Todd A. Richards

An analysis of responses to levosimendan in the pulmonary vascular bed of the cat.

Calcium-sensitizing drugs, such as levosimendan, are a novel class of drug therapy for heart failure. We investigated the hypothesis that levosimendan is a pulmonary vasodepressor mediated through inhibition of phosphodiesterase, adenosine triphosphate (ATP)-dependent potassium channels, or both. We investigated responses to the calcium sensitizer levosimendan in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure when lobar arterial pressure was increased to a high steady level with the thromboxane A2 analog U-46619. Under increased-tone conditions, levosimendan caused dose-related decreases in lobar arterial pressure without altering systemic arterial and left atrial pressure. Responses to levosimendan were significantly attenuated, although not completely, after the administration of U-37883A, a vascular selective nonsulfonylurea ATP-sensitive K+-channel-blocking drug. Responses to levosimendan were not significantly different after the administration of the nitric oxide synthase inhibitor l-N5-(1-iminoethyl)-ornithine or the cyclooxygenase inhibitor sodium meclofenamate or when lung ventilation was interrupted. These data show that levosimendan has significant vasodilator activity in the pulmonary vascular bed of the cat. They also suggest that pulmonary vasodilator responses to levosimendan are partially dependent on activation of ATP-sensitive K+ channels and independent of the synthesis of nitric oxide, activation of cyclooxygenase enzyme, or changes in bronchomotor tone in the pulmonary vascular bed of the cat.

Ultrarapid opiate detoxification: a review

PurposeThis review on ultrarapid detoxification examines the pharmacology, techniques, and efficacy of this potentially promising technique and contrasts it with conventional treatment modalities.SourceThe information found here is derived from experiences at the Texas Tech University, government reports, and peer reviewed journals.Principal findingsIncidence and prevalence of heroin use is on the rise. Social and treatment costs suggest that this problem is staggering. Approximately 400,000 patients are enrolled in or are actively seeking methadone therapy. While many of these individuals want to undergo detoxification, traditional techniques, including methadone tapering are usually unsuccessful. The withdrawal syndrome is extremely unpleasant, may be fatal, and deters patients from completing the detoxification process. Ultrarapid detoxification entails general anesthesia in conjunction with large boluses of narcotic antagonists. This combination allows the individual to completely withdraw from the opiate without suffering the discomfort of the withdrawal syndrome. Unless performed properly, this procedure can be dangerous due to the sympathetic outflow. However, with proper support, this danger can be mitigated.ConclusionUltrarapid opiate detoxification, performed under the proper circumstances, is associated with few adverse events and is relatively comfortable for patients who seek treatment for their addition.RésuméObjectifLa présente étude portant sur la désintoxication ultrarapide revoit la pharmacologie, les techniques et l’efficacité de cette technique potentiellement prometteuse et la compare avec les modalités thérapeutiques traditionnelles.SourceNos informations sont tirées des expériences à la Texas Tech University, des rapports officiels et des journaux scientifiques. Constatations principales : L’incidence et la prévalence de l’usage d’héroïne sont en hausse. Les coûts sociaux et thérapeutiques de ce problème sont renversants. Environ 400 000 patients suivent, ou cherchent activement, un traitement à la méthadone. Beaucoup acceptent une désintoxication, mais les techniques traditionnelles, incluant l’approche dégressive avec la méthadone, sont habituellement infructueuses. Le syndrome de sevrage est très désagréable, peut être fatal et décourage les patients d’aller jusqu’au bout. La désintoxication ultrarapide nécessite une anesthésie générale conjointement avec d’importants bolus d’antagonistes narcotiques. Cette combinaison permet la suppression complète des opiacés sans subir l’inconfort du syndrome de sevrage. Si elle n’est pas réalisée correctement, cette intervention comporte un danger, lié à l’influx sympathique, danger réduit par une assistance appropriée.ConclusionLa désintoxication ultrarapide aux opiacés, réalisée dans des conditions appropriées, est associée à peu d’événements indésirables et est relativement confortable pour les patients qui cherchent un traitement à leur dépendance.

Anesthetic considerations in patients with Alzheimer’s disease

Alzheimers disease is a form of dementia that is estimated to affect approximately 3 to 4 million Americans. Given the substantial number of people affected with this disease, it is likely that anesthesiologists will encounter many patients with Alzheimers disease. Questions as to potential problems including informed consent, drug interactions, and preoperative progression of the disease may arise. This review describes anesthetic considerations, including pharmacologic and physiologic issues, in this growing population.

Pulmonary Vascular Responses to Ma Huang Extract

OBJECTIVE To test the hypothesis that ma huang induces a pressor response in the pulmonary vascular bed of the cat by activating alpha(1)-adrenergic receptors DESIGN Prospective vehicle-controlled study. SETTING Research laboratory at Texas Tech University School of Medicine, Lubbock, TX. SUBJECTS Intact chest preparation; adult mongrel cats. INTERVENTIONS The effects of phentolamine, a nonselective alpha receptor blocker, and prazosin, an alpha(1) selective antagonist, were investigated on pulmonary arterial responses to ma huang, phenylepherine, norepinephrine, and U-46619, a thromboxane A(2) mimic. MEASUREMENTS AND MAIN RESULTS Lobar arterial perfusion pressure was continuously monitored, electronically averaged, and recorded with constant flow in the isolated left lower lobe vascular bed of the cat. Phentolamine and prazosin significantly reduced vasoconstrictor pulmonary perfusion pressure increases induced by ma huang. CONCLUSIONS Ma huang has significant vasopressor activity in the pulmonary vascular bed of the cat mediated predominantly by alpha(1)-adrenergic receptor activation.

Analysis of Responses to Valerian Root Extract in the Feline Pulmonary Vascular Bed

OBJECTIVES This study was undertaken to investigate pulmonary vascular response to valerian (Valeriana officinalis) in the feline pulmonary vasculature under constant flow conditions. DESIGN In separate experiments, the effects of NG-L-nitro-L-arginine methyl ester (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an adenosine triphosphate (ATP)-sensitive potassium (K+) channel blocker, meclofenamate, a nonselective cyclooxygenase (COX) inhibitor, bicuculline, a GABA(A) receptor antagonist, and saclofen, a GABA(B) antagonist, were investigated on pulmonary arterial responses to various agonists in the feline pulmonary vascular bed. These agonists included valerian, muscimol, a GABA(A) agonist, SKF-97541 a GABA(B) agonist, acetylcholine (ACh), and bradykinin, both inducers of nitric oxide synthase, arachidonic acid, a COX substrate, and pinacidil, an ATP-sensitive K+ channel activator, during increased tone conditions induced by the thromboxane A2 mimic, U46619. SETTINGS/LOCATION Laboratory investigation. SUBJECTS Mongrel cats of either gender. INTERVENTIONS Injections of the abovementioned agonists and antagonists were given. OUTCOME MEASURES Baseline pulmonary tone, responses to the agonists, and responses to the agonists after injections of antagonists were all measured via a pulmonary catheter transducer and recorded. RESULTS Valerian root extract is a potent smooth muscle dilator in the feline pulmonary vascular bed. The vasodilatory effects of valerian root extract were unchanged after the administration of L-NIO, glibenclamide, and meclofenamate. These effects were ablated, however, by both saclofen and bicuculline. The ability of saclofen and bicuculline to modulate the dilatory effects of valerian root extract was not statistically different. CONCLUSIONS The vasodilatory effects of valerian root extract are mediated by a nonselective GABA mechanism.

Influence of TMB-8 and thapsigargin on vasoconstrictor responses in the pulmonary vascular bed of the cat.

The effects of 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), a protein kinase C (PKC) inhibitor, and thapsigargin, a Ca2+ATPase inhibitor, on pressor responses were studied in the pulmonary vascular bed of the intact-chest anesthetized cat. Under conditions of constant lobar blood flow in the cat, injections of the angiotensin peptides (ANG II), norepinephrine (NE), serotonin (5-HT), Bay K 8644, and the thromboxane A2 mimic U46619 into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure and responses were reproducible with respect to time. Intravenous infusion of TMB-8 at 1.0 μg · kg−1 reduced the pressor response to the ANG II and to NE. However, TMB-8 did not alter pressor responses to 5-HT, U46619, or Bay K 8644. In a separate series of experiments, the effects of thapsigargin were investigated and intravenous infusion of the Ca2+ATPase inhibitor at 1.0 μg · kg−1 also reduced pressor responses to the ANG II and to NE but did not alter pressor responses to 5-HT, U46619, and Bay K 8644. The data provide support for the hypothesis that vasoconstrictor responses to ANG II and NE in the pulmonary vascular bed are mediated in part by the activation of protein kinase C (PKC) and sarcoplasmic reticulum Ca2+ATPase-sensitive mechanisms in the cat. The present data suggest that pulmonary pressor responses to U46619, 5-HT, and Bay K 8644 are not mediated by PKC or Ca2+ATPase activation in the pulmonary vascular bed of the cat.

Ephedrine in the cat lung vasculature.

Background:  Ephedrine is one of the most commonly used non‐catecholamine sympathomimetic agents. It is used in operating rooms and critical care settings worldwide. While it has many side effects, its ability to rapidly raise blood pressure makes it an ideal agent to maintain homeostasis as well as in emergency situations. While its effects are known to be mediated by an α‐mediated mechanism, the exact α subtype is unknown. In addition, no studies using ephedrine have been performed in the pulmonary vascular bed of the cat.