Biomedical subjects

I M Rebeyka

Publications and source records attributed to I M Rebeyka.

47 records · Page 3Linked to original sources

PubMed1991

Skeletal muscle extraaortic counterpulsation. A true arterial counterpulsation.

Reduction of left ventricular work load during systole, a critical component of arterial counterpulsation, has not previously been documented for skeletal muscle-powered extraaortic counterpulsation. To assess its capacity for afterload reduction, a skeletal muscle extraaortic counterpulsator was connected to the thoracic aorta and counterpulsated. Canine hearts (n = 7) were instrumented with left ventricular Millar catheters (Millar Instruments, Inc., Houston, Tex.) for pressure measurements and with piezoelectric ultrasonic crystals for measurement of the left ventricular minor axis dimension and wall thickness. During systole, skeletal muscle extraaortic counterpulsation resulted in a significant change in all three determinants of left ventricular circumferential wall stress compared with control conditions (no counterpulsation). Pressure decreased (peak systole, 100 +/- 5 versus 75 +/- 6 mm Hg; p less than 0.05 by paired t test), minor axis dimension decreased (end systole, 46.4 +/- 1.1 versus 45.8 +/- 1.1 mm; p less than 0.05 by paired t test), and wall thickness increased (end systole, 10.4 +/- 0.7 versus 10.6 +/- 0.7 mm; p less than 0.05 by paired t test). Left ventricular wall stress/dimension work loops showed a shift downward and to the left, a shift consistent with afterload reduction. The mean systolic left ventricular wall stress was significantly reduced, from 67.3 +/- 10.6 to 47.7 +/- 8.1 10(3) dyne/cm2 (p less than 0.05 by paired t test). Skeletal muscle extraaortic counterpulsation increased the diastolic aortic pressure from 72 +/- 6 to 105 +/- 8 mm Hg (p less than 0.05 by paired t test). Our data, which documented the counterpulsator's direct effects on left ventricular functional mechanics, showed that skeletal muscle extraaortic counterpulsation is capable of both diastolic augmentation of arterial pressure and systolic unloading of the left ventricle. Skeletal muscle extraaortic counterpulsation has potential application for ventricular unloading in the treatment of chronic end-stage heart failure.

Animals↗

PubMed1990

Superior myocardial preservation with modified UW solution after prolonged ischemia in the rat heart.

Cardiac transplantation remains constrained by poor graft tolerance of prolonged cold ischemia. University of Wisconsin solution has remarkably extended ischemic preservation in pancreas, kidney, and liver transplantation. To assess its efficacy in cardiac preservation, modified University of Wisconsin solution flush and storage were tested against St. Thomas' cardioplegia flush and normal saline solution storage after six hours of ischemia at 0 degrees C in 46 isolated rat hearts. After ischemia, groups were compared before and after reperfusion. After ischemia but before reperfusion, University of Wisconsin solution hearts had significantly less tissue water (3.8%), superior tissue sodium, potassium, calcium, and magnesium profiles, and elevated adenosine and inosine levels, and tended toward better histological preservation. After reperfusion, University of Wisconsin solution more effectively preserved left ventricular compliance (75% versus 35% of baseline), developed pressure (71% versus 45% of baseline), histological integrity, and tissue potassium and calcium profiles than St. Thomas' solution. The University of Wisconsin solution provided superior preservation of systolic and diastolic ventricular function, tissue histology, tissue water, and tissue electrolytes than did St. Thomas' cardioplegia and normal saline solution storage in this experimental model, and might result in improved graft tolerance of ischemia in clinical cardiac transplantation.

Adenine Nucleotides↗

PubMed1990

Altered contractile response in neonatal myocardium to citrate-phosphate-dextrose infusion.

The clinical use of citrate-phosphate-dextrose during blood-product transfusion is known to affect ionized calcium levels and can result in depression of myocardial contractility. The immature heart appears to have an intrinsic reduction in contractile state compared with the adult heart and may be more dependent on transsarcolemmal calcium flux for regulation of contraction. The myocardial contractile response to citrate infusion was compared in neonatal and adult rabbit hearts using clinically comparable citrate-phosphate-dextrose concentrations. Isovolumic left ventricular pressures were monitored in an isolated, crystalloid-perfused heart model before, during, and after 15 minutes of citrate-phosphate-dextrose infusion. Developed pressure decreased 42.1 +/- 4.9% from control within 1 minute in the neonatal group versus 24.3 +/- 4.3% in the adult group (p less than 0.02). The effect on diastolic function was paradoxical in the neonate with a 43.1 +/- 11.9% increase in end-diastolic pressure compared with a 9.7 +/- 7.8% decrease in the adult (p less than 0.01). These results indicate that the neonatal heart appears more sensitive to the myocardial effects of citrate infusion with impairment of both systolic and diastolic function. The decreased ventricular compliance in the neonate with citrate-phosphate-dextrose suggests that the myocardial effects may not be simply due to changes in ionized calcium concentration.

Animals↗

PubMed1990

Warm induction blood cardioplegia in the infant. A technique to avoid rapid cooling myocardial contracture.

The use of profound hypothermia and total circulatory arrest for repair of heart defects in neonates usually involves a period of systemic and myocardial bypass cooling. Rapid cooling of muscle (skeletal, smooth, and myocardial) can result in contracture through elevation of cytosolic calcium levels. The increased myocardial tone caused by cooling might render the heart more vulnerable to a subsequent period of cardioplegic ischemic arrest. Infants may be more susceptible to contracture because their small body mass allows more rapid myocardial temperature change when prearrest bypass cooling is used. The influence of avoiding rapid myocardial cooling before induced cardioplegic arrest was analyzed in a group of infants weighing less than 6 kg at the time of open cardiac operation. Myocardial ischemic arrest by warm (37 degrees C) induction blood cardioplegia was used in 57 infants and compared with results in 440 infants treated with standard blood cardioplegia. Multivariate logistic regression analysis revealed that patient diagnosis, weight, and age at operation were significant risk factors for operative mortality. The use of warm induction blood cardioplegia had a strongly positive independent effect on survival (p = 0.0003) for any patient weight, age, or diagnostic group. We recommend the avoidance of rapid myocardial cooling on bypass in all patients before induction of cardioplegic ischemic arrest.

Blood↗

PubMed1990

Calcium paradox in an in vivo model of multidose cardioplegia and moderate hypothermia. Prevention with diltiazem or trace calcium levels.

The production and prevention of calcium paradox injury in myocardium was studied in a canine model of cardiopulmonary bypass with multidose, moderately hypothermic, crystalloid cardioplegic solution. During 4 1/2 hours of global ischemia, three groups of six dogs each received one of three histidine-buffered cardioplegic solutions (500 ml initially and 250 ml every 30 minutes) at 27 degrees C. Group 1 cardioplegic solution was calcium free, group 2 solution contained a trace amount of calcium chloride (70 mumols /L), and group 3 cardioplegic solution was calcium free but contained diltiazem (150 micrograms/kg body weight). Left ventricular function measured as percent control of developed pressure revealed significantly greater (p less than 0.05) recovery in groups 2 and 3. Triphenyltetrazolium chloride staining showed 35% +/- 9% (mean +/- standard error) of heart mass necrosis in group 1 versus 0% and 0.5% +/- 0.4% in groups 2 and 3, respectively (p less than 0.001). Electron microscopy revealed ultrastructural changes characteristic of calcium paradox injury in group 1 myocardium. Calcium paradox injury was produced in an in vivo model of global myocardial ischemia and multidose cardioplegia despite moderate hypothermia and non-coronary collateral flow. The addition of either trace levels of calcium or diltiazem to the cardioplegic solution was effective in preventing this injury.

Animals↗

PubMed1990

Rapid cooling contracture of the myocardium. The adverse effect of prearrest cardiac hypothermia.

Hypothermic total circulatory arrest for repair of congenital heart lesions in neonates requires a period of rapid core cooling on cardiopulmonary bypass during which the myocardium is also exposed to hypothermic perfusion. Myocardial hypothermia in the nonarrested state results in an increase in contractility due to elevation of intracellular calcium levels. This study was designed to test the hypothesis that rapid myocardial cooling before cardioplegic ischemic arrest results in damage, with impaired recovery during reperfusion. Two groups of 10 rabbit hearts were perfused on an isolated Langendorff apparatus. Group N (normothermia) was perfused at 37 degrees C before 2 hours of cardioplegic ischemic arrest at 10 degrees C. Group C (cooling) was perfused at 15 degrees C in the unarrested state for 20 minutes before the same cardioplegic arrest conditions as group N. Left ventricular isovolumic pressure measurements, biochemical measurements from right ventricular biopsy specimens, and ventricular necrosis as defined by tetrazolium staining were used to compare the groups at 30 and 60 minutes of normothermic reperfusion. Developed pressure at a constant volume was preserved in group N at 90.7 +/- 4.5 mm Hg versus 76.9 +/- 6.3 in group C after reperfusion (p less than 0.05). Diastolic compliance showed significant deterioration in group C, with marked elevation of diastolic pressure during reperfusion (group N = 6.8 +/- 2.5 mm Hg versus group C = 38.9 +/- 6.1 after reperfusion; p less than 0.001). Adenosine triphosphate levels were significantly higher in group N both at end-ischemia and after reperfusion versus group C (group N = 17.0 +/- 1.1 nmol/mg protein versus group C = 7.7 +/- 1.0 after reperfusion; p less than 0.001). Group N had 0.4% +/- 0.4% necrosis of ventricular mass versus 19.3% +/- 2.2% with prearrest cooling in group C (p less than 0.0001). These results indicate that, when combined with cardioplegic ischemic arrest, rapid myocardial cooling in the unarrested state results in significant damage. The mechanism may be related to the cytosolic calcium loading effect of hypothermia that is not relieved during the subsequent period of cardioplegic arrest. Although hypothermia is an essential component to ischemic preservation, rapid cooling contracture can adversely influence cardioplegic myocardial protection.

Animals↗

PubMed1989

Asanguineous reperfusion in a canine model of cardiopulmonary bypass and controlled postischemic work.

This study was designed to test the hypothesis that asanguineous reperfusion with a standard crystalloid cardioplegic solution results in improved myocardial salvage after a period of global ischemia. Four groups of 6 dogs each were placed on cardiopulmonary bypass. Control group A (work only) performed two hours of controlled work by contracting against a saline-filled left intraventricular balloon. Control group B (ischemia only) underwent 45 minutes of global normothermic ischemia before simple blood reperfusion while supported on bypass. Groups C and D were subjected to ischemia and reperfusion as in group B, followed by controlled work stress as in group A. Group D, however, received 500 mL of St. Thomas' Hospital solution immediately before blood reperfusion. Morphological analysis showed no significant injury in groups A and B, whereas group C had 11.4% +/- 2.4% necrosis of heart mass versus 2.5% +/- 1.1% in group D (p less than 0.001). Biochemical data from left ventricular biopsies showed no significant differences between groups B, C, and D. Functional analyses showed deterioration of diastolic compliance in group C (p less than 0.05), although a significant difference in systolic functional indexes could not be detected. Myocardial protection and salvage was improved by initial reperfusion with an asanguineous cardioplegic solution versus reperfusion with blood alone.

Animals↗

PubMed1988

Loss of the somatosensory evoked response as an indicator of reversible cerebral ischemia during hypothermic, low-flow cardiopulmonary bypass.

We assessed somatosensory evoked response (SSER) as a monitor of cerebral protection during nonpulsatile, hypothermic cardiopulmonary bypass (CPB). In 13 dogs under CPB, extracorporeal flow rate (EFR) thresholds for loss of SSER were determined by stepwise reduction of the EFR from 2.0 to 0.25 L/min/m2 at perfusion temperatures of 35 degrees C, 30 degrees C, 25 degrees C, and 20 degrees C. Testing began at 35 degrees C in Group 1 (N = 6) and at 20 degrees C in Group 2 (N = 7). Immediately on loss of SSER (denoted as a decrease of 80% or more in the amplitude of the somatosensory evoked potentials), EFR was restored to 2.0 L/min/m. Thresholds for loss of SSER ranged between 0.75 and 0.25 L/min/m2. SSER was always restored on return of EFR to 2.0 L/min/m2; thus loss of SSER was a reversible ischemic change. Both groups had similar threshold values at 35 degrees C, but at lower temperatures, Group 1 thresholds were significantly higher than those in Group 2. Since 35 degrees C was the first test temperature for Group 1 but the last for Group 2, EFR reduction at 35 degrees C apparently caused neurophysiological changes (depletion of cortical energy reserves), which diminished subsequent tolerance to ischemia, but EFR reduction at 20 degrees C did not. Our findings show that loss of SSER warns of reversible cerebral ischemia, and support SSER monitoring as a useful measure of cerebral function during low-flow, hypothermic CPB.

Animals↗

PubMed1987

The effect of low-flow cardiopulmonary bypass on cerebral function: an experimental and clinical study.

Systemic flow rates (Q) during nonpulsatile hypothermic cardiopulmonary bypass (CPB) that are consistent with preservation of cerebral function have not to our knowledge been objectively defined. The effect of a sequential reduction in flow rates on cerebral cortical metabolism and function was evaluated in 6 mongrel dogs during hypothermic (25 degrees C) CPB. Cerebral function was assessed using somatosensory cortical evoked potentials (SSEP); cerebral metabolism was assessed by adenosine triphosphate (ATP) and lactate content of snap-frozen gray matter biopsies taken from the hemisphere contralateral to that monitored for SSEP. A progressive decline in ATP levels was observed during flow reduction with virtually complete depletion of ATP at 0.25 L min-1 m-2(p = .0003). The significant (p = .028) dependence of cortical ATP levels on perfusion pressure was no longer evident after adjusting for the effects of flow rate. Lactate levels increased during flow reduction (p = .028), especially at flow rates less than 0.5 L min-1 m-2. Somatosensory neural transmission remained intact until flow was reduced to 0.25 L min-1 m-2 in 5 animals and until total circulatory arrest in 1, at which time loss of the signal occurred. In addition, 5 patients were subjected to brief periods of low-flow CPB (Q = 1.0 L min-1 m-2) at 21 degrees to 25 degrees C. SSEPs remained intact during flow reduction, and postoperative neurologic evaluation was normal in all patients. We conclude that, in the absence of cerebral vascular disease, the flow rate threshold for incurring functional cerebral injury during hypothermic (25 degrees C) nonpulsatile CPB is less than 1.0 L min-1 m-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1985

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↗

PubMedDate not supplied

Effects of hyperkalemia on neonatal endothelium and smooth muscle.

BACKGROUND: Contradictory results have been reported regarding the effect of hyperkalemic cardioplegic or organ preservation solutions on endothelial and smooth muscle cells. The present study was designed to determine the effects of potassium concentrations and exposure times to hyperkalemia on endothelium-derived relaxing factor (nitric oxide) biosynthesis and release, and smooth muscle function in neonatal vessels. METHODS: Aortic rings taken from neonatal rabbits were studied in organ baths at physiologic pressure. The effect of Krebs' solution containing 5, 25, 50, or 100 mmol/L potassium incubated for 45 minutes (group 1), St. Thomas' Hospital cardioplegic solution containing 16, 25, 50, or 100 mmol/L potassium for 45 minutes (group 2), and Krebs' solution containing 5 and 50 mmol/L potassium or St. Thomas' Hospital cardioplegic solution containing 16 and 50 mmol/L potassium for 135 minutes (group 3) or 270 minutes (groups 4 and 5) was examined. The rings were then washed and contracted with U46619 (30 nmol/L). The ability to release endothelium-derived relaxing factor (nitric oxide) in response to acetylcholine was tested. RESULTS: The maximal relaxation induced by acetylcholine did not decrease in any group. Evidence of slight alteration of smooth muscle contraction was seen only in the rings incubated in Krebs' solution with 50 mmol/L potassium for 270 minutes (group 4) with unchanged maximal contraction and sensitivity to potassium (group 5). CONCLUSIONS: We conclude that after exposure for a limited time (4 1/2 hours), hyperkalemia per se does not significantly alter the function of endothelium to release endothelium-derived relaxing factor (nitric oxide) in response to acetylcholine and only slightly alters the contraction speed of smooth muscle in the neonatal rabbit aorta.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗