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Biomedical subjects

S Levitsky

Publications and source records attributed to S Levitsky.

At least 109 records · Page 6Linked to original sources

Assessment of the intrinsic contractile state within an area of myocardium.

Afterload independent, inotropic state sensitive indices of regional function were sought in 31 canine hearts instrumented with piezoelectric crystals to depict trapezoidal areas in the left anterior descending and circumflex arterial beds. Control and postinterventional end-systolic pressure versus regional length and area relationships and regional stroke work versus end-diastolic length and area relationships were inscribed during incremental volume loading on right heart bypass. Hearts were randomized to undergo afterload variation with phenylephrine infusion, contractility augmentation by calcium chloride, or 20 minutes of ischemia in the region of the left anterior descending artery with 30 minutes of reperfusion. All relationships were linear before and after each intervention (mean r = 0.726 to 0.974). The slopes of each correlation were interpreted to quantify intrinsic regional contractility, and all were afterload insensitive (unaffected by phenylephrine). Regional stroke work versus end-diastolic area and length relationships were depressed 55% and 62%, respectively, after ischemia (p less than 0.001 each), whereas neither end-systolic pressure versus regional area nor regional length was significantly altered. Calcium chloride increased regional stroke work versus area 45% in both arterial beds, but significantly increased the other indices only in the left anterior descending and not the left circumflex region. Unlike previous studies of global contractility, correlation of end-systolic events alone did not reliably discriminate perturbations in regional function. The superiority of regional stroke work versus end-diastolic area may be due to incorporating pressure-area changes during the entire cardiac cycle and obviating variability owing to crystal orientation inexactly parallel to fiber shortening.

Animals↗

Amelioration of postischemic stunning by deferoxamine-blood cardioplegia.

Limitation of oxygen free-radical injury was assessed in canine hearts by sonomicrometrically quantifying regional stroke work (RSW) in areas of myocardium perfused by the left anterior descending (LAD) and left circumflex (LCX) arteries. Volume loading of the left ventricle was performed on modified right-heart bypass before and 30 minutes after 20 minutes of LAD occlusion followed by 60 minutes of global cardioplegic arrest with either blood cardioplegia (group 1), blood cardioplegia with adjuvant deferoxamine (500 mg/l) plus 100 mg infused into the aortic root for 5 minutes after unclamping (group 2), or blood cardioplegia with adjuvant deferoxamine (600 mg/l) with unmodified reperfusion (group 3). Surgical revascularization was modeled by reopening the LAD with the first cardioplegia reinfusion. The slope of the RSW versus preload relation (a load-independent index of contractility) was decreased by a mean amount of 44% in the LAD region of group 1 hearts but was preserved in group 2 and 3 hearts. The slope of the LCX region was preserved in all groups. The use of adjuvant deferoxamine in this model of early surgical reperfusion eliminates measurable postischemic stunning.

Animals↗

Preloading history influences pressure-volume-derived indices of myocardial contractility in the ejecting canine left ventricle.

The dependency of indices of myocardial contractility on the immediate preloading protocol was assessed in 14 pentobarbital anesthetized open-chest dogs. An intracavitary micromanometer and epicardially placed ultrasonic dimension transducers allowed acquisition of dynamic left ventricular pressure-volume relationships while varying preload on right heart bypass. A resting cardiac output of 75 ml/kg/min was either increased twofold or reduced to zero flow over a 20-second interval. Linear regression analysis of the mechanical parameters permitted construction of the end-systolic pressure-volume relationship, rate of pressure rise-end-diastolic volume relationship, and the preload recruitable stroke work relationship. The slopes of the end-systolic pressure-volume relationship and rate of pressure rate-end-diastolic volume relationship were significantly higher when measured during volume depletion than during volume expansion (17.2 +/- 1.3 versus 8.5 +/- 0.8 mm Hg/ml and 205 +/- 14 versus 126 +/- 11 mm Hg/sec/ml, p less than 0.001, respectively). This finding was also evident when data analysis was confined to the initial 10 seconds of the loading interval. Nonlinear regression analysis of pooled data from both preloading protocols revealed curvilinear characteristics for each relationship. In contrast, the slope of the preload recruitable stroke work relationship was lower as a result of volume unloading (16.8 +/- 2.0 versus 22.8 +/- 1.7 mJ/beat/100 gm left ventricle/ml, p less than 0.01) and was independent of loading protocol when data analysis was confined to the initial 10-second acquisition period. Furthermore, second-order regression analysis of the pooled data showed no curvilinearity. These findings emphasize the importance of both the timing and method of varying cardiac preload in the determination of intrinsic myocardial contractility and suggest that the preload recruitable stroke work relationship may be a more linear contractile index that is less affected by preloading history over brief intervals.

Animals↗

The conundrum of the effect of beta-blockade on myocardial oxygen consumption.

The effect of propranolol on myocardial oxygen consumption was studied in in situ canine hearts. In 12 afterload independent isovolumic hearts propranolol increased MVO2 an average of 19 +/- 3% (P less than 0.01) for all peaked developed pressure intervals from 75 to 175 mm Hg, secondary to increased wall stress. In 10 hearts instrumented for computer acquisition of pressure-volume workloops during progressive volume loading on right heart bypass, propranolol decreased preload recruitable stroke work an average of 36% (P less than 0.05). However, propranolol failed to decrease the amount of oxygen consumed for basal metabolism or external mechanical work when MVO2 is indexed for heart rate, heart weight, and stroke work. Therefore, propranolol does not decrease MVO2 for individual contractions and does not affect the energy requirements for basal metabolism, excitation-contraction coupling, and heat generation, in contrast to results obtained with beta agonists.

Adrenergic beta-Antagonists↗

Effect of cardiopulmonary bypass on vancomycin and netilmicin disposition.

The effect of cardiopulmonary bypass (CPB) on the disposition of vancomycin (15 mg/kg) and of netilmicin (3 mg/kg) was studied in 10 adults. The concentration-time profile of the drug in serum and renal clearance were characterized pre-CPB, during CPB, and post-CPB. Vancomycin and netilmicin exhibited initial decreases in mean concentrations in serum of 4.0 mg/liter (16.8%) and 2.2 mg/liter (29.1%), respectively, upon initiation of CPB. Netilmicin concentrations in serum rebounded to a mean of 0.6 mg/liter (15.4%) within 90 min on CPB and then continuously decreased. Vancomycin concentrations in serum demonstrated a rebound increase of 2.3 mg/liter (23.5%) at the end of CPB when the aorta was unclamped. Mean renal clearance throughout CPB was decreased for vancomycin (58.4 to 43.4 ml/min per m2) and netilmicin (53.4 to 31.5 ml/min per m2). The rebound in vancomycin concentration in serum strongly correlated with the length of time between unclamping the aorta and coming off CPB (r = 0.94), as well as with the increase in temperature upon rewarming (r = 0.92).

Adult↗

Pulmonary hypertension from chronic pulmonary thromboembolism.

Pulmonary hypertension may develop whenever chronic obstruction of pulmonary arterial blood flow occurs. Although repeated pulmonary embolism is thought to be the usual underlying cause, there is little clinical evidence to support this theory. Studies of the pulmonary vascular endothelium have shown that perturbations of the normal endothelium can create a procoagulant environment, which could lead to the development of thrombosis in situ at the level of the large or smaller pulmonary vessels. Some patients develop proximal pulmonary thromboemboli, which may be the result of retrograde propagation of thrombus after an initial pulmonary embolus. Others present with unexplained pulmonary hypertension secondary to thrombotic occlusion of the pulmonary microvasculature. A perfusion lung scan will show abnormalities that should lead to correct clinical diagnosis and confirmatory evaluation. Thromboendarterectomy in selected cases provides dramatic clinical improvement in patients with proximal thromboemboli. Vasodilators may be effective in some patients with obstruction at the arteriolar level. Both groups should be treated with chronic warfarin anticoagulant therapy to protect against progression of thromboembolism.

Angiography↗

Developmental changes in reperfusion injury. Comparison of intracellular ion accumulation in ischemic and cardioplegic arrest.

Developmental differences in ischemic and potassium cardioplegic arrest were evaluated in newborn (birth to 7 day old) and adult (6 to 12 month old) New Zealand white rabbit hearts isolated and perfused by Langendorff's method. An extracellular space washout technique was used to measure intracellular sodium and calcium in the two age groups after ischemia alone, after normothermic and hypothermic cardioplegia, and after cardioplegia with reperfusion. Although the intracellular ionic contents of nonreperfused adult hearts after 30 and 40 minutes of ischemia were identical, there was a twofold elevation in intracellular sodium level after 40 minutes of ischemia in the newborn hearts. Adult hearts arrested by normothermic potassium cardioplegia demonstrated no alteration in the intracellular ionic content, whereas in the newborn hearts, potassium cardioplegia produced excess intracellular calcium loading before reperfusion, which was greater than that occurring with ischemia alone. When hypothermia (12 degrees C) was combined with cardioplegic arrest, a prereperfusion influx of sodium and calcium was not observed in the newborn hearts, and ionic reperfusion injury was blunted in both newborn and adult hearts. These studies demonstrate that the newborn heart is more susceptible than the adult to both ischemia and cardioplegia. This may be due to age-dependent differences in transmembrane passive diffusion, sodium/calcium exchange, or calcium slow channel properties and suggests alternative myocardial protective strategies for the newborn infant.

Aging↗

Correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting heart. Effect of unprotected and protected global ischemia.

Previous studies noted augmented postischemic myocardial oxygen consumption as a subtle indicator of ischemic injury in the isovolumically contracting left ventricle. The present study was done to determine if the linear relationship between oxygen utilization and stroke work present in the ejecting heart would facilitate compartmentalization of this increased oxygen consumption into resting and working metabolic demands. Therefore, 18 canine hearts instructed for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during incremental volume infusion while undergoing right heart bypass. Data acquisition before and after either 20 minutes of 37 degrees C global ischemia or 2 hours of 20 degrees C cardioplegic arrest allowed construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least squares regression analysis. Although contractility was depressed 48% (p less than 0.01) after unprotected ischemia and was unchanged after cardioplegic arrest, neither group demonstrated a change in the efficiency of converting consumed oxygen to external mechanical work. In contrast, in both groups the oxygen utilization for unloaded contraction was comparably augmented by 21% and 16% (p less than 0.05), despite the varying ischemic conditions and disparate preservation of contractile function. These data suggest a highly linear correlation between oxygen consumption and external mechanical work that persists after ischemia and discriminates the components of postischemic energetic derangements. This model may be useful in the development and assessment of specific myoprotective strategies.

Animals↗

Electrophysiologic drug testing in symptomatic ventricular arrhythmias after repair of tetralogy of Fallot.

Nine patients with symptomatic ventricular arrhythmias were evaluated a mean interval of 16 years after surgical repair of tetralogy of Fallot. The clinical arrhythmia was sustained ventricular tachycardia (VT) in 4 patients (group I) and premature ventricular contractions in 5 (group II). All patients underwent cardiac catheterization and electrophysiologic studies. Ventricular tachycardia was induced at electrophysiologic study in all patients in group I and in 3 patients in group II. Six patients with inducible sustained monomorphic VT underwent chronic drug testing based on electrophysiologic study. A mean of 3.3 drugs per patient was tested. Patients with right ventricular systolic hypertension did not respond to any drug tested, and underwent surgery. Five patients received drug treatment based on the results of electrophysiologic study. During a mean follow-up period of 2.2 years, no patient in either group had recurrent episodes of VT or syncope. In the postoperative patient with tetralogy of Fallot with symptomatic ventricular arrhythmias, it is concluded that electrophysiologic study is useful in reproducing clinical episodes of VT and in selecting effective antiarrhythmic medication; a small number of patients with ventricular premature complexes alone will have inducible sustained VT during electrophysiologic study; prognosis of these patients may be improved by treatment that results in prevention of VT induction; and in patients with right ventricular hypertension, VT is likely to be refractory to drug treatment.

Adolescent↗

Outcome of coronary artery bypass grafting in black persons.

Relatively little attention has been given to coronary artery disease in black persons in the United States. During 31 months, 73 consecutive black patients drawn from an urban working class inner city population who had undergone coronary artery bypass grafting were studied. In the total series of elective and emergency operations, 3 patients (4%) died within the first 30 days and 3 more died by the end of the first year of follow-up. Functional capacity was assessed by interviews and a questionnaire in a subset (n = 39) at least 6 months after operation. Although 79% of the patients felt that the operation had resulted in improvement of symptoms, half of them continued to report angina. Only one-third of the patients were working in the period immediately before the operation; 13% were working postoperatively. Coronary artery bypass grafting had an acceptable mortality risk in these patients, although the functional outcome was disappointing.

Adult↗

Reconstruction of infected median sternotomy wounds.

Infected median sternotomy represents a major complication of cardiac surgery, with significant morbidity and mortality. The treatment of choice is immediate drainage and closure over suction irrigation catheters. However, when this conservative approach fails or radical debridement makes primary closure impossible, muscle flap closure is indicated. This form of reconstruction facilitates the obliteration of large mediastinal wounds; prevents spreading of infection on the heart, suture lines, grafts, or prosthetic material; and significantly decreases morbidity and mortality. We performed muscle flap closure in 11 consecutive patients in whom conservative treatment of infected median sternotomy wounds failed. All patients required closure with at least two muscle flaps or omentum for the complete obliteration of the mediastinal wounds. There was one postoperative death in our series due to acute heart failure. There were two superficial skin losses requiring skin grafting and one persistent draining sinus after reconstruction. Based on our experience and that of others, we conclude that muscle flap reconstruction should be considered as an important technique for the reconstruction of infected median sternotomy wounds.

Cardiac Surgical Procedures↗

Intracellular sodium and calcium in the postischemic myocardium.

Intracellular sodium and calcium were measured in 30 isolated perfused rat hearts exposed to normothermic ischemic intervals varying from 0 to 40 minutes followed by 35 minutes of reperfusion. Accumulation of these elements was correlated with alterations in postischemic isovolumic contractile function. There were increases in calcium of 207%, 390%, and 681% of the non-ischemic control following reperfusion after respective ischemic intervals of 30, 35, and 40 minutes. These corresponded to decrements in peak developed pressure of 23.8% after 30 minutes, 68.6% after 35 minutes, and no recovery of function after 40 minutes of ischemia. Thirty-five and 40 minutes of ischemia produced 138% and 170% increases in intracellular sodium, respectively. These data show that there is a graded accumulation of intracellular sodium and calcium that correlates with the duration of ischemia and the degree of functional impairment in the postischemic heart. Measurement of intracellular sodium and calcium may, therefore, serve as an adjunct to other biochemical and functional factors used to quantitate postischemic and postcardioplegic damage in the development of new myoprotective regimens.

Animals↗

Developmental changes in reperfusion injury. A comparison of intracellular cation accumulation in the newborn, neonatal, and adult heart.

Intracellular sodium and calcium accumulation were measured after 30 and 40 minutes of ischemia and 30 minutes of reperfusion in newborn (0 to 7 day), neonatal, (14 to 21 day), and adult (4 to 6 month) New Zealand white rabbit heart preparations. Newborn hearts showed twofold and threefold elevations of calcium when exposed to 30 and 40 minutes of ischemia and reperfusion, respectively, whereas sodium increase was noted only in the 40 minute group. Conversely, adult hearts exhibited sodium elevation if exposed to ischemia for 30 minutes and calcium accumulation occurred only after 40 minutes of ischemia. There was no significant alteration in intracellular sodium and calcium levels after ischemic intervals of 30 and 40 minutes in the neonate. These studies demonstrate that the immature newborn heart is the most susceptible and the neonatal heart is the least susceptible to injury sustained by ischemia followed by reperfusion. These differences in susceptibility to ischemia may be due to age-dependent alterations of intramembrane ionic pumps and channels.

Age Factors↗

Correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting heart. Afterload independence and sensitivity to inotropic state.

Previous studies suggest that the relationship between end-diastolic volume and stroke work calculated as the area of the pressure-volume work loop is linear, afterload independent, and sensitive to the inotropic state. The correlation of myocardial oxygen consumption with this stroke work could provide an integrated measure of cardiac performance and metabolism to assess perturbations induced by ischemia or pathologic loading conditions. Fourteen canine hearts instrumented for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during progressive volume infusion on right heart bypass (1.5 to 3.5 L/min in 250 ml/min increments). Data acquisition both in the control state and during continuous infusion of calcium chloride (0.03 mEq/kg/min, n = 7) to increase contractility or phenylephrine (2 micrograms/kg/min, n = 7) to alter afterload facilitated the construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least-squares regression analysis. The cardiac mechanics assessment for this group of dogs confirmed a highly linear (mean r = 0.984) work versus preload relationship that was unaffected by changes in afterload but sensitive to increased contractility (71% increase in slope). The myocardial energetics correlation was also linear (mean r = 0.939) and demonstrated an increased oxygen utilization characteristic of the higher inotropic state produced by calcium chloride infusion (0.047 +/- 0.003 versus 0.070 +/- 0.008 ml oxygen/beat/100 gm left ventricular weight, p = 0.008). Although phenylephrine administration produced variable perturbations of myocardial oxygen consumption, the energetics relationship for this subgroup was not statistically altered by changes in afterload. The features of this cardiac energetics assessment suggest its value as a biological marker to evaluate the postischemic, hypertrophied, or failing heart.

Animals↗