R. F. Albrecht

Cardiovascular effects and acid-base and blood gas changes during laparoscopy.

Abstract Laparoscopy in 10 women with intraperitoneal carbon dioxide insufflation up to 20 mm. Hg was accompanied by circulatory stimulation with elevated arterial and central venous blood pressures, tachycardia, hypercarbia, and decrease in pH. Further increase in intra-abdominal pressure above 20 mm. Hg was accompanied by an inverse effect, depression in central venous, systolic, pulse pressure and cardiac output, suggesting inhibited venous return. High peripheral resistance, elevated peak respiratory pressure, as well as high arterial halothane concentration observed concomitantly might contribute to circulatory depression. With abdominal decompression all values returned to normal. In one patient, a dramatic vasovagal reflex was observed during CO 2 insufflation which could have resulted in cardiac arrest; it was immediately reversed after atropine sulfate injection. During laparoscopy, elevation of intraperitoneal pressure above 20 mm. Hg may be potentially dangerous and seems not necessary for good visualization.

Ketamine Decreases Plasma Catecholamines and Improves Outcome from Incomplete Cerebral Ischemia in Rats

Central neuroexcitatory receptors (N-methyl-D-aspartate [NMDA], non-NMDA) may affect outcome from cerebral ischemia by altering sympathetic nervous system activity. We tested whether ketamine, an NMDA antagonist, and NBQX, a non-NMDA antagonist, improve outcome from incomplete cerebral ischemia in the rat and whether a change in outcome is related to changes in plasma catecholamines. There were five treatment groups: group 1 (control, n = 10) received a fentanyl infusion at a rate of 25 microgram.kg-1.h-1 and ventilation with 70% N2O in O2. Group 2 (n = 10) received the same anesthetic treatment and were given an intraperitoneal injection of 30 mg/kg NBQX 15 min prior to ischemia. Group 3 (n = 10) received a ketamine infusion of 1.0 mg.kg-1.min-1 and ventilation with room air. Group 4 (n = 10) received a ketamine infusion of 1.5 mg.kg-1.min-1. Group 5 received a ketamine infusion of 1 mg.kg-1.min-1 plus a 6 ml/kg intraperitoneal injection of 40% glucose solution 15 min before the start of ischemia. Ischemia was produced by right common carotid ligation combined with hemorrhagic hypotension to 35 mmHg for 30 min. Blood gases, pH, and skull temperature were controlled during ischemia. Plasma glucose increased during ischemia in all groups but was lower in ketamine-anesthetized rats (groups 3 and 4). Glucose-loaded ketamine-anesthetized rats (group 5) had plasma glucose concentrations similar to the control group. Plasma epinephrine and norepinephrine concentrations were significantly less in ketamine-anesthetized rats (groups 3, 4, and 5) during ischemia compared to controls (P less than 0.05). Neurologic outcome was significantly better (P less than 0.05) in all ketamine-treated rats (groups 3, 4, and 5) compared to the control group, regardless of plasma glucose concentration during ischemia. NBQX did not improve neurologic outcome. These results suggest that ketamine improves neurologic outcome from incomplete cerebral ischemia by a mechanism related to a decrease in plasma catecholamine activity.

Cerebral blood flow and metabolism following ketamine administration.

The effects of kelamine on cerebral blood flow (CBF), cerebral metabolic rate (CMRo2) and intracranial pressure (ICP) were evaluated in ventilated or spontaneously breathing goats after peripheral administration of 5mg.kg-1 and central administration of 0.1 -2.0 mg.In mechanically ventilated normocarbic goats intravenous ketamine 5 mg . kg-1 had no effect on CBF, but did produce a significant reduction in CMRo2 (4.3 ± 0.4 vs 3.7 ± 0.3 ml O2 min-1/100g) five minutes after injection. However, in spontaneously breathing goats, ketamine caused a significant increase in CBF (77 ± 7 vs 109 ± 12 ml min-1/100g), a significant reduction in CMRo2 (4.3 ± 0.3 vs 3.8 ± 0.4) and an increase of Pco2 from 4.5 ± 0.5 to 5.4 ± 0.9 kPa (34 ± 4 to 41 ±7 torr). Small doses of ketamine (0.1-2.0mg) injected directly into the cerebral circulation failed to cause any significant change in CBF.Intracranial pressure showed a significant increase from 13 ± 3 to 19 ± 3 mm Hg in spontaneously breathing goats and no change in ventilated goats.These data suggest that ketamine is a mild depressant of cerebral metabolic rate and has no other cerebral vascular effects.RésuméLes effets de la kétamine administrée par voie intraveineuse à la dose de 5 mg . kg-1 ainsi que ceux produits par l’administration directe d’une petite dose (0.1 à 2 mg) de cet agent dans l’artère temporale faisaient l’objet de cette étude effectuée chez la chèvre. Les paramètres mesurés étaient le débit sanguin cérébral, le métabolisme cérébral et la pression intracranienne. Dans onze des cas, l’étude a été faite chez l’animal en respiration spontanée, alors que la ventilation était contrôlée dans dix-sept autres cas.Chez la chèvre en respiration contrôlée (avec maintien d’une Pco2 normale), l’administration intraveineuse de 5 mg . kg-1 de kétamine ne modifiait pas le débit sanguin cérébral, mais une diminution significative du métabolisme cérébral (4.3 ± 0.4 vs 3.7 ± 0.3 ml O2 min-1 par 100 g) était observée cinq minutes après l’injection.Chez l’animal en respiration spontanée, la même dose de kétamine amenait une augmentation significative du débit sanguin cérébral qui passait de 77 ± 7 à 109 ± 12 ml . min-1/100 g ; cette dose causait également une diminution significative du métabolisme cérébral (4.3 ± 0.3 vs 3.8 ± 0.4 ml O2. min-1/100 g, ainsi qu’une élévation de la Pco2 qui passait de 4.5 ± 0.5 à 5.4 ± 0.9kPa (34 ± 4 à 41 ±7 torr).De petites doses de kétamine (0.1 à 2mg.) injectées directement dans la circulation cérébrale ne modifiaient pas de façon significative le débit sanguin cérébral.Une élévation significative de la pression intracranienne (qui passait de 13 ± 3 à 19 ± 3mmHg) a été observée chez lez chèvres en respiration spontanée, alors qu’aucun changement n’était observé chez les animaux en ventilation contrôlée.Ces résultats suggèrent que la kétamine est un dépressant léger du métabolisme cérébral sans autres effets vasculaires cérébraux.

Effects of sufentanil on cerebral blood flow, cerebral blood flow velocity, and metabolism in dogs.

&NA; The intracranial and systemic hemodynamic effects of sufentanil (20 μg/kg) were studied in 10 mongrel dogs. Baseline anesthesia was maintained with 0.7% end‐tidal isoflurane and 50% nitrous oxide in oxygen. Catheters were inserted for blood pressure measurement, arterial and sagittal sinus blood sampling, radioactive microsphere injections, and intracranial pressure monitoring. Blood flow velocity was measured continuously in the middle cerebral artery using a transtemporal approach through a cranial window with a pulsed 8 MHz transcranial Doppler system (TCD). Cardiac output was measured using an electromagnetic flow probe on the pulmonary artery. After baseline measurements, sufentanil was injected and data were recorded at 5, 25, and 30 min. In group 1 (n = 5) blood pressure was not controlled, whereas in group 2 (n = 5) blood pressure was maintained at baseline levels with a phenylephrine infusion. Sufentanil decreased blood pressure from 120 ± 10 mm Hg (mean ± SEM) to 82 ± 11 mm Hg in group 1. Cardiac output decreased 40%‐50% in both groups. Intracranial pressure did not change. Cerebral blood flow (CBF) and TCD blood flow velocity decreased significantly (35%‐40%) with no difference between groups. Relative decreases in CBF and TCD blood flow velocity were closely correlated (r = 0.82). The cerebral hemodynamic changes were associated with a 35%‐40% decrease in cerebral oxygen consumption. We conclude that sufentanil decreases CBF in response to decreased metabolic demand without significantly affecting intracranial pressure. Relative changes in CBF can be reproducibly monitored using TCD.

Sodium Nitroprusside and Cerebral Blood Flow in the Anesthetized and Unanesthetized Goat

The effects of sodium nitroprusside (SNP) on total, ipsilateral cerebral blood flow (CBF) in the unanesthetized and anesthetized goat was evaluated under four conditions: 1) bolus injection of SNP into the cerebral circulation via the temporal artery; 2) continuous infusion of SNP into the temporal artery in amounts too small to affect the peripheral circulation (0.57–1.14 µg/kg/min); 3) intravenous infusion of SNP; 4) continuous intravenous infusion of SNP with a bolus injection of angiotensin. Small doses (20, 40, and 80 µg) of SNP injected directly in the cerebral circulation of the awake goat produced immediate increases of 21 ± 8, 36 ± 8, and 48 ± 10 per cent, respectively, in CBF lasting 1 to 3 min without causing peripheral cardiovascular changes. The effects of SNP were attenuated by 1.5 per cent halothane anesthesia. Continuous infusion of SNP into the temporal artery in amounts too small to cause peripheral cardiovascular effects produced sustained increases in CBF averaging 31 ± 8 per cent; CBF returned to preinfusion values upon cessation of infusion. Intravenous infusion of SNP in both anesthetized and unanesthetized animals in recommended clinical dosages (3–8 µg/kg/min) produced hypotension but did not significantly alter CBF. However, upon injection of angiotensin (1.43 µg/kg), both peripheral blood pressure and CBF increased sharply, suggesting that SNP may impair autoregulation of CBF. The results of this study indicate that SNP dilates the cerebral vascular system in a way that is probably similar to its effects on other vascular beds.

The influence of aging and hypertension on cerebral autoregulation

Cerebral autoregulation was tested here in 3- and 18-month-old spontaneously hypertensive rats (SHR) and Wistar Kyoto controls (WKY). Cerebral blood flow (CBF) was measured in each rat using radioactive micropheres under unanesthetized control conditions and after hypotension induced by ganglionic blockade. Under control conditions there was no significant difference in CBF between SHR and WKY. During drug induced hypotension CBF decreased significantly in all except 3 month WKY. CBF was decreased significantly more in 18 month SHR after ganglionic blockade compared to other test groups. These results indicate an influence of both age and hypertension in altering the ability of the cerebrovasculature to autoregulate.

Comparative Ventilatory Effects of Intravenous Versus Fourth Cerebroventricular Infusions of Morphine Sulfate in the Unanesthetized Dog

The ventilatory pharmacodynamics of morphine sulfate (MS) in the awake dog (n = 14) were investigated. Two routes of MS administration were employed: 1) 4 h continuous intravenous (iv) infusion (1 mg.kg-1 loading dose, 10 micrograms.kg-1.min-1 thereafter); and 2) fourth ventricle to cisterna magna perfusion (VCP) at increasing infusate morphine concentrations (0.1-100 micrograms.ml-1). The former was associated with a constant plasma and cisternal CSF (and presumably tissue) free morphine concentration. The latter produced, over 1 h at a constant infusate morphine delivery, a cisternal CSF free morphine concentration that leveled off by 30 min, little or no distribution of drug beyond superficial dorsal and superficial ventral brainstem tissue, and no detectable levels of morphine in plasma. When comparing the two routes of administration, ventilatory depression for a given cisternal free morphine level in the iv infusion studies was of a much greater magnitude than that seen in VCP experiments. Differences in the ventilatory patterns were also noted. Thus, iv delivery produced a decrease in tidal volume (VT) and no change or reduced respiratory frequency (f) with prolonged exposure. VCP delivery was also associated with reduction in VT but produced significant increases in f. An apparent maximal ventilatory depression with 1 h VCP administration was observed at morphine infusate levels of greater than 10 micrograms.ml-1, with higher infusate concentrations and extension of the perfusion period to 3 h producing no significant additional changes. Finally, VCP delivery of the mu-antagonist nalbuphine could only partially reverse the ventilatory depression accompanying iv morphine administration. These findings suggest that the ventilatory depression associated with iv morphine is a result of interactions with brain u-opiate receptors in superficial brainstem tissue and in deep brainstem and/or suprapontine tissue as well.

Cerebrovascular and cerebral metabolic responses of aged rats to changes in arterial PCO2

Cerebrovascular and cerebral metabolic responses to changes in arterial PCO2 were tested in young (4 month) and aged (24 month) Sprague-Dawley rats. Rats were anesthetized with 70% nitrous oxide and 30% oxygen, paralyzed with tubocurare and artificially ventilated. Cerebral blood flow (CBF) was measured with radioactive microspheres and cerebral oxygen metabolism (CMRO2) was analyzed from arterial and sagittal sinus oxygen content differences. CBF increased in both young and aged rats with increasing arterial PCO2. Aged rats had significantly depressed cerebrovascular reactivity to changes in CO2 compared to young rats (p less than 0.05). CMRO2 was not significantly different between young and aged rats and did not significantly change with changes in arterial PCO2.

Blood flow to oral tissues: An experimental study with enflurane, sodium nitroprusside, and nitroglycerin

Hypotensive anesthesia is currently being used in oral and maxillofacial surgery to reduce blood loss and provide a relatively bloodless surgical field. Radioactively labeled microspheres were used to determine and compare the hemodynamic effects of sodium nitroprusside (SNP), nitroglycerin (NTG), and deep enflurane anesthesia on oral tissues during controlled hypotension when compared with controls. Sodium nitroprusside and NTG produced significant reductions in blood flow to the maxilla, mandible, and tongue, while deep enflurane anesthesia did not. In the masseter and suprahyoid muscles, increases in tissue blood flow were found with SNP and enflurane. Nitroglycerin produced no significant change in blood flow in the masseter and the suprahyoid. These results demonstrate that in spite of a similar cardiac index with all agents tested, local oral blood flow varied significantly with the different agents tested. These differences in tissue blood flow suggest that SNP and NTG may be preferable to deep enflurane anesthesia for maxillary osteotomies to achieve greater flow reduction and diminish blood loss.

Central cardiovascular activity of prostaglandin E2, prostagladin F2∝ and prostacyclin

Abstract Prostacyclin (PGI2), prostaglandin E2 (PGE2) and prostaglandin F2∝ (PGF2∝) were tested here in unanesthetized male Sprague-Dawley rats for their effects on the cardiovascular system as mediated by the Central nervous system. Cannulae were chronically implanted into the third cerebral ventricle, femoral arteries and femoral veins of rats. Both PGE2 and PGF2∝ induced increased arterial blood pressure and tachycardia by an action on the central nervous system. The changes seen with PGE2 were larger than those observed with PGF2∝. Only transient depressor effects were seen with PGI2 and these changes appeared to be due to the leakage of the substance into the peripheral vascular system.