High-energy phosphates, myocardial contractile function and material properties after short periods of oxygen deficiency.

To investigate myocardial performance and diastolic properties after repeated periods of oxygen deficiency auxotonic and isovolumic measurements were performed after three periods (4 min) of asphyxia in Wistar rats (n = 19). Additionally, the response of the peak isovolumic left ventricular pressure to postextrasystolic potentiation was measured. The hemodynamic results were compared to the levels of high-energy phosphates. Already after 15 min of recovery from asphyxia auxotonic measures of systolic function were completely normal compared to the control group (n = 19). Isovolumic measurements after 20 min of postasphyctic recovery, however, demonstrated a considerable reduction of the peak left ventricular pressure (226.5 +/- 7.5 mm Hg vs. 262.6 +/- 3.4 mm Hg in controls, mean +/- SEM (p less than 0.01) indicating persistence of decreased postischemic contractile performance. The relative effect of postextrasystolic potentiation was similar in both groups, but could not compensate for the reduced performance of the postasphyctic hearts: the absolute postextrasystolic peak isovolumic pressure of the postasphyctic hearts was lower than the value of the regular isovolumic peak pressure in the controls. Diastolic properties (pressure/volume and stress/strain relationships) of the postasphyctic myocardium remained unchanged. The total sum of the adenine-nucleotides decreased from 7.2 +/- 0.2 to 5.6 +/- 0.3 mumol/gww (p less than 0.01). ATP was reduced from 4.8 +/- 0.2 to 3.9 +/- 0.3 mumol/gww (p less than 0.01). Phosphocreatine was elevated to 7.0 +/- 0.6 mumol/gww, x +/- SEM (p less than 0.01). Our results demonstrated normal postasphyctic basal hemodynamics and material properties. Thus, the energy supply was sufficient to maintain steady state conditions - in spite of decreased overall adenine-nucleotide levels. Isovolumic measurements and postextrasystolic potentation tests, however, indicated that the contractile performance of the postischemic myocardium was still reduced. This functional limitation cannot be explained by altered material properties and is probably not causally related to the decreased overall ATP content.

Effects of graded intensity of oxygen deficiency on function and energy metabolism in post-ischaemic myocardium.

The effect of graded ischaemic injury on post-ischaemic myocardium was examined in rat hearts after three 4 min periods of asphyxia. Systolic function under steady state conditions and during isovolumic beats, the content of high energy phosphates and glycogen, and myocardial material properties were determined. Severity of the oxygen deficiency was varied by manipulating myocardial oxygen demand (MVO2) either by rapid atrial pacing or by vagal stimulation. After 20 min of post-asphyxial recovery, steady state haemodynamics were almost normal. In the high MVO2 group (atrial pacing) the dp/dtmax was reduced to 90%(NS). The isovolumic indices of function were decreased in all post-asphyxial groups. This was most pronounced in the high MVO2 group, with a reduction in peak left ventricular systolic pressure to 85.7 (SEM 3.4)% and a decrease in peak left ventricular systolic stress to 82.3(3.9)% (p less than 0.01). The post-asphyxial myocardial performance recovered better in the low MVO2 group (vagal stimulation). Material properties were altered only in the high MVO2 group. The decreased content of ATP and glycogen were comparable in all post-asphyxial groups. A phosphocreatine overshoot phenomenon was most marked in the high MVO2 group: 11.4(2.8) mumol.g-1 v 4.7(0.9) mumol.g-1 (control), p less than 0.01. The results indicate that post-ischaemic contractile dysfunction of reversibly injured is not closely related to the previous O2 deficit or to the functional impairment. We also obtained no correlation between ATP content and material properties in modestly injured post-ischaemic myocardium.

Relationship between the high-energy phosphate content and various left ventricular functional parameters of the normal and hypertrophied heart after global ischemia and reperfusion.

Using an isolated rat heart preparation (Langendorff perfusion, perfusion pressure 100 cm H2O) the correlation between the high-energy phosphate content and various left ventricular (lv) functional parameters of the hypertrophied heart (spontaneous hypertensive rats lv/body weight ratio 3.6 +/- 0.5 x 10(-3) was determined after normo- (30 min) and hypothermic (25 degrees C, 120 min) cardioplegic arrest and reperfusion, and compared with normal hearts (Wistar rats lv/body weight ratio 2.0 +/- 0.3 x 10(-3). St. Thomas Hospital solution was used as the cardioplegic agent. Before ischemia hypertrophied hearts had a significantly higher developed left ventricular pressure, pressure rate product and dp/dtmax, but a significantly lower ATP and total adenine nucleotide content. Irrespective of the mode and temperature of cardiac arrest there was a strong correlation both for normal and for hypertrophied hearts between the high-energy phosphate content expressed as ATP, total adenine nucleotides or the "energy charge" and the left ventricular functional parameters pressure rate product and dp/dtmax. The correlation coefficient ranged from 0.80 to 0.89 and was highest when the ATP content was plotted against pressure rate product (r = 0.89). There was a different slope for normal and hypertrophied hearts with a steeper decline of the left ventricular function in hypertrophied hearts for any given reduction of the myocardial adenine nucleotide content. Our results indicate that a similar reduction of the ATP or total adenine nucleotide content in both the normal and hypertrophied heart reduces left ventricular function to a greater degree in the hypertrophied heart.

Phosphocreatine and adenine nucleotides in postasphyxial hearts with normal basal function and normal oxygen demand.

We investigated whether there is a relationship between the prolonged dysfunction after myocardial ischaemia and the postischaemic phosphocreatine overshoot phenomenon. In 16 open-chest rats 3 periods of 4 minutes of oxygen deficiency were performed and basal haemodynamic variables and the myocardial oxygen demand were determined during the recovery period. At the end of the 20 minutes recovery period, left ventricular pressure, dp/dtmax, ejection fraction, and myocardial oxygen demand were completely recovered. High energy phosphate levels, however, were still altered. The sum of adeninenucleotides was decreased to 78 +/- 4% of control (mean +/- SEM, p less than 0.05). The level of phosphocreatine was markedly elevated to 162 +/- 14 (mean +/- SEM). The persistence of the phosphocreatine overshoot phenomenon, while basal function was already normalized, indicates that a reduced function and thus a reduced energy demand of the contractile apparatus are not the cause of the phosphocreatine overshoot. We found no close relationship between high energy levels and basal function or oxygen demand in myocardium after mild oxygen deficiency.

Function and energy-rich phosphate content of the hypertrophied ventricle after global ischemia and reperfusion.

Using an isolated rat heart preparation (Langendorff perfusion, perfusion pressure 100 cm H2O) the response of the hypertrophied heart (spontaneous hypertensive rats lv/bw ratio 3.6 +/- 0.5) to global normothermic (30 min) and hypothermic (25 degrees C, 120 min) ischemic and cardioplegic arrest and reperfusion (30 min) was examined and compared with normal hearts (Wistar rats lv/bw ratio 2.0 +/- 0.3). St. Thomas solution and verapamil (2 mg/l Ringer solution) were used as cardioplegic agents. Before ischemia hypertrophied hearts had a significantly higher pressure-rate product, a lower myocardial perfusion/g myocardium and a lower myocardial ATP and adenine nucleotide content. Unmodified ischemia reduced myocardial function in the hypertrophied hearts to a greater degree than in normal hearts in both normo- and hypothermia. St. Thomas solution and verapamil protected significantly the myocardial function in the normal and hypertrophied heart after normothermic ischemia in a similar manner (60-70% of the initial value). In the hypertrophied ventricle ATP decay and adenine nucleotide loss was greater in verapamil than in St. Thomas solution treated hearts. In hypothermic ischemia only St. Thomas solution protected left ventricular function and adenine nucleotide loss in both normal and hypertrophied hearts. Verapamil was ineffective in the normal ventricle and protected left ventricular function but not the ATP and adenine nucleotide decay in the hypertrophied heart.