Ellis S. Benson

Myocardial creatine phosphate and nucleotides in anoxic cardiac arrest and recovery

In isolated perfused dog hearts, myocardial concentrations of creatine phosphate (CrP) and adenosine triphosphate (ATP) decreased following a 45-min period of anoxia. After partial resuscitation by perfusion of oxygenated blood for 30 min, CrP had risen again to approximately control values but ATP concentration had fallen lower. Increased concentrations of deaminated derivatives of ATP, chiefly inosine, were found in the myocardium and in the perfusion effluent after anoxia. The myocardial inosine was still elevated after resuscitation. We conclude that the dynamic equilibrium involving breakdown and resynthesis of ATP through deamination and reamination is disturbed by periods of anoxia as carried out in these experiments and, in addition, inosine is lost by diffusion into extracellular compartments.

Composition and State of Protein in Heart Muscle of Normal Dogs and Dogs with Experimental Myocardial Failure

In comparing protein composition of cardiac muscle of normal dogs and dogs with experimental valvular lesions and chronic heart failure, it was found that the concentration of actomyosin was lower in the experimental than in normal dogs. Furthermore, cardiac actomyosin in the experimental animals showed decreased viscosity, decreased viscosity response to ATP, and sedimentation patterns that differed from the normal.

Studies on the effect of reagent and protein charges on reactivity of the β93 sulfhydryl group of human hemoglobin using selected mutations

Abstract The reactivity of the β93 sulfhydryl (SH) group of human oxyhemoglobins with the negatively charged 5,5′-dithiobis(2,2′-nitrobenzoate) and the uncharged 2,2′-dithiodipyridine was determined as a function of pH. Selected mutant hemoglobins having increased oxygen affinity and having residue substitutions altering charge near the SH group (Wood, Malmo, Yakima, Kempsey, Andrew-Minneapolis, Osler, and Chesapeake) were compared to hemoglobin (Hb) A. Although both reagents reacted with GSH at the same rate and with the same enthalpies of activation, the rates with Hb were different and the difference showed a pronounced pH dependence. The charged reagent was sensitive to charges near the SH group; a positive charge increased the rate and a negative one decreased the rate. The uncharged reagent which reacted with Hb A with activation enthalpies similar to those for GSH was insensitive to neighboring charges, but was sensitive to tertiary and quaternary structural changes. The rates obtained with the latter reagent did not correlate with oxygen affinity. The evolutionary aspects of the β93 cysteine in relation to structure and function are reviewed.

The use of the differential leukocyte count for inpatient casefinding

The differential leukocyte count is a nonspecific, imprecise, error-prone, usually labor-intensive, and expensive test to perform. Although the differential count is frequently ordered in the absence of clinical suspicion in both inpatient and outpatient settings, its effectiveness as a screening test has been studied little. From a detailed chart review of 287 cases randomly drawn from a population of 2682 adult patients for whom a differential count was performed on admission, we found that 23 per cent of the cases met criteria for admission screening, that abnormal results were found in approximately one half of these screening differential examinations, and that one third of the abnormal examinations were acknowledged in the medical record by a physician. In no instance did a screening differential count appear to have had clinical significance. It may be medically prudent to consider discontinuing the differential leukocyte count as an inpatient screening test for adults.

Contractile Properties of Glycerol-Extracted Muscle Bundles from the Chronically Failing Canine Heart

Chronic congestive heart failure was induced in dogs by the surgical production of tricuspid insufficiency and pulmonary stenosis. Glycerol-extracted trabecular bundles from the right and left ventricles of these dogs developed significantly less tension than did similar preparations from the hearts of normal dogs. The maximum working capacity of the bundles from failing hearts was lower than that of bundles from normal hearts, hut the rate of hydrolysis of adenosinetriphosphate was the same as that of normal heart preparations. Since glycerol-extracted muscle bundles retain the basic contractile properties of fresh, surviving whole muscle but are free from membrane, neurohormonal, ionic and pH effects and are isolated from energy-supplying systems of muscle, defective contractility and decreased working capacity of muscle bundles from failing hearts may be appropriately ascribed to physiochemical changes in the contractile protein, actomyosin. Such alterations are undoubtedly of structural significance, and are related to the conformation changes in actomyosin which characterize the contractile cycle of muscle.

Initiatives toward effective decision making and laboratory use

Escalating health care costs constitute a public issue of paramount importance today, Among the leading growth factors in this rise is the cost of hospital services, notably laboratory services. With respect to the clinical laboratory, rising costs appear to be almost entirely attributable to expanding utilization and introduction of new services. The clinical laboratory has gone through a technological revolution in two decades that has changed it from a largely manual to a highly automated system of great speed and capacity. This change had produced a change in the style of providing services, a change that includes the provision of quantities of unsolicited data. A parallel change in the style of use of the laboratory has taken place on the part of patient care physicians from a relatively sparing, problem oriented use pattern to a relatively lavish, data oriented one. These reciprocal changes have transformed medicine, in the United States, at least, into a relatively high laboratory use culture. Abandonment of the new technology and return to a simpler, more primitive laboratory world would be a drastic and most inappropriate response to the new situation. Furthermore, arbitrary measures such as rationing, quotas, and tariffs are, if enacted, almost certain to fail. The most effective long term strategies, though more demanding of time and effort, lie through modification of physician behavior through the pathways of education and research. Education and research initiatives now in progress can in time influence laboratory use patterns of physicians at all career levels, improving the logic of test use and providing more strategic, prudent, and cost effective overall laboratory utilization practices. These approaches will require much improved communication between laboratory and bedside and a new intense involvement of laboratory physicians and scientists in the tasks of helping to improve the use of laboratory tests and laboratory data.

Extraction and Quantitative Characteristics of Actomyosin in Canine Heart Muscle

The conditions for quantitative extraction of actomyosin from dog heart ventricular muscle were studied. By use of appropriate techniques and conditions, yields of actomyosin comparable to those found by others for a variety of muscles were obtained. The method used could be standardized to give reproducible values with both fresh and frozen muscle. Actomyosin so obtained retained its characteristic properties as evidenced by its viscosity response to ATP and its enzymatic activity.

Partial reduction of aquomethemoglobin on a sephadex G-25 column as detected by magnetic circular dichroism spectroscopy and revised extinction coefficients for aquomethemoglobin

In a typical preparation of aquomethemoglobin, oxyhemoglobin is oxidized with potassium ferricyanide, and the resultant mixture of methemoglobin and potassium ferro- and ferricyanides is separated on a Sephadex G-25 column. We find that about 1% of the heme is reduced on the column and is eluted with the methemoglobin. Magnetic circular dichroism spectra show that the reduced species is oxyhemoglobin. Magnetic circular dichroism is more sensitive than is absorption spectroscopy to small amounts of oxyhemoglobin in such solutions; we can detect its presence at the 0.1% level. A redetermination of the extinction coefficients for methemoglobin gives a value of 0.80 for the absorbance ratio A570A630 at pH 6. This value lies clearly outside the currently accepted range of 0.83 to 0.87.

The responsible use of the clinical laboratory

Concern about spiralling health care costs is leading to a reexamination of the use of the clinical laboratory and other diagnostic technologies in patient care. Laboratory resources are viewed as limited and their use must be measured to meet real needs. Several observers have noted significant overutilization and inappropriate utilization of laboratory services by patient care physicians, especially at teaching hospitals. Efforts to modify physician behavior by use of educational programs, positive incentives and similar means have been largely disappointing. Several laboratory-based initiatives aimed at bringing about more responsible use of the laboratory are discussed. Improved education in the judicious use of the laboratory, beginning in medical school and carrying on through the early stages of a physicians career, is considered the most promising long-term approach. This, along with improved communication between the laboratory and the clinic, is the avenue most likely to bring about more responsible use of the clinical laboratory in health care.

Blood Viscosity Changes in Acute Myocardial Infarction

Plasma protein changes of acute tissue injury are seen in acute myocardial infarction, and the increase in hematocrit and blood viscosity represents increased strain on the heart. The phenomenon of intravascular sludging will appear, effecting either a temporary drop in viscosity or a more prolonged drop in both viscosity and hematocrit. Improved hydration alone does not reduce viscosity as measured, but dextran of low molecular weight significantly reduces blood viscosity during the period of its administration. This action should materially reduce the work of the heart and, in effect, rest it during this period of acute stress.