Photosynthetic phenological variation may promote coexistence among co-dominant tree species in a Madrean sky island mixed conifer forest.

Across much of western North America, forests are predicted to experience a transition from snow- to rain-dominated precipitation regimes due to anthropogenic climate warming. Madrean sky island mixed conifer forests receive a large portion of their precipitation from summertime convective storms and may serve as a lens into the future for snow-dominated forests after prolonged warming. To better understand the linkage between physiological traits, climate variation, and the structure and function of mixed conifer forests, we measured leaf photosynthetic (A) responses to controlled variation in internal CO2 concentration (Ci) to quantify interspecific phenological variation in A/Ci-derived ecophysiological traits among ponderosa pine (Pinus ponderosa Lawson and C. Lawson), southwestern white pine (Pinus strobiformis Engelm.) and Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco). Species had similar, positive responses in net photosynthesis under ambient conditions (Anet) to the onset of summertime monsoonal precipitation, but during the cooler portions of the year P. ponderosa was able to maintain greater Anet than P. menziesii and P. strobiformis. Moreover, P. ponderosa had greater Anet in response to ephemerally favorable springtime conditions than either P. menziesii or P. strobiformis. Monsoonal precipitation was associated with a sharp rise in the maximum rates of electron transport (Jmax) and carboxylation (VCmax) in P. menziesii in comparison with P. ponderosa and P. strobiformis. In contrast, species shared similar low values of Jmax and VCmax in response to cool winter temperatures. Patterns of relative stomatal limitation followed predictions based on species' elevational distributions, reinforcing the role of stomatal behavior in maintaining hydraulic conductivity and shaping bioclimatic limits. Phenological variation in ecophysiologial traits among co-occurring tree species in a Madrean mixed conifer forest may promote temporal resource partitioning and thereby contribute to species' coexistence. Moreover, these results provide a physiological basis for predicting the ecological implications of North American mixed conifer forests currently transitioning from snow- to rain-dominated precipitation regimes.

Effect of adenosine antagonism on metabolically mediated coronary vasodilation in humans.

OBJECTIVES: This study was performed to assess the importance of adenosine in mediating metabolic coronary vasodilation during atrial pacing stress in humans. BACKGROUND: Numerous animal studies have examined the role of adenosine in the regulation of coronary blood flow, with inconsistent results. METHODS: The effect of the adenosine antagonist aminophylline (6 mg/kg body weight intravenously) on coronary functional hyperemia during rapid atrial pacing was determined in 12 patients. The extent of inhibition of adenosine vasodilation was assessed using graded intracoronary adenosine infusions before and after aminophylline administration in seven patients. Coronary blood flow changes were measured with a 3F intracoronary Doppler catheter. RESULTS: After aminophylline administration, the increase in coronary flow velocity during adenosine infusions was reduced from 84 +/- 48% (mean +/- SD) to 21 +/- 31% above control values (p < 0.001) at 10 micrograms/min and from 130 +/- 39% to 59 +/- 51% above control values (p < 0.001) at 40 micrograms/min. During rapid atrial pacing under control conditions, coronary blood flow velocity increased by 26 +/- 16%. The flow increment during paced tachycardia after aminophylline (23 +/- 10%) was unchanged from the control value, despite substantial antagonism of adenosine coronary dilation by aminophylline. CONCLUSIONS: These data suggest that adenosine does not play an important role in the regulation of coronary blood flow in response to rapid atrial pacing in humans.

Acute effect of cigarette smoking on the coronary circulation: constriction of epicardial and resistance vessels.

OBJECTIVES: This study was performed to determine the acute effect of cigarette smoking on proximal and distal epicardial conduit and coronary resistance vessels. BACKGROUND: Cigarette smoking causes constriction of epicardial arteries and a decrease in coronary blood flow in patients with coronary artery disease, despite an increase in myocardial oxygen demand. The role of changes in resistance vessel tone in the acute coronary hemodynamic effect of smoking has not been examined. METHODS: Twenty-four long-term smokers were studied during cardiac catheterization after vasoactive medications had been discontinued. The effect of smoking one cigarette 10 to 15 mm long on proximal and distal conduit vessel segments was assessed before and immediately after smoking and at 5, 15 and 30 min after smoking (n = 8). To determine the effect of smoking on resistance vessels, coronary flow velocity was measured in a nonobstructed artery with a 3F intracoronary Doppler catheter before and for 5 min after smoking (n = 8). Eight patients were studied without smoking to control for spontaneous changes in conduit arterial diameter (n = 5) and resistance vessel tone (n = 3). RESULTS: The average diameter of proximal coronary artery segments decreased from 2.56 +/- 0.12 mm (mean +/- SEM) before smoking to 2.41 +/- 0.09 mm 5 min after smoking (-5 +/- 2%, p < 0.05). Distal coronary diameter decreased from 1.51 +/- 0.07 to 1.39 +/- 0.06 mm (-8 +/- 2%, p < 0.01). Marked focal vasoconstriction after smoking was observed in two patients. Coronary diameter returned to baseline by 30 min after smoking. There was no change in vessel diameter in control patients. Despite a significant increase in the heart rate-mean arterial pressure product, coronary flow velocity decreased by 7 +/- 4% (p < 0.05) and coronary vascular resistance increased by 21 +/- 4% (p < 0.01) 5 min after smoking. There was no change in these variables in the control subjects. CONCLUSIONS: Smoking causes immediate constriction of proximal and distal epicardial coronary arteries and an increase in coronary resistance vessel tone, despite an increase in myocardial oxygen demand. These acute coronary hemodynamic effects may contribute to the adverse cardiovascular consequences of cigarette smoking.

Cocaine-induced myocardial infarction in patients with normal coronary arteries.

OBJECTIVE: To review the reported cases of myocardial infarction temporally related to recreational and topical anesthetic use of cocaine, with special regard for underlying etiologic factors in patients subsequently found to have normal coronary arteries. DATA SOURCES: Personal records of three cases and a comprehensive literature review using MEDLINE and supplemented by Index Medicus and the bibliographies of case reports. DATA SYNTHESIS: A total of 114 cases of cocaine-induced myocardial infarction were identified. The coronary anatomy was defined by angiography or autopsy in 92 patients, 38% of whom had normal coronary arteries. In these 35 patients (average age, 32; range, 21 to 60 years), myocardial infarction typically involved the anterior left ventricular wall (77%). Moderate cigarette smoking with one or fewer associated coronary risk factors was prevalent (68%). Focal coronary vasospasm was shown convincingly in only two cases. Intracoronary thrombus was initially found on 9 of 11 angiograms (82%) done within 12 hours of the myocardial infarction. Experimental evidence suggests that cocaine has direct and indirect sympathomimetic effects on vascular smooth muscle, attenuates endothelium vasodilator capacity, exerts a potent depressant effect on cardiac myocytes, and promotes atherogenesis. CONCLUSIONS: Cocaine-induced myocardial infarction in patients with normal coronary arteries probably involves adrenergically mediated increases in myocardial oxygen consumption, vasoconstriction of large epicardial arteries or small coronary resistance vessels, and coronary thrombosis. Accelerated atherosclerosis and impairment of endothelium vasodilator function may occur after chronic cocaine use.

EDRF: nitrosylated compound or authentic nitric oxide.

Endothelium-derived factor (EDRF) from bovine aortic endothelial cells was compared to solutions of authentic nitric oxide (NO) and to solutions of the nitrosothiol S-nitroso-L-cysteine. EDRF was produced from endothelial cells by basal release or by stimulation with the calcium ionophore A23187. Biological activity was measured as relaxation of porcine coronary arteries preconstricted with prostaglandin F2 alpha, and chemical analysis was made of the nitrosyl content by measurement of NO released after chemical reduction with 1% sodium iodide in glacial acetic acid. EDRF, NO, and nitrosocysteine had identical half-lives, were all inactivated by hemoglobin and methylene blue, and were all augmented in their biological activity by superoxide dismutase. When solutions were analyzed for their biological activity as a function of the NO content (after NaI/acetic acid reduction), nitrosocysteine showed more vasodilation per amount of contained NO than did authentic NO. Solutions containing EDRF (basal release or by stimulation with A23187) subjected to the same analysis appeared similar to nitrosocysteine, and were distinct from solutions of NO. These experiments show that nitrosyl compounds other than NO can have properties very similar or identical to EDRF, and that in this system EDRF appears more similar to nitrosocysteine than to NO.

Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta.

We examined the hypothesis that impaired endothelium-dependent vasodilation in atherosclerosis is associated with decreased synthesis of nitrogen oxides by the vascular endothelium. The descending thoracic aortae of rabbits fed either normal diet, a high cholesterol diet for 2-5 wk (hypercholesterolemic, HC), or a high cholesterol diet for 6 mo (atherosclerotic, AS) were perfused in a bioassay organ chamber with physiologic buffer containing indomethacin. Despite a dramatic impairment in the vasodilator activity of endothelium-dependent relaxing factor (EDRF) released from both HC and AS aortae (assessed by bioassay), the release of nitrogen oxides (measured by chemiluminescence) from these vessels was not reduced, but markedly increased compared to NL. Thus, impaired endothelium-dependent relaxation in atherosclerosis is neither due to decreased activity of the enzyme responsible for the production of nitrogen oxides from arginine nor to arginine deficiency. Because the production of nitrogen oxides increased in response to acetylcholine in both hypercholesterolemic and atherosclerotic vessels, impairments in signal transduction are not responsible for abnormal endothelium-dependent relaxations. Impaired vasodilator activity of EDRF by cholesterol feeding may result from loss of incorporation of nitric oxide into a more potent parent compound, or accelerated degradation of EDRF.

Sarcoidosis and giant splenomegaly.

Splenomegaly is often a manifestation of sarcoidosis, but giant splenomegaly is rare. Only 25 cases of sarcoidosis presenting as massive splenomegaly have been reported. Splenectomy was performed before the diagnosis of sarcoidosis was made in more than half of these patients. Serious complications of giant splenomegaly including rupture, severe thrombocytopenia and hemolytic anemia were not consistently present preoperatively. A case of disseminated sarcoidosis presenting with giant splenomegaly and normal chest roentgenograms is described. Prednisone therapy improved the patient's pulmonary function testing while constitutional symptoms, splenomegaly and elevated angiotensin-converting enzyme levels completely resolved. Sarcoidosis should be considered in the differential diagnosis of massive splenomegaly. A trial of steroids is warranted as initial treatment, and in selected cases may prevent unnecessary splenectomy, thereby precluding a compromise in host defenses against encapsulated bacteria.

Evidence for an astrocyte-derived vasorelaxing factor with properties similar to nitric oxide.

To determine whether astrocytes release nonprostanoid vasodilators, cells on microcarrier beads were superfused with various agents in the presence of indomethacin, and the effluent was bioassayed and also analyzed for nitric oxide by a chemiluminescence technique. Bradykinin and A23187 induced release of a factor that relaxed arterial rings, an effect that was blocked by hemoglobin. The effluent contained either nitric oxide or a related compound that could be reduced to nitric oxide. Production of this factor was competitively inhibited by the arginine analogs NG-nitro-L-arginine and NG-methyl-L-arginine and could be restored with L-arginine. Quisqualate and norepinephrine were also effective in causing the release of nitric oxide from astroglial cells. Thus, astrocyte-derived relaxing factor has properties similar to those of an endothelium- and neuron-derived relaxing factor.

Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide.

Studies of cultured bovine aortic endothelial cells using quantitative chemiluminescence techniques have shown that the amount of nitric oxide released under basal conditions, or in response to either bradykinin or the calcium ionophore A23187 is insufficient to account for the vasorelaxant activities of the endothelium-derived relaxing factor (EDRF) derived from the same source. This observation contradicts previous suggestions that nitric oxide and EDRF are the same compound, but may be explained if EDRF is a compound that contains nitric oxide within its structure but is a much more potent vasodilator than nitric oxide. Such a molecule could be one of several nitrosothiols which may yield nitric oxide after a one-electron reduction. The present experiments were carried out to test the possibility that the biological activities of the endothelium-derived relaxing factor might more closely resemble those of one of these compounds, S-nitrosocysteine, than nitric oxide. Nitric oxide release from cultured bovine aortic endothelial cells was detected by chemiluminescence and bioassay experiments compared the vasodilator potencies of nitric oxide, S-nitrosocysteine, and EDRF. The results suggest that EDRF is much more likely to be a nitrosylated compound such as a nitrosothiol than authentic nitric oxide.

Rhabdomyolysis and myoglobinuric renal failure following cardioversion and CPR for acute MI.

A 50-year-old man suffered an MI with VFIB at work, and efforts at resuscitation were initiated immediately. Ninety minutes of CPR and 14 cardioversions were given by trained personnel before VFIB converted to sinus rhythm. Reversible myoglobinuric renal failure ensued, requiring two weeks of hemodialysis. Scanning with technetium-99m pyrophosphate revealed extensive muscle injury in the regions of cardioversion and a large anterolateral MI. Prolonged resuscitative efforts involving repeated cardioversion may predispose to myoglobinuric renal failure.

Disseminated Fusarium infections in patients following bone marrow transplantation.

Intensive immunosuppressive therapy and broad spectrum antibiotics predispose cancer patients to opportunistic fungal infections. Fusarium has rarely been reported as a pathogen in immunocompromised patients, but is almost uniformly fatal. Only six cases of disseminated Fusarium infection have been described in patients following bone marrow transplantation (BMT). We report here two additional cases. Fusarium infection initially presented with pyomyositis in one patient and with embolic skin lesions in another following T cell-depleted BMT. Both patients died with active Fusarium infection despite an extensive course of amphotericin B, rifampicin and granulocyte transfusions. From this experience and from a review of the literature, Fusarium infections appear to be increasing in prevalence as significant pathogens in immunocompromised hosts and are resistant to many conventional forms of therapy.

Pyomyositis in a patient with progressive systemic sclerosis. Case report and review of the literature.

Pyomyositis has become an increasingly recognized disease in temperate climates. A patient receiving chlorambucil for progressive systemic sclerosis, in whom streptococcal pyomyositis developed, is presented. Magnetic resonance imaging led to the early diagnosis. To our knowledge, this is the first case report of pyomyositis in a patient with scleroderma, and the first association with group G streptococcus infection in an adult. Connective tissue diseases and immunosuppression may emerge as risk factors for the development of this entity.

Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance.

Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from less than 10 min to 40 h, reduces immunogenicity, and decreases sensitivity to proteolysis. Because PEG has surface active properties and can induce cell fusion, we hypothesized that PEG conjugation could enhance cell binding and association of normally membrane-impermeable enzymes. Incubation of cultured porcine aortic endothelial cells with 125I-PEG-catalase or 125I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Endothelial cell cultures incubated with PEG-superoxide dismutase and PEG-catalase for 24 h and then extensively washed were protected from the damaging effects of reactive oxygen species derived from exogenous xanthine oxidase as judged by two criteria: decreased release of intracellular 51Cr-labeled proteins and free radical-induced changes in membrane fluidity, measured by electron paramagnetic resonance spectroscopy of endothelial membrane proteins covalently labeled with 4-maleimido-2,2,6,6-tetramethylpiperidinooxyl. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species.

Augmentation of antioxidant enzymes in vascular endothelium.

The endothelium is a key site of injury from reactive oxygen species that can potentially be protected by the antioxidant enzymes superoxide dismutase and catalase. Large proteins, such as superoxide dismutase and catalase, do not readily penetrate cell membranes, which limits their efficacy in protecting cells from cellular reactions involving both intracellularly and extracellularly generated reactive oxygen species. Two methods are described that promote enzyme delivery to cultured endothelial cells and confer increased resistance to oxidative stress. The first method is to entrap the antioxidant enzymes within liposomes, which then become incorporated by endothelial cells and can increase enzyme specific activities by as much as 44-fold within 2 h. The second method involves covalent conjugation of polyethylene glycol (PEG) to superoxide dismutase and catalase, a technique that increases circulatory half-life and reduces protein immunogenicity. Conjugation of PEG to superoxide dismutase and catalase increased cellular-specific activities of these enzymes in cultured endothelial cells (but at a slower rate than for liposome entrapped enzymes) and rendered these cells more resistant to oxidative stress. Both liposome-mediated delivery and PEG conjugation offer an additional benefit over native superoxide dismutase and catalase because they can increase cellular antioxidant activities in a manner that can provide protection from both intracellular and extracellular superoxide and hydrogen peroxide.