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M Booke

Publications and source records attributed to M Booke.

62 records · Page 4Linked to original sources
PubMed1996

Nitric oxide synthase inhibition versus norepinephrine in ovine sepsis: effects on regional blood flow.

Hypotension is a serious problem in septic patients. We investigated regional perfusion in several organs during treatment of hyperdynamic sepsis in sheep. Sepsis was induced and maintained for the entire experiment with a continuous infusion of live Pseudomonas aeruginosa. Treatment with either norepinephrine or the nitric oxide synthase inhibitor L omega-mono-methyl-arginine (L-NMMA) was begun after 24 h of sepsis and continued for 24 h. The norepinephrine dosage was adjusted to achieve the same increase in mean arterial pressure as that obtained by a fixed dose of L-NMMA (7 mg/kg/h). Blood flows were analyzed by the microsphere technique. Both compounds restored blood pressure effectively, but only L-NMMA caused a significant increase in systemic vascular resistance, concomitant with a significant fall in cardiac output. Sepsis caused an increase in myocardial blood flow and a redistribution of blood flow away from the pancreas and the stomach. Renal blood flow was not significantly elevated. During treatment with either compound, renal blood flow remained unchanged, despite a fall in cardiac output in the L-NMMA group. Unchanged renal blood flow combined with the restoration of arterial blood pressure caused a significant increase in urine output. Both L-NMMA and norepinephrine caused a redistribution of blood flow to the colon. Pancreatic blood flow was further reduced by L-NMMA but the oxygen extraction improved simultaneously, so that oxygen availability in the pancreas might have been unchanged. Because ischemic pancreatitis in sepsis is likely to trigger multiorgan failure, further investigations in that area are desirable.

Animals↗
PubMed1995

S-ethylisothiourea, a nonamino acid inhibitor of nitric oxide synthase, reverses septic vasodilation in sheep.

S-ethylisothiourea (3936W92) is a nonamino acid antagonist of nitric oxide synthase. Its selectivity for the inducible form of nitric oxide synthase is twice as high as for the constitutive form of the enzyme. We tested 3936W92 in 20 sheep, which were surgically prepared for chronic study. In all sheep, a hyperdynamic sepsis was induced by a continuous infusion of live Pseudomonas aeruginosa. After 24 h of sepsis, nine sheep received a continuous infusion of 3936W92 over the next 24 h, whereas the control group (n = 9) received saline instead. Two sheep died within the first 24 h of sepsis. 3936W92 caused a complete reversal of the hyperdynamic circulation, while sheep in the control group remained hyperdynamic. Although the cardiac index decreased significantly during treatment with 3936W92 (7.9 +/- .8 vs. 6.0 +/- .7 l/min/m2), a simultaneous increase in oxygen extraction prevented oxygen consumption from falling.

Animals↗
PubMed1995

Use of nitric oxide synthase inhibitors in animal models of sepsis.

Sepsis, as a general inflammatory process, affects the whole organism, mainly because of the intense vasodilation and reduced perfusion pressures associated with it. The high mortality rates seen with sepsis are correlated with a reduction in mean arterial pressure. Therefore, the restoration of adequate arterial pressures is imperative. Nitric oxide (NO.) is at least partly responsible for the vasodilation. Inhibition of nitric oxide synthase (NOS) is, therefore, a logical approach for the treatment of sepsis. As with any other vasoconstrictive drug, NOS inhibitors are clinically indicated only in hyperdynamic sepsis. In animal models, their administration leads to an immediate restoration of blood pressure, accompanied by improved myocardial, pulmonary, and renal function. An increase in oxygen extraction prevents oxygen consumption from decreasing, despite a marked reduction in cardiac output to normal concentrations. In sepsis, virtually all regional blood flows are increased. In our experiments, no organ systems showed a reduction below preseptic baseline values when NOS inhibitors were administered. Furthermore, NOS inhibition did not cause an increase in lactate concentrations, indicating adequate nutritive organ blood flow. Consequently, NOS inhibitors seem to be beneficial and safe when administered under the right circumstances and in a controlled fashion.

Amino Acid Oxidoreductases↗
PubMed1995

Endotoxin versus bacteremia: a comparison focusing on clinical relevance.

All phenomena seen under ovine endotoxemia or bacteremia are typically observed in septic humans as well. The lethality (approximately 20%) in both sepsis models underlines the severity of the experimental sepsis in these models. As mentioned above, both models are ideal to objectify the effects of new therapeutic approaches for the treatment of sepsis, because they provide stable conditions. We tested the inhibition of nitric oxide synthase in both models: Nitric oxide is the main mediator of the vasodilation and the hyperdynamic circulation seen in sepsis. Since the restoration of the perfusion pressure is the major therapeutic goal to prevent further tissue damage (Chernow et al. 1990), the blockade of the nitric oxide synthase seems to be a logical approach for the treatment of hyperdynamic sepsis. Therefore, we tested the nitric oxide synthase inhibitor N(W)-nitro-L-arginine methyl ester (L-NAME) in the endotoxemic sheep model as well as in the bacteremic model. L-NAME reversed the hyperdynamic circulation of sepsis (Meyer et al.1992; Dehring et al.1993). The cardiac output was lowered back to baseline, and at the same time, the arterial pressure was elevated to baseline niveau, both resulting in a marked increase in systemic vascular resistance (figure 3). The pulmonary artery pressure showed only a slight increase, but due to the marked reduction in cardiac output the pulmonary vascular resistance increased significantly. The oxygen extraction was elevated to an extent, which prevented the oxygen consumption to fall, although the oxygen delivery dropped significantly because of the lowered cardiac output (figure 4). The intrapulmonary shunt was brought back to baseline (Meyer et al.1994a), allowing an improved pulmonary oxygen uptake. The renal function improved significantly after nitric oxide synthase inhibition in endotoxemia as well as in bacteremia (Hinder et al.1994; Lingnau et al.1994). Not only was the creatinine clearance elevated, but the urine output also increased, lowering the positive fluid balance. Another inhibitor of nitric oxide synthase N(W)-Mono-Methyl-L-Arginine (L-NMMA) was recently tested in these models as well. This drug is now already in clinical trials. The fact that the effects of these nitric oxide synthase inhibitors in septic humans are similar to the effects in the described experimental sepsis models proves the clinical relevance of the endotoxemic and the bacterimic sheep model.

Animals↗
PubMedDate not supplied

Enhancement of axillary brachial plexus block anesthesia by coadministration of neostigmine.

BACKGROUND AND OBJECTIVES: The acetylcholinesterase inhibitor neostigmine has shown peripherally mediated analgesic action in recent preclinical and clinical studies. The present study investigates the effectiveness of adding neostigmine to a local anesthetic, mepivacaine, in patients receiving axillary brachial plexus block for upper extremity surgery. METHODS: In a double-blind, randomized study 34 patients were assigned to the treatment group: Neostigmine (NM) (500 microg) + mepivacaine (M) (500 mg) (NM, n = 17) as drugs for the plexus block, or to control group: mepivacaine (500 mg) + saline (0.9%, 1 mL) (M, n = 17). RESULTS: The onset and duration of sensory and motor block was similar in both groups. Patients receiving NM had significantly lower pain ratings [visual analogue scores (VAS): 14.7 +/- 9.9 vs 32.4 +/-23.5; P < .05] 24 hours after surgery, and a lower number of patients in the NM group needed supplemental analgesics during the first 24 hours postoperatively. No adverse events were recorded for either group. CONCLUSIONS: Peripherally administered neostigmine improves postoperative analgesia in axillary brachial plexus block.

Adjuvants, Anesthesia↗
PubMedDate not supplied

Inhaled nitric oxide selectively reduces pulmonary hypertension after ovine smoke inhalation but does not improve oxygenation.

Inhaled nitric oxide (NO) is known to selectively reduce pulmonary hypertension and improve the ventilation-perfusion relationship in subjects with lung injury of various origin. However, some forms of lung injury do not react to inhaled NO at all, or show only a reduction in pulmonary arterial pressure. Very little is known about the effects of inhaled NO after smoke inhalation injury. We investigated the effects of inhaled NO in an established model of ovine smoke inhalation injury. Chronically instrumented sheep (n = 8) had tracheostomies and were insufflated with smoke generated from burning cotton cloth (4 times at 12 breaths each). They were then connected to a ventilator with oxygen-enriched air to achieve arterial oxygen tensions within the normal range. After 48 hours, NO was added to the inspired gas in ascending concentrations of up to 100 ppm. Systemic and pulmonary hemodynamics as well as oxygen transport were analyzed. Inhaled NO dose dependently lowered the pulmonary hypertension. Concentrations higher than 20 ppm did not further reduce the pulmonary artery pressure. Right ventricular stroke work index was significantly improved owing to the reduction in pulmonary vascular resistance. Arterial oxygenation, however, was not optimized by inhaled NO, probably because of interstitial edema formation.

Administration, Inhalation↗