Biomedical subjects

J Häggendal

Publications and source records attributed to J Häggendal.

At least 19 recordsLinked to original sources

PubMed1995

Effects of propranolol pretreatment on cerebral blood flow, oxygen uptake and catecholamines during metabolic acidosis following E. coli endotoxin in dogs.

After an intravenous injection of E. coli endotoxin in dogs a decrease in cerebral blood flow (CBF) and an increase in cerebral metabolic rate of oxygen (CMRo2) have been shown to occur. In metabolic acidosis following endotoxin CMRo2 increased with decreasing pH. A possible explanation for the increased CMRo2 after endotoxin and metabolic acidosis seems to be a damage of the blood-brain barrier (BBB) by endotoxin. This gives possibilities for a leakage of hydrogen ions and circulating monoamines from the blood to the brain, thus affecting the cerebral blood flow and metabolism. The effects of an E. coli endotoxin injection on CBF and CMRo2 during metabolic acidosis and beta-adrenoceptor blockade were studied in eight anaesthetized dogs. All the dogs were pretreated with propranolol (PPL), per os 12.5 mg.kg-1 twice a day for one week. Metabolic acidosis (pH 7.01-7.30) was achieved by an intravenous infusion of hydrochloric acid. Endotoxin E. coli lipopolysaccharide O 111:B 4 was given as an intravenous injection of 1 mg.kg-1 bodyweight over a 5 min period. Another five animals, published earlier, with the same experimental protocol but without PPL, constituted a control group. After endotoxin no increase in CMRo2 or CBF was observed with increasing acidosis in the PPL-group. In the control group, after endotoxin, both CBF and CMRo2 increased with decreasing pH. This resulted in a significant difference in both CBF and CMRo2 between the groups in the pH range 7.01-7.15. The present results indicate that the increase in CMRo2 and CBF with metabolic acidodis in endotoxinaemia is mediated via beta-adrenoceptors.

Acidosis↗

PubMed1995

Effects of arterial hypoxia and beta-adrenoceptor blockade on cerebral blood flow and oxygen uptake following E. coli endotoxin in dogs.

Earlier studies in normoxia have shown that an endotoxin injection in dogs leads to an increase in cerebral metabolic rate of oxygen (CMRo2), a decrease in cerebral blood flow (CBF) and increased concentrations of monoamines in blood and cerebrospinal fluid (CSF). In animals pretreated with propranolol (PPL) the CMRo2 increase was abolished and thus beta-adrenoceptor mediated. Arterial hypoxia normally increases CBF without any influence on CMRo2. The aim of this study was to investigate the effects of moderate arterial hypoxia on CBF, CMRo2 and catecholamine concentrations in blood and CSF after endotoxin with and without pretreatment with PPL. Three groups of dogs were studied. Group 1: Six animals were subjected to arterial hypoxia without any other intervention. Group 2: Six animals were given an endotoxin injection (E. coli lipopolysaccharide O 111: B 4), before the induction of hypoxia. Group 3: Eight animals were pretreated with PPL per os, 12.5 mg.kg-1 twice a day for one week before the experiments, and the effects of arterial hypoxia were studied both before and after an intravenous injection of endotoxin. Two levels of hypoxia were studied; oxygen saturation in arterial blood aiming at 75 and 50%. Endotoxin was given intravenously in a dose of 1 mg.kg-1 bodyweight over a 5 minute period. After an endotoxin injection, the response to arterial hypoxia was an increase in CMRo2, in contrast to the unchanged CMRo2 without endotoxin. After pretreatment with PPL the increase in CMRo2 after endotoxin was prevented. The CBF reaction to hypoxia was uniformly an increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effects of metabolic pH-alterations on cerebral blood flow and oxygen uptake following E. coli endotoxin in dogs.

The aim of the present study was to investigate if metabolic pH-alterations have an influence on cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) after an injection of E. coli endotoxin. Following endotoxin in dogs with normal pH a decreased CBF and an increased CMRO2 have earlier been found. Thirteen anaesthetized dogs were subjected to metabolic pH-variations in blood by infusion of hydrochloric acid or sodium bicarbonate. Ten dogs received E. coli endotoxin in a dose of 1 mg.kg-1 bodyweight. CBF, CMRO2 and noradrenaline and adrenaline concentrations in blood and cerebrospinal fluid were measured repeatedly during normoxia and normocarbia. Measurements before endotoxin served as controls, together with three additional animals, where endotoxin was never given. In control measurements pH showed no influence on the variables studied. After endotoxin CBF, CMRO2 and noradrenaline in cerebrospinal fluid increased with decreasing arterial blood pH. The influence exerted by metabolic pH alterations in blood after endotoxin may be explained by hydrogen ions and monoamines passing over a blood-brain barrier (BBB), damaged by endotoxin, into the brain tissue causing vasodilation and neuronal activation.

Acidosis↗

PubMed1994

Reduction of heart lesions after experimental restraint stress: a study in stress-susceptible pigs.

Pigs, crossbreeds of Swedish Landrace and Yorkshire, about 6 months old and susceptible to develop malignant hyperthermia when exposed to halothane, were subjected to a 12-min experimental stress provoked by the myorelaxant succinylcholine. The experimental pigs were pre-treated before the stress: five were given propranolol for one week, six were given alpha-tocopherol (vitamin E) combined with selenium for 11 days, and five pigs were pre-treated with zinc (ZnSO4) for 1 month. A total of 12 untreated, stress-susceptible pigs served as controls. The blood levels of noradrenaline and adrenaline recorded during the stress were significantly reduced in the groups pre-treated with propranolol or alpha-tocopherol combined with selenium. The results show significant reduction of myocardial necrosis by beta-adrenoceptor-blocking agents and free-radical scavengers during stress-induced increased sympathetic activity.

Animals↗

PubMed1993

Blood chemistry and skeletal muscle metabolic responses to exercise in horses with recurrent exertional rhabdomyolysis.

Six horses with a history of recurrent exertional rhabdomyolysis (RER) and 7 control horses performed both a 55-min submaximal and later a 10-min near-maximal exercise test on a treadmill. Blood samples were obtained during exercise and gluteus medius muscle biopsies were obtained before and immediately after each exercise test and at 24 h after completion of the submaximal test. Rhabdomyolysis was developed by 3 of 6 RER horses during submaximal exercise and in 1 of the RER horses during near-maximal exercise. Concentrations of potassium, glucose, free fatty acids, ammonia, lactate, cortisol, adrenaline and noradrenaline in the blood were measured. None of these variables appeared useful in predicting which RER horses would develop rhabdomyolysis. The RER horses that developed rhabdomyolysis (RERa) had higher cortisol and blood glucose concentrations but otherwise had blood chemistry and muscle metabolic responses during submaximal and near-maximal exercise similar to those of RER horses which did not develop rhabdomyolysis (RERb) and to controls. At rest, muscle glycogen concentrations were significantly higher (> 650 mmol/kg dry wt) in RERa and RERb horses than in controls. Lactate concentrations in muscle after submaximal and near-maximal exercise were similar or lower, respectively, in RERa horses compared with controls. The results of this study indicate that, although horses with RER had high resting intramuscular glycogen concentrations, rhabdomyolysis did not appear to be caused by an excessively rapid rate of anaerobic glycolysis with lactate accumulation.

Adenosine Triphosphate↗

PubMed1993

The effect of thiopentone-sodium anesthesia and surgery, relocation, grouping, and hydrocortisone treatment on the blood levels of cortisol, corticosteroid-binding globulin, and catecholamines in pigs.

Eight crossbred, ovariectomized gilts (Swedish Landrace x Swedish Yorkshire x Hampshire), with a mean age of 7.5 mo, were studied during anesthesia and surgery, control-sampling, relocation, and grouping during a period of 3 wk. Acute treatment with a hydrocortisone injection (5 mg, i.v.) was also given. Blood samples were taken frequently (every 10 min) during the intensive part of the experimental days. The blood samples were analyzed for catecholamines (CA), adrenaline (A) and noradrenaline (NA), cortisol, and corticosteroid-binding globulin (CBG). The surgical period with anesthesia and surgery showed significant effects on CA, cortisol, and CBG. The A level increased immediately after the surgery. A biphasic increase in the cortisol level was observed on the day of surgery; the greatest increase was seen when the animals had regained consciousness after surgery but still were drowsy and staggering. The CBG level decreased on the day after the surgery. The study showed that the levels of the analyzed substances were back to normal 2 d after surgery. During relocation and grouping there was a short, significant increase in CA and cortisol levels, whereas the CBG level was not affected. Treatment with hydrocortisone significantly increased the cortisol level, but no change was seen in plasma CA or CBG levels. In conclusion, anesthesia and surgery induced significant effects on the levels of CA, cortisol, and CBG in gilts and the animals needed 2 d to recover before regaining their normal condition. During relocation and a limited grouping period, the significant increases in CA and cortisol levels were of short duration and CBG did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

PubMed1993

The effect of transport stress on plasma levels of catecholamines, cortisol, corticosteroid-binding globulin, blood cell count, and lymphocyte proliferation in pigs.

The effect of transport stress on the plasma levels of catecholamines, cortisol, and corticosteroid-binding globulin were studied in 6 gilts. To assess the effect on immune status, white blood cells were also counted and the cell-mediated immunity was estimated. The adrenaline level increased significantly during transport, from a basal mean level of 0.03 ng/ml to a plateau level of 0.11 to 0.12 ng/ml. The noradrenaline level fluctuated, but not constantly, during transport. The mean plasma cortisol level before loading was approximately 40 nmol/l and rose immediately after the start of transport to 70 nmol/l (p < 0.05) and to 87 nmol/l (p < 0.01) within 10 and 30 min, respectively. After unloading the cortisol level rapidly decreased and a minimum level was seen 4 h after the transport, whereafter the diurnal rhythm was resumed. The plasma corticosteroid-binding globulin level increased nonsignificantly during the day of transport, from 25 nmol/l to a level of 34 nmol/l, and it continued to increase until a plateau level was reached on the second day after transportation. The total white blood cell number increased significantly (from 13.7 to 15.5 x 10(9) cells/l), the number of lymphocytes decreased significantly (from 8.4 to 7.0 x 10(9) cells/l), and the number of polymorphonuclear neutrophils increased significantly (from 4.3 to 7.2 x 10(9) cells/l) during transport. No significant variation in the proliferation response was seen in the whole blood cell cultures. The main results were the significant signs of simultaneous activity of both the adrenal cortex and the adrenal medulla during transport.

Animals↗

PubMed1992

Inefficiency of bilateral amygdaloid lesions to reduce the transient motor reactions exhibited by swine during exposure to CO2.

The aim of the study was to evaluate from the ethical point of view the importance of transient muscular jerks commonly exhibited by swine at an early stage of pre-slaughter CO2-anaesthesia. The influence of 5 min restraint upon plasma concentrations of adrenaline (A) and noradrenaline (NA) was studied in swine (n = 6) before and after bilateral lesioning of the amygdaloid region of the brain, as were the motor reactions of the same and three other animals during 1 min exposure to 80% CO2. The A and NA responses to the restraint became almost extinguished after amygdaloid lesioning in three of the animals, were reduced by about 50% in one swine, whereas no reduction was seen in the other two animals investigated. The amygdaloid lesioning did not visibly influence the latency for, and the duration and intensity of the muscular jerks manifested by the swine during the CO2-exposure. The results do not favour the possibility that transient motor reactions exhibited by swine during pre-slaughter CO2-exposure are manifestations of emotional stress. Instead, the study indirectly supports the idea that the cause of the muscular jerks may be disinhibition of subcortical motor centres being inactivated by the CO2-anaesthesia somewhat later than neocortical cells normally exerting the inhibition.

Amygdala↗

PubMed1991

Prevention of endotoxin-induced increase of cerebral oxygen consumption in dogs by propranolol pretreatment.

Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were studied in experimental endotoxic shock in dogs. Eight animals were pretreated with a beta-adrenoceptor blocking agent, propranolol (PPL), per os 12 mg/kg once a day for 7 days. Ten animals served as controls. After an intravenous injection of endotoxin, 1 mg/kg, CBF decreased in both groups, with no significant differences between the groups. CMRO2 increased in the control animals by about 18% from the baseline value both 1 and 2 h after the injection of endotoxin. CMRO2 in the PPL-pretreated animals was unchanged after endotoxin. The CMRO2-reactions to endotoxin in control and PPL animals were significantly different after both 1 and 2 h (P less than 0.05). The present results indicate that the increase in CMRO2 following intravenous endotoxin is mediated via beta-adrenoceptors.

Animals↗

PubMed1990

The role of sympathetic activity in initiating malignant hyperthermia.

The role of sympathetic activity in triggering malignant hyperthermia (MH) is controversial. Increased sympathetic activity has been considered by some to be the causal factor, whilst other believe this activity to be secondary to metabolic events in the MH syndrome. In this study, a number of parameters, including the blood levels of noradrenaline and adrenaline, were followed in pigs susceptible to MH during exposure to halothane. Seven pigs, crossbreeds of Swedish Landrace and Yorkshire, females and castrated males, aged about 9 months were used. Results are presented for individual pigs. One of the pigs was a non-responder. The time of onset for different signs of MH varied greatly, as judged by ten independent observers. Onset of changes in heart rate, muscle temperature, blood PCO2 and pH, plasma adrenaline and noradrenaline could be scored. The metabolic events (increased PCO2 and decreased pH in blood) significantly preceded the signs of increased sympathetic activity (increased heart rate and elevated levels of catecholamines in blood). Our results support the view that increased sympathetic activity does not initiate MH. The sympathetic activity, however, strongly contributes to the fulminant MH syndrome.

Animals↗

PubMed1990

Effects of histamine H2-receptor blockade on the cardiovascular reflex response to lower-body negative pressure in man.

The role of histamine H2-receptors in cardiovascular control is unknown. In seven healthy volunteers, we studied how histamine H2-receptor blockade affected the reflex response to hypovolaemia induced by lower-body negative pressure (LBNP). In placebo-treated individuals, LBNP down to -40 mmHg did not change systolic pressure but increased diastolic pressure, heart rate, forearm vascular resistance, plasma noradrenaline concentration and plasma renin activity. After pretreatment with ranitidine, a specific histamine H2-receptor antagonist, the diastolic pressure rise no longer sufficed to maintain a constant systolic pressure during LBNP. Ranitidine pretreatment also attenuated the heart rate response and the rise in plasma renin activity induced by LBNP, but did not significantly change the reflex forearm vasoconstriction or the forearm plasma noradrenaline response. The results suggest that histamine H2-receptor blockade attenuates the reflex vasoconstrictor response to lower-body negative pressure. The mechanism behind this effect remains unknown, but the data do not support the idea that the effect is exerted in the skeletal muscle vascular bed.

Adult↗

PubMed1990

Attenuation of gastric sham feeding response during reflex sympathetic activation in man.

In six human volunteers we studied the effects of hypovolemia on the secretory activity of the gastric mucosa. The secretion of acid and HCO3 from the stomach was calculated from continuous measurements of pH and Pco2 in gastric effluent. Gastric secretion was stimulated by sham feeding (SF), and cardiac filling pressure was decreased by pooling blood in the lower extremities (lower body negative pressure (LBNP]. LBNP at -20 mmHg had no significant effects on systemic arterial pressure or heart rate but increased plasma norepinephrine concentration by 48 +/- 6% (p less than 0.001). Both the acid and the alkaline responses to SF were significantly attenuated during LBNP (-38 +/- 8%, p less than 0.01, and -55 +/- 14%, p less than 0.05, respectively). Analysis of the relationship between acid and HCO3 secretion in individual experiments suggested a relatively more pronounced inhibition of HCO3 secretion. The results imply that a decreased responsiveness of the gastric mucosa may be one component of the cardiovascular reflex adaptation to hypovolemia. A downregulation of active secretion will lead to smaller metabolic demands from the secreting cells and may thereby help to maintain a vasoconstriction in the gastric mucosa.

Adult↗

PubMed1990

Regional changes in sympathetic nerve activity and baroreceptor reflex function and arterial plasma levels of catecholamines, renin and vasopressin during naloxone-precipitated morphine withdrawal in rats.

The aim of the study was to examine regional changes in sympathetic nerve activity (SNA) and baroreceptor function and arterial plasma catecholamines, arginine vasopressin (AVP) and plasma renin activity during morphine withdrawal in chloralose-anesthetized rats. Dependence was induced by s.c. morphine base pellets. Adrenal, renal and splanchnic SNA and SNA from the lumbar sympathetic chain were recorded before and after i.v. injections of naloxone. Baroreceptor function was examined with phenylephrine-induced increases in mean arterial pressure. In separate experiments, arterial plasma norepinephrine, epinephrine, dopamine, plasma renin activity and AVP were measured before and after naloxone-precipitated withdrawal. Naloxone administration elicited an increase in mean arterial pressure and heart rate. Although renal SNA was inhibited by approximately 50%, adrenal SNA and lumbar SNA increased by approximately 400 and 80%, respectively. Splanchnic SNA did not change significantly. The baroreceptor-mediated inhibition of adrenal SNA was facilitated while that for renal SNA was attenuated. The arterial plasma level of norepinephrine was doubled and epinephrine increased almost 20-fold. AVP increased about 15-fold, whereas plasma renin activity showed only a minor increase after naloxone. This study shows that a marked differentiation of the SNA response occurs during morphine withdrawal in rats, which suggests an interaction between opioid receptors and the control of regional sympathetic output. Furthermore, large amounts of AVP and epinephrine are released, which probably contribute to the cardiovascular changes seen in the withdrawal phase.

Animals↗

PubMed1989

Changes in muscle sympathetic nerve activity, venous plasma catecholamines, and calf vascular resistance during mechanical ventilation with PEEP in humans.

The sympathetic reflex response to mechanical ventilation with PEEP was studied in conscious human volunteers (n = 8). Muscle sympathetic nerve activity (MSNA) was measured from the peroneal nerve, calf blood flow, forearm venous plasma catecholamines, blood pressure, heart rate, airway pressure, and end-tidal CO2 (%) during spontaneous breathing and during mechanical ventilation with 0-20 cmH2O PEEP. MSNA increased (P less than 0.01) during PEEP ventilation, from 22 bursts.min-1 at spontaneous breathing to 39 bursts.min-1 at 20 PEEP. This increase in MSNA was accompanied by an increase (P less than 0.01) in calf vascular resistance (CVR) from 35 PRU100 at spontaneous breathing to 48 PRU100 at 15 PEEP with no further increase at 20 PEEP. Venous plasma norepinephrine concentrations increased (P less than 0.01) during PEEP ventilation from 0.19 ng.ml-1 at spontaneous breathing to 0.31 ng.ml-1 at 20 PEEP, whereas plasma epinephrine and dopamine were less than 0.03 ng.ml-1 during the experiment. Blood pressure and heart rate were not affected by PEEP ventilation except at 20 PEEP, where blood pressure and heart rate increased (P less than 0.01). The results show that PEEP ventilation induces a considerable reflex increase of MSNA, reflected also by an increase in CVR and venous plasma norepinephrine. It is proposed that the main mechanism responsible for these reflex adjustments is caused by a decreased activity of the cardiopulmonary low-pressure baroreceptors, in turn resulting from a decrease in cardiac transmural pressures due to PEEP ventilation.

Adult↗

PubMed1989

Cardiac manifestation and blood catecholamine levels during succinylcholine-induced stress of malignant hyperthermia sensitive pigs.

Fifteen crossbred pigs of Swedish Landrace and Yorkshire, about 6 months of age and susceptible to develop malignant hyperthermia (MH) when exposed to halothane, were subjected to stress provoked by the myorelaxant succinylcholine. The results were compared with those of 12 normal pigs. During the stress the halothane-sensitive (HS) pigs showed much higher levels of plasma noradrenaline and adrenaline and more severe ventricular arrhythmias than the controls. The degree of myocardial degeneration and necrosis being similar to catecholamine induced myocardial damage was significantly higher in the HS pigs than in the controls. The ultrastructural examination revealed three main types of changes in affected myocardial cells. One type of myocardial cell damage was characterized by various degree of hypercontraction, enlarged mitochondria with dense bodies and dilated sarcoplasmic reticulum. The other type showed mitochondria with tubular configuration whereas the third type of cell damage was characterized by almost normal mitochondria combined with a severe damage of the myofilaments. Three HS pigs which died within 30 min after stress showed signs of malignant hyperthermia. No signs of the disease were observed in the other 12 HS pigs.

Animals↗

PubMed1988

A possible mechanism for the release of serotonin from the gut caused by pentagastrin.

Pentagastrin (PG) is a potent agent causing release of serotonin (5-HT) from patients with carcinoid tumors. The physiological release of 5-HT from gut enterochromaffin cells is controlled by beta-adrenoceptors. Studies on carcinoid tumor cell suspensions, acute or in culture, have shown that catecholamines (CA), but not PG, release 5-HT, thus indicating an indirect mode of action by the peptide. In this study the mechanism for release of 5-HT from the gut induced by PG was investigated in animal models. The test protocol for patients was used in anesthetized cats. Portal blood samples were drawn after PG injection (0.6 microgram/kg iv), which resulted in significantly increased levels of 5-HT at 3 and 5 min postinjection. The PG-induced release was totally inhibited after blockade of beta-adrenoceptors (propranolol) or of slow calcium channels (verapamil) as well as after adrenalectomy. Blockade of beta-adrenoceptors or slow calcium channels decreased the basal levels of 5-HT, while adrenalectomy caused no change. In separate experiments CA were measured after PG injection in caval blood, drawn at the level of the adrenal veins. There was a significant increase in the levels of dopamine and epinephrine postinjection, while the levels of norepinephrine were stable. The changes of CA levels after PG injection could be prevented by adrenalectomy. These results further suggest an indirect action of PG in the release of 5-HT from the feline gut via activation of beta-adrenoceptors by epinephrine released from the adrenals.

Animals↗

PubMed1988

Effects of dopamine on the portal circulation after therapeutic hepatic artery ligation.

The effects of exogenous dopamine (2, 4 and 6 micrograms.kg-1.min-1 i.v.) on the portal circulation were studied in six patients following therapeutic hepatic artery ligation. Portal blood flow (PBF) was measured by the continuous thermodilution technique. Portal venous pressure (PVP, n = 3) was monitored through the thermodilution catheter to allow derivation of preportal vascular resistance (PVR). Blood samples were taken through the portal venous catheter for measurement of dopamine. A significant increase in PBF and a decrease in PVR were observed during graded i.v. dopamine infusion. Thus, PBF was 961 +/- 119 ml.min-1 during control conditions and increased to 1446 +/- 221 ml.min-1 during the dopamine infusion at 6 micrograms.kg-1.min-1. No significant changes in mean arterial pressure or PVP were observed during dopamine administration. The pharmacokinetics of dopamine did not differ from that previously reported in patients with an intact arterial supply. In conclusion, our data indicate that exogenous dopamine consistently increases PBF by preportal vasodilation, also in patients with a surgically restricted hepatic arterial blood supply.

Adult↗

PubMed1988

Disordered catecholamine release in pigs susceptible to malignant hyperthermia.

Pigs, crossbreeds of Swedish Landrace and Yorkshire, females and castrated males about 6 months old, were exposed to experimental stress. The pigs were either considered normal or shown to be susceptible to develop malignant hyperthermia when tested with halothane at about 6 weeks of age (stress-susceptible pigs). The stress was of the restraint type, produced by two different myorelaxant agents, the depolarizing succinylcholine or the non-depolarizing pancuronium. The blood levels of the catecholamines (CA) noradrenaline (NA) and adrenaline (A) were measured during the stress. The severity of myocardial cell necrosis observed 1 to 2 days after the stress was morphologically graded. In normal pigs the levels of NA during the stress and the degree of myocardial cell necrosis were about the same after both succinylcholine and pancuronium. In stress-susceptible pigs, however, succinylcholine produced very high NA and A levels and severe heart lesions, whereas after pancuronium the NA and A levels were rather low and the heart lesions significantly reduced when compared to those after succinylcholine-induced stress. After pretreatment with dantrolene intravenously the succinylcholine-induced stress only induced slightly increased blood CA levels and no signs of myocardial cell necrosis in pigs susceptible to develop malignant hyperthermia. Dantrolene, an efficient drug in treatment of malignant hyperthermia, probably acts by interfering with release of calcium from the sarcoplasmic reticulum in skeletal muscles. The results indicate that peripheral sympathetic neurones in MHS pigs also react abnormally, probably due to defective calcium turn-over.

Animals↗