Effect of the no-flow interval and hypothermia on cerebral blood flow and metabolism during cardiopulmonary resuscitation in dogs

BACKGROUND and PURPOSE: We sought (1) to determine the effect of brief periods of no flow on the subsequent forebrain blood flow during cardiopulmonary resuscitation (CPR) and (2) to test the hypothesis that hypothermia prevents the impact of the no-flow duration on cerebral blood flow (CBF) during CPR. METHODS: No-flow intervals of 1.5, 3, and 6 minutes before CPR at brain temperatures of 28 degreesC and 38 degreesC were compared in 6 groups of anesthetized dogs. Microsphere-determined CBF and metabolism were measured before and during vest CPR adjusted to maintain cerebral perfusion pressure at 25 mm Hg. RESULTS: Increasing the no-flow interval from 1.5 to 6 minutes at 38 degreesC decreased the CBF (18. 6+/-3.6 to 6.1+/-1.7 mL/100 g per minute) and the cerebral metabolic rate (2.1+/-0.3 to 0.7+/-0.2 mL/100 g per minute) during CPR. Cooling to 28 degreesC before and during the arrest eliminated the detrimental effects of increasing the no-flow interval on CBF (16. 8+/-1.0 to 14.8+/-1.9 mL/100 g per minute) and cerebral metabolic rate (1.1+/-0.1 to 1.3+/-0.1 mL/100 g per minute). Unlike the forebrain, 6 minutes of preceding cardiac arrest did not affect brain stem blood flow during CPR. CONCLUSIONS: Increasing the no-flow interval to 6 minutes in normothermic animals decreases the supratentorial blood flow and cerebral metabolic rate during CPR at a cerebral perfusion pressure of 25 mm Hg. Cooling to 28 degreesC eliminates the detrimental impact of the 6-minute no-flow interval on the reflow produced during CPR. The brain-protective effects of hypothermia include improving reflow during CPR after cardiac arrest. The effect of hypothermia and the impact of short durations of no flow on reperfusion indicate that increasing viscosity and reflex vasoconstriction are unlikely causes of the "no-reflow" phenomenon.     

Carotid artery balloon test occlusion: combined clinical evaluation and xenon-enhanced computed tomographic cerebral blood flow evaluation without patient transfer or balloon reinflation: technical note

OBJECTIVE: Clinical evaluation was combined with xenon-enhanced computed tomographic (CT) cerebral blood flow (CBF) evaluation during carotid artery balloon test occlusion (BTO), without patient transfer from the angiography suite to the CT scanner or balloon reinflation. TECHNIQUE: Thirteen patients underwent carotid artery BTO. Placement of temporary occlusion balloons was performed with patients positioned on the CT scanner table. If neurological testing revealed no changes within 10 minutes after balloon inflation, patients were positioned within the CT scanner gantry for xenon-enhanced CT CBF evaluation. CBF evaluations were begun 12 to 15 minutes after balloon inflation and required 8 minutes for completion. After completion of CBF evaluation, neurological testing continued during 30 minutes of arterial occlusion. RESULTS: One patient did not tolerate BTO, with the development of reversible hemiparesis. Reliable CBF data were not obtained because of patient motion in one case. Eleven patients clinically tolerated BTO and completed CBF evaluation. For five patients, xenon-enhanced CT scanning revealed no regions with CBF of less than 30 ml/100 g/min. For four patients, xenon-enhanced CT scanning revealed small regions with CBF of less than 30 ml/100 g/min within the anterior frontal lobe on the occluded side. For two patients, ipsilateral CBF decreased dramatically during BTO, with CBF in many regions of less than 30 ml/100 g/min and in some of less than 20 ml/100 g/min. CONCLUSION: Xenon-enhanced CT CBF evaluation can be combined with clinical testing during BTO without patient transfer, balloon reinflation, or increases in the duration of the procedure. We recognize that the value of CBF evaluation during BTO remains to be proven; our technique does, however, eliminate abbreviated clinical neurological evaluation, patient transfer, and balloon reinflation, which were previously associated with the use of xenon-enhanced CT CBF evaluation during carotid artery BTO.     

Preconditioning improves myocardial function and reflow, but not vasodilator reactivity, after ischaemia and reperfusion in anaesthetized dogs

1. The present study examines whether three cycles of brief coronary artery occlusion and reperfusion (i.e. ischaemic preconditioning; PC) can prevent vasodilator dysfunction and the impairment of myocardial reflow caused by prolonged ischaemia. Coronary blood flow, left ventricular dP/dt, systemic arterial blood pressure and heart rate were measured in open-chest anaesthetized dogs. 2. Sixty minute occlusion of the left circumflex coronary artery (LCx) and 60 min LCx reperfusion (ISC/REP; group 1) significantly reduced resting coronary blood flow (CBF, initial 29 +/- 3 mL/min; ISC/REP 20 +/- 3 mL/min, P < 0.05 vs initial) and increased coronary vascular resistance (CVR, initial 4.1 +/- 0.6 mmHg/min per mL; ISC/REP 5.8 +/- 1.0 mmHg/min per mL, P < 0.05 vs initial). By contrast CBF and CVR were not affected in dogs subjected to preconditioning before ischaemia (group 2: CBF, initial 24 +/- 4 mL/min; PC+ISC/REP 23 +/- 4 mL/min; CVR, initial 4.7 +/- 0.6 mmHg/min per mL; PC+ ISC/REP 5.3 +/- 1.0 mmHg/min per mL). These data suggest that ischaemic preconditioning prevents the ischaemia-induced impairment of myocardial reflow. 3. Ischaemia and reperfusion impaired coronary dilator responses to the endothelium-dependent dilator acetylcholine (delta CBF, after ISC/REP: 50 +/- 6% of initial) and the endothelium-independent dilator glyceryl trinitrate (delta CBF, ISC/REP: 46 +/- 6% of initial). Despite the improvement in reperfusion in the preconditioned group, there was no significant improvement in responses to acetylcholine (PC+ISC/REP 52 +/- 6% of initial) or glyceryl trinitrate (PC+ISC/REP 59 +/- 6% of initial) after ischaemia and reperfusion. 4. The reduction in left ventricular dP/dt after ischaemia and reperfusion was significantly smaller in the preconditioned group indicating a lower level of impairment of cardiac contractility. In addition, we confirmed that preconditioning caused a significant reduction in infarct size and a reduction in the release of lactate dehydrogenase indicating less cardiac injury. 5. These results suggest that although ischaemic preconditioning was able to improve both myocardial reperfusion and contractility, it was not able to preserve vasodilator function. Such a reduction in vasodilator reserve could prevent adequate myocardial perfusion under conditions of elevated oxygen demand.     

In vivo uptake of [3H]nimodipine in focal cerebral ischemia: modulation by hyperglycemia

Cell membrane depolarization and tissue acidosis occur rapidly in severely ischemic brain. Preischemic hyperglycemia is recognized to increase ischemic tissue acidosis and the present studies were undertaken to correlate depolarization and tissue acidosis during acute focal cerebral ischemia and hyperglycemia. We used a dual-label autoradiography method to simultaneously measure the in vivo distribution of [3H]nimodipine and [14C]DMO (5,5-dimethyl-2,4-oxazolidinedione) in brain to identify regions of ischemic depolarization and measure regional net tissue pH. Regional cerebral blood flow (CBF) was measured in separate studies. Measurements were made 30 minutes after combined middle cerebral artery and ipsilateral common carotid artery occlusion in normoglycemic and hyperglycemic rats. Tissue pH in the ischemic cortex was depressed to 6.76 +/- 0.11 in normoglycemic rats (n = 12) and 6.57 +/- 0.13 in hyperglycemic rats (n = 12), with significantly greater acidosis in the hyperglycemic group (P < 0.001). In contrast the ratio of [3H]nimodipine uptake in the ischemic cortex relative to the contralateral nonischemic cortex was significantly greater in normoglycemic (1.83 +/- 0.45) than hyperglycemic (1.40 +/- 0.50) rats (P < 0.05). Within this region of ischemic cortex CBF was 31 +/- 22 mL/100 g in normoglycemic rats (n = 8) and 33 +/- 22 mL/100 g/min in hyperglycemic rats (n = 9). Cerebral blood flow did not differ between these two groups in any region. Thus hyperglycemia reduced the extent of ischemic depolarization within the cortex during the first 30 minutes of focal cerebral ischemia. This effect may be related to the increased tissue acidosis or to other factors that may lessen calcium influx and preserve cellular energy stores in the ischemic cortex of the hyperglycemic rats.     

Cerebral blood flow response pattern during balloon test occlusion of the internal carotid artery

PURPOSE: To evaluate the risk of temporary or permanent internal carotid artery occlusion. METHODS: In 156 patients intraarterial balloon test occlusion in combination with a stable xenon-enhanced CT cerebral blood flow study was performed before radiologic or surgical treatment. All 156 patients passed the clinical balloon test occlusion and underwent a xenon study in combination with a second balloon test. Quantitative flow data were analyzed for absolute changes as well as changes in symmetry. RESULTS: Fourteen patients exhibited reduced flow values between 20 and 30 mL/100 g per minute, an absolute decrease in flow, and significant asymmetry in the middle cerebral artery territory during balloon test occlusion. These patients would be considered at high risk for cerebral infarction if internal carotid artery occlusion were to be performed. With one exception they belonged to a group (class I) of 61 patients who showed bilateral or ipsilateral flow decrease and significant asymmetry with lower flow on the side of occlusion. The other 95 patients, who showed a variety of cerebral blood flow response patterns including ipsilateral or bilateral flow increase, were at moderate (class II) or low (class III) stroke risk. In contrast to these findings, exclusively qualitative flow analysis failed to identify the patients at high risk: a threshold with an asymmetry index of 10% revealed only 16% specificity whereas an asymmetry index of 45% showed only 61% sensitivity for detection of low flow areas (< 30 mL/100 g per minute). CONCLUSION: For achieving a minimal hemodynamic related-stroke rate associated with permanent clinical internal carotid artery occlusion we suggest integration of a thorough analysis of quantitative cerebral blood flow data before and during balloon test occlusion.     

Subcortical hypoperfusion associated with asymptomatic white matter lesions on magnetic resonance imaging

BACKGROUND AND PURPOSE: We examined whether hemodynamic and metabolic abnormalities in the cerebral white matter, basal ganglia, and thalamus are associated with asymptomatic white matter lesions (WML) depicted on MR images. METHODS: A positron emission tomographic study with H2(15)O, C15O, and 15O2 was performed in eight normal control subjects without any WML (mean +/- 1 SD age, 68.5 +/- 10.2 years) and in 15 asymptomatic subjects with WML (71.3 +/- 8.5 years) to measure regional cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and oxygen metabolic rate. RESULTS: In the cerebral white matter in the asymptomatic subjects with WML, significantly lower CBF (20.3 +/- 3.9 mL/100 mL per minute; P < .05) and significantly higher OEF (0.43 +/- 0.08; P < .05) were found compared with those for control subjects (23.5 +/- 2.6 mL/100 mL per minute and 0.37 +/- 0.06, respectively). The severity of WML was not related to the magnitude of hypoperfusion. In the basal ganglia, significantly lower CBF (44.9 +/- 6.9 mL/100 mL per minute; P < .01) and significantly higher OEF (0.54 +/- 0.08; P < .01) were found in the WML group than in control subjects (70.1 +/- 12.0 mL/100 mL/min and 0.39 +/- 0.03, respectively). In the thalamus, there was no significant difference in CBF and OEF between the control and WML groups. CONCLUSIONS: Hypoperfusion of the cerebral white matter and basal ganglia in asymptomatic WML subjects may be induced by the arteriosclerosis of long penetrating medullary arteries and lenticulostriate arteries but may not be directly related to the production of WML. The role of hypoperfusion in the production of WML and acceleration of its development remains to be elucidated.     

Activation-induced resetting of cerebral oxygen and glucose uptake in the rat

In the clinical setting it has been shown that activation will increase cerebral glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon further, this study presents an experimental setup that enables precise determination of the ratio between cerebral uptake of glucose and oxygen in the awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio between cerebral uptake rates for oxygen, glucose, and lactate was calculated from cerebral arterial-venous differences. During baseline conditions, rats were kept in a closed box designed to minimize interference. During baseline conditions CBF was 1.08 +/- 0.25 mL x g(-1) x minute(-1), and the cerebral oxygen to glucose uptake ratio was 5.5. Activation was induced by opening the sheltering box for 6 minutes. Activation increased CBF to 1.81 mL x g(-1) x minute(-1). During activation cerebral glucose uptake increased disproportionately to cerebral oxygen uptake, and the cerebral oxygen to glucose uptake ratio was 4.2. The accumulated excess glucose uptake during 6 minutes of activation amounted to 2.4 micromol/g. Activation was terminated by closure of the sheltering box. In the postactivation period, the cerebral oxygen to glucose uptake ratio rose to a maximum of 6.4. This response is exactly opposite to the excess cerebral glucose uptake observed during activation.     

Spatial stability of extracellular potassium ion and blood flow distribution in rat cerebral cortex after permanent middle cerebral artery occlusion

Extracellular potassium ion activity ([K+]o) increases precipitously during brain ischemia when blood flow falls below threshold values less than approximately 15 mL/100 g/min. This flow threshold for increase of [K+]o occurs also in focal ischemia producing gradient from ischemic core to adjacent normally perfused brain. In this study we investigated the spatial and temporal stability of extracellular potassium ion and blood flow gradients after permanent middle cerebral artery occlusion (MCAO) in rats. [K+]o and regional CBF were measured, respectively, with K+-sensitive and polarographic hydrogen-sensitive microelectrodes at different cortical locations in the middle cerebral artery distribution region. Spatial assessment of [K+]o and regional CBF was conducted at 30, 90, and 180 minutes after MCAO. [K+]o in the more lateral cortex (core) increased from near 3 mmol/L before MCAO to greater than 50 mmol/L and was associated with flow values less than 25% of pre-ischemic levels. Measurements medial to the core (penumbra) indicated progressively decreasing levels of [K+]o and improvement of CBF. There was a tendency for [K+]o in penumbral zones to decrease toward normal levels with time, but there was little dissipation of [K+]o in core regions. In contrast, the spatial CBF profile remained remarkably constant for the entire recording period. Thus, unlike infarction which has been reported to expand with time after focal ischemia, the spatial [K+]o disturbance tends to contract primarily due to decreasing [K+]o with time in the penumbra. Thus, steady state levels of [K+]o after focal ischemia may not be a valuable predictor of cell viability.     

Reduction of infarct volume by halothane: effect on cerebral blood flow or perifocal spreading depression-like depolarizations

Halothane is a strong inhibitor of potassium evoked spreading depression (SD) in cats. In the current study, we investigate halothane effects on induction of perifocal SD-like depolarizations, CBF, and infarct evolution in focal ischemia. Calomel and platinum electrodes measured cortical direct current potential and CBF in ectosylvian, suprasylvian, and marginal gyri. Left middle cerebral artery occlusion (MCAO) induced permanent focal ischemia for 16 hours in artificially ventilated cats (30% oxygen, 70% nitrous oxide) under halothane (0.75%, n = 8) or alpha-chloralose anesthesia (60 mg/kg intravenously, n = 7). Under alpha-chloralose, MCAO induced severe ischemia in ectosylvian and suprasylvian gyri(mean CBF < 10 mL/100 g/min), and direct current potentials turned immediately into terminal depolarization. In marginal gyri, CBF reduction was mild (more than 20 mL/100 g/min), and in six of seven animals, frequent SD-like depolarizations turned into terminal depolarization at a later stage of the experiments. Under halothane, MCAO induced severe ischemia (less than 10 mL/100 g/min) and immediate terminal depolarization only in ectosylvian gyrus. In suprasylvian gyrus, residual CBF remained significantly higher (more than 10 mL/100 g/min) than under alpha-chloralose, whereas in marginal gyri, CBF did not differ between groups. Compared with chloralose, the number of transient depolarizations was significantly reduced in marginal gyrus, and in suprasylvian gyrus transient but significantly longer depolarizations than in marginal gyrus were recorded. Except for one animal, transient depolarizations did not turn into terminal depolarization under halothane, and infarct volume reduction was particularly seen in suprasylvian gyrus. We conclude that halothane, the most commonly used anesthetic in studies of experimental brain ischemia, has protective properties, which may depend on both cerebrovascular and electrophysiologic influences.     

Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm

The extent and timing of posttraumatic cerebral hemodynamic disturbances have significant implications for the monitoring and treatment of patients with head injury. This prospective study of cerebral blood flow (CBF) (measured using 133Xe clearance) and transcranial Doppler (TCD) measurements in 125 patients with severe head trauma has defined three distinct hemodynamic phases during the first 2 weeks after injury. The phases are further characterized by measurements of cerebral arteriovenous oxygen difference (AVDO[2]) and cerebral metabolic rate of oxygen (CMRO[2]). Phase I (hypoperfusion phase) occurs on the day of injury (Day 0) and is defined by a low CBF calculated from cerebral clearance curves integrated to 15 minutes (mean CBF 32.3 +/- 2 ml/100 g/minute), normal middle cerebral artery (MCA) velocity (mean V[MCA] 56.7 +/- 2.9 cm/second), normal hemispheric index ([HI], mean HI 1.67 +/- 0.11), and normal AVDO(2) (mean AVDO[2] 5.4 +/- 0.5 vol%). The CMRO, is approximately 50% of normal (mean CMRO(2) 1.77 +/- 0.18 ml/100 g/minute) during this phase and remains depressed during the second and third phases. In Phase II (hyperemia phase, Days 1-3), CBF increases (46.8 +/- 3 ml/100 g/minute), AVDO(2) falls (3.8 +/- 0.1 vol%), V(MCA) rises (86 +/- 3.7 cm/second), and the HI remains less than 3 (2.41 +/- 0.1). In Phase III (vasospasm phase, Days 4-15), there is a fall in CBF (35.7 +/- 3.8 ml/100 g/minute), a further increase in V(MCA) (96.7 +/- 6.3 cm/second), and a pronounced rise in the HI (2.87 +/- 0.22). This is the first study in which CBF, metabolic, and TCD measurements are combined to define the characteristics and time courses of, and to suggest etiological factors for, the distinct cerebral hemodynamic phases that occur after severe craniocerebral trauma. This research is consistent with and builds on the findings of previous investigations and may provide a useful temporal framework for the organization of existing knowledge regarding posttraumatic cerebrovascular and metabolic pathophysiology.     

A method for galactose-1-phosphate uridyltransferase assay and the separation of its isozymes by DEAE-cellulose column chromatography

The resistance to coronary blood flow in various parts of the myocardium was studied with the tracer microspheres technique before and immediately after an acute coronary occlusion and several weeks after a more slowly occurring coronary occlusion by Ameroid constrictor. All experiments were carried out in the isolated, metabolically supported, empty, beating dog heart at maximal coronary vasodilation induced with adenosine. Coronary resistance of the normal empty beating heart at maximal coronary vasodilation was 0.20 mm mm Hg/(ml/min) per 100 g of tissue (subepicardium) and 0.16 mm Hg/(ml/min) per 100 g of tissue (subendocardium). After acute coronary occlusion the perfusion of the subtended myocardium was maintained at a much lower level by way of collateral vessels, which showed a resistance to flow of 3.52 mm Hg/(ml/min) per 100 g. If coronary artery occlusion proceeded more slowly the collateral vessels became more functional and myocardial infarction was avoided. During collateral enlargement collateral resistance fell from 3.52 to 0.22 mm Hg/(ml/min) per 100 g within a period of 8 weeks after implantation of the constricting device. The degree of compensation by collaterals for the loss of the occluded native coronary artery was 33% of its former conductance.     

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.     

The isolated and perfused working heart of the frog, Rana esculenta: an improved preparation

The present study describes extraction fraction and uptake measurements of the [11C]methyl triphenyl phosphonium (11C-MTP), a promising positron emission tomography (PET) agent for cardiac imaging. PET imaging was performed in mongrel dogs. Under physiological flow conditions 11C-MTP uptake reached a maximum within the first 10 minutes after injection and remained constant during the entire observation period of 80 minutes. Over the same time period, the heart/blood ratio was 46-106:1, and the heart/lung ratio 14:1. Following permanent occlusion of the left anterior descending coronary artery, 11C-MTP uptake in the normally perfused myocardium also reached a maximum at 10 minutes after injection, whereas in the infarcted area there was no significant accumulation of 11C-MTP. For a time period of 80 minutes the noninfarcted/infarcted myocardium ratio was 12:1. Extraction was measured in anesthetized dogs with a double isotope method using 99mTc-HSA as the reference tracer. The extraction fraction was 91% at a flow of 69 mL/min/100g. As flow increased to five-fold (342 mL/min/100g) following administration of adenosine, extraction fell to 61%. Following coronary artery occlusion, the 11C-MTP content in the myocardium was highly correlated (r = 0.93, p < 0.01; y = 10.46 + 0.92x) with the microsphere determined regional myocardial blood flow.     

Effect of transluminal angioplasty on cerebral blood flow in the management of symptomatic vasospasm following aneurysmal subarachnoid hemorrhage

In this study the authors have examined the effects of transluminal angioplasty on cerebral blood flow (CBF) in the management of intractable vasospasm following aneurysmal subarachnoid hemorrhage (SAH). Fourteen consecutively enrolled patients underwent attempted angioplasty with or without intraarterial infusion of papaverine. Twelve patients underwent pre- and postangioplasty xenon-enhanced computerized tomography (Xe-CT) scanning to measure regional CBF in 55 to 65 regions of interest (ROIs) per patient. Angioplasty was possible in 13 (93%) of 14 patients, with angiographically demonstrated improvement in all 13. Twelve (92%) of the 13 patients were neurologically improved following angioplasty; seven (58%) of the 12 patients who improved had a complete reversal of all delayed ischemic deficits. Angioplasty significantly decreased the mean number of ROIs at risk (11.4 ROIs pre- and 0.9 ROIs postangioplasty) (p < 0.00005, t-test). All patients had a reduction in the number of ROIs at risk after angioplasty; six (50%) of 12 no longer had any ROIs remaining at risk after angioplasty. Angioplasty significantly increased the mean CBF within at-risk ROIs (13 ml/100 g/minute pre- and 44 ml/100 g/minute postangioplasty) (p < 0.00005, t-test). All patients experienced an improvement in mean CBF in at-risk ROIs after angioplasty, with the mean CBF improving to above 20 ml/100 g/minute in all cases. No differences in the degree of improvement were found in patients who received intraarterial papaverine compared with those who did not. In the majority of patients with refractory vasospasm following SAH, angioplasty effectively dilated spastic arteries, reversed delayed neurological deficits, and significantly improved CBF in areas of brain at risk of infarction.     

Calcitonin gene-related peptide reduces brain injury in a rat model of focal cerebral ischemia

BACKGROUND AND PURPOSE: Calcitonin gene-related peptide is an endogenous vasodilating neuropeptide with a dense concentration in the trigeminocerebrovascular system. It is hypothesized that depletion of this peptide contributes to delayed cerebral ischemia after subarachnoid hemorrhage and that an exogenous supply of calcitonin gene-related peptide will augment ischemic cerebral blood flow and reduce neuronal injury. METHODS: In this study we have investigated the effect of an intravenous infusion of calcitonin gene-related peptide (100 ng/kg per minute), started 1 hour before and continued throughout 4 hours of focal cerebral ischemia, on cerebral blood flow and the volume of brain injury in a rat model of middle cerebral artery occlusion. RESULTS: Calcitonin gene-related peptide produces a significant improvement in ischemic cerebral blood flow (32 +/- 2 compared with 13 +/- 2 mL/100 g per minute in the controls; t = 6.92, P < .0001) with a concomitant reduction in the volume of ischemic brain injury (102 +/- 22 compared with 234 +/- 19 mm3; t = 4.47, P < .001). CONCLUSIONS: These findings lend support for the potential use of this peptide in the prophylactic treatment of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.     

Aortic dissection decades following internal carotid artery dissection--report of two cases

BACKGROUND: In patients with cirrhosis, portosystemic shunts allow intestinal bacteria and endotoxin to enter the systemic circulation. Endotoxemia may induce increased synthesis of nitric oxide, thereby contributing to arterial vasodilation. OBJECTIVE: To test the hypothesis that the antibiotic norfloxacin blocks the effects of nitric oxide. DESIGN: Placebo-controlled, double-blind, crossover study. SETTING: Alfred Hospital, Melbourne, Australia. PATIENTS: 9 patients with alcohol-related cirrhosis and 10 healthy controls. INTERVENTION: Norfloxacin, 400 mg twice daily, for 4 weeks. MEASUREMENTS: Peripheral blood flow was measured by using forearm venous occlusion plethysmography. RESULTS: Basal forearm blood flow was higher in patients with cirrhosis than in controls (3.69 +/- 0.27 mL/100 mL per minute and 2.47 +/- 0.40 mL/100 mL per minute; P = 0.014) but returned toward normal after norfloxacin was given (2.64 +/- 0.31 mL/100 mL of tissue per minute in patients with cirrhosis). Responses to NG-monomethyl-L-arginine were greater in patients with cirrhosis but returned to normal after norfloxacin was given. CONCLUSION: Bacterial endotoxemia in patients with cirrhosis induces increased synthesis of nitric oxide that can be corrected with norfloxacin.     

The influence of extracellular calcium on muscarinic receptors in vascular smooth muscle

The time course and mechanism of vulnerability to ventricular fibrillation (VF) a 10-minute occlusion of the left anterior descending coronary artery and following its release were studied in 48 dogs. VF threshold was determined by inducing a sequence of three extrasystoles (sequential R/T pulsing). Within 1 minute of occlusion, the fibrillation current decreased to the level required for eliciting a propagated diastolic response. This state of enhanced vulnerability lasted for approximately 6 minutes, after which the VF threshold returned to preocclusion values. The vulnerability changes upon reperfusion, by comparison, occurred within seconds of release and persisted only transiently. Three minutes of occlusion was the minimal time which resulted in a reduction in VF threshold after release. Alpha and beta-adrenergic blockade with phentolamine and propranolol, respectively, prevented the decrease in VF threshold during occlusion but were without effect upon threshold changes during coronary artery release. Lidocaine failed to alter the pattern of vulnerability. It is concluded that adrenergic mechanisms play a key role in the increased susceptibility to VF associated with acute myocardial ischemia, whereas the changes in VF threshold following reperfusion may be due to washout products of cellular ischemia. These findings support the view that protection against VF during coronary artery occlusion and release may require different antiarrhythmic measures.     

Preconditioning during simulated MIDCABG attenuates blood flow defects and neutrophil accumulation

BACKGROUND: Ischemic preconditioning (IP) may be cardioprotective in minimally invasive direct coronary artery bypass where cardioplegia is not used. This study tested the hypothesis that IP of the area at risk (AAR) would attenuate postischemic injury from transient coronary artery occlusion. METHODS: In 19 anesthetized dogs, the left anterior descending coronary artery was occluded for 30 minutes (simulating coronary occlusion during anastomosis) followed by 3 hours of reperfusion. In 10 dogs, occlusion was preceded by 5 minutes of occlusion and 5 minutes of reperfusion (IP), whereas 9 other dogs had no IP (control, C). RESULTS: Thirty minutes of left anterior descending occlusion caused comparable dyskinesis (systolic shortening, sonomicrometry) in the AAR in C (baseline, 29% +/- 3% to 3% +/- 2%) and in IP (baseline, 29% +/- 2% to -0.3% +/- 2%). After 3 hours of reperfusion, systolic shortening was significantly depressed in C (20% +/- 4%), and was not significantly improved by IP (24% +/- 3%, p = 0.8 versus C). Postischemic diastolic stiffness in the AAR was not altered by IP versus C (0.60 +/- 0.12 versus 0.41 +/- 0.13). Plasma creatine kinase activity was similar between C and IP at the end of reperfusion (20 +/- 11 versus 16 +/- 5 U/g). Postischemic AAR blood flow (in milliliters per minute per gram of tissue) at 180 minutes of reperfusion decreased by 56% versus baseline in C (from 1.04 +/- 0.4 to 0.46 +/- 0.12; p < 0.05) compared with no change in IP (from 0.74 +/- 0.23 to 0.60 +/- 0.10), but there was no significant group difference at this time. Myeloperoxidase activity as an index of neutrophil accumulation in AAR was decreased in IP versus C (0.4 +/- 0.09 versus 0.7 +/- 0.04 U/microg tissue). CONCLUSIONS: Ischemic preconditioning does not decrease postischemic wall motion and only modestly increases postischemic blood flow abnormalities in the AAR, but does significantly inhibit neutrophil accumulation.     

Ischemic and pressure-induced hyperemia: a comparison

OBJECTIVE: There is reason to question whether hyperemia after pressure occlusion is caused solely by local ischemia. This study quantitatively compared the response to the two forms of occlusion on the finger. DESIGN: Blood flow was measured by laser Doppler continuously before, during, and for 40 minutes after a 2-minute occlusion of flow at the finger dorsum and at the plantar surface of the finger tip (finger pulp), which has a much higher arteriolar density than the dorsum. Occlusion to the same low level was carried out either with a cuff at the base of the finger or by direct pressure of the laser Doppler probe head. Comparison experiments were performed with the probe head heated to 44 degrees C to elicit maximal local vasodilation. SETTING: Outpatient clinic. PARTICIPANTS: Eleven healthy volunteers. MAIN OUTCOME MEASURES: Magnitude and duration of skin blood flow after occlusion. RESULTS: Cuff occlusion at the base of the finger produced a typical, short-lived hyperemic response at both finger dorsum and finger pulp. The peak level at finger dorsum was 17.6 +/- 1.4mL/min/100g, approximately a twofold increase over the baseline flow level. The duration of the hyperemic response was 3.6 +/- 0.8 minutes. The baseline flow at the finger pulp was three times greater than at the finger dorsum, and peak flow after occlusion was also three times higher (44.3 +/- 2.6 mL/min/100g). The duration of hyperemia at finger pulp was 4.2 +/- 0.9 minutes. After pressure occlusion at the finger dorsum the hyperemic peak was higher (26.7 +/- 4.2 mL/min/100g; p < .05) and the duration of hyperemia was four times longer (16.9 +/- 2.3 minutes; p < .01) than after cuff occlusion. At the finger pulp, the pressure-induced hyperemic peak was also greater than the peak after cuff occlusion (56.3 +/- 1.7mL/min/100g; p < .05), with a longer duration than after cuff occlusion (11.1 +/- 1.1min; p < .01). Thermal stimulation significantly reduced the differences between cuff- and pressure-induced occlusion. There was a slow increase in flow over the 40-minute monitoring period. The maximal flow reached was approximately 100mL/min/100g at both finger dorsum and finger pulp. At both sites, however, the maximal flow level was attained more rapidly than the control condition without prior occlusion. CONCLUSIONS: These results confirmed that the pressure-induced hyperemic response is greater and of longer duration than that produced by flow ischemia alone. Thermal stimulation essentially abolishes the differences, suggesting that there is a common mechanism of vasodilatation. The mechanistic differences between pressure-induced and ischemic hyperemia remain to be determined.     

Ischemic changes in the canine heart as affected by the dimethyl quaternary analog of propranolol, UM-272 (SC-27761)

The effects of the dimethyl quarternary analog of propranolol, UM-272, on myocardial infarct volume were studied in the canine heart. Myocardial infarction was produced by occlusion of the left circumflex coronary artery for 60 minutes followed by reperfusion and quantitation of infarct volume 24 hours later. Groups of dogs were either untreated or pretreated with UM-272 with an initial loading dose of 5.0 mg/kg (group A) or 2.5 mg/kg (group B) 30 minutes before occlusion of the left circumflex coronary artery. Both group A and group B animals received additional doses of 2.5 mg/kg of UM-272 every 90 minutes for a period of 6 hours so that the total respective doses were 15 and 12.5 mg/kg. Control animals received comparable volumes of 0.9% sodium chloride solution. All animals were followed throughout the 6-hour procedure with continuous electrocardiographic recordings which were used to assess the effects of acute myocardial ischemia upon disturbances in cardiac rhythm and the effects of drug treatment. Dogs which survived the procedure were given tetracycline i.v. the next day and sacrificed 1 hour later by an overdose of pentobarbital sodium. The hearts were removed and the left ventricle was sliced and examined first under ultraviolet light to localize the ischemic zone by noting the tetracycline fluorescence. The ventricular slices were next incubated in nitro blue tetrazolium which stains normal myocardial tissue, thus allowing one to quantitate the volume of infarcted myocardium by excising and weighing the nonstained and stained muscle separately. The untreated control group had an infarct volume of 23.8 +/- 3.2 g/100 g of left ventricle. The treated animals in groups A and B had respective infarct volumes of 2.3 +/- 0.8 g/100 g (P less than .001) and 7.0 +/- 3.3 g/100 g (P less than .025) of left ventricle. During the acute phase of ischemia and reperfusion, arrhythmias and alterations in the ST-segment, R-wave amplituted and development of pathologic Q-waves were more prominent in the untreated animals and almost totally absent in the treated animals. UM-272 produced a dose-dependent decrease in heart rate as well as a decrease in developed isometric tension. Pretreatment with UM-272 did not prevent the derangement of function in the ischemic zone nor did it permit a return of function upon reperfusion, even though it reduced the degree of cellular damage resulting from 60 minutes of regional ischemia. A possible mechanism for the protective effect of UM-272 may be through its ability to reduce myocardial contractility and heart rate, both of which would reduce myocardial oxygen consumption and thus produce a more favorable balance between myocardial oxygen supply and myocardial oxygen demand.