Transmural distribution of myocardial blood flow and coronary vasodilator reserve (15-microns-diam radionuclide-labeled microspheres) was studied in 11 adult, healthy ponies at rest and during moderate and severe exercise performed on a treadmill (heart rate 56 +/- 4, 154 +/- 3, and 225 +/- 7 beats . min-1, respectively.). Exercise resulted in a marked increase in cardiac output, mean aortic pressure, right ventricular (RV) systolic and end-diastolic pressure, left ventricular (LV) end-diastolic pressure, and the maximum rate of rise of LV pressure LV (dP/dtmax). Accompanying these changes was a pronounced increase in transmural myocardial perfusion. During severe exercise, subendocardial/subepicardial (endo/epi) perfusion ratio for the LV (0.99 +/- 0.02) decreased significantly from control value (1.27 +/- 0.03) but it was not significantly different from 1.00. With adenosine infusion during severe exercise, transmural myocardial blood flow throughout the cardiac ventricles was able to increase significantly further (delta from severe exercise to severe exercise with adenosine, 75% for LV, 68% for septum, and 57% for RV) despite the fact that heart rate, aortic pressure, and RV and LV end-diastolic pressures were unaltered. During severe exercise with adenosine, endo:epi perfusion ratios were 1.11 +/- 0.15 and 1.32 +/- 0.10 for LV and RV, respectively. In the LV, the coronary vasodilator reserve was found to be the least in papillary muscles, where the increment in blood flow during severe exercise with adenosine was only 46% above severe exercise without adenosine. Coronary vasodilator reserve was largest in the middle layers of the LV myocardium (88%). With adenosine infusion during severe exercise, coronary vascular resistance in both LV and RV decreased significantly from that observed during severe exercise alone (27 +/- 2 and 30 +/- 2 mmHg . ml-1 . min . g, respectively) to levels observed during maximal coronary vasodilation induced by adenosine infusion at rest (20 +/- 2 and 18 +/- 2 mmHg . ml-1 . min . g, respectively). These data clearly demonstrate that there remains a marked coronary vasodilator reserve transmurally in the pony myocardium during severe exercise.

No abstract

Isoflurane has been hailed as the anaesthetic of the eighties. We examined the effects of isoflurane anaesthesia on regional distribution of brain and myocardial blood flow in 11 healthy isocapnic pigs using 15 micron diameter radionuclide labelled microspheres that were injected into the left atrium. Each animal was studied during five of the following six conditions: (i) unanaesthetised (control; n = 8); (ii) 1.45% end-tidal (ET; 1.0 MAC) isoflurane anaesthesia (n = 10); (iii) 2.18% ET (1.5 MAC) isoflurane anaesthesia (n = 9); (iv) 0.95% ET isoflurane + 50% N2O anaesthesia (equivalent to 1 MAC; n = 8); (v) 1.68% ET isoflurane + 50% N2O anaesthesia (equivalent to 1.5 MAC; n = 8); and (vi) 50% N2O alone (n = 8). The order of anaesthetised steps was randomised for each pig. At every step 50 to 55 min were allowed for equilibration with isoflurane, and for N2O 35 to 40 min were allowed for equilibration. Recovery periods of 60 min each were interposed between anaesthetised steps to allow pigs to recover towards control values. Control values of blood flow in the cerebrum, cerebellum, and brain-stem were 81 +/- 5, 87 +/- 8, and 64 +/- 6 ml X min-1 X 100 g-1, respectively. During 1.45% isoflurane anaesthesia, cerebral, cerebellar and brainstem blood flows were 120%, 152%, and 145% of respective control values. With 2.18% isoflurane, perfusion in these regions of the brain was 140%, 200%, and 226% of respective control values. Substitution of 50% N2O to maintain equipotent anaesthesia markedly exaggerated the increment in cerebral blood flow, while changes in cerebellar and brain-stem blood flow were similar. Cerebral blood flow during 0.95% isoflurane + 50% N2O and 1.68% isoflurane + 50% N2O anaesthesia was 137% and 210% of the control value, respectively. Regional brain blood flow was only insignificantly altered by 50% N2O alone. It is concluded that isoflurane caused dose-dependent vasodilatation in all regions of the brain, the magnitude being greater in the cerebellum and the brain-stem. The administration of N2O with isoflurane to maintain equipotent anaesthesia exaggerated cerebral vasodilatation, especially at deeper level of anaesthesia. Myocardial blood flow in isoflurane anaesthetised pigs decreased, especially in the inner layers, in a dose-related manner. The use of 50% N2O with isoflurane permitted higher heart rate, perfusion pressure, rate-pressure product, and transmural myocardial blood flow.

A nonfusing variant, fu-1, of the L8 line of rat myoblasts was isolated and characterized with respect to its growth in vitro and developmental properties. Comparative analyses of density-dependent inhibition of growth, serum requirements, cell adhesiveness, colony formation-in soft agar, and hexose transport in L8 and fu-1 cells support the conclusion that the fu-1 cells are transformed. In addition, fu-1, but not Le, cells promote the development of tumors in athymic nude mice. fu-1 cells also do not make increased levels o creatine kinase (ATP:creatine N-phosphotransferase, EC 2.7.3.2) or myosin and they express an endogenous type-C virus. Both L" and fu-1 cells express myokinase (ATP:AMP phosphotransferase, EC 2.7.4.3) activities in single cells. In contrast to fu-1 cells, the parent L8 line has increased creatine kinase and myosin after fusion and spontaneously contracts; expression of an endogenous virus could not be detected in these cells. These results suggest that loss of the ability to differentiate normally is associated with the loss of the normal control of cell division of myoblasts grown in vitro and in vivo.Myoblasts, the precursors of highly differentiated skeletal muscle, proliferate in cell culture as single cells. Upon reaching a critical stage in their development, the myoblasts withdraw from the cell cycle and fuse into multinucleate cells (myotubes) (1)(2)(3)(4) of rat myoblasts (fu-i) that is defective in fusion from the myogenic L8 line. Analysis of several parameters that are usually attributed to transformed cells in vitro suggests that the nonfusing variant fu-i cells are transformed when compared to the parent L8 cells. In addition, only fu-l cells will form tumors in athymic mice. We have also found that the fu-i cells express an endogenous C-type virus; the L8 cells do not express this virus.MATERIALS AND METHODS Cell Culture Conditions. The L8 cells, kindly provided by D. Yaffe, were cloned and maintained by serial passage. Cloned cells were retrieved from frozen stocks as needed. fu-i cells were selected from the cloned L8 line as described in the text. All cells were grown in Dulbecco's modified Eagle's medium (GIBCO) supplemented with 10% horse serum (ISI), 0.5% chick embryo extract, penicillin at 100 units/ml, and streptomycin at 100 ,ug/ml, at 370 and in a 10% CO2 atmosphere. Stock cultures of 2 X 105 cells were seeded in 10 ml of medium and grown on 100-mm Falcon tissue culture dishes coated with 0.1% gelatin. To maintain the myogenic capacity of L8 cells, it is essential to subculture the cells before they become confluent. Cells were routinely harvested by detachment with 0.05% trypsin in Ca2+,Mg2+-free Earle's solution. In experimental cultures, 3 ml of medium containing 1 to 2 X 105 cells were seeded in 50-mm dishes; medium was changed every day or as indicated. The cells were found free of mycoplasma.Uptake of 2-Deoxyglucose. Cells (2 X 105) were plated in 3 ml of medium on 50-mm dishes coated with gelatin. To determine uptake of 2-deoxyglucose (dGlc), the cel...

SUMMARY1. Right and left atrial pressures were measured in eight chronically instrumented fetal and neonatal lambs. Flows were measured with a combination ofelectromagnetic flow sensor and microsphere techniques.2. Three of the fetuses were ventilated in utero during the measurements. Four fetuses were studied as neonates immediately after spontaneous term delivery and one was studied as a normal fetus in utero. Data from these preparations were augmented with seven sets of previously reported data from normal fetuses in utero for analysis.3. Linear least-squares regression analysis demonstrated that inferior caval vein flow into the right atrium was inversely related to right atrial pressure. This flow could not be demonstrated to depend on the velocity of blood in the inferior caval vein.4. Non-linear least-squares regression analysis of foramen ovale flow as a function of a power ofthe flow in the inferior caval vein revealed that the square of the velocity of blood in the inferior caval vein predicted foramen ovale flow. Of the two forces that determine foramen ovale flow in the fetus, pressure difference and kinetic energy, the latter was far larger than the former.5. These results support the theory that the fetal foramen ovale is maintained in an open position by the kinetic energy of the blood in the inferior caval vein.