Malignant renal tumor with extension to the inferior vena cava.

BACKGROUND: Management of malignant renal tumors involving the inferior vena cava (IVC) depends on tumor extension within the cava. METHODS: Of 295 patients treated for renal cancer, propagation of tumor mass through the renal vein to IVC was seen in 22 (7%) patients. Cephalad extension of the tumor was suprarenal: infrahepatic in 12, retrohepatic in 6, and within the right atrium in 4 patients. All patients had radical nephrectomy, cavotomy, and complete resection of tumors except 1 with diffuse peritoneal metastasis. RESULTS: Twenty-one patients had curative resections. No operative deaths and no instances of pulmonary embolism or exsanguination occurred. Seventeen patients were alive at 2 years and 12 at 5 years, resulting in 77% and 55% survival rates, respectively. CONCLUSIONS: An aggressive approach for vena cava involvement from malignant renal neoplasms resulted in prevention of tumor embolus, minimization of blood loss, and maintenance of venous return to the heart.

Downregulation of right ventricular phosphodiesterase PDE-3A mRNA and protein before the development of canine heart failure.

Phosphodiesterase III (PDE-3) inhibitors are inotropes used to treat congestive heart failure (HF). Previous studies showed PDE-3A mRNA levels were reduced in the left ventricle (LV) in dogs subjected to pacing-induced HF. The present study evaluated a time-course for RV-specific changes in PDE-3A mRNAs and proteins after pacing for 3 wk (n = 4) or in HF (4-5 wk; n = 4-6). Total RNA from LV/RV tissues was isolated for Northern analyses; cytosolic and microsomal proteins were prepared for PDE-3A immunoblots. PDE-3A mRNAs (7-8 and 10 kb) were normalized against glyceraldehyde-3-phosphodehydrogenase (GAPDH) or ribosomal 18s with similar results. PDE-3A/GAPDH ratios in 3 wk were unchanged in LV, but significantly (p < 0.05) reduced by 48% in RV vs unpaced controls (n = 8). In contrast, PDE-3A (7-8 kb)/GAPDH ratios were significantly reduced in HF by 50-59% in both ventricles. Consistent with mRNA levels, significant reductions in microsomal 135 kDa (93-96%) and cytosolic 120 kDa PDE-3A (57-69%) were seen in both ventricles in HF or in the RV at 3 wk; an LV-specific reduction (50%) in cytosolic 80 kDa PDE-3A in HF was also detected. In summary, RV-specific downregulation of PDE-3A mRNA/protein(s) at 3 wk suggests that hemodynamic rather than humoral mechanisms are responsible, and provides a molecular basis for the limited efficacy of milrinone in the progression of HF.

Development of decompensated dilated cardiomyopathy is associated with decreased gene expression and activity of the milrinone-sensitive cAMP phosphodiesterase PDE3A.

BACKGROUND: Phosphodiesterase III (PDE3) inhibitors are inotropic agents used to treat congestive heart failure (CHF) and are less effective in patients with severe CHF. Little is known about relative changes in PDE3 activity or gene expression during the evolution of cardiomyopathy. METHODS AND RESULTS: In the present study, we evaluated temporal changes in PDE3A gene expression before and after pacing-induced CHF in nine mongrel dogs. Three weeks of left ventricular (LV) pacing produced LV end-diastolic pressures of 15+/-1.7 mm Hg, whereas overt CHF at 4 to 5 weeks was associated with LV end-diastolic pressures of 24+/-1.7 mm Hg; prepacing values were 6.6+/-0.6 mm Hg. Total RNA isolated from LV tissues was analyzed on Northern blots; 10 unpaced normal hearts served as tissue controls. Signals for PDE3A mRNAs (7, 8, and 10 kb) or PDE4D (7.6 kb) were normalized against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or ribosomal 18S RNA. Before the onset of CHF, PDE3A/GAPDH ratios were not different between the control and 3-week paced groups. In contrast, all PDE3A/GAPDH ratios were selectively reduced by 52%, and PDE3A/18S was reduced by 70% (P<.05) in CHF; PDE4D/GAPDH (or 18S) was unchanged. LV tissues from four control and four CHF dogs were also processed to isolate cytosolic and microsomal membrane protein for cAMP PDE3 activity assays. CHF was associated with a significant 54% reduction (P<.05) in microsomal but not cytosolic PDE3 activity. CONCLUSIONS: Selective downregulation of PDE3A may account in part for the ineffectiveness of milrinone in the treatment of severe CHF.

Comparison of heparinized and nonheparinized solutions for maintaining patency of arterial and pulmonary artery catheters.

BACKGROUND: Arterial and pulmonary artery catheters are often used in the management of critically ill patients. If heparin were not necessary to maintain the patency of arterial and pulmonary artery catheters, these patients could avoid exposure to heparin. OBJECTIVES: The purpose of this study was to determine if the failure rate of arterial and pulmonary artery catheters differs depending on whether a nonheparinized or heparinized solution is used. The null hypothesis was that catheter failure rates would not differ. METHODS: The study was done at a large tertiary medical center in the northeastern United States, and all subjects who had pulmonary artery or arterial catheters inserted were included in the study. A solution of 1 U of heparin per 1 mL of normal saline was used to maintain the patency of the arterial catheter and the distal portion of the pulmonary artery catheter in one group; normal saline alone was used in the other group. Variables used to monitor catheter patency and the reasons for catheter removal were recorded. RESULTS: Failure rates of pulmonary artery catheters were not significantly different between the two groups. For arterial catheters, however, the failure rate was significantly different between the two groups, regardless of whether the subjects had received other anticoagulants. CONCLUSION: The failure rate of pulmonary artery catheters was not affected by the use of nonheparinized solutions. Arterial catheters failed less often when they were maintained with heparinized solutions. The authors recommend that all arterial catheters be maintained with heparinized solutions, unless use of heparin is contraindicated.

Immediate-early gene expression in human saphenous veins harvested during coronary artery bypass graft operations.

Saphenous vein graft occlusion is a common late complication of coronary bypass grafting. Intimal smooth muscle cell hyperplasia is a component of this pathobiology, but the underlying molecular events are poorly understood. Immediate-early genes are activated shortly after growth stimulation and subserve cellular functions, which may contribute to intimal smooth muscle cell accumulation. In the present study, human saphenous vein grafts were harvested with minimal manipulation during coronary bypass and processed for isolation of total ribonucleic acid to examine change in immediate-early gene expression of messenger ribonucleic acid by Northern blotting techniques. Thirty saphenous vein grafts were incubated at 4 degrees C in Dulbecco's modified Eagle media from 30 minutes to 10 hours. The messenger ribonucleic acids for immediate-early genes c-fos and c-myc were weak or undetectable in controls but were increased (> 10 times controls) within 1 hour (c-fos) and persisted for at least 6 hours (c-myc) after harvest. Our results demonstrate, for the first time in human vascular tissue, incipient immediate-early gene induction. This information may lead to molecular therapies to control saphenous vein graft disease.

Unplanned extubation in the intensive care unit: a quality-of-care concern.

A 1-month prospective quality improvement audit was performed to determine the incidence of self-extubation in the intensive care units (ICUs) at the Westchester County Medical Center (WCMC), a 625-bed tertiary care hospital with 92 intensive care beds in 11 ICUs. During the 1-month study period, there were seven unplanned extubations in six of 121 intubated patients, or one unplanned extubation for every 136 patient-ventilator days. Based on the initial review, a corrective action plan was initiated that consisted of education of nurses and house staff about the problem of unplanned extubation, daily assessment on rounds of patient risk of unplanned extubation, and careful documentation of any episodes of unplanned extubation. A 5-month follow-up review identified 12 unplanned extubations in 11 patients, which resulted in a reduced rate of one unplanned extubation per 455 patient-ventilator days. Risk factors for unplanned extubation included documented anxiety, routine care intervention, and a history of previous unplanned extubation. Unplanned extubation can be a serious complication associated with mortality and therefore is a quality-of-care concern. However, the majority of patients with this complication did well and were discharged from the hospital. The incidence of unplanned extubation can be reduced but not eliminated by a program of education and attention to risk factors for unplanned extubation.

Experience with the Mitroflow aortic bioprosthesis.

From October 1985 to May 1990, the Mitroflow bovine pericardial valve was placed in the aortic position in 168 patients (97 men, 71 women) with a mean age of 69.7 years. Eighty-nine patients had isolated aortic valve replacement, and 79 had aortic valve replacement and additional procedures. Follow-up over 7 1/2 years includes 781 patient years (426 for isolated aortic valve replacement). Mean follow-up time is 56 months. Peak-to-peak gradients (in millimeters of mercury) measured in the intraoperative period averaged 11.0 +/- 8.7, 11.8 +/- 10.8, and 8.6 +/- 8.2 for 19 mm, 21 mm, and 23 mm valves, respectively. Hospital mortality was 7.3% (14 patients); all deaths were non-valve related. Late mortality of 20.1% in 31 patients resulted from cardiac failure (n = 8), sepsis (n = 4), valve reoperation (n = 1), non-cardiac causes (n = 15) and sudden, unknown causes (n = 3). Fifteen thromboembolic episodes occurred, but only three late thromboembolic episodes occurred in isolated aortic valve replacement without other risk factors. Four early and four late episodes of endocarditis occurred. Seven patients had clinical valve dysfunction, and five others required reoperation for structural deterioration, with one death. At 94 months, overall survival was 64% +/- 5%. Freedom from thromboembolic episode was 87% +/- 3% and 90% +/- 4% for isolated aortic valve replacement. Freedom from combined reoperation or clinical dysfunction was 75% +/- 8%: 64% +/- 15% for those under 70 years of age, and 87% +/- 7% for those 70 years of age and older. The valve has favorable hemodynamics. Durability begins to decline during the sixth year after implantation, possibly at a slower rate in patients older than 70 years of age.

Aortic annular abscess complicating prosthetic valve endocarditis with group G streptococcus: detection during life with transesophageal echocardiography.

Infection with group G streptococcus is an unusual but virulent cause of endocarditis. Aortitis and abscess formation due to this organism have been described in one previous report, but only at necropsy. We present here a patient with group G streptococcal endocarditis and aortic annular abscess diagnosed during life by transesophageal echocardiography, leading to successful surgical intervention.

Primary cardiac tumors. Diagnosis and management in 14 cases.

In our experience over a 10-year period at Westchester County Medical Center (Valhalla, NY), we diagnosed 11 left atrial myxomas and three primary cardiac malignancies in ten females and four males, aged 18-74 years. Two-dimensional echocardiography enabled the correct diagnosis of these lesions. Detailed characteristics of the cardiac tumors were provided by magnetic resonance imaging (MRI) scanning in five patients. Two of three malignancies were only biopsied; the myxomas were completely excised. We emphasized removal of tumor and its attachments to the atrial wall, accomplished by left or biatrial incision, full-thickness excision of the area of attachment, and pericardial patch closure of the atrial or free-wall defects. Associated procedures included mitral valve repair (three) and coronary artery bypass grafting (two). There was no mortality associated with the surgery. Two patients with malignancy died three and 36 months after surgery; a third is alive at 30 months after surgery. No patients with myxoma has had recurrence from 16 to 100 months. Preoperative diagnosis of cardiac tumors is enhanced by MRI scanning and may help in planning the surgical procedure. Complete and timely removal of these tumors contributes to long-standing patient survival.

Identification of calcified intracardiac lesions using gradient echo MR imaging.

Gradient echo signal imaging (GEI) has expanded the clinical role of magnetic resonance (MR) imaging of the heart. The role of GEI to evaluate intracardiac calcified lesions was studied. All patients were imaged with both conventional spin echo (SE) techniques and GEI. The GEI demonstrated that calcific cardiac lesions exhibit magnetic susceptibility differences and produce marked hypointensity throughout the calcified area. All patients had echocardiographic and fluoroscopic evidence of cardiac calcification and surgical confirmation of calcified lesions. The SE MR was unable to define the intracardiac calcification. Gradient echo imaging may be a helpful adjunct in the complete definition of intracardiac calcific lesions. When profound signal void areas are detected on cardiac GEI studies, calcification should be suspected.

Use of the centrifugal flow pump for vena caval shunting.

We have used the Bio-Medicus centrifugal flow pump for vena cava shunting during surgical resection of renal cell carcinoma with extension of the tumor into the inferior vena cava. The active shunt can provide optimal blood return to the heart to promote hemodynamic stability, help provide an isolated field for resection of the involved kidney and its tumor extension into the vena cava, and avoid use of full-dose heparin to minimize blood loss in this extensive operation.

MR imaging in the definition of coronary artery anomalies.

Coronary angiography remains the standard imaging technique to study coronary artery anatomy. Coronary artery aneurysms and fistulas are often incompletely visualized with routine angiography. Magnetic resonance (MR) imaging of such coronary anomalies is presented. The MR images improve the preoperative assessment of patients with coronary artery aneurysms and fistulas.

Postoperative evaluation of ascending aortic prosthetic conduits by magnetic resonance imaging.

Operative repair of ascending thoracic aortic dissection and aneurysm often involves the placement of prosthetic aortic conduits and stents with wrapping of the native aorta around the prosthetic device. Postoperative assessment has been clinical because of the absence of an adequate noninvasive imaging modality and a reluctance to perform invasive contrast aortography. Magnetic resonance imaging was performed on ten patients after operative placement of a prosthetic ascending aortic graft. The MR images were reviewed and a grading system was devised based on appearance of the operative site. An increase in MR signal was noted in some patients between the graft and wrapped native vessel. In 20 percent of patients vascular lumen compromise was noted. Magnetic resonance imaging offers a noninvasive technique to assess postoperative complications and offers a viable alternative to invasive contrast aortography.

Simplified method for reoperation on the mitral valve.

Reoperation on the mitral valve is becoming more common because of the degeneration of bioprosthetic valves, endocarditis, and malfunction or thrombosis of mechanical valves. We advocate a technique that transforms a technically difficult operation into one that is much less tedious, time-consuming, and dangerous than reopening a sternal-split operative site the second, third, or fourth time. Favorable experience in 11 patients using right anterolateral thoracotomy without aortic or right atrial cannulation and without aortic cross-clamping or cardioplegia is presented.

Shortening velocity and myosin and myofibrillar ATPase activity related to myosin isoenzyme composition during postnatal development in rat myocardium.

The relation between functional properties of the contractile apparatus, such as shortening velocity and ATPase activity, and myosin isoenzyme composition was studied in ventricular myocardium of adult (60-90-day-old) rats and of newborn (3-day-old) and young (10- and 20-day-old) rats. In adult animals, variations of isomyosin pattern were produced by reducing food intake and by changing the thyroid state. Hyperthyroidism was induced with triiodothyronine daily injection for 15 days; hypothyroidism was induced with iodine-free diet and KClO4 in drinking water for 50-60 days. The following parameters were studied: 1) calcium-magnesium-activated and magnesium-activated ATPase activity of washed and purified myofibrils, 2) calcium-activated ATPase activity of purified myosin, 3) isomyosin composition and relative content of alpha-myosin heavy chains (alpha-MHCs), and 4) force-velocity curve of left and right ventricle papillary muscles. To take into account the difference in excitation-contraction coupling between newborn and adult myocardium, the determination of the force-velocity curve was repeated in Krebs' solution with normal [CaCl2] (2.5 mM) and in Krebs' solution with high [CaCl2] (10 mM). During postnatal growth, the relative content of alpha-MHC increased and reached a maximum at about 20 days. Pronounced increases of myofibrillar and myosin ATPase activity and in shortening velocity occurred during the same period. In adult hyperthyroid rats, alpha-MHC content as well as enzymatic activity and shortening velocity were higher than in control adult animals. Hypothyroidism and food deprivation caused a decrease of alpha-MHC content and a reduction of both enzymatic activities and shortening velocity. The study of the relations between alpha-MHC relative content and functional parameters showed that 1) in ventricular myocardium of adult rats a linear relation existed between alpha-MHC content and myosin and myofibrillar ATPase activity and shortening velocity, and 2) in newborn and young rat ventricular myocardium, both enzymatic activities and shortening velocity were lower than would have been expected on the basis of the linear relation described above. This latter observation could be accounted for by a variation in specific activity of myosin during postnatal development or by the presence of peculiar isomyosins that cannot be detected with usual electrophoretic techniques.

Reduction of myofibrillar ATPase activity and isomyosin shift in delayed doxorubicin cardiotoxicity.

The aim of this study was to determine whether variations of isomyosin expression occurred during doxorubicin-induced cardiomyopathy. A suitable experimental model in which pure delayed cardiotoxic effects could be easily studied was adopted. Young adult female Sprague Dawley rats received 9 mg/kg of doxorubicin (DXR) i.v. divided into three subdoses of 3 mg/kg every third day. Control animals received equal volumes of saline. The animals were examined 9 weeks after treatment. At this time the animals treated with DXR showed ECG alterations, reduction of body weight and a marked decrease of both atrial and ventricular mass, but were still fully hemodynamically compensated. Loss of myofibrillar material could be documented by the reduced recovery of myofibril and myosin. The contractile response of papillary muscles isolated from the right ventricle of treated animals was markedly impaired. Ca-Mg-activated and Mg-activated myofibrillar ATPase activity and Ca-activated myosin ATPase activity were determined on ventricular myocardium of control and treated animals. Both myofibrillar and myosin ATPase activities were found to be significantly reduced. Pyrophosphate gel electrophoresis of purified myosin was carried out. The isomyosin pattern of DXR-treated animals showed a pronounced shift towards V3, the percent of alpha heavy chains being 54.6% in treated rats (80.5% in control rats). This isomyosin shift can explain the reduced myofibrillar and myosin ATPase activity found in treated animals.

The dual effect of thyroid hormones on contractile properties of rat myocardium.

This study was designed to investigate the changes in cardiac contractile properties induced by triiodothyronine (T3) administration in adult rats. Myofibrils and myosin were isolated from ventricular muscles from euthyroid and hyperthyroid animals and enzymatically and electrophoretically characterized. The time course of the isometric response, the force velocity curve, the force interval relation were studied in papillary muscles isolated from the right ventricles of euthyroid and hyperthyroid rats. T3 administration induced significant increases in Mg2+ activated myofibrillar ATPase activity (+11.4%) and in Ca2+ activated myosin ATPase activity (+20.1%). Significant increases in shortening velocity at low and zero loads (+20.4%) were found in papillary muscles from treated animals when compared with the control muscles. These variations in enzymatic activity and shortening velocity could be related to the increase in the amount of the fast isomyosin V1, as shown by pyrophosphate gel electrophoresis. The negative force-frequency relation at steady state, typical of rat cardiac preparations, was observed in treated and control animals; its slope was, however, halved in hyperthyroid papillary muscles when compared with control ones. In accordance with this finding, the potentiating effect of a prolonged diastolic interval was significantly reduced in hyperthyroid papillary muscles. In the frame of an interpretation of the force interval relation on the basis of the excitation contraction coupling processes, these latter observations might indicate an enhanced activity of the sarcoplasmic reticulum. We conclude that thyroid hormone administration has a dual effect on cardiac contractility, on one hand regulating the synthesis of the different isomyosin and, on the other hand, stimulating the activity of the sarcoplasmic reticulum.

Prevention of ventricular fibrillation after aortic declamping during cardiac surgery.

Ventricular fibrillation is common after aortic declamping during cardiac surgery, and the metabolic demands of such fibrillation, or its treatment by means of countershock, may contribute to myocardial injury. To determine the effects of administering intravenous lidocaine just before aortic declamping, we randomly divided 194 cardiac surgery patients into 2 groups. One hundred patients (group A) received lidocaine, 200 mg intravenously, 3 minutes before aortic declamping; and 94 patients (group B) received no medication before declamping. Multiple baseline variables, including clamp times, medications, electrolyte values, ventricular function, and the extent and type of surgery, were similar for both groups. After aortic declamping, 31 of the 100 patients in group A had ventricular fibrillation, as did 57 of the 94 patients in group B (p < 0.001). Of those who fibrillated, the group-A patients required a mean of 1.76 countershocks, whereas the group-B patients required a mean of 2.68 countershocks (p < 0.05). Serum potassium level also affected the incidence of ventricular fibrillation, independently of lidocaine. Elevated serum potassium levels were associated with a lower incidence of ventricular fibrillation. Although lidocaine was independently protective at all potassium levels, the combination of lidocaine and a high serum potassium level had the greatest effect in preventing fibrillation. In patients who had potassium levels higher than 5.1 mEq/l and who were also given lidocaine, the incidence of ventricular fibrillation was lower than 15%.

Circadian rhythms of acid secretion and electric parameters in rat gastric mucosa in vitro.

In male Wistar rats standardized from birth in LD 12:12 conditions (with light from 0700 to 1900 hr), samples of mucosa from the body of the stomach were isolated in vitro and mounted in a Ussing-type chamber. Spontaneous secretion of the hydrogen ion (H+)during 45 min of incubation was measured. Some electric parameters [transmucosal potential difference (PD) and electrical resistance (R)] were detected in the gastric mucosa both during H+ secretion and during inhibition of acid secretion by cimetidine. The variables studied were analyzed with the single cosinor method, and all revealed a circadian rhythm with acrophases during the dark span. The higher values of PD and R found during the dark hours are unrelated to acid secretion and may indicate a greater efficiency of ionic pumps and a limited passive permeability.

Coronary revascularization in young patients.

From 1978 to 1982, 92 of our 1704 patients undergoing coronary bypass surgery were 40 years of age or younger. Eighty-six were male and six were female. The main indications for surgery were refractory angina and unstable angina. A family history of heart disease, smoking, and hypertension were major risk factors. The majority of patients had triple vessel disease, and six had left main lesions. Left ventricular function was moderately or severely impaired in 24. Coronary revascularization was performed with internal mammary and saphenous vein conduits, with a mean of 3.7 grafts per patient (range, 1 to 7). There was no operative mortality, but one patient required an intraaortic balloon pump. Perioperative infarction determined by Q waves occurred in one patient, while eight had enzymatic evidence of infarction. Late follow-up to 60 months showed three late deaths of cardiac origin. Eighty-three survivors were greatly improved, and 50 were asymptomatic. Sixty-five patients returned to work. Seventy percent of smokers stopped smoking; half the patients exercised regularly, and half maintained dietary modifications. Coronary bypass grafting is an effective rehabilitation procedure in the young. Long-term attention to risk factors and life style is required to maintain a beneficial outcome.