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An analysis of the economic impact of divorce settlements in the United States is presented using data for a white cohort taken from the National Longitudinal Study of the High School Class of 1972. "The effects of spouses' incomes on the divorce transfer are estimated and used to simulate the welfare effects of divorce on husbands, wives, and children under alternative assumptions about marriage contracts and the ability of a couple to continue coordinating resources in the aftermath of divorce. We find a positive (negative) relationship between divorce transfers and the growth of husband's (wife's) earnings during marriage. The estimated expenditure on children in the divorce state is only half the accustomed level during marriage.", (excerpt)

The marine natural product, halistanol trisulfate, has a relatively low critical micelle concentration of 0.001% m/v (14.5 microM) and strong hemolytic potency with an EC50 of 0.00046% m/v (6.67 microM). As expected of a detergent, it inhibits the growth of gram-positive but not gram-negative bacteria. The hemolytic activity of halistanol trisulfate and other detergents has been shown to correlate with critical micelle concentration. This correlation may have important implications in the mechanism of membranolytic bioactivity.

The aim of this study was to determine whether acute changes in [Mg2+]free occur during increased hydrolysis of cytosolic ATP, and whether these changes were of sufficient magnitude to be involved in the modulation of myocardial metabolism. 31P-NMR was used to estimate free cytosolic Mg2+ levels ([Mg2+]free) during hypoxia, isoproterenol stimulation, and graded low-flow ischemia in crystalloid perfused, isovolumic rat hearts. Cytosolic [Mg2+]free was calculated to be 0.73 +/- 0.12 mM in control hearts (100 mmHg hydrostatic pressure, 95% O2, n = 18). Cytosolic [Mg2+]free increased gradually during 10 min periods of hypoxia (65%, 50%, 35%, 5% O2), and 20 min infusions of isoproterenol (0.4, 3.0, 75 nM), to maximum values greater than 250% of control (P less than 0.05). During 8 min periods of graded low-flow ischemia (12.0, 7.2, 5.3, 3.4, and 1.6 ml/min/g), [Mg2+]free did not change significantly. [Mg2+]free displayed an inverse linear correlation with total cytosolic [ATP] during isoproterenol infusion (r = 0.87), and an exponential correlation during hypoxia (r = 0.82). The data indicate that acute changes in cytosolic [Mg2+]free can occur during conditions of net ATP hydrolysis although changes in ATP alone do not appear to be solely responsible for the changes in [Mg2+]free. Since the magnitude of the changes in [Mg2+]free are sufficient to alter equilibria of enzymes such as creatine kinase and myokinase, it is possible that these changes are involved in the acute modulation of myocardial metabolism.

Confronted with the Holocaust, I pose the question: How could the human beingas a mature person survive? Through examining the writings of one survivor, Elie Wiesel, we may discover how he pictures personal humanity conquering impersonal death. By placing his reflections in an analytical psychological structure, we may illustrate responses to threat, both healthy and unhealthy responses. At the same time, we may illumine the struggle to grapple humanly with an inhuman environment. Such a discussion may encourage reflection on our own daily dealings with stressful situations; it may also serve to guide the professional assisting in the human struggle with mortality.

The pathogenesis of post-ischaemic depression of contractility in myocardium was examined in isovolumic rat heart. 31P-NMR was used to monitor changes in ATP, creatine phosphate (CrP), inorganic phosphate (Pi), and [H+] during brief periods of ischaemia and reperfusion with and without allopurinol treatment. During 5, 10, or 15 min of total global ischaemia, the decline in function (rate-pressure product) correlated inversely with [Pi] (r = 0.92, P less than 0.01). Cardiac function exhibited a slow progressive recovery during 20 min of reperfusion, ultimately reaching only 85%, 78%, and 69% of its pre-ischaemic value following 5, 10, and 15 min of global ischaemia respectively. Following each ischaemic period [ATP], [CrP], [Pi], and [H+] all recovered to control levels within 5-10 min of initiating reperfusion. Allopurinol (2 mM) treatment of hearts made ischaemic for 15 min significantly improved contractile recovery to 89 +/- 7%. Allopurinol also exhibited significant anti-arrhythmic activity during the reperfusion period, decreasing the incidence of premature contractions and the duration of tachy-arrhythmias. Allopurinol had no effect on the final repletion of [ATP] and [CrP], or the recovery of [Pi] and [H+], although the rate of ATP repletion was elevated in the initial 5 min of reperfusion. These results show that neither depletion of the cytosolic high-energy phosphate pool, nor sustained elevations in [Pi] or [H+] are important in the production of post-ischaemic contractile impairment. The beneficial action of allopurinol suggests that xanthine oxidase derived oxygen free-radicals may be involved in the sustained contractile dysfunction following brief ischaemic episodes.

Mooted controllers of adenosine formation in heart are the oxygen supply:demand ratio, myocardial oxygen consumption (MVO2), the cytosolic phosphorylation potential (log[ATP]/[ADP][Pi]). The relationship between these parameters and purine release (adenosine + inosine) into the venous effluent was examined in isovolumic rat hearts perfused at 20 and 12 mL.min-1.g-1 with a glucose containing crystalloid buffer and stimulated with inotropic agents (isoproterenol, norepinephrine, 3-isobutyl-1-methylxanthine, and ouabain). The oxygen supply:demand ratio and MVO2 were continuously determined using an oxygen electrode to monitor oxygen supply and consumption. The phosphorylation potential was calculated from phosphorus metabolite levels determined by 31P-NMR spectroscopy and HPLC analysis. Left ventricular function was assessed as the rate-pressure product. All inotropic agents increased the rate-pressure product, with increases in function being greater in the hearts perfused at 20 mL.min-1.g-1. MVO2 was linearly related to the rate-pressure product at each flow rate; however, the hearts perfused at 20 mL.min-1.g-1 exhibited approximately twofold greater MVO2 values for similar rate-pressure product values. All inotropic agents increased adenosine release into the venous effluent. While there was a significant linear relation between adenosine formation and MVO2 in hearts perfused at both flow rates and stimulated with drugs, the relations differed with adenosine release being approximately fourfold greater in hearts perfused at 12 mL.min-1.g-1 under similar conditions of MVO2. Adenosine formation correlated exponentially with the ratio of oxygen supply:demand under all conditions (r = 0.97) and the relation did not differ significantly between hearts perfused at different rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Fifty percent of the ascorbic acid content of sliced rat lung was released from the tissue to the media within a few minutes by either washing or incubating the slices with Krebs-phosphate solution. Measurement of the lactate dehydrogenase and potassium content of the medium after incubating lung slices for 5 min showed that about 20% of the cells were damaged by slicing. Sephadex chromatography of tissue extracts prepared from washed lung slices showed that none of the ascorbic acid in these slices were bound to protein. Also, metabolic poisons were shown to deplete the ascorbic acid content of washed lung slices. Approx. 57% of the lung ascorbic acid of guinea pigs that had been supplemented with ascorbic acid and 78% of the lung ascorbic acid of ascorbic acid-deficient guinea pigs were found in the medium when lung slices from these animals were incubated with Krebs-phosphate solution. These results were taken to indicate the presence of an extracellular pool of ascorbic acid in lung which is maintained even during scurvy.

The role of adenosine as a mediator of the bradycardia associated with graded global ischaemia in rat heart was examined. Hearts were perfused at 37 degrees C in the isovolumic mode with Krebs-bicarbonate medium at 12.0 ml/min/g. After equilibration, the coronary flow was reduced to 0.5, 2.5, or 5.0 ml/min/g for 20 min. Effluent was collected and assayed for adenosine and inosine by HPLC. Heart rate was measured and bipolar electrograms were obtained in severely ischaemic hearts. Basal adenosine release was 124 +/- 15 pmol/min/g. Adenosine release increased by approximately 50% in hearts perfused at 5.0 ml/min/g. In hearts perfused at 2.5 and 0.5 ml/min/g, adenosine release increased by approximately 1300 and 2300% respectively. The pattern of adenosine release at 0.5 and 2.5 ml/min/g was phasic, with adenosine release rate increasing to a maximum after about 10 min then dropping to values slightly higher than initial values. Ischaemia produced significant bradycardia and first degree AV block. Adenosine antagonism with 5 micron 8-phenyltheophylline blocked up to 25% of this bradycardia and significantly reduced the conduction delay. Adenosine release rate correlated closely with that component of heart rate slowing which was inhibited by 8-phenyltheophylline. It is concluded that adenosine released during graded global ischaemia mediates up to a quarter of the associated bradycardia. The effect of adenosine is phasic. Adenosine acts primarily to depress the sinus pacemaker. First degree AV block also occurs. These effects were only apparent at coronary flow rates below 5.0 ml/min/g.

This study reports the results of a double-blind, parallel-group comparison of intravenous methadone with morphine for the control of postoperative pain. Twenty patients (ASA Status 1 or 2) undergoing a surgical procedure involving an upper abdominal incision were randomly allocated to the methadone (n = 10) or morphine (n = 10) treatment groups. The patients were administered a 20-mg intraoperative opioid dose and 5-mg intravenous increments of opioid from precoded syringes in response to pain in the recovery and surgical wards. There was no significant difference between the mean +/- SD amount of supplementary methadone (8 +/- 6.3 mg) and morphine (9 +/- 9 mg) required in the recovery ward to provide initial pain control. The time from initial pain control to the first supplementary dose in the surgical ward was significantly different (P less than 0.01) in the methadone group (20.7 +/- 20.2 h) when compared to the morphine group (6.2 +/- 3.0 h). Further, patients required significantly less (P less than 0.001) methadone (11.5 +/- 8.5 mg) than morphine (41 +/- 14.1 mg) in the surgical ward to provide adequate pain relief throughout the duration of the study (i.e., 60 h). There was a significant difference in visual analogue pain scores between the methoadone and morphine groups on postoperative days 1 and 2, suggesting the quality of pain relief was similar for both treatment groups. Blood opioid-concentration monitoring indicated that there was a relationship between blood opioid concentration and pain relief.(ABSTRACT TRUNCATED AT 250 WORDS)

Mice were exposed to concentrations of 20, 40 and 200 ppm ozone in air for 30 min. Ozone exposure decreased lung ascorbic acid levels and increased lung weight by up to 50% in a dose related manner. On incubation in Krebs-phosphate solution, lung slices from mice exposed to 200 ppm ozone released a smaller fraction of their content of ascorbic acid into the medium than did lung slices from control mice, suggesting that there was a preferential loss of extracellular ascorbic acid during oxone exposure. These results are consistent with the proposed function of ascorbic acid as an extracellular antioxidant in lungs.

Rat lungs were perfused by recycling Krebs-bicarbonate solution in an apparatus which allowed negative pressure ventilation of the lungs. After addition of either reduced or oxidized ascorbic acid to the perfusion fluid serial samples were taken over 60 min and assayed for ascorbic acid. At the end of perfusion, lungs were assayed for ascorbic acid. The results show that reduced ascorbic acid was taken up by the lung and concentrated in the tissue. No appreciable transport of oxidized ascorbic acid was measured.

The aim of the study was to establish whether there exists a relationship between blood methadone concentration and analgesic response and the intrasubject and intersubject variability in this relationship. Sixteen general surgical (upper abdominal) and orthopedic (spinal fusion) patients were administered methadone (20 mg, iv) as part of the general anesthetic and supplementary methadone doses (usually 5 mg, iv) in the recovery ward until postoperative pain was controlled effectively. The criteria established for the administration of supplementary methadone doses were the co-existence of 1) spontaneous reporting of significant pain by the patient; 2) an unstimulated respiratory rate of greater than 10 breaths/min, and 3) no significant depression of the level of consciousness. A median of two supplementary iv methadone doses (range 1-3) were administered to the patient by a titration method in the recovery ward to obtain effective pain control. This was achieved by a median dose of 10 mg (range 5-20 mg) in addition to the 20 mg intraoperative dose. Serial blood samples were collected for the estimation of blood methadone concentration following all doses. The methadone concentration in the blood sample collected immediately prior to a supplementary dose was termed the minimum effective concentration (MEC [methadone]). The mean (+/- SD) coefficient of variation in MEC (methadone) for the 16 patients was 21 +/- 10% (range: 7-38%), while the mean MEC for methadone was 57.9 +/- 15.2 ng/ml (range: 34.5-80.3 ng/ml) in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Why formulate a philosophy statement? How may this statement influence organizational life? Answers to these questions affirm the practical utility of a philosophy within a health care facility. In addressing the first question, consideration is given to the philosophical questions by whom, to whom, and for what purpose is the organization sent. Also considered are its purpose in relating to and mode of relating to its patients. The practical place of a philosophy is illustrated through the difference between for-profit and non-profit corporations. A close analysis of organizational structure, systems, and strategies details this difference.

Rat red blood cells will hemolyze if they are present in vitro in mixtures of rat liver microsomes in which lipid peroxidation has been initiated by NADPH. Recent work from this laboratory indicated that a toxic factor not having radical properties could be generated from the lipids of the peroxidizing microsomes. This toxic factor produced prelytic damage in rat red blood cells. In this communication we show that if Ca(++)-aggregated microsomes are first peroxidized and then sedimented by centrifugation, the resuspended peroxidized microsomes are capable of hemolyzing red cells in the absence of any further microsomal lipid peroxidation. This result shows conclusively that the microsomal lipid peroxidation step can be separated from the attack on red cells leading to frank hemolysis. Furthermore, lipids extracted from the peroxidized microsomes with chloroform-methanol account quantitatively for the degree of hemolysis produced. The active hemolytic material could not be detected in resuspended microsomal centrifugates obtained during the first 10 minutes of NADPH-stimulated microsomal lipid peroxidation. It appeared rapidly after 10 minutes. It was maximal at 20 minutes, and fell to a low level of activity by 60 minutes. Peak hemolytic activity correlated with peak generation of lipid soluble peroxides. High, but less than maximal levels of peroxides appearing at 10 minutes did not cause hemolysis, and high, but less than maximal levels remaining at 60 minutes were only weakly hemolytic. The extracted lipoidal material with hemolytic potency is more reactive than hydrogen peroxide in a peroxide assay.

Lipid peroxidation was induced in rat liver microsomes by the addition of NADPH. When mixed with red cells in the presence of EDTA, these peroxidized microsomes caused hemolysis. All of the hemolytic activity of peroxidized microsomes could be extracted with lipid solvents and recovered as an aqueous lipid emulsion.

Alterations in cytosolic metabolites and [Mg2+]i were monitored using 31P magnetic resonance spectroscopy during inotropic stimulation of isolated rat heart [10 nM isoproterenol, 0.6 microM isobutyl-1-methylxanthine (IBMX), 5 microM ouabain]. All drugs significantly elevated contractile function (rate-pressure product) and MVO2 by approximately 100-150% (P less than 0.001), decreased cytosolic [creatine phosphate] ([CrP]) and [ATP] (approximately 65 and 80% of control values, respectively) (P less than 0.001), increased [Pi] to more than 180% of pretreatment values, and decreased [H+] by less than 15% (P less than 0.05). A significant relative shift in the alpha-P and beta-P resonances of ATP (P less than 0.01) occurred with inotropic stimulation. [Mg2+]i calculated on the basis of these shifts was found to be 0.78 +/- 0.1 mM in control hearts, and increased to maxima of 1.9 +/- 0.2, 2.0 +/- 0.2, and 2.9 +/- 0.2 mM during infusion of isoproterenol, IBMX, and ouabain, respectively. Changes in [Mg2+]i correlate with cytosolic [ATP] + [CrP] in all hearts (r = 0.89, 0.91, and 0.88 in isoproterenol-, IBMX-, and ouabain-treated hearts, respectively). The significantly higher [Mg2+]i with ouabain infusion (P less than 0.01) at similar workloads and [ATP] + [CrP] supports the proposal that a ouabain-inhibited Mg2+ pump exists in the plasma membrane. The data support acute changes in [Mg2+]i during alterations in inotropic state that may be important in modulating metabolic and contractile function.

Adenosine may modulate blood flow and electrical activity in heart in response to changes in myocardial energy metabolism. In the present study, 31P NMR spectroscopy was used to examine the relation between cytosolic phosphate metabolite levels and release of adenosine into the venous effluent of isovolumic heart during graded low-flow ischaemia or metabolic stimulation with isoproterenol. When coronary flow rate was varied in steps between 1.6 and 12 ml/min/g, cytosolic ATP levels did not change significantly but the phosphorylation potential exhibited a linear correlation with flow rate below approximately 7 ml/min/g. Purine release (adenosine and inosine) correlated linearly with the cytosolic phosphorylation potential and free AMP concentration. Metabolic stimulation of hearts with isoproterenol (0.4, 3.0, and 60 nM), produced a significant fall in cytosolic ATP levels and decreased the cytosolic phosphorylation potential. Purine release in these hearts increased exponentially as the cytosolic phosphorylation potential dropped, and as cytosolic free AMP increased. These results support a link between the phosphorylation potential and the mechanism of adenosine production during ischaemia and metabolic stimulation. Presumably, this link is the activity of the enzyme 5'-nucleotidase, which is responsible for converting AMP to adenosine, together with the concentration of its substrate, AMP. In low-flow ischaemia, cytosolic AMP may control adenosine formation. With isoproterenol stimulation, a more complex relationship exists, indicating possible allosteric regulation of the enzyme(s) responsible for adenosine formation, in addition to changes in AMP concentration.

Isolated hearts repleted with calcium after a short period of perfusion with a calcium-free medium undergo the injury of the calcium paradox and release cellular protein. In the present experiments, 15 min perfusion with a calcium containing HEPES solution subsequent to 10 min calcium-free perfusion resulted in the loss of 42.7 +/- 3.9 mg of protein/g heart. If hearts were repleted with calcium for 30 s only, then returned to calcium-free perfusion, resultant protein loss was the same. When calcium repletion was further decreased to 20 s, 23.9 +/- 1.3 mg/g of protein was lost. This critical period coincided with the onset of contracture but was prior to major ion movements. It is concluded that the transition to irreversible injury occurs within 30 s of calcium repletion and that subsequent removal of extra-cellular calcium does not alter the course of events leading to cell death.

Clinical proton NMR imaging uses magnetic field strengths in the range 0.1 to 0.5 T. In addition to the large static magnetic field, patients are exposed to magnetic field gradients during imaging and under extreme conditions, such as power failure or quenching, the field may collapse precipitously. A potential source of hazard to patients under these conditions is the induction of thoracic currents which may trigger ventricular fibrillation. In the present experiments, a 0.16 T resistive magnet with a time constant of 60 ms, powered by a programmable power supply, was used to examine any possible effects of static and changing magnetic field on the ECG and arterial blood pressure of anesthetized rats and guinea pigs. Animals were exposed to the following field conditions: static fields of 0.16 T; sine, triangular, and square wave modulated fields from 0.1 to 2 Hz; rapid field switches in excess of 2.0 T/s for 25 ms timed to occur at different stages of the cardiac cycle, including the vulnerable period during ventricular repolarization; and AC fields of 50 Hz. No change was observed in the blood pressure, heart rate, or ECG under any of the field conditions examined.

Although the importance of proper management of acute epiglottitis has been well recognized, little attention has been paid to the vulnerable period of time before the patient reaches the hospital. The courses of 23 children with acute epiglottitis were reviewed to determine prehospitalization management and morbidity.

The relation between the PC/ATP ratio and left ventricular function was examined in the Langendorff-perfused guinea-pig heart over a range of perfusion flow rates. PC/ATP ratios were determined from the 31P-nuclear magnetic resonance spectra of hearts obtained at 80.98 MHz and ventricular function estimated by measuring pressure in the left ventricle. When flow rates were increased over the range 0.6 to 6.0 ml/min, the PC/ATP ratio increased from 0.64 +/- 0.05 at 0.6 ml/min to 1.82 +/- 0.12 at 3.8 ml/min with no further increase up to a flow rate of 6.0 ml/min. Developed pressure (DP) increased with the flow rate up to 6.0 ml/min but the end diastolic pressure (EDP) also increased. The DP/EDP ratio was found to correlate closely with the PC/ATP ratio over the range of flow rates examined. The PC/ATP ratio may be a practical index of myocardial function available to the clinician when the topical magnetic resonance technique is fully developed.

Work reviewed in this paper indicates the potential importance of endogenous toxigenic lipids in amplifying the pathological consequences of lipid peroxidation in CCl4 poisoning. Formation of trichloromethane free radicals and the mixed function oxidase locus in the smooth endoplasmic reticulum of the hepatocyte and subsequent initiation of lipid peroxidation at this site are the first of a complex series of events that lead to the expression of CCl4 toxicity. Since lipid peroxidation is highly focal, it has been proposed that toxic products of lipid peroxidation could be released from the endoplasmic reticulum and that such substances might be responsible for the proliferation of intracellular damage. At least two classes of toxigenic substances are generated by microsomes undergoing NADPH-dependent lipid peroxidation. One group is a mixture of phospholipids of about 750 daltons to which are attached peroxidized fatty acids. A second group is a collection of low-molecular-weight compounds, which are decomposition products of peroxidized fatty acids. Both groups may act as intracellular toxigenic agents. Furthermore, fatty acids cleaved from peroxidized membrane phospholipids possess pharmacological activity resembling the activity of prostaglandins and these compounds also may contribute to cellular injury.

The isolated, perfused heart is known to exhibit a linear relation between aortic pressure, coronary flow rate, oxygen consumption and contractile function (rate-pressure product) over a wide range of aortic pressures. Our study sought to determine whether the cytosolic phosphorylation potential [( ATP]/[ADP][Pi]) is the link between mitochondrial respiration and contractile function in this preparation. 31P NMR spectroscopy was used to measure phosphate metabolite levels in isovolumic rat hearts during graded perfusion from 1.6 to 12.8 ml/min/g. It was found that an increase in contractile function paralleled the increase in flow rate, but that marked changes in creatine phosphate, inorganic phosphate and hydrogen ion concentration occurred only at lower flow rates. The cytosolic phosphorylation potential showed a high, positive correlation with contractile function at flow rates below 7.2 ml/min/g, which suggested that mitochondrial respiration was oxygen-limited and that the heart was ischemic. Thus, when oxygen limits myocardial oxidative phosphorylation, cytosolic energy metabolite levels may limit contractile function. At the higher flow rates studied, other metabolic controls may operate to link mitochondrial respiration and workload.

This study was part of an extensive survey of drug use patterns at a small private college in suburban New Jersey during the fall, 1975. Selected items from a questionnaire developed by the Inter-University Drug Survey Council of Metropolitan New York were cross-tabulated in order to examine the relationship between 379 college students' use of marijuana and their parents' attitudes and behavior relative to drug use. Significant results at the 0.01 level were found between (1) time of first marijuana use and parental attitudes toward alcohol and marijuana; (2) time of first marijuana use and parental use of barbiturates, marijuana, and pain-killers; (3) current frequency of marijuana use and parental attitudes toward alcohol and marijuana; and (4) current frequency of marijuana use and parental use of pain-killers.

Double-resonance laser emission at 283.3 and 600.2 nm was used to excite gas-phase atomic lead present in an electrothermal atomizer. Buffer-gas-induced collisional energy transfer occurs to states as much as 6000 cm(-1) below the highest optically pumped level. Single photons emitted from these states, whose wavelengths are as short as 202.2 nm, were detected. This study illustrates the utility and versatility of the saturated double-resonance technique for ultrasensitive and specific atomic detection (detection limits in the 10(-15)-g range) as well as its potential in atomic-spectroscopy and excited-state-dynamics studies.

Injury is sustained by isolated hearts on repletion with calcium after a short period of perfusion with calcium-free medium at 37 degrees. A possible mechanism for the 'calcium paradox' is that exposure to a calcium-fre medium removes extracellular calcium rendering the sarcolemma more permeable to calcium. On calcium repletion, cell injury is triggered by calcium influx. Since lanthanum is known to displace calcium from extracellular pools in heart, it was used in an attempt to modulate the injury of the calcium paradox. The presence of 10 microM lanthanum in the calcium-free perfusion fluid was found to inhibit totally protein release normally produced by subsequent calcium exposure. When lanthanum was added after the calcium-free period and before calcium repletion, protein release was only partly prevented. This shows that a change in membrane properties occurred during the calcium-free perfusion period which could be prevented, but not reversed, by the addition of lanthanum.

Significant progress in two areas will be required before the application of magnetic resonance spectroscopy in clinical cardiology is realized. On the technical side, methods must be developed to allow NMR spectra to be obtained non-invasively from the heart uncontaminated by surrounding tissue and with sufficient spatial resolution and signal to noise to be of practical use. On the application side, the potential value of the information derived from the NMR spectrum to diagnosis must be demonstrated. This review addresses the latter problem by evaluating the information content of the 31P-spectrum of heart within the framework of the practical constraints imposed by its possible clinical application as opposed to its acknowledged research application.

The 31P NMR spectrum of freshly prepared guinea-pig heart perfused in the Langendorff mode at 37 degrees C with medium containing either glucose or pyruvate as an energy source exhibited no inorganic phosphate peak making the determination of intracellular pH from the chemical shift of this peak impossible. By incorporating 2-deoxyglucose-6-phosphate into the heart to act as an alternative pH indicator, intracellular pH was determined to be 6.98 +/- 0.02 (mean +/- S.E.M. for eight animals). 2-Deoxyglucose was not taken up and phosphorylated by guinea-pig heart in the presence of glucose. Uptake and phosphorylation did proceed if glucose was omitted from the perfusion medium, but a large inorganic phosphate peak was present in the initial spectrum prior to 2-deoxyglucose addition. With pyruvate as sole energy source, an inorganic phosphate peak was absent initially and 2-deoxyglucose was taken up and phosphorylated. During a 12 min period of global ischaemia at 20 degrees C, when inorganic phosphate was visible together with 2-deoxyglucose-6-phosphate, a close correlation was found between the pH estimated from the chemical shift of inorganic phosphate and 2-deoxyglucose-6-phosphate over the pH range 6.3 to 6.9.

The extent to which endogenous, extracellular adenosine mediates increased coronary flow in crystalloid-perfused, isovolumic rat hearts stimulated with either norepinephrine or isoproterenol was examined. When infused into the coronary circulation, norepinephrine (1 x 10(-7) M) rapidly increased left ventricular developed pressure (LVDP) from 81 +/- 6 to 235 +/- 13 mmHg (1 mmHg = 133.3 Pa) and coronary flow from 12.7 +/- 0.8 to 18.4 +/- 0.7 mL.min-1.g-1. The presence of either adenosine deaminase (2 U.mL-1) or the adenosine receptor antagonist, 8-phenyltheophylline (5 x 10(-6) M) in the perfusate of norepinephrine-stimulated hearts augmented the increase in LVDP and +/- dP/dtmax by 10-20% but reduced the increase in coronary flow by 34%. Doubling the rate of adenosine deaminase infusion, or infusing the enzyme and 8-phenyltheophylline together did not alter their inhibitory effectiveness. Similar results were observed with hearts stimulated with isoproterenol (5 x 10(-8) M). These data show that about a third of the vasodilation that results from the metabolic stimulation of rat heart by catecholamines is due to the receptor-mediated action of extracellular adenosine.

Haemolytic substances are generated by rat liver microsomes undergoing NADPH-dependent lipid peroxidation. In the present experiments, vitamin E-deficient red cells were found to be haemolysed in an NADPH-dependent process by rat liver microsomes in the presence of EDTA, an inhibitor of microsomal lipid peroxidation. This is in contrast to the behaviour of normal, vitamin E-adequate red cells which are resistant to lysis under similar conditions. Aminopyrine (AP), a substrate for the microsomal mixed function oxidase system, was found to prevent lysis of vitamin E-deficient red cells in NADPH-microsome-EDTA mixtures. Experiments designed to detect only the more stable haemolysins formed in such mixtures involved sampling and assaying for haemolytic activity in the presence of AP. The result support the conclusion that haemolysis was due to a short-lived species. If EDTA is omitted from the NADPH-microsome mixture other more stable haemolysins are produced.

The optical performance of a cw PIE CO(2) laser has been substantially improved through the adoption of a burst-mode gain switching technique. The approach has provided a doubling of the average beam power extractable from the device. With appropriate optimization, the process could possibly permit the attainment of pulsed energy extraction in the kilohertz range, and with average optical powers within the several tens of kilowatt category.

Only lately having recovered their bodies and feelings, Western devotees of various meditative practices are in increasing numbers striving to transcend both. Is such a turning inward healthy for individuals and our society? A full response requires both a clarifying discussion of exactly what meditation is and a review of its effects. Meditation, essentially a way of life, is marked by four stages: preparation, attention, active reception, and higher consciousness. Even though the Western traditions aim finally at union with the Infinite and Eastern traditions seek primarily an internal unity through the negation of consciousness, both describe essentially the same four stages, reached through the meditative pathways of the intellect, emotions, body, and action. Present scientific research is only beginning to provide data on the effects of meditation upon the person. To date, most research findings point out psychophysiological changes during meditation, indicating a low-stress state. Meditative experience lends support to the conclusion that successful meditation also positively affects growth by touching man's inner life source, expanding his consciousness, and revealing personal life directions.

The recovery of high energy phosphate compounds in perfused guinea-pig heart at 20 degrees C after a 12 min period of global ischaemia was examined using 31P-NMR with a time resolution of 12 s. This time resolution was achieved by overlaying the data acquired from five successive ischaemic periods by arresting and restoring the flow of perfusion fluid to the heart in synchrony with the data acquisition sequence. The rate of creatine phosphate resynthesis after the ischaemic period proceeded 14 times faster than its rate of loss during the ischaemic period. ATP levels did not decrease during ischaemia and ADP was undetectable at any time. Estimates of intracellular pH from the chemical shift of the inorganic phosphate peak were impossible in normal guinea-pigs since the inorganic phosphate peak was not clearly defined. During the ischaemic period the inorganic phosphate peak increased in size and shifted upfield. On restoration of flow, the inorganic phosphate peak collapsed in a complex way following a different path to its formation during ischaemia.

To investigate the cause for the greater susceptibility of hypertrophied hearts to ischemic injury, we determined the interrelations of total work output, contractile function and energy metabolism in isolated, perfused normal and hypertrophied rat hearts subjected to graded global ischemia. Cardiac hypertrophy was induced by giving rats seven daily injections of either triiodothyronine (0.2 mg/kg) or isoproterenol (5 mg/kg). All hearts were perfused at an aortic pressure of 100 mmHg in the isovolumic mode in an NMR spectrometer (7.05 Tesla). Heart rate, developed pressure, and coronary flow were monitored simultaneously with changes in pH, creatine phosphate, ATP and inorganic phosphate. During pre-ischemic perfusion, the total work output (rate-pressure product) of hyperthyroid hearts was 28% higher than that of control hearts, whereas hearts from isoproterenol-treated animals showed no difference. However, when related to unit muscle mass, work was normal in hyperthyroid hearts and 26% lower after isoproterenol. Contractile function per unit myocardium (developed pressure/g wet weight) was lower in the hypertrophied hearts. ATP content was the same in all groups. Creatine phosphate decreased 41% after triiodothyronine and 25% after isoproterenol. Inorganic phosphate levels and intracellular pH were similar in control and isoproterenol-treated rat hearts, but were higher in the hyperthyroid rat hearts. The phosphorylation potential and the free energy change of ATP hydrolysis were lowered by hypertrophy, the levels correlating with the depressed contractile function. At each ischemic flow rate, both work and contractile function per unit myocardium were the same for all hearts, but the relations between flow and phosphorylation potential were different for each type of heart. Thus, at low flow rates, hypertrophied hearts perform the same amount of work and have the same contractile function as control hearts, but with abnormal changes in energy metabolism, indicating that the relations of energy status to coronary flow, total work output and contractile function are altered during the process of hypertrophy.

Toxic substances are generated by microsomes undergoing NADPH-dependent lipid peroxidation. In the present experiments the nature of the haemolytic material extracted from peroxidized microsomes is further examined. Suspensions of peroxidized rat liver microsomes were extracted with lipid solvents and the haemolytic material obtained subjected to gel exclusion chromatography. The haemolytic activity eluted as a single broad peak with an average size of 720 daltons. There was no evidence of haemolytic compounds less than 500 daltons. On a silicic acid column the activity eluted with the phospholipid. In both separations the presence of haemolytic activity correlated well with the peroxide content.

This study examines the possibility that endogenous adenosine modulates efficiency in isovolumic perfused rat hearts stimulated with isoproterenol or norepinephrine. Efficiency in these hearts is calculated as the rate of pressure work divided by the myocardial oxygen consumption. Within 2 min of infusion of isoproterenol (50 nM), heart rate increased by 35%, the rate pressure product by 290%, oxygen consumption by 142%, and efficiency by 67%. Infusion of adenosine deaminase (2-4 IU/ml), or 8-phenyltheophylline (5 microM), into stimulated hearts augmented the increase in heart rate by 40-45%, rate-pressure product by 18-20%, and oxygen consumption by 50-55%. Efficiency was reduced by 30-35%. Adenosine release into the coronary venous effluent increased from 195 +/- 20 pmol/min/g to 2400 +/- 180 pmol/min/g after 5 min. A similar pattern of results was observed when norepinephrine (0.1 mM) was used. The results indicate that extracellular adenosine, released by catecholamine treatment, inhibits the effects of the catecholamines on rate and contractility. Consequently, adenosine reduces cardiac work (rate-pressure product), but in so doing, improves efficiency.

1. The effects of adenosine antagonism (8-phenyltheophylline) and beta-blockade (1-propranolol) were examined during low-flow ischaemia (0.5 mL/min per g for 20 min) in rat heart. 2. Myocardial adenosine release, heart rate, and left ventricular developed pressure were monitored to determine whether endogenous adenosine affected ischaemic function directly, and/or via interaction with endogenous catecholamines. 3. Adenosine release increased more than 10-fold during low-flow ischaemia. Release displayed a phasic pattern, with maximal release occurring at 10 min. Ischaemia produced bradycardia (-180 beats/min) which was reduced by 8-phenyltheophylline infusion (P less than 0.001, n = 10). Adenosine antagonism also significantly increased left ventricular developed pressure in the initial 5 min of ischaemia (P less than 0.001, n = 10). 4. beta-blockade alone was without effect in ischaemic hearts, however, beta-blockade significantly reduced the initial increases in heart rate and developed pressure observed during infusion of 8-phenyltheophylline (P less than 0.001, n = 10). The effect of beta-blockade was transient, occurring in the initial 5-6 min of ischaemia. 5. The data indicate that endogenous adenosine directly mediates greater than 30% of the bradycardia associated with low-flow ischaemia, and that endogenous adenosine inhibits the release and/or the effects of endogenous catecholamines produced during the initial 5-6 min of ischaemia.