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Biomedical subjects

N A Silverman

Publications and source records attributed to N A Silverman.

At least 55 records · Page 3Linked to original sources
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Repair of right ventricular free wall defect with a pedicled muscle flap.

A unique case of repair of a full-thickness cardiac defect and simultaneous reconstruction of an infected median sternotomy wound is presented. A right ventricular defect, 6 cm in diameter, was closed with a fascia lata graft and reinforced with a rectus abdominis muscle flap. The superior portion of the mediastinum was obliterated with a pectoralis major muscle flap. The patient tolerated the procedure well and remains free of cardiac symptoms seven months postoperatively, with no evidence of residual infection.

Cardiac Surgical Procedures↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

The effect of cardioplegic oxygenation on the correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting postischemic heart.

To ascertain whether oxygenated cardioplegia is beneficial during surgically induced global ischemia, 27 canine hearts underwent sonomicrometric determination of cardiac mechanics and energetics during volume loading on right heart bypass before and after 2 hr of potassium cardioplegic arrest with crystalloid, oxygenated crystalloid, or blood vehicles. The slope of the linear stroke work vs end-diastolic volume relationship, an index of contractility, was preserved by each vehicle. Similarly, oxygen utilization to perform external mechanical work during reperfusion was unaffected in all groups. However, there were significant 119% and 122% increases in basal oxygen utilization after both unoxygenated and oxygenated crystalloid cardioplegia (p less than .05) that were prevented by the blood-based vehicle. These data suggest that the salutary effects of blood cardioplegia on postischemic myocardial energetics may not be solely mediated by its oxygen-carrying capacity.

Animals↗
PubMed1986

Temperature-specific effects of adjuvant diltiazem therapy on myocardial energetics following potassium cardioplegic arrest.

Adjuvant slow calcium channel blockade theoretically minimizes the calcium influx attendant to potassium-induced cardioplegic arrest, particularly if clinically acceptable levels of cardiac hypothermia are not maintained. The present study assessed the efficacy of diltiazem therapy in ameliorating perturbations of myocardial oxygen consumption that could be attributable to postischemic intracellular calcium accumulation. In 30 canine hearts, myocardial oxygen consumption was determined during incremental isovolumic pressure-volume loading before and 30 minutes after 2 hours of either 20 or 28 degrees C potassium cardioplegic arrest. The intracoronary perfusate in randomized hearts was modified by the addition of diltiazem, 150 micrograms/kg. Although systolic performance (as defined by peak developed pressure as compared with balloon volume curves) was unchanged after 20 degrees C ischemia, adjuvant diltiazem therapy prevented the 44 +/- 2% (p less than .01) decrease in peak developed pressure after 28 degrees C arrest. Moreover, the 39% augmentation of postischemic myocardial oxygen consumption at specific peak developed pressure following both 20 and 28 degrees C ischemia was attenuated with diltiazem only after the warmer ischemic interval. This difference was characterized by a larger (35 +/- 2 vs. 26 +/- 2%; p less than .025) decrease in postischemic oxygen extraction despite a comparable hyperemia. These data suggest that adjuvant diltiazem therapy during potassium-induced cardioplegic arrest preserves energy-efficient pump function only after warmer ischemia, thereby limiting the clinical application of this myoprotective regimen.

Animals↗
PubMed1986

Characterization of postischemic myocardial oxygen utilization.

To define the pertubations in myocardial oxygen consumption (MVO2) previously noted after potassium-induced arrest, MVO2 was determined in 19 canine hearts during isovolumetric pressure-volume loading before and serially after 2 hr of cardioplegic ischemia at 20 degrees C. Starling curves were initially unchanged after cardioplegic arrest, but postischemic propranolol (0.2 mg/kg) depressed peak developed pressure 36 +/- 4% and heart rate 24 +/- 1% (p less than .01, for both). MVO2 indexed per beat and for left ventricular weight at defined ranges of peak developed pressure was augmented postischemically by 40% (p less than .05) and this increased oxygen utilization persisted after attenuation of coronary hyperemia, normalization of oxygen extraction, 1 hr of reperfusion, and effective beta-adrenergic-receptor blockade. These data suggest that increased MVO2 to generate physiologic pressures is a sensitive biological marker for cardioplegic efficacy that is independent of coronary flow and oxygen uptake and is not solely attributable to increased beta-adrenergic stimulation.

Animals↗
PubMed1985

Effect of coronary artery occlusion on myocardial protection by retroperfusion of cardioplegic solutions.

Coronary artery stenoses impede delivery of cardioplegic solutions infused through the aortic root. Therefore, the efficacy of retroperfusion of cardioplegic solution through the coronary sinus was assessed in dogs subjected to cold, potassium cardioplegic arrest. Group I (N = 15) had the left anterior descending (LAD) coronary artery occluded throughout ischemia while Group II (N = 15) had a patent LAD. Transmural biopsies of both the left ventricular (LV) apex and right ventricle (RV) were assayed for adenosine triphosphate (ATP) and creatine phosphate (CP). Regional wall temperatures were sequentially monitored. The time from aortic cross-clamping to electrical arrest varied widely, but the mean arrest time of each group was similar (174 +/- 22 vs 175 +/- 28 sec). (table; see text) Comparable depletion of ATP stores (vs preischemia) occurred in each ventricle regardless of coronary artery patency. Similarly, CP stores were depleted 60-72% (P less than 0.01) during ischemia. Mean temperatures during arrest of the RV and LV (17.2-19.5 degrees C) did not differ and were not affected by LAD occlusion. Coronary venous resistance remained constant with repetitive infusions. These data suggest that myocardial protection with coronary sinus retroperfusion is independent of arterial patency, but is suboptimal, perhaps due to the prolonged time needed to induce ventricular arrest.

Adenosine Triphosphate↗
PubMed1985

Effect of carnitine on myocardial function and metabolism following global ischemia.

Carnitine has therapeutic potential for the postischemic heart by facilitating the oxidation of acylated fatty acid metabolites, the intracellular accumulation of which has a deleterious effect on myocardial function and metabolism. To test this hypothesis, two groups of dogs were given preischemic treatment with carnitine, 50 mg per kilogram of body weight (Group 1) or 100 mg/kg (Group 2), and were compared with untreated controls (N = 12 for all groups). The canine hearts underwent 30 minutes of global 37 degrees C ischemic arrest with reperfusion. Left ventricular systolic and diastolic function was assessed by an intracavitary balloon while metabolic derangements were quantitated by serial myocardial biopsies assayed for adenosine triphosphate (ATP). Comparable 49 to 53% (p less than 0.01) declines in preischemic ATP levels occurred during the study period in the controls and both experimental groups. However, postischemic systolic left ventricular function was better preserved in Group 2: these hearts generated 61 +/- 3% of preischemic peak developed pressure compared with 37 +/- 4% in the controls and 42 +/- 3% in Group 1 (p less than 0.01 for each), and 60 +/- 2% of preischemic maximum rate of rise of left ventricular pressure as opposed to 45 +/- 4% in the controls and 49 +/- 6% in Group 1 (p less than 0.02 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1985

The surgeon's role in the treatment of acute myocardial infarction.

Most acute myocardial infarctions are associated with thrombotic occlusion superimposed on a significant coronary arterial atherosclerotic plaque. Restoration of coronary flow can limit ultimate infarct size if accomplished within 4 to 6 hours of the onset of symptoms. Thrombolytic therapy with intracoronary and intravenous streptokinase or by tissue-specific plasminogen activator is effective as a rapid means of reperfusing infarcting myocardium. Percutaneous coronary angioplasty and surgically constructed bypass grafts can convert a tenuous source of coronary flow to reliable, unrestricted myocardial perfusion. Although acute surgical revascularization can be performed during an evolving infarction, the time restraints imposed by ischemic cellular injury dictate that bypass grafting serve as an adjunct to thrombolytic therapy as a means of preventing rethrombosis and providing global as well as regional revascularization. The vast potential benefit for minimizing morbidity and mortality resulting from quantitative limitation of acute myocardial necrosis mandates scientific evaluation of the new armamentarium directed at medical-surgical reperfusion.

Angioplasty, Balloon↗
PubMed1985

Efficacy of crystalloid cardioplegic solutions in patients undergoing myocardial revascularization. Effect of infusion route and regional wall motion on preservation of adenine nucleotide stores.

The effect of varying the mode of cardioplegic delivery and the presence of regional wall motion abnormalities on myocardial protection by crystalloid cardioplegic solutions was assessed in 68 patients undergoing coronary artery bypass grafting. Serial transmural biopsy specimens from the left ventricular apex were assayed for adenosine triphosphate. All patients had more than 75% stenosis of the left anterior descending coronary artery. They were prospectively randomized into Groups I and II to receive (I) all cardioplegic solution infused via the aortic root or (II) reinfusions of cardioplegic solution given both centrally and through the completed distal left anterior descending anastomosis. Patients were also stratified as to the presence of normal (N) or impaired (Ab) apicoanterior regional wall motion. Inadequate delivery of cardioplegia during ischemia in Group I was manifested by a 41% (p less than 0.01) depletion of adenosine triphosphate stores in abnormally contracting myocardium distal to the left anterior descending stenosis that was not repleted after restoration of coronary flow and a 27% (p less than 0.05) decline in ATP stores during reperfusion in myocardium with normal preoperative wall motion. In contrast, nucleotide stores were preserved at preischemic levels throughout ischemia and reperfusion in Group II regardless of preoperative wall motion. Preservation of ATP did not correlate with duration of ischemia, highest recorded septal temperature, or volume of cardioplegic solution infused. Two patients in each group had a new perioperative infarction. However, 38% of patients in Group IAb required transient inotropic support versus 5% in Group IIAb (p less than 0.05). These data emphasize that reinfusion of cardioplegic solutions distal to coronary obstructions is mandatory for optimal myocardial protection during coronary revascularization.

Adenosine Triphosphate↗
PubMed1984

Etiology of atrioventricular-conduction abnormalities following cardiac surgery.

Atrioventricular-nodal-conduction abnormalities following cardiac surgery have been attributed to the potassium ion in cardioplegic solutions. To clarify the etiology of these rhythm problems, 15 dogs were subjected to (I) 60 min 4 degrees C potassium cardioplegic arrest; (II) 30 min normothermic ischemic arrest; or (III) cardiac hypothermia without ischemia. In sinus rhythm and during atrial pacing, A-H and H-V intervals, Wenckebach cycle length (WCL), atrial- and AV-nodal refractory periods (ARP and NRP) were measured at 37 degrees C before and 30 min after arrest (groups I and II) and at various myocardial temperatures (group III). Following cardioplegic arrest and reperfusion, all AV-nodal-conduction properties were unchanged from preischemic values. In contrast, unprotected ischemia significantly prolonged AV-nodal-conduction time (P less than 0.01) and myocardial hypothermia resulted in prolonged WCL (P less than 0.01), prolonged functional NRP (P less than 0.05), in addition to delayed A-H interval (P less than 0.05). The data suggest that properties of AV-nodal conduction are preserved following potassium cardioplegic arrest, but impaired by ischemic injury or persistent local cardiac hypothermia.

Animals↗