Immunological release of histamine and slow-reacting substance of anaphylaxis from human lung : I. Modulation by agents influencing cellular levels of cyclic 3',5'-adenosine monophosphate.

The sensitization of human lung with atopic serum is both time and temperature dependent. Highly purified IgE myeloma protein is capable of blocking sensitization of human lung with atopic serum whereas myeloma proteins of the IgG subgroups are inactive. Drugs capable of increasing cellular levels of CAMP such as beta-adrenergic agents and methylxanthines inhibit the antigen-induced release of both histamine and SRS-A from human lung and these agents demonstrate synergism when used together. The beta-adrenergic blocking agent, propranolol, prevents epinephrine-induced inhibition of the immunologic release of the mediators. Diethylcarbamazine also inhibits the antigen-induced release of histamine and SRS-A from human lung and a synergism between this drug and epinephrine is observed. Predominantly alpha-adrenergic stimulation achieved by combining propranolol with epinephrine or norepinephrine not only prevented the inhibitory activity of the sympathomimetic amines but also resulted in an enhanced release of histamine and SRS-A. These observations suggest that whereas increases in cellular levels of CAMP are inhibitory, decreases in cellular levels of CAMP enhance the antigen-induced release of the mediators.

Significance of internal mammary lymph nodes in patients after mastectomy with tissue-expander reconstruction: a case-control study.

AIM: To retrospectively assess the frequency of internal mammary lymph nodes (IMNs) in patients after mastectomy and tissue-expander reconstruction. MATERIALS AND METHODS: Statistical analysis was performed for all available data in patients with mastectomy and tissue-expander reconstruction from 2004-2007 (study group). The data were compared with that of a control population with mastectomy who did not have reconstruction (control group). Patients with recurrent breast cancers, previous breast reconstruction, surgeries performed at outside hospitals, no available pre- or postoperative computed tomography (CT) or magnetic resonance imaging (MRI) data, or inadequate imaging follow-up were excluded. RESULTS: There were eight patients in the study group (median age 50.5 years, seven breast cancers), and eight patients in the control group (median age 52 years, seven breast cancers). No patients had IMNs on their preoperative imaging examinations. New IMNs were present in postoperative imaging in seven of eight patients (7/8, 87.5%) in the study group. All of them were stable or decreased in size on subsequent imaging examinations. None of the patients in the control group had IMNs (0/8). CONCLUSION: IMNs are common on imaging after mastectomy and tissue-expander placement. The IMNs decreased or remained stable on follow-up imaging and may represent reactive nodes.

Long-term survival of patients with treated aortic dissection.

Retrospective data on the treatment of aortic dissection at the Massachusetts General Hospital from 1963 to 1978 are reported. During this period, 160 patients with spontaneous aortic dissection were treated by definitive medical or definitive surgical therapy. Patients were classified according to type (proximal versus distal) and duration (acute versus chronic) of dissection. Long-term follow-up (mean 48 months, range 1 to 147) was available in 156 cases. Hospital and late survival in each of the categories of dissection were evaluated in relation to those features of the dissection itself and of the subsequent therapy that correlated with ultimate survival. Results show that: 1) chronic presentation was the most significant determinant of both hospital and late survival; 2) in acute dissection, prognosis was determined largely by the presence or absence of major complications, regardless of ultimate therapy; the only complication without adverse effect on survival was aortic insufficiency; 3) late survival after discharge from the hospital was similar for patients with all types of dissection and modes of therapy; and 4) the incidence of late complications from aortic dissection was lower than previously reported. Thus, the success of early definitive medical and surgical treatment was sustained on long-term follow-up.

Late prosthetic valve endocarditis: clinical features influencing therapy.

To assess the clinical features which might influence therapy, we studied 43 patients with late prosthetic valve endocarditis (LPVE). Twenty patients (47 per cent) survived. Of patients with streptococcal LPVE 61 per cent (11 of 18) survived compared to 36 per cent (nine of 25) of the patients with nonstreptococcal LPVE (p less than 0.10). Among patients with new regurgitant murmurs 33 per cent (nine of 27) survived versus 69 per cent (11 of 16) with such murmurs (p less than 0.03). Of patients with moderate to severe congestive heart failure (CHF) 16 per cent (three of 19) survived compared to 71 per cent (17 of 24) with mild or no CHF (p less than 0.001). The concurrence of two of these three features, i.e., nonstreptococcal etiology, a new regurgitant murmur or moderate to severe CHF, was associated with a mortality rate of 50 to 90 per cent. Persistent fever during therapy, a regurgitant murmur, atrioventricular conduction disturbances and relapse frequently reflected myocardial invasion. In view of the poor outcome with medical therapy and late reoperation, early surgical intervention should be considered when two of the three features noted are present or when myocardial invasion is suspected.

Electrophysiologic studies before and after myocardial revascularization in patients with life-threatening ventricular arrhythmias.

Electrophysiologic studies with programmed cardiac stimulation were performed in a selected group of 17 patients with severe proximal coronary artery disease involving at least 2 major vessels and left ventricular ejection fractions greater than 30% who were undergoing coronary artery bypass graft surgery after prehospital cardiac arrest or ventricular tachycardia (VT) unassociated with acute myocardial infarction. Before surgery and without antiarrhythmic drug therapy, programmed cardiac stimulation induced ventricular fibrillation (VF) in 4 patients, and VT (greater than or equal to 5 beats) in 11 patients. Inducible VT or VF was suppressed by antiarrhythmic drugs in 7 of 13 patients in whom they were tried. Patients underwent coronary artery bypass graft surgery unassociated with perioperative myocardial infarction. When studied again an average of 19 days after surgery, 10 patients had no inducible VT or VF without antiarrhythmic drug therapy; 6 had induced VT. One patient had spontaneous VT. An effective antiarrhythmic regimen that suppressed inducible or spontaneous VT, or both, was defined by serial electrophysiologic studies in 4 patients, whereas 3 patients continued to manifest electrically inducible VT with all antiarrhythmic regimens tested. All but 1 patient, in whom postoperative VT could not be suppressed, are free of arrhythmias after a mean follow-up period of 23 months (range 6 to 53). It is concluded that myocardial revascularization alone may improve the abnormal electrophysiologic findings in certain patients; however, this effect of coronary artery bypass graft surgery is unpredictable, and pre- and postoperative electrophysiologic studies are recommended as part of the evaluation of these patients.

Soluble P-selectin moderates complement dependent injury.

P-selectin is an adhesion molecule expressed on activated endothelial and platelet membranes containing 9 short consensus repeats (SCRs) similar to the composition of complement regulatory proteins. In our murine model of intestinal ischemia and reperfusion where local injury is mediated by the classical complement pathway we hypothesized the SCRs would moderate the complement response. Confirmatory data were sought following hindlimb ischemia and reperfusion where injury is both complement- and neutrophil-mediated. Mice deficient in P-selectin (P-/-) were found to have similar intestinal and hindlimb permeability compared to normal wild types mice (P+/+). When reconstituted with P+/+ platelets, but not P-/- platelets, P-/- mice subjected to intestinal ischemia had a significant 29% decrease in permeability (P < 0.05) and after hindlimb ischemia the decrease was 33% (P<0.05). Reperfusion after intestinal ischemia led to a 76% fall in CH50 in P-/- compared to sham animals (P < 0.05) indicating complement activation and consumption, but only a 36% fall in animals reconstituted with P+/+ platelets (P < 0.05). Full-length, soluble P-selectin (sPsel) derived from processed platelets, but not the truncated version of sPsel has been shown to adhere to a heat labile fraction of serum and sensitized red blood cells thereby reducing Clq adherence to the sensitized red cell. From these data we conclude that sPsel moderates complement activation by competing with C1q binding to antibody, thereby limiting activation of the classical pathway that mediates murine reperfusion injury.

Mast cells mediate complement activation after acid aspiration.

A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 but not C4 genetic knockout mice are protected from permeability edema. Using mast cell-deficient mice (W/Wv), we tested the hypothesis that mast cells mediate complement activation after acid aspiration. Tracheostomy tubes were placed in anesthetized mice and 2 mL/kg 0.1 N HCL was instilled in the trachea. After 4 h, extravasation of 125I-albumin was used to calculate lung vascular permeability. The serum alternative complement pathway hemolytic activity was examined, and lung immunohistochemistry was performed. Lung permeability in W/Wv mice was 62% less than that of mast cell sufficient (+/+) animals and similar to +/+ mice treated with the chymase inhibitor chymostatin (65% decrease). Treatment of +/+ mice with D-PRO2,D-TRP(7,9)-Substance P, an antagonist to the neuropeptide substance P, reduced injury by 66%. Serum complement hemolytic activity was intact in injured w/wv mice and +/+ animals treated with chymostatin or dpdt-sp, but was decreased to 65% in the injured untreated +/+ group. Alveolar C3 deposition was intense in injured untreated +/+ mice but absent in the other groups. We interpret these data to indicate that mast cells mediate complement activation, via chymase degranulation, after acid aspiration. This mast cell activity likely is regulated by the release of substance P.

Pulmonary valve replacement. Report of an operation performed for calcific pulmonic stenosis associated with total anomalous pulmonary venous drainage and atrial septal defect.

Calcification of the pulmonic valve is an uncommon lesion that is usually associated with other congenital cardiac defects. Prior attempts at valvotomy or partial excision of the puolmonic valve have carried a high mortality rate. Pulmonary valve replacement itself is an equally uncommon surgical procedure and, in the past, has been performed only during reconstruction of the right ventricular outflow tract, when the pulmonic valve itself had to be utilized as an aortic prosthesis, and in one patient in whom pulmonary regurgitation following valvotomy was not well tolerated. A case of calcific pulmonic stenosis in association with an atrial septal defect and total anomalous pulmonary venous drainage is reported. The patient was treated successfully by pulmonary valve replacement with a Hancock stented porcine xenograft aortic prosthesis in association with correction of the other congenital cardiac lesions.

Survival following fracture of strut from mitral prosthesis with disc translocation.

Mechanical complications of prosthetic valves are increasingly rare. The acute, catastrophic nature of the symptoms associated with massive transvalvular regurgitation preclude survival except with immediate operation. In the patient described herein, two weld fractures of a Björk-Shiley mitral prosthetic strut led to displacement of the valve occluder into the left atrium. The patient survived reoperation, following which the strut was detected radiologically in the left ventricular free wall. A slow, limited recovery resulted from his 5 preoperative hours of deep shock and coma. No complication attributable to the retained ventricular foreign body has been identified.

Influence of contractility on myocardial water distribution during cardiopulmonary bypass.

Water equilibrium within heart muscle during cardiopulmonary bypass is an important aspect of ventricular physiology which must be considered in efforts to optimize myocardial protection. This study focuses on the influence of the inotropic state of the ventricle in determining the amount of heart water and its regional distribution within the free wall of the left ventricle. Experiments involving cardiopulmonary bypass were performed in 57 dogs. Three spontaneous levels of myocardial contractility were identified under conditions of standard preload, afterload, and heart rate. Each increase in level (grade) was associated with a significantly higher myocardial wet weight/drug weight (W/D) ratio. In addition, higher levels of contractility were associated with a marked shift in water distribution within the left ventricular wall; water tended to accumulate in the inner half of the better contracting left ventricular wall, the reverse of the distribution seen at lower levels of contractility. These three grades of contractility and myocardial water content were not associated with any significant differences in total or regional myocardial blood flow, as determined by the use off radioactive microspheres. Maintenance of low levels of contractility during cardiopulmonary bypass may be desirable in order to prevent the occurrence of subendocardial edema.

The influence of prearrest factors on the preservation of left ventricular function during cardiopulmonary bypass.

Uniformly excellent myocardial protection during global ischemia in cardiac procedures requiring cessation of aortic root perfusion remains an elusive goal. This study establishes the importance of the preischemic inotropic state of the left ventricle and the arterial blood glucose concentration ([glucose]) immediately prior to an elective period of myocardial ischemia. Thirty-one experiments were performed on dogs subjected to 90 minutes of global ischemia on cardiopulmonary bypass at 28 degrees C with perfusion pressure constantly maintained at 90 mm Hg. The maximum rate of development of left ventricular pressure (LVdp/dtmax) at constant arterial and left atrial (LAP) pressures was used as a measure of contractility prior to ischemia. In a group of 18 of these dogs undergoing anoxic cardiac arrest, arterial blood [glucose], in conjunction with the preischemic LVdp/dtmax and the cross-clamp to asystole time interval (metabolic supply/demand index), significantly predicted (p less than 0.01) the functional result following the standard ischemic insult. In 13 other dogs with [glucose] greater than 120 mg/100 ml and treated with potassium cardioplegia, "normal" preischemic LVdp/dtmas (N = 7) was associated with a good functional result, but an elevated preischemic LVdp/dtmax (N = 6) produced severe functional impairment following ischemia. Optimum myocardial protection thus involves minimizing metabolic demands and maximizing metabolic supply immediately prior to and during the period of aortic cross-clamping.

Hemodynamic effects and oxygen transport properties of a new blood substitute in a model of massive blood replacement.

Recent concerns regarding the safety of the national blood supply have rekindled interest in the development of blood substitutes. Clinical studies have dampened the initial enthusiasm for fluorocarbon solutions as blood substitutes. The potential of hemoglobin solutions as blood substitutes has continued to stimulate investigations. However, the development of an ideal hemoglobin-derived blood substitute has eluded investigators for the past century. A persistent problem has been the inability to develop hemoglobin solutions that provide adequate oxygen and carbon dioxide exchange, while avoiding toxicity that precludes clinical safety and long-term survival. Traditionally, investigators have focused on human hemoglobin solutions. The use of outdated banked blood or pedigree human donor blood as a hemoglobin source poses continued disease transmission risks and a prohibitively limited supply. We evaluated the hemodynamic and gas transport effects of a new purified, polymerized bovine hemoglobin preparation. Bovine hemoglobin oxygen affinity is regulated by chloride ion. The concentration of chloride ions in human plasma results in excellent oxygen transport properties in a stroma-free environment. In addition, unlike human blood, bovine blood is a more disease-free hemoglobin source that is available in large supply. We exchange-transfused eight conscious sheep with this new polymerized bovine hemoglobin solution. All animals tolerated greater than or equal to 95% exchange transfusion to reach a final ovine hematocrit of 2.4 +/- 0.5% with stable hemodynamics and no clinical evidence of distress. The exchange transfusion with bovine hemoglobin polymer resulted in a final plasma hemoglobin concentration of 6.1 +/- 1.6 gm/dl, which supported oxygen consumption at baseline levels. All animals that were exchange transfused with this preparation survived long term with rapid resynthesis of ovine erythrocytes.

Myocardial revascularization with combined aortic and mitral valve replacements.

Although the results of coronary artery bypass grafting plus single aortic or mitral valve replacement have been documented, the risk of myocardial revascularization with combined aortic and mitral valve replacement is not well defined. We present a series of 33 consecutive patients undergoing myocardial revascularization with combined aortic and mitral valve replacement during a period of almost seven years. There were 21 men and 12 women with a mean age of 67 years. All patients had congestive heart failure, and 21 (64%) had angina pectoris. Mean New York Heart Association functional classification was 3.4; eight patients (24%) had ejection fractions less than 0.40, and 13 patients (41%) had cardiac indices less than 2.0 L/min/m2. All operations were performed with hypothermic crystalloid potassium cardioplegia. The number of coronary arteries grafted varied from one to four (mean, 1.7 grafts per patient). Four patients died while in the hospital (12.1%). There were no perioperative myocardial infarctions. At a follow-up of 2 to 80 months (mean 40.7 months), death had occurred in eight (27.6%) of the 29 hospital survivors. Actuarial survival rate at 72 months was 60.7%. Although no preoperative factors predicted late death, early deaths were related significantly to severe mitral regurgitation, low ejection fraction, high New York Heart Association classification and extensive coronary artery disease (p less than 0.05). Myocardial revascularization with combined aortic and mitral valve replacement can be performed with an acceptable early mortality rate but with an appreciable late mortality rate.

Role of procaine and washed red cells in the isolated dog heart perfused at 5 degrees C.

Isolated dog hearts were perfused for 24 hours at 5 degrees C with one of three solutions: plain Krebs solution, Krebs solution containing 167 mg/L of procaine hydrochloride, or Krebs-procaine solution with washed red cells (hematocrit 2%). Coronary vascular resistance (CVR) of hearts perfused with Krebs solution alone increased sharply between the eighth and the twelfth hours of perfusion and then stabilized. Increase of myocardial firmness paralleled the increase of CVR. The addition of procaine to Krebs perfusate kept the heart flaccid and suppressed the steplike increase in CVR but failed to improve significantly the preservation of the hearts. The addition of washed red cells to Krebs perfusate kept CVR near baseline level, improved coronary perfusion flow, doubled myocardial oxygen consumption, reduced edema formation, and improved left ventricular stroke work (LVSW) of the preserved heart. This improvement seems mostly related to a mechanical effect of red blood cells on capillary flow distribution of the heart.

Myocardial protection with hypothermia and potassium cardioplegia during operation for ascending aortic aneurysms.

The operative management of aneurysms of the ascending aorta continues to present a technical challenge to the surgeon, and the results obtained provide a useful clinical assessment of the means of myocardial protection. We present a series of 35 consecutive patients who underwent operations for aneurysms of the ascending aorta during which myocardial protection was achieved with hypothermia and potassium cardioplegia. Twenty-three patients underwent aortic valve replacement and resection and grafting of a chronic ascending aortic aneurysm. Aortic valve replacement and aneurysmorrhaphy of a chronic ascending aneurysm were performed in five patients. Four patients underwent resection and grafting of a chronic ascending aortic aneurysm and three patients resection and grafting of acute aortic aneurysms. Aortic cross-clamp times varied from 48 minutes to 2 hours, 32 minutes, with a mean cross-clamp time of 1 hour, 29 minutes. There was one death in the hospital in this series of 35 patients for a mortality rate of 2.8%. Of the 34 survivors, there has been one late death from recurrent sternal wound infection. This clinical series documents the efficacy and safety of hypothermic potassium cardioplegia for protection of the myocardium during extended periods of ischemia attending operative correction of ascending aortic aneurysms.

Selective arterialization of the coronary venous system. Encouraging long-term flow evaluation utilizing radioactive microspheres.

The long-term effectiveness of a retrograde coronary venous bypass graft (CVBG) to an ischemic left ventricle was evaluated in 18 dogs. A saphenous vein was interposed between the aorta and left anterior descending (LAD) vein. The LAD vein was ligated cephalad to the CVBG to prevent an arteriovenous fistula. The LAD artery was ligated at its origin to create anterior wall ischemia. Operative graft flow averaged 53 ml. per minute. The 14 surviving dogs were catheterized 3 to 5 months later. Ten of the 14 CVBG's were patent angiographically. The chests were opened and graft flow now averaged 50 ml. per minute. 141Ce microspheres were injected into the left atrium to measure myocardial flow to the anterior wall. In the 10 dogs with patent grafts, transmural flow was 39 +/- 1 (S.E.M.) ml. per 100 Gm. of tissue per minute. The endocardial/epicardial flow ratio was 1.4/1, indicating that retrograde venous perfusion effectively delivered blood to the subendocardium. After ligation of the CVBG, microsphere measured flow dropped to 15 +/- 1 ml. per 100 Gm. per minute. In 15 control dogs, anterior wall flow was 100 +/- 3 ml. per 100 Gm. per minute, decreasing to 13 +/- 2 ml. 45 minutes after ligation of the LAD artery and vein. None of the eight control dogs with simple ligation of the LAD artery and vein survived more than 5 days. Histologic examination of the anterior wall of the left ventricle, the area served by the CVBG's for 3 to 5 months, disclosed no evidence of venous sclerosis or thrombosis and no evidence of interstitial edema or hemorrhage. Thus a CVBG permitted long-term survival in an otherwise nonviable anatomic preparation. Moreover, restoration of flow with a CVBG was effective because it perfused all layers of the myocardium, especially the subendocardium--the crucial layer of myocardial muscle.

Plasma vasopressin levels and urinary flow during cardiopulmonary bypass in patients with valvular heart disease: effect of pulsatile flow.

The effect of pulsatile flow on plasma vasopressin levels during cardiopulmonary bypass (CPB) was studied in 20 patients undergoing open valve replacement. Routine bypass was used in 10 patients and the AVCO pulsatile bypass pump was utilized in the other 10. In Group I (nonpulsatile) during CPB, the vasopressin level was markedly elevated (3.1 +/- 2 to 80 +/- 22 pg/ml) as was urine flow (0.6 +/- 0.2 to 5.9 +/- 2 ml/min) and urine Na+ concentration (69 +/- 19 to 116 +/- 7 mEq/L). In Group II (pulsatile) during CPB, the vasopressin level (3.8 +/- 3 to 54 +/- 14 pg/ml), urine flow (0.6 +/- 0.1 to 16.2 +/- 4.8 ml/min), and urine Na+ concentrations (61 +/- 13 to 97 +/- 10 mEq/L) were also elevated. The rise in vasopressin and urine Na+ was less in the pulsatile group (p less than 0.05) whereas the urine flow was higher (p less than 0.05). To maintain comparable blood pressure, the pulsatile flow group required significantly higher flows (4.5 +/- 0.2 compared to 3.8 +/- 0.2; p less than 0.05). These data suggest that CPB produces a marked vasopressin stress response which is beyond the physiological range for an antidiuretic effect on the kidney. At these levels vasopressin can exert a vasopressor effect to maintain resistance and affect renal blood flow, as well as producing an Na+ diuresis. The addition of pulsatile flow creates a more physiological situation attenuating the vasopressin response and producing a decrease in systemic resistance and a less pronounced Na+ diuresis.

Intraaortic balloon pumping for cardiac support: trends in practice and outcome, 1968 to 1995.

OBJECTIVES: A total of 4756 cases of intraaortic balloon pump support have been recorded at the Massachusetts General Hospital since the first clinical insertion for cardiogenic shock in 1968. This report describes the patterns of intraaortic balloon use and associated outcomes over this time period. METHODS: A retrospective record review was conducted. RESULTS: Balloon use has increased to more than 300 cases a year at present. The practice of balloon placement for control of ischemia (2453 cases, 11.9% mortality) has become more frequent, whereas support for hemodynamic decompensation (congestive heart failure, hypotension, cardiogenic shock) has been relatively constant (1760 cases, 38.2% mortality). Mean patient age has increased from 54 to 66 years, and mortality has fallen from 41% to 20%. Sixty-five percent (3097/4756) of the total patient population receiving balloon support underwent cardiac surgery. Placement before the operation (2038 patients) was associated with a lower mortality (13.6%) than intraoperative (771 patients, 35.7% mortality) or postoperative use (276 patients, 35.9% mortality). Independent predictors of death with balloon pump support were insertion in the operating room or intensive care unit, transthoracic insertion, age, procedure other than angioplasty or coronary artery bypass, and insertion for cardiogenic shock. Independent predictors of death with intraoperative balloon insertion were age, mitral valve replacement, prolonged cardiopulmonary bypass, urgent or emergency operation, preoperative renal dysfunction, complex ventricular ectopy, right ventricular failure, and emergency reinstitution of cardiopulmonary bypass. CONCLUSIONS: Balloons are being used more frequently for control of ischemia in more patients who are elderly with lower mortality. An institutional bias toward preoperative use of the balloon pump appears to be associated with improved outcomes.

Etiology, incidence, and prognosis of renal failure following cardiac operations. Results of a prospective analysis of 500 consecutive patients.

A prospective study of 500 consecutive patients surviving the first 24 hours following cardiac surgical procedures was undertaken to determine the prevalence, etiology and results of therapy for postoperative acute renal failure (ARF). Thirty-five patients developed either moderate or severe ARF and an additional 102 developed mild preprenal azotemia. Positive risk factors noted inthe development of postoperative renal failure included age, elevated preoperative concentrations of blood urea nitrogen (BUN), serum creatinine, and decreased 24 hour urine creatinine clearance. The duration of cardiopulmonary bypass (CPB), aortic cross-clamping, and the total duration of the operation also closely correlated with the incidence of ARF. In the early postoperative period, clinical assessment of hemodynamic change was most helpful in predicting postoperative ARF. Significant negative risk factors included type of operation performed, New York Heart Association classification, the use of preoperative diuretic therapy, and associated other chronic illnesses. During the operation itself, the lowest and mean blood pressures, flow rates on CPB and the presence of hemoglobinuria failed to correlate with subsequent ARF. The mortality rate for established ARF was extremely poor (88.8 per cent), and there were no survivors among those requiring dialysis. ARF following cardiac surgery is a highly lethal complication which arises in a setting of inadequate cardiac function and is associated with a multiple organ system failure. Therapy of this postoperative complication, therefore, appears to be better directed toward its prevention rather than treatment once established.