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Biomedical subjects

D A Mickle

Publications and source records attributed to D A Mickle.

At least 127 records · Page 7Linked to original sources

The role of cardioplegic solution buffering in myocardial protection. A biochemical and histopathological assessment.

The advantages of buffering cardioplegic solutions to improve adenosine triphosphate preservation and postarrest hemodynamic function have been previously promoted. We evaluated the benefit of histidine buffering (195 mmol/L) in a low sodium (27 mEq/L) cardioplegic solution (Roe's) in a canine model of multidose cardioplegic arrest. Four solutions, two unbuffered (K+ = 10 mEq/L and K+ = 30 mEq/L) and two buffered (K+ = 10 mEq/L and K+ = 30 mEq/L), were tested in four groups of dogs for a 4 1/2 hour arrest period followed by 1 hour of reperfusion. Use of the unbuffered solution resulted in a drop in myocardial adenosine triphosphate from 29 +/- 1 mmol/kg (mean +/- standard error of the mean) (K+ = 30 mEq/L) and 28 +/- 2 mmol/kg (K+ = 10 mEq/L) to 8 +/- 2 mmol/kg and 7 +/- 2 mmol/kg, respectively, during the arrest period. In both buffered groups, adenosine triphosphate remained at preischemic levels during the entire arrest period. Myocardial glycogen followed the same pattern as adenosine triphosphate in the buffered groups. Lactate production was markedly elevated in all groups during ischemia. Postarrest hemodynamic function, as assessed by intraventricular isovolumic developed pressure measurements, was better (p less than 0.05) in the buffered low-potassium group than in the other three groups. The extent of myocardial necrosis, measured by triphenyl tetrazolium staining and confirmed by electron microscopy, was minimal (2% +/- 1% of biventricular mass) in the buffered low-potassium group, significantly greater (7% +/- 2% and 10% +/- 2%) in the unbuffered high-potassium and low-potassium groups, respectively, and highest (35% +/- 9%) in the buffered high-potassium group. These findings indicate that significant buffering capacity (similar to that of blood) in a crystalloid cardioplegic solution can be effective in preserving myocardial adenosine triphosphate stores, improving postarrest contractile function, and minimizing myocardial necrosis, provided the combination of high extracellular potassium and high pH levels is avoided.

Adenosine Triphosphate↗

The effect of fasting and hypocaloric diets on the functional and metabolic characteristics of rat gastrocnemius muscle.

Previous observations have shown that in human subjects with malnutrition and after prolonged fasting, there are characteristic changes in the force-frequency response, relaxation rate and power of muscle during a 30 s stimulus (fatigue). In order to characterize these findings under carefully controlled conditions, in different types of muscle and to correlate them with changes in muscle structure, composition and biochemical status, we developed an animal model in rats. In this model, nutrient restriction, both after an acute fast and after chronic hypocaloric feeding, resulted in: (a) loss of force during high frequency stimulation but preservation of contraction-relaxation characteristics during low frequency stimulation; (b) slower muscle relaxation rate at high frequency stimulation; (c) increased muscle fatiguability at high frequency stimulation. Measurements of muscle enzymes showed that acute fasting resulted in a reduced content of glycolytic enzymes, but preservation of oxidative enzymes, while chronic hypocaloric dieting resulted in a reduction in both classes of enzyme. There was no significant change in ATP, AMP or energy charge, or in intracellular sodium, potassium and magnesium levels. Creatine phosphate was normal in acutely fasted animals but low in those fed hypocalorically. By contrast, increased intracellular calcium and ADP levels were seen in both fasted and hypocalorically fed animals. These findings suggest that subtle disturbances of intracellular energy states with altered calcium flux may be of importance in the genesis of muscle dysfunction caused by malnutrition.

Animals↗

Metabolic and structural changes in skeletal muscle during hypocaloric dieting.

Hypocaloric dieting and fasting alter the contraction-relaxation characteristics of skeletal muscle and result in low frequency fatigue. We report the metabolic and structural changes in skeletal muscle in five morbidly obese female subjects who had biopsies of the gastrocnemius muscle on a base-line diet (2500 kcal/day) followed by a repeat biopsy after 2 wk of a 400-kcal/day carbohydrate diet. Hypocaloric dieting resulted in a significant increase in the intracellular muscle calcium content (p less than 0.05), which may account for the observed changes in muscle function. There were no significant changes in muscle glycogen, lactate, pyruvate, or free energy stores. There was a significant decrease in muscle enzymes [phosphofructokinase (p less than 0.05), succinate dehydrogenase (p less than 0.02)] and some muscle amino acid levels [glutamine (p less than 0.025), glycine (p less than 0.01), and alanine (p less than 0.02)], while muscle histochemistry showed type II fiber atrophy (p less than 0.025). However, these changes reflect a generalized response to hypocaloric dieting and probably do not explain the specific functional changes. Change in the muscle calcium content is probably an important mediator of the adverse functional effects of malnutrition.

Adolescent↗

Decreased uptake of exogenous substrates following graded muscle stimulation.

An exercising in vivo canine hindlimb model was used to assess the pattern of exogenous substrate delivery and uptake as a function of contraction frequency. The limb was stimulated to contract at 0, 4, 8, 12 8, 4, and 0 Hz for 10-min periods. Blood flow was proportional to stimulatory frequency. Oxygen consumption increased to a maximum at 12 Hz and subsequently declined. Glucose, free fatty acid, and lactate uptakes decreased despite increased deliveries and maintained arterial concentrations at 12 Hz. At this point there was a net release of glycerol and lactate from the muscle. Microvascular shunting was not the cause of decreased exogenous substrate uptake at 12 Hz. A switch from exogenous to endogenous muscle substrates occurred with the onset of decreased substrate uptake. The mechanism that facilitates this switch from exogenous to endogenous substrates remains unknown.

Animals↗

Limitations of blood conservation.

Blood conservation has been most successful when blood salvage techniques have been combined with postoperative normovolemic hemodilution. The hemodynamic and myocardial metabolic responses to normovolemic hemodilution were assessed in a prospective randomized trial. Twenty-seven patients were randomized to receive either blood and colloid solutions (colloid group, 13 patients) or crystalloid fluids (crystalloid group, 14 patients) following elective coronary revascularization. Although seven patients in the crystalloid group received blood products when the hemoglobin level fell below 7 gm/dl, blood bank requirements were less in the crystalloid group (colloid, 3.6 +/- 1.2 L; crystalloid, 1.5 +/- 1.0 L, p less than 0.01). The crystalloid group received twice as much fluid to maintain normovolemia (left atrial pressure between 8 and 10 mm Hg) in the first 72 hours postoperatively (colloid, 6.5 +/- 1.9 L; crystalloid, 14.5 +/- 3.1 L, p less than 0.01). The infusion of large volumes of crystalloid fluids resulted in a progressive postoperative anemia (hemoglobin: colloid, 12.1 +/- 1.6 gm/dl, crystalloid 8.9 +/- 1.7 gm/dl, p less than 0.01, 20 hours postoperatively). Although the crystalloid-treated patients had peripheral edema, pulmonary edema could not be documented and there was no difference in the physiological shunt fractions between the two groups. Preload (left atrial pressure), afterload (mean arterial pressure), and cardiac index were similar in the two groups. The crystalloid group had a delayed recovery of myocardial oxygen and lactate extraction postoperatively. Volume loading and atrial pacing 3 to 5 hours postoperatively maintained myocardial lactate extraction in the colloid group but decreased myocardial lactate extraction to ischemic levels in the crystalloid group. The use of crystalloid rather than colloid fluids in the early postoperative period conserved blood products but resulted in postoperative anemia and was associated with a delay in myocardial metabolic recovery. Normovolemic hemodilution should be employed with caution in patients who are at risk of perioperative ischemic injury.

Blood Transfusion↗

A clinical trial of blood and crystalloid cardioplegia.

Although experimental studies suggest that blood cardioplegia provides better protection than crystalloid cardioplegia, clinical studies have been inconclusive. Ninety patients undergoing coronary bypass grafting were randomized to receive either blood (n = 43) or crystalloid cardioplegia (n = 47). The incidence of perioperative myocardial infarction was lower with blood cardioplegia (blood, n = 0; crystalloid, n = 5; p = 0.06), and the maximum MB isoenzyme of creatine kinase was significantly less with blood cardioplegia (blood, 26.3 +/- 12.6 U/L; crystalloid, 35.6 +/- 17.0 U/L, mean +/- standard deviation; p less than 0.02.) Sixty patients (blood cardioplegia, n = 28; crystalloid cardioplegia, n = 32) had more sensitive measurements to assess the metabolic response to aortic occlusion and to compare the metabolic and functional recovery from the operation. Coronary sinus blood flow (by the continuous thermodilution technique) was significantly lower after cross-clamp removal with blood cardioplegia (blood, 160 +/- 100 ml/min; crystalloid, 220 +/- 120 ml/min; p less than 0.05), indicating less reactive hyperemia. The cardiac production of lactate was significantly less with blood cardioplegia during aortic occlusion (blood, -0.5 +/- 0.9 mmol/L; crystalloid, -0.9 +/- 0.9 mmol/L; p less than 0.05) and immediately after aortic declamping (blood, -0.2 +/- 0.4 mmol/L; crystalloid, -0.7 +/- 0.7 mmol/L; p less than 0.01). Thermodilution cardiac output measurements permitted calculation of the left ventricular stroke work index, and nuclear ventriculograms permitted calculation of the left ventricular end-diastolic volume index and end-systolic volume index. Myocardial performance, systolic elastance, and diastolic compliance were determined from volume loading studies (250 to 500 ml colloid) performed 2 to 4 hours postoperatively. Myocardial performance (the left ventricular stroke work index-left ventricular end-diastolic volume index relation) and systolic elastance (the systolic blood pressure-left ventricular end-systolic volume index relation) were significantly better with blood cardioplegia (p less than 0.01 by multivariate analysis); diastolic compliance (the left atrial pressure-left ventricular end-diastolic volume index relation) was similar. Blood cardioplegia reduced ischemic injury, decreased anaerobic metabolism during arrest, and permitted better functional recovery. Blood cardioplegia provides superior protection for elective coronary bypass grafting and may improve the clinical results in patients with unstable angina and in other high-risk patients.

Anti-Arrhythmia Agents↗

Improved myocardial protection with blood and crystalloid cardioplegia.

Although the results of coronary artery bypass surgery have been excellent, recent studies have demonstrated transient alterations in myocardial function and metabolism in spite of apparently adequate cardioplegic protection. Blood cardioplegia may provide better protection than crystalloid cardioplegia, but clinical studies remain inconclusive. Critical coronary stenoses limit cardioplegic delivery, and myocardial protection would be improved with either blood or crystalloid cardioplegia if the solution could be delivered beyond the coronary stenosis. The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period permits more uniform cardioplegic delivery and immediate reperfusion when the cross clamp is released. This technique was used in a prospective randomized trial comparing blood and crystalloid cardioplegia. The long cross-clamp technique eliminated temperature gradients induced when cardioplegia was delivered into the aortic root. The technique of cardioplegic delivery may be as important as the solution used for cardioplegic protection.

Blood↗

A comparison of volume loading and atrial pacing following aortocoronary bypass.

Although cold potassium cardioplegia provides adequate myocardial protection, transient hemodynamic and metabolic instability occasionally occurs after uncomplicated coronary bypass surgery. Two methods to increase cardiac output were compared 2 to 6 hours postoperatively in 24 patients recovering from elective coronary bypass operation. Volume loading increased cardiac index (CI) from 2.1 +/- 0.5 to 2.7 +/- 0.6 L/min/m2 by increasing left atrial pressure (LAP) from 8.6 +/- 3.6 to 13.0 +/- 4.1 mm Hg. Atrial pacing at a rate of 112 +/- 8 beats per minute increased CI from 2.4 +/- 0.5 to 2.7 +/- 0.8 L/min/m2 without a change in LAP. Ejection fraction by nuclear angiography did not change, but the calculated left ventricular end-diastolic volume index (stroke index/ejection fraction) increased with volume loading and decreased with atrial pacing--a decrease in diastolic compliance. Myocardial oxygen extraction did not change, but myocardial lactate extraction increased with volume loading and decreased with atrial pacing. Coronary sinus blood flow was measured in 5 patients and increased with both methods studied. Volume loading demonstrated that myocardial performance was normal and myocardial metabolism increased commensurate with the increase in work. Atrial pacing increased CI but resulted in anaerobic metabolism and a decrease in diastolic compliance. Volume loading rather than atrial pacing will improve CI without producing ischemia in the early postoperative period.

Adult↗

Improved myocardial protection during a prolonged cross-clamp period.

Severe coronary stenoses limit delivery of cardioplegic solution to ischemic regions in patients undergoing bypass operations. A prospective randomized trial was undertaken to determine whether the construction of proximal as well as distal anastomoses during a prolonged cross-clamp period would provide more uniform cardiac cooling and better myocardial protection. Ninety-one consecutive patients undergoing elective coronary bypass operations were randomized into two groups. The long cross-clamp technique was used in 46 patients (Group 1), and a proximal anastomosis was constructed after each distal anastomosis. The short cross-clamp technique was employed in 45 patients (Group 2), and distal anastomoses were constructed during aortic occlusion. Cardiopulmonary bypass time was identical, but the cross-clamp period was longer in Group 1 (59 +/- 15 minutes versus 46 +/- 17 minutes in Group 2; p less than 0.001). The mean temperature in the most ischemic region was colder with the long cross-clamp technique (12.5 +/- 3.1 degrees C in Group 1 versus 14.8 +/- 3.2 degrees C in Group 2; p less than 0.01). The total amount of the myocardial isoenzyme of serum creatine kinase released was greater in Group 2 than in Group 1 (332 +/- 34 IU/L per hour in Group 1 versus 469 +/- 45 IU/L per hour in Group 2). Thirty-six patients had coronary sinus catheters inserted (18 patients in each group). Myocardial lactate extraction returned to normal sooner in the patients who had a long cross-clamp period; time to a normal lactate extraction was 0.8 +/- 0.8 hours in Group 1 versus 2.2 +/- 2.1 hours in Group 2 (p less than 0.001). Volume loading and atrial pacing 2 to 4 hours postoperatively produced a similar hemodynamic response in the two groups, but myocardial lactate extraction increased in Group 1 and decreased in Group 2 (p less than 0.05). The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period produced more uniform cooling and improved myocardial protection.

Constriction↗

Measurement of human skeletal muscle acetylcholine receptor antibodies using monkey receptors.

Human skeletal muscle acetylcholine receptor (AChR) antibodies were assayed by a double immunoprecipitation technique using 125I-alpha-bungarotoxin as the label. Monkey AChRs were found to be superior to those from diabetic humans for analytical and practical reasons. The analytical sensitivity is 0.05 nmol alpha-bungarotoxin/L serum. The between-run and within-run precision (1 c.v.) of the assay are 13% and 3%, respectively. The normal range is 0-0.2 nmol alpha-bungarotoxin/L. There was no correlation between the antibody concentration and the clinical severity of myasthenia gravis. The clinical sensitivity and specificity of the assay for generalized myasthenia gravis are 79% and 96%, and for ocular myasthenia gravis 29% and 96%, respectively.

Animals↗

Optimal postoperative volume loading.

Intravenous infusions are required to maintain ventricular preload after uneventful coronary bypass operation. During the early postoperative period, when myocardial metabolic recovery is incomplete, volume loading is intended to stabilize ventricular function and metabolism and to prevent progressive ischemic injury. This study attempts to define the optimal preload for both metabolism and performance. Thirty-seven patients recovering from elective coronary bypass operations and cold potassium cardioplegia underwent volume loading with whole plasma. The initial response (VLA) from a low left atrial pressure (LAP = 7.3 +/- 3.3 mm Hg) was compared with the subsequent response (VLB) from a higher filling pressure (LAP = 10.9 +/- 2.7 mm Hg). Both VLA and VLB produced a similar increase in cardiac index, stroke work index, and end-diastolic volume index (EDVI), and a decrease in ejection fraction (measured by nuclear angiography). Myocardial lactate extraction increased with VLA, but myocardial lactate production resulted with VLB. A careful analysis of these volume loading studies suggested that myocardial performance and compliance were not altered in the early postoperative period. The decrease in ejection fraction with volume loading may have resulted from a combination of increased wall tension and decreased inotropic stimulation. After uneventful coronary bypass surgery, an LAP between 5 and 12 mm Hg corresponded to an EDVI between 30 and 80 ml/m2 and produced adequate cardiac index, stroke work index, and lactate extraction. A lower or higher preload did not improve function and resulted in abnormal metabolism.

Coronary Artery Bypass↗

Effects of postoperative hypertension and its treatment.

Hypertension following aorta-coronary bypass operations can contribute to myocardial ischemia. Nitroprusside therapy will reduce afterload, preload, and coronary perfusion pressure. Since both hypertension and its treatment can result in ischemic injury, nitroprusside must be carefully titrated to optimize cardiac function and metabolism. Thirty-one patients undergoing elective coronary bypass grafting were studied during a hypertensive episode (mean arterial pressure [MAP] = 119 +/- 18 mm Hg) and during nitroprusside therapy at an MAP of 97 +/- 11 mm Hg and at an MAP of 80 +/- 11 mm Hg (normotension). Nitroprusside also produced a significant (p less than 0.05) decrease in left atrial pressure (LAP), left ventricular end-diastolic volume index (EDVI) (stroke index divided by ejection fraction by nuclear angiography), stroke index, and stroke work index (SWI). Cardiac lactate extraction (LEx) and the ratio LEx/SWI increased (p less than 0.05) with the initial nitroprusside therapy, but lactate production resulted when the MAP was lowered to 80 mm Hg. Volume loading studies were performed during hypertension in four patients and during nitroprusside therapy in 15 patients. Neither performance nor compliance was significantly altered at an MAP of 97 mm Hg, but compliance decreased at normotension. Both hypertension and its treatment can result in inadequate myocardial metabolism. Nitroprusside should be titrated to maintain MAP between 90 and 100 mm Hg.

Adult↗

Comparison of alternative cardioplegic techniques.

Cold potassium cardioplegia provides adequate protection for coronary bypass operations, but severe coronary stenoses limit cardioplegic delivery to ischemic regions. The traditional technique delivers cardioplegic solution into the aortic root during the performance of distal anastomoses. The proposed alternative technique constructs proximal as well as distal anastomoses during a prolonged cross-clamp period, but permits more uniform cooling. The two techniques were compared in a prospective concurrent trial of 45 patients undergoing elective coronary bypass grafting. The traditional technique was employed in 26 patients (Group A) and the alternative technique in 19 patients (Group B). In both groups, 700 to 1,000 ml of a crystalloid cardioplegic solution was infused into the aortic root after application of the aortic cross-clamp. In Group A (traditional technique), 500 ml was infused into the aortic root after each distal anastomosis. In Group B (alternative technique), cardioplegic solution was administered through the vein graft after each distal anastomosis, and a proximal anastomosis was constructed after distal anastomoses to the most ischemic regions to permit continued cardioplegic delivery to these regions. The cross-clamp period was shorter in Group A than in Group B (44 +/- 15 versus 60 +/- 18 minutes, p less than 0.01), but the mean temperature in the most ischemic region was warmer (Group A, 19 degrees +/- 3 degrees C; Group B, 15 degrees +/- 3 degrees C, p less than 0.05). The postoperative CK-MB was higher in Group A (Group A, 47 +/- 36; Group B, 21 +/- 9 IU/L, p less than 0.01). Cardiac lactate production persisted longer in Group A (Group A, 4 +/- 1; Group B, 1 +/- 1 hours postoperatively, p less than 0.05). Volume loading 4 hours postoperatively produced a similar increase in left atrial pressure and cardiac index in both groups. In response to volume loading, Group A patients produced lactate, but Group B patients extracted lactate (change in cardiac lactate extraction: Group A, -1.7 +/- 2.3; Group B, +2.5 +/- 5.1 mg/dl, p less than 0.05). The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period permits more uniform cooling and immediate reperfusion. This alternative technique resulted in less injury (CK-MB release) and more rapid recovery of myocardial metabolism.

Aged↗

The hemodynamic and metabolic response to pacing after aortocoronary bypass.

Long-term follow-up of aortocoronary bypass has shown good preservation of ventricular function. However, myocardial reserve in the immediate postoperative period may not be optimal. Nineteen patients who underwent elective aortocoronary bypass protected with cold potassium cardioplegia were studied in the early postoperative period at rest and during the stress of atrial and ventricular pacing. Performance was assessed by hemodynamic, metabolic and nuclear angiographic measurements. In the first 2--6 hours after aortic cross clamping, myocardial performance was preserved at rest and there was no evidence of ischemic metabolism. Atrial pacing at a rate of 119 beats/min caused a significant increase in cardiac index (p less than 0.01) without deterioration in hemodynamics, ejection fraction or metabolic status. At the same rate, ventricular pacing did not change the cardiac index and there was a decrease in hemodynamic function. Ejection fraction decreased from 56% to 44% (p less than 0.05) without a change in end-diastolic volume. Lactate, pyruvate and beta hydroxybutyrate extractions were changed to net production. Ventricular performance was preserved at rest immediately after aortocoronary bypass done with multidose cold potassium cardioplegia, with adequate reserve to meet the stress of atrial but not ventricular pacing. We conclude that the therapeutic implications of the type of pacing selected in the immediate postoperative period may be important.

Atrial Function↗

Improved technique for developing creatine kinase isoenzyme bands by using a substrate in gelatin matrix.

We describe a simple technique for reacting CK isoenzymes with a substrate in gelatin to make them visible after they have been separated by cellulose acetate electrophoresis. The electrophoresed strip requires only 5 min of contact with the substrate in gelatin and about 12 min of drying in an oven at 55 degrees C. The developed isoenzyme bands are discrete, intense, and rectangular in shape. The technique has a sensitivity of 2 to 5 U/liter, and results for isoenzyme MB can be reported about 30 min from the time a specimen is received.

Creatine Kinase↗

Urolithiasis risk factors in continent reservoir ileostomy patients.

Conventional ileostomy patients are at an increased risk to urinary stone formation compared to normal controls. This study was designed to evaluate any further risk factors to urinary stone formation in patients with Kock ileostomies. Nine Kock ileostomy patients were matched for age, sex, and body weight with nine conventional ileostomy patients and nine controls. Two 24-hour urine samples from each patient were analyzed for volume, pH, Na+/K+ ratio, oxalate, and uric acid concentration. Both ileostomy groups demonstrated reduced urinary volume and Na+/K+ ratio as compared to the control groups (P less than 0.05). The Kock ileostomy group had the lowest urinary volume. There was no significant reduction in urinary pH or elevation in urine uric acid concentration in the Kock ileostomy group. The results suggest that there is no significantly added risk to uric acid stone formation in Kock ileostomy patients.

Calcium↗