A B S T R A C T Arterio-venous differences across forearm muscle in man in both prolonged starvation and in the postabsorptive state, show an uptake of glutamate and a relatively greater production of glutamine. Splanchnic arteriovenous differences in the postabsorptive state show a net uptake of glutamine and lesser rate of glutamate production. These data suggest that muscle is a major site of glutamine synthesis in man, and that the splanchnic bed is a site of its removal. The relative roles of liver and other tissues in the splanchnic circuit were not directly assessed, only the net balance. These data in man are in conflict with most previous studies in other species attributing the major proportion of glutamine production to the liver and, pari passu, to the splanchnic bed. INTRODUCTIONDuring starvation, muscle protein catabolism provides amino acid substrate for both hepatic and renal gluconeogenesis. Recent studies have emphasized the central role of alanine in hepatic amino acid extraction (1) and amino acid release from muscle (2). This report includes data on peripheral and splanchnic metabolism of glutamate and glutamine in man, and, in contrast to current opinion as reviewed by Lotspeich (3), suggests that under physiologic circumstances, muscle in man is an important site of glutamine production, and the splanchnic bed is a site of its removal. Hence glutamine in man appears to be as prominent a vehicle as alanine for both glucogenic precursor and nitrogen fluxes from muscle to the splanchnic bed and to the kidney.

In general, continued resuscitation efforts in the emergency department for victims of cardiopulmonary arrest in whom prehospital resuscitation has failed are not worthwhile, and they consume precious institutional and economic resources without gain.

This study tested the hypothesis that a reduction in blood viscosity by means of isovolumetric hemodilution will permit an increase in maximal oxygen delivery to myocardium distal to a moderate coronary arterial stenosis. It is known that blood viscosity is a determinent of resistance to blood flow at both the stenotic and the arteriolar levels. Accordingly, a reduction in blood viscosity could exert a favorable influence on maximal myocardial oxygen delivery in the setting of stenosis, provided that the oxygen-carrying capacity of the blood is not compromised excessively. Closed-chest, sedated domestic swine (n = 8) were instrumented with an artificial coronary arterial stenosis that reduced vessel diameter by 64%. Measurements of hemodynamics, regional myocardial blood flow (microspheres), lactate and oxygen metabolism, and whole blood viscosity were made at control and after two successive 10 min intracoronary infusions of adenosine (400 and 800 ,ug/min) distal to the stenosis. Next, albumin/saline solution was given intravenously to reduce the animal's hematocrit by approximately 50%. Repeat measurements of all experimental variables were then made at a second control and again after two successive 10 min intracoronary infusions of adenosine (400 and 800 gg/min) distal to the stenosis. Myocardial blood flow (ml/min/g) distal to the stenosis increased from 1.52 + 0.21 (mean 1 SD) to 4.10 0.86 in response to adenosine (peak dose) before hemodilution (p < .01) and from 2.07 + 0.59 to 4.08 + 0.93 (p < .01) after hemodilution. Minimum resistance (mm Hg/ml/min/g) distal to the stenosis, however, was approximately 33% lower (p < .05) during infusion of adenosine after hemodilution than it was before hemodilution (endocardium 15.8 6.3 vs 24.5 14.1 and epicardium 9.0 ± 2.3 vs 14.0 ± 8.0). Maximal oxygen delivery (ml/min/lOOg) to myocardium distal to the stenosis failed to improve and in fact was reduced (p < .01 vs before hemodilution) after hemodilution (34.6 ± 9.5 vs 19.9 ± 6.8 to endocardium and 65.5 ± 16.4 vs 38.0 + 10.5 to epicardium). Regional myocardial lactate metabolism, however, did not change vs initial control during the study. Finally, hematocrit was reduced from 32 3% to 17 + 3% (p < .01) and blood viscosity was reduced from 3.4 ± 0.2 to 2.4 ± 0.3 centipoise (p < .01) by hemodilution. The results of the study indicate that reducing blood viscosity by isovolumetric hemodilution may not enhance maximal myocardial oxygen delivery in the setting of a moderate coronary arterial stenosis. However, because minimal endocardial resistance is lowered by a reduction in blood viscosity, it is likely that maximal oxygen delivery could be improved by this intervention if hemodilution were accomplished with a fluid capable of transporting oxygen (e.g., perfluorocarbon emulsion). Circulation 74, No. 5, 1085No. 5, -1092No. 5, , 1986 DELIVERY OF OXYGENATED blood to the myocardium in the setting of a coronary arterial stenosis is influenced by a number of factors. Many of these (e.g., stenosis dimensions, heart...

SUMMARY To determine whether a reduction in myocardial oxygen demand or an increase in coronary blood flow or both are responsible for the salutory effect of intraaortic balloon counterpulsation (IABP) in relieving medically refractory angina, we assessed these variables in six patients in whom IABP was required for relief of myocardial ischemia. IABP decreased the rate7pressure product and aortic enddiastoliczpressure, and the peak systolic aortic pressure and regional myocardial oxygen consumption declined in-all but one patient. Peak and mean aortic diastolic pressures increased. Changes in regional coronary blood flow paralleled changes in peak systolic aortic pressure (r = 0.92, p < 0.007). Thus, relief of angina during IABP could not be ascribed to an increase in regional coronary blood flow. Reduction of myocardial oxygen consumption is the most likely mechanism by which IABP relieves myocardial ischemia in patients with unstable angina pectoris. The mechanism-by which IABP relieves myocardial ischemia is unclear. Possible explanations include enhancementof coronary blood flow through obstructed or collateral coronary vessels,3-22reduction in myocardial oxygen demand,23-28 or both. An increase in coronary blood flow during IABP might be anticipated because marked augmentation of diastolic blood pressure is a fundam'ental and consistent effect of this intervention. Nevertheless, data reported regarding the coronary blood flow response are inconsistent. An important limiting factor in assessing the coronary hemodynamic effect of IABP in patients with coronary artery disease -has been the difficulty in measuring regional-rather than global left ventricular myocardial blood flow.An investigation from our laboratory using a fixed, high-grade coronary stenosis in the awake pig indicates that coronary-blood flow to ischemic myocardium does not consistently increase with IABP.29 Rather, regional blood flow distal to the stenosis tends to decrease in association with the observed reduction in myocardial oxygen demand that results from IABP. Accordingly, the results of our animal study suggest the hypothesis that IABP lessens myocardial ischemia primarily by reducing myocardial oxygen demand rather than by increasing oxygen supply. The objective of the present investigation was to test this hypothesis in patients with medically refractory unstable angina pectoris.Methods The patients were carefully selected to include only those with high-grade left anterior descending stenosis and objective evidence of anterior wall ischemia to permit regional assessment of coronary blo'od flow and myocardial metabolism in the area of myocardium responsible for the clinical syndrome. Nine patients were identified as being suitable candidates for investigation. The thermodilution catheter could not be properly positioned in two patients and satisfactory. diastolic augmentation was not achieved in one patient. The remaining six patients constitute the study group. There were four males and two females, ages 48-71 years (mean 62 year...

Rat papillary muscles were used to study the influence of glucose (5 HIM), linoleate (1 to 1.75 mMJ, octanoate (0.5 to 1.75 HIM) and pent-4-enoic acid (1 to 5 DIM) on mechanical performance under oxygenated, hypoxic and anoxic conditions. The buffer solution contained 0.3 DIM albumin. Free fatty acids (FFA) (1.0 to 1.75 DIM) did not alter mechanical performance under oxygenated conditions. During hypoxia or anoxia, FFA (0.5 to 1.75 HIM) depressed contractility and increased resting force; glucose improved mechanical performance and modified the depressant effects of FFA. The depressant effect of the nonmetabolized FFA, pentenoic acid, was similar to that of other FFA. This suggests that the effect was mediated directly by FFA or acyl CoA derivatives rather than their metabolic products, and that it might be due to a detergent effect or calcium binding by FFA present in excess of intracellular FFA binding capacity at low pH. Force development during anoxia could be augmented by calcium, implying that the reduced ability of the myofilaments to contract could not be attributed entirely to a reduction of high energy stores. ADDITIONAL KEY WORDSlinoleate octanoate pent-4-enoic acid calcium binding detergent action of free fatty acids optimal oxygen requirement of rat myocardium paired stimulation• It has been demonstrated that glucose improves the mechanical performance and prolongs the survival of anoxic hearts (1-4), but the possible influence of free fatty acids (FFA) under conditions of oxygen deprivation has received little attention. High concentrations of FFA have been shown to increase myocardial oxygen consumption (MV02) in aerobically perfused rat hearts (5) and to cause arrhythmias in dogs with experimentally induced infarction (6). Furthermore, high serum levels of FFA have been correlatedFrom the Cardiovascular Division, Peter Bent

Adaptation to exercise or the "warm up phenomenon" has been observed in some patients with angina pectoris. To investigate adaptation, eleven patients with exertional angina pectoris and angiographic evidence of coronary artery disease underwent two identical bouts of sequential tachycardia stress separated by a brief recovery period. Manifestations of ischemia were less during the second stress, as evidenced by a reduction in the severity of angina pectoris, less ST segment depression, and improved lactate extraction. Peak coronary blood flow during the second stress (81 + 20 ml/min) was not significantly different from that during the first (95 + 32 ml/min). Regional myocardial oxygen consumption, however, was significantly (p = .03) lower during the second stress (8.8 2.4 ml 02/min) when compared with the first (1 1.4 + 3.0 ml 02/min). Thus, patients with coronary artery disease can develop anginal tolerance to the stress of tachycardia similar to that observed after repeated bouts of exercise. A relative reduction in myocardial oxygen consumption, rather than an increase in coronary blood flow, appears to account for this phenomenon. Circulation 71, No. 4, 687492, 1985. IN 1785, William Heberdeen described a patient in whom angina pectoris initially developed during exercise but then paradoxically disappeared as exercise was continued.' This phenomenon has been termed "walk through" or "second wind" angina. A related form of angina has also been acknowledged wherein a patient, after terminating exercise because of the development of angina, is subsequently able to resume angina-free exercise. This latter adaptation has been termed the "warm up phenomenon" or "angina of first effort."Several investigators have documented reduced myocardial ischemia in patients demonstrating either walk-through angina or the warm-up phenomenon during exercise stress testing. MacAlpin and Kattus2 described 12 patients who were able to adapt to treadmill exercise. Nine patients demonstrated the disappearance or lessening of anginal pain and ischemic ST segment depression with continued walking. Three patients showed increased exercise capacity after having been "warmed up" by a prior exercise period that re-

Limited data are available concerning the effects of mild-to-moderate, sustained reductions of coronary blood flow on myocardial aerobic metabolism. This study tested the hypothesis that a sustained flow reduction distal to a severe coronary artery stenosis may be well tolerated (after the initial insult is passed) because of gradual improvement in the balance between myocardial oxygen supply and demand. Studies were performed in eight sedated, closed-chest domestic swine that were instrumented with an artificial coronary arterial stenosis (80% diameter reduction). Hemodynamics, regional myocardial blood flow and oxygen, lactate, acid, and base metabolism were measured before stenosis and at 5, 20, 60, 120, and 180 minutes after stenosis insertion. Regional myocardial function (ultrasonic length sensors) was measured serially during 2 hours in three additional swine. After stenosis placement, endocardial and transmural flows declined (p<0.05) compared with flows before stenosis (from 1.54±0.37 to 0.73 ± 0.24 ml/min/g [mean ± SD] and from 1.44 ± 0.31 to 1.19 ± 0.25 ml/min/g, respectively). Thereafter, flows remained unchanged for the duration of the study. Similarly, prestenosis heart rate (135 ± 7 beats/min), aortic mean pressure (113 ± 17 mm Hg), and tension time index (27.1 ± 3.6 mm Hg * sec) remained constant for the duration of the study. In contrast, regional coronary venous pH declined (p<0.05) compared with prestenosis levels (7.35±0.02) 5 minutes after stenosis (7.28±0.04), but it returned to prestenosis levels during the next hour. Regional coronary venous Pco2 exhibited a similar pattern (i.e., acute increase during poststenosis with gradual return to prestenosis levels). Lactate consumption at prestenosis (36.7 ± 27.3 ,umol/min/100 g) changed to production 5 minutes poststenosis (-80.3 ± 46.8; p<0.05) and then gradually returned toward consumption during the ensuing 3 hours (1.6 ± 10.7 at 180 minutes, p<0.05 vs. 5 minutes). Regional myocardial oxygen consumption declined compared with prestenosis consumption (16.8 ±4.1 ml/min/100 g) at 5 minutes poststenosis (13.7±2.8, p<0.05) and remained unchanged thereafter. Regional shortening declined abruptly immediately after stenosis placement in a separate group of three animals and decreased further until a steady state was achieved 40 minutes after stenosis. Thus, the data demonstrate that metabolic indexes of myocardial ischemia improve over time in a clinically relevant animal model of human ischemic heart disease. Such changes occur in the absence of significant alterations in either regional myocardial blood flow or external determinants of myocardial oxygen demand. The mechanism that is involved likely is related to a time-dependent adjustment in which myocardial oxygen demand declines and stabilizes at a level more appropriate to reduced myocardial oxygen supply. (Circulation 1988;78:729-735) Recent advances in the treatment of patients with ischemic heart disease, notably coronary angioplasty and thrombolysis, at times From

To compare the length of stay and charges for patients with pneumonia admitted in 1995 to the teaching and nonteaching services of a Northeastern teaching hospital, we reviewed the charts of 237 patients. Patients cared for by hospitalbased generalists working with housestaff (teaching service) were discharged more quickly and with lower or equivalent charges than patients cared for by community-based attending physicians working either with housestaff (private teaching service) or alone (nonteaching service). Academic teaching services staffed by general medicine faculty may provide efficient inpatient pneumonia care. A t a time when managed care contracting has created fiscal pressures at academic centers, hospital stays continue to account for a high proportion of overall patient care costs. Not surprisingly, traditional models of inpatient care at teaching hospitals are being reevaluated. 1 Residency teaching services are thought to be particularly inefficient in providing care. The average cost of hospitalization has been reported to be 30% to 40% higher at academic centers than in nonacademic institutions. 2 Whether this reported difference derives from overutilization of services, differences in severity mix, or a higher intrinsic cost structure remains unclear. Although medical decisionmaking at teaching hospitals is shared between housestaff and attending physicians, at most programs housestaff independently order tests and arrange for consultations, which may accelerate or impede hospital discharge. Again, it has been assumed that housestaff participation adds to the cost of care, and educational programs targeted at unnecessary diagnostic tests by housestaff have been attempted. 3 At Rhode Island Hospital, three models of inpatient care exist, providing the grounds for a natural experiment. Using a single diagnosis, pneumonia, that has a well-defined measure of severity of illness, we compare the economic implications of three models of inpatient care in order to gain insight into practice style differences between housestaff teaching services and a nonteaching service.