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B G Hattler

Publications and source records attributed to B G Hattler.

At least 37 records · Page 2Linked to original sources
PubMed1996

Primary cardiac lymphoma: echocardiographic characterization and successful resection.

We present a case of primary cardiac lymphoma in a patient with dyspnea and hypoxemia. Transesophageal echocardiography reveals a large right atrial mass and an atrial septal aneurysm with right-to-left shunting through a patent foramen ovale. The patient underwent resection and atrial reconstruction. Pathology was a B cell lymphoma with diffuse large cell histology. There was no evidence of extracardiac involvement, and the patient is well 3 months postoperatively with a normal transthoracic echocardiogram.

Combined Modality Therapy↗
PubMed1996

A prospective trial of tacrolimus (FK 506) in clinical heart transplantation: intermediate-term results.

Between January 1, 1989, and December 31, 1994, we have treated 122 primary heart recipients with FK 506 (group I) and 121 with cyclosporine (group II). Fifty patients in the cyclosporine (CyA) group received no lympholytic induction (CyA alone) and 71 others received lympholytic induction with either rabbit antithymocyte globulin or OKT3 (CyA+LI). The mean follow-up was longer in the FK 506 group than in the CyA groups (3.2 +/- 1.3 vs 2.3 +/- 1.8 years; p< 0.01). Patient survival did not differ on the basis of the type of immunosuppression used. At 3 months after transplantation, the freedom from rejection in the FK 506 group was higher than that of the CyA-alone group (47% vs 22%, p < 0.01) but similar to that of the CyA+LI group (47% vs 53%). The linearized rejection rate (episodes/100 patient-days) of the FK 506 group (0.09 episodes) was lower (p < 0.05) than that of the CyA-alone group (0.26) and the CyA+LI group (0.13). The requirement for pulsed steroids to treat rejection was less in common in the FK 506 group than in either CyA group. Eighteen patients in the CyA group had refractory rejections; all resolved with FK 506 rescue. Two patients in the FK 506 group had refractory rejection that resolved with total lymphoid irradiation (n=1) and methotrexate therapy (n=1). Patients receiving FK 506 had a lower risk of hypertension and required a lower dose of steroids. Although the mean serum creatinine concentration at 1 year was higher in the FK 506 group, this difference disappeared after 2 years. No patients required discontinuation of FK 506 because of its side effects. Our intermediate-term results indicate that FK 506 compares favorably with CyA as a primary immunosuppressant in heart transplantation.

Adult↗
PubMed1996

Transplant candidate's clinical status rather than right ventricular function defines need for univentricular versus biventricular support.

We have studied our experience since 1988 with 31 patients who required a mechanical circulatory bridge to transplantation and also had biventricular failure (mean right ventricular ejection fraction 11.8%) to better define the need for biventricular or total artificial heart support versus univentricular support. Clinical factors including preoperative inotropic need, fever without detectable infection, diffuse radiographic pulmonary edema, postoperative blood transfusion, and right ventricular wall thickness were compared with hemodynamic parameters including cardiac index, right ventricular ejection fraction, central venous pressure, mean pulmonary arterial pressure, and total pulmonary resistance for ability to predict need for mechanical or high-dose inotropic support for the right ventricle. Patients were grouped according to need for right ventricular support after left ventricular-assist device implantation: none (group A, 14) inotropic drugs (group B1, 7), and right ventricle mechanical support (group B2, 10). There were no differences in preimplantation hemodynamic variables. Groups B1 and B2 had significantly lower mixed venous oxygen saturation (39.2% vs 52.5% in group A; p < 0.001), greater level of inotropic need (p < 0.02), greater impairment of mental status, and lower ratio of right ventricular ejection fraction to inotropic need (0.37 vs 0.56 for group A; p < 0.02) before left ventricular-assist device implantation. A significant discriminator between groups B1 and B2 was the presence of a fever without infection within 10 days of left ventricular-assist device implantation (43% in group B1 vs 70% in group B2). Group B2 had more patients with preimplantation pulmonary edema seen on chest radiography and a greater requirement for postoperative blood transfusion (5 units of cells in group B1 vs 14.8 units in group B2. Right ventricular wall thickness at left ventricular-assist device explantation was 0.83 cm in group B2 vs 0.44 cm in group B1 (p < 0.05). Transplantation rates after bridging were 100% in group A, 71% in group B1, and 40% in group B2. Clinical factors that reflect preimplantation degree of illness and perioperative factors that result in impairment of pulmonary blood flow or reduced perfusion of the right ventricle after left ventricular-assist device implantation are now considered to be more predictive of the need for additional right ventricular support than preimplantation measures of right ventricular function or hemodynamic variables.

Adolescent↗
PubMed1996

Sweep gas flowrate and CO2 exchange in artificial lungs.

A simple analysis and graphic result are presented for characterizing the dependence of CO2 exchange on the sweep gas (ventilating gas) flowrate in artificial lungs. The analysis requires no knowledge of the device-specific mass transfer characteristics of an artificial lung, nor does it require detailed mathematical modeling or computer simulation. Rather, it uses appropriate normalization to establish generic features of the gas flow dependency of CO2 exchange that are applicable to all artificial lung devices. Principal results are that the transition from relatively gas flow-sensitive to gas flow-insensitive CO2 exchange occurs at sweep gas flowrates of approximately 40-60 times the CO2 exchange rate. Achieving a CO2 exchange rate within 85% of maximal (for a given oxygenator and blood-side conditions) requires a sweep gas flowrate of no less than approximately 50 times the nominal CO2 exchange rate. When the sweep gas flowrate is less than 20 times the CO2 exchange rate, CO2 exchange is highly gas flow dependent and less than one-half the maximal possible rate.

Artificial Organs↗
PubMed1996

Protein kinase A activation is required for IL-1-induced nitric oxide production by cardiac myocytes.

We have previously reported that interleukin-1 beta (IL-1) alone induced the transcription of inducible nitric oxide synthase (iNOS) mRNA and nitric oxide (NO) production by isolated neonatal rat cardiac myocytes (CM). The present studies were undertaken to explore the signal transduction pathways involved in IL-1-induced NO production by CM. The addition of IL-1 to CM resulted in a peak rise in both adenosine 3',5'-cyclic monophosphate (cAMP) and protein kinase A (PKA) activities by 10 min followed by rapid declines and return to basal levels within 60 min. The PKA inhibitor KT-5720 completely blocked NO-2 production by IL-1-stimulated CM (P < 0.01; n = 12). The protein kinase C (PKC) inhibitor, calphostin C, had no effect on NO2- production by IL-1 stimulated CM [P = not significant (NS); n = 12]. The addition of PKA+cAMP to cytosols derived from IL-1-treated CM did not directly enhance iNOS enzyme activity (P = NS; n = 3). CM treated with IL-1 alone stained positively for iNOS protein by immunohistochemistry. iNOS staining was absent in CM treated with IL-1+KT-5720. KT-5720 resulted in an earlier disappearance of iNOS mRNA from IL-1-treated CM, as detected by semiquantitative reverse transcriptase-polymerase chain reaction. We report for the first time that PKA (but not PKC) activation is required for IL-1-induced NO production by CM.

Animals↗
PubMed1996

Suspended animation for delayed resuscitation.

Suspended animation is defined as the therapeutic induction of a state of tolerance to temporary complete systemic ischemia, i.w., protection-preservation of the whole organism during prolonged circulatory arrest ( > or = 1 hr), followed by resuscitation to survival without brain damage. The objectives of suspended animation include: a) helping to save victims of temporarily uncontrollable (internal) traumatic (e.g., combat casualties) or nontraumatic (e.g., ruptured aortic aneurysm) exsanguination, without severe brain trauma, by enabling evacuation and resuscitative surgery during circulatory arrest, followed by delayed resuscitation; b) helping to save some nontraumatic cases of sudden death, seemingly unresuscitable before definite repair; and c) enabling selected (elective) surgical procedures to be performed which are only feasible during a state of no blood flow. In the discussion session, investigators with suspended animation-relevant research interests brainstorm on present knowledge, future research potentials, and the advisability of a major research effort concerning this subject. The following topics are addressed: the epidemiologic facts of sudden death in combat casualties, which require a totally new resuscitative approach; the limits and potentials of reanimation research; complete reversibility of circulatory arrest of 1 hr in dogs under profound hypothermia ( < 10 degrees C), induced and reversed by portable cardiopulmonary bypass; the need for a still elusive pharmacologic or chemical induction of suspended animation in the field; asanguinous profound hypothermic low-flow with cardiopulmonary bypass; electric anesthesia; opiate therapy; lessons learned by hypoxia tolerant vertebrate animals, hibernators, and freeze-tolerant animals (cryobiology); myocardial preservation during open-heart surgery; organ preservation for transplantation; and reperfusion-reoxygenation injury in vital organs, including the roles of nitric oxide and free radicals; and how cells (particularly cerebral neurons) die after transient prolonged ischemia and reperfusion. The majority of authors believe that seeking a breakthrough in suspended animation is not utopian, that ongoing communication between relevant research groups is indicated, and that a coordinated multicenter research effort, basic and applied, on suspended animation is justified.

Animals↗
PubMed1995

Regulation of constitutive nitric oxide synthase activity by the human heart.

We and others have provided indirect evidence for the presence of a constitutive nitric oxide synthase (cNOS) in the mammalian heart. We now provide more direct evidence for the regulation of a myocardial cNOS in the hearts of patients undergoing elective cardiopulmonary bypass (CPB). cNOS enzyme activity was demonstrable in both cytosolic (8.3 +/- 0.02 pmol/min/mg) and membrane (11.1 +/- 0.4 pmol/min/mg) preparations derived from human atrial pectinate muscles obtained at the time of CPB (n = 6). Plasma nitrite (NO2-) + plasma nitrate (NO3-) levels from the beating hearts of patients before bypass were reduced from 146 +/- 33 to 5.1 +/- 50 pmol/min/g after cardiac arrest during CPB (n = 23; p < 0.002 by Student's t test). Thus, the human myocardium constitutively produces nitric oxide that is regulated by the contractile state of the heart.

Adult↗
PubMed1995

Changes in electrocardiographic morphology reflect instantaneous changes in left ventricular volume and output in cardiac surgery patients.

We examined the relation between changes in R-to-T wave amplitude ratios (R:T) and left ventricular (LV) performance as cardiac output was rapidly varied by inferior vena caval occlusion in 6 subjects prior to cardiopulmonary bypass. To assess the influence of contractility, paired studies before and after bypass were performed in 4 subjects. Stroke volume and cardiac output were assessed by aortic flow probe, and transesophageal echocardiographic LV area measures using the automated border-detection method were used to give LV stroke area, stroke force, maximal LV area, fractional area change, end-systolic elastance, and preload recruitable stroke force. Data were collected on computer and analyzed by linear regression. Significant changes in R:T and measured LV variables during the inferior vena caval occlusion were stroke volume (r = 0.81), LV stroke area (r = 0.77), LV stroke force (r = 0.81), maximal LV area (r = 0.78), and cardiac output (r = 0.80). However, R:T varied inconsistently in relation to fractional area change. After cardiopulmonary bypass, the linear relation between R:T with LV stroke force, LV stroke volume, and maximal LV area persisted, but at a lesser slope. Although absolute pre-inferior vena caval occlusion R:T did not correlate with end-systolic elastance or preload recruitable stroke force, the change in the slope of these linear relations correlated well with the change in end-systolic elastance after surgery (r = 0.92). Instantaneous changes in electrocardiographic morphology reflect changes in LV preload-dependent variables, whereas long-term changes in electrocardiographic morphology may also reflect changes in contractile state.

Aged↗
PubMed1995

Solid tumors after heart transplantation: lethality of lung cancer.

BACKGROUND: Prolonged nonspecific immunosuppression after solid-organ transplantation is associated with an increased risk of certain cancers. This study examined the development of solid-organ tumors after cardiac transplantation. METHODS: Thirty-eight solid tumors were identified in 36 (5.9%) of 608 cardiac transplant recipients who survived more than 30 days. Two patients had two types of skin tumors (basal cell and squamous cell). The tumors included the following types: skin (15), lung (10), breast (1), bladder (2), larynx (2), liver (1), parotid (1), testicle (1), uterus (2), melanoma (2), and Merkel's cell (1). Four immunosuppression regimens based on cyclosporin A or FK 506 were used during this period. RESULTS: There was no association between the incidence of solid tumors and the use of lympholytic therapy. After the diagnosis of tumor was made, the actuarial 2-year survival rates of recipients with skin, lung, and other solid tumors were 71%, 22%, and 23%, respectively. Eight of 10 patients with lung cancer were in stage IIIA or higher at the time of diagnosis. CONCLUSION: Skin and lung tumors are the most frequent solid tumors in heart transplant recipients. Skin tumors (except Merkel's cell carcinoma and melanoma) usually have a benign course, whereas lung and other tumors developing in cardiac transplant recipients carry a poor prognosis. Advanced disease stage at the time of diagnosis is responsible for the dismal outcome of recipients in whom solid tumors develop. Close postoperative tumor surveillance after cardiac transplantation is warranted.

Actuarial Analysis↗
PubMed1995

Perioperative donor bone marrow infusion augments chimerism in heart and lung transplant recipients.

BACKGROUND: We and others have demonstrated that a low level of donor cell chimerism was present for years after transplantation in tissues and peripheral blood of heart and lung recipients; it was associated, in the latter, with a lower incidence of chronic rejection. To augment this phenomenon, we initiated a trial combining simultaneous infusion of donor bone marrow with heart or lung allotransplantation. METHODS: Between September 1993 and January 1995, 15 nonconditioned patients received either heart (n = 10) or lung (n = 5) allografts concurrently with an infusion of unmodified donor bone marrow (3.0 x 10(8) cells/kg), and were maintained on immunosuppressive regimen consisting of tacrolimus and steroids. RESULTS: There was no complication associated with the infusion of donor bone marrow. Chimerism was detectable in 73% of bone marrow-augmented patients up to the last sample tested. Of the 5 control recipients who did not receive bone marrow infusion, only 1 had detectable chimerism by flow on postoperative day 15, which dwindled to an undetectable level by postoperative day 36. None of the patients had evidence of donor-specific immune modulation by mixed lymphocyte reaction. CONCLUSIONS: The combined infusion of donor bone marrow and heart or lung transplantation, without preconditioning of the recipient, is safe and is associated with an augmentation of donor cell chimerism.

Adult↗
PubMed1995

The need for accurate risk-adjusted measures of outcome in surgery. Lessons learned through coronary artery bypass.

OBJECTIVE: The authors review the Pennsylvania Health Care Cost Containment Council reports on coronary artery surgery and compare this reporting structure to others, including the Society for Thoracic Surgeons database, currently used by their own program. The authors review the growing likelihood of a need for outcome measures for all of the surgical subspecialties. SUMMARY AND BACKGROUND DATA: Pressure from consumers and insurers will require surgical specialties to be graded by objective outcome measures. Practitioners must be prepared and become involved in the process. METHODS: The authors reviewed the data, which grades all of Pennsylvania's hospitals at which coronary artery bypass is performed. Apparently, the major risk factors commonly employed in most other risk adjustment schemes for cardiac surgery have been deleted, and the practitioners might be judged unfairly. The Pennsylvania system appears to be insurance driven to reward low-cost providers who operate on patients with the lowest risk. RESULTS: Review of data suggests that the Pennsylvania Health Care Cost Containment Council's annual publication, A Consumer's Guide for Coronary Artery Bypass Surgery, misrepresents fair risk adjustment in favor of lower-risk patients, thereby encouraging better score cards for those institutions with patients who are less ill. Data regarding charges for the procedure have not been risk adjusted or related to a regional economic index. CONCLUSIONS: Surgeons must prepare to better understand relevant models that evaluate outcome. Cardiothoracic surgery is one of the first specialties to feel the pressures of mandated evaluations, and the lessons learned in Pennsylvania should be applicable to other states and their practitioners.

Coronary Artery Bypass↗
PubMed1995

Cytokine induction during cardiac surgery: analysis of TNF-alpha expression pre- and postcardiopulmonary bypass.

Cytokines are soluble mediators that possess both intra- and intercellular signaling properties. Their function has been investigated most thoroughly in the context of immune reactions. Cytokines, however, form an important component of the inflammatory response to trauma and are found in elevated concentrations following cardiopulmonary bypass (CPB). We were, therefore, interested in studying mRNA expression for the cytokine tumor necrosis factor alpha (TNF-alpha) in patients undergoing cardiac surgery. White cells isolated from the circulation of seven patients before and after CPB were assayed for the expression of mRNA with TNF-alpha specific primers using the polymerase chain reaction. Message for TNF-alpha was found in all patients, with the highest values demonstrated in patients whose CPB times exceeded 1 1/2 hours. Enhanced message expression was seen as early as 1 hour after the start of CPB. Genes responsible for cytokine (TNF-alpha) expression and production are activated during cardiac surgery.

Base Sequence↗
PubMed1995

cAMP enhances inducible nitric oxide synthase mRNA stability in cardiac myocytes.

The effects of adenosine 3',5'-cyclic monophosphate (cAMP) on cardiac myocyte nitric oxide (NO) production were studied. Maximal nitrite (NO2(-)) production by cultured neonatal rat cardiac myocytes was achieved with 500 U/ml interleukin-1 beta (IL-1 beta) for 48 h (4.6 +/- 0.3 nmol/1.25 x 10(5) cells; n = 12). Cardiac myocytes exposed to 500 U/ml IL-1 beta for 48 h stained positively for inducible nitric oxide synthase (iNOS) by immunohistochemistry. Forskolin (FSK; adenylate cyclase stimulator) or dibutyryl cAMP (DBcAMP; membrane-permeable cAMP analogue) administration alone had no effect on NO2(-) production. The addition of FSK or DBcAMP to IL-1 beta significantly increased NO2-) levels vs. IL-1 beta alone (9.7 +/- 0.6 and 10.9 +/- 0.8 vs. 4.6 +/- 0.3 nmol/1.25 x 10(5) cells per 48 h, respectively; P < 0.01; n = 12). Semiquantitative reverse transcriptase-polymerase chain reaction revealed increased iNOS mRNA in myocytes treated with FSK+IL-1 beta or DBcAMP+IL-1 beta vs. those treated with IL-1 beta alone. The addition of FSK or DBcAMP to IL-1 beta increased iNOS mRNA half-life over IL-1 beta treatment alone (10.6, 11.7 vs. 2.4 h, respectively). Cardiac myocytes do not express iNOS in response to cAMP alone. Rather, cAMP enhances iNOS mRNA stability following cytokine exposure.

Animals↗
PubMed1995

Nitric oxide synthase inhibitor alters papillary muscle force-frequency relationship.

We provide evidence for an immediate effect of NG-monomethyl-L-arginine (L-NMMA) on the force-frequency relationship in isolated hamster papillary muscles. L-NMMA (competitive inhibitor of nitric oxide synthase) reversed the force-frequency relationship (staircase effect) in isolated hamster papillary muscles from negative to positive (P < .01; ANOVA; n = 6). The addition of L-arginine (substrate for nitric oxide synthase) blocked the L-NMMA effect (P < .01; ANOVA; n = 6). The addition of the nitric oxide (NO) donor, sodium nitroprusside (NTP), significantly increased the level of cGMP in the tissue bath (P < .01; test; n = 6) and reversed the positive inotropic effect of L-NMMA on staircase (P < .01; ANOVA; n = 6). The addition of 8-Br-cGMP to the bath resulted in a concentration-dependent decrease in tension generated by the papillary muscles (n = 6). Methylene blue (known inhibitor of cGMP) mimicked the effect of L-NMMA on staircase (P < .01; ANOVA; n = 6). L-NMMA also significantly blunted the negative inotropic effect of ryanodine (SR calcium release channel regulator) (P < .01; ANOVA; n = 6). The positive inotropic effect of Bay K 8644 (sarcolemmal, L-type calcium channel regulator) was not affected by L-NMMA (P = NS; ANOVA; n = 6). L-NMMA had no effect on either [3H]ryanodine or [3H]PN200-110 (sarcolemmal, L-type calcium channel regulator) binding to cardiac membranes. These findings support a cGMP-dependent role for endogenous NO in myocardial E-C coupling.

Amino Acid Oxidoreductases↗
PubMed1994

Chronotropic effects of cytokines and the nitric oxide synthase inhibitor, L-NMMA, on cardiac myocytes.

We and others have proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. An effect of NO on cardiac sarcolemmal L-type calcium channels has also recently been proposed. The spontaneous beating rate of neonatal cardiac myocytes is regulated by the sarcolemmal L-type calcium channel. Accordingly, we sought to determine if cytokine-stimulated NO production could also regulate beating rates of neonatal cardiac myocytes. Treatment of neonatal rat cardiac myocytes with TNF, IL-1, IL-6, 10(-5)M NMA, or 10(-3)M NMA significantly enhanced spontaneous beating rates compared to untreated myocytes in serum-free media for 48 hours (p < or = .01; n = 12 for each). Only IL-1 treatment resulted in significant nitrite levels vs. control over 48 hours (4.2 +/- 0.7 vs. 0.3 +/- 0.2 nmoles/1.25 x 10(-5) cells, respectively) (n = 12). Nitrite production by IL-1 was inhibited by 10(-3)M NMA but not 10(-5)M NMA (0.3 +/- 0.2 vs. 4.1 +/- 0.6 nmoles; p < .01; n = 12). The addition of 10(-5)M NMA to TNF, IL-1, and IL-6 did not alter the effect of the cytokines on the spontaneous beating rates of the cardiac cells (p < or = .01; n = 12 for each). These results strongly suggest that cytokines and NMA affect cardiac myocyte spontaneous beating rates through mechanisms independent of NO.

Amino Acid Oxidoreductases↗
PubMed1994

Catalytic conversion of L-arginine to nitrate by platinum electrodes.

Platinum electrodes (PLE) have been used recently to study the physiologic effects of the enzymatic conversion of L-arginine (L-arg) to nitric oxide (NO) by nitric oxide synthase (NOS). We sought to determine if PLE alone could catalytically convert L-arg to NO without NOS. Accordingly, NO2- + NO3- levels (NOx) were measured by HPLC from a physiologic Tyrode's buffer in the presence and absence of electrical stimulation with PLE or silver chloride electrodes (SCE) for 10 min (n = 6 for each condition). PLE stimulated at 1Hz produced 24 +/- 0.7 and 15.4 +/- 2.8 microM NOx from D-arg and L-arg (100mM) respectively. PLE + L-arg stimulated from 0 to 5 Hz produced increasing NOx (2.9 +/- 0.27;15.4 +/- 2.8;19.7 +/- 4;32 +/- 5;37 +/- 6.2;43 +/- 7 microM). SCE+L-arg showed no increase in NOx above background. The addition of 1% BSA to the Tyrode's buffer further increased NOx levels. NO2- levels were undetectable, indicating all NOx levels were NO3-. We conclude that PLE can catalytically convert L-Arg to NO3- via electron transfer without NOS.

Arginine↗
PubMed1994

Risk stratification using the Society of Thoracic Surgeons Program.

In an era of progressive cost containment and public scrutiny, the wisdom of aggressive surgical therapy for high-risk candidates has been questioned. At our center in the previous 24 months, 728 patients with coronary artery disease were entered into The Society of Thoracic Surgeons national database, and the hospital outcomes plus length of stay were analyzed. Patients were separated according to the predicted mortality based on the groupings in The Society of Thoracic Surgeons database: 0 to 5% (453 patients); 5% to 10% (126 patients); 10% to 20% (96 patients); 20% to 30% (17 patients); and 30% and greater (36 patients). There was a close correlation with the predicted rates of mortality. Importantly, the preoperative risk stratification demonstrated a strong correlation with the significant morbidity and excessive length of stay in the highest-risk groups (predicted risk of 20% to > or = 30%). The incidences of the most common complications in the group with the highest predicted risk (> or = 30%) were 28%, renal failure; 33%, ventilator dependence; and 17%, cardiac arrest. In addition, at short-term follow-up (6 to 8 months), a 24.3% mortality was identified in patients with a predicted mortality that exceeded 20%. These data quantify the risks and morbidities associated with the care of seriously ill patients with coronary artery disease and demonstrate the need for professional and public discussions focusing on the association of a high preoperative risk status and the consumption of resources.

Aged↗