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W E Jacobus

Publications and source records attributed to W E Jacobus.

At least 55 records · Page 3Linked to original sources
PubMed1982

Use of an isolated heart model to test the utilization of substrates for inclusion in cardioplegic solutions.

Previous studies from our laboratory utilized an isolated isovolumic Langendorff heart preparation to study myocardial metabolism and preservation of left ventricular function following global ischemia and reperfusion. The present study employed a similar preparation to assess the utilization of various glycolytic substrates by monitoring the level of left ventricular developed pressure. Twenty-one rabbit hearts were perfused with an oxygenated but substrate-free Krebs-Ringer-bicarbonate solution in order to deplete the hearts of endogeneous substrate stores. Following a brief period of anoxic, substrate-free perfusion, hearts were perfused with one of seven test substrates under anaerobic, then aerobic conditions. Under anaerobic conditions only perfusion of glucose resulted in a measurable increase in ventricular function which was still less than 20% of control. Under aerobic conditions, provision of glucose, pyruvate, or the combination of alpha-glycerol phosphate and pyruvate resulted in significant increases in contractile function which were 40-70% of control. These results obtained in normal hearts will provide a base line for future studies of the metabolism of postischemic hearts which may have altered cell membrane permeability and/or enzymatic activity.

Animals↗
PubMed1982

Mechanisms of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance.

Phosphorus-31 nuclear magnetic resonance (31P NMR) can estimate tissue intracellular pH as well as the content of high-energy phosphate metabolites in isolated perfused hearts. We used 31P NMR to examine mechanisms associated with the recovery of ventricular function in hearts subjected to global ischemia and reperfusion, with special emphasis on intracellular pH, a previously unreported variable. Single-dose and multiple-dose administration of a hyperkalemic cardioplegic solution were compared with hypothermia alone in 18 isolated perfused rabbit hearts. Hearts in group 1 were subjected to 24 degrees C hypothermia during 60 minutes of global ischemia; group 2 hearts received a single injection of 37-mM KCL cardioplegic solution at 10 degrees C at the onset of ischemia; and group 3 hearts received a similar initial cardioplegic injection followed by two subsequent 24 degrees C injections at 20-minute intervals during the ischemic period. Using an intraventricular balloon, maximal dP/dt provided a quantitative index of left ventricular performance before and after ischemia. Return of ventricular function expressed as a percentage of control was 54 +/- 11% for group 1, 84 +/- 6% for group 2, and 101 +/- 18% for group 3. Differences in the rate of development of intracellular acidosis were noted during the 60-minute ischemic period. Intracellular pH fell to 6.09 +/- 0.12 in group 1, 6.31 +/- 0.09 in group 2, an 6.79 +/- 0.03 in group 3. In all three groups intracellular pH returned to control (pH 7.20) within 10 minutes of reflow. The metabolic correlates of functional recovery appeared to be the tissue content of ATP at the end of ischemia and after reflow. ATP content at the end of ischemia was 22 +/- 2% of control in group 1 hearts, 31 +/- 4% in group 2 and 64 +/- 2% in group 3. After 45 minutes of reperfusion, ATP levels recovered to 33 +/- 9% of control in group 1, to 71 +/- 9% in group 2 and to 86 +/- 6% in group 3. Although there were no differences between groups in the content of creatine phosphate after 60 minutes of ischemia, the rates of creatine phosphate decline were dissimilar. Further, during the early reflow period, a marked overshoot in tissue creatine phosphate was detected, especially in groups 1 and 2. Histologic damage assessed by light microscopy correlated with the metabolic data, confirming that multidose cardioplegia provided the best preservation of cellular morphology. These results demonstrate that the magnitude of intracellular acidosis and the associated increase in inorganic phosphate correlate inversely with recovery of postischemic ventricular structure and function. ATP, but not creatine phosphate, content correlates with return of contractile performance after reperfusion. The overshoot in creatine phosphate during early reperfusion might impede optimal restoration of ATP content and, as a result, optimal recovery of cell functions.

Adenosine Triphosphate↗
PubMed1980

Mass spectrometry and phosphorus-31 nuclear magnetic resonance demonstrate additive myocardial protection by potassium cardioplegia and hypothermia during global ischemia.

Previous studies from this laboratory utilized mass spectrometry to measure myocardial oxygen (PO2) and carbon dioxide (PCO2) tensions in isolated feline hearts subjected to periods of global ischemia and reperfusion. Myocardial carbon dioxide tension was found to increase during ischemia, and its rate of increase was found to correlate inversely with subsequent recovery of myocardial function following reflow. The present study utilized phosphorus-31 nuclear magnetic resonance (NMR) to assess whether the severity of intracellular acidosis or the depletion of high energy phosphate stores would show a similar correlation with recovery of function. Hyperkalemic cardioplegia employed as a myocardial preservation technqiue in combination with hypothermia was compared with hypothermia alone as the control intervention. The experimental results demonstrated that intracellular pH fell to 6.09 +/- 0.13 with hypothermia alone and to 6.31 +/- 0.09 with cardioplegia plus hypothermia. Furthermore, myocardial ATP content fell to 22% +/- 2% of control with hypothermia alone, while falling to 36% +/- 4% of control with the combined therapy. Recovery of myocardial performance was found to correlate inversely with the severity of intracellular acidosis and depletion of ATP during ischemia. In contrast, no relationship was observed between preservation of phosphoryl-creatinine levels either during ischemia or after reflow and recovery of ventricular function. These results suggest that, similar to mass spectrometry, which allows monitoring of myocardial PCO2, 31P NMR permits the on-line monitoring of intracellular pH as well as high energy phosphate compounds, and thereby provides useful metabolic indices of the severity of ischemia. Since tight coupling was found between changes in these parameters and subsequent recovery of contractile performance, further development of 31P NMR for evaluation of techniques designed to minimize the severity of ischemic damage would seem indicated.

Acidosis↗
PubMed1975

Aspects of energy-linked calcium accumulation by rat heart mitochondria.

When intact rat heart mitochondria were pulsed with 150 nmol of CaCl2/mg of mitochondrial protein, only a marginal stimulation of the rate of oxygen consumption was observed. This result was obtained with mitochondria isolated in either the presence or absence of nagarse. In contrast, rat liver mitochondria under similar conditions demonstrated a rapid, reversible burst of respiration associated with energy-linked calcium accumulation. Direct analysis of calcium retention using 45Ca and Millipore filtration indicated that calcium was accumulated by heart mitochondria under the above conditions via a unique energy-dependent process. The rate of translocation by heart mitochondria was less than that of liver mitochondria; likewise the release of bound calcium back into the medium was also retarded. These results suggest that the slower accumulation and release of calcium is characteristic of heart mitochondria. The amound of calcium bound was independent of penetrant anions at low calcium concentrations. Above 100 nmol/mg of mitochondrial protein, the total calcium bound was increased by the presence of inorganic phosphate. Under nonrespiring conditions, a biphasic Scatchard plot indicative of binding sites with different affinities for Ca2+ was observed. The extrapolated constants are 7.5 nmol/mg bound with an apparent half-saturation value of 75 muM and 42.5 nmol/mg bound with half-saturation at 1.15 mM. The response of the reduced State 4 cytochrome b to pulsed additions of Ca2+ was used to calculate an energy-dependent half-saturation constant of 40 muM. When the concentration of free calcium was stabilized at low levels with Ca2+-EGTA buffers, the spectrophotometrically determined binding constant decreased two orders of magnitude to an apparent affinity of 4.16 X 10(-7) M. Primary of calcium transport over oxidative phosphorylation was not observed with heart mitochondria. The phosphorylation of ADP competed with Ca2+ accumulation, depressed the rates of cation transport, and altered the profile of respiration-linked H+ movements. Consistent with these result was the observation that with liver mitochondrial the magnitude of the cytochrome b oxidation-reduction shift was greater for Ca2+ than for ADP, whereas calcium responses never surpassed the ADP response in heart mitochondria. Furthermore, Mg2+ ingibited calcium accumulation by heart mitochondria while having only a slight effect upon calcium transport in liver mitochondria. The unique energetics of heart mitochondrial calcium transport are discussed relative to the regulated flux of cations during the cardiac excitation-relaxation cycle.

Adenosine Diphosphate↗
PubMedDate not supplied

Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants.

To evaluate changes in coronary blood flow during allograft rejection, 16 beagles with cervical cardiac allografts from mongrel donors were immunosuppressed postoperatively for 7 days with cyclosporine (20 mg/kg orally) and prednisone (0.5 mg/kg orally). They were weaned from immunosuppression over 3 days and then treated with methylprednisolone (30 mg/kg/day IV), cyclosporine (20 mg/kg orally), and prednisone (0.5 mg/kg orally) for 4 days. Previous experiments with this model have suggested the utility of phosphorus 31 nuclear magnetic resonance spectroscopy (31P NMR) in the diagnosis of rejection. Therefore in 10 dogs (NMR group) bioenergetic changes during rejection were assessed using the 31P NMR index of the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). To correlate coronary blood flow and graft ischemia with allograft rejection, six dogs (FLOW group) underwent placement of a magnetic flow probe on the left anterior descending coronary artery to determine mean and peak coronary flow. In both NMR and FLOW groups, grafts were evaluated by endomyocardial biopsy (grading 0 to 8 for increasing rejection), and measurement of lactate production and left ventricular end-diastolic pressure. During the initial 7 days of immunotherapy, cellular rejection was effectively suppressed, and the bioenergetic status of the grafts remained stable (day 7: PCr/Pi = 70% of baseline, biopsy score = 2.0). During weaning of immunotherapy, however, the metabolic profile of the grafts decayed (day 10: PCr/Pi = 45% of baseline, biopsy score = 5.8; p less than 0.05 vs day 0). After 4 days of augmented immunosuppression, PCr/Pi recovered to 83% of baseline; this metabolic recovery corresponded with an improvement in mean biopsy score to 3.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗