Effects of chlorpromazine on experimental delayed cerebral vasospasm

Experimental delayed cerebral vasospasm was produced in the canine basilar artery by intracisternal injections of blood 2 days apart. The spastic basilar artery was exposed via the transclival route under a surgical microscope, and was dilated by topical application of chlorpromazine, a calmodulin antagonist. Dilatation was dose-dependent, with a median effective dose of 37 +/- 16 microM. In addition, 100 microM chlorpromazine was inserted into the cisterna magna until the intracranial pressure (ICP) reached 200 mm H2O for 30 minutes, inducing a complete reversal of angiographic delayed cerebral vasospasm in two of five animals. In other studies, the intracisternal perfusion of 100 microM chlorpromazine at 1.48 ml/min for 30 minutes with an ICP of less than 200 mm H2O induced no serious abnormalities in mean arterial blood pressure and pulse rate of normal animals. Electroencephalography during the intracisternal perfusion of chlorpromazine showed a slight to moderate increase in occurrence of theta waves. No neurological deficits or significant histological abnormalities ascribable to intracisternal chlorpromazine were found.     

Myocardial hemodynamics during induced hypotension: a comparison between sodium nitroprusside and adenosine triphosphate

Adenosine triphosphate (ATP) has been reported to be a hypotensive agent similar in effect to sodium nitroprusside (SNP). The purpose of this study was to examine and compare the effects of both SNP and ATP on general coronary hemodynamics, myocardial O2 consumption, and circulating catecholamines. Twelve dogs were anesthetized with 1.0% halothane and given either SNP or ATP by controlled infusion to reduce their systemic blood pressure by 50% for a 2-h period followed by a (blood pressure) recovery period. The ATP-induced hypotension was rapid, easily controlled, not accompanied by tachyphylaxis over the 120 min studied, and resulted in an increase in coronary sinus blood flow (CSBF), which plateaued at 260% above control. The increase in CSBF was almost immediate and remained at this elevated level for the duration of the induced hypotension. During the ATP-induced hypotension, there was no change in heart rate or circulating catecholamines. A 60% reduction in myocardial O2 uptake was observed, presumably from the cardiac unloading. In contrast, SNP-induced hypotension required a marked increase in dose over time, did not significantly increase CSBF, did increase heart rate, and resulted in large increases in circulating plasma catecholamines. Neither agent affected cardiac output. ATP-induced hypotension resulted in no change in cardiac lactic acid uptake, while SNP caused lactic acid production, indicating possible cardiac ischemia or cyanide toxicity.     

Effects of prostacyclin and indomethacin on experimental delayed cerebral vasospasm

Isolated canine basilar artery contracted by prostaglandin E2, hemoglobin, or serum was relaxed in a dose-dependent manner by the addition of 10(-8)M to 10(-6)M prostacyclin (PGI2), and was scarcely relaxed by 10(-9)M PGI2. In other studies, intravenous administration of PGI2 (25 or 75 ng/kg/min), indomethacin (4 mg/kg), or indomethacin (4 mg/kg) plus PGI2 (25 ng/kg/min) failed to reverse angiographic delayed vasospasm produced in vivo in the canine basilar artery by an intracisternal injection of blood. In addition, no significant increase occurred in mean values of regional cerebral blood flow (rCBF) with any treatments, and mean rCBF difference in dogs treated by PGI2 infusion at 25 ng/kg/min was 2.5 +/- 1.2 ml/100 gm/min and only significantly increased (p less than 0.01). Mean arterial blood pressure was significantly reduced by PGI2 infusion at 25 (p less than 0.05) or 75 ng/kg/min (p less than 0.005).     

Blood and cerebrospinal fluid lactate during induced hypotension

Cerebral anaerobism during induced arterial hypotension to mean arterial pressure (HOH) and trimethaphan infusion (TIH) was evaluated in 11 dogs by comparison of lactate in cerebrospinal fluid (CSF) and arterial blood. In six HOH dogs average normotensive control CSF and blood lactates were 1.79 (range 1.45–2.2) and 1.21 (range 0.7–1.8) mmoles/liter. At 5, 30, and 60 min posthypotension, average CSF and blood lactates were 1.93 (range 1.4–2.7), 2.33 (range 2.1–2.6), 3.16 (range 2.6–4.8) mmoles/liter and 2.35 (range 1.4–3.9), 6.30 (range 2.4–12.4), 8.54 (range 5.0–12.6) mmoles/liter, respectively. In five TIH dogs average control CSF and blood lactates were 1.74 (range 1.5–1.9) and 1.18 (range (0.32–2.10) mmoles/liter. At 5, 30, and 60 min posthypotension average CSF and blood lactates were 1.74 (range 1.4–2.1), 2.48 (range 1.6–3.5), 2.68 (range 1.9–3.7) and 1.56 (range 0.79–2.60), 3.76 (range 1.6–5.4), 4.16 (range 2.3–5.4) mmoles/liter respectively. Statistical analysis of CSF data shows that there is no significant difference between HOH and TIH lactate accumulation, and that 5–30 min are required for significant elevation over controls. Analysis of blood lactate shows significant elevation over controls during HOH by 5 min and during TIH by 30 min, with greater lactate accumulation in HOH than TIH by 60 min. Futility of using CSF lactate and advantage of employing blood lactate to monitor cerebral metabolism during hypotension is demonstrated.     

Effects of ML-9 on experimental delayed cerebral vasospasm

Experimental delayed cerebral vasospasm was produced in a two-hemorrhage canine model. The spastic basilar artery was exposed via the transclival route under a surgical microscope and was dilated by the topical application of 1-(5-chloronaphthalenesulfonyl)-1H-hexa-1,4-diazepine (ML-9), a selective antagonist of myosin light chain kinase. Dilation was dose-dependent, with a median effective dose (+/- standard deviation) of 51.4 +/- 6.9 microM. In addition, 50 microM of ML-9 was injected into the cisterna magna until the intracranial pressure (ICP) reached 200 mm H2O for 30 minutes, including a complete reversal of angiographic delayed vasospasm in three of seven dogs; in contrast, 150 microM of ML-9 was infused at 1.52 ml/min into the vertebral artery for 30 minutes, producing little dilation of the spastic basilar artery. In another study, the intracisternal perfusion of 50 microM of ML-9 at 1.48 ml/min for 30 minutes in dogs with an ICP of less than 200 mm H2O produced no serious electroencephalographic abnormalities, and the mean arterial blood pressure and pulse rate remained normal; no neurological deficits or significant histological abnormalities ascribable to the intracisternal ML-9 were found.     

Heart rate and blood pressure power spectral analysis during calcium channel blocker induced hypotension

PURPOSE: To observe heart rate (HRV) and blood pressure variability (BPV) as indices of neurocirculatory responses to induced hypotension with diltiazem and/or nicardipine for hip surgery. METHODS: Thirty-six ASA I-II patients received diltiazem (group D, n = 12), nicardipine (group N, n = 12) or combination of diltiazem/nicardipine (group DN, n = 12). The intensity of HRV and BPV, was determined by spectral analysis of HRV and BPV before anesthesia (T0), just before induced hypotension (T1), and at 10 and 30 min after the start of induced hypotension (T2 and T3, respectively). The logarithmic HRV and BPV were integrated: sympathetic and parasympathetic mediated low frequency area (0.06-0.1 Hz, LF), parasympathetic related high frequency area (0.15-0.4 Hz, HF) and total frequency area (0.01-0.4 Hz). Blood loss was assessed by weighing gauzes and measuring suction. RESULTS: Group DN had less blood loss (466 +/- 46 ml, mean +/- SEM) than group D (733 +/- 100 ml, P < 0.05). Diltiazem (11.4 +/- 0.9 microg x kg(-1) x min(-1)), and combination of diltiazem (0.25 +/- 0.01 mg x kg(-1)) and nicardipine (5.9 +/- 0.9 microg x kg(-1) x min(-1)) decreased LF-HRV at T2 and T3 (P < 0.05 vs T0 and T1), while nicardipine (8.1 +/- 0.8 microg x kg(-1) x min(-1)) showed increase in LF-HRV at T2 (P < 0.05 vs T1). HF-HRV unchanged through hypotension except for a decrease in group N at T3 (P < 0.05 vs T1). There were no increases in HF-BPV, and LF-BPV, except for a diltiazem induced decrease in LF-BPV at T3 (P < 0.05 vs T0 and T1). CONCLUSION: Group D and group DN can be used for deliberate hypotension without an increase in sympathetically mediated LF-HRV.     

Accuracy of the BoMED NCCOM3 bioimpedance cardiac output monitor during induced hypotension: an experimental study in dogs.

Changes in thoracic electrical bioimpedance during the cardiac cycle are utilised by the BoMed NCCOM3 monitor to measure cardiac output (COTEB). The technique provides a continuous noninvasive measurement but it has not been widely accepted. To determine the accuracy of the monitor, we compared its measurement with cardiac output measured by dye dilution (CODD) during induced hypotension and recovery in 23 dogs. After calibration of the NCCOM3 monitor during a resting state in each dog [mean blood pressure 112 +/- 17 (SD), mean CODD 3.22 +/- 0.99 l/min], the mean difference (COTEB-CODD) between paired measurements at the nadir of hypotension (blood pressure 55 +/- 24 mmHg) was 0.29 +/- 0.47 l/min whose limits of agreement (mean difference +/- 2 SD) were + 111.8% and -59.1% of the mean hypotensive CODD (1.10 +/- 0.66 l/min). Upon recovery from hypotension (mean blood pressure 102 +/- 20 mmHg), the mean difference between paired measurements was -0.28 +/- 0.66 l/min, whose limits of agreement were +44.1% and -67.8% of the mean CODD (2.36 +/- 1.01 l/min). The mean difference between the two techniques is too variable and excessive to permit substitution of one technique for the other. These results do not support the accuracy and reliability of the BoMed NCCOM3 cardiac output monitor.     

Circulatory and metabolic changes in the brain during induced hypotension

Induced hypotension was carried out using trimetaphan (TMP), glycerin trinitrate (GTN) and prostaglandin E(1) (PGE(1)) in 45 patients received elective abdominal surgery under anesthesia with enflurane in N(2)O/O(2) in order to evaluate and compare the effects of these three agents on cerebral circulation and metabolism. Upon reduction of mean arterial blood pressure to 60-65 mmHg, cerebral blood flow decreased in the TMP and GTN groups but increased in the PGE(1) group. The changes were quite proportional to those in cardiac index in the three groups. Cerebral oxygen consumption decreased only in the TMP group. Changes in cerebrospinal fluid pressure were not in parallel with those in cerebral blood flow. The former decreased slightly in the TMP group but increased in the GTN and PGE(1) groups. These results offered a great caution for induction of artificial hypotension using these agents.