Local relation between oxidative metabolism and perfusion in leg muscles of patients with heart failure studied by magnetic resonance imaging and spectroscopy.

BACKGROUND: We studied the local relation of muscle perfusion and metabolism in patients with severe chronic heart failure. Alterations of skeletal muscle blood flow and oxidative capacity contribute to exercise intolerance in these patients. The interdependence of both parameters has often been questioned. METHODS AND RESULTS: With the use of nuclear magnetic resonance, we quantified leg and muscle perfusion during reactive hyperemia in 7 patients with heart failure (New York Heart Association class III and IV) and 7 age-matched control subjects from the difference in longitudinal relaxation rate (1/T1). By using 31P nuclear magnetic resonance spectroscopy, we assessed oxidative metabolism from the creatine rephosphorylation time constant after a short ischemic exercise. Phosphocreatine recovery is slowed (74.6 +/- 11.3 vs 49.9 +/- 13.9 seconds, p = .002) and reactive hyperemic flow is reduced (48.5 +/- 24.9 vs 113 +/- 30.4 mL/100 mL per minute, p = .0005). CONCLUSIONS: By using a totally noninvasive protocol, we demonstrated that reactive hyperemic flow correlates with oxidative capacity in calf muscles from patients with heart failure, showing that exercise performance and local circulatory dysfunction are decreased in parallel in severe heart failure.

Interrelationship of oxidative metabolism and local perfusion demonstrated by NMR in human skeletal muscle.

Using nuclear magnetic resonance (NMR), we have examined the relationship of high-energy phosphate metabolism and perfusion in human soleus and gastrocnemius muscles. With 31P-NMR spectroscopy, we monitored phosphocreatine (PCr) decay and recovery in eight normal volunteers and four heart failure patients performing ischemic plantar flexion. By using echo-planar imaging, perfusion was independently measured by a local [inversion-recovery (T1-flow)] and a regional technique (NMR-plethysmography). After correction for its pH dependence, PCr recovery time constant is 27.5 +/- 8.0 s in normal volunteers, with mean flow 118 +/- 75 (soleus and gastrocnemius T1-flow) and 30.2 +/- 9.7 ml.100 ml-1.min-1 (NMR-plethysmography-flow). We demonstrate a positive correlation between PCr time constant and local perfusion given by y = 50 - 0.15x (r2 = 0.68, P = 0.01) for the 8 normal subjects, and y = 64 - 0.24x (r2 = 0.83, P = 0.0001) for the 12 subjects recruited in the study. Regional perfusion techniques also show a significant but weaker correlation. Using this totally noninvasive method, we conclude that aerobic ATP resynthesis is related to the magnitude of perfusion, i.e., O2 availability, and demonstrate that magnetic resonance imaging and magnetic resonance spectroscopy together can accurately assess muscle functional status.

Contralateral shoe-lift: effect on oxygen cost of walking with an immobilized knee.

OBJECTIVE: Evaluate the effect of a contralateral shoe-lift on the oxygen cost of walking with an artificially immobilized knee. DESIGN: A prospective quantitative evaluation of oxygen cost of walking under varying conditions. Subjects walked (1) normally (N), (2) with one knee immobilized (1), (3) with one knee immobilized and with a one-half-inch shoe-lift applied to the contralateral shoe (I1/2"L), and (4) with one knee immobilized and with a one-inch shoe-lift (I1"L). SETTING: Exercise physiology laboratory. SUBJECTS: Ten able-bodied subjects without known cardiopolmonary or musculoskeletal problems. MAIN OUTCOME MEASURE: Breath-by-breath oxygen consumption measurements in mL/kg/m. RESULTS: Oxygen cost on average was 20% more with the knee immobilized (I) compared to normal (N) (mean difference = .0298 +/- .0245mL/kg/m, p = .002). Oxygen cost was significantly less (11% versus 20% above that of normal walking) with the half-inch shoe-lift (mean difference between I1/2" and I = .0167 +/- .0138mL/kg/m, p = .002). Similarly, oxygen cost was significantly less (12% versus 20% above that of normal walking) with the one-inch shoe-lift (mean difference between I1"L and I = .0142 +/- .0116, p = .002). CONCLUSION: This study demonstrates that a subject with an immobilized knee requires less energy to walk with a contralateral shoe-lift and provides scientific evidence for prescribing a shoe-lift in patients with an immobilized knee as a result of knee joint fusion, knee immobilization as a result of casting or orthotics, or spastic paretic stiff-legged gait associated with upper motor neuron disease.

Perfusion changes in human skeletal muscle during reactive hyperemia measured by echo-planar imaging.

Muscle performance is markedly influenced by tissue perfusion. Techniques that allow quantification of microvascular flow are limited by the use of ionizing radiation. In this investigation, we apply an NMR model previously developed by Detre et al. to the measurement of human muscle perfusion during reactive hyperemia. We compare our results with conventional plethysmography adapted to NMR. Using echo-planar imaging, T1 and T2 were measured in 14 subjects during rest, ischemia, and reactive hyperemia. Mean leg muscle T1 in healthy volunteers is 850 ms at rest and 834 ms at reperfusion, leading to a calculated reactive hyperemia flow increase (T1 flow) of 103 +/- 40 ml/100 ml/min. T1 flows correlate well with NMR-plethysmography values. Changes in T2, which are sensitive to both deoxyhemoglobin content and vessel diameter variations, are also correlated with perfusion measurements. T1 changes allow quantification of regional perfusion in human muscle during reactive hyperemia.

Measured versus predicted vertical displacement of the sacrum during gait as a tool to measure biomechanical gait performance.

The vertical displacement of the sacrum during walking is proposed as an estimation of the overall biomechanical performance of walking, independent of cardiopulmonary factors. Vertical sacral displacement during walking was measured using an optoelectronic motion analysis system in 10 normal volunteers at variable speeds. Oxygen consumption was simultaneously measured. The actual vertical displacement of the sacrum, when correlated with body weight, reliably predicted oxygen consumption (r2 = 0.91). The relationship between vertical sacral displacement and oxygen consumption persisted when controlling for the variables, velocity, square of velocity, cadence or stride length, each known to co-vary with cardiopulmonary performance. A mathematic model designed to predict the vertical displacement of the sacrum, based on sacral height and average stride length, was tested. The actual vertical sacral displacement correlated with predicted displacement (r = 0.94). Unilateral immobilization of each subject's knee resulted in a greater average vertical sacral displacement during gait than predicted. Comparing measured with predicted vertical sacral displacement may provide a clinically useful and specific overall assessment of biomechanical gait performance.

Hemoglobin blood substitutes in extended preoperative autologous blood donation: an experimental study.

BACKGROUND: The risks of homologous blood transfusion have stimulated interest in developing possible alternatives. In this study we examined the efficacy of using a hemoglobin-derived blood substitute to augment and extend preoperative autologous blood donation. METHODS: In an ovine model, two experimental groups (n = 6 each) of animals donated either 45% or 80% or more of calculated blood volume, which was replaced with a polymerized bovine hemoglobin solution. Two control groups (n = 6 each) either did not donate or donated 45% of calculated blood volume, which was replaced with a 6% hetastarch solution. Twenty-four hours after blood donation, sheep underwent a measured surgical stress with standardized intraoperative blood loss; donated blood was reinfused. RESULTS: Extended autologous blood donation and replacement with this blood substitute were efficacious in supporting oxygen consumption; there was no systemic toxicity. After the postoperative replacement of autologous blood, animals that donated 80% or more of red cell mass exhibited overall blood conservation with a final hematocrit of 25.7% +/- 3.6%, compared with 20.5% +/- 2.0% (p < 0.05) and with 21.5% +/- 1.1% (p < 0.05) in both control groups. CONCLUSIONS: This study suggests that the benefits of a blood substitute can be combined with autologous blood donation to (1) safely increase the amount of autologous blood donated while supporting oxygen consumption, (2) avoid the need for advanced preoperative donation, and (3) decrease the need for homologous blood transfusion.

Nitrous oxide does not depress left ventricular contractility in ischemic rat heart.

The direct effects of nitrous oxide on left ventricular contractility and myocardial oxygen consumption (MVO2) in the ischemic isolated rat heart were studied. The rat heart was isolated and perfused by a Langendorf technique. The aortic stump was cannulated and the heart was perfused with Kumpeis solution bubbled with 95% O2 and 5% CO2 (control phase). A latex balloon was inserted into the left ventricle (LV) to measure LV pressures and dP/dt. Coronary flow was measured and MVO2 was calculated. After the control phase, perfusion pressure was decreased to induce global ischemia (ischemic phase). There were four groups of eight hearts each: control, nitrogen, nitrous oxide, and halothane groups. After 15 min of ischemic phase, the perfusion pressure was increased and the gas mixture was changed to the standard gas mixture (reperfusion phase). Nitrous oxide did not further depress myocardial contractility compared with nitrogen in the ischemic phase, and did not alter MVO2 in the ischemic phase compared with nitrogen. Halothane significantly depressed myocardial contractility and decreased MVO2 in the ischemic phase compared with the control.

Variables associated with a poor prognosis in patients with an ischemic thallium-201 exercise test.

To determine the exercise workload, ECG, and thallium-201 image parameters that are most closely associated with a poor prognosis from ischemic heart disease, the test results of 268 patients were reviewed. Only patients with unequivocal thallium-201 redistribution were selected. A multivariate analysis was performed to find the variables that were most strongly associated with the outcomes of coronary revascularization, myocardial infarction, and cardiac death during a follow-up period of 25 +/- 19 months. Patients who underwent early elective revascularization had poorer exercise tolerance and more thallium image abnormalities than those with no events. In the remaining patients myocardial infarction was most closely related to the extent and severity of thallium ischemia (p = 0.0086), whereas cardiac death was associated with abnormal thallium lung uptake (p = 0.0082) and an inability to exercise to 9.6 MET (p = 0.0144). Thus unlike myocardial infarction, cardiac death is best predicted by variables that reflect poor left ventricular function rather than those that indicate ischemia.

Determinants of maximal right ventricular function.

After heart transplantation, right ventricular failure can occur because of increased afterload. Previous studies have suggested that the maximal pressure the right ventricle can develop is determined primarily by right ventricular perfusion pressure. However, the interaction of the left ventricle and the pericardium as functional co-determinants of maximal right ventricular function is unknown. This study was undertaken to determine the interaction of the pericardium, left ventricular pressure, and right coronary artery perfusion pressure as potential determinants of maximal right ventricular function. In an acute canine preparation, with progressive pulmonary artery constriction, maximal generated right ventricular pressure was determined over a range of left ventricular systolic pressures. Additional groups of dogs were studied with the right coronary artery cannulated and were maintained at constant perfusion pressure. In all preparations, the maximal pressure the right ventricle could generate was linearly related to left ventricular systolic pressure. Having a closed pericardium markedly enhanced this effect; some effect was present with an open pericardium, although the magnitude of the influence of left ventricular pressure on maximal right ventricular pressure was much less. Maintaining constancy of right coronary artery perfusion pressure, either at high or low values, did not alter these findings nor did it alter the influence of the pericardium. These results suggest that right ventricular perfusion may not be the sole determinant of maximal right ventricular function. Furthermore, with the pericardium open, such as in the posttransplantation state, the left ventricular contribution to maximal right ventricular function may be diminished, increasing vulnerability for right ventricular failure caused by increased afterload.

Ultra-pure polymerized bovine hemoglobin blood substitute: effects on the coronary circulation.

The effects of stroma-free hemoglobin (SFHgb) on the coronary circulation remain unclear. An intact canine model utilizing intracoronary adenosine to abolish the confounding effect of autoregulation was used to study maximal myocardial oxygen delivery during progressive hemodilution with polymerized bovine SFHgb. The circumflex coronary artery was instrumented with a flow probe, hydraulic constrictor, and proximal and distal catheters for adenosine infusion and distal pressure measurement, respectively. This preparation was used to generate diastolic coronary pressure-flow relations during maximal vasodilation. Maximal coronary conductance and maximal myocardial oxygen delivery were determined in two groups of 7 dogs each following hemodilution, first with 6% hetastarch (Control), followed by further hemodilution with ultra-pure, polymerized, bovine SFHgb. After hemodilution with SFHgb, maximal coronary flow increased slightly without evidence of coronary vasoconstriction. Since hemodilution with this material increases oxygen carrying capacity, maximal oxygen delivery is greater than Control, despite the very low canine hematocrit. These findings suggest: 1) SFHgb can provide adequate oxygen delivery to the myocardium despite extreme degrees of hemodilution, and 2) in this intact model, there is no evidence of adverse coronary vasomotion.

Silent versus symptomatic ischemia during a thallium-201 exercise test.

One hundred thirty-four patients with redistribution on a thallium-201 exercise test who did not experience angina (group 1) were compared with 134 patients also having redistribution who had angina during the test (group 2). The groups were matched by age, sex, and peak exercise heart rate. Although patients in both groups achieved an equivalent exercise level, patients in group 1 had less frequent (53 vs 71%, p less than 0.005) and less severe (0.15 +/- 0.13 vs 0.20 +/- 0.13 mV, p less than 0.005) ischemic ST-segment depression. Group 1 also had less ischemic thallium-201 images in terms of the number of redistributing defects, the severity of the worst redistributing defect, and an ischemic index composite of both extent and severity. Patients in group 1 were less likely to undergo early revascularization (12 vs 29%, p less than 0.005), but in the remaining patients the occurrence of adverse cardiac events was similar (21% vs 29%, p = not significant). By multivariate analysis, only the ischemic index correlated with early revascularization in group 1 (p = 0.0017), whereas the percent maximal predicted heart rate correlated best in group 2 (p = 0.0003). In group 1 the ratio of lung/heart thallium-201 uptake correlated best with an outcome of nonfatal myocardial infarction or cardiac death (p = 0.0024); in group 2 the presence of fixed left ventricular dilatation did (p = 0.0022). Thus, patients with exercise-induced thallium-201 redistribution without angina have less ischemia than patients experiencing angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of predischarge low-level exercise thallium testing after thrombolytic treatment of acute myocardial infarction.

Low-level exercise thallium testing is useful in identifying the high-risk patient after acute myocardial infarction (AMI). To determine whether this use also applies to patients after thrombolytic treatment of AMI, 64 patients who underwent early thrombolytic therapy for AMI and 107 patients without acute intervention were evaluated. The ability of both the electrocardiogram and thallium tests to predict future events was compared in both groups. After a mean follow-up of 374 days, there were 25 and 32% of cardiac events in the 2 groups, respectively, with versus without acute intervention. These included death, another AMI, coronary artery bypass grafting or angioplasty with 75% of the events occurring in the 3 months after the first infarction. The only significant predictors of outcome were left ventricular cavity dilatation in the intervention group and ST-segment depression and increased lung uptake in the nonintervention group. The sensitivity of exercise thallium was 55% in the intervention group and 81% in the nonintervention group (p less than 0.05). Therefore, in patients having thrombolytic therapy for AMI, nearly half the events after discharge are not predicted by predischarge low-level exercise thallium testing. The relatively weak correlation of outcome with unmasking ischemia in the laboratory before discharge may be due to an unstable coronary lesion or rapid progression of disease after the test. Tests considered useful for prognostication after AMI may not necessarily have a similar value if there has been an acute intervention, such as thrombolytic therapy.

Hemodynamic effects and oxygen transport properties of a new blood substitute in a model of massive blood replacement.

Recent concerns regarding the safety of the national blood supply have rekindled interest in the development of blood substitutes. Clinical studies have dampened the initial enthusiasm for fluorocarbon solutions as blood substitutes. The potential of hemoglobin solutions as blood substitutes has continued to stimulate investigations. However, the development of an ideal hemoglobin-derived blood substitute has eluded investigators for the past century. A persistent problem has been the inability to develop hemoglobin solutions that provide adequate oxygen and carbon dioxide exchange, while avoiding toxicity that precludes clinical safety and long-term survival. Traditionally, investigators have focused on human hemoglobin solutions. The use of outdated banked blood or pedigree human donor blood as a hemoglobin source poses continued disease transmission risks and a prohibitively limited supply. We evaluated the hemodynamic and gas transport effects of a new purified, polymerized bovine hemoglobin preparation. Bovine hemoglobin oxygen affinity is regulated by chloride ion. The concentration of chloride ions in human plasma results in excellent oxygen transport properties in a stroma-free environment. In addition, unlike human blood, bovine blood is a more disease-free hemoglobin source that is available in large supply. We exchange-transfused eight conscious sheep with this new polymerized bovine hemoglobin solution. All animals tolerated greater than or equal to 95% exchange transfusion to reach a final ovine hematocrit of 2.4 +/- 0.5% with stable hemodynamics and no clinical evidence of distress. The exchange transfusion with bovine hemoglobin polymer resulted in a final plasma hemoglobin concentration of 6.1 +/- 1.6 gm/dl, which supported oxygen consumption at baseline levels. All animals that were exchange transfused with this preparation survived long term with rapid resynthesis of ovine erythrocytes.

Complete heart block as the sole presentation of Lyme disease.

We report a case of Lyme myocarditis presenting solely as complete heart block in a previously healthy 32-year-old white man. Indium cardiac antimyosin scan showed diffuse uptake (2+, on a scale of 0 to 4+) during the acute phase of the illness. The electrocardiogram and the indium cardiac antimyosin scan were normal 6 weeks after completion of tetracycline and prednisone treatment. Lyme carditis should be considered in the differential diagnosis of complete heart block of unclear origins, even in patients presenting without other signs or symptoms suggestive of Lyme disease.

Cardiac evaluation during physical rehabilitation of the complex medical patient.

Many rehabilitation patients have cardiovascular disease as a primary or secondary diagnosis. Such patients require careful evaluation before institution of vigorous therapeutic exercise and activity regimens. However, conventional exercise tests are often inappropriate due to orthopedic, neurologic, or functional limitations. This article introduces a new method of cardiac assessment, called the Trendscriber Evaluation (TE). The TE uses the Trendscriber, a cardiac telemetry unit which provides a hard-copy single-lead electrocardiogram (SECG) printout and digital heart rate monitor. The TE was developed to assess SECG, hemodynamic, and symptomatic responses during preestablished submaximal levels of activity. Specially trained physical and occupational therapists conduct the evaluation, directing the patient and monitoring vital signs. Results are interpreted by a staff cardiologist. For two years this technique was evaluated for 100 patients in the form of a medical records review. Eighty-nine percent of the patients' TEs identified cardiac abnormalities with heart rhythms, hemodynamic response, or both. Arrhythmia activity not detected on the routine 12-lead electrocardiogram (ECG) was recorded in 49.5% of the TEs performed. Fifty-seven percent of the records revealed activity-related ventricular ectopic activity. Data uncovered by the TE resulted in alteration of medical and/or rehabilitation therapy in 63% of the patients. The review suggests that the TE is a valuable tool in identifying problems related to cardiovascular performance and in providing the health care team with information important for patient management.

Thallium kinetics in rat cardiac transplant rejection.

Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection.

Comparison of washed blood and oxygenator whole blood as vehicles for sanguinous multidose cardioplegia.

The effects of washed blood or oxygenator-traumatized whole blood as vehicles for sanguinous cardioplegia were studied utilizing the isolated blood-perfused dog heart preparation. Hearts were subjected to 2 hr of potassium-induced arrest at 27 degrees C followed by 90 min of normothermic reperfusion. Washed blood cardioplegia (n = 7) contained blood washed thrice with saline while oxygenator blood cardioplegia (n = 6) contained whole blood which had been exposed to an extracorporeal circuit for 30 to 45 min. Cardioplegic solutions were administered at a perfusion pressure of 100 mm Hg every 15 min during arrest. While the arrest-reperfusion sequence caused minor variations in the mechanical, metabolic, and biochemical parameters tested, generally insignificant differences were found to exist between groups. Differences in coronary washout PCO2 appeared to be due to inherent differences between the two cardioplegic solutions. Thus, while washing blood may be thought to be beneficial and whole blood from the extracorporeal circuit may be theorized to have a deleterious effect on the myocardium, excellent recovery of mechanical function was observed with both cardioplegic solutions. The present study suggests that it is unnecessary to wash the sanguinous cardioplegic solution obtained from the cardiopulmonary circuit.

Myocardial temperature variation: effect on regional function and coronary flow in dogs.

Incremental changes in the temperature (28-42.5 degrees C) of the anterior left ventricular wall in a canine, working, beating right heart bypass preparation (constant preload, afterload, and heart rate) were produced to measure the effect of regional temperature on myocardial function and blood flow. Circumferential-axis segment lengths were measured with sonomicrometry in both the temperature-varied, left-anterior descending coronary artery (LAD)-supplied myocardium and the normothermic (38 degrees C) circumflex-supplied myocardium. Fast thermistors (time constant less than 0.25 s) continuously monitored midmyocardial temperature in both areas. A Silastic loop with heat exchanger, thermistors, strain gauge, and flow probe was inserted into the LAD and allowed precise control of regional myocardial temperature. Nine-micron microspheres injected into left atrium were used to evaluate coronary flow and distribution. In six anesthetized dogs, relative to normothermic control (38 degrees C), regional systolic shortening decreased 42.2 +/- 10% at 41 degrees C and increased 23.3 +/- 6% at 31 degrees C. There was no significant change in coronary blood flow or distribution at the three temperatures. Pressure-length areas varied inversely with myocardial temperature. These data demonstrate that there is a reversible inverse relationship between midwall T and ventricular function when heart rate, preload, and after-load are controlled.

Effect of experimental cardiopulmonary bypass on systemic and transcardiac thromboxane B2 levels.

Systemic and cardiac metabolism of thromboxane was studied in a canine model (n = 13) of standard cardiopulmonary bypass and surgical cardioplegia. Sterile techniques were applied and no donor blood was used. Systemic samples (thoracic aorta) and transcardiac gradients (coronary sinus - aortic root) were obtained (1) 5 minutes after cannulation, (2) 20 minutes after the onset of partial bypass, (3) 5 seconds after the first administration of cardioplegic solution (CP-1), and (4) 5 seconds after the second administration of cardioplegic solution (CP-2). Cardioplegic doses were administered 30 minutes apart and consisted of 500 ml of hypothermic (8 degrees C), hyperkalemic (25 mEq potassium chloride) solution infused into the aortic root at 60 to 70 mm Hg. Thromboxane B2 was determined by a double-antibody radioimmunoassay (picograms per milliliter +/- standard error of the mean). Onset of partial bypass was followed by a significant rise in systemic arterial thromboxane B2 levels: after cannulation, 115 +/- 21 pg/ml; after the onset of partial bypass, 596 +/- 141 pg/ml; p less than 0.01). Significant transcardiac thromboxane B2 gradients were found during the first and second cardioplegic washouts (CP-1: aortic root 73 +/- 12 pg/ml, coronary sinus 306 +/- 86 pg/ml, p less than 0.01; CP-2: aortic root 65 +/- 11 pg/ml, coronary sinus 355 +/- 98 pg/ml, p less than 0.01). Transcardiac gradients of 6-keto-prostaglandin F1 alpha and thromboxane B2 were obtained at CP-1 and CP-2. Gradients of 6-keto-prostaglandin F1 alpha were not different from thromboxane B2 gradients during CP-1 but were significantly higher than thromboxane B2 gradients during CP-2. In a subgroup of five dogs, transcardiac thromboxane B2, lactate, and platelet gradients were measured simultaneously. Cardiac thromboxane B2 generation was found only in the presence of cardiac lactate production. Transcardiac platelet gradients were significantly higher at CP-1 (13,900 +/- 3,000/mm3) than at CP-2 (4,000 +/- 1,230/mm3) (p less than 0.05), whereas thromboxane B2 gradients were similar at CP-1 and CP-2. Our study demonstrates that thromboxane B2 is released into the coronary circulation during surgical cardioplegic arrest with anaerobiosis.

Influence of coronary artery obstruction on cardiac prostaglandin metabolism during experimental cardioplegic arrest.

In order to test the influence of coronary artery obstruction on cardiac prostaglandin metabolism during surgically induced cardioplegia (CP), we have measured transcardiac veno-arterial gradients of prostacyclin and thromboxane A2 (TXA A2) during experimental canine cardiopulmonary bypass. Cardiac arrest was induced by infusion of 500 ml of hypothermic (8 degrees C), hyperkalemic (25 meq) crystalloid CP solution into the aortic root with (group I) and without (group II) occlusion of the left anterior descending artery (LAD). After 30 minutes of cardioplegic arrest the LAD occlusion in group I was released and a second set of CP infusion was applied in both groups. Transcardiac gradients were obtained 5 seconds after onset of the first and second CP washouts. Significant prostacyclin and TXA A2 gradients were observed at both times. Prostacyclin gradients did not differ between group I and group II. In contrast, TXA A2 gradients were significantly higher during the second CP washout in group I as compared to the unoccluded group (group I 918 +/- 221, group II 244 +/- 144 pg/ml, p less than 0.05). The results of our study suggest that cardiac TXA A2 metabolism during cardioplegic arrest is increased distal to a coronary artery obstruction. Cardiac TXA A2 production might contribute to the increased ischemic myocardial injury observed in this setting.