Red cell oxygen transport in man in relation to gender and age

P50 values, the O2-partial pressure at 50% O2-saturation of hemoglobin, 2,3-DPG, hematological parameters and the plasma concentrations of sexual hormones were determined in 135 subjects of both sexes aged from 10 to 60 years. P50 was significantly higher in sexually mature women than in men, but did not differ between sexes before puberty and after menopause. In females P50 increased with sexual maturation by about 2 mmHg (0.27 kPa). RBC, Hb and Hct remained unchanged. In males Hb-O2-affinity, RBC, Hb and Hct increased with aging. In sexually mature females 2,3-DPG was significantly higher (2 mumol/gHb) than in males, although before puberty and postmaturity no difference was found. In males, 2,3-DPG increased slightly with maturation although P50 decreased. P50 values (pH = 7.4) correlated positively with red cell 2,3-DPG only when data from all groups were pooled (r = 0.330, P less than or equal to 0.0001). Hb was negatively correlated with P50 (r = 0.221, P less than or equal to 0.01). The data suggest a sex hormone and maturation induced influence in the development of the red cell O2-transport system. Estrogens seem to favour a decrease in Hb-O2-affinity rather than an elevation in O2-transport capacity, whereas androgens do the reverse.     

Lowering of blood pressure by increasing hematocrit with non nitric oxide scavenging red blood cells

Isovolemic exchange transfusion of 40% of the blood volume in awake hamsters was used to replace native red blood cells (RBCs) with RBCs whose hemoglobin (Hb) was oxidized to methemoglobin (MetHb), MetRBCs. The exchange maintained constant blood volume and produced different final hematocrits (Hcts), varying from 48 to 62% Hct. Mean arterial pressure (MAP) did not change after exchange transfusion, in which 40% of the native RBCs were replaced with MetRBCs, without increasing Hct. Increasing Hct with MetRBCs lowered MAP by 12 mm Hg when Hct was increased 12% above baseline. Further increases of Hct with MetRBCs progressively returned MAP to baseline, which occurred at 62% Hct, a 30% increase in Hct from baseline. These observations show a parabolic "U" shaped distribution of MAP against the change in Hct. Cardiac index, cardiac output divided by body weight, increased between 2 and 17% above baseline for the range of Hcts tested. Peripheral vascular resistance (VR) was decreased 18% from baseline when Hct was increased 12% from baseline. VR and MAP were above baseline for increases in Hct higher than 30%. However, vascular hindrance, VR normalized by blood viscosity (which reflects the contribution of vascular geometry), was lower than baseline for all the increases in Hct tested with MetRBC, indicating prevalence of vasodilation. These suggest that acute increases in Hct with MetRBCs increase endothelium shear stress and stimulate the production of vasoactive factors (e.g., nitric oxide [NO]). When MetRBCs were compared with functional RBCs, vasodilation was augmented for MetRBCs probably due to the lower NO scavenging of MetHb. Consequently, MetRBCs increased the viscosity related hypotension range compared with functional RBCs as NO shear stress vasodilation mediated responses are greater.     

Flying high: a theoretical analysis of the factors limiting exercise performance in birds at altitude

The ability of some bird species to fly at extreme altitude has fascinated comparative respiratory physiologists for decades, yet there is still no consensus about what adaptations enable high altitude flight. Using a theoretical model of O(2) transport, we performed a sensitivity analysis of the factors that might limit exercise performance in birds. We found that the influence of individual physiological traits on oxygen consumption (Vo2) during exercise differed between sea level, moderate altitude, and extreme altitude. At extreme altitude, haemoglobin (Hb) O(2) affinity, total ventilation, and tissue diffusion capacity for O(2) (D(To2)) had the greatest influences on Vo2; increasing these variables should therefore have the greatest adaptive benefit for high altitude flight. There was a beneficial interaction between D(To2) and the P(50) of Hb, such that increasing D(To2) had a greater influence on Vo2 when P(50) was low. Increases in the temperature effect on P(50) could also be beneficial for high flying birds, provided that cold inspired air at extreme altitude causes a substantial difference in temperature between blood in the lungs and in the tissues. Changes in lung diffusion capacity for O(2), cardiac output, blood Hb concentration, the Bohr coefficient, or the Hill coefficient likely have less adaptive significance at high altitude. Our sensitivity analysis provides theoretical suggestions of the adaptations most likely to promote high altitude flight in birds and provides direction for future in vivo studies.     

Deferoxamine lowers tissue damage after 80% exchange transfusion with polymerized hemoglobin

Hemoglobin (Hb) solutions have been proposed as potential substitutes for erythrocytes to maintain oxygen-carrying capacity in situations in which blood is not available. This study investigated systemic and microvascular hemodynamics as well as tissue oxygenation and viability after an 80% exchange transfusion with an oxygen-carrying blood substitute based on polymerized bovine hemoglobin (PBH). Studies were carried in unanesthetized hamsters prepared with a window-chamber model for microcirculation evaluation. Heme iron-mediated injury to the tissue was analyzed by using deferoxamine (an iron chelator), which reduces free iron toxicity. Exchange transfusion led to a significant decrease in hematocrit (Hct) and an increase in plasma Hb, in addition to a significant decrease of arteriolar and venular diameters, flow velocity, and, therefore, microvascular blood flow. Capillary perfusion was severely compromised after exchange, but tissue pO2 increased above baseline, and oxygen extraction was reduced. Apoptotic and necrotic cells increased significantly after the exchange; however, this effect was only partially due to the toxicity of free iron. Iron therapy decreased the microvascular and oxygenation changes but did not fully reverse the adverse effects. Assessment of tissue viability after exchange suggests that chelation treatment in cases of large exchange transfusions with acellular Hb could be potentially beneficial.     

Oxygen transport capacity of the capillary blood within the carotid body

Local deltaPo2 deltat in the carotid body after perfusion stop depends on the oxygen consumption of the tissue and the apparent O2 solubility coefficient alpha of the blood. Oxygen consumption of the carotid body tissue can be determined by measuring the local deltaPo2 deltat with Po2 needle electrodes after Krebs-Henseleit perfusion. Assuming the same deltaPo2 deltat for the blood-perfused carotid body the actual Po2 decrease can be used to estimate the hemoglobin content of the tissue. The influence of hemoglobin is described by the factor alpha/alpha. Control values measured in the Krebs-Henseleit-perfused carotid body yielded values of alpha/alpha = 0.8-3. In a series of 11 blood-perfused carotid body preparations with 105 perfusion stops the quotient alpha/alpha changed with arterial Po2. At Po2 values higher than 100 Torr alpha/alpha was between 0.8 and 2. This value thus was in the same range as the control values. Below 100 Torr higher values up to 11 were observed. Since a blood-perfused tissue (15 g% Hb) would have an alpha/alpha of about 128, we conclude that the carotid body is mainly perfused by plasma, and that with decreasing arterial Po2 more red cells flowed through the carotid body.     

Increased cardiovascular and metabolic tolerance to acute hypoxia in the rat with increased hemoglobin-O(2) affinity induced by Na-cyanate treatment.

Cyanate derivatives such as NaOCN have been known to increase the hypoxia tolerance of animals by increasing the affinity of hemoglobin (Hb) to O(2). To clarify the mechanism of this increase in hypoxia tolerance, we examined changes in metabolic rate and cardiovascular parameters during a hypoxia test in halothane-anesthetized, NaOCN-treated and spontaneously breathing rats (50 mg/kg/d S.C., 10 d). Control animals received saline. The capillary density in the skeletal muscle (sternocleidomastoid muscle), cardiac papillary muscle and medulla oblongata was also examined histologically. The Hb-O(2) affinity index, P(50), decreased from 38 (control rat) to 24 mmHg in NaOCN-treated rats. During hyperoxic gas breathing, the rat treated with NaOCN showed a significantly lower metabolic rate (V(.)O(2), V(.)CO(2)), higher cardiac stroke volume, slower heart rate, lower PvO(2), and lower O(2) extraction ratio than those in control rats. The NaOCN-treated rats exhibited well-maintained arterial blood pressure and a larger cardiac output response to reduction in FIO(2) to 0.10-0.08. The increase in O(2) extraction ratio with reduction in FIO(2) was larger in NaOCN-treated than in control rats. The circulatory and metabolic depressions at FIO(2) 0.05 were effectively attenuated in NaOCN-treated rats. The capillary density of the cardiac muscle and medulla oblongata but not the skeletal muscle was significantly higher in NaOCN-treated rats than in control rats. The greater hypoxia tolerance in NaOCN-treated rats is ascribed to the combined effects of left shift of Hb-O(2) dissociation curve, lower basal V(. )O(2), higher capillary density in the heart, and brain, and other adaptive mechanisms induced probably by prolonged tissue hypoxia.     

Short-term effects of normobaric hypoxia on the human spleen

Spleen contraction resulting in an increase in circulating erythrocytes has been shown to occur during apnea. This effect, however, has not previously been studied during normobaric hypoxia whilst breathing. After 20 min of horizontal rest and normoxic breathing, five subjects underwent 20-min of normobaric hypoxic breathing (12.8% oxygen) followed by 10 min of normoxic breathing. Ultrasound measurements of spleen volume and samples for venous hemoglobin concentration (Hb) and hematocrit (Hct) were taken simultaneously at short intervals from 20 min before until 10 min after the hypoxic period. Heart rate, arterial oxygen saturation (SaO(2)) and respiration rate were recorded continuously. During hypoxia, a reduction in SaO(2) by 34% (P < 0.01) was accompanied by an 18% reduction in spleen volume and a 2.1% increase in both Hb and Hct (P < 0.05). Heart rate increased 28% above baseline (P < 0.05). Within 3 min after hypoxia SaO(2) had returned to pre-hypoxic levels, and spleen volume, Hb and Hct had all returned to pre-hypoxic levels within 10 min. Respiratory rate remained stable throughout the protocol. This study of short-term exposure to eupneic normobaric hypoxia suggests that hypoxia plays a key role in triggering spleen contraction and subsequent release of stored erythrocytes in humans. This response could be beneficial during early altitude acclimatization.     

Red blood cell pH, the Bohr effect, and other oxygenation-linked phenomena in blood O2 and CO2 transport

The discovery of the S-shaped O2 equilibrium curve and the Bohr effect in 1904 stimulated a fertile and continued research into respiratory functions of blood and allosteric mechanisms in haemoglobin (Hb). The Bohr effect (influence of pH/CO2 on Hb O2 affinity) and the reciprocal Haldane effect (influence of HbO2 saturation on H+/CO2 binding) originate in the Hb oxy-deoxy conformational change and allosteric interactions between O2 and H+/CO2 binding sites. In steady state, H+ is passively distributed across the vertebrate red blood cell (RBC) membrane, and intracellular pH (pHi) changes are related to changes in extracellular pH, Hb-O2 saturation and RBC organic phosphate content. As the Hb molecule shifts between the oxy and deoxy conformation in arterial-venous gas transport, it delivers O2 and takes up CO2 and H+ in tissue capillaries (elegantly aided by the Bohr effect). Concomitantly, the RBC may sense local O2 demand via the degree of Hb deoxygenation and release vasodilatory agents to match local blood flow with requirements. Three recent hypotheses suggest (1) release of NO from S-nitroso-Hb upon deoxygenation, (2) reduction of nitrite to vasoactive NO by deoxy haems, and (3) release of ATP. Inside RBCs, carbonic anhydrase (CA) provides fast hydration of metabolic CO2 and ensures that the Bohr shift occurs during capillary transit. The formed H+ is bound to Hb (Haldane effect) while HCO3- is shifted to plasma via the anion exchanger (AE1). The magnitude of the oxylabile H+ binding shows characteristic differences among vertebrates. Alternative strategies for CO2 transport include direct HCO3- binding to deoxyHb in crocodilians, and high intracellular free [HCO3-] (due to high pHi) in lampreys. At the RBC membrane, CA, AE1 and other proteins may associate into what appears to be an integrated gas exchange metabolon. Oxygenation-linked binding of Hb to the membrane may regulate glycolysis in mammals and perhaps also oxygen-sensitive ion transport involved in RBC volume and pHi regulation. Blood O2 transport shows several adaptive changes during exposure to environmental hypoxia. The Bohr effect is involved via the respiratory alkalosis induced by hyperventilation, and also via the pHi change that results from modulation of RBC organic phosphate content. In teleost fish, beta-adrenergic activation of Na+/H+ exchange rapidly elevates pHi and O2 affinity, particularly under low O2 conditions.     

Relative contributions of strain-dependent permeability and fixed charged density of proteoglycans in predicting cervical disc biomechanics: a poroelastic C5-C6 finite element model study

Disc swelling pressure (P(swell)) facilitated by fixed charged density (FCD) of proteoglycans (P(fcd)) and strain-dependent permeability (P(strain)) are of critical significance in the physiological functioning of discs. FCD of proteoglycans prevents any excessive matrix deformation by tissue stiffening, whereas strain-dependent permeability limits the rate of stress transfer from fluid to solid skeleton. To date, studies involving the modeling of FCD of proteoglycans and strain-dependent permeability have not been reported for the cervical discs. The current study objective is to compare the relative contributions of strain-dependent permeability and FCD of proteoglycans in predicting cervical disc biomechanics. Three-dimensional finite element models of a C5-C6 segment with three different disc compositions were analyzed: an SPFP model (strain-dependent permeability and FCD of proteoglycans), an SP model (strain-dependent permeability alone), and an FP model (FCD of proteoglycans alone). The outcomes of the current study suggest that the relative contributions of strain-dependent permeability and FCD of proteoglycans were almost comparable in predicting the physiological behavior of the cervical discs under moment loads. However, under compression, strain-dependent permeability better predicted the in vivo disc response than that of the FCD of proteoglycans. Unlike the FP model (least stiff) in compression, motion behavior of the three models did not vary much from each other and agreed well within the standard deviations of the corresponding in vivo published data. Flexion was recorded with maximum P(fcd) and P(strain), whereas minimum values were found in extension. The study data enhance the understanding of the roles played by the FCD of proteoglycans and strain-dependent permeability and porosity in determining disc tissue swelling behavior. Degenerative changes involving strain-dependent permeability and/or loss of FCD of proteoglycans can further be studied using an SPFP model. Future experiments are necessary to support the current study results.     

The role of hemoglobin oxygen affinity in oxygen transport at high altitude

Hemoglobin is involved in the regulation of O(2) transport in two ways: a long-term adjustment in red cell mass is mediated by erythropoietin (EPO), a response to renal oxgyenation. Short-term, rapid-response adjustments are mediated by ventilation, cardiac output, hemoglobin oxygen affinity (P50), barriers to O(2) diffusion, and the control of local microvascular tissue perfusion. The distribution of O(2) between dissolved (PO2) and hemoglobin-bound (saturation) is the familiar oxygen equilibrium curve, whose position is noted as P50. Human hemoglobin is not genetically adapted for function at high altitude. However, more specialized species native to high altitudes (guinea pig and bar-headed goose, for example) seem to have a lower P50 than their sea level counterparts, an adaptation that presumably promotes O(2) uptake from a hypoxic environment. Humans, native to very high altitude either in the Andes or Himalayan mountains, also can increase O(2) affinity, not because of a fundamental difference in hemoglobin structure or function, but because of extreme hyperventilation and alkalosis.     

Erythrocyte 2,3-diphosphoglycerate, PO2 50% and available O2 in rabbits with bleeding anaemia superimposed on the early post-natal fall in haemoglobin

Erythrocyte 2,3-diphosphoglycerate (2,3-DPG), PO2 50%, whole blood haemoglobin (Hb), haematocrit (Hct) and available O2 were determined in two matched groups of suckling rabbits from the 17th to the 34th day after birth. One group was subjected to repeated bleeding, amounting to 1.0-1.5% of the body weight, on day 17, 19, 22 and 25, while the other served as control. The bleeding group had markedly lower Hb and Hct than the control group, which showed the ordinary post-natal fall in Hb. There were, however, no differences between 2,3-DPG and PO2 50% in the two groups. The changes were essentially the same as observed previously in animals in which the post-natal anaemia was avoided by iron-treatment. Thus, these and previously reported data show that the post-natal rise in 2,3-DPG and PO2 50% within wide limits is uninfluenced by marked variations in Hb, even severe bleeding anaemia, and support the assumption that the post-natal rise in 2,3-DPG and PO2 50% is dominated by processes related to the growth and maturation of the animals.     

Exhaled nitric oxide and pulmonary artery pressures during graded ascent to high altitude

Nitric oxide (NO) is a potent vasodilator that regulates pulmonary vascular tone. During ascent to high altitude, pulmonary vascular tone increases leading to pulmonary hypertension. To explore the mechanisms underpinning this effect, we investigated the relationship between exhaled NO (P(E(NO)); nm Hg) and pulmonary artery systolic pressure (PASP; mm Hg) in 11 healthy adults during hypoxic challenge at sea level [with oxygen saturations (S(P(O(2)))) of 80% and 90%] and at intervals during graded ascent to 5050 m. During normobaric hypoxia, PASP progressively increased from 22.7 mm Hg to 33.5 mm Hg (p=0.006), whilst P(E(NO)) remained unchanged. In contrast, during ascent to high altitude, PASP increased progressively from 22.7 mm Hg to 39.1 mm Hg (p<0.001), but P(E(NO)) decreased from 18.8 nm Hg to 9.0 nm Hg (p<0.001). However, after appropriate adjustments, P(E(NO)) had no significant effect on PASP at altitude (p=0.309). These findings indicate that although exhaled NO decreases with altitude, it does not appear to be a major contributor to hypoxic pulmonary vasoconstriction.     

Iron, transferrin, and haptoglobin levels after a single bout of exercise in men.

Twelve, healthy male university student volunteers, between the ages of 20 and 23, were studied. All subjects were considered normal after cardiopulmonary and electrocardiographic examination. The maximal aerobic capacity (Vo2 max) of each subject was determined. The exercise programmes were performed on a mechanically braked Monark cycle ergometer. The subjects were required to perform the three tests, one per week. Each subject had a catheter inserted in an antecubital vein and blood samples were drawn at rest and at the end of exercise. Before and immediately after each exercise session total proteins (TP), hematocrit (Hct), hemoglobin (Hb), and other hematological parameters were measured. Serum iron (Fe), transferrin (TRF), and haptoglobin (HPT) were also determined. Immediately after the end of the exercise (TPT, RST, and IET), TP, Hb, Hct, and RBC increased significantly. TRF and HPT concentrations remained unchanged and iron decreased significantly after maximum sustained test (RST).     

Local flow velocities in the cat carotid body tissue

With the aid of a new three-dimensional mathematical model local flow velocities in the specific carotid body tissue of the cat measured by hydrogen clearances were calculated to have a mean value of 0.006 cm/s at a perfusion pressure of 50 mm Hg, 0.014 cm/s at a perfusion pressure of 120 mm Hg, and 0.018 cm/s at a perfusion pressure of 170 mm Hg. These results indicate that the carotid body specific tissue possesses a distinct flow heterogeneity with normal capillary flow velocities and a high shunt flow. During hypoxia, the smallest decrease in tissuePO₂ was significantly correlated with the highest decrease in flow velocity. This suggests that the carotid body capillary network itself exhibits aPO₂ sensor mechanisms amplifying the chemoreceptive process in the specific cell elements.     

The influence of the position of the oxygen dissociation curve on oxygen-dependent functions of the isolated perfused rat liver

The influence of a 2,3-diphosphoglycerate (2,3-DPG)-induced displacement of the oxygen dissociation curve (O.D.C.) on the isolated perfused rat liver was studied at different levels of anaemic hypoxia. Rat livers were perfused either with fresh or with 2,3-DPG-depleted human erythrocytes at different haematocrit values (from 30% to 2.5%) at constant Po2 of the inflowing perfusate and at constant blood flow rate. The 2,3-DPG-induced difference in oxygen affinity of the red cells did not cause a significant difference in perfusion pressure during the perfusion experiments. Therefore, there is no evidence that 2,3-DPG did alter the vascular resistance of the liver, since blood flow rate could be adusted at equal values. The decrease in oxygen supply brought about by decrease of haematocrit caused a decrease of O2 consumption, of bile flow rate and of venous Po2 and an increase of lactate/pyruvate (L/P) ratio and of beta-hydroxybutyrate/acetoacetate (betaOH/Acac) ratio. There was no influence of a difference in 2,3-DPG content of the erythrocytes on the above-metioned parameters during severe anaemic hypoxia. At moderate anaemic hypoxia the venous Po2 was higher during perfusion with fresh erythrocytes than during perfusion with 2,3-DPG-depleted erythrocytes. Thus, although 2,3-DPG may play a compensatory role during conditions of mild anaemia, no such effects can be observed during conditions of severe hypoxia.     

Blood oxygen affinity and alveolar ventilation in relation in body weight in mammals.

The validity of the concept relating blood oxygen affinity and alveolar ventilation to body weight in homeothermic mammals was reexamined with blood pH used as the fixed variable. Blood Po2 at 50% saturation at pH 7.4 (P50(7.4)) and PCO2 of oxygenated blood at pH 7.4 (PCO2(7.4)) from a variety of homeothermic mammals were determined at 37 degrees C by in vitro equilibration techniques. In some species, arterial PCO2, PO2, and pH were also measured. PCO2(7.4), which was similar to arterial PCO2, showed a correlation coefficient of +0.33 with body weight over the range of 28-100,000 g and +0.90 among the species under 200 g. P50(7.4) values, which ranged from 26.0 to 38.7 mmHg for all the species, were not well correlated (r = -0.43) with body weight. For the small mammals (less than 200 g) the correlation coefficient was -0.91. In vivo P50 at the body temperature and arterial pH, although different from P50(7.4), showed a similar correlation with body weight. The lack of valid generalization suggests that body weight is only one of the composite factors that influence O2 transport systems.     

Blood substitute resuscitation as a treatment modality for moderate hypovolemia

Blood substitute resuscitation as a treatment modality for moderate hypovolemia (approximately 40% blood loss) in a canine model has been evaluated using Oxyglobin (Biopure Hemoglobin Glutamer-200/ Bovine; a hemoglobin-based oxygen-carrier) and Hespan (6% hetastarch; a nonoxygen-carrier) as resuscitants. Autologous (shed) blood served as control. Nine dogs were studied--after splenectomy, each dog was hemorrhaged (32-36 mL/kg; MAP = approximately 50 mmHg) and randomly assigned to the three resuscitation groups. Microvascular, systemic function and oxygenation characteristics were monitored and/or measured simultaneously in prehemorrhagic (baseline), posthemorrhagic and postresuscitation phases for correlation-real-time microvascular changes in the bulbar conjunctiva were noninvasively measured via computer-assisted intravital microscopy and systemic function and oxygenation changes were monitored and/or measured via instrumentation and devices incorporated into our bioengineering station in an operating room setting. Blood chemistry was also studied for relevant measurements. Prehemorrhagic microvascular characteristics were similar in all animals (venular diameter = 41 +/- 12 microm, A:V ratio = approximately 1:2, red-cell velocity = 0.5 +/- 0.3 mm/s). All animals also showed similar prehemorrhagic systemic function and oxygenation measurements comparable to a previous study and were consistent with normal measurements in dogs. At the completion of hemorrhaging to achieve moderate hypovolemia (approximately 40% blood loss with MAP at approximately 50 mmHg), all nine animals showed similar significant (P < 0.01) posthemorrhagic microvascular changes, including approximately 17% decrease in diameter (34 +/- 7 microm), A:V ratio = variable, and approximately 80% increase in velocity (0.9 +/- 0.5 mm/s). All animals also showed similar significant (P < 0.01) posthemorrhagic systemic function and oxygenation changes, with decreases in Hct, aHb(total), MPAP, MAP, SAP, DAP, CO, SVI, CaO2, and CvO2 and increases in HR and lactic acidosis. Shed blood (control) resuscitation restored posthemorrhagic microvascular changes close to prehemorrhagic values (diameter = 39 +/- 6 microm, A:V ratio = approximately 1:2, velocity = 0.6 +/- 0.4 mm/s). Oxyglobin and Hespan restored microvascular changes in similar manner close to prehemorrhagic values (Oxyglobin: diameter = 38 +/- 3 microm, A:V ratio = approximately 1:2, velocity = 0.6 +/- 0.4 mm/s; Hespan: diameter = 38 +/- 7 microm, A:V ratio = 1:2, velocity = 0.5 +/- 0.4 mm/s). After resuscitation, shed blood (control) restored all systemic function and oxygenation changes close to prehemorrhagic values. However, both Oxyglobin and Hespan resuscitation restored systemic function changes, but not oxygenation changes, to prehemorrhagic values. This was an interesting finding because of the different oxygen-carrying capability of Oxyglobin (oxygen-carrying) and Hespan (nonoxygen-carrying). The result suggests that either volume replenishment alone (and not oxygen-carrying capability) is needed to treat moderate hypovolemia or oxygenation measurements obtained by standard methods (oximetry, blood chemistry) may not reflect tissue oxygenation levels.     

Contractile properties of bundles of fiber segments from skeletal muscles

Our purpose was to determine whether contractile properties of bundles of skeletal muscle fiber segments were significantly different from those of bundles of intact fibers. In frog muscles, the only difference between the contractile properties of fiber segments and intact fibers was a lower maximum velocity of shortening (Vo) for the fiber segments. In mammalian muscles, the contraction time (TPT), relaxation time (RT1/2), and maximum tetanus tension (Po) of bundles of fiber segments were not different from those of intact fibers, but the rate of tension development (dP/dt), twitch-to-tetanus ratio (Pt/Po) and Vo were lower. The lower dP/dt and Pt/Po resulted from increased compliance due to damaged sarcomeres near cut ends. Within 4-9 mm of a cut end, membrane potentials were less than control values, and sarcomeres lengthened during a fixed-end contraction. after the length of fiber segments was corrected for the exact portion that was not shortening, the Vo of fiber segments was not different from that of intact fibers. We conclude that valid estimates of contractile properties can be obtained from bundles of skeletal muscle fiber segments.     

Left ventricular inotropic and peripheral vasomotor responses from independent changes in pressure in the carotid sinuses and cerebral arteries in anaesthetized dogs

1. The pressure perfusing the isolated carotid sinuses and the pressure perfusing the cerebral circulation were changed independently, and the resulting inotropic responses in the left ventricle and peripheral vasomotor responses were determined.2. Inotropic responses were assessed by measuring changes in the maximum rate of change of left ventricular pressure (dP/dt max) with heart rate and mean aortic pressure held constant. Vascular resistance changes were usually assessed by perfusing the descending thoracic aorta at constant flow and measuring changes in perfusion pressure.3. Decreases in carotid sinus pressure over the baroreceptor sensitivity range resulted in a 45% increase in dP/dt max and a 59% increase in vascular resistance.4. Unless arterial oxygen tension was abnormally low, lowering cerebral perfusion pressure to 50 mm Hg resulted in little or no inotropic and vasomotor responses. In the presence of hypoxaemia (P(a,O2) < 60 mm Hg), lowering cerebral perfusion pressure to below about 80 mm Hg resulted in marked responses.5. These experiments suggest that, unless arterial oxygen tension is abnormally low, the carotid sinus reflex and not cerebral hypotension is important in the control of the inotropic state of the heart and of vasomotor activity. With hypoxaemia, responses from cerebral hypotension may also be important.