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1.
Am J Physiol Heart Circ Physiol ; 308(12): H1540-6, 2015 Jun 15.
Article in English | MEDLINE | ID: mdl-25888515

ABSTRACT

Hypoxia increases the heart rate response to exercise, but the mechanism(s) remains unclear. We tested the hypothesis that the tachycardic effect of hypoxia persists during separate, but not combined, inhibition of ß-adrenergic and muscarinic receptors. Nine subjects performed incremental exercise to exhaustion in normoxia and hypoxia (fraction of inspired O2 = 12%) after intravenous administration of 1) no drugs (Cont), 2) propranolol (Prop), 3) glycopyrrolate (Glyc), or 4) Prop + Glyc. HR increased with exercise in all drug conditions (P < 0.001) but was always higher at a given workload in hypoxia than normoxia (P < 0.001). Averaged over all workloads, the difference between hypoxia and normoxia was 19.8 ± 13.8 beats/min during Cont and similar (17.2 ± 7.7 beats/min, P = 0.95) during Prop but smaller (P < 0.001) during Glyc and Prop + Glyc (9.8 ± 9.6 and 8.1 ± 7.6 beats/min, respectively). Cardiac output was enhanced by hypoxia (P < 0.002) to an extent that was similar between Cont, Glyc, and Prop + Glyc (2.3 ± 1.9, 1.7 ± 1.8, and 2.3 ± 1.2 l/min, respectively, P > 0.4) but larger during Prop (3.4 ± 1.6 l/min, P = 0.004). Our results demonstrate that the tachycardic effect of hypoxia during exercise partially relies on vagal withdrawal. Conversely, sympathoexcitation either does not contribute or increases heart rate through mechanisms other than ß-adrenergic transmission. A potential candidate is α-adrenergic transmission, which could also explain why a tachycardic effect of hypoxia persists during combined ß-adrenergic and muscarinic receptor inhibition.


Subject(s)
Adrenergic beta-Antagonists/pharmacology , Exercise , Heart Rate/drug effects , Hypoxia/complications , Muscarinic Antagonists/pharmacology , Receptors, Adrenergic, beta/drug effects , Receptors, Muscarinic/drug effects , Tachycardia/etiology , Adult , Bicycling , Cardiac Output , Denmark , Exercise Tolerance , Humans , Hypoxia/metabolism , Hypoxia/physiopathology , Male , Receptors, Adrenergic, beta/metabolism , Receptors, Muscarinic/metabolism , Respiration , Tachycardia/metabolism , Tachycardia/physiopathology , Tachycardia/prevention & control , Time Factors , Young Adult
2.
Scand J Med Sci Sports ; 25(1): e20-7, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24646113

ABSTRACT

Several techniques assessing cardiac output (Q) during exercise are available. The extent to which the measurements obtained from each respective technique compares to one another, however, is unclear. We quantified Q simultaneously using four methods: the Fick method with blood obtained from the right atrium (Q(Fick-M)), Innocor (inert gas rebreathing; Q(Inn)), Physioflow (impedance cardiography; Q(Phys)), and Nexfin (pulse contour analysis; Q(Pulse)) in 12 male subjects during incremental cycling exercise to exhaustion in normoxia and hypoxia (FiO2 = 12%). While all four methods reported a progressive increase in Q with exercise intensity, the slopes of the Q/oxygen uptake (VO2) relationship differed by up to 50% between methods in both normoxia [4.9 ± 0.3, 3.9 ± 0.2, 6.0 ± 0.4, 4.8 ± 0.2 L/min per L/min (mean ± SE) for Q(Fick-M), Q(Inn), QP hys and Q(Pulse), respectively; P = 0.001] and hypoxia (7.2 ± 0.7, 4.9 ± 0.5, 6.4 ± 0.8 and 5.1 ± 0.4 L/min per L/min; P = 0.04). In hypoxia, the increase in the Q/VO2 slope was not detected by Nexfin. In normoxia, Q increases by 5-6 L/min per L/min increase in VO2, which is within the 95% confidence interval of the Q/VO2 slopes determined by the modified Fick method, Physioflow, and Nexfin apparatus while Innocor provided a lower value, potentially reflecting recirculation of the test gas into the pulmonary circulation. Thus, determination of Q during exercise depends significantly on the applied method.


Subject(s)
Cardiac Output/physiology , Exercise Test/methods , Exercise/physiology , Hypoxia/physiopathology , Oxygen Consumption/physiology , Adult , Cardiac Catheterization/methods , Cardiography, Impedance/methods , Humans , Male , Nitrous Oxide/analysis , Pulse Wave Analysis/methods , Young Adult
3.
Br J Anaesth ; 103(6): 840-7, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19808774

ABSTRACT

BACKGROUND: We considered whether haemorrhage after a liver trauma would be reduced by early administration of a pro-haemostatic agent and evaluated the effect of i.v. vs i.m. administration of the coagulation factor VIIa analogue NN1731 on haemorrhage after a liver trauma in the pig. METHODS: The pharmacokinetics of i.v. and i.m. NN1731 was evaluated in eight minipigs, and the effects of dose and administration route of NN1731 (i.v. 180 microg kg(-1), n=6; i.m. 540 microg kg(-1), n=4, or 2000 microg kg(-1), n=6) vs vehicle (n=16) were studied on a liver laceration injury in pigs. To simulate a pre-hospital setting, the administration of NN1731 was delayed by 1 min for i.m. administration and 7 min for i.v. administration, at which time fluid resuscitation also began. RESULTS: In the minipigs, NN1731 exposure was similar after i.v. 180 microg kg(-1) and i.m. 540 microg kg(-1), with a bioavailability of approximately 35%. The injury and blood loss at 7 min was comparable between the four groups of pigs; however, after 60 min, the blood loss was lower in the i.v. treated animals: 1.3 (0.3) (i.v.) vs 2.2 (0.8) litres (i.m.(540), i.m.(2000), and vehicle) (P<0.001). Also, the survival time was increased: 117 (14) (i.v.) vs 84 (28) min (i.m.(540), i.m.(2000), and vehicle) (P<0.001). CONCLUSIONS: After a liver trauma in the pig, i.v. administration of NN1731 reduced the bleeding and increased the survival time. In contrast, i.m. administration had no effect, presumably because reduced muscle perfusion during haemorrhage reduced the uptake of NN1731.


Subject(s)
Factor VII/therapeutic use , Hemorrhage/drug therapy , Hemostatics/therapeutic use , Liver Diseases/drug therapy , Liver/injuries , Animals , Disease Models, Animal , Factor VII/administration & dosage , Factor VIIa/administration & dosage , Factor VIIa/therapeutic use , Hemorrhage/physiopathology , Hemostatics/administration & dosage , Injections, Intramuscular , Injections, Intravenous , Liver Diseases/physiopathology , Oxygen Consumption/drug effects , Random Allocation , Recombinant Proteins/administration & dosage , Recombinant Proteins/therapeutic use , Survival Analysis , Sus scrofa , Swine , Swine, Miniature , Treatment Outcome
4.
Clin Physiol Funct Imaging ; 29(6): 427-30, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19656165

ABSTRACT

We considered that a moderate reduction of the central blood volume (CBV) may activate the coagulation system. Lower body negative pressure (LBNP) is a non-invasive means of reducing CBV and, thereby, simulates haemorrhage. We tested the hypothesis that coagulation markers would increase following moderate hypovolemia by exposing 10 healthy male volunteers to 10 min of 30 mmHg LBNP. Thoracic electrical impedance increased during LBNP (by 2.6 +/- 0.7 Omega, mean +/- SD; P < 0.001), signifying a reduced CBV. Heart rate was unchanged during LBNP, while mean arterial pressure decreased (84 +/- 5 to 80 +/- 6 mmHg; P < 0.001) along with stroke volume (114 +/- 22 to 96 +/- 19 ml min(-1); P < 0.001) and cardiac output (6.4 +/- 2.0 to 5.5 +/- 1.7 l min(-1); P < 0.01). Plasma thrombin-antithrombin III complexes increased (TAT, 5 +/- 6 to 19 +/- 20 microg l(-1); P < 0.05), indicating that LBNP activated the thrombin generating part of the coagulation system, while plasma D-dimer was unchanged, signifying that the increased thrombin generation did not cause further intravascular clot formation. The plasma pancreatic polypeptide level decreased (13 +/- 11 to 6 +/- 8 pmol l(-1); P < 0.05), reflecting reduced vagal activity. In conclusion, thrombin generation was activated by a modest decrease in CBV by LBNP in healthy humans independent of the vagal activity.


Subject(s)
Blood Coagulation Factors/physiology , Blood Coagulation/physiology , Hemostasis/physiology , Lower Body Negative Pressure/methods , Adult , Humans , Male
5.
Br J Anaesth ; 102(2): 221-6, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19074153

ABSTRACT

BACKGROUND: This study tested the circulatory effectiveness of post-trauma administration of a large intravascular volume expander, hydroxyethyl starch 130/0.4 (HES), vs standard lactated Ringer's solution (RL). METHODS: Liver injury was inflicted in 14 pigs [31 (4) kg; mean (sd)] and treatment simulated an acute pre-hospital event: after a standard first-respond delay (7 min), volume administration was provided in three phases to simulate increasing intravascular access. In the first two phases, the fluid was administered either by HES or by RL and, during the last phase, all animals received HES to stabilize the intravascular volume. RESULTS: The liver trauma severed an equal number of 1-3 mm diameter blood vessels [1.4 (0.6)] and after 7 min, the blood loss was 184 (127) ml and mean arterial pressure had decreased by 19 (13) mm Hg (P<0.01). The intravascular volume expansion effect was 115 (25)% for HES and 76 (21)% for RL (P<0.05), yet oxygen uptake was maintained in zero of seven vs three of seven pigs and the survival was three of seven vs seven of seven, respectively (P<0.05). In these animals, the initial administration of HES provoked uncontrolled bleeding, whereas the administration of RL was associated with attenuated bleeding: total blood loss 2455 (1919) vs 311 (208) ml, respectively (P<0.01), reflecting that bleeding ceased in six of the pigs administered RL. CONCLUSIONS: After injury, the intravascular volume expanding effect of HES was larger than that for RL. However, initial administration of HES provoked uncontrolled haemorrhage, suggesting that prioritizing intravascular volume expansion did not result in stabilization of the circulation after haemorrhage.


Subject(s)
Hydroxyethyl Starch Derivatives/therapeutic use , Isotonic Solutions/therapeutic use , Liver/injuries , Plasma Substitutes/therapeutic use , Animals , Drug Evaluation, Preclinical/methods , Fluid Therapy/adverse effects , Fluid Therapy/methods , Hemodynamics , Hemorrhage/etiology , Hemorrhage/physiopathology , Hemorrhage/therapy , Hydroxyethyl Starch Derivatives/adverse effects , Isotonic Solutions/adverse effects , Liver Diseases/etiology , Liver Diseases/physiopathology , Liver Diseases/therapy , Oxygen Consumption , Plasma Substitutes/adverse effects , Ringer's Lactate , Sus scrofa , Thrombelastography/methods
6.
Meat Sci ; 18(3): 191-200, 1986.
Article in English | MEDLINE | ID: mdl-22055647

ABSTRACT

Two simple, accurate, rapid and economical methods for determining variations in drip loss of lean, prepackaged, post-rigor porcine musculature during storage have been developed. Laboratory grade filter paper having a 45 mm diameter was placed on the cut surface of the muscle (after 10-15 minutes' exposure) and scored for wetness (0 to 5) within 3 s or weighed for fluid accumulation. The tests on 40 randomly selected longissimus muscles that appeared to represent 'normal' quality characteristics proved to be nearly perfectly and positively correlated to % 48 h drip loss. Statistically, the relationship was non-curvilinear and, when regression equations were used to predict drip losses on a separate group of 27 muscles having considerable variation in quality, the correlations between the predicted and actual values were nearly perfect (r = 0·97 for score and 0·95 for weight). These two methods have not been compared to other, more sophisticated, ones currently used, but the results of this investigation suggest that the two methods may be useful to the meat industry, especially for practical applications.

7.
Meat Sci ; 18(4): 307-22, 1986.
Article in English | MEDLINE | ID: mdl-22055735

ABSTRACT

Water-holding capacity (WHC) of muscle is important because it affects both qualitative and quantitative aspects of meat and meat products. For assessment of WHC under field and laboratory conditions, there are several methods available, but they have not been compared in a single experiment to determine accuracy and repeatibility. The Longissimus dorsi from each of 28 porcine loins representing three distinct levels of WHC (DFD, PSE, normal) was separated into eighteen parts that were randomly assigned to individual methods. The following methods were compared: Grau-Hamm and Braunschweiger-Gerät filter paper press techniques using five approaches of evaluation for each method; transmission per cent; swelling due to added water; centrifugation; 48-h fresh and cooked shrink: imbibition of surface fluids, kapillar volumeter, permittivity; and score or weight of surface fluids accumulating on filter paper. Results indicated that most methods separated the three muscle types. However, the cooking loss tests failed to differentiate between PSE and normal samples, and the transmission, imbibition and pressed fluid methods did not always distinguish between DFD and normal. The tests that appeared to be most reliable included drip loss originating from size-standardized samples, swelling of homogenized samples by added water and absorption of surface fluids on filter paper.

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