained from patients aged 50 to 76 years at coronary artery bypass grafting. Eighteen ring segments from 12 women and 35 ring segments from 17 men were mounted on a strain-gauge apparatus, and internal diameter at a transmural pressure of 100 mm Hg was determined from length-tension curves. Contractions to potassium chloride and a dose-response curve to norepinephrine or serotonin were obtained to simulate physiologic vasospasm. Sodium nitroprusside determined arterial relaxation. Linear regression was used to determine correlation of these parameters with age. Internal mammary arteries from women and men were of equal size. They had equal strength of contraction to potassium chloride and norepinephrine, but female IMAs had greater strength of contraction to serotonin. Female IMAs had weaker contraction to norepinephrine as a percent of maximum contraction to potassium chloride than IMAs from men. Internal mammary arteries from women had equal relaxation to sodium nitroprusside compared with IMAs from men. There was no correlation between age and arterial reactivity to vasoconstrictors, relaxation to sodium nitroprusside, or size. These data suggest that IMAs from women and the elderly are not more susceptible to reduction in flow due to smaller size. Postoperatively, it may be important that women be kept on platelet inhibitors because of their greater absolute contraction to serotonin and men on nitrovasodilators because of their greater relative contraction to norepinephrine.

Coronary artery endothelial cell and smooth muscle dysfunction after global myocardial ischemia.

We hypothesized that coronary artery endothelial cell function and smooth muscle function are modified by global myocardial ischemia and used bradykinin-induced secretion of endothelium-derived relaxing factor as a marker of endothelial cell function. Bradykinin and sodium nitroprusside together determined maximum smooth muscle relaxation. Potassium chloride-induced contraction determined smooth muscle contractility. Endothelium-mediated smooth muscle relaxation expressed as a ratio of total coronary smooth muscle relaxation before and after ischemia quantified endothelial cell function. The effect of global normothermic ischemia on in situ coronary arteries from 7 swine hearts was studied. Coronary arterial rings taken from 0 to 220 minutes of ischemia at 20-minute intervals were studied in vitro. The data revealed unexpected tolerance of endothelium-mediated relaxation to ischemia. Endothelium-derived relaxing factor function was maintained to 160 minutes and smooth muscle function, to 120 minutes of ischemia. Coronary artery dysfunction seen in other studies after less ischemia may be the result of injury introduced during reperfusion, may be the consequence of myocardial injury, or may be due to events operative at the level of small arterioles.

Reactivity of gastroepiploic and internal mammary arteries. Relevance to coronary artery bypass grafting.

The gastroepiploic artery is an alternate conduit for coronary artery bypass grafting. To test the hypothesis that its vasoreactive properties are different from those of the internal mammary artery, we obtained gastroepiploic artery segments from human gastrectomy specimens. Trimmed internal mammary artery segments were obtained during coronary artery bypass. Ring segments were mounted on a strain gauge and stretched to optimum resting length (90% of the internal circumference at 100 mm Hg). Potassium chloride, serotonin, and norepinephrine were chosen to simulate physiologic vasospasm induced by depolarization, platelet aggregation, or adrenergic stimulation, respectively. Contractions to potassium and a concentration-response curve to serotonin or norepinephrine were obtained. Sodium nitroprusside was used to assess relaxation. Gastroepiploic artery segments had stronger contractions to the depolarizing agent (potassium chloride), adrenergic stimulation (norepinephrine), and product of platelet aggregation (serotonin). The gastroepiploic and internal mammary arteries showed equal sensitivity, measured by concentration causing half-maximal contraction to norepinephrine and serotonin. There was no difference in relaxation to sodium nitroprusside. These data suggest that prevention of platelet-, adrenergic-, or potassium-induced contraction may be more important when the gastroepiploic artery is used as an alternate conduit for coronary artery bypass, reinforcing consideration of nitrovasodilators and platelet inhibitors in the perioperative interval.

Spectral analysis of the EEG in craniocerebral trauma.

The objectives of the present study were to evaluate the relationship between the fractional amplitudes of the EEG derived from power spectral analysis (PSA) of the electroencephalogram (EEG) and depth of coma measured clinically with the Glasgow Coma Score, and to assess the accuracy of PSA in predicting long-term outcome. Thirty-two patients rendered unconscious by blunt head injury (mean (GCS = 7) had intermittent EEG recordings daily from 1-10 days post injury. There was a significant correlation between fractional amplitude of the EEG and the GCS. The rate and magnitude of change in the EEG and GCS were also correlated. There were significant differences in PSA parameters between improved and deteriorated patient groups at the termination of monitoring (p = .02) and in the change of PSA parameters over time (p = .02). Using linear discriminant analysis of PSA parameters, the accuracy of outcome prognostication based on the six month outcome was approximately 75%. Accurate classification of outcome was possible in a number of patients in whom there was little or no change in the GCS during the period of monitoring.

Pressure-volume index in head injury.

The authors studied intracranial pressure (ICP) and intracranial compliance as defined by the pressure-volume index (PVI) in 34 severely head-injured patients with a Glasgow Coma Scale score of 8 or less. The objective of the research was to determine if there was a correlation between the pressure-volume status and subsequent increase in ICP. The PVI and ICP measurements were obtained serially, and the temporal course of the pressure-volume status and ICP was determined during the 5-day period following injury. Aggressiveness of ICP was quantified by a therapy intensity level scale. A clear relationship between the PVI measured soon after injury and subsequent development of ICP emerged. Following mechanical trauma the PVI is reduced, and the degree of reduction and extent of biomechanical recovery are closely related to outcome and development of raised ICP.

Contribution of CSF and vascular factors to elevation of ICP in severely head-injured patients.

The authors studied the relative contribution of cerebrospinal fluid (CSF) and vascular parameters to the level of intracranial pressure (ICP) in 34 severely head-injured patients with a Glasgow Coma Scale score of less than 8. This was accomplished by first characterizing the temporal course of CSF formation and outflow resistance during the 5-day period postinjury. The CSF formation and outflow resistance were obtained from pressure responses to bolus addition and removal of fluid from an indwelling ventricular catheter. The vascular contribution to the level of ICP was assessed by withdrawing fluid at its rate of formation and observing the resultant change in equilibrium ICP level. It was found that, with the exception of patients with subarachnoid hemorrhage, CSF parameters accounted for approximately one-third of the ICP rise after severe head injury, and that a vascular mechanism may be the predominant factor in elevation of ICP.

Effect of mannitol on ICP and CBF and correlation with pressure autoregulation in severely head-injured patients.

In a previous paper, the authors showed that mannitol causes cerebral vasoconstriction in response to blood viscosity decreases in cats. The present paper describes the changes in intracranial pressure (ICP) and cerebral blood flow (CBF) after mannitol administration in a group of severely head-injured patients with intact or defective autoregulation. The xenon-133 inhalation method was used to measure CBF. Autoregulation was tested by slowly increasing or decreasing the blood pressure by 30% and measuring CBF again. Mannitol was administered intravenously in a dose of 0.66 gm/kg; 25 minutes later, CBF and ICP were measured once again. In the group with intact autoregulation, mannitol had decreased ICP by 27.2%, but CBF remained unchanged. In the group with defective autoregulation, ICP had decreased by only 4.7%, but CBF increased 17.9%. One of the possible explanations for these findings is based on strong indications that autoregulation is mediated through alterations in the level of adenosine in response to oxygen availability changes in cerebral tissue. The decrease in blood viscosity after mannitol administration leads to an improved oxygen transport to the brain. When autoregulation is intact, more oxygen leads to decreased adenosine levels, resulting in vasoconstriction. The decrease in resistance to flow from the decreased blood viscosity is balanced by increased resistance from vasoconstriction, so that CBF remains the same. This might be called blood viscosity autoregulation of CBF, analogous to pressure autoregulation. Vasoconstriction also reduces cerebral blood volume, which enhances the effect of mannitol on ICP through dehydration of the brain. When autoregulation is not intact there is no vasoconstriction in response to increased oxygen availability; thus, CBF increases with decreased viscosity. With the lack of vasoconstriction, the effect on ICP through dehydration is not enhanced, so that the resulting decrease in ICP is much smaller. Such a mechanism explains why osmotic agents do not change CBF but decrease ICP in normal animals or patients with intact vasoconstriction, but do (temporarily) increase CBF in the absence of major ICP changes after stroke.

Improved confidence of outcome prediction in severe head injury. A comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure.

An analysis of clinical signs, singly or in combination, multimodality evoked potentials (MEP's), computerized tomography scans, and intracranial pressure (ICP) data was undertaken prospectively in 133 severely head-injured patients to ascertain the accuracy, reliability, and relative value of these indicants individually, or in various combinations, in predicting one of two categories of outcome. Erroneous predictions, either falsely optimistic (FO) or falsely pessimistic (FP), were analyzed to gain pathophysiological insights into the disease process. Falsely optimistic predictions occurred because of unpredictable complications, whereas FP predictions were due to intrinsic weakness of the indicants as prognosticators. A combination of clinical data, including age, Glasgow Coma Scale (GCS) score, pupillary response, presence of surgical mass lesions, extraocular motility, and motor posturing predicted outcome with 82% accuracy, 43% with over 90% confidence. Nine percent of predictions were FO and 9% FP. The GCS score alone was accurate in 80% of predictions, but at a lower level of confidence (25% at the over-90% level), with 7% FO and 13% FP. Computerized tomography and ICP data in isolation proved to be poor prognostic indicants. When combined individually with clinical data, however, they increased the number of predictions made with over 90% confidence to 52% and 55%, respectively. Data from MEP's represented the most accurate single prognostic indicant, with 91% correct predictions, 25% at the over-90% confidence level. There were no FP errors associated with this indicant. Supplementation of the clinical examination with MEP data yielded optimal prognostic power, an 89% accuracy rate, with 64% over the 90% confidence level and only 4% FP errors. The clinical examination remains the strongest basis for prognosticating outcome in severe head injury, but additional studies enhance the reliability of such predictions.

Further experience in the management of severe head injury.

A prospective and consecutive series of 225 patients with severe head injuries who were managed in a uniform way was analyzed to relate outcome to several clinical variables. Good recovery or moderate disability were achieved by 56% of the patients, 10% remained severely disabled or vegetative, and 34% died. Factors important in predicting a poor outcome included the presence of intracranial hematoma, increasing age, abnormal motor responses, impaired or absent eye movements or pupil light reflexes, early hypotension, hypoxemia or hypercarbia, and elevation of intracranial pressure over 20 mm Hg despite artificial ventilation. Most of these predictive factors were assessed on admission, but a subset of 158 patients was identified in whom coma was present on admission and was known to have persisted at least until the following day. Although the mortality in this subset (40%) was higher than in the total series, it was lower than in several comparable reported series of patients with severe head injury. Predictive correlations were equally strong in the entire series and in the subset of 158 patients with coma. A plea is made for inclusion in the definition of "severe head injury" of all patients who do not obey commands or utter recognizable words on admission to the hospital after early resuscitation.