Cerebral and intestinal perfusion and metabolism in normocythemic hyperviscous hypoxic newborn pigs.

We studied the effects of hypoxia on cerebral cortical and intestinal perfusion and metabolism in normocythemic hyperviscous newborn pigs. Seven pigs were made hyperviscous by an injection of cryoprecipitate, increasing viscosity from 5.8 +/- 0.9 to 9.0 +/- 1. 2 (SD) cycles/s. Six normoviscous pigs received 0.9% NaCl. Reducing the inspired O(2) decreased the arterial O(2) content (Ca(O(2))) from 9.5 +/- 1.6 to 3.6 +/- 1.3 ml O(2)/100 ml. Increases in brain and decreases in gastrointestinal blood flow at the lower Ca(O(2)) values were similar between the groups. During hypoxia, blood flow to stomach, distal intestinal mucosa, and large intestines was lower (-50, -23, and -28%, respectively) in the hyperviscous than normoviscous group. At the lower Ca(O(2)) values, cerebral cortical vascular resistance decreased in both groups and intestinal vascular resistance increased (+257%) in the hyperviscous but not in the normoviscous group. During hypoxia, systemic oxygen delivery decreased, extraction increased, and uptake did not change; cerebral cortical O(2) delivery, extraction, and uptake did not change; and intestinal O(2) delivery decreased, extraction increased, and uptake did not change in both groups. Our study demonstrated that 1) during hypoxia, increases in systemic O(2) extraction compensated for decreases in delivery and systemic uptake did not change; vasodilation sustained cerebral cortical O(2) delivery and preserved metabolism; increases in intestinal oxygen extraction offset decreases in delivery and uptake was preserved; and 2) nonpolycythemic hyperviscosity did not have a major influence on cardiovascular or metabolic responses to hypoxia, except for modest effects on intestinal resistance and perfusion to certain gastrointestinal regions. We conclude that, under normocythemic conditions, a moderate increase in viscosity does not have a major impact on hemodynamic or metabolic adjustments to hypoxia in newborn pigs.     

Alterations in cerebral autoregulation and cerebral blood flow velocity during acute hypoxia: rest and exercise

We examined the relationship between changes in cardiorespiratory and cerebrovascular function in 14 healthy volunteers with and without hypoxia [arterial O(2) saturation (Sa(O(2))) approximately 80%] at rest and during 60-70% maximal oxygen uptake steady-state cycling exercise. During all procedures, ventilation, end-tidal gases, heart rate (HR), arterial blood pressure (BP; Finometer) cardiac output (Modelflow), muscle and cerebral oxygenation (near-infrared spectroscopy), and middle cerebral artery blood flow velocity (MCAV; transcranial Doppler ultrasound) were measured continuously. The effect of hypoxia on dynamic cerebral autoregulation was assessed with transfer function gain and phase shift in mean BP and MCAV. At rest, hypoxia resulted in increases in ventilation, progressive hypocapnia, and general sympathoexcitation (i.e., elevated HR and cardiac output); these responses were more marked during hypoxic exercise (P < 0.05 vs. rest) and were also reflected in elevation of the slopes of the linear regressions of ventilation, HR, and cardiac output with Sa(O(2)) (P < 0.05 vs. rest). MCAV was maintained during hypoxic exercise, despite marked hypocapnia (44.1 +/- 2.9 to 36.3 +/- 4.2 Torr; P < 0.05). Conversely, hypoxia both at rest and during exercise decreased cerebral oxygenation compared with muscle. The low-frequency phase between MCAV and mean BP was lowered during hypoxic exercise, indicating impairment in cerebral autoregulation. These data indicate that increases in cerebral neurogenic activity and/or sympathoexcitation during hypoxic exercise can potentially outbalance the hypocapnia-induced lowering of MCAV. Despite maintaining MCAV, such hypoxic exercise can potentially compromise cerebral autoregulation and oxygenation.     

Myocardial oxygenation and adenosine release in isolated guinea pig hearts during changes in contractility

Previous work from this laboratory using near-infrared optical spectroscopy of myoglobin has shown that approximately 20% of the myocardium is hypoxic in buffer-perfused hearts that are perfused with fully oxygenated buffer at 37 degrees C. The present study was undertaken to determine cardiac myoglobin saturation in buffer-perfused hearts when cardiac contractility was increased with epinephrine and decreased during cardiac arrest with KCl. Infusion of epinephrine to achieve a doubling of contractility, as measured by left ventricular maximum pressure change over time (dP/dt), resulted in a decrease in mean myoglobin saturation from 79% at baseline to 65% and a decrease in coronary venous oxygen tension from 155 mmHg at baseline to 85 mmHg. Cardiac arrest with KCl increased mean myoglobin saturation to 100% and coronary venous oxygen tension to 390 mmHg. A previously developed computer model of oxygen transport in the myocardium was used to calculate the probability distribution of intracellular oxygen tension and the hypoxic fraction of the myocardium with an oxygen tension below 0.5 mmHg. The hypoxic fraction of the myocardium was approximately 15% at baseline, increased to approximately 30% during epinephrine infusion, and fell to approximately 0% during cardiac arrest. The coronary venous adenosine concentration changed in parallel with the hypoxic fraction of the myocardium during epinephrine and KCl. It is concluded that catecholamine stimulation of buffer-perfused hearts increases hypoxia in the myocardium and that the increase in venous adenosine concentration is a reflection of the larger hypoxic fraction of myocardium that is releasing adenosine.     

Effects of Hypoxic Exposure during Feeding on SDA and Postprandial Cardiovascular Physiology in the Atlantic Cod,Gadus morhua

Some Atlantic cod in the Bornholm Basin undertake vertical foraging migrations into severely hypoxic bottom water. Hypoxic conditions can reduce the postprandial increase in gastrointestinal blood flow (GBF). This could subsequently postpone or reduce the postprandial increase in oxygen consumption (MO₂), i.e. the SDA, leading to a disturbed digestion. Additionally, a restricted oxygen uptake could result in an oxygen debt that needs to be compensated for upon return to normoxic waters and this may also affect the ability to process the food. Long-term cardio-respiratory measurements were made on fed G. morhua in order to understand how the cardio-respiratory system of feeding fish respond to a period of hypoxia and a subsequent return to normoxia. These were exposed to 35% water oxygen saturation for 90 minutes, equivalent to the time and oxygen level cod voluntarily endure when searching for food in the Bornholm Basin. We found that i) gastric and intestinal blood flows, cardiac output and MO₂ increased after feeding, ii) gastric and intestinal blood flows were spared in hypoxia, and iii) there were no indications of an oxygen debt at the end of the hypoxic period. The magnitude and time course of the measured variables are similar to values obtained from fish not exposed to the hypoxic period. In conclusion, when cod in the field search for and ingest prey under moderate hypoxic conditions they appear to stay within safe limits of oxygen availability as we saw no indications of an oxygen debt, or negative influence on digestive capacity, when simulating field observations.     

Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs

The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.     

Arginine vasopressin reduces intestinal oxygen supply and mucosal tissue oxygen tension

We investigated intestinal oxygen supply and mucosal tissue PO2 during administration of increasing dosages of continuously infused arginine vasopressin (AVP) in an autoperfused, innervated jejunal segments in anesthetized pigs. Mucosal tissue PO2 was measured by employing two Clark-type surface oxygen electrodes. Oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. Microvascular blood flow was assessed by laser-Doppler velocimetry. Systemic hemodynamic variables, mesenteric venous and systemic acid-base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline and at 20-min intervals during incremental AVP infusion (n = 8; 0.007, 0.014, 0.029, 0.057, 0.114, and 0.229 IU.kg(-1).h(-1), respectively) or infusion of saline (n=8). AVP infusion led to a significant (P < .05), dose-dependent decrease in cardiac index (from 121 +/- 31 to 77 +/- 27 ml.kg(-1).min(-1) at 0.229 IU.kg(-1).h(-1)) and systemic oxygen delivery (from 14 +/- 3 to 9 +/- 3 ml.kg(-1).min(-1) at 0.229 IU.kg(-1).h(-1)) concomitant with an increase in systemic oxygen extraction ratio (from 31 +/- 4 to 48 +/- 10%). AVP decreased microvascular blood flow (from 133 +/- 47 to 82 +/- 35 perfusion units at 0.114 IU.kg(-1).h(-1)), mucosal tissue PO2 (from 26 +/- 7 to 7 +/- 2 mmHg at 0.229 IU.kg(-1).h(-1)), and microvascular hemoglobin oxygen saturation (from 51 +/- 9 to 26 +/- 12% at 0.229 IU.kg(-1).h(-1)) without a significant increase in mesenteric venous lactate concentration (2.3 +/- 0.8 vs. 3.4 +/- 0.7 mmol/l). We conclude that continuously infused AVP decreases intestinal oxygen supply and mucosal tissue PO2 due to a reduction in microvascular blood flow and due to the special vascular supply in the jejunal mucosa in a dose-dependent manner in pigs.     

Cardiac performance of an isolated eel heart: effects of hypoxia and responses to coronary artery perfusion.

The pericardial sac containing the heart was removed from large (2.7-6.3 kg) long-finned eels (Anguilla dieffenbachii). Coronary arteries were cannulated in preparation for perfusion with eel Ringer or red cell suspensions. The hearts were maintained by Ringer perfusion while the performance of the heart was assessed. Responses of the hearts to increases in filling pressure and output pressure were recorded. Maximum cardiac output was 22.3 +/- 1.4 ml/min/kg body mass (mean +/- 1 SEM; N = 9). The highest cardiac power output was measured at maximum cardiac output and was 3.39 +/- 0.32 mW/g ventricle mass (mean +/- 1 SEM; N = 9). Eel hearts could sustain output pressures near 80 cm H2O, but cardiac output was reduced and cardiac power output was 1.89 +/- 0.24 mW/g ventricular mass (mean +/- 1 SEM; N = 9). Maximum cardiac output decreased by 14% when hearts pumped hypoxic Ringer with a PO2 of 11.5 torr. At high input pressures concomitant with high output pressures (80 cm H2O), cardiac power output decreased by 38% upon exposure to hypoxic Ringer. Coronary perfusion of hypoxic hearts with red cell suspensions (mean hematocrit 10.4%) at a rate of 2% of control cardiac output (0.20 ml/min/kg body mass) had no effect on maximum cardiac output. However, coronary perfusion enabled hypoxic hearts to maintain cardiac output when output pressure was raised to 80 cm H2O. Under conditions of high input pressure and high output pressure, power output increased by 20% compared to hypoxic hearts without coronary perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Understanding Guyton's venous return curves

Based on observations that as cardiac output (as determined by an artificial pump) was experimentally increased the right atrial pressure decreased, Arthur Guyton and coworkers proposed an interpretation that right atrial pressure represents a back pressure restricting venous return (equal to cardiac output in steady state). The idea that right atrial pressure is a back pressure limiting cardiac output and the associated idea that "venous recoil" does work to produce flow have confused physiologists and clinicians for decades because Guyton's interpretation interchanges independent and dependent variables. Here Guyton's model and data are reanalyzed to clarify the role of arterial and right atrial pressures and cardiac output and to clearly delineate that cardiac output is the independent (causal) variable in the experiments. Guyton's original mathematical model is used with his data to show that a simultaneous increase in arterial pressure and decrease in right atrial pressure with increasing cardiac output is due to a blood volume shift into the systemic arterial circulation from the systemic venous circulation. This is because Guyton's model assumes a constant blood volume in the systemic circulation. The increase in right atrial pressure observed when cardiac output decreases in a closed circulation with constant resistance and capacitance is due to the redistribution of blood volume and not because right atrial pressure limits venous return. Because Guyton's venous return curves have generated much confusion and little clarity, we suggest that the concept and previous interpretations of venous return be removed from educational materials.     

Effects of aging on cardiac output, regional blood flow, and body composition in Fischer-344 rats

The purpose ofthis study was to determine the effects of maturation and aging oncardiac output, the distribution of cardiac output, tissue blood flow(determined by using the radioactive-microsphere technique), and bodycomposition in conscious juvenile (2-mo-old), adult (6-mo-old), andaged (24-mo-old) male Fischer-344 rats. Cardiac output was lower injuvenile rats (51 ± 4 ml/min) than in adult (106 ± 5 ml/min) oraged (119 ± 10 ml/min) rats, but cardiac index was not differentamong groups. The proportion of cardiac output going to most tissuesdid not change with increasing age. However, the fraction of cardiacoutput to brain and spinal cord tissue and to skeletal muscle wasgreater in juvenile rats than that in the two adultgroups. In addition, aged rats had a greater percentcardiac output to adipose tissue and a lower percent cardiac output tocutaneous and reproductive tissues than that in juvenile and adultrats. Differences in age also had little effect on mass-specificperfusion rates in most tissues. However, juvenile rats had lower flowsto the pancreas, gastrointestinal tract, thyroid and parathyroidglands, and kidneys than did adult rats, and aged rats had lower flowsto the white portion of rectus femoris muscle, spleen, thyroid andparathyroid glands, and prostate gland than did adult rats. Body massof juvenile rats was composed of a lower percent adipose mass and agreater fraction of brain and spinal cord, heart, kidney, liver, andskeletal muscle than that of the adult and aged animals. Relative tothe young adult rats, the body mass of aged animals had a greaterpercent adipose tissue mass and a lower percent skeletal muscle andskin mass. These data demonstrate that maturation and aging have asignificant effect on the distribution of cardiac output but relativelylittle influence on mass-specific tissue perfusion rates in conscious rats. The old-age-related alterations in cardiac output distribution toadipose and cutaneous tissues appear to be associated with theincreases in percent body fat and the decreases in the fraction of skinmass, respectively, whereas the decrease in the portion of cardiacoutput directed to reproductive tissue of aged rats appears to berelated to a decrease in mass-specific blood flow to the prostate gland.

     

Progressive hypoxia until brain electrical silence: a useful model for studying protective interventions

Anesthetized spontaneously breathing rats, fitted with epicortical electrodes and catheters for sampling arterial, venous, and cerebral venous blood, were exposed to standardized progressive hypoxia. Three minutes of hypoxia sequentially caused hyperpnea, hypopnea, apnea, and cessation of electrocorticogram "spiking," of synchronization, and of background in electroencephalogram (EEG). Blood data and cerebral blood flow and metabolism were measured throughout and at "insults," i.e., at apnea and cessation events, to clarify their interdependence. Arterial and brain venous PO2 fell linearly with inspired oxygen (final value of 2% at 280 s). Hyperpnea induced arterial alkalosis; subsequent hypopnea led to near-normal PCO2 and pH when EEG ceased. Hypercapnia was more pronounced in cerebral than in systemic venous blood; time courses of pH changes were similar. Sagittal sinus blood pressure and outflow were linearly related and resembled the time course of local cerebral blood flow. Blood flow increased by 25% at apnea and only 60% at EEG silence. Cerebral metabolic rate of O2 rose during the hyperpnea phase and fell exponentially thereafter. Cerebral glucose uptake and lactate release increased within the first 3 min but fell abruptly when cortico-electric spiking ceased. Time courses of cerebral O2 consumption and spike rate were linearly related; both showed inverse linear relations to cerebral perfusion. The hypoxic insults were well defined by blood data; critical PO2 values were lower than previously assumed. This model is proving to be a useful, controlled method by which mechanisms of cerebral hypoxia tolerance may be studied in vivo.     

Inosine, not adenosine, initiates endothelial glycocalyx degradation in cardiac ischemia and hypoxia

Ischemia/reperfusion and hypoxia/reoxygenation of the heart both induce shedding of the coronary endothelial glycocalyx. The processes leading from an oxygen deficit to shedding are unknown. An involvement of resident perivascular cardiac mast cells has been proposed. We hypothesized that either adenosine or inosine or both, generated by nucleotide catabolism, attain the concentrations in the interstitial space sufficient to stimulate A3 receptors of mast cells during both myocardial ischemia/reperfusion and hypoxia/reoxygenation. Isolated hearts of guinea pigs were subjected to either normoxic perfusion (hemoglobin-free Krebs-Henseleit buffer equilibrated with 95% oxygen), 20 minutes hypoxic perfusion (buffer equilibrated with 21% oxygen) followed by 20 minutes reoxygenation, or 20 minutes stopped-flow ischemia followed by 20 minutes normoxic reperfusion (n = 7 each). Coronary venous effluent was collected separately from so-called transudate, a mixture of interstitial fluid and lymphatic fluid appearing on the epicardial surface. Adenosine and inosine were determined in both fluid compartments using high-performance liquid chromatography. Damage to the glycocalyx was evident after ischemia/reperfusion and hypoxia/reoxygenation. Adenosine concentrations rose to a level of 1 μM in coronary effluent during hypoxic perfusion, but remained one order of magnitude lower in the interstitial fluid. There was only a small rise in the level during postischemic perfusion. In contrast, inosine peaked at over 10 μM in interstitial fluid during hypoxia and also during reperfusion, while effluent levels remained relatively unchanged at lower levels. We conclude that only inosine attains levels in the interstitial fluid of hypoxic and postischemic hearts that are sufficient to explain the activation of mast cells via stimulation of A3-type receptors.     

Rho kinase and Ca2+ entry mediate increased pulmonary and systemic vascular resistance in L-NAME-treated rats

The small GTP-binding protein and its downstream effector Rho kinase play an important role in the regulation of vasoconstrictor tone. Rho kinase activation maintains increased pulmonary vascular tone and mediates the vasoconstrictor response to nitric oxide (NO) synthesis inhibition in chronically hypoxic rats and in the ovine fetal lung. However, the role of Rho kinase in mediating pulmonary vasoconstriction after NO synthesis inhibition has not been examined in the intact rat. To address this question, cardiovascular responses to the Rho kinase inhibitor fasudil were studied at baseline and after administration of an NO synthesis inhibitor. In the intact rat, intravenous injections of fasudil cause dose-dependent decreases in systemic arterial pressure, small decreases in pulmonary arterial pressure, and increases in cardiac output. L-NAME caused a significant increase in pulmonary and systemic arterial pressures and a decrease in cardiac output. The intravenous injections of fasudil after L-NAME caused dose-dependent decreases in pulmonary and systemic arterial pressure and increases in cardiac output, and the percent decreases in pulmonary arterial pressure in response to the lower doses of fasudil were greater than decreases in systemic arterial pressure. The Ca(++) entry blocker isradipine also decreased pulmonary and systemic arterial pressure in L-NAME-treated rats. Infusion of sodium nitroprusside restored pulmonary arterial pressure to baseline values after administration of L-NAME. These data provide evidence in support of the hypothesis that increases in pulmonary and systemic vascular resistance following L-NAME treatment are mediated by Rho kinase and Ca(++) entry through L-type channels, and that responses to L-NAME can be reversed by an NO donor.     

Vasoconstrictor-mediated thermogenesis present in perfused skeletal muscle but absent from perfused heart

Resting muscle thermogenesis as controlled by vasocontrictors was compared in rat hindlimb and cardiac muscle. An α-adrenergic agonist combination of phenylephrine+atenolol increased oxygen uptake and perfusion pressure in the constant flow hindlimb and neither increase was blocked by 10 μM tetrodotoxin. The same adrenergic combination also increased oxygen uptake and perfusion pressure in the perfused heart but the former along with beating was completely blocked by tetrodotoxin. Vasoconstriction by phenylephrine occurs in the heart but is not linked to thermogenic increases as in hindlimb, implying that all metabolic energy in heart is conserved for contractile activity. The findings highlight a fundamental difference between skeletal and cardiac muscle.     

WISE 2005: stroke volume changes contribute to the pressor response during ischemic handgrip exercise in women.

The mechanism of the pressor response to small muscle mass (e.g., forearm) exercise and during metaboreflex activation may include elevations in cardiac output (Q) or total peripheral resistance (TPR). Increases in Q must be supported by reductions in visceral venous volume to sustain venous return as heart rate (HR) increases. Therefore, this study tested the hypothesis that increases in Q, supported by reductions in splanchnic volume (portal vein constriction), explain the pressor response during handgrip exercise and metaboreflex activation. Seventeen healthy women performed 2 min of static ischemic handgrip exercise and 2 min of postexercise circulatory occlusion (PECO) while HR, stroke volume and superficial femoral artery flow (Doppler), blood pressure (Finometer), portal vein diameter (ultrasound imaging), and muscle sympathetic nerve activity (MSNA; microneurography) were measured followed by the calculation of Q, TPR, and leg vascular resistance (LVR). Compared with baseline, mean arterial blood pressure (MAP) (P < 0.001) and Q (P < 0.001) both increased in each minute of exercise accompanied by a approximately 5% reduction in portal vein diameter (P < 0.05). MAP remained elevated during PECO, whereas Q decreased below exercise levels. MSNA was elevated above baseline during the second minute of exercise and through the PECO period (P < 0.05). Neither TPR nor LVR was changed from baseline during exercise and PECO. The data indicate that the majority of the blood pressure response to isometric handgrip exercise in women was due to mobilization of central blood volume and elevated stroke volume and Q rather than elevations in TVR or LVR resistance.     

Reflex control of vascular capacitance during hypoxia, hypercapnia, or hypoxic hypercapnia

We tested the hypothesis that the changes in venous tone induced by changes in arterial blood oxygen or carbon dioxide require intact cardiovascular reflexes. Mongrel dogs were anesthetized with sodium pentobarbital and paralyzed with veruronium bromide. Cardiac output and central blood volume were measured by indocyanine green dilution. Mean circulatory filling pressure, an index of venous tone at constant blood volume, was estimated from the central venous pressure during transient electrical fibrillation of the heart. With intact reflexes, hypoxia (arterial PaO2 = 38 mmHg), hypercapnia (PaCO2 = 72 mmHg), or hypoxic hypercapnia (PaO2 = 41; PaCO2 = 69 mmHg) (1 mmHg = 133.32 Pa) significantly increased the mean circulatory filling pressure and cardiac output. Hypoxia, but not normoxic hypercapnia, increased the mean systemic arterial pressure and maintained the control level of total peripheral resistance. With reflexes blocked with hexamethonium and atropine, systemic arterial pressure supported with a constant infusion of norepinephrine, and the mean circulatory filling pressure restored toward control with 5 mL/kg blood, each experimental gas mixture caused a decrease in total peripheral resistance and arterial pressure, while the mean circulatory filling pressure and cardiac output were unchanged or increased slightly. We conclude that hypoxia, hypercapnia, and hypoxic hypercapnia have little direct influence on vascular capacitance, but with reflexes intact, there is a significant reflex increase in mean circulatory filling pressure.     

Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep

Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS.     

Venous return in systemic haemodynamics

The paper generalizes unclear problems of venous return to the heart under different conditions. Data are presented on the venous return/cardiac output ratio, general peripheral resistance, arterial pressure and vascular bed capacity. A concept of double wave nature of formation of the circulation pressor systemic responses is advanced.     

Redistribution of intestinal microcirculatory oxygenation during acute hemodilution in pigs.

Acute normovolemic hemodilution (ANH) compromizes intestinal microcirculatory oxygenation; however, the underlying mechanisms are incompletely understood. We hypothesized that contributors herein include redistribution of oxygen away from the intestines and shunting of oxygen within the intestines. The latter may be due to the impaired ability of erythrocytes to off-load oxygen within the microcirculation, thus yielding low tissue/plasma Po(2) but elevated microcirculatory hemoglobin oxygen (HbO(2)) saturations. Alternatively, oxygen shunting may also be due to reduced erythrocyte deformability, hindering the ability of erythrocytes to enter capillaries. Anesthetized pigs underwent ANH (20, 40, 60, and 90 ml/kg hydroxyethyl starch; ANH group: n = 10; controls: n = 5). We measured systemic and mesenteric perfusion. Microvascular intestinal oxygenation was measured independently by remission spectrophotometry [microcirculatory HbO(2) saturation (muHbO(2))] and palladium-porphyrin phosphorescence quenching [microcirculatory oxygen pressure in plasma/tissue (muPo(2))]. Microcirculatory oxygen shunting was assessed as the disparity between mucosal and mesenteric venous HbO(2) saturation (HbO(2)-gap). Erythrocyte deformability was measured as shear stress-induced cell elongation (LORCA difractometer). ANH reduced hemoglobin concentration from 8.1 to 2.2 g/dl. Relative mesenteric perfusion decreased (decreased mesenteric/systemic perfusion fraction). A paralleled reduction occurred in mucosal muHbO(2) (68 +/- 2 to 41 +/- 3%) and muPo(2) (28 +/- 1 to 17 +/- 1 Torr). Thus the proposed constellation indicative for oxygen off-load deficits (sustained muHbO(2) at decreased muPo(2)) did not develop. A twofold increase in the HbO(2)-gap indicated increasing intestinal microcirculatory oxygen shunting. Significant impairment in erythrocyte deformability developed during ANH. We conclude that reduced intestinal oxygenation during ANH is, in addition to redistribution of oxygen delivery away from the intestines, associated with oxygen shunting within the intestines. This shunting appears to be not primarily caused by oxygen off-load deficit but rather by oxygen/erythrocytes bypassing capillaries, wherein a potential contributor is impaired erythrocyte deformability.     

Effects of systemic arterial hypoperfusion on splanchnic hemodynamics and hepatic arterial buffer response in pigs

The hepatic arterial buffer response (HABR) tends to maintain liver blood flow under conditions of low mesenteric perfusion. We hypothesized that systemic hypoperfusion impairs the HABR. In 12 pigs, aortic blood flow was reduced by cardiac tamponade to 50 ml. kg(-1). min(-1) for 1 h (short-term tamponade) and further to 30 ml. kg(-1). min(-1) for another hour (prolonged tamponade). Twelve pigs without tamponade served as controls. Portal venous blood flow decreased from 17 +/- 3 (baseline) to 6 +/- 4 ml. kg(-1). min(-1) (prolonged tamponade; P = 0.012) and did not change in controls, whereas hepatic arterial blood flow decreased from 2 +/- 1 (baseline) to 1 +/- 1 ml. kg(-1). min(-1) (prolonged tamponade; P = 0.050) and increased from 2 +/- 1 to 4 +/- 2 ml. kg(-1). min(-1) in controls (P = 0.002). The change in hepatic arterial conductance (DeltaC(ha)) during acute portal vein occlusion decreased from 0.1 +/- 0.05 (baseline) to 0 +/- 0.01 ml. kg(-1). min(-1). mmHg(-1) (prolonged tamponade; P = 0.043). In controls, DeltaC(ha) did not change. Hepatic lactate extraction decreased, but hepatic release of glutathione S-transferase A did not change during cardiac tamponade. In conclusion, during low systemic perfusion, the HABR is exhausted and hepatic function is impaired without signs of cellular damage.     

Effect of endothelin-1 and vasoactive intestinal contractor on blood flow and output of vasoactive intestinal polypeptide in the feline colon

Injection of the structurally related peptides, endothelin-1 and vasoactive intestinal contractor (VIC), into a branch of the superior mesenteric artery in anesthetized cats caused dose-dependent reductions in blood flow in the portal vein and inferior mesenteric artery. The maximum effect occurred after 1 minute and was more prolonged in the portal vein. The effects of the two peptides were not significantly different. The colonic output of vasoactive intestinal polypeptide (VIP) into portal venous blood was decreased significantly by endothelin-1 and VIC, returning to baseline more rapidly than blood flow. When norepinephrine was injected to produce comparable reductions in blood flow, the output of VIP into portal venous blood was not altered significantly. These results suggest that inhibition of output of the vasodilator VIP contributes to the vasoconstrictor effects of endothelin-1 and VIC in the feline colonic vascular bed.