Biomedical subjects
Publications and source records attributed to H Gesser.
Electrically paced atrial strips of hearts from rat and rainbow trout were exposed to increasing extracellular Ca2+ concentration, [Ca2+]o. This resulted in increases in the peak force in oxygenated atria from both species. During anoxia this response was suppressed for the rat, but accentuated for trout atrium.
The evolutionary step involving transition from water- to air-breathing exposed the vertebrate cell to an increased risk of becoming acidotic. This is due to the fact that water-breathers generally excrete CO2 more easily than air-breathers. CO2 rapidly diffuses into the cell, where it may result in an excess of hydrogen ions. This is of interest as to the cardiac muscle, since these ions depress contractility, to a large extent probably by inhibiting the inotropic action of calcium ions in a competitive way. The present review, however, concerns the fact that the heart muscle may have an inherent ability to resist the negative inotropic effects of hydrogen ions. This is not a general property of the vertebrate heart, as it shows a clear tendency to be present in most air-breathers, whereas it is absent in most pure water-breathers, i.e. in most fishes. Measurements of the intracellular pH and of the tissue buffer capacity indicate that this ability to maintain force at a normal level in spite of an ongoing CO2-acidosis involves neither neutralization nor excretion of excess hydrogen ions. Instead, studies involving calcium-flux measurements and interventions in the cellular calcium-distribution suggest that the intracellular calcium ion deficit due to acidosis is compensated for by an increase of the calcium pool involved in the beat to beat regulation of cardiac force. How this is accomplished is unclear, although evidence was obtained that mitochondrial calcium stores may be involved.
Vanadate in the range 0-5 mM has positive inotropic effects on myocardial strips of frog and to a lesser extent on those of rat. Inhibiting the sarcolemmal Na+, Ca2+ exchange by a solution free of Ca2+ and Na+ caused a drop in 45Ca efflux and a transient increase in resting tension. These effects were more expressed for the frog than for the rat myocardium, which suggests that the Na+ for Ca2+ exchange across the cell membrane is more important in the frog than in the rat myocardium. A subsequent addition of vanadate at 2 or 5 mM had no effect on 45Ca efflux, while it increased the resting tension. This increase was higher for the frog than for the rat myocardium. These results suggest that the inotropic effects of vanadate may be due to an effect on membrane-bound Ca2+-ATPase.
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The influence of hypercapnic acidosis upon the heart was examined in four vertebrate species. The CO2 in the tissue bath was increased from 2.7 to 15% at 12 degrees C for flounder (Platichthys flesus) and cod (Gadus morhua) and from 3 to 13% at 22 degrees C for turtle (Pseudemys scripta) and rainbow trout (Salmo gairdneri). During hypercapnia, as previously described, there was a decline and recovery of contractility in heart strips of flounder and turtle, and a sustained decrease in cod and rainbow trout. At high CO2 the increase in contractile force following increases in the extracellular Ca-concentration were smaller for the cod myocardium than for the other myocardia. The intracellular pH (pHi), measured with the DMO method, in heart strips of turtle and trout was significantly lower at high than at low CO2. This acidifying effect expressed as the increase in the intracellular concentration of hydrogen ions was larger in the turtle than in the trout myocardium. Intracellular Ca-activity, measured by efflux of 45Ca from preloaded heart strips, was unaffected by high CO2 in trout, but was raised in the other three species. Thus the ability to counteract the negative inotropic effect of hypercapnia is apparently not due to cellular buffering or extrusion of hydrogen ions. More probably it involves (a) a release of intracellular Ca; (b) a positive inotropic effect of an increase in intracellular Ca-activity.
There is a large variation in the tolerance of myocardial tissue to cellular acidosis. Assuming the cytoplasmic acid-base status to be mainly a result of intracellular processes, this variation could be produced by variations in the tissue non-bicarbonate buffer value. In the myocardial tissue from nine vertebrate species, the non-bicarbonate buffer value did not correlate either with ability to develop tension under hypercapnic acidiosis or with the indirectly estimated capacity for anaerobic glycolysis. Therefore, differences in myocardial tolerance to acidosis must be explained either by an active pH regulation or by other compensatory mechanisms.
A negative-inotropic effect of CO2 on myocardial contractility presumably occurs because increasing H+ concentration competes with Ca2+ at cellular membranes and proteins. Since air-breathing vertebrates have higher blood and tissue CO2 concentration than water breathers the question was raised whether the cardiac cell has a modified sensitivity to CO2 correlated with the evolutionary transition of vertebrates from water breathers to air breathers. The water-breathing fish, Salmo gairdneri, and the air-breathing turtle, Pseudemys scripta, were selected as experimental animals, since their total CO2 concentration differs markedly (3.0 and 16.0 mmol.kg-1). Electrically paced isometric ventricular strips from both species were subjected to a stepwise increase in PCO2 from 25 to 114 Torr (pH0 7.80 to 7.0; HCO3- 30 mM). Trout were additionally exposed to the same pH0 changes at 5 mM HCO3- by a stepwise increase in PCO2 (4.5-12 Torr). At each increase in PCO2 the turtle heart showed a lesser negative inotropic effect than trout. The present findings offer direct evidence that the negative inotropic effect of CO2 on heart muscle is inversely proportional to the in vivo levels of tissue CO2 concentration. The results obtained are discussed in relation to phylogenetical and ecological aspects of acid-base balance.
1. Tissue oxygen uptake and enzyme activities were investigated in the naked mole rat, Heterocephalus glaber, a mammal notable for its low body temperature and metabolism and poor temperature regulating ability. 2. Q10 for O2 uptake of Heterocephalus crude liver homogenates ranged from 1.91 for the temperature interval 25-30 degrees C to 1.76 within the range 30-38 degrees C, values similar to those reported for typical homoiotherms. 3. Km pyruvate of lactate dehydrogenase in heart muscle had the same temperature dependence in the mole rat and mouse. 4. O2 uptake and cytochrome oxidase activity of skeletal muscle were higher for mole rat than mouse. The reverse was true for heart muscle. Brain and liver O2 uptake showed similar values for both species, while kidney O2 uptake was highest in the mouse. 5. Pyruvate kinase activity in heart and skeletal muscle was higher in mouse than mole rat, suggesting a greater reliance on glycolysis in the former. 6. Na+, K+ -ATPase activity of liver and kidney was 60% higher in mouse than mole rat, while brain was 30% higher in mouse. 7. The results indicate that the effects of temperature on tissue metabolism in the mole rat conform to those in typical homoiotherms. The low body temperature and O2 uptake in the mole rat find no expression in the tissue respiratory capacity.
Isometrically mounted and electrically paced myocardial ventricular strips of carp have a much higher capacity to develop force during severe hypoxia and to redevelop force after it than those of rainbow trout. When the concentrations of CO2 and HCO3-in the solutions surrounding the strips were increased together, such that pH remained constant, the force developed during hypoxia increased. The concentration of CO2 was raised from 0-4%; that of HCO3-from 0-25 mM. The effect was much more pronounced in the carp strips than in the trout strips. With the carp strips, the force recovery upon reoxygenation was unaffected by the variations in CO2 and HCO3-. The trout strips, however, recovered better when CO2 and HCO3-had been raised during either hypoxia or reoxygenation.
1. The influence of the carbon dioxide-bicarbonate buffer system on anaerobic energy production during severe hypoxia was studied in isolated right hemidiaphragms of rats.--2. When the tissue was incubated in a Ringer solution containing 25 mM HCO-3 aerated with 7% CO2 in N2 at pH 7.4, the lactate production and lactate content of the tissue increased.--3. At an extracellular (tissue bath) pH OF 6.9 the lactate production was stimulated when carbon dioxide and bicarbonate were changed to 19% and 25 mM, respectively. This stimulatory effect disappeared when these values were lowered to 7% and 7 mM.--4. At pH 7.4 the stimulatory effect of the carbon dioxide-bicarbonate system persisted when the buffer value was lowered from 60 to 3 mM by changing the system from an open (i.e. continuous gas equilibration) to a closed one (i.e. without any gas phase). Decreasing the glucose in the media from 22 to 0 mM reduced the lactate production and abolished the stimulatory effect of the carbon dioxide--bicarbonate system.--5. There was no direct effect of this system on the glycolytic enzymes (i.e. lactate production and activity of phosphofructokinase of homogenates).
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The contractility of isolated ventricle strips of the frog heart (Rana pipiens) was studied under temporary N2 hypoxia and during subsequent recovery after reoxygenation under different extracellular H ion concentrations (pH 6.0-8.5). The recovery of contractile force was three times more pH-sensitive than force decay. Under slow pacing (12/min) at +12 degrees C there was almost complete recovery to control values within 60 min at pHe above 7.0. Under this pH level recovery was largely delayed (pH 6.5) or did not occur (pH 6.0). Prolongation of contraction during the reoxygenation phase, observed at low H ion concentrations, was largely delayed or absent under high concentrations of H ions.
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