Biomedical subjects

N Roewer

Publications and source records attributed to N Roewer.

At least 109 records · Page 6Linked to original sources

PubMed1995

Assessment of changes in left ventricular wall stress from the end-systolic pressure-area product.

We have measured the left ventricular (LV) end-systolic (ES) pressure-area product in 30 patients under general anaesthesia. We multiplied systolic arterial pressure with the ES cavity area obtained by transoesophageal echocardiography, and compared the product with M-mode derived ES wall stress before and during cardiovascular treatment. To attain appropriate mean arterial pressure during major non-cardiac surgery, 10 hypertensive patients required treatment with nitroglycerin, 10 septic patients received noradrenaline and 10 patients with intraoperative cardiac failure were given adrenaline. Baseline values and relative changes in the ES pressure-area product correlated well (r = 0.85 and r = 0.87; P < 0.05) with those of ES wall stress. Changes in the ES pressure-area product by more than 10% reflected ES wall stress changes with a sensitivity of 88% and a specificity of 94%. With adrenaline, the ES pressure-area product and ES wall stress did not change significantly, while systemic vascular resistance increased by 20%. The ES pressure-area product seems suitable for the detection of intraoperative LV wall stress changes.

Adult↗

PubMed1995

Can pulmonary aspiration of gastric contents be prevented by balloon occlusion of the cardia? A study with a new nasogastric tube.

Rapid-sequence induction of anesthesia and the application of cricoid pressure are the two most common maneuvers performed when patients requiring general anesthesia are at risk of pulmonary aspiration. However, these procedures are quite elaborate and entail risks and dangers in themselves. A new disposable nasogastric balloon tube was developed to prevent the reflux of gastric contents by blocking the cardia with a balloon. The effectiveness of this tube was investigated in animals and healthy volunteers. In addition, we describe the initial experience with the tube during ventilation via a mask in patients with an increased risk of aspiration. Twelve pigs with a blocked cardia did not show any gastroesophageal reflux under six different procedures to provoke vomiting and regurgitation (gastric fluid filling with different volumes, head-down positioning, drug-induced vomiting, external gastric compression before and after surgical ligation of the pyloric orifice), whereas 37 of 48 provocation maneuvers led to a reflux in eight additional pigs with an unblocked cardia. In 26 test subjects with a blocked cardia, reflux of gastric contents was not observed when vomiting was provoked. After elimination of the cardia blockade, a reflux could be triggered in 24 of the 26 subjects. Among 42 patients in danger of aspiration, anesthesia could be induced without any problems using a nasogastric balloon tube with ventilation via a mask. The present experimental findings in animals and test subjects show that the nasogastric balloon tube can prevent gastroesophageal reflux under provocation of vomiting and regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Abnormal action potential responses to halothane in heart muscle isolated from malignant hyperthermia-susceptible pigs.

BACKGROUND: During human and porcine malignant hyperthermia (MH), cardiac dysrhythmias and altered myocardial function can be observed. It is unknown whether a primary abnormality in cardiac muscle contributes to the cardiac symptoms during MH. An abnormal response to halothane has recently been demonstrated in action potentials (APs) from MH-susceptible (MHS) human skeletal muscles. We investigated the electrophysiologic properties in trabeculae isolated from the right ventricles of normal (MHN) and MHS pigs. METHODS: The experiments were performed on electrically stimulated (1 Hz) trabeculae isolated from the right ventricles of MHS and MHN pigs. Resting membrane potentials, APs, and tension were measured with and without the presence of 1% halothane. In addition, the halothane-equilibrated muscles were exposed to caffeine in increasing doses (1, 2, and 4 mM). RESULTS: In the absence of halothane, resting potential and AP characteristics in MHS and MHN muscles did not differ significantly. Halothane did not alter resting potentials but produced different alterations in the APs in MHS and MHN muscles, whereas the decrease in twitch tension was identical. In contrast to reductions in the AP amplitude and duration in MHN muscle, halothane produced an enlargement of the APs in MHS muscle. The addition of caffeine caused nearly identical prolongations of AP duration in MHS and MHN muscles. CONCLUSIONS: This in vitro study demonstrates that halothane produces abnormal alterations in the dynamic electric properties of the ventricular excitable membrane from MHS pigs. These results suggest a latent defect in the myocardium of MHS pigs that becomes apparent in the presence of MH-triggering agents.

Action Potentials↗

PubMed1995

Cardiovascular and metabolic responses to anesthetic-induced malignant hyperthermia in swine.

BACKGROUND: Several cardiovascular disturbances, such as tachycardia and hypotension, are observed during human and porcine malignant hyperthermic (MH) crises. However, the pathophysiologic mechanisms responsible for the deterioration of cardiovascular function during MH are not completely known. The purpose of this study was to elucidate the changes in left ventricular (LV) function and metabolism and the systemic and regional hemodynamics during anesthetic-induced MH in swine. METHODS: The study was carried out in 12 open-chest MH-susceptible pigs and in 8 healthy control (non-MH-susceptible) pigs under the same conditions. The cardiovascular and metabolic responses to halothane (1% inspired) and succinylcholine (3 mg.kg-1 intravenously 15 min after the start of halothane administration) were studied. Global hemodynamic and LV variables (expressed as means +/- SEM) were determined over a period of 90 min after the beginning of halothane exposure. Simultaneous investigations were performed on hindleg and cardiac muscle to compare the regional functional and metabolic changes in these tissues. RESULTS: MH was triggered in all MH-susceptible pigs. Early (10-30 min) cardiovascular changes during the development of MH consisted of a rapid increase in heart rate (from 86 +/- 4 to 204 +/- 8 beats.min-1), cardiac index (+84%), and peak rate of change in LV pressure (+150%); stroke volume index (-24%) and mean aortic pressure (-13%) decreased progressively even in the early stage of MH. These alterations were accompanied by an early and persistent reduction in systemic vascular resistance (maximally -57%) with an increase in aortic pressure amplitude. Early changes in coronary and peripheral hemodynamics during the development of MH consisted of a three-fold increase in coronary blood flow in conjunction with a marked decrease (-77%) in coronary vascular resistance. The early circulatory changes were associated with a fourfold increase in myocardial and a 2.5-fold increase in peripheral O2 consumption. The ratio of the LV stroke work index (LVWI) to myocardial O2 consumption (MVO2) was significantly decreased, by a factor of 5. Increased catecholamine concentrations and myocardial lactate and H+ production could be demonstrated throughout the MH crisis. In the late stage of MH (> 30 min), pronounced hypotension and a subsequent decrease in cardiac index were noted. These changes were associated with a significant reduction in LV end-diastolic pressure, from 9 +/- 1 to 6 +/- 1 mmHg (P < 0.05), and in the rate of change in LV pressure, by a maximum of -25%. Coronary vascular resistance remained reduced while coronary blood flow decreased. Peripheral (hind-leg) blood flow initially increased by 48% while peripheral vascular resistance decreased by 42%, followed by a fivefold increase in peripheral vascular resistance with a marked decrease in peripheral blood flow (-88%) in the late phase of MH. CONCLUSIONS: The current findings indicate that metabolic status during MH is characterized by a demand ischemia of the heart and of the skeletal muscle. Insufficient coronary blood flow and increased metabolism as a result of tachycardia and increased concentrations of catecholamines are the dominant factors contributing to the dramatic alteration in cardiac performance during porcine MH. Acidosis, hypovolemia, and hyperkalemia, especially in the late phase of MH, are additional essential factors responsible for the progressive cardiovascular deterioration and cardiac death.

Animals↗

PubMed1995

Modulation of ryanodine-induced contractures in human skeletal muscle pretreated with dantrolene.

Dantrolene seems to be the causal therapy in malignant hyperthermia (MH) crisis but the complex mechanisms of MH and dantrolene therapy are still not fully understood. The influence of dantrolene on ryanodine-induced contractures has been reported in animal studies only. In the present study 20 patients from 17 families were tested for MH using the protocol of the European Malignant Hyperthermia Group. In addition ryanodine-induced contractures were evaluated following bolus application of 10.0 mumol.l-1 ryanodine. After pretreatment with 1 mumol.l-1 dantrolene ryanodine-provoked contractures developed significantly later in MHS (15.8 +/- 1.8 min) and MHN (46.0 +/- 4.2 min) muscle specimens than after ryanodine alone (MHS 4.8 +/- 0.7 min. (MHN 13.7 +/- 0.9 min). They were no longer observed in either group after pretreatment with 5 mumol.l-1 dantrolene. We conclude that dantrolene is able to attenuate ryanodine-induced contractures dose-dependently, and therefore it is speculated that dantrolene could specifically act at the ryanodine receptor binding site.

Adolescent↗

PubMed1995

Discordance, in a malignant hyperthermia pedigree, between in vitro contracture-test phenotypes and haplotypes for the MHS1 region on chromosome 19q12-13.2, comprising the C1840T transition in the RYR1 gene.

A point mutation in the gene encoding the skeletal muscle calcium release channel (RYR1) has been proposed as the probable cause of malignant hyperthermia (MH) in swine, where it segregates with the disease in all MH-prone strains investigated. The same C-to-T exchange in nucleotide position 1840 of the human RYR1 cDNA sequence was found in a few human MH pedigrees. We report a German MH pedigree where in vitro contracture test (IVCT) results and haplotypes of markers for the MHS1/RYR1 region including this base transition have yielded several discrepancies. The MH-susceptible phenotype was defined by IVCT performed according to the European standard protocol. Haplotypes were constructed for markers for the MHS1/RYR1 region on chromosome 19 and include the C1840T base exchange. Discussing the probabilities for a number of hypotheses to explain these data, we suggest that our results may challenge the causative role of this mutation--and possibly the role of the RYR1 gene itself--in human MH susceptibility, at least in some cases.

Calcium Channels↗

PubMed1994

[Prevention of pulmonary aspiration of stomach contents using a new balloon gastric tube. Animal experimental studies, proband studies and initial clinical results].

The rapid sequence induction of anaesthesia in patients with an increased risk of pulmonary aspiration is a quite involved procedure associated with many potential dangers. A new nasogastric balloon tube has been developed, which will prevent the reflux of gastric contents by blocking the cardia with a balloon. It was the aim of this initial study to assess the efficiency of the tube in animals, healthy volunteers and patients. METHODS. With the approval of the Animal Ethics Committee, a total of 16 anaesthetised pigs were used for the animal experiments. Balloon occlusion of the cardia was performed in 10 pigs. Six further pigs with an unblocked cardia served as controls. Vomiting and regurgitation was provoked in each animal using six different manoeuvres while the gastro-oesophageal (lower oesophageal) sphincter and intragastric pressures were monitored and the lower oesophagus was continuously inspected using an endoscope. With local Ethics Committee approval and informed written consent, (1) repeated vomiting was provoked in 16 awake, healthy adult volunteers (10 females, 6 males, 29 +/- 4 years) with a fluid-filled stomach in the presence and in the absence of balloon occlusion of the cardia, while intragastric pressure was monitored, and (2) 30 patients (21-89 years) with an increased risk of pulmonary aspiration scheduled for abdominal or traumatologic surgery received conventional induction of anaesthesia after blocking of the cardia with the balloon. RESULTS. Pigs (n = 10) with a blocked cardia showed no gastro-oesophageal reflux during a total of 60 manipulations to provoke vomiting and regurgitation, while 28 of the 36 provoking manipulations induced reflux in pigs (n = 6) with an unblocked cardia. Among the healthy volunteers with a blocked cardia (n = 16), reflux of gastric contents was not observed during repeated attempts to stimulate vomiting. After termination of the occlusion of the cardia, reflux was able to be induced by 14 of the 16 volunteers. In 30 patients with an increased risk of pulmonary aspiration the cardia was blocked and anaesthesia was induced using a mask and manual ventilation without encountering any problems. The average time from loss of consciousness to tracheal intubation was 164 +/- 8 s. CONCLUSIONS. It is concluded from the present results, with further clinical studies pending, that the gastric balloon probe permits low-risk conventional induction sequence of anaesthesia in patients with an increased risk for pulmonary aspiration and that the device may also be safely used during the extubation phase.

Adult↗

PubMed1994

[Perioperative applications of transesophageal echocardiography].

Transoesophageal echocardiography (TEE) is a visualising ultrasound technique that has entered the arena of anaesthesiology and intensive care shortly after its clinical introduction in the early 80s. Due to transducer positioning close to the heart, two-dimensional echocardiograms render high spatial resolution of cardiac structures and in adequate views continuously demonstrate the complete course of cardiac filling and contraction. The high sensitivity of the method, numerous options to assess morphological and functional parameters, and the low related risk involved for the patient explain the growing interest in TEE as a perioperative monitoring device. This utilisation, however, is currently limited by the high costs of the ultrasound equipment, the demand for specialists knowledge, the cost-benefit relation not yet thoroughly explored and the little propagated knowledge of the method's capacity. In addition, the need for information is growing due to the permanent technological progress of the equipment, which recurrently requires actualization in evaluating TEE.

Cardiovascular Diseases↗

PubMed1994

[Transesophageal echocardiography for determining left-ventricular end-diastolic myocardial tension].

OBJECTIVE: Left ventricular end-diastolic wall stress (EDWS) ist an index for left ventricular preload. Utilising transoesophageal echocardiography, left ventricular dimensions can be obtained by two-dimensional (2d-) as well as M-Mode measurements, and each can be combined with pulmonary capillary wedge pressure (PCWP) for the calculation of EDWS. In the present examination, both methods were compared with regard to their technical accomplishment and reproducibility under clinical conditions. METHODS: EDWS was obtained in 24 ventilated patients by 2d-echocardiography (2d-EDWS) and M-mode-echocardiography (M-EDWS) before and after a change in PCWP by 3mmHg. In 12 patients, volume therapy with hydroxyethylstarch (HAES) was started when PCWP < 11 mmHg; in another 12 patients, continuous intravenous administration of nitroglycerine was begun, when PCWP > 14 mmHg. 2d-EDWS and M-EDWS were compared and their relation to thermodilution stroke volume and stroke work index analysed. RESULTS: 2d-EDWS and M-EDWS correlated well in both groups (HAES: r = 0.91; NITRO: r = 0.93), with M-EDWS being systematically lower than 2d-EDWS. The relative difference between 2d-EDWS and M-EDWS, and their mean value--calculated as the mean per cent error--was 11.2%. Directional changes in preload were reflected in all patients by 2d-EDWS and M-EDWS in accordance. Both correlated better with stroke volume and stroke work index than PCWP. Determination of 2d-EDWS showed better inter- and intraobserver variability in the echocardiographic measurements. CONCLUSIONS: With regard to direction and quantity, changes of preload as seen with echocardiographic EDWS were according reflected by the 2d- and the M-mode technique. Determination of 2d-EDWS compared to M-EDWS was superior in reproducibility and more useful for the estimation of stroke volume changes.

Adult↗

PubMed1994

High-purity ryanodine and 9,21-dehydroryanodine for in vitro diagnosis of malignant hyperthermia in man.

Susceptibility to malignant hyperthermia (MH) is currently diagnosed by the in vitro contracture test (IVCT) in skeletal muscle. However, this test does not possess absolute specificity. Thus, in addition to the established procedure, the "ryanodine contracture test" has been proposed to improve discrimination between MH-susceptible (MHS) and normal (MHN) patients. In all previous studies, the ryanodine used was a mixture consisting of high-purity ryanodine (HPR) and 9,21-dehydroryanodine (DHR). Therefore, in this study the effects of both substances were investigated in concentrations of 2, 5 and 10 mumol litre-1. With all concentrations, contractures appeared earlier in MHS than in MHN muscles, but these differences were significant at all contracture levels with HPR only. Moreover, with the smallest concentration (2 mumol litre-1), the best discrimination between MHS and MHN was observed. Classification of MH-equivocal patients (MHE) as MHS or MHN seems to be possible with the use of ryanodine-induced contractures. The contracture test with HPR should therefore be added to the established procedure of the IVCT.

Adolescent↗

PubMed1993

[High purity ryanodine for in vitro diagnosis of malignant hyperthermia].

OBJECTIVE AND STUDY DESIGN: The identification of disposition for malignant hyperthermia (MH) is performed by the halothane-caffeine contracture test in skeletal muscle. However, testing currently renders about 14% of the patients MH equivocal (MHE). To reduce this number the "ryanodine contracture test" has been proposed in addition to the established procedure. As all ryanodine preparations used until now are combinations of ryanodine and dehydroryanodine, we investigate in this study the effects of the now available high-purity ryanodine (HPR) in concentrations of 2,5 and 10 mumol/l. RESULTS: With all concentrations contractures appeared significantly earlier in MHS (malignant hyperthermia susceptible) than in MHN (malignant hyperthermia non-susceptible). However, only at 2 mumol/l a time overlap between both groups was not observed. By defining a time interval for MHS and MHN, three of the MHE patients could be assigned to MHS and three to MHN following their ryanodine-induced contractures. CONCLUSION: The ryanodine contracture test should be added to the current diagnostics of malignant hyperthermia.

Adolescent↗

PubMed1993

Accelerated contractures after administration of ryanodine to skeletal muscle of malignant hyperthermia susceptible patients.

A genetic disorder of the calcium releasing ryanodine receptor has recently been postulated in malignant hyperthermia (MH) and ryanodine-induced contractures differ between subjects who are malignant hyperthermia susceptible (MHS) and non-susceptible (MHN). We tested 39 patients from 26 families for MH, using the procedure of the European Malignant Hyperthermia Group. A ryanodine contracture test was performed by both cumulative (0.4-10.0 mumol litre-1 every 3 min) and bolus (10.0 mumol litre-1) application. Contracture with cumulative ryanodine application started significantly earlier in MHS (9.6 (SEM 0.5) min) than in MHN patients (24.6 (1.3) min). A significant difference in start of contracture between MHS (4.8 (0.6) min) and MHN (14.5 (0.6) min) patients occurred also after bolus application of ryanodine. The ryanodine contracture test seems to be a potentially specific in vitro diagnostic test for MH.

Adolescent↗

PubMed1993

Biochemical changes in malignant hyperthermia susceptible swine: cyclic AMP, inositol phosphates, alpha 1, beta 1- and beta 2-adrenoceptors in skeletal and cardiac muscle.

It has been presumed that alteration in the concentrations of second messengers leads to alterations in the function of the ryanodine receptor. Consequently, we have determined the basal content of cyclic AMP and inositol phosphates in skeletal and cardiac muscle of malignant hyperthermia (MH) susceptible (MHS) and healthy normal control (MHN) swine. Since alpha 1- and beta-adrenoceptors are linked to these second messenger systems, the densities of alpha 1- and beta-adrenoceptors were also determined. In skeletal as well as cardiac muscle, a higher basal concentration of almost all of the inositol phosphates was found. Of all inositol phosphates measured, the presumed second messenger inositol 1,4,5-trisphosphate (1,4,5-IP3) was mostly concentrated in both tissues. Each MHS sample contained more 1,4,5-IP3 than the highest value observed in MHN muscle, indicating that a threshold of 1,4,5-IP3 concentration for determination of MHS or MHN status can be defined. In addition, MHS skeletal muscle contained more cAMP than MHN, whereas there was no difference between MHS and MHN in cardiac muscle. The changes observed in the different inositol phosphate and cAMP contents were not accompanied by an altered alpha 1- or beta-adrenoceptor density in skeletal or cardiac muscle between MHS and MHN. However, the total number of beta-adrenoceptors of MHN and MHS was significantly higher in cardiac (about 80 fmol/mg protein) than skeletal muscles (about 30 fmol/mg protein). The cardiac muscles revealed about 80% beta 1- and beta 2- and 20% beta 2-adrenoceptors, whereas skeletal muscles were characterized by over 95% beta 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

[Early detection of traumatic aortic aneurysms using transesophageal Doppler echocardiography].

The early diagnosis of traumatic aortic dissections and aneurysms involving the thoracic aorta is of crucial importance for the outcome of patients suffering chest injuries. This subject is presented using two case reports; one illustrates the problems resulting from an overlooked traumatic aneurysm of the thoracic aorta and the second shows the possibilities of detecting such potentially lethal injuries early in patients with thoracic or multiple injuries, using the transesophageal Doppler echocardiography (TDE). The advantages and disadvantages of using TDE as compared to the more conventional methods such as the precordial Doppler echocardiography, computed tomography and angiography, are discussed. The particular advantage of this hardly invasive or burdening method is its immediate availability in the emergency room to assess patients with evident thorax trauma. In the intensive care unit TDE may be of value in screening polytraumatised patients who offered no primary evidence for chest injury upon arrival.

Adult↗

PubMed1991

[Malignant hyperthermia today].

Besides offering a concise recapitulation of known facts, experiences and related viewpoints concerning malignant hyperthermia (MH), the present article offers a review of the most relevant new aspects in this field. Special emphasis is on genetics and pathogenesis of MH. The contents of the review are as follows: History; Definition of MH; Epidemiological aspects; Inheritance; Molecular genetics; Pathogenesis; Triggering agents; Awake Triggering; Sympathetic nervous system; Serotoninergic system; Involvement of other organs and cell systems; Clinical symptoms and diagnosis; MH and myopathies; Associated disorders; Treatment; Prophylaxis; Identification of susceptibility; MH testing centres in the FRG; Hot-line for MH emergencies

Europe↗

PubMed1991

[Malignant hyperthermia and inositol phosphate metabolism in the heart and skeletal musculature].

There are recent reports that inositol phosphate metabolism is involved in the development of malignant hyperthermia (MH). Consequently, we investigated the basal concentration of inositol phosphate products in skeletal and heart muscles of malignant hyperthermia-susceptible (MHS) and healthy control (MHN) swine. Different inositol phosphates were measured by high pressure liquid chromatography, including inositol trisphosphate, tetrakisphosphate, pentakisphosphate and hexakisphosphate. All inositol phosphate products measured had a higher concentration in MHS than MHN in skeletal (304-1330%) as well as heart muscles (134-440%). An activation of the inositol phosphate metabolism has been shown to mobilise intracellular calcium from the sarcoplasmic reticulum. It is therefore concluded that, firstly, besides involvement of the skeletal muscles a primary myocardial abnormality in MHS is possible; and secondly, the idea that the inositol phosphate metabolism could be involved in the development of MH is additionally supported.

Animals↗

PubMed1991

[Ryanodine-induced contractures for the diagnosis of malignant hyperthermia susceptibility].

The halothane-caffeine contracture test is presently the most well-established method for identification of malignant hyperthermia susceptibility (MHS) or non-susceptibility (MHN). However, 10-20% of the patients tested are classified as equivocal (MHE), i.e. their susceptibility remains uncertain. A genetic disorder of the calcium releasing ryanodine receptor has been postulated recently. Therefore, 12 patients were tested in addition to the protocol of the European Malignant Hyperthermia Group (EMHG) for dose- and time-dependent contracture after ryanodine application. In this study, contracture of 0.2g appeared significantly earlier in MHS patients (17.5 +/- 1.7 min; n = 5) during cumulative ryanodine exposition (0.4-0.8-1.6-10.0 mumol/l) than in MHN (38.2 +/- 5.4 min; n = 5). A significant difference between MHS (10.0 +/- 1.7 min; n = 6) and MHN (19.8 +/- 0.6 min; n = 3) was also seen after bolus application of ryanodine (10.0 mumol/l). One patient classified as MHE according to the EMHG protocol, manifested as MHN after the ryanodine contracture test. This study supports previous work suggesting the ryanodine contracture test as an improvement in the in-vitro diagnosis of MH susceptibility.

Adolescent↗

PubMed1991

Possible involvement of inositol-lipid metabolism in malignant hyperthermia.

Alpha-adrenoceptor stimulation may induce malignant hyperthermia (MH) in vivo. Consequently, we have investigated the effects of the alpha-adrenoceptor agonist phenylephrine and, for comparison, the effects of the beta-adrenoceptor agonist isoproterenol on inositol-lipid metabolism of malignant hyperthermia susceptible (MHS) and healthy control (MHN) swine. The experiments were performed on electrically stimulated (frequency 0.2 Hz) trabeculae isolated from the right ventricles of the hearts of MHS and MHN animals. After labelling with [3H]inositol for 6 h, different inositol phosphates were measured by high pressure liquid chromatography, including inositol 1-phosphate, inositol 1,4-bisphosphate, inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP3) and inositol 1,3,4,5-tetrakisphosphate. After stimulation with isoproterenol, the inositol phosphate content did not increase or vary between muscle from MHS and MHN animals. In contrast, all inositol phosphates increased after stimulation with phenylephrine in both muscle types, the effects being greater in MHS than in MHN, especially as regards 1,4,5-IP3 content. As 1,4,5-IP3, a presumed second messenger, has been shown to mobilize intracellular calcium, it is concluded that an enhanced alpha-adrenergic response is involved in the development of MH.

Animals↗