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Biomedical subjects

N A Silverman

Publications and source records attributed to N A Silverman.

At least 73 records · Page 4Linked to original sources
PubMed1984

A model of cyanotic heart disease: functional, pathological, and metabolic sequelae in the immature canine heart.

To assess the etiology of depressed ventricular function in cyanotic congenital heart disease, an experimental model in immature puppies was devised in which the left atrial appendage is directly anastamosed to the distally banded pulmonary artery. The preparation results in significant cyanosis during a 3-month study period (PO2 = 91 +/- 4 vs 43 +/- 3, hematocrit = 33 +/- 3 vs 55 +/- 5). Compared to age- and weight-matched unoperated controls, cyanotic animals developed significant depression of biventricular ejection fraction (P less than 0.05), increased heart weight indexed for body weight (P less than 0.05), increased right ventricular weight (P less than 0.02), and increased right ventricular free wall thickness (P less than 0.05). There was no alteration in ventricular volumes. In addition, mean myocardial stores of high-energy phosphate compounds were unaltered. The model allows a reproducible level of hypoxemia to be produced in young animals, utilizes no prosthetic materials, and allows future experiments to be performed to ascertain the metabolic response of the cyanotic myocardium to exercise or surgically induced ischemia.

Animals↗
PubMed1984

Chronic hypoxemia depresses global ventricular function and predisposes to the depletion of high-energy phosphates during cardioplegic arrest: implications for surgical repair of cyanotic congenital heart defects.

Persistence of impaired ventricular function after repair of cyanotic congenital heart defects may be due to previous exposure to chronic hypoxemia or to perioperative ischemic injury. Clarification of this phenomenon was sought in a canine model of cyanotic cardiovascular disease (Group I), in which the left atrium was anastomosed proximal to the banded pulmonary artery. Animals that had pulmonary artery banding alone (Group II) or no prior surgical intervention (Group III) served as controls. All Group I animals became cyanotic during the study period (arterial oxygen tension, 38 +/- 4 mm Hg; hematocrit, 55 +/- 5%). Radionuclide-determined ejection fractions performed three months after operation showed significant depression of global biventricular function by 16 to 29% (p less than 0.05) compared with groups II and III. On cardiopulmonary bypass, all hearts were subjected to 4 degrees C potassium cardioplegic arrest and reperfusion with serial assays for myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels. The ATP and CP stores in each ventricle were similar at all sampling intervals, and preischemic levels were comparable in cyanotic and control groups. However, ATP levels were significantly depressed 37 to 43% from preischemic levels (p less than 0.02) after arrest and reperfusion in cyanotic dogs, but they were preserved in Groups II and III. During ischemia, CP stores were depleted to 27% of preischemic values in Group I but only to 46 to 63% of preischemic levels in the control groups (p less than 0.05). These data indicate that chronic hypoxemia impairs global ventricular function and predisposes to the accelerated depletion of high-energy phosphates during cardioplegic arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1984

Acute endocarditis in drug addicts: surgical treatment for multiple valve infection.

In 72 drug abusers surgically treated for acute infective endocarditis, 14 patients (19%) required surgical procedures on two valves. The predominant infecting organisms were Staphylococcus aureus and Pseudomonas aeruginosa (29%). In contrast to single valve infection, congestive heart failure was the most common operative indication (86%, p less than 0.05) and was uniformly present when both left-sided valves were involved. Surgery was performed 20 +/- 13 days after initiation of antibiotic therapy, yet 7 of the 14 patients had perivalvular abscess formation. In nine patients with solely left-sided infection, aortic and mitral valve replacements were performed. In five patients with bilateral infection, partial or complete tricuspid valvectomy was performed in conjunction with one aortic and four mitral valve replacements. Tricuspid valve competence was reestablished by valve insertion or anuloplasty in two patients, and these patients experienced less perioperative heart failure than did those with tricuspid excision alone. There was no early (less than 30 day) mortality. However, long-term follow-up revealed a reoperative incidence of 21% and a 36% late mortality rate due to prosthetic valve infection with or without dehiscence at 3 to 18 months (mean 7.2 +/- 6) after the initial operation. These late infectious complications were not related to infecting organism or prosthetic material in the tricuspid anulus, but did occur in four (57%) of seven patients with intracardiac abscess. The data indicate that multiple valve infection does not preclude successful early surgical therapy, maintaining tricuspid competence may be hemodynamically preferable, and reinfection in this addict population increases late mortality.

Adult↗
PubMed1984

Optimal intraoperative protection of myocardium distal to coronary stenoses.

Metabolic evidence of improved delivery of cardioplegic solutions by adjuvant use of nitroglycerin (NTG) and reinfusing these solutions distal to an obstructed coronary artery was sought in 40 dogs subjected to cold cardioplegic arrest. The left anterior descending coronary artery was occluded prior to initiating arrest by intra-aortic root infusion. Cardioplegic solution was reinfused with the left anterior descending occluded throughout ischemia (Group I), or with this artery reopened, to simulate a completed distal anastomosis (Group II). Serial biopsy specimens of the left ventricular apex were assayed for adenosine triphosphate and creatine phosphate, while specimens from the posterior left ventricular wall served as controls. Regional myocardial temperatures were recorded throughout ischemia. Half of the hearts in each group received 300 micrograms of nitroglycerin in the cardioplegic solution. Adenosine triphosphate was preserved in myocardium distal to a patent coronary artery whether nitroglycerin was added to the cardioplegic solution or not (control, control + NTG). Moreover, nitroglycerin did not prevent the 26% to 34% (p less than 0.05) decline in adenosine triphosphate levels when the left anterior descending remained obstructed throughout ischemia (Group I, I + NTG). However, opening the left anterior descending for reinfusion of cardioplegic solution allowed adenosine triphosphate to be preserved at end-ischemia (Group II, II + NTG). In addition, the metabolic reperfusion injury manifested by a 37% (p less than 0.01) decline in adenosine triphosphate levels after aortic unclamping (Group II) was obviated when nitroglycerin was added to the cardioplegic solution delivered in this manner (II + NTG). The depletion of cardioplegic solution stores during ischemia was more severe in the experimental groups than in controls (p less than 0.05). These metabolic changes did not correlate with regional myocardial temperature gradients. The data indicate that myocardium jeopardized by coronary stenoses can be preserved as well as myocardium supplied by a patent coronary artery by adjuvant use of nitroglycerin and varying the mode of delivery of the cardioplegic solution.

Adenosine Triphosphate↗
PubMed1983

Prevention and reperfusion injury following cardioplegic arrest by pulsatile flow.

To assess the efficacy of pulsatile flow in minimizing reperfusion injury following cardioplegic arrest, 20 dogs supported by cardiopulmonary bypass underwent 60 minutes of hypothermic, hyperkalemic crystalloid cardioplegic arrest. The effects of pulsatile flow (Group 2), initiated during 30 minutes of reperfusion, on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores, coronary blood flow, and myocardial water content were compared with the effects of linear flow reperfusion (Group 1). Myocardial ATP stores were maintained at preischemic levels by this mode of myocardial protection. However, pulsatile flow prevented the significant decline in ATP levels incurred during linear reperfusion. Creatine phosphate stores, although depleted during arrest, were restored equally, regardless of the mode of reperfusion. The decline in ATP stores was associated with no pathological increase in myocardial water content, but was associated with persistent reactive hyperemia. In contrast, after 30 minutes of pulsatile reperfusion, coronary blood flow was significantly decreased compared with preischemic flow. These data indicate that pulsatile reperfusion can prevent the unique decline in ATP levels associated with the restoration of coronary flow after cardioplegic arrest (reperfusion injury), and support its continuing evaluation as an adjunct to adequate intraoperative myocardial protection.

Adenosine Triphosphate↗
PubMed1983

Valve replacement for left-sided endocarditis in drug addicts.

Eighteen drug addicts with left-sided valvular endocarditis requiring operation are reviewed. Gram-positive bacteria were the most common organisms cultured (61%), with Staphylococcus aureus present in 7 of 11 patients. Gram-negative bacteria, exclusively Pseudomonas aeruginosa, were cultured in the remaining 39%. Indications for operation included sepsis (61%), heart failure (78%), and systemic emboli (22%). Abscesses formed in 6 of 11 patients with gram-positive endocarditis, while only one abscess was present with gram-negative endocarditis. Normal valves were infected in 17 of 18 patients (94%). Early surgical mortality (less than 30 days) was 11%. There were major complications in 79% of these patients, including persistent sepsis (50%), valvular dehiscence, prosthetic endocarditis or perivalvular leakage (37%), and mycotic aneurysms (22%). These complications were directly related to a late mortality of 44%, yielding an overall mortality of 50% in the first nine months after operation. Contrary to previous reports of acceptable surgical survival for valvular endocarditis, these data suggest that endocarditis involving the aortic or mitral valve in a drug addict is a highly lethal disease due to the virulence of the organisms, the severity of the complications encountered, and the predisposition to continued addiction.

Adolescent↗
PubMed1983

Beneficial metabolic effect of nucleoside augmentation on reperfusion injury following cardioplegic arrest.

Restoration of coronary flow after hyperkalemic cardioplegic arrest (HCA) is associated with a unique metabolic reperfusion injury (RI) manifested by declining nucleotide stores despite their end-ischemic preservation. Prevention of this RI by exogenous provision of adenosine with or without inhibition of adenosine's major catabolic enzyme was assessed in 27 dogs subjected to 60 minutes of HCA. The effect of aortic root infusion of 40 mg/kg of adenosine in addition to adenosine deaminase inhibition by 10 mg/kg of EHNA (group 2) initiated during 60 minutes of reperfusion on myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores and coronary blood flow (CBF) were compared to animals having adenosine infusion alone (group 3) or controls (group 1). Although ATP levels were preserved at the end of HCA in all groups, adenosine infusion with or without EHNA prevented the significant 23 percent decline in ATP stores incurred during unmodified reperfusion (p less than 0.01, group 1). The CP stores decreased (p less than 0.05, all groups) during arrest, but were restored to preischemic levels during reperfusion. When measured 60 minutes after aortic unclamping, CBF was 312 percent of preischemic flow in group 3 (p less than 0.01), only 170 percent in group 2 (p less than 0.05), and unchanged in controls (group 1). The data indicate that provision of adenosine as a nucleotide precursor prevents the metabolic RI following HCA. In addition, inhibition of adenosine catabolism is not necessary for this salutary effect, nor is adenosine's efficacy solely mediated by augmentation of CBF.

Adenine↗
PubMed1983

Induction of cardioplegia with blood and crystalloid potassium solutions during prolonged aortic cross-clamping.

Recent controversy concerns the proper vehicle for delivery of potassium cardioplegia. In the present study, adult dogs supported by cardiopulmonary bypass were subjected to 2 hours of multidose, hypothermic potassium cardioplegic arrest with 30 minutes of reperfusion with either autologous blood or crystalloid solution as the cardioplegic vehicle. Preservation of myocardial high-energy nucleotide stores was assessed by serial left ventricular biopsies assayed for adenosine triphosphate (ATP) and creatine phosphate. Preischemic and postischemic ventricular function was assessed by the use of an isovolumic intraventricular balloon. ATP stores were equally maintained at preischemic levels after ischemia and reperfusion by both autologous blood and crystalloid solution. Although creatine phosphate stores significantly declined (P less than 0.01, both groups) after 2 hours of arrest, reperfusion allowed equal restoration of preischemic levels. Maximum first derivative of left ventricular pressure and measured velocity were not depressed by either mode of protection. Similarly, myocardial compliance, as assessed by length-tension curves, showed no change following either autologous blood or crystalloid solution. The data show equal and significant myocardial protection by multidose, hypothermic potassium cardioplegia when both delivery vehicles were used.

Animals↗
PubMed1982

Efficacy of low-dose propranolol in preventing postoperative supraventricular tachyarrhythmias: a prospective, randomized study.

A prospective, randomized study was performed in 100 consecutive patients undergoing coronary artery bypass surgery to assess the efficacy of the early reinstitution of propranolol in reducing the incidence of postoperative supraventricular tachyarrhythmias (SVT). Patients were randomized to receive propranolol 10 mg every 6 hours enterally starting the morning after surgery (Group I, 50 patients) or to serve as controls (Group II, 50 patients). No patient was excluded because of poor ventricular function, need for urgent revascularization, or transient necessity for ionotropic support. Both groups had a comparable incidence of risk factors, previous infarction, unstable angina, and abnormal ventricular function. The extent of coronary disease, preoperative propranolol dose, and number of grafts performed were also similar. SVT occurred in 3/50 (6%) patients in Group I compared with 14/50 (28%) in Group II (p less than 0.01). There were no preoperative or intraoperative discriminators to predict the occurrence of SVT. In addition, perioperative infarction and the need for mechanical or pharmacologic circulatory support did not predispose to SVT. The data indicate that early administration of propranolol should be given to all patients after myocardial revascularization to decrease the incidence of these postoperative rhythm disturbances.

Arrhythmias, Cardiac↗
PubMed1982

Pulsatile reperfusion does not modify global myocardial ischemic injury.

In an attempt to arbitrate the reputed clinical efficacy of pulsatile flow during reperfusion in minimizing ischemic injury, 32 mongrel dogs supported by normothermic cardiopulmonary bypass were subjected to 30 minutes (Groups IC and IP) or 60 minutes (Groups IIC and IIP) of global myocardial ischemia. The effect of pulsatile flow (P) initiated during 30 minutes of reperfusion on the recovery of myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) stores, coronary blood flow, and myocardial water content (MWC) was compared to the effect of linear reperfusion (C) in another group of animals. ATP stores, which significantly decreased to 43% and 53% of preischemic levels (Groups IC and IP, respectively, p less than 0.01) and 36% and 31% of control values (Groups IIC and IIP, respectively. p less than 0.001), did not increase with either pulsatile or linear reperfusion. CP stores, depleted 97% during ischemia in all groups, returned to preischemic levels regardless of the mode of reperfusion flow. Coronary blood flow measured 30 minutes after aortic unclamping was not significantly different from control flow in any group. MWC significantly decreased during ischemia from 80.5% +/- 0.8% to 76.5% +/- 1.1% in Group IC and from 81.8% +/- 1.2% to 76.8% +/- 0.8% in Groups IP (p less than 0.05) and returned to preischemic levels with reperfusion. However, following 60 minutes of ischemia, pulsatile reperfusion prevented the significant increase in MWC that accrued after linear reperfusion (80.7% +/- 1.5% to 84.0% +/- 0.7%, p less than 0.05). These data indicate that pulsatile reperfusion initiated after an ischemic injury that results in a 50% or greater depletion of myocardial ATP stores does not restore myocardial nucleotide levels or enhance coronary blood flow, although the pathological increase in MWC may be avoided.

Adenosine Triphosphatases↗
PubMed1982

Acute endocarditis in drug addicts: surgical treatment for gram-negative sepsis.

We studied 37 consecutive patients, all drug addicts, who underwent 48 valve operations from 1976 through 1981. GN bacteria were the major organisms in 25 patients (64%), compared with a previous reported incidence of 10%. Operative indications were uncontrolled sepsis in 49%, embolism in 27% and heart failure in 24% of the patients. Primary operations included nine tricuspid valvectomies and 14 aortic, 10 mitral and four aortic/mitral valve replacements. Early (30-day) mortality was 2.7% (one of 37 patients); five of nine patients who had 11 reoperations survived. Long-term follow-up revealed a late mortality of 39% (11 of 28) in patients with left-sided disease; eight of the 11 patients who died had GN infection with perivalvular abscess. Thus, the subgroup with GN sepsis and left-sided disease had a combined early and late mortality of 50%, with all deaths occurring within 8 months postoperatively. We conclude that valve replacement in the presence of active sepsis can be safely performed, but GN sepsis in addicts increases the risk of early reinfection and late mortality.

Acute Disease↗
PubMed1982

Platelet deposition after surgically induced myocardial ischemia. An etiologic factor for reperfusion injury.

Despite meticulous adherence to presently known principles of myocardial preservation, reperfusion after aortic cross-clamping results in a unique injury manifested by decreasing high-energy phosphate levels and increased coronary resistance. We hypothesize that platelet deposition into the coronary microvasculature is a major factor in reperfusion injury. To differentiate platelet deposition due to subendocardial hemorrhage from deposition due to vascular entrapment, we infused 111In-labeled platelets together with 51Cr-labeled erythrocytes into 15 dogs that were on normothermic bypass and subjected to 60 minutes of global ischemia followed by 30 minutes of reperfusion. Platelet deposition is indicated only when the proportion of platelets to erythrocytes in tissue exceeds that measured by peripheral blood. Myocardial biopsy specimens were obtained after 10 minutes of bypass, 120 minutes of continuous bypass (Group I), and at the end of reperfusion after global ischemia (Group II). In five dogs (Group III), dipyridamole (1 mg/kg), an antiplatelet activation agent, was administered in the preischemic period. Platelet deposition was expressed as the number of radioactive-labeled platelets deposited per gram of tissue. Bypass for 120 minutes resulted in only a minimal increase in platelet deposition. However, normothermic ischemia followed by reperfusion resulted in over a twofold increase in platelet deposition compared to controls. Pretreatment with dipyridamole appeared to avoid platelet deposition. These data indicate that platelet deposition in the coronary microcirculation following surgically induced myocardial ischemia may be associated with reperfusion injury and that antiplatelet drugs after this sequence.

Animals↗
PubMed1980

Acquired left ventricular-right atrial fistula following aortic valve replacement.

Intracardiac communications produced as a complication of valve replacement can result in left-to-right shunts and a poor surgical result. The successful surgical closure of a left ventricular-right atrial fistula following aortic valve replacement is discussed. The intricate relationships of the membranous interventricular septum, the aortic, mitral, and tricuspid valves, and the aortic root predispose to the creation of abnormal intracardiac shunts when aggressive debridement of extensive valvular calcification is performed at the time of valve excision and replacement.

Aged↗
PubMed1980

Primary cardiac tumors.

Cardiac tumors are a rare, but potentially curably form of heart disease. A high index of clinical suspicion is necessary for diagnosis as these tumors have protean manifestations that mimic a variety of other cardiac and noncardiac diseases. Presently, M-mode and two-dimensional echocardiography are utilized as safe, reliable, and noninvasive imaging modalities. Seventy-five per cent of these tumors are benign, with myxoma accounting for 50% and rhabodomyoma comprising 20% of lesions. Various histologic types of sarcoma are the predominant malignant cardiac neoplasms. With strict attention to avoiding perioperative tumor embolization, surgical resection of these lesions can be accomplished with minimal morbidity and mortality. Sixteen consecutive primary tumors of the heart have been surgically treated at Duke University Medical Center since 1966 with no perioperative deaths and no late recurrences.

Adolescent↗