Ronald F. Albrecht

Cardiovascular effects of intraperitoneal insufflation with carbon dioxide and nitrous oxide in the dog.

Cardiovascular changes caused by intraperitoneal insufflation with CO2 or N2O were measured in 15 mongrel dogs. Moderate progressive increases in intra-abdominal pressure (to 40 mm Hg) with either gas produced increases in mean arterial, right atrial, pleural, and femoral-vein pressures. Cardiac output and inferior vena caval flow were momentarily increased following the commencement of insufflation. However, both flows decreased precipitously as insufflation pressure was increased. At an intra-abdominal pressure of 40 mm Hg cardiac output and inferior vena caval flow were reduced more than 60 per cent in most cases. Peripheral resistance increased by approximately 200 per cent. Upon sudden release of abdominal pressure cardiac output and inferior vena caval flow increased but then returned to pre-insufflation values within seconds. Directly measured right atrial pressure increased with increasing insufflation pressure, but calculated transmural right atrial pressure decreased with the increase in intra-abdominal pressure. Insufflation with CO2. produced significant increases in PaCO2. However, cardiostimulatory effects due to elevated blood CO2. levels were not seen. The data from this study indicate that intraperitoneal insufflation produces serious hemodynamic alterations which are manifested by low cardiac output and elevated total peripheral resistance. In addition, directly measured right atrial pressure cannot be used clinically as an indicator of venous return to the heart since it reflects a composite of pleural and intra-abdominal insufflation pressures.

Dexmedetomidine Improves Neurologic Outcome from Incomplete Ischemia in the Rat Reversal by the α2-Adrenergic Antagonist Atipamezole

Dexmedetomidine is an alpha 2-adrenergic agonist that decreases central sympathetic activity and reduces the anesthetic requirement for halothane. We evaluated the effect of dexmedetomidine on neurologic and histopathologic outcome from incomplete cerebral ischemia in the rat. Anesthesia was maintained with a 25-micrograms.kg-1.h-1 fentanyl infusion combined with 70% nitrous oxide. Incomplete ischemia was produced by unilateral carotid artery ligation combined with hemorrhagic hypotension to 35 mmHg for 30 min. Arterial blood gas tensions, pH, and head temperature were maintained at normal levels during the experiment. Four ischemic groups were tested: group 1 (n = 15) received an intraperitoneal (ip) saline injection (control); group 2 (n = 10) received an ip injection of 10 micrograms/kg dexmedetomidine 30 min before ischemia; group 3 (n = 10) received 100 micrograms/kg dexmedetomidine; and group 4 (n = 10) received 100 micrograms/kg dexmedetomidine plus 1 mg/kg atipamezole (an alpha 2-adrenergic antagonist). Neurologic outcome was evaluated for 3 days using a graded deficit score. Histopathology was evaluated in coronal section in caudate and hippocampal tissue segments. Dexmedetomidine (10 and 100 micrograms/kg) significantly decreased plasma catecholamines and improved neurologic and histopathologic outcome in a dose-dependent manner compared to control rats (P less than 0.05). Atipamezole abolished the decrease in catecholamines and the improvement in outcome seen with dexmedetomidine, confirming that these effects were mediated by alpha 2-adrenergic receptors. It is concluded that alpha 2-adrenoreceptor stimulation decreases sympathetic activity and decreases ischemic injury in a model of incomplete cerebral ischemia.

The role of neuronal nitric oxide synthase in regulation of cerebral blood flow in normocapnia and hypercapnia in rats

The nitric oxide synthase (NOS) inhibitors, nitro-L-arginine, its methyl ester, and N-monomethyl-L-arginine, have been shown to attenuate resting CBF and hypercapnia-induced cerebrovasodilation. Those agents nonspecifically inhibit the endothelial and neuronal NOS (eNOS and nNOS). In the present study, we used a novel nNOS inhibitor, 7-nitroindazole (7-NI) to examine the role of nNOS in CBF during normocapnia and hypercapnia in fentanyl/N2O-anesthetized rats. CBF was monitored using laser-Doppler flowmetry. Administration of 7-NI (80 mg kg−1 i.p.) reduced cortical brain NOS activity by 57%, the resting CBF by 19–27%, and the CBF response to hypercapnia by 60%. The 60% reduction was similar in magnitude to the CBF reductions observed in previous studies in which nonspecific NOS inhibitors were used. In the present study, 7-NI did not increase the MABP. Furthermore, the CBF response to oxotremorine, a blood–brain barrier permeant muscarinic agonist that induces cerebrovasodilation via endothelium-derived NO, was unaffected by 7-NI. These results confirmed that 7-NI does not influence eNOS; they also indicated that the effects of 7-NI on the resting CBF and on the CBF response to hypercapnia in this study were solely related to its inhibitory action on nNOS. The results further suggest that the NO synthesized by the action of nNOS participates in regulation of basal CBF and is the major, if not the only, category of NO contributing to the hypercapnic CBF response.

The Effects of Propofol on Brain Electrical Activity, Neurologic Outcome, and Neuronal Damage Following Incomplete Ischemia in Rats

This study compares the effects of propofol and fentanyl/N2O on spontaneous brain electrical activity, neurologic outcome, and neuronal damage due to incomplete cerebral ischemia in rats. Thirty Sprague-Dawley rats were assigned to one of three groups: group 1 (n = 10) received 70% N2O in O2 plus fentanyl (bolus 10 micrograms.kg-1, infusion 25 micrograms.kg-1.h-1); group 2 (n = 10) received 70% N2 in O2 and propofol (infusion 0.8-1.2 mg.kg-1.min-1) adjusted to maintain EEG burst suppression during ischemia; group 3 (n = 10) was anesthetized with propofol and received 6 ml.kg-1 10% glucose intraperitoneally 15 min before the start of ischemia. Incomplete cerebral ischemia was produced by right common carotid artery occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Arterial blood gases, pH, and rectal temperature were kept constant in all groups. Plasma glucose was lower during ischemia in propofol-anesthetized rats compared to that in fentanyl/N2O- (P = 0.009) and glucose-loaded propofol-treated rats (P = 0.008). Neurologic outcome and brain tissue injury were significantly better in propofol-anesthetized compared to fentanyl/N2O-anesthetized rats (P less than 0.05). Elevated plasma glucose in propofol-treated rats resulted in similar neurologic outcome and histopathologic injury as seen in propofol-anesthetized rats given no glucose. Recovery of EEG theta-alpha activity after ischemia was inversely correlated to neurologic deficit (fentanyl/N2O: r = -0.71; propofol: r = -0.83; P less than 0.01). These results show that propofol improves neurologic outcome and decreases neuronal damage from incomplete cerebral ischemia when compared to fentanyl/N2O. This effect is not dependent on plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

cardiovascular Effects of Centrally Administered Ketamine in Goats

&NA; The cardiovascular effects of centrally and peripherally administered ketamine were evaluated in unanesthetized goats and in goats anesthetized with pentobarbital. Small doses of ketamine (0.1 to 4 mg.) were injected directly into the central nervous system (CNS) of the unanesthetized goats via a temporal artery catheter, while cerebral blood flow (CBF), cardiac output (C.O.), systemic blood pressure (B.P.), and heart rate (H.R.) were continuously monitored. Administered by this route, ketamine produced an immediate increase in mean systemic B.P., C.O., and H.R. Changes in CBF were variable, increasing on some occasions and decreasing on others. Cardiovascular changes were not the result of alterations in blood gases, since these remained unchanged. When ketamine, 0.1 to 4 mg., was injected into the temporal artery of goats anesthetized with pentobarbital, no changes were observed in B.P., C.O., H.R. or CBF. Ketamine (2 mg./kg.) intravenously administered to unanesthetized goats produced anesthesia and an increase in B.P., C.O., H.R., CBF, and arterial carbon dioxide (Paco2) levels. Administered by the same route and dosage in mechanically ventilated goats previously anesthetized with sodium pentobarbital, ketamine did not produce any changes in cardiovascular or blood‐gas measurements. It was therefore concluded that ketamine produces peripheral sympathomimetic effects primarily by direct stimulation of CNS structures, and that when these structures are depressed by pentobarbital, the peripheral effects of ketamine are ameliorated.

Neurologic Outcome in Rats Following Incomplete Cerebral Ischemia during Halothane, Isoflurane, or N2O

Using rats in which incomplete cerebral ischemia was induced, the authors evaluated the effects of halothane (H) and isoflurane (I) on neurologic outcome compared to nitrous oxide (N2O) controls. Incomplete cerebral ischemia was produced by right carotid artery occlusion combined with hemorrhagic hypotension. Neurologic outcome was evaluated using a graded deficit score from 0 to 5 (0 = normal, 5 = death associated with stroke). Two levels of cerebral ischemia were tested. At moderate ischemia with hypotension of 30 mmHg, an FIO2 of 0.3, and ischemic periods of 30 or 45 min, N2O produced a deficit of 4.7–5.0 and a mortality rate of 90–100%. In contrast, halothane (1 MAC) and isoflurane (1 MAC) resulted in similar deficit scores (H = 1.1–1.8, I = 1.4–1.6) and mortality rates (H = 17–30%, I = 17–20%). Cerebral blood flow (CBF) measured with radioactive microspheres showed a 60–65% decrease in the ischemic hemisphere at this level of hypotension. With severe ischemia with hypotension = 25 mmHg, FIO2 = 0.2, and a 30-min period of ischemia, deficit scores increased to 3.0 and 3.9 with 1 MAC halothane and 1 MAC isoflurane, respectively. Morality rates also increased to 40% with halothane and 70% with isoflurane. Increasing the concentration of halothane or isoflurane to 2 MAC did not significantly improve outcome. Brain histology demonstrated extensive neuronal damage in striatal, hippocampal, and neocortical regions of N2O control treated rats, and less damage with little difference between H-and I-treated rats at each level of ischemia. Using this model of incomplete cerebral ischemia, halothane and isoflurane provided significantly better neurologic and histologic outcomes when compared to N2O controls, with little difference between the two volatile anesthetics.

Effects of Remifentanil, a New Short-acting Opioid, on Cerebral Blood Flow, Brain Electrical Activity, and Intracranial Pressure in Dogs Anesthetized with Isoflurane and Nitrous Oxide

BackgroundA new short-acting opioid, remifentanil, is metabolized by esterase activity in blood and tissue. It is important to know whether remifentanil may decrease the time to recovery of opioid-induced cardiovascular and cerebral effects compared to that of other short-acting agents such as alfentanil. MethodsBaseline measures were made during 1% end-tidal isoflurane and 50% N2O in oxygen in dogs. Approximately equipotent low- and high-dose remifentanil (0.5 and 1.0

Cerebral autoregulation in awake versus isoflurane-anesthetized rats

mUg. kg−1. min−1) or alfentanil (1.6 and 3.2

Nitrous oxide markedly increases cerebral cortical metabolic rate and blood flow in the goat

mUg. kg−1. min−1) were infused for 30 min each (total infusion time 60 min) followed by a 30-min recovery period. Blood pressure, heart rate, and intracranial pressure were recorded continuously. Electroencephalogram measurements were made using aperiodic analysis, and regional cerebral blood flow using radioactive microspheres. ResultsBoth remifentanil and alfentanil decreased blood pressure and heart rate 25–30%. Cortex, hippocampus, and caudate blood flow decreased 40–50% during opioid infusion, but flow changes in lower brain regions were modest or absent. The electroencephalogram showed a shift from low-amplitude, high-frequency activity during baseline to high-amplitude, low-frequency activity during opioid infusion. During a 30-min recovery period, heart rate, electroencephalogram, and regional cerebral blood flow recovered to baseline levels in remifentanil- but not in alfentanil-treated dogs. Blood pressure and intracranial pressure decreased during opioid infusion and increased above baseline levels during the recovery period in remifentanil-treated dogs. ConclusionsThese results show that the cardiovascular and cerebral effects of remifentanil and alfentanil are similar but that recovery of these parameters occurs sooner following remifentanil.

Role of nitric oxide, adenosine, N-methyl-D-aspartate receptors, and neuronal activation in hypoxia-induced pial arteriolar dilation in rats.

We evaluated regional cerebral and spinal cord blood flow in rats during isoflurane anesthesia. Tissue blood flow was measured in cerebral cortex, subcortex, midbrain, and spinal cord using radioactive microspheres. Blood flow autoregulation was measured within the following arterial blood pressure ranges (mm Hg): 1 = less than 50, 2 = 50-90, 3 = 90-130, 4 = 130-170, 5 = greater than 170. Arterial blood pressure was increased using phenylephrine infusion and decreased with ganglionic blockade and hemorrhage. Three treatment groups were studied: 1 = awake control, 2 = 1.0 minimum alveolar anesthetic concentration (MAC) isoflurane, 3 = 2.0 MAC isoflurane. Autoregulation was seen in awake rats from 50 to 170 mm Hg in all tissues. The autoregulatory coefficient (change in blood flow/change in blood pressure) was increased in midbrain and spinal cord during 1.0 MAC isoflurane and in all tissues during 2.0 MAC isoflurane (P less than 0.05). Within the arterial blood pressure range of 90-130 mm Hg, isoflurane produced the following changes in tissue blood flow (percent of awake control): 1.0 MAC isoflurane: cortex = 87% +/- 8% (P greater than 0.30), subcortex = 124% +/- 11% (P greater than 0.05), midbrain = 263% +/- 20% (P less than 0.001), spinal cord = 278% +/- 19% (P less than 0.001); 2.0 MAC isoflurane: cortex = 137% +/- 13% (P less than 0.05), subcortex = 272% +/- 24% (P less than 0.001), midbrain = 510% +/- 53% (P less than 0.001), spinal cord = 535% +/- 50% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)