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Biomedical subjects

R A Theye

Publications and source records attributed to R A Theye.

16 recordsLinked to original sources
PubMed1977

Porcine malignant hyperthermia: role of skeletal muscle in increased oxygen consumption.

During malignant hyperthermia (MH) induced by halothane and succinylcholine, oxygen consumption (VO2) of whole body, muscle and the splanchnic area was calculated from measurements of blood flow and arteriovenous oxygen content difference. Caudal body blood flow was isolated and measured (six animals) for determination of average muscle VO2 in the hind limbs, buttocks, and flanks. The increase in muscle VO2 was extrapolated to total skeletal muscle and compared with the increase in whole body VO2 (same six animals). The average increase in VO2 for both total muscle and whole body during the period of maximum increase was about 6 ml O2/min/kg body weight. Splanchnic VO2 (four animals) tended to decrease during MH. The data support the hypothesis that the metabolic changes in MH are due to a disorder of skeletal muscle and that the increase in whole body VO2 is due to the increase in muscle VO2.

Animals↗
PubMed1977

Canine systemic and cerebral effects of hypotension induced by hemorrhage, trimethaphan, halothane, or nitroprusside.

In 62 dogs, hypotension to a mean arterial pressure of either 40 or 50 torr (equivalent to a cerebral perfusion pressure of 30 or 40 torr, respectively) for one hour was induced by hemorrhage (oligemia), trimethaphan, halothane, or sodium nitroprusside. Before and during the period of hypotension, the following were measured: mean arterial blood pressure, cardiac output, whole-body O2 consumption, cerebral blood flow, cerebral O2 consumption, arterial blood gases, blood O2 content, and lactate, pyruvate, glucose, epinephrine, and norepinephrine concentrations. At the end of the period of hypotension, brain biopsies were taken for determination of adenosine triphosphate, phosphocreatine, lactate, and pyruvate concentrations. In an additional eight dogs following one hour of hypotension (at 40 torr) induced by one of the four techniques, the brains were perfused with carbon black, removed, and examined. In another ten dogs following hypotension (at 40 torr) induced with either halothane or trimethaphan, the animals were observed for three days and then killed for examination of the brain. Dogs maintained at a mean arterial pressure of 40 torr, despite differences in cerebral blood flow, demonstrated metabolic disturbances compatible with systemic and cerebral hypoxia. These were greatest in those dogs given nitroprusside in excess of 1.0 mg/kg, presumably due to cyanide toxicity. In dogs maintained at 50 torr, metabolic disturbances were minimal or absent in the halothane- and nitroprusside-treated dogs but were still apparent in the oligemic and trimethaphan-treated dogs. Carbon black infusions revealed no evidence of non-homogeneous flow. Three of the ten dogs observed for three days had persistent post-hypotension neurologic dysfunction. Two of these were given trimethaphan. The results suggest that the systemic and cerebral effects of halothane and nitroprusside (at doses less than 1.0 mg/kg) are similar and at a mean arterial pressure of 50 torr are of little consequence. By contrast, hypotension induced by trimethaphan or oligemia results in detectable metabolic alterations even at a pressure of 50 torr.

Adenosine Triphosphate↗
PubMed1977

Oxygen uptake of canine whole body and hind limb with hypocapnic alkalosis.

The effect of hypocapnic alkalosis induced by hyperventilation on whole-body and hind-limb oxygen uptake (VO2) was studied in dogs anesthetized with pentobarbital. In the intact dog with a self-perfused hind limb, increasing pHa from 7.41 to 7.58 increased whole-body VO2 8% and decreased hind-limb VO2 6%. Isolated hind limbs perfused with heparinized whole blood had similar decreases in VO2 with increases in arterial blood pH (pHa). However, isolated hind limbs perfused with whole blood containing citrate, phosphate, and dextrose (CPD) showed muscle twitches, had larger VO2 values at identical pHa's, and had an increase in VO2 with increase in pHa. These changes with a CPD perfusate were associated with low levels of ionized calcium (less than 0.5 mEq/1), disappeared when calcium ion spontaneously increased to 1.0 mEq/1, and could be prevented or abolished by the addition of calcium chloride, dantrolene, d-tubocurarine, or succinylcholine. These results are in accord with the findings of others regarding an increase in whole-body VO2 with hypocapnic alkalosis, but do not support a contributory role of skeletal muscle to the overall increase.

Alkalosis↗
PubMed1976

Suxamethonium-induced porcine malignant hyperthermia.

Metabolic, haemodynamic and neuroendocrine responses to suxamethonium (SCh) were measured in five normal swine and five swine susceptible to malignant hyperthermia (MH), to compare the responses with those previously reported for halothane. Following SCh, the onset of MH was sooner and more abrupt than following halothane. The maximal changes in aerobic metabolism and body temperature sere similar, while the changes in lactate, potassium, hydrogen ion and catecholamine concentrations were smaller than those observed following halothane. These results are discussed in terms of the action of chemical depolarizing drugs such as suxamethonium and acetylcholine. The propagated muscle action potentials produce an increase in the free intracellular calcium concentration which may be self-regenerative, but which may become uncontrollable because of the peculiarities of MH that effect the calcium pump or storage areas.

Animals↗
PubMed1976

Halothane-induced porcine malignant hyperthermia: metabolic and hemodynamic changes.

Metabolic, hemodynamic and neuroendocrine responses to halothane were measured in five normal and five malignant hyperthermia-susceptible (MHS) swine. Constant-volume ventilation was used. There was no therapeutic intervention. In NHS animals, blood lactate concentrations increased first, and the initial increases appeared to be non-hypoxic in origin. Lactate concentrations increased progressively to more than 20 mum/ml. Whole-body oxygen consumption increased almost twofold, and hind limb muscle oxygen consumption increased almost threefold. Extrapolated increases in muscle oxygen consumption accounted for about 55 per cent of the increase in whole-body oxygen consumption. Respiratory and metabolic acidosis, marked hyperkalemia, and increases in catecholamines and temperature occurred secondarily and were accompanied by progressive circulatory failure.

Animals↗
PubMed1976

Porcine malignant hyperthermia induced by halothane and succinylcholine: failure of treatment with procaine or procainamide.

Metabolic, hemodynamic and neuroendocrine responses to the combined use of halothane and succinylcholine (SCh) were measured in five normal swine and five swine susceptible to malignant hyperthermia (MH). Constant-volume ventilation was used, and no therapy was instituted. The overall response in susceptible swine was fulminant, in that it involved the rapid onset of SCh-induced MH combined with the more severe metabolic, endocrine, and cardiovascular effects of halothane-induced MH. Maximal changes in VO2 were equivalent with either drug or both combined, while changes in lactate, potassium (K+), pH, and catecholamines were perhaps synergistic. Utilizing similar measurements, procaine or procainamide was used in 20 susceptible swine in attempts to prevent MH initiated by halothane, SCh, or both. Recommended therapeutic doses of either drug did not prevent characteristic MH changes in oxygen consumption, cardiac output, lactate, K+, pH, catecholamines, or temperature.

Animals↗
PubMed1976

Dantrolene in porcine malignant hyperthermia.

The effectiveness of intravenous administration of dantrolene in prevention and treatment of fulminant malignant hyperthermia (MH) initiated by halothene and succinylcholine (SCh) in genetically susceptible swine was assessed. In six animals, prior administration of dantrolene in doses of 5 mg/kg or more prevented MH, while 1 or 3 mg/kg attenuated MH, and 0.1 mg/kg had no effect. In ten additional swine, therapy was not started until MH was fulminant. Five of these were then given supportive therapy only (discontinuation of anesthesia, hyperventilation with oxygen, surface cooling, and NaHCO3). The remaining five received the same supportive therapy, plus dantrolene (7.5 mg/kg). With supportive therapy only, arterial blood pH, Po2 and Pco2 returned toward normal, but oxygen consumption (Vo2), blood lactate, potassium (K+), catecholamines, and temperature continued to increase and the course of MH was unaltered. When dantrolene was added to supportive therapy, Vo2, lactate, K+, catecholamines, and temperature decreased, and the course of MH was dramatically slowed and, apparently, reversed.

Animals↗
PubMed1975

Whole-body and organ Vo2 changes with enflurane, isoflurane, and halothane.

This study was designed to determine the effects of enflurane on canine whole-body and individual organ oxygen consumption (Vo2). Whole-body, myocardial, splanchnic, renal, and skeletal muscle Vo2 were determined at enflurane concentrations equivalent to those used in previous studies with halothane and isoflurane. With increasing enflurane concentrations, whole-body Vo2 decreased progressively. The major component of the decrease was a reduction in myocardial Vo2 resulting from a decrease in myocardial external work as a result of a decrease in cardiac output and arterial pressure. Other organs contributed to a lesser extent to the overall decrease in whole-body Vo2. In each respect the findings with enflurance were not significantly different from those with halothane and isoflurane. These findings did support to the view that anaesthetic agents are not general metabolic depressants and that observed changes in whole-body Vo2 reflect the summated changes in individual organ Vo2 occasioned by an anaesthetic-induced change in organ function and metabolic requirements.

Animals↗
PubMed1975

Individual organ contributions to the decrease in whole-body Vo2 with isoflurane.

The present study was designed to determine whether there were differebnces between the effects of isoflurane and halothane on canine whole-body Vo2 and myocardial, splanchnic, renal, and skelatal muscle Vo2's were determined at isoflurane concentrations equivilent to those used in a previous study with holothane. With increases in isoflurane, whole-body Vo2 decreased progressively. As with halothane, the major comdial Vo2 that was related to a reduction in cardiac output and arterial blood pressure; contributions from other organs were minor. No significant difference between the effects of isoflurane and halothane on whole-body or individual organ Vo2's was found. These finding support the view that anesthetic agents are no general metabolic depressants and that observed changed in whole-body Vo2 reflect the su-mated changes in individual argan Vo2's occasioned by an anesthetic-induced change in organ function and metabolic requirements.

Anesthetics↗
PubMed1975

Pathophysiology of hyperkalemia induced by succinylcholine.

SCh is unequivocally contraindicated in the management of patients who have sustainded thermal trauma or direct muscle trauma and those who have neurologic disorders involving motor deficits, including tetanus. The mechanism is clear in some, but not all, of these conditions, and is related to increased chemosensitivity of the muscle membrane due to the development of receptor sites in extrajunctional areas. Though SCh induces a small release of K+ in normal muscle, it produces a potentially lethal efflux in the presence of increased sensitivity. This K+-releasing action of SCh begins about 5 to 15 days after injury and persists for 2 to 3 months in patients who have sustained burns or trauma, and perhaps 3 to 6 months in patients with upper motor neuron lesions.

Acetylcholine↗
PubMed1975

Plasma dopamine-beta-hydroxylase activity and catecholamine levels in anesthetized dogs following acute hemorrhage.

Because dopamine-beta-hydroxylase (DBH) is released from storage vesicles in adrenergic nerves and the adrenal medulla along with catecholamines, determination of circulating levels of this enzyme might serve as an index of sympathoadrenal activity. This hypothesis has been studied in dogs anesthetized with cyclopropane, isoflurane, and thiopental that were subjected to a single acute hemorrhage and followed for 5 hours. Plasma DBH activity and catecholamine levels were determined before and every 30 minutes after the hemorrhage. Changes in DBH activity did not correlate well with changes in levels of circulating catecholamines in the dog in response to this form of stress.

Acute Disease↗
PubMed1975

In vivo toxic effects of halothane on canine cerebral metabolic pathways.

The effects of high concentrations of halothane on cerebral metabolism were examined in dogs with the aid of an extracorporeal circuit to support the systemic circulation. At blood levels exceeding those representing equilibration with 2.3% halothane, a dose-related decrease in cerebral oxygen consumption (CMR02) occurred that was unrelated to the presence or absence of an active electroencephalogram. In this circumstance, despite adequate oxygen delivery, a dose-related alteration in oxidative phosphorylation also occurred as evidenced by progressive decreases in cerebral concentrations of ATP and phosphocreatine and concomitant increases in cerebral lactate and lactate/pyruvate ratio. These effects were totally reversible, except for persistence of increased of increased CMR02, after return to low halothane concentrations. It is concluded that the mechanisms of the cerebral metabolic effects of halothane differ from those of thiopental and, at high concentrations, are at least in part related to interference with oxidative phosphorylation. These in vivo studies confirm the potentially detrimental effects of high halothane concentrations on cerebral metabolic pathways as demonstrated by others in vitro.

Adenosine Triphosphate↗