Impairments in the initial horizontal vestibulo-ocular reflex of older humans.

To determine age-related changes, the initial horizontal vestibulo-ocular reflex (VOR) of 11 younger normal subjects (aged 20-32 years) was compared with that of 12 older subjects (aged 58-69 years) in response to random transients of whole-body acceleration of 1,000 and 2,800 degrees/s2 delivered around eccentric vertical axes ranging from 10 cm anterior to 20 cm posterior to the eyes. Eye and head positions were sampled at 1,200 Hz using magnetic search coils. Subjects fixed targets 500 cm or 15 cm distant immediately before the unpredictable onset of rotation in darkness. For all testing conditions, younger subjects exhibited compensatory VOR slow phases with early gain (eye velocity/head velocity, interval 35-45 ms from onset of rotation) of 0.90 +/- 0.02 (mean +/- SEM) for the higher head acceleration, and 0.79 +/- 0.02 for the lower acceleration. Older subjects had significantly (P < 0.0001) lower early gain of 0.77 +/- 0.04 for the higher head acceleration and 0.70 +/- 0.02 for the lower acceleration. Late gain (125-135 ms from onset of rotation) was similar for the higher and lower head accelerations in younger subjects. Older subjects had significantly lower late gain at the higher head acceleration, but gain similar to the younger subjects at the lower acceleration. All younger subjects maintained slow-phase VOR eye velocity to values > or = 200 degrees/s throughout the 250-ms rotation, but, after an average of 120 ms rotation (mean eccentricity 13 degrees), 8 older subjects consistently had abrupt declines (ADs) in slow-phase VOR velocity to 0 degree/s or even the anticompensatory direction. These ADs were failures of the VOR slow phase rather than saccades and were more frequent with the near target at the higher acceleration. Slow-phase latencies were 14.4 +/- 0.4 ms and 16.8 +/- 0.4 ms for older subjects at the higher and lower accelerations, significantly longer than comparable latencies of 10.0 +/- 0.5 ms and 12.0 +/- 0.6 ms for younger subjects. Late VOR gain modulation with target distance was significantly attenuated in older subjects only for the higher head acceleration.

Dynamic visual acuity during transient and sinusoidal yaw rotation in normal and unilaterally vestibulopathic humans.

The vestibulo-ocular reflex (VOR) stabilizes gaze to permit clear vision during head movements. It has been supposed that VOR function might be inferred from dynamic visual acuity (DVA), the acuity during imposed head motion. We sought to determine effectiveness of DVA for detection and lateralization of unilateral vestibulopathy, using rigorous psychophysical methods. Seventeen normal and 11 unilaterally vestibulopathic subjects underwent measurement of optically best corrected DVA during head motion. A variable size letter "E" 6 m distant was displayed in oblique random orientations to determine binocular DVA by a computer controlled, forced choice method. Three types of whole-body yaw rotation were delivered by a servo-controlled chair synchronized with optotype presentation. Two types of motion were predictable: (1) steady-state 2.0-Hz rotation at 10-130 degrees/s peak velocity with repetitive optotype presentation only during head velocity exceeding 80% of peak; and (2) directionally predictable transients at peak accelerations of 1000, 1600 and 2800 degrees/s2 with optotype presentation for 300 ms. For neither of these predictable motions did DVA in vestibulopathic subjects significantly differ from normal, with suggestions from search coil recordings that this was due to predictive slow and saccadic eye movements. Unilaterally vestibulopathic subjects experienced a significant decrease in DVA from the static condition during ipsilesional rotation for all three peak head accelerations. Only during directionally unpredictable transients with 75 ms or 300 ms optotype presentation was the sensitivity of DVA in unilaterally vestibulopathic subjects significantly abnormal during ipsilesional rotation. The ipsilesional decrease in DVA with head motion was greater for 75 ms than 300 ms optotype presentation. Search coil recordings confirmed hypometric compensatory eye movements during DVA testing with unpredictable, ipsilesional rotation. Receiver-operator characteristic analysis indicated ideal detection and lateralization of unilateral vestibulopathy by DVA tested with a 75-ms optotype exposure for unpredictable transient rotations to a peak acceleration of 2800 degrees/s. DVA can reliably detect unilateral deafferentation only if precautions are taken to prevent compensation by predictive slow eye movements and saccades.

Blockade of adenosine triphosphate-sensitive potassium channels eliminates isoflurane-induced coronary artery vasodilation.

BACKGROUND: The mechanisms by which volatile anesthetics induce vasodilation are unknown. Recent studies of adenosine triphosphate-sensitive potassium channels (KATP channels) in the vascular smooth muscle of the coronary circulation suggest that these channels play a role in the coronary artery dilation produced by hypoxemia, the coronary blood flow (CBF) reactive hyperemic response, and in CBF auto regulation. We therefore conducted this study to determine the role of KATP channels in isoflurane-induced coronary vasodilation. METHODS: Studies were conducted in six open-chest, anesthetized swine. The left anterior descending coronary artery was cannulated and perfused by blood passed through a membrane oxygenator. This preparation allowed us to administer drugs and volatile anesthetics regionally to the perfused myocardium, minimizing systemic effects. Regional CBF response to 1.5% and 3.0% isoflurane administered via the membrane oxygenator was measured before and after blockade of KATP channels, and was compared to the vasodilation produced by regional administration of several doses of sodium nitroprusside and adenosine. Blockade of KATP channels was achieved by regional intracoronary administration of glibenclamide (1-22 micrograms.kg-1.min-1), a specific blocker of these channels. RESULTS: Administration of 1.5 and 3.0 percent isoflurane increased regional CBF by 29 +/- 29% and by 62 +/- 28%, respectively. Under control conditions, blockade of KATP channels decreased mean CBF by 18%, but did not cause ischemia. KATP channel blockade totally eliminated the vasodilator response to both doses of isoflurane. During KATP channel blockade the response to 3% isoflurane was converted to net vasoconstriction: mean delta CBF = -5% +/- 6%, P = < 0.05 versus control. Negative inotropic effects of isoflurane were not eliminated by glibenclamide. Because KATP channel blockade was so effective in eliminating isoflurane-induced coronary vasodilation, the dose of glibenclamide was decreased in sequential experiments, but total blockade of isoflurane vasodilation was achieved even at the smallest dose of glibenclamide studied (1 microgram.kg-1.min-1). The vasodilator response to nitroprusside was not affected, and the vasodilator response to adenosine was partially inhibited (consistent with their known mechanisms of action). CONCLUSIONS: Blockade of KATP channels by glibenclamide completely inhibits isoflurane-induced coronary vasodilation in the regionally perfused swine myocardium. The response to sodium nitroprusside, a drug that induces vasodilation via a different mechanism, was unaffected. The response to adenosine, a drug whose vasodilation is partially mediated via KATP channels, was partially inhibited. These results suggest that in vivo isoflurane-induced coronary artery vasodilation is predominantly mediated by KATP channels.

Regional vasodilating properties of isoflurane in stunned swine myocardium.

Studies about the coronary vasodilating properties of isoflurane indicate that this drug induces coronary vasodilation. No work has examined isoflurane-induced vasodilation in known stunned myocardium. This study was conducted to determine isoflurane's coronary vasodilation potency in stunned myocardium and to compare the results obtained with normal myocardium. We determined the vasodilating properties of isoflurane in regionally perfused swine myocardium. Six domestic swine were anesthetized with pentobarbital and fentanyl. The left anterior descending artery (LAD) was cannulated and perfused with blood drawn from the carotid artery and passed thorough a membrane oxygenator. LAD arterial flow was controlled by a calibrated roller pump with continuous digital readout, and LAD arterial pressure was measured directly. The anterior interventricular vein was cannulated and dimension crystals placed in the LAD-perfused myocardium. Myocardial stunning was induced by reduction of coronary blood flow (CBF) to 30% of control flow for 20 minutes. One hour after reperfusion, the vasodilatory response to 0%, 1%, and 2% isoflurane administered via the membrane oxygenator was determined and compared to maximum vasodilatation produced by regional intracoronary administration of adenosine. Systemic blood pressure and heart rate remained constant throughout the experiment. At 2% isoflurane, systolic shortening and regional myocardial oxygen consumption decreased 53% and 17%, respectively. The same concentration increased CBF by 33% and reduced coronary vascular resistance (CVR) by 25%. One percent isoflurane affected neither CBF nor CVR. Regional coronary administration of adenosine produced much greater changes in CBF (+509) and CVR (-89.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic hyperoxia diminishes myocardial stunning.

UNLABELLED: We used a model of isolated coronary perfusion to answer the question: Does high PO2 during low flow myocardial ischemia diminish postischemic myocardial contractile dysfunction? In 12 anesthetized, open chest swine, the left anterior descending (LAD) coronary artery was cannulated and perfused via an extracorporeal circuit. Normoxic arterial blood was pumped through a pediatric membrane oxygenator, which was used to control arterial PO2 in the perfusion bed. Myocardial stunning was created by reducing LAD coronary artery flow to 40% of control values for 30 minutes. After 5 minutes of ischemia, swine were randomized to either continued coronary normoxia or to coronary hyperoxia. In the hyperoxic group, oxygen was substituted for nitrogen in the oxygenator, thus increasing coronary PO2 to 382 +/- 32 mmHg. After 30 minutes of ischemia, all swine were reperfused with normoxic blood. RESULTS: There were no significant baseline differences between the two groups with regard to baseline hemodynamics, myocardial blood flow, or oxygen delivery parameters. Preischemic systolic shortening was comparable in the normoxic and hyperoxic groups: 23.6 +/- 6.8% and 24.9 +/- 3.9%, respectively. Increasing coronary arterial PO2 to 382 mmHg during ischemia led to a significant decrease in myocardial stunning in the hyperoxic group. Postischemic systolic shortening in the hyperoxic treatment group, measured at 15, 30, 45, and 60 minutes of reperfusion, was 14.8% +/- 6.3% (p < 0.05), 13.4% +/- 6.4% (p < 0.05), 13.8% +/- 6.7% (p < 0.05), and 14.3% +/- 5.8% (p < 0.05) compared to comparable measurements in the normoxic control group of 9.0% +/- 5.4%, 7.8% +/- 5.0%, 7.8% +/- 5.2%, and 7.2% +/- 5.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional vasodilating properties of isoflurane in normal swine myocardium.

BACKGROUND: Studies of the coronary vasodilating properties of isoflurane have produced inconsistent results. Isoflurane has been reported to cause minimal or no coronary vasodilation, mild dose-related vasodilation, or even near-maximal coronary vasodilation. The current study was performed to clarify the direct coronary vasodilating potency of isoflurane. METHODS: We determined the vasodilating properties of isoflurane in regionally perfused swine myocardium. Six domestic swine were anesthetized with pentobarbital and fentanyl. The left anterior descending artery (LAD) was cannulated and perfused with blood drawn from the carotid artery and passed thorough a membrane oxygenator. LAD arterial flow was controlled by a calibrated roller pump with continuous digital readout, and LAD arterial pressure was measured directly. The anterior interventricular vein was cannulated and dimension crystals placed in the LAD-perfused myocardium. The vasodilation response to 0, 1, 2, and 3% isoflurane administered via the membrane oxygenator was determined and compared to maximal vasodilation produced by regional intracoronary administration of adenosine. RESULTS: Systemic blood pressure and heart rate remained constant throughout the experiment. With 3% isoflurane, systolic shortening and regional myocardial oxygen consumption decreased by 60 and 20%, respectively. The same concentration increased coronary blood flow by 51 +/- 34% and reduced coronary vascular resistance by 32.9 +/- 11.0%. Neither coronary blood flow nor coronary vascular resistance was affected with 1% isoflurane. Regional coronary administration of adenosine produced much greater changes in both coronary blood flow (+591%) and coronary vascular resistance (-92.5%). Isoflurane increased the venous oxygen content of the anterior interventricular vein in a dose-dependent fashion from 4.85 vol% at control to 6.17, 7.01, and 8.63 vol% at 1, 2, and 3% isoflurane, respectively. CONCLUSIONS: We conclude that isoflurane is a mild dose-dependent coronary vasodilator. At a 1% concentration, the coronary vasodilating properties of isoflurane are minimal.