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The origin of the nuclear magnetic resonance (NMR)-measurable ATP in equilibrium Pi exchange and whether it can be used to determine net oxidative ATP synthesis rates in the intact myocardium were examined by detailed measurements of ATP in equilibrium Pi exchange rates in both directions as a function of the myocardial oxygen consumption rate (MVO2) in (1) glucose-perfused, isovolumic rat hearts with normal glycolytic activity and (2) pyruvate-perfused hearts where glycolytic activity was reduced or eliminated either by depletion of their endogenous glycogen or by use of the inhibitor iodoacetate. In glucose-perfused hearts, the Pi----ATP rate measured by the conventional two-site saturation transfer (CST) technique remained constant while MVO2 was increased approximately 2-fold. When the glycolytic activity was reduced, the Pi----ATP rate decreased significantly, demonstrating the existence of a significant glycolytic contribution. Upon elimination of the glycolytic component, the measured Pi----ATP rates displayed a linear dependence on MVO (micromoles of O consumption rate) with a slope of 2.36 +/- 0.15 (N = 8, standard error of the mean). This linear relationship is expected if the rate determined by CST is the net rate of ATP synthesis by the oxidative phosphorylation process, in which case the slope must equal the P:O ratio. The ATP----Pi rates and rate:MVO ratios measured by the multiple-site saturation transfer method at two MVO2 levels were equal to the corresponding Pi----ATP rates and rate:MVO ratios obtained in the absence of a glycolytic contribution. The following conclusions are drawn from these studies: (1) unless the glycolytic contribution to the ATP in equilibrium Pi exchange is inhibited or is specifically shown not to exist, the myocardial Pi in equilibrium ATP exchange due to oxidative phosphorylation cannot be studied by NMR; (2) at moderate MVO2 levels, the reaction catalyzed by the two glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase and 3-phosphoglycerate kinase is near equilibrium; (3) the ATP synthesis by the mitochondrial H+-ATPase occurs unidirectionally (i.e., the reaction is far out of equilibrium); (4) the "operative" P:O ratio in the intact myocardium under our conditions is significantly less than the canonically accepted value of 3.

The protocol was associated with a significant increase in the number of lung donors and transplant procedures without compromising pulmonary function, length of stay, or survival of the recipients.

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BackgroundThe STOPP study (Surgical Treatment Outcomes for Patients with Psychiatric Disorders) analyzed variation in rates and types of major surgery by serious mental illness status among patients treated in the Veterans Health Administration (VA). VA patients are veterans of United States military service who qualify for federal care by reason of disability, special service experiences, or poverty.MethodsSTOPP conducted a secondary data analysis of medical record extracts for seven million VA patients treated Oct 2005-Sep 2009. The retrospective study aggregated inpatient surgery events, comorbid diagnoses, demographics, and postoperative 30-day mortality.ResultsSerious mental illness -- schizophrenia, bipolar disorder, posttraumatic stress disorder, or major depressive disorder, was identified in 12 % of VA patients. Over the 4-year study period, 321,131 patients (4.5 %) underwent surgery with same-day preoperative or immediate post-operative admission including14 % with serious mental illness. Surgery patients were older (64 vs. 61 years) and more commonly African-American, unmarried, impoverished, highly disabled (24 % vs 12 % were Priority 1), obese, with psychotic disorder (4.3 % vs 2.9 %). Among surgery patients, 3.7 % died within 30 days postop. After covariate adjustment, patients with pre-existing serious mental illness were relatively less likely to receive surgery (adjusted odds ratios 0.4-0.7).ConclusionsVA patients undergoing major surgery appeared, in models controlling for comorbidity and demographics, to disproportionately exclude those with serious mental illness. While VA preferentially treats the most economically and medically disadvantaged veterans, the surgery subpopulation may be especially ill, potentially warranting increased postoperative surveillance.