James J. McGrath

Studies on the mechanism of carbon monoxide-induced vasodilation in the isolated perfused rat heart.

We investigated the effects of dissolved CO on isolated potassium-arrested (K+) perfused rat hearts. Hearts from male Sprague-Dawley rats were perfused via the aorta with oxygenated Krebs-Henseleit solution containing 20 mM K+. Coronary flow (Qt) averaged 48.8 +/- 1.6 (SE), 48.1 +/- 1.7, and 55.6 +/- 1.7 ml/min/g dry wt when the perfusate was equilibrated with 95% O2-5% CO2, 5% N2-90% O2-5% CO2, and 5% CO-90% O2-5% CO2, respectively. The change in Qt was statistically significant when CO was present in the perfusion medium, but was not significant when N2 was present. Furthermore, the effect was reversible because coronary flow returned to control levels when CO was removed. Myocardial oxygen consumption (MVO2) did not change significantly when hearts were perfused with either N2 or CO. The magnitude of CO-induced vasodilation was not affected significantly by the addition of either 5 microM propranolol, 2 microM phentolamine, 1 unit of adenosine deaminase, or 0.1 mM indomethacin to the perfusate. In addition, CO reversed the vasoconstrictive effects of the alpha-agonist methoxamine. These results indicate that CO exerts a vasodilatory effect on coronary vasculature that is not the result of decreased O2 content in the perfusate and is not mediated by adrenergic influences, adenosine, or prostaglandins.

Continually Measured Fungal Profiles in Sick Building Syndrome

Abstract. Buildings with indoor air quality (IAQ) complaints frequently have high airborne concentrations of Penicillium species, while buildings with few IAQ complaints have an indoor air (IDA) fungal ecology similar to outdoor air (ODA), where Cladosporium species is usually the dominant microorganism. These studies compared fungal air profiles, measured continually over 6 h in a documented sick building, in IDA in a room experiencing IAQ problems with fungal profiles measured concurrently in ODA. The dominant species collected at both sites were Penicillium species, Cladosporium species, and Alternaria species. In the IDA, Penicillium species were always the dominant organisms, ranging from 150 to 567 cfu/m3 (89.8–100% of the total fungi). In the ODA, Cladosporium species were dominant in four samples (40.0–70.6%), while Penicillium species were dominant (52.7–79.6%) in two. These data demonstrate that, even though ODA fungal profiles are changing continuously, IDA fungal profiles in “sick” buildings tend to remain unchanged.

Response of Rat Coronary Circulation to Carbon Monoxide and Nitrogen Hypoxia

Abstract The effects of nitrogen (N2) or carbon monoxide (CO) hypoxia on coronary flow were assessed in the isolated nonworking rat heart perfused via the aorta with oxygenated (95% O2–5% CO2) Krebs Henseleit solution. After 30 min, the hearts were challenged with solutions containing either CO (10% CO–85% O2–5% CO2) or N2 (10% N2–85% O2–5% CO2) for 2 min (Challenge I). After recovery in oxygenated solution, the hearts were challenged with the alternate test solution (Challenge II). There were no significant differences in heart rate or pulse pressure between the hearts challenged with CO or N2. Coronary flow was significantly higher in the hearts challenged with CO regardless of the challenge sequence. Coronary flows (ml·min-1·g dry wt) in the CO- and N2-treated hearts, respectively, were 61.5 ± 4.5 and 52.9 ± 1.3 after Challenge I, and 64.3 ± 2.6 and 56.4 ± 3.0 after Challenge II. Because PO2 and oxygen content were the same in both test solutions, the results suggest that CO has a direct effect on coronary artery vascular smooth muscle.

Carbon monoxide effects on calcium levels in vascular smooth muscle.

Previously we showed that carbon monoxide (CO) relaxes vascular smooth muscle in the working heart and thoracic aorta preparations perfused with hemoglobin-free, Krebs-Henseleit (KH) solution. The CO-induced relaxation was not caused by hypoxia, nor was it mediated by adrenergic influences, adenosine, or prostaglandins. In these studies the effect of CO on calcium (Ca++) concentrations in vascular smooth muscle was determined using 45Ca as a tracer. Isolated rat thoracic aorta segments were incubated with 45Ca and gassed with O2, N2, or CO for 60 min. Verapamil was used to verify the effectiveness of the test system. Ca++ concentrations were 488 +/- 35 and 515 +/- 26 mM/g tissue (X +/- SE) in aortic rings gassed with O2 and N2, respectively. CO reduced Ca++ concentrations significantly (P less than 0.01) by 29% to 369 +/- 18 mM/g tissue. Verapamil treatment reduced Ca++ concentrations by 40% to 314 +/- 23 mM/g tissue. These results suggest that CO relaxes vascular smooth muscle and dilates blood vessels by decreasing Ca++ concentrations in vascular smooth muscle.

Effects of altitude on endogenous carboxyhemoglobin levels.

The effects of carbon monoxide (CO) on blood carboxyhemoglobin (COHb) levels, though well studied at sea level, have not been investigated in populations at altitude. COHb levels were measured in laboratory rats following 6 wk exposure to either clean air or air containing 9 ppm CO at ambient altitude (3300 ft), 10,000 ft, or 15,000 ft simulated high altitude. In animals breathing clean air, COHb levels increased with increasing altitude from 0.68 +/- 0.09% at 3300 ft to 1.16 +/- 0.28% and 1.68 +/- 0.14%, respectively, at 10,000 and 15,000 ft. The relationship between COHb levels and increasing altitude is linear with a correlation coefficient of 0.90 (p less than .001). In animals breathing 9 ppm CO, COHb levels also increased with increasing altitude from 0.99 +/- 0.06% at 3300 ft to 1.77 +/- 0.17% and 2.10 +/- 0.08%, respectively, at 10,000 and 15,000 ft. The relationship between COHb levels and increasing altitude in animals breathing CO is also linear with a correlation coefficient of .92 (p less than .001). These data indicate that, compared with animals at sea level, animals at altitude have an increased body burden of COHb and will attain the COHb level associated with the National Ambient Air Quality Standard for CO more quickly when breathing CO.

Effects of NO2 on immune responses.

The effects of NO2 on immune responses of mice were investigated. Mice were exposed to various concentrations of NO2 in inhalation chambers. After exposure the following parameters were measured: phagocytosis of polystyrene beads by both peritoneal and alveolar macrophages, production of antibody-forming cells from mice immunized with sheep erythrocytes, lymphocyte blastogenesis of splenic cells, and susceptibility to influenza virus. The production of antibody-forming cells was reduced in mice that were exposed to 5 ppm NO2. The serum antibody titers, phagocytosis, and other immune parameters measured were not affected. Exposure to NO2 did not affect mortality to influenza virus. These data indicate that certain immune parameters were altered by exposure to NO2; however, NO2 does not appear to be a major immunosuppressive factor at the concentrations tested.

The effects of carbon monoxide on the heart: An in vitro study

Experiments were conducted to assess the effects of increasing concentrations of carbon monoxide (CO) on the isolated spontaneously beating rat heart. Hearts removed from male Sprague Dawley rats were perfused via the aorta with Krebs-Henseleit solution. Coronary flow was timed and collected in a calibrated vessel. Heart rate and pulse pressure were measured by a catheter inserted in the left ventricle and attached to a pressure transducer. After 30 min, the hearts were challenged for 10 min with perfusate containing increasing concentrations of CO and decreasing concentrations of 02. Coronary flow increased in response to CO concentrations below 50%. After 8 min, coronary flow increased by 40% in response to 10% CO challenge. Heart rate and pulse pressure were generally depressed by CO. Heart rate was depressed at the end of 8 min by 5, 10, 38, and 64%, respectively, by solutions equilibrated against 10, 25, 50, and 95% CO. Pulse pressure decreased with concentrations of 50% CO and above. These results indicate that coronary flow appears to be the most sensitive indicator of CO toxicity in the isolated heart.

Carboxyhemoglobin Levels in Humans: Effects of Altitude

AbstractThese studies were conducted to determine the effects of altitude on endogenous blood carboxyhemoglobin (COHb) concentrations and on COHb concentrations produced by breathing carbon monoxide (CO). COHb concentrations were determined at sea level (SL) and at altitude (HA) in human volunteers breathing ambient air (group I) or 9 ppm CO for 1 hr (group II). Breath CO measurements were also made in both groups. The first measurements were made at College Station, Texas (elevation 330 ft) and the second at Hoosier Pass, Colorado (elevation 11,540 ft) after 20 hr at altitude. Blood drawn from the finger was immediately frozen for COHb and hemoglobin analysis in Lubbock, Texas. Alveolar air samples, collected in aluminized Mylar bags, were analyzed for CO in Warren, Michigan. In group 1 subjects, COHb levels increased significantly (p <.05) from 0.790% and 0.795%, respectively, in males and females at SL to 0.947% and 0.945% at HA. The overall increase for both groups was approximately 20%. In group 2 su...

Effects of Nitrogen Dioxide on Resistance to Klebsiella pneumoniae in Mice

We studied the effects of nitrogen dioxide (NO2) exposure on host resistance in mice. Mice were exposed continuously in inhalation chambers to 0.5, 1.0, or 1.5 ppm NO2 for 3 months or to 5 ppm NO2 for 3 days. Chamber NO2 concentrations were monitored continuously by a Thermoelectron chemiluminescent analyzer verified by the Saltzman procedure in accordance with Federal Register procedures. After the NO2 exposure, the mice were placed in an infectivity chamber and exposed to aerosolized cultures of Klebsiella pneumoniae for 15 minutes. Chamber clouds contained 55.2 ± 9.3 organisms (1–3 μ in size) per liter of air. The animals were removed from the infectivity chamber and observed for 15 days, after which percent mortalities and relative mean survival times (RMST) were determined. Control mice and mice exposed to 0.5, 1.0, or 1.5 ppm NO2 for 3 months did not differ significantly in mortality or RMST. In mice exposed to 5 ppm NO2 for 3 days, percent mortality was significantly higher and RMST was significantly lower. Lung index (lung weight/body weight) and body weight did not differ significantly after exposure to 0.5, 1.0, and 1.5 ppm NO2 for 3 months or to 5 ppm NO2 for 3 days. These results indicate that inhalation of 5 ppm NO2 for 3 days depresses host resistance to K. pneumoniae, whereas inhalation of 1.5 ppm NO2 for up to 3 months does not.

Body and organ weights of rats exposed to carbon monoxide at high altitude

Although chronic exposure to carbon monoxide (CO) or high altitude produces pronounced cardiovascular changes in humans as well as animals, there is little information on the effects elicited by these stressors combined. Theoretical considerations, as well as data from acute studies, suggest that CO inhaled at high altitude may be more detrimental than CO inhaled at low altitude. The purpose of these studies was to construct a system in which CO and altitude could be controlled precisely, and to investigate the effects of continuous exposure to CO and high altitude on body weights and hematocrit ratios, as well as heart, spleen, adrenals, kidneys, and pituitary weights. Male, laboratory rats were exposed for 6 wk in steel barometric chambers to (1) 100 ppm CO, (2) 15,000 ft simulated high altitude (SHA), and (3) CO at SHA. Altitude was simulated by a system of gate valves and a vacuum pump, and measured by an altimeter. CO, from high-pressure cylinders, was introduced into the air supplying each chamber through a mass flow controller and measured by a nondispersive infrared (NDIR) analyzer. Although SHA had no affect on left ventricle plus septum (LV + S), adrenal, spleen, or kidney weights, SHA decreased body weights, and increased hematocrit ratios, as well as right ventricle (RV), total heart (HT), and pituitary weights. CO had no affect on body weights, RV, HT, adrenal, spleen, or kidney weights, but CO increased hematocrit ratios and LV + S weights. There was no significant interaction between SHA and CO on any parameter except kidney weight. These results indicate that, in general, the effects produced by 15,000 ft SHA are not intensified by exposure to 100 ppm CO.