Percent carboxyhemoglobin in resting humans exposed repeatedly to 1,500 and 7,500 ppm CO

Eleven nonsmoking male resting subjects were exposed to two transient CO profiles to examine whether the resultant carboxyhemoglobin (HbCO) differs with CO concentration for a fixed total CO dose and to determine the predictive capability of the theoretical model of Coburn et al. (J. Clin. Invest. 44: 1899-1910, 1965) using measured alveolar ventilation. One profile consisted of five sequential exposures to 1,500 ppm CO for 5 min each and spaced 3 min apart. The other consisted of five sequential exposures to 7,500 ppm CO for 1 min each and spaced 7 min apart. The subjects, therefore, were exposed to the same overall nominal dose of 37,500 ppm.min. During the experiment, the subject's ventilatory functions and respiratory gases were recorded continuously, and the resultant HbCO% was measured in venous blood samples by gas chromatography. Mean increase (+/- SD) in HbCO% per exposure was 2.08 +/- 0.27% for the 1,500 ppm CO exposures and 2.05 +/- 0.29% for the 7,500 ppm CO exposures with no significant difference between the two. When the measured values of the subject's alveolar ventilation were applied to the theoretical model of Coburn et al., the predicted rate of HbCO% formation was found to agree with the experimental results.     

Effects of anesthetics on systemic hemodynamics in mice

The aim of this study was to compare the systemic hemodynamic effects of four commonly used anesthetic regimens in mice that were chronically instrumented for direct and continuous measurements of cardiac output (CO). Mice (CD-1, Swiss, and C57BL6 strains) were instrumented with a transit-time flow probe placed around the ascending aorta for CO measurement. An arterial catheter was inserted into the aorta 4 or 5 days later for blood pressure measurements. After full recovery, hemodynamic parameters including stroke volume, heart rate, CO, mean arterial pressure (MAP), and total peripheral resistance were measured with animals in the conscious state. General anesthesia was then induced in these mice using isoflurane (Iso), urethane, pentobarbital sodium, or ketamine-xylazine (K-X). The doses and routes of administration of these agents were given as required for general surgical procedures in these animals. Compared with the values obtained for animals in the conscious resting state, MAP and CO decreased during all anesthetic interventions, and hemodynamic effects were smallest for Iso (MAP, -24 +/- 3%; CO, -5 +/- 7%; n = 15 mice) and greatest for K-X (MAP, -51 +/- 6%; CO, -37 +/- 9%; n = 8 mice), respectively. The hemodynamic effects of K-X were fully antagonized by administration of the alpha(2)-receptor antagonist atipamezole (n = 8 mice). These results indicate that the anesthetic Iso has fewer systemic hemodynamic effects in mice than the nonvolatile anesthetics.     

The effects of inspiratory intrathoracic pressure production on the cardiovascular response to submaximal exercise in health and chronic heart failure

We sought to determine whether the normal inspiratory intrathoracic pressures (P(ITP)) produced during exercise contribute to the blunted cardiac output and locomotor limb blood flow responses observed in chronic heart failure (CHF). Five chronically instrumented dogs exercised on a treadmill at 2.5 mile/h at 5% grade while healthy or after the induction of tachycardia-induced CHF. We observed several key differences in the cardiovascular responses to changes in the inspiratory P(ITP) excursion between health and CHF; namely, 1) removing approximately 70% of the normally produced inspiratory P(ITP) excursion during exercise (with 15 cmH(2)O inspiratory positive pressure ventilation) significantly reduced stroke volume (SV) in healthy animals by 5 +/- 2% (P < 0.05) but significantly increased SV and cardiac output (Q(TOT)) in animals with CHF by 5 +/- 1% (P < 0.05); 2) doubling the magnitude of the inspiratory P(ITP) excursion had no effect on SV or Q(TOT) in healthy animals but significantly reduced steady-state Q(TOT) and SV in animals with CHF by -4 +/- 3% and -10 +/- 3%, respectively; 3) removing the majority of the normally produced inspiratory P(ITP) excursion had no effect on blood flow distribution in healthy animals but increased hindlimb blood flow (9 +/- 3%, P < 0.05) out of proportion to the increases in Q(TOT); and 4) the only similarity between healthy and CHF animals was that increasing the inspiratory P(ITP) excursion significantly reduced steady-state locomotor limb blood flow by 5 +/- 2% and 6 +/- 3%, respectively (P < 0.05 for both). We conclude that 1) the normally produced inspiratory P(ITP) excursions are required for a maximal SV response to submaximal exercise in healthy animals but detrimental to the SV and Q(TOT) responses to submaximal exercise in CHF, 2) the respiratory muscle ergoreflex tonically restrains locomotor limb blood flow during submaximal exercise in CHF, and 3) excessive inspiratory muscle work further compromises cardiac function and blood flow distribution in both health and CHF.     

Expiratory threshold loading impairs cardiovascular function in health and chronic heart failure during submaximal exercise.

We determined the effects of augmented expiratory intrathoracic pressure (P(ITP)) production on cardiac output (Q(TOT)) and blood flow distribution in healthy dogs and dogs with chronic heart failure (CHF). From a control expiratory P(ITP) excursion of 7 +/- 2 cmH2O, the application of 5, 10, or 15 cmH2O expiratory threshold loads increased the expiratory P(ITP) excursion by 47 +/- 23, 67 +/- 32, and 118 +/- 18% (P < 0.05 for all). Stroke volume (SV) rapidly decreased (onset <10 s) with increases in the expiratory P(ITP) excursion (-2.1 +/- 0.5%, -2.4 +/- 0.9%, and -3.6 +/- 0.7%, P < 0.05), with slightly smaller reductions in Q(TOT) (0.8 +/- 0.6, 1.0 +/- 1.1, and 1.8 +/- 0.8%, P < 0.05) owing to small increases in heart rate. Both Q(TOT) and SV were restored to control levels when the inspiratory P(ITP) excursion was augmented by the addition of an inspiratory resistive load during 15 cmH2O expiratory threshold loading. The highest level of expiratory loading significantly reduced hindlimb blood flow by -5 +/- 2% owing to significant reductions in vascular conductance (-7 +/- 2%). After the induction of CHF by 6 wk of rapid cardiac pacing at 210 beats/min, the expiratory P(ITP) excursions during nonloaded breathing were not significantly changed (8 +/- 2 cmH2O), and the application of 5, 10, and 15 cmH2O expiratory threshold loads increased the expiratory P(ITP) excursion by 15 +/- 7, 23 +/- 7, and 31 +/- 7%, respectively (P < 0.05 for all). Both 10 and 15 cmH2O expiratory threshold loads significantly reduced SV (-3.5 +/- 0.7 and -4.2 +/- 0.7%, respectively) and Q(TOT) (-1.7 +/- 0.4 and -2.5 +/- 0.4%, P < 0.05) after the induction of CHF, with the reductions in SV predominantly occurring during inspiration. However, the augmentation of the inspiratory P(ITP) excursion now elicited further decreases in SV and Q(TOT). Only the highest level of expiratory loading significantly reduced hindlimb blood flow (-4 +/- 2%) as a result of significant reductions in vascular conductance (-5 +/- 2%). We conclude that increases in expiratory P(ITP) production-similar to those observed during severe expiratory flow limitation-reduce cardiac output and hindlimb blood flow during submaximal exercise in health and CHF.     

Renal response to hemorrhage in dogs with subacute biliary obstruction

In the present study, we tested the hemodynamic and renal response of 15 sham-operated dogs and 15 dogs with subacute (5-9 days) biliary obstruction to either acute or more chronic hemorrhage. All studies were conducted on sedated but unanaesthetized animals. Both groups were comparable before blood withdrawal with respect to central hemodynamics and renal perfusion. Serum bilirubin was 0.70 +/- 0.09 mg/dL for control dogs and 8.25 +/- 0.14 for experimental dogs (P less than 0.05). In the acute protocol, nine control and seven jaundiced dogs were bled over a period of 30-40 min to lower blood pressure by 19.1 and 19.5%, respectively. Blood volumes required to achieve this drop were 21.3 and 20.05 mL/kg, respectively (P greater than 0.05). Cardiac output declined by an equivalent value for each group and glomerular filtration rate and clearance of p-aminohippurate remained unchanged from control values. In six control and eight experimental dogs, 500 mL of blood was withdrawn over 5 days. Although blood pressure and cardiac output declined for each group by an equivalent amount, renal perfusion remained unchanged for each group from control values. We conclude that acute or chronic hemorrhage of modest degree does not predispose to acute renal insufficiency in dogs with subacute biliary obstruction.     

Thermoregulatory responses to exercise in dehydrated dogs

Measurements of rectal temperature (Tre), water lost by evaporation (Eresp) and drooling, cardiac output (CO), and common carotid blood flow (CCBF) were made in dogs (mean hydrated wt 31.0 +/- 1.5 kg) running for 1 h on a level treadmill at 7.5 km/h at an ambient temperature of 25 degrees C. Each animal was studied when it was hydrated ad libitum and when it had been dehydrated by removal of drinking water until 9-10% of the initial body weight had been lost. Dehydrated exercising animals had significantly higher Tre and lower rates of Eresp, CO, and CCBF. Tre and Eresp were measured in seven animals. Average Tre during running was 39.11 +/- 0.10 degrees C in hydrated and 39.80 +/- 0.25 degrees C in dehydrated animals (P less than 0.01). Average Eresp during running was 3.9 +/- 0.3 g/min in hydrated animals and 2.3 +/- 0.3 g/min in dehydrated animals (P less than 0.01). Average CO during exercise, measured in five animals, was 11.1 +/- 0.7 1/min in the hydrated state and 8.6 +/- 0.5 1/min in the dehydrated state (P less than 0.01). Unilateral CCBF during exercise, measured in four animals, was 602 +/- 40 ml/min in the hydrated state and 418 +/- 22 ml/min in the dehydrated state (P less than 0.01). Water lost by drooling in seven exercising animals was 41.5 +/- 11 g/h when they were hydrated and 0.6 +/- 0.4 g/h when they were dehydrated. It is concluded that dehydrated dogs doing mild exercise can save water by reducing Eresp and regulating body temperature above hydrated levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of alpha-adrenergic receptors in carbon monoxide hypoxia

The importance of alpha-adrenergic receptors in the cardiac output and peripheral circulatory responses to carbon monoxide (CO) hypoxia was studied in anesthetized dogs. Phenoxybenzamine (3 mg/kg i.v.) was injected to block alpha-receptor activity and the data obtained were then compared with those from a previous study of CO hypoxia in unblocked animals. Values for cardiac output, hindlimb blood flow, vascular resistance, and oxygen uptake were obtained prior to and at 30 and 60 min of CO hypoxia which reduced arterial oxygen content by approximately 50%. alpha-Adrenergic blockade resulted in a lower (p less than 0.05) control value for cardiac output than observed in unblocked animals, but no differences were present between the two groups at 30 or 60 min of CO hypoxia. Similarly, limb blood flow was lower (p less than 0.05) during the control period in the alpha-blocked group but rose to the same level as that in the unblocked animals at 60 min of COH. No change in limb blood flow occurred during CO hypoxia in the unblocked group. These findings demonstrated that during CO hypoxia alpha-receptor mediated venoconstriction does not contribute to the cardiac output response and alpha-receptor mediated vasoconstriction probably does prevent a rise in hindlimb skeletal muscle blood flow.     

A comparison of the natural survival of beagle dogs injected intravenously with low levels of 239Pu, 226Ra, 228Ra, 228Th, or 90Sr

The natural survival, relative to properly chosen controls, of 26 beagle dogs injected once intravenously with an average of 0.58 +/- 0.04 kBq 239Pu/kg, 23 dogs injected with 2.31 +/- 0.43 kBq 226Ra/kg, 13 dogs injected with 1.84 +/- 0.26 kBq 228Ra/kg, 12 dogs injected with 0.56 +/- 0.030 kBq 228Th/kg, and 12 dogs injected with 21.13 +/- 1.74 kBq 90Sr/kg was evaluated statistically. The amounts of these radionuclides are related directly to the estimated maximum permissible body burdens for humans suggested in ICRP II (1959). They constitute a level of exposure that initially was assumed to cause no deleterious effects in dogs. This study had two objectives: (1) identification of homogeneous control groups against which to evaluate the survival of the irradiated groups and (2) comparison of the survival characteristics and estimation of mortality or hazard rate ratios for control dogs vs dogs injected with the baseline dosages given above. It was shown, by goodness-of-fit plots, that the Cox proportional hazards model was an appropriate method of analysis. Therefore, covariates that possibly could influence survival were tested for significance. Only the effects of grand mal seizure, which is caused in epileptic dogs by an external stimulus and can be fatal if untreated, were significant (P less than 0.0001). Consequently, in the final model, death from grand mal seizure was considered as accidental. After censoring the dogs dying from grand mal seizure, it was established that the data for the control groups from previous and contemporary experiments could be pooled. The change in hazard rates relative to controls resulting from exposure to the baseline radionuclide level was modest, 1.6 times for 239Pu (P = 0.033), 1.0(4) for 226Ra (P = 0.86), 1.9 for 228Ra (P = 0.035), 2.5 for 228Th (P less than 0.001), and 0.52 for 90Sr (P = 0.041). Bone tumor induction was clearly elevated in dogs injected with 239Pu and 228Th. When the effect of these bone tumors on survival was removed by censoring, the dogs injected with 239Pu were indistinguishable from the controls. In contrast, the effects of bone tumor on group survival of the 228Ra and 228Th dogs were not significant. Thus, no additional life-shortening effects beyond those attributable to bone tumor were suggested by these data for 239Pu, but other, as yet unspecified, confounders are suggested for 228Ra and 228Th.     

Hemodynamic effects of synchronous high-frequency jet ventilation during acute hypovolemia

We studied the effects of synchronous cardiac cycle-specific high-frequency jet ventilation (HFJV) in pentobarbital-anesthetized, splenectomized, closed-chest dogs to test the hypothesis that phasic inspiratory increases in intrathoracic pressure (ITP) selectively timed to specific periods of the cardiac cycle have different hemodynamic effects during both hypovolemia (acute hemorrhage, 20 ml/kg) and neurogenic vasomotor shock (hexamethonium, 10 mg/kg) than those observed during normovolemic control conditions. Ventricular stroke volumes (SV) were measured by electromagnetic flow probes. The influence of changes in venous return (VR) on the subsequent hemodynamic response to synchronous HFJV was analyzed using instantaneous VR curves (M. R. Pinsky, J. Appl. Physiol. 56:765-771, 1984). During hemorrhage the VR curve was shifted leftward with concomitant reductions in apneic SV (15.4 +/- 3.8 to 11.2 +/- 3.6 ml, mean +/- SD), (P less than 0.01) that were accentuated by HFJV (P less than 0.01), except when the phasic inspiratory increases in ITP during HFJV were timed to occur during late diastole (-4% apneic SV, NS). SV was greater with late diastolic pulses than with other timed synchronous ITP pulses during hypovolemia (P less than 0.01). During ganglionic blockade, arterial pressure decreased (139 +/- 14 to 76 +/- 18 Torr, P less than 0.001), but VR was preserved at control levels, and no significant cardiac cycle-specific HFJV effects occurred. We conclude that SV reductions associated with positive-pressure ventilation during acute hypovolemia are minimized by HFJV synchronized to late diastole but that this effect is preload dependent.     

Cardiac response to submaximal exercise in dogs susceptible to sudden cardiac death

The hemodynamic response to submaximal exercise was investigated in 38 mongrel dogs with healed anterior wall myocardial infarctions. The dogs were chronically instrumented to measure heart rate (HR), left ventricular pressure (LVP), LVP rate of change, and coronary blood flow. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise. Nineteen dogs had ventricular fibrillation (susceptible) while 19 animals did not (resistant) during this test. The cardiac response to submaximal exercise was markedly different between the two groups. The susceptible dogs exhibited a significantly higher HR and left ventricular end-diastolic pressure (LVEDP) but a significantly lower left ventricular systolic pressure (LVSP) in response to exercise than did the resistant animals. (For example, response to 6.4 kph at 8% grade; HR, susceptible 201.4 +/- 5.1 beats/min vs. resistant 176.2 +/- 5.6 beats/min; LVEDP, susceptible 19.4 +/- 1.1 mmHg vs. resistant 12.3 +/- 1.7 mmHg; LVSP, susceptible 136.9 +/- 7.9 mmHg vs. resistant 154.6 +/- 9.8 mmHg.) beta-Adrenergic receptor blockade with propranolol reduced the difference noted in the HR response but exacerbated the LVP differences (response to 6.4 kph at 8% grade; HR, susceptible 163.4 +/- 4.7 mmHg vs. resistant 150.3 +/- 6.4 mmHg; LVEDP susceptible 28.4 +/- 2.1 mmHg vs. resistant 19.6 +/- 3.0 mmHg; LVSP, susceptible 122.2 +/- 8.1 mmHg vs. resistant 142.8 +/- 10.7 mmHg). These data indicate that the animals particularly vulnerable to ventricular fibrillation also exhibit a greater degree of left ventricular dysfunction and an increased sympathetic efferent activity.     

Exercise training normalizes altered calcium-handling proteins during development of heart failure.

The cardiac sarcoplasmic reticulum calcium-ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX1), and ryanodine receptor (RyR2) are proteins involved in the regulation of myocyte calcium. We tested whether exercise training (ET) alters those proteins during development of chronic heart failure (CHF). Ten dogs were chronically instrumented to permit hemodynamic measurements. Five dogs underwent 4 wk of cardiac pacing (210 beats/min for 3 wk and 240 beats/min for the 4th wk), whereas five dogs underwent the same pacing regimen plus daily ET (5.1 +/- 0.3 km/h, 2 h/day). Paced animals developed CHF characterized by hemodynamic abnormalities and reduced ejection fraction. ET preserved resting hemodynamics and ejection fraction. Left ventricular samples were obtained from all dogs and another five normal dogs for mRNA (Northern analysis, band intensities normalized to glyceraldehyde-3-phosphate dehydrogenase) and protein level (Western analysis, band intensities normalized to tubulin) measurements. In failing hearts, SERCA2a was decreased by 33% (P < 0.05) and 65% (P < 0.05) in mRNA and protein level, respectively, compared with normal hearts; there was only an 8.6% reduction in mRNA and a 32% reduction in protein in exercised animals (P < 0.05 from CHF). mRNA expression of NCX1 increased by 44% in paced-only dogs compared with normal (P < 0.05) but only by 22% in trained dogs (P < 0.05 vs. CHF); protein level of NCX1 was elevated in paced-only dogs (71%, P < 0.05) but partially normalized by ET (33%, P < 0.05 from CHF). RyR2 was not altered in any of the dogs. In conclusion, long-term ET may ameliorate cardiac deterioration during development of CHF, in part via normalization of myocardial calcium-handling proteins.     

Vasopressin vs norepinephrine in endotoxic shock: systemic, renal, and splanchnic hemodynamic and oxygen transport effects.

The effects of intravenous norepinephrine (NE, group 1) and vasopressin (AVP, group 2) infusions on systemic, splanchnic, and renal circulations were studied in anesthetized dogs under basal conditions and during endotoxic shock. Under basal conditions, AVP infusion induced a 12 +/- 7% drop in left ventricular stroke work, a 45 +/- 5% fall in portal venous blood flow, and a 31 +/- 13% decrease in intestinal mucosal blood flow (P < 0.05). AVP also decreased splanchnic oxygen delivery (Do2) and increased splanchnic and renal oxygen extraction significantly during basal conditions. Except for more pronounced brady-cardia among animals in group 2, the systemic and splanchnic changes were comparable between study groups during endotoxic shock. AVP infusion restored renal blood flow and Do2 in endotoxic shock compared with animals resuscitated with NE, which had persistently low renal blood flow and Do2. Our data demonstrate that, in contrast to NE, administration of AVP effectively restores renal blood flow and Do2 with comparable systemic and splanchnic hemodynamic and metabolic effects in endotoxin-induced circulatory shock.     

Effects of crystalloid and colloid fluids on extravascular lung water in hypoproteinemic dogs

We compared the effect of crystalloid to colloid fluid infusion on extravascular lung water (EVLW) in hypoproteinemic dogs. Plasmapheresis was used to decrease plasma colloid osmotic pressure (COP) to less than 40% of its base-line level. Five animals were then infused with 0.9% sodium chloride (saline), five with 5% human serum albumin (albumin), and five with 6% hydroxyethyl starch (hetastarch) to increase the pulmonary arterial occlusive pressure by 10 Torr in comparison to the postplasmapheresis level for a 5-h study interval. On completion of the procedure, the lungs were harvested and EVLW measured by the blood-free gravimetric technique. Three to six times the volume of saline compared with albumin or hetastarch (P less than 0.001) was infused. In the saline animals, COP was decreased to 3.3 +/- 1.3 Torr, whereas COP was increased to 18.1 +/- 1.4 Torr in albumin animals (P less than 0.001) and 20.1 +/- 1.6 Torr in the hetastarch group (P less than 0.001). The saline-treated dogs developed gross signs of systemic edema. The EVLW was 8.1 +/- 0.9 ml/kg in saline animals compared with 5.3 +/- 2.1 ml/kg in the albumin (P less than 0.05) and 4.1 +/- 1.4 ml/kg in the hetastarch (P less than 0.01) groups. These data indicate that crystalloid fluid infusion during hypoproteinemia is associated with the development of both systemic and pulmonary edema.     

Radiofrequency electromagnetic fields have no effect on the in vivo proliferation of the 9L brain tumor

The intracranial 9L tumor model was used to determine if exposure to a radiofrequency (RF) electromagnetic field similar to those used in cellular telephone has any effects on the growth of a central nervous system tumor. Fischer 344 rats implanted with different numbers of 9L gliosarcoma cells were exposed to 835.62 MHz frequency-modulated continuous wave (FMCW) or 847.74 MHz code division multiple access (CDMA) RF field with nominal slot-average specific absorption rates in the brain of 0.75 +/- 0.25 W/kg. The animals were exposed to the RF field for 4 h a day, 5 days a week starting 4 weeks prior to and up to 150 days after the implantation of tumor cells. Among sham-exposed animals injected with 2 to 10 viable cells (group 1), the median survival was 70 days, with 27% of the animals surviving at 150 days. The median survival length and final survival fraction for animals injected with 11 to 36 viable cells (group 2) were 52 days and 14%, respectively, while the values for those injected with 37 to 100 cells (group 3) were 45 days and 0%. The animals exposed to CDMA or FMCW had similar survival parameters, and the statistical comparison of the survival curves for each of the groups 1, 2 and 3 showed no significant differences compared to sham-exposed controls.     

Bronchoalveolar eosinophilia in random-source versus purpose-bred dogs.

Eosinophils (EOS) have been implicated in changes in airway and vascular reactivity in a variety of disease states. Analysis of cells in bronchoalveolar lavage samples from chronic, heartworm-free random-source (RS) dogs indicated higher leukocyte counts with markedly higher percent and total numbers of EOS than were present in purpose-bred (PB) animals. Bronchoalveolar lavage fluid (BALF) obtained from RS dogs had a significantly elevated total nucleated cell count: 0.8 x 10(6) vs 0.4 x 10(6) for the PB dogs. RS dogs had 24% +/- 5% and PB dogs had 3% +/- 0.7% EOS. The RS animals with elevated EOS had similar percentages of neutrophils: 4% +/- 0.6% as the PB animals. Despite aggressive anthelminthic treatment, the abnormal BALF cellular profile of the RS animals persisted even though circulating levels of EOS in this group decreased. Analysis of BALF for thromboxane B2 (TxB2) and 6-keto-prostaglandin F1(1a) (6-keto-PGF1a) indicated that only the TxB2 levels were significantly different between groups. The RS BALF TxB2 levels were 73 +/- 14 pg/ml vs 23 +/- 3 pg/ml for the PB group (P < 0.05). Regression analysis of the relationship between increasing TxB2 levels and the absolute number of EOS per milliliter of BALF obtained from the RS dogs indicated a significant correlation (r = 0.83, P < 0.0001). No difference in plasma levels of these mediators was observed. Other physiologic parameters also differed between the two groups: the RS group had significantly increased heart rates and cardiac output under baseline conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitation of urinary 3-methylhistidine excretion in growing dogs as an index of in vivo skeletal muscle catabolism

Purpose: To quantitate urinary 3-methylhistidine (3-mh) excretion as an index of in vivo muscle catabolism in dogs fed diets containing either normal or high protein levels.Methods: Twelve male, 5-month-old Beagle dogs were housed individually in metabolism cages and fed a non-meat, purified diet. They were divided into two diet groups of six dogs each, receiving 22.6% (NP) or 41.1% (HP) DM crude protein, respectively. Three dogs from each group received an intravenous injection of 385 +/- 29 kBq [14C] 3-mh. HCl. Urine and feces were collected daily until radioactivity returned to background levels (17 days). Urinary 3-mh was measured using an amino acid analyzer and percentage of bound 3-mh was estimated via acid hydrolysis.Results: Results are reported as means +/- SEM. 3-mh recovery in urine and feces of dogs were 263 +/- 28 kBq and 50.7 +/- 2.2 kBq and 327 +/- 45 kBq and 25.9 +/- 25.9 kBq for the NP and HP groups, respectively. The total cumulative 3-mh recoveries for the NP and HP groups were 81.8% +/- 2.8 and 91.4% +/- 2.7, respectively. Bound 3-mh accounted for 2.1 to 4.8% of urinary 14C-3-mh.Conclusions: Growing Beagle dogs excrete a higher percentage of 3-mh in feces (13.5% vs. 6.7%) when consuming the NP versus the HP diet. It appears that some of the 14C was lost in CO(2) and/or re-circulated in the body, as reported for sheep and pigs. We conclude that urinary 3-mh does not appear to be a quantitative index of in vivo muscle catabolism in growing dogs.     

Distribution of extravascular lung water after acute smoke inhalation

Anesthetized dogs with thoracotomy were injected with Evans blue dye and were exposed acutely (5 min) to wood smoke inhalation. Thin slices from freeze-dried samples were photographed and assessed for periarterial and perivenous cuff area and for blue coloration with a score of 0 to 5. Bloodless extravascular lung water (EVLW) was also measured. The smoke-exposed animals were compared with controls and with animals exposed to alloxan or to high-pressure-induced pulmonary edema. EVLW at 2 h after smoke (6.46 +/- 0.80) was above control value (4.30 +/- 0.63) but not different from the alloxan (6.13 +/- 0.70) or high-pressure (6.88 +/- 1.30) groups. Despite the similarity in EVLW in the edematous lungs, there were marked differences in the intensity of blue color and size of cuffing around arteries and veins: the smoke, alloxan, and high-pressure groups had blue color scores of 1.0 +/- 0.1, 2.9 +/- 0.3, and 0.3 +/- 0.1, respectively. These scores indicated a large increase in microvascular permeability to proteins in the alloxan group, a moderate increase in the smoke group, and minimal change in the high-pressure group. The perivascular cuff area was largest in the alloxan group and moderate in the smoke and high-pressure groups. The cuff area was higher for arteries than for veins in all groups except the 0.5-h smoke group. We conclude that smoke inhalation causes a moderate increase in permeability and EVLW compared with alloxan. The extravascular lung water accumulates preferentially around the arteries, but the size of the perivascular cuff is not similar for all causes of pulmonary edema.     

Passive serum therapy with polyclonal antibodies against Mycobacterium tuberculosis protects against post-chemotherapy relapse of tuberculosis infection in SCID mice

We investigated the protective role of immune-sera against reactivation of Mycobacterium tuberculosis infection in SCID mice and found that passive immunization with sera obtained from mice treated with detoxified M. tuberculosis extracts (delivered in liposomes in a composition known as RUTI) exerted significant protection. Our SCID mouse model consisted of aerosol infection by M. tuberculosis, followed by 3 to 8weeks of chemotherapy with isoniazid+rifampicin (INH+RIF) (25 and 10mg/kg, respectively). After infection and antibiotic administration, two groups of mice were treated for up to 10weeks with intraperitoneal passive immunization using hyperimmune serum (HS) obtained from mice infected with M. tuberculosis, treated with chemotherapy (INH+RIF) for 8weeks and inoculated with RUTI (HS group) or with normal serum (CT group). Significant differences were found between HS and CT groups in the number of bacilli in the lungs (3.68+/-2.02 vs. 5.72+/-1.41log(10) c.f.u.), extent of pulmonary granulomatomous infiltration (10.33+/-0.67 vs. 31.2+/-1.77%), and percentage of animals without pulmonary abscesses (16.7% vs. 45.5%). These data strongly suggest a protective role of specific antibodies against lung dissemination of M. tuberculosis infection.     

An evaluation of ventilation in dystrophic Syrian hamsters

Ventilatory responses of 10 control and 10 dystrophic male hamsters to air, hypercapnia, and hypoxia were evaluated at four ages (40, 70, 100, and 140 days). Tidal volume (VT), frequency (f), minute ventilation (VE) as well as inspiratory and expiratory time of awake animals were measured with a plethysmograph. There was a small increase of VT in both groups with age. Although there was no change of f in the control group with age, there was a progressive decrease in f (means +/- SE: 92 +/- 8, 97 +/- 9, 74.5 +/- 10, and 68 +/- 8 breaths/min) in the dystrophic group. Consequently VE on air decreased in the dystrophic group. Both groups showed similar responses to hypoxia (13 and 10% O2) and hypercapnia (3, 5, and 8% CO2) at 40 days. By 70 days the hypercapnic, but not hypoxic, response of the dystrophic animals was significantly decreased compared with that of the control group (at 8% CO2, VE = 47.4 +/- 4.1 vs. 75.7 +/- 7.6 ml/min, P less than 0.01). At both 100 and 140 days the response of the dystrophic group to CO2 was flat; i.e., the slope VE vs. fractional concentration of inspired CO2 was close to zero, and the hypoxic responses were greatly diminished. Because hamsters increase VE in response to CO2 primarily by increasing VT, the data suggest that dystrophic hamsters are unable to increase VT at a very early age, presumably due to muscle weakness. The normal response of hamsters to hypoxia, which is primarily to increase f, appears to be maintained for a longer time.     

Role of tracheal and bronchial circulation in respiratory heat exchange

Due to their anatomic configuration, the vessels supplying the central airways may be ideally suited for regulation of respiratory heat loss. We have measured blood flow to the trachea, bronchi, and lung parenchyma in 10 anesthetized supine open-chest dogs. They were hyperventilated (frequency, 40; tidal volume 30-35 ml/kg) for 30 min or 1) warm humidified air, 2) cold (-20 degrees C dry air, and 3) warm humidified air. End-tidal CO2 was kept constant by adding CO2 to the inspired ventilator line. Five minutes before the end of each period of hyperventilation, measurements of vascular pressures (pulmonary arterial, left atrial, and systemic), cardiac output (CO), arterial blood gases, and inspired, expired, and tracheal gas temperatures were made. Then, using a modification of the reference flow technique, 113Sn-, 153Gd-, and 103Ru-labeled microspheres were injected into the left atrium to make separate measurements of airway blood flow at each intervention. After the last measurements had been made, the dogs were killed and the lungs, including the trachea, were excised. Blood flow to the trachea, bronchi, and lung parenchyma was calculated. Results showed that there was no change in parenchymal blood flow, but there was an increase in tracheal and bronchial blood flow in all dogs (P less than 0.01) from 4.48 +/- 0.69 ml/min (0.22 +/- 0.01% CO) during warm air hyperventilation to 7.06 +/- 0.97 ml/min (0.37 +/- 0.05% CO) during cold air hyperventilation.