Anthony J. DeLucia

Avoided Heat-Related Mortality through Climate Adaptation Strategies in Three US Cities

Heat-related mortality in US cities is expected to more than double by the mid-to-late 21st century. Rising heat exposure in cities is projected to result from: 1) climate forcings from changing global atmospheric composition; and 2) local land surface characteristics responsible for the urban heat island effect. The extent to which heat management strategies designed to lessen the urban heat island effect could offset future heat-related mortality remains unexplored in the literature. Using coupled global and regional climate models with a human health effects model, we estimate changes in the number of heat-related deaths in 2050 resulting from modifications to vegetative cover and surface albedo across three climatically and demographically diverse US metropolitan areas: Atlanta, Georgia, Philadelphia, Pennsylvania, and Phoenix, Arizona. Employing separate health impact functions for average warm season and heat wave conditions in 2050, we find combinations of vegetation and albedo enhancement to offset projected increases in heat-related mortality by 40 to 99% across the three metropolitan regions. These results demonstrate the potential for extensive land surface changes in cities to provide adaptive benefits to urban populations at risk for rising heat exposure with climate change.

Glutathione status of isolated rabbit lungs. Effects of nitrofurantoin and paraquat perfusion with normoxic and hyperoxic ventilation.

Thirty-minute perfusion of isolated rabbit lungs with a Krebs-Ringer bicarbonate buffer containing 420 microM paraquat (PQ) or nitrofurantoin (NF) resulted in increases in lung oxidized glutathione (GSSG) content of 589 and 2656%, respectively, over control levels. The degree of glutathione efflux was also increased with both agents, i.e. 77 and 238% above control leakage for PQ and NF respectively. The pulmonary toxicity of both compounds is known to be heightened by conditions of hyperoxia(O2). Ventilation of lungs with 95% O2-5% CO2 did not, in itself, significantly alter glutathione efflux, GSH or GSSG levels. However, ventilation with 95% O2-5% CO2 increased lung GSSG levels in PQ-perfused lungs 225% over PQ-air-perfused lungs, a combined effect not observed with NF-O2, wherein mean GSSG levels were only 72% of that observed with NF-air. Glutathione efflux in PQ-O2-treated lungs declined somewhat (20%) compared to that observed with PQ-air, but a significant increase in the amount of glutathione efflux was seen with NF-O2-treated lungs, i.e. 120 and 310%, respectively, over that attributable to NF or O2 alone. Although the biochemical mechanisms of toxicity of these compounds are thought to be very similar, the disparate degree of GSH oxidation observed with equimolar levels of PQ and NF may indicate differences in reactivity towards glutathione and other lung sulfhydryl pools. The stimulation of the oxidative effects of PQ and NF on lung GSH due to hyperoxic ventilation may be related to the reported O2 enhancement of their toxicity.

Immune responsiveness of monkeys exposed chronically to cigarette smoke.

Eleven adult male stumptailed monkeys (Macaca arctoides) were chronically exposed to either a low dose (human equivalent of 1 pack/day) or a high dose (human equivalent of 3 packs/day) of high-tar, high-nicotine University of Kentucky reference cigarette smoke for 4-8 years. Several parameters of their immunological response were compared to six nonsmoked control animals. The results from these experiments suggest that cigarette smoking does not significantly affect the response of spleen cells to the mitogens phytohemagglutinin or lipopolysaccharide. However, spleen cells from animals subjected to the heavy dose of cigarette smoke demonstrated a significant reduction in their natural killer cell-mediated lytic activity and a decreased response to concanavalin A. These results suggest that cigarette smoking may have a differential effect on lymphocyte subpopulations, and that the effects on the immune response are related to the dose of cigarette smoke.

Prolonged, intravenous paraquat infusion in the rat: I. Failure of coinfused putrescine to attenuate pulmonary paraquat uptake, paraquat-induced biochemical changes, or lung injury

Paraquat (PQ) was administered to rats for 7 days by iv infusion from osmotic minipump at dosage rates of 250 and 500 nmol PQ/hr. The efficacy of putrescine in attenuating pulmonary PQ accumulation in vivo and the resulting PQ-induced biochemical changes and lung injury were assessed in these animals by coinfusion of putrescine at rates of 2500 or 5000 nmol/hr. Dose-dependent, steady-state blood levels of both PQ and putrescine were achieved by 18 hr and maintained throughout the infusion period. Lung PQ content at 7 days was dose-dependent and up to 18-fold greater than corresponding blood levels. No evidence of toxicity was observed in low-dose PQ animals while weight loss and overt toxicity was observed in high-dose PQ rats between Days 4 and 5. Histopathological examination of high-dose PQ rat lungs revealed qualitative changes typical of PQ toxicity. Significant (p less than 0.05) increases in lung glutathione and activities of glucose-6-phosphate dehydrogenase and GSSG reductase resulted from both PQ doses, reflecting PQ-induced oxidant stress and increased demand on lung NADPH. A net decrease in lung NADPH (p less than 0.05) was directly measured in high-dose PQ rats and may have contributed to the PQ-induced lung injury. Although putrescine is an effective inhibitor of pulmonary PQ uptake in vitro, the blood putrescine levels achieved in this study did not appear to inhibit this process in vivo. This was evidenced by putrescines failure to decrease 7-day lung PQ content, PQ-induced biochemical changes, or lung injury.

Sensitivity of air pollution-induced premature mortality to precursor emissions under the influence of climate change.

The relative contributions of PM2.5 and ozone precursor emissions to air pollution-related premature mortality modulated by climate change are estimated for the U.S. using sensitivities of air pollutants to precursor emissions and health outcomes for 2001 and 2050. Result suggests that states with high emission rates and significant premature mortality increases induced by PM2.5 will substantially benefit in the future from SO2, anthropogenic NOX and NH3 emissions reductions while states with premature mortality increases induced by O3 will benefit mainly from anthropogenic NOX emissions reduction. Much of the increase in premature mortality expected from climate change-induced pollutant increases can be offset by targeting a specific precursor emission in most states based on the modeling approach followed here.

Failure of chronic cigarette smoke exposure to alter plasma lipoproteins of stumptailed macaques (Macaca arctoides)

Twenty-one 8-14 kg adult male stumptailed macaques, Macaca arctoides, were fed a standard laboratory diet and divided into 3 groups. The high-dose group and low-dose group were exposed to cigarette smoke at the human equivalent of 3 packs and 1 pack per day, respectively, 7 days per week, for 3-5 years. Eight animals served as cage an sham controls. Peak blood carboxyhemoglobin (COHb) levels measured immediately after smoking showed levels of 0.5+/- 0.1%, 3.6+/-1.0%, and 5.7+/-2.8% for sham controls, low, and high dose smokers, respectively. Hemoglobin and hematocrit values were 2-7% higher (N.S. to P less than 0.05) for smoking groups, presumably as a consequence of chronically elevated COHb levels. No significant differences were seen in total plasma cholesterol and lipoprotein cholesterol concentration measured at four intervals over period of one year. We conclude from these data that, while fed a low fat diet, chronic cigarette smoke inhalation fails to alter plasma lipoprotein levels in this animal model.

Prolonged, intravenous paraquat infusion in the rat: II. Paraquat-induced alterations in lung polyamine metabolism

The effects of paraquat (PQ) on lung putrescine, spermidine, and spermine levels, and ornithine decarboxylase (ODC) activity were assessed in rats after 7 days of iv infusion of the herbicide via osmotic minipump. Paraquat administration at a rate of 250 nmol/hr [673 +/- 40 nmol/kg/hr (n = 15)] had no effect on these parameters. In contrast, significant (p less than 0.05) elevations in lung putrescine (407% of control), spermidine (202% of control), and ODC activity (174% of control were measured in lungs of rats given 500 nmol PQ/hr [1.31 +/- 0.53 mumol/kg/hr (n = 14)]. Since evidence of lung damage was, likewise, observed only in the high-dose PQ rats, these changes in polyamine metabolism could have been a nonspecific response to PQ-induced lung injury rather than a direct biochemical effect of PQ. The results suggest that stimulation of polyamine biosynthesis may play an important role in PQ-induced lung injury. This role may involve regulation of repair mechanisms or, conversely, the polyamines may actually mediate PQ-induced fibrotic changes in the lung.

An inverse relationship between plasma carnitine and triglycerides in selected Macaca arctoides and Macaca nemistrina fed a low-fat chow diet

Plasma carnitine and triglycerides were measured in five male Macaca arctoides and one female Macaca nemistrina during the course of feeding a low-fat (5.2% w/w), high carbohydrate diet and a high-fat (15.9% w/w), low carbohydrate diet. For each individual monkey, an inverse relationship was observed between plasma carnitine and triglyceride levels when the low-fat diet was fed but not when the high-fat diet was fed. The mechanism of the different responses to diet was not investigated but may be related to the primary source of the plasma triglycerides (i.e. endogenous origin or exogenous origin) or to differing hormonal effects. A close coupling between carnitine and triglyceride metabolism may be part of a sensitive homeostatic control mechanism that responds to endogenously-synthesized triglyceride.