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Biomedical subjects

S Levitsky

Publications and source records attributed to S Levitsky.

At least 73 records · Page 4Linked to original sources
PubMed1994

Fura 2 determination of [Ca2+]i in isolated perfused heart using R wave-gated electromechanical shutters.

We describe a novel and relatively inexpensive spectrofluorescence system that supplies rapidly alternating wavelengths to either a standard cuvette or an isolated perfused heart. Its use is illustrated by determining changes in cytosolic intracellular Ca2+ concentration ([Ca2+]i) by using the Ca(2+)-sensitive fluorescent dye fura 2 in a rabbit heart preparation. The system uses two precision electromechanical shutters (capable of gating with respect to the electrocardiographic R wave for signal averaging) allowing alternate fura 2 excitation wavelengths (340 and 380 nm) without moving optical components and uses a fiber optic for conducting excitation and collecting epifluorescence. Sample recordings tracing the [Ca2+]i transient in an entire cardiac cycle and in capturing specific isolated regions (diastole and systole) of the cycle are presented. Limitations of this low-cost but easily implemented system are discussed.

Animals↗
PubMed1994

Right ventricular volume overload results in depression of left ventricular ejection fraction. Implications for the surgical management of tricuspid valve disease.

BACKGROUND: Right ventricular volume overload (RVVO) occurring in conditions such as Ebstein's anomaly may result in depression of left ventricular ejection fraction (LVEF). This study tests this hypothesis by measuring LVEF in 10 patients with RVVO due to tricuspid valve resection for isolated tricuspid valve endocarditis and in 10 age-matched healthy persons. METHODS AND RESULTS: When the modified Simpson's rule was applied to echocardiographic images, LVEF for patients with RVVO measured significantly lower than for age-matched healthy subjects (51 +/- 4% versus 60 +/- 4%, P < .0001). Depression of LVEF does not result simply from reduced venous return to the left ventricle, since left ventricular end-diastolic volume was not significantly different between patients with RVVO and age-matched healthy persons (84 +/- 26 versus 77 +/- 20 mL, NS). Possible explanations for the depression in LVEF may relate to the decreased relative contribution of left atrial systole to left ventricular filling (demonstrated by transmitral pulsed Doppler) or to the mechanical effects of ventricular septal paradox (demonstrated by the abnormal leftward ventricular septal flattening and increase in short-axis cavity eccentricity at end diastole, which returns to normal at end systole) in patients with RVVO. CONCLUSIONS: These findings suggest that surgical excision of the tricuspid valve results in isolated RVVO, which creates not only diastolic overload of the right heart but also depression of LVEF.

Adult↗
PubMed1994

Heat-shock protein 70 mRNA is induced by anaerobic metabolism in rat hearts.

BACKGROUND: Both heat-shock protein (HSP) 70 and its mRNA are induced in the ischemic myocardium. The inductor stimuli are, however, not known. Stretch and ischemic metabolic alterations are the two most likely HSP70 inductors. METHODS AND RESULTS: To assess whether anaerobic metabolism induces HSP70 mRNA expression, 61 rat hearts were perfused with Krebs-Henseleit buffer (37 degrees C) in a modified Langendorff apparatus built for rapid switching between pressure-controlled and flow-controlled perfusions. Each heart was initially perfused for 30 minutes at a constant perfusion pressure of 65 mm Hg. Subsequently, separate hearts were perfused at a constant flow of 8, 6, 4, 2, 1, 0.5, or 0 mL/min for 30 minutes using a nonpulsatile pump (n = 5, each perfusion level). Hemodynamic measurements demonstrated a linear correlation between coronary flow and both perfusion pressure and developed pressure (r = .94 and r = .89, respectively; P < .0001 for both comparisons). Diastolic pressure at the end of the perfusions increased only in globally ischemic hearts (34 +/- 3 mm Hg at 0 mL/min versus 5 +/- 1 mm Hg at 8 mL/min; mean +/- SEM, P < .05). The highest lactate release during the 30-minute constant-flow period was observed at a flow level of 4 mL/min (177 +/- 1 versus 71 +/- 8 mumol at 8 mL/min). Creatine kinase release was detected at 2 mL/min (28 +/- 8 mU/mL after 25 minutes of constant flow versus < 8 mU/mL at 4 mL/min). The highest flow level showing cessation of mechanical activity despite pacing of the hearts was at 2 mL/min (2 of 5 hearts). An increased level of HSP70 mRNA expression was found only at 4 mL/min (10-fold increase). Blocking lactate production by substituting glucose with 2-deoxyglucose in the perfusion buffer reduced the HSP70 mRNA level by 44% at 4 mL/min. No increase of HSP/70 was detected (Western blots) at any flow level. CONCLUSIONS: These results indicate that anaerobic metabolism is a strong stimulus for HSP70 transcription and that cessation of anaerobic metabolism in severe ischemia is associated with a shutdown of HSP70 mRNA expression.

Anaerobiosis↗
PubMed1993

Myocardial protection and cardioplegia.

Over the past year there has been a tremendous enthusiasm for the novel technique of warm heart surgery. In contradistinction to hypothermic myocardial preservation, warm cardiac surgery provides for operative repair in a nonischemic heart. Warm cardioplegia can be administered in an antegrade or retrograde manner, continuously, and perhaps even intermittently. It may have beneficial effects on systemic perfusion and may be a useful adjunct in the setting of acute cardiac ischemia. There likewise has been a burgeoning enthusiasm for the retrograde cardioplegic delivery route. Many reviews of clinical work using both warm and cold retrograde cardioplegia have identified the advantage of this technique, particularly in the setting of valve replacement and reoperation for coronary revascularization. Finally, new avenues of investigation in ischemia and reperfusion including inquiry into the role of neutrophils in reperfusion injury and modification of the reduced thiol pool to modulate the postischemic burst of oxygen-free radical production.

Cardiac Surgical Procedures↗
PubMed1993

Pharmacokinetics of intravenous vancomycin in pediatric cardiopulmonary bypass surgery.

The purposes of this investigation were to characterize the disposition of vancomycin in children undergoing cardiopulmonary bypass (CPB) surgery and to determine whether a 15-mg/kg intravenous dose provides adequate serum concentrations during and after CPB. Six children (age range, 0.8 to 4.8 years) received intravenous vancomycin 15 mg/kg 1 to 2 hours before CPB surgery. Serial blood samples (mean, 10/patient) were collected before, during and after CPB surgery. The mean (+/- SD) vancomycin concentrations at the end of the infusion and 5 hours after the infusion were 27.3 +/- 5.7 and 5.9 +/- 3.0 mg/liter, respectively. The initiation of CPB resulted in an abrupt decrease (44.5%) in serum vancomycin concentrations; however, concentrations remained constant (range, 6.2 to 14.1 mg/liter) throughout the rest of the CPB procedure. The mean (+/- SD) values for the apparent volume of distribution, total body clearance and elimination half-life were 0.59 +/- 0.15 liter/kg, 2.94 +/- 0.93 ml/min/kg and 2.4 +/- 0.8 hours, respectively. These values were similar to those reported in the literature for children not undergoing CPB surgery. A single vancomycin dose of 15 mg/kg before pediatric CPB surgery provides serum concentrations greater than 5 mg/liter throughout the duration of the CPB procedure. To sustain these concentrations subsequent dosing of vancomycin is necessary within 6 hours after the initial vancomycin dose.

Cardiopulmonary Bypass↗
PubMed1993

Effects of cardiopulmonary bypass surgery on intravenous ciprofloxacin disposition.

The pharmacokinetic parameters of intravenous ciprofloxacin were examined in five adult male patients on three separate occasions of open heart surgery: the 24 h before cardiopulmonary bypass (CPB) surgery, (PRE), during surgery (SURG), and 48 to 72 h after surgery (POST). Serial blood (n = 16), urine, and SURG tissue samples were collected after intravenous administration of a single 300-mg dose of ciprofloxacin during each study period. All samples were assayed for ciprofloxacin by a specific high-performance liquid chromatographic method. Serum ciprofloxacin concentrations remained constant or continued to decline during the course of CPB surgery. A significant (P < 0.05) decrease in total body clearance was observed during the SURG and POST phases (298 and 306 ml/min/1.73 m2, respectively) compared with that during the PRE phase (364 ml/min/1.73 m2). Renal clearances and elimination half-lives were similar during all three study phases. A nonsignificant decline occurred in the apparent volume of distribution, from mean values of 2.1 and 2.0 liters/kg during the PRE and POST phases, respectively, to 1.7 liters/kg during the SURG phase. The mediastinal fat tissue ciprofloxacin concentrations ranged from 0.45 to 2.89 micrograms/g. Overall, little significant difference was noted in the disposition of intravenous ciprofloxacin during CPB surgery compared with that before and after surgery.

Adipose Tissue↗
PubMed1993

Redistribution of myocardial calcium during ischemia. Relationship to onset of contracture.

Cytosolic calcium accumulation has been proposed as a mediator for the pathologic changes that occur during myocardial ischemia. Whether the rise in cytosolic calcium is a result of influx or redistribution from internal stores has not been elucidated. Isolated retroperfused rabbit hearts were subjected to ischemia at 37 degrees C. The distribution of calcium between cytosol and internal membrane stores and the relationship between cytosolic calcium and the onset of left ventricular contracture were investigated. One group of hearts was loaded with the fluorescent calcium probe Fura 2-AM to measure cytosolic calcium and a second group with chlortetracycline to indicate changes in membrane-bound calcium. After the onset of ischemia there is a rise in cytosolic calcium, at least in part attributable to redistribution of calcium from intraorganellar sites to cytosol. The release of membrane-bound calcium and rise in cytosolic calcium preceded the onset of irreversible ischemic injury, that is, contracture.

Animals↗
PubMed1993

Recovery of postischemic contractile function is depressed by antegrade warm continuous blood cardioplegia.

To assess the effectiveness of warm antegrade continuous blood cardioplegia in the setting of an acute coronary arterial occlusion, we instrumented 19 Yorkshire swine to quantitate left ventricular global, systolic, diastolic, and regional mechanics. Data were acquired before and after 10 minutes of mid-left anterior descending coronary artery occlusion followed by 60 minutes of aortic crossclamping. Cardiac arrest was induced by the antegrade infusion of 20 ml/kg of warm (37 degrees C) or cold (4 degrees C) oxygenated blood cardioplegic solution followed by either continuous warm (75 ml/min, n = 9) or intermittent cold (10 ml/kg every 20 minutes, n = 10) cardioplegic reinfusions. Left anterior descending coronary artery occlusion was released 20 minutes after aortic crossclamping and resulted in warm-arrested hearts developing a 139% increase in global oxygen consumption compared with values obtained with the left anterior descending coronary artery occluded (p < 0.02). Recovery of global left ventricle contractility, quantitated by the linear preload recruitable stroke-work relationship, was significantly worse after warm cardioplegia (52.4% +/- 5.1% versus 68.0% +/- 5.9%, warm versus cold, p < 0.05). Similarly, left anterior descending coronary artery regional ischemic zone contractility recovered 34.5% +/- 7.3% of control function with cold cardioplegia, whereas warm cardioplegia resulted in -11.36% +/- 7.46% functional recovery indicative of dyssynchronous contraction (p < 0.05). Diastolic compliance, calculated with an exponential end-diastolic pressure-versus-volume relationship, was not changed postischemically in either group. These data suggest that warm antegrade blood cardioplegia may potentiate acute ischemic injury and provide inadequate myocardial protection.

Animals↗
PubMed1992

Doppler echocardiographic demonstration of the differential effects of right ventricular pressure and volume overload on left ventricular geometry and filling.

To compare the effects of isolated right ventricular pressure and volume overload on left ventricular diastolic geometry and filling, 11 patients with primary pulmonary hypertension, 11 patients with severe tricuspid regurgitation due to tricuspid valve resection and 11 normal subjects were studied with use of Doppler echocardiographic techniques. Right ventricular systolic overload in primary pulmonary hypertension resulted in substantial leftward ventricular septal shift that was most marked at end-systole and early diastole and decreased substantially by end-diastole. Right ventricular diastolic overload after tricuspid valve resection resulted in maximal leftward ventricular septal shift at end-diastole sparing end-systole and early diastole. The early diastolic distortion of left ventricular geometry associated with right ventricular pressure overload resulted in prolongation of isovolumetric relaxation of the left ventricle (129 +/- 39 ms) and a reduction in early diastolic filling compared with values in normal subjects. Late diastolic distortion of left ventricular geometry associated with right ventricular volume overload had no influence on the duration of left ventricular isovolumetric relaxation (52 +/- 32 ms) but caused a reduction in the atrial systolic contribution to late diastolic filling of the left ventricle compared with values in normal subjects. In patients with right ventricular pressure overload, 52 +/- 16% of left ventricular filling occurred in early diastole compared with 78 +/- 11% in patients with right ventricular volume overload (p less than 0.001). The differential effects of systolic and diastolic right ventricular overload on the pattern of left ventricular filling appear to be related to the timing of leftward ventricular septal displacement.

Adult↗
PubMed1992

Preoperative risk factors that predict hospital length of stay in coronary artery bypass patients > 60 years old.

BACKGROUND: The ability to predict prolonged length of stay (LOS) is essential to control escalating hospital costs. Operative mortality is a poor predictor of LOS; morbidity as defined by hospitalization for > 14 days after coronary artery bypass graft surgery (CABG), appears to be responsible for increasing costs. The purpose of this study was to measure preoperative predictive indicators of increased LOS with an eventual plan to offer alternative cost-benefit therapeutic options. METHODS AND RESULTS: Nine hundred twenty-four consecutive patients (age, 60-86 years) undergoing CABG were retrospectively studied by means of the Cox proportional hazards model. Seventeen variables, excluding death, were analyzed and quantified as to importance, and point totals were calculated for each patient. Scores were 12 for congestive heart failure and intra-aortic balloon assist device; 10, creatinine > 2; 6, intra-aortic balloon assist device only; 5, congestive heart failure only; 3, obesity; 6, age > 75 years; 3, age 70-75 years; and 2, 65-69 years. CONCLUSIONS: Increasing index score directly correlated with an exponential increase in LOS. These data substantiate the hypothesis that a mathematical model can predict LOS in CABG patients and may offer rational alternative strategies in delivering cost-effective health care.

Age Factors↗
PubMed1992

Effect of aging on intracellular Ca2+, pHi, and contractility during ischemia and reperfusion.

BACKGROUND: To investigate the effect of aging on myocardial ischemic and reperfusion injury, cytosolic calcium (Ca2+), intracellular pH (pHi), and mechanical performance were measured in isolated perfused rabbit hearts. METHODS AND RESULTS: Hearts of mature (4-5-month-old) and aged (28-38-month-old) rabbits were loaded with 10 microM of fura-2 or 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and subjected to 30 minutes of normothermic ischemia and reperfusion. Cytosolic Ca2+ levels ([Ca2+]) during the nonbeating ischemic period and end-diastolic Ca2+ levels ([EDCa2+]) during reperfusion were determined from the fura-2 fluorescence ratio of emission at 510 nm during excitation at 340 and 380 nm. pHi was obtained from the ratio of emission at 530 nm during excitation at 450 and 490 nm. [Ca2+] of the mature group (n = 8) increased from 188 +/- 19 nM (mean +/- SEM) to 373 +/- 32 nM during ischemia, and that of the aged group (n = 7) increased from 242 +/- 17 to 465 +/- 20 nM. The rise of [Ca2+] of the aged group was significantly greater (p < 0.05) than that of the mature group. Immediately after reperfusion, [EDCa2+] in both groups returned to the preischemic level. pHi decreased to the same extent (from 7.2 to 6.7) during ischemia and returned to preischemic values during reperfusion. The mature group recovered 84 +/- 3% of left ventricular peak pressure after ischemia, whereas the aged group recovered only 55 +/- 3% (p < 0.005). Functional recovery was inversely correlated to the increase of [Ca2+] during ischemia (r = 0.66). CONCLUSIONS: Aged hearts exhibit greater accumulation of [Ca2+] during ischemia and less functional recovery after ischemia than mature hearts. The greater rise of [Ca2+] in aged hearts is not a result of the difference of buffering capacity for ischemia-induced acidosis.

Aging↗
PubMed1992

Retrograde is superior to antegrade continuous warm blood cardioplegia for acute cardiac ischemia.

BACKGROUND: Theoretically, the efficacy of continuous warm blood cardioplegia may be improved when administered retrogradely (RCWBC) rather than antegradely (ACWBC) in the setting of acute regional ischemia because of enhanced oxygen and substrate delivery to myocardial tissue distal to an acute coronary artery occlusion. METHODS AND RESULTS: Eighteen Yorkshire swine were instrumented for quantification of global left ventricular systolic, diastolic, and regional left anterior descending coronary artery (LAD) zone mechanics before and after 10 minutes of mid-LAD occlusion, followed by 60 minutes of cardiac arrest using continuous warm blood cardioplegia. Initially, 20 ml/kg of 37 degrees C oxygenated blood cardioplegia (hematocrit, 22 +/- 0.6%) was infused antegradely, followed by maintenance of 75 ml/min ACWBC (n = 9) or 60-100 ml/min of RCWBC (n = 9). LAD occlusion was released 20 minutes after cardiac arrest (30 minutes total LAD ischemia), simulating surgical revascularization. Postischemic recovery of global preload recruitable stroke work was nearly complete with RCWBC but significantly depressed with ACWBC (84.9 +/- 9.5% versus 52.4 +/- 5.1%, respectively; p < 0.01). LAD regional stroke work was also well preserved postischemically with RCWBC but showed no functional recovery and systolic bulging after ACWBC (87.4 +/- 13.7% versus -11.36 +/- 7.46% of control values; p < 0.01). Global diastolic stiffness calculated using the beta-coefficient of an exponential end-diastolic pressure-versus-volume relation was unchanged with ACWBC but increased significantly after RCWBC (from 0.027 +/- 0.002 to 0.028 +/- 0.003 mm Hg/ml and from 0.028 +/- 0.003 to 0.036 +/- 0.004 mm Hg/ml, respectively). CONCLUSIONS: These data suggest that with acute regional ischemia, both global and ischemic zone regional systolic function are depressed by ACWBC, whereas RCWBC affords adequate protection of contractile performance. However, a loss of diastolic compliance may result as a consequence of warm retrograde delivery.

Animals↗
PubMed1992

Age-related differences in cardiac susceptibility to ischemia/reperfusion injury. Response to deferoxamine.

Age-related differences in susceptibility to ischemia/reperfusion injury and the response to the iron chelator deferoxamine during reperfusion were studied in isolated nonworking rabbit hearts subjected to 30 or 40 minutes of ischemia at 37 degrees C followed by 30 minutes of reperfusion. In the experimental group, hearts received a bolus of deferoxamine just before the moment of reflow, followed by a continuous infusion during the first 10 minutes of reperfusion. Isovolumic systolic (peak developed pressure) and diastolic (diastolic pressure versus balloon volume relationship) function was assessed with an intracavity balloon and incremental volume changes. In separate groups of hearts, adenine nucleotide content (adenosine triphosphate, diphosphate, and monophosphate) was measured before ischemia, at end-ischemia, and 30 minutes after reperfusion. The cardiac function measurements showed that after 30 minutes of ischemia and 30 minutes of reperfusion, peak developed pressure in newborn hearts recovered to 89% +/- 5% of preischemic levels; this recovery was significantly better than that of adult hearts, which exhibited 67% +/- 6% (p less than 0.01) recovery. Deferoxamine significantly improved cardiac function only in adult hearts (p less than 0.01). However, after 40 minutes of ischemia and 30 minutes of reperfusion, peak developed pressure in newborn hearts was reduced to 61% +/- 3% and was not significantly better than that of adult hearts (54% +/- 5%). Deferoxamine significantly improved systolic function in both newborn and adult hearts (p less than 0.01) exposed to 40 minutes of ischemia. Myocardial adenosine triphosphate content fell markedly by the end of 30 and 40 minutes of ischemia in both groups. After 30 minutes of ischemia, newborn but not adult hearts were able to completely recover adenosine triphosphate content by 30 minutes of reperfusion. This advantage was lost after 40 minutes of ischemia. Deferoxamine had no effect on recovery of adenosine triphosphate content in any group. We conclude that (1) newborn hearts recover postischemic function and metabolism faster than adult hearts after shorter periods of ischemia; (2) this advantage is lost as the ischemic period is prolonged; (3) deferoxamine improved postischemic cardiac function after longer ischemic periods, in both age groups, but failed to improve the recovery of myocardial adenosine triphosphate content.

Adenine Nucleotides↗
PubMed1992

Age-dependent sensitivity to unprotected cardiac ischemia: the senescent myocardium.

Six young, sexually mature sheep and seven senescent sheep (aged 0.75 +/- 0.11 years and 7.1 +/- 0.45 years) were instrumented with sonomicrometric crystals and micromanometers to assess global left ventricular mechanics while preload was varied during right heart bypass both before and 30 minutes after 15 minutes of global normothermic ischemia. Left ventricular weight and end-diastolic volume were not significantly different between age groups when indexed to body weight. Contractility was quantitated by the slope of the linear preload-recruitable stroke work relationship and diastolic mechanics by an exponential end-diastolic pressure versus volume function generated over physiologic cardiac workloads. Postischemic systolic functional recovery was markedly worse in the older group (22.7% +/- 10.7% versus 54.2% +/- 9.5%, old versus young, p less than 0.05). However, diastolic stiffness was not changed in either group postischemically. These data demonstrate that the senescent myocardium is less tolerant of ischemia and may require specific intraoperative myocardial management strategies to preserve global pump function.

Aging↗
PubMed1991

Endogenous vasoconstrictor prostanoids: role in serotonin and vasopressin-induced coronary vasoconstriction.

A vasoconstrictor-induced prostacyclin (PGI2) production in a perfused rat heart was found, suggesting a mitigating role of PGI2 on coronary vasoconstriction. Treatment of the heart with cyclooxygenase inhibitors (aspirin or indomethacin) decreased PGI2 production by more than 90% and paradoxically reduced the vasoconstriction response. The attenuating effect of cyclooxygenase blockade suggested that endogenous prostanoids contribute to serotonin-, vasopressin- or U46619-induced vasoconstriction. Two prostaglandin (PG) H2/thromboxane A2 (TXA2) receptor antagonists, i.e., 13-azaprostanoic acid (13-APA) and SQ 29,548 were used to investigate putative endogenous vasoconstrictor prostanoids on the exogenously induced vasoconstriction. Retrogradely perfused (5-6 ml/min) rat hearts were rendered guiescent, yet responsive to stimuli, by local injection of lidocaine to the atrioventricular node. Changes in coronary vascular resistance (i.e., perfusion pressure at constant flow) were monitored and the cardiac effluent was collected for analysis of 6-keto PGF1 alpha (the stable metabolite of PGI2) as well as PGF2 alpha by radioimmunoassay. Three vasoconstrictors, i.e., serotonin, vasopressin and the TXA2/PGH2 analog U46619, as well as authentic PGD2, PGE2 and PGF2 alpha were infused. PGD2, PGE2 and PGF2 alpha exerted a dose-related coronary vasoconstriction, as did U46619, serotonin and vasopressin. Treatment with 13-APA (100 microM) or SQ 29,548 (100 nM) almost abolished U46619-induced vasoconstriction. The addition of PGH2/TXA2 receptor antagonists also significantly reduced the pressor effect of exogenously administered PGs, serotonin and vasopressin, with the exception that SQ 29,548 did not significantly antagonize PGE2-induced vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Valve replacement in patients with endocarditis and cerebral septic emboli.

Cerebral septic emboli complicate the cases in 20% to 40% of patients with left-sided endocarditis but the management of these patients who require a valvar operation remains unclear. From 1980 to 1988, the incidence of cerebral septic embolus was 42% (n = 45) among 106 patients with endocarditis who underwent valve replacement at the University of Illinois Hospital in Chicago. Of these 45 patients, 69% (n = 31) had symptomatic cerebral septic infarctions and 31% (n = 14) were asymptomatic. Findings on cerebral computed tomographic scans included ischemic infarcts (n = 36, 80%), hemorrhagic infarcts (n = 5, 11%), normal studies (n = 2, 4%), and unknown (n = 2, 4%). Neurological complications after valve replacement included postoperative strokes (n = 6, 6%), cerebral abscesses (n = 2, 2%), and seizure (n = 1, 1%). The presence of a hemorrhagic infarct preoperatively predisposed to a perioperative stroke (p less than 0.05). In conclusion, cerebral septic infarctions, both symptomatic and asymptomatic, are common among patients with endocarditis referred for valvar operation. In the absence of a hemorrhagic infarct, valve replacement can be performed with minimal risk of a perioperative stroke.

Adolescent↗