Decrease In PvO2 Research Articles

High Intensity Exercise Improves Cardiorespiratory Capacity in a Mouse Model of Hypertrophic Cardiomyopathy

IntroductionCardiorespiratory capacity (pVO2) is an important prognostic indicator in patients with HCM. Individuals with HCM that have a lower pVO2 possess a greater risk for heart failure (HF) and mortality. High intensity exercise (HIE) can increase pVO2 to a greater degree compared to other training modalities, including when used for cardiac rehabilitation for in cardiac disease states (e.g., HF and Cardiovascular disease). The effects of HIE on HCM, however, are largely unknown. Our study sought to evaluate the effects of High Intensity Interval Training (HIIT) on pVO2, as well as cardiac structural and functional parameters, in a preclinical mouse model of HCM.MethodsFemale and male C57BL/6J non‐transgenic nTG (n=27) and TG (n=32) mice were subjected to HIIT protocol that mirrored methods used clinically in cardiac rehabilitation. A single treadmill training session included 4‐4 minute high intensity intervals (~80% preVO2 max speed) interspersed by 5‐3 minute recovery intervals (~50% preVO2 max speed) for 31 total minutes. Exercise training sessions were repeated 3 times per week for 6 weeks. Pre and post pVO2 and murine echocardiography were measured and analyzed by a blinded technician.ResultsFollowing 6 weeks of the HIIT, nTG female (+13.5 mL/kg/min ± 3.6, p<0.01), nTG male (+13.5 mL/kg/min ± 3.6, p<0.01) and TG female (+7.06 ± 3.3 mL/kg/min, p<0.05) mice demonstrated an average increase in pVO2. A change in pVO2 observed in TG male mice did not reach statistical significance (+4.34 ± p=0.12). Sedentary female (‐15.9 mL/kg/min ± 3.3, p<0.001) and male (‐13.1 mL/kg/min ± 3.9, p<0.01) TG control mice experienced a significant decrease in pVO2 following the same period, while no change was observed in nTG sedentary controls. Independent of sex, nTG and TG HIIT mice had a significantly greater change in pVO2 compared to sedentary counterparts. HIIT training did not result in changes to the following echocardiography measures in either nTG or TG mice: LV mass, LA volume, cardiac output, or stroke volume.ConclusionOur results indicate that a translationally derived HIIT protocol improved cardiorespiratory capacity in a preclinical HCM mouse model, absent of adverse events or worsening of organ level disease pathology.

Evaluation of Xylazine HCl as a Potential Anesthetic for Laprogastrotomy Operation in Dogs

The present study aimed to evaluate intramuscular xylazine HCl 2% as an anesthetic for laparogastrotomy in dogs at different doses. Twenty-seven dogs were divided randomly and equally into three groups; group A received 4 mg/kg, group B, received 8 mg/kg, and group C received 14 mg/kg. Anesthetic indices, effect on physiological parameters, blood gases, and biochemical parameters were recorded. The onset was 4.00 ± 0.00, 3.50 ± 0.33, and 5.00 ± 0.33 min, and the duration was 18.00 ± 2.50, 21.00 ± 7.20, and 28.00 ± 4.30 min in the groups A, B, and C, respectively. Pedal reflex was absent in groups A and B from 5 - 30 min post-injection. Palpebral reflex was absent in all groups from 20 - 30 min post-injection. All dogs recorded a non-significant decrease in the rectal temperature, but a significant decrease in respiratory and heart rates. There was a significant increase in the PvCO2 level and significant hyperglycemia in all dogs. Dogs in groups B and C exhibited a significant decrease in PvO2. There was a significant decrease in the serum cortisol level in the group B. Creatinine level recorded non-significant decrease in the group A, while there was a non-significant increase in the group B. There was non-significant decrease in GGT levels in the groups A and C. Xylazine at dose of 14 mg/kg established a satisfactory stable anesthesia that was enough to conduct laparogastrotomy in dogs.

Effects of xylazine-ketamine, xylazine-propofol and xylazine-ketamine-propofol administration on free radical generation and blood gases in sheep

This study was aimed at investigating the effects of xylazine-ketamine, xylazine-propofol and xylazine-ketamine-propofol combinations on oxidative stress, antioxidant capacity and blood gases in sheep. Excluding the control animals, the sheep included in Groups 1, 2 and 3 were administered with combinations of xylazine-ketamine, xylazine-propofol and xylazine-ketamine-propofol, respectively, by intravenous route. The comparison of the three treatment groups with the control group showed that no significant difference existed for TAS, TOS, MDA and CAT levels. The evaluation of blood gas and electrolyte levels demonstrated a significant decrease in PvO2, cSO2, Na, and Ca levels, and a significant increase in glucose levels. In result, this study showed that the three anaesthetic combinations tested did not have any adverse effect on the oxidant/antioxidant status, but caused significant alterations in blood gas levels.

Decline in peak oxygen consumption over time predicts death or transplantation in adults with a Fontan circulation

We analyzed a cohort of adults (≥18 years old) with a Fontan circulation who underwent at least 2 maximal CPETs separated by 6-30 months at Boston Children's Hospital between 2000 and 2015. Survival analysis was performed to determine whether changes in CPET variables, including pVO2 between consecutive tests, were associated with subsequent clinical events. The primary outcome was transplant-free survival. The study included 130 patients with 287 CPET test pairs. Average age was 26.6±9.5 years. Baseline pVO2 averaged 22.0±5.7 mL/kg/min or 60.9%±13.7% predicted. In the cohort overall, there was no change in mean pVO2 between sequential CPETs. Eleven patients died and 2 underwent transplant. On average, pVO2 declined for patients who subsequently died or underwent transplant but remained stable among those who did not (-9.8%±14.6% vs 0.0±13.0%, P<.01). Those with a decline in pVO2 between CPETs were at greater risk of death or transplantation (per 10% decrease in pVO2: HR=2.0, 95% CI 1.2-3.1, P=.004). Change in pVO2 remained a significant predictor of death or transplant after adjusting for pVO2 at first CPET (per 10% decline in pVO2: HR=2.5, 95% CI 1.5-4.2, P<.001). A decline in pVO2 between consecutive CPETs predicts increased risk for death or transplant in adults with a Fontan circulation independent of baseline pVO2. These results support the additive clinical value of serial CPET in this population.

Unloaded skeletal muscle O2 uptake decreases with decreased venous PO2 at high-frequency stimulation.

The aim of the present study was to clarify the effects of O2 diffusion limitation resulting from hypoxic interventions on O2 uptake (V.O2) in unloaded (that is, near-zero initial force) and loaded skeletal muscle in a high-frequency stimulation. We measured V.O2, muscle venous PO2 (PvO2) and initial force in gastrocnemius-plantaris muscle in situ of anesthetized dogs: (1) during hypoxic hypoxia at 1 Hz tetanic stimulation, and (2) during hypoxia induced by the perfusion with high O2-affinity erythrocytes (having a low value of PO2 at 50% saturation of hemoglobin (P50)) at 4 Hz twitch stimulation. Averaged unloaded V.O2 during normoxia was 10.2 ml.min-1.100 g-1 at averaged blood flow of 74 ml.min-1.100 g-1 (n = 6). Hypoxic hypoxia of a decreased O2 delivery (arterial O2 concentration x flow) significantly decreased both unloaded and loaded V.O2 with a decrease in PvO2 (p<0.05). The unloaded V.O2 was reduced to 8.5 ml.min-1.100 g-1. Low P50-hypoxia decreased V.O2 at high and low initial force conditions with a decrease in PvO2 (p<0.05) at the same O2 delivery. If these decreases in V.O2 correspond with a decrease in V.O2 at zero initial force (unloaded V.O2), the unloaded V.O2 value is calculated to be 7.57 ml.min-1.100 g-1 from V. O2-initial force data. Despite the different conditions of O2 delivery, the unloaded V.O2 decreased by both hypoxia showed similar values. Thus the decreased unloaded V.O2 does not seem to be derived from only the limited O2 delivery. Some other factors such as the limitation of O2 diffusion may contribute to the decreased V.O2.

Effect of blood blow and haematocrit on the relationship between muscle venous PO2 and oxygen uptake in dog maximally contracting gastrocnemius in situ.

1. To clarify the limiting factors for peak VO2 (VO2,peak), we measured muscle venous PO2, (PVO2) and VO2,peak under various O2 delivery conditions (arterial O2 concentration x flow) via the alteration of blood flow and haematocrit (Hct) in anaesthetized dog gastrocnemius muscle (n = 11) stimulated by 1 Hz isometrically and tetanically. 2. Two levels of flow (high and moderate) were maintained by using a pump (150 and 100 mL/min per 100 g, respectively). Haematocrit was adjusted to 45 and 30% by isovolaemic haemodilution with dextran (MW 40,000). 3. The decrease in Hct induced a 31% decrease in O2 delivery (P < 0.05), a 9-12% decrease in PVO2, a 23% decrease in VO2,peak (P < 0.05) and a 12-14% increase in O2 extraction (VO2/O2 delivery) at both flow levels. The decrease in flow induced a 24-25% decrease in O2 delivery (P < 0.05), a 15-17% decrease in PVO2 (P < 0.05), a 9% decrease in VO2,peak (P < 0.05) and a 19-22% increase in O2 extraction (P < 0.05) at both Hct levels. 4. The results suggest that the limiting factor of VO/,peak, unrelated to O2 diffusion limitation (i.e. the change in the heterogeneity of VO2 to O2 delivery ratio among capillaries), due to lowering Hct may be different from that due to lowering blood flow in maximally contracting muscle.

Muscle blood flow and distribution determine maximal VO2 of contracting muscle

During repetitive contractions, the VO2 of the dog gastrocnemius-plantaris muscle rose with the contraction frequency up to a maximal value and then decreased as contraction frequency was increased further. PVO2 was constant over most of the contraction frequency range. Reducing perfusion pressure/blood flow reduced VO2max with a constant PVO2. During these maneuvers the diffusion conductance, DCO2 (VO2/PVO2), changed with VO2. Raising the perfusion pressure/flow with a pump increased VO2 with a small rise in PVO2 so that DCO2 also increased. Removing tension from the muscle between contractions elevated VO2 and DCO2 without a change in perfusion pressure. Hypoxemia decreased VO2 with a decrease in PVO2; DCO2 remained constant. A three-compartment mathematical model, based on microsphere measurements of regional flow, was used to illustrate how regional flow variations may exist, and how they are poorly revealed in the mixed whole-muscle venous blood. The model shows VO2.g-1 strongly related to flow. As VO2.g-1 increased as Q.g-1 increased, extraction decreased, and DCO2 increased.

Pulmonary circulation during inhalation anaesthesia

Any disturbance of the balance between pulmonary ventilation and perfusion alters the efficacy of gas exchange. General anaesthesia changes respiratory mechanics leading to an altered distribution of inspired gas that increases VA/Q inequalities and provokes atelectasis with right-to-left shunting. In contrast, anaesthetic agents seem to have little apparent effect on pulmonary circulation. Although in vitro studies have demonstrated that inhalation anaesthetics, but not intravenous agents, inhibit the major regulator of pulmonary blood flow distribution (i.e. HPV), the depression of HPV in vivo is less pronounced than expected because of compensatory mechanisms. Presumably the most important compensatory mechanism is associated with the anaesthesia-induced reduction of cardiac output and a concomitant decrease in PvO2 that stimulates the HPV response. During one-lung anaesthesia, when active HPV is most desirable, inhalation anaesthetics are generally not contraindicated because venous admixture rarely increases sufficiently to produce severe hypoxaemia. Some patients, however, may develop hypoxaemia and create a challenge for the anaesthetist. Other factors that characterize the variability of individual responses need to be considered, such as age, meatabolic state, drugs, underlying disease, and, particularly, pre-existing cardiopulmonary abnormalities and surgical trauma.

Oxygen Delivery and Consumption during Hypothermia and Rewarming in the Dog

Changes in oxygen consumption (VO2) and oxygen delivery (DO2) were compared in three groups of paralyzed, sedated dogs: 1) a group (n = 5) cooled to 29 degrees C and immediately rewarmed to 37 degrees C; 2) a group (n = 5) cooled to and maintained at 29 degrees C for 24 h, and then rewarmed; and 3) a group (n = 5) maintained at 37 degrees C for 24 h. During the cooling phase, in both the acute and prolonged hypothermia animals, VO2 and DO2 decreased significantly from control values (P less than 0.05). The decrease in DO2 occurred as a result of a similar decrease in cardiac index (CI; P less than 0.05) that was associated with a significant increase in systemic vascular resistance index (SVRI; P less than 0.05). Arteriovenous oxygen content difference (C(a-v)O2), O2 extraction ratio, mixed venous oxygen tension (PVO2), pH, and base deficit (BD) were not different from control values even during prolonged hypothermia. Normothermic control dogs also demonstrated a significant decrease in CI (P less than 0.05) at 24 h. Surface rewarming increased VO2 back to control values in the acute hypothermia group and to values above control (P less than 0.05) in the prolonged hypothermia group. DO2 remained below control in both groups, resulting in a significant increase in O2 extraction (P less than 0.05) and a decrease in PVO2 (P less than 0.05) in the prolonged hypothermia animals. Following rewarming administration of sodium nitroprusside returned DO2, CI, and SVRI to control values but did not increase VO2. All animals survived the study without need for inotropic support.(ABSTRACT TRUNCATED AT 250 WORDS)

The Influence of Position on Ventilation-Perfusion Distribution After Abdominal Surgery

The effects of a change in position on gas exchange and ventilation perfusion (VA/Q) distribution were studied in 12 patients, after abdominal surgery. VA/Q distribution was determined from retention and excretion curves of six inert gases of different solubilities, in supine and sitting patients, during spontaneous breathing. Changing position from supine to sitting resulted in an increase in minute ventilation and a decrease in PaCO2 without any change in PaO2. With regard to VA/Q distribution, an estimated shunt of 5.2% +/- 3.4 was documented in all the patients in the supine position, and was associated with a large percentage of low VA/Q regions (20.0% +/- 13.0) in six of them. Patients with associated estimated shunt and low VA/Q regions were those with the greatest amount of venous admixture (respectively: 27.3% +/- 7.2, and 14.9% +/- 3.0, for patients without low VA/Q regions, P less than 0.01). When patients were placed in the sitting position, the estimated shunt was not reduced, but the percentage of low VA/Q regions decreased when it was documented. Despite the improvement of VA/Q distribution in the sitting position, the lack of significant change in PaO2 may be explained by the simultaneous decrease in PVO2 caused by a decrease in cardiac output.

The influence of position on ventilation-perfusion distribution after abdominal surgery.

The effects of a change in position on gas exchange and ventilation perfusion (VA/Q) distribution were studied in 12 patients, after abdominal surgery. VA/Q distribution was determined from retention and excretion curves of six inert gases of different solubilities, in supine and sitting patients, during spontaneous breathing. Changing position from supine to sitting resulted in an increase in minute ventilation and a decrease in PaCO2 without any change in PaO2. With regard to VA/Q distribution, an estimated shunt of 5.2% +/- 3.4 was documented in all the patients in the supine position, and was associated with a large percentage of low VA/Q regions (20.0% +/- 13.0) in six of them. Patients with associated estimated shunt and low VA/Q regions were those with the greatest amount of venous admixture (respectively: 27.3% +/- 7.2, and 14.9% +/- 3.0, for patients without low VA/Q regions, P less than 0.01). When patients were placed in the sitting position, the estimated shunt was not reduced, but the percentage of low VA/Q regions decreased when it was documented. Despite the improvement of VA/Q distribution in the sitting position, the lack of significant change in PaO2 may be explained by the simultaneous decrease in PVO2 caused by a decrease in cardiac output.

FAILURE TO INDUCE MALIGNANT HYPERTHERMIA IN MYOTONIC GOATS

Six goats with myotonia congenita were exposed for 1 h to 1% halothane and a single injection of suxamethonium i.v. in an attempt to induce malignant hyperthermia. No evidence of malignant hyperthermia occurred. Suxamethonium did produce a myotonic response in each goat, lasting 10-20s, which was accompanied by a transient increase in aerobic metabolism as indicated by a decrease in PvO2 from 6.6 to 5.7 kPa, an increase in PaCO2 from 5.1 to 6.1 kPa and an increase in PVCO2 from 5.5 to 6.3 kPa. There was no evidence of any metabolic acidosis since the transient changes in pH and buffer base were consistent with the increase in carbon dioxide tension. It is concluded that in goats myotonia congenita does not predispose to susceptibility to malignant hyperthermia.

Effect of acute and established anemia on O2 transport at rest, submaximal and maximal work

Effects of acute and maintained isovolemic anemia on oxygen transport was studied during rest and exercise in normal males. Following 34% reduction in hemoglobin concentration (Hb), supine and standing Q rose acutely by 56% and 20%, respectively, but returned nearly to the control value by 10-14 days, producing a decrease in PVO2. Redistribution of blood flow appeared to compensate significantly for the decrease in systemic oxygen transport. 2,3-Diphosphoglycerate rose by 18%, in vivo PO2 at half-saturation of hemoglobin (P50) rose by approximately 2 mm over 7-9 days and probably afforded some compensation. The relationship between VO2 and external work intensity was independent of Hb. During exercise, Q/VO2 and VE/VO2 were increased in acute anemia, but PVO2, for a given VO2, decreased below control levels. After 10-14 days the relative increase in VE with exercise persisted; the increase in Q was less pronounced; and PVO2 was further decreased. With both acute and extablished anemia maximal exercise capacity and maximal VO2 (VO2 max) decreased in proportion to the Hb reduction.