Biomedical subjects

S Murali

Publications and source records attributed to S Murali.

At least 55 records · Page 3Linked to original sources

PubMed1996

Prediction of mortality in patients awaiting cardiac transplantation: increased risk of sudden death in ischemic compared to idiopathic dilated cardiomyopathy.

A major problem in cardiac transplantation is the death of candidates due to the increasing shortage of donors and the consequent longer waiting periods. To determine whether clinical markers for death could be identified in these patients, 168 adult candidates with heart failure (NYHA class III and IV) listed between August 1987 and December 1989 were analyzed. There were 104 patients with ischemic cardiomyopathy (ISCM) and 64 with idiopathic dilated cardiomyopathy (IDCM). Transplantation was performed in 93 patients (55%). Actuarial 1 year survival was 61% in the ISCM group and 78% in the IDCM group (P = NS). Freedom from sudden death at one year was significantly lower in the ISCM group (73%) than in the IDCM group (96%) (P < 0.01). The rate of patients who did not die from terminal myocardial failure was 83% in the ISCM group and 81% in the IDCM group (P = NS). There were no significant differences between the two groups in right atrial, pulmonary artery, and pulmonary wedge pressures, transpulmonic pressure gradient, pulmonary vascular resistance, cardiac index, and ejection fraction. We conclude that candidates for cardiac transplantation with ISCM are at higher risk for sudden death during the first year on the waiting list than patients with IDCM. These results warrant consideration of aggressive arrhythmia control measures, including an automatic implantable defibrillator, to "bridge" these high risk patients to transplantation.

Actuarial Analysis↗

PubMed1995

Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group.

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.

Aged↗

PubMed1995

Strategies for pharmacologic modulation of the heart failure phenotype.

The end-stage heart failure phenotype is characterized by marked dyspnea on exertion, edema, and overwhelming fatigue, and by a high incidence of sudden death. Patients who display the end-stage phenotype have transitioned from a normal phenotype with myocardial damage at a cellular level. This transition appears to be mediated by events at both the cellular and molecular levels. Until recently, it was generally believed that this transition was irreversible. However, recent clinical trials have demonstrated that the phenotype can be changed with pharmacologic agents. These agents have been demonstrated to improve exercise capability, increase ventricular function, and improve symptoms. Important recent studies have shown that pharmacologic agents can substantially alter the high mortality rates associated with the end-stage heart failure phenotype. As we learn more about the molecular and cellular events that initiate and support the transition from cardiac compensation to decompensation, we will be able to improve our pharmacologic targeting and, we hope, be able to delay the development of the end-stage heart failure phenotype to an even greater degree.

Adrenergic beta-Antagonists↗

PubMed1995

Neurohormonal activation and exercise function in patients with severe heart failure and patients with left ventricular assist system. A comparative study.

OBJECTIVES: The aim of this study was to evaluate the effects of implantation of a left ventricular assist system (LVAS) on the neurohormonal status, exercise capacity and symptomatic state in patients with severe congestive heart failure (CHF). BACKGROUND: Severe CHF is characterized by decreased exercise tolerance and activation of several neurohormonal systems. METHODS: Parameters of neurohormonal activation and exercise capacity in patients with LVAS (n = 7) were compared with those in groups of New York Heart Association (NYHA) class 3 (n = 121) and class 4 (n = 81) patients. Plasma levels of norepinephrine (NE), plasma renin activity (PRA), and atrial natriuretic peptide (ANP) and maximal and submaximal exercise capacities were measured monthly in LVAS patients and compared with results in CHF patients. RESULTS: Plasma NE and PRA levels were significantly lower in LVAS patients than in NYHA class 4 patients, and plasma ANP levels in LVAS patients were significantly lower than those in NYHA class 3 and 4 patients. The distance walked during submaximal exercise testing and peak oxygen consumption during maximal exercise testing were similar for the LVAS and NYHA class 3 patients. The class 4 patients were unable to exercise. CONCLUSIONS: We conclude that the LVAS lessens the neurohormonal activation and exercise intolerance characteristic of the CHF state and that the exercise capacity early after LVAS (< 4 months) is similar to that observed in NYHA class 3 patients.

Adolescent↗

PubMed1994

Increased plasma atrial natriuretic peptide levels after heart transplant: relation to ventricular expression and severity of rejection.

To determine whether elevated plasma atrial natriuretic peptide (ANP) levels observed after cardiac transplant are related to ventricular ANP expression and/or the severity of rejection, 59 ambulatory patients with cardiac transplant underwent hemodynamic evaluation, endomyocardial biopsy, and plasma ANP sampling. Forty-two of the 59 patients had right ventricular (RV) biopsy specimens immunohistochemically stained for the presence of ANP. Plasma ANP levels were elevated (p < 0.0001) in transplant patients (172 +/- 12 pg/ml) compared to normal subjects (36 +/- 4 pg/ml). Sixty-four percent of transplant patients showed stainable RV ANP on endomyocardial biopsy. There was no significant difference in plasma ANP levels between patients with or without RV ANP. The degree of RV staining did not correlate with plasma ANP levels, degree of rejection, mean atrial or systemic pressures, or specific immunosuppressive regimen. Plasma ANP levels were higher in patients with moderate or severe rejection (237 +/- 17 pg/ml) compared to patients with mild or no rejection (163 +/- 12 pg/ml; p 0.03), but there was significant overlap of values. These data suggest that ventricular ANP secretion may account for some of the increase in plasma ANP levels in cardiac transplant patients. However, increased plasma ANP levels in some transplant patients who have no RV ANP and the lack of correlation between the amount of stainable RV ANP and plasma ANP levels suggest that other mechanisms are also likely responsible for plasma ANP elevations in this setting.

Adult↗

PubMed1994

Chronic mechanical circulatory support: rehabilitation, low morbidity, and superior survival.

Because of donor scarcity, 12 (39%) of a series of 31 Novacor left ventricular assist system recipients required mechanical circulatory support for an average of 125 days before transplantation (range, 61 to 303 days). Ten received a heart transplant and all survived to discharge. Two died of infection before transplantation after 93 and 303 days of support. Significant reductions were noted from preimplantation values of right and left cardiac filling pressures. Right ventricular ejection fraction and cardiac index increased. The 4-month actuarial freedom from infection during support was 75%. Three patients benefited from chronic outpatient housing for 5, 18, and 131 days, respectively, with improvements in quality of life measures. Ten chronically supported patients participated in an intensive rehabilitative exercise program resulting in an improvement of New York Heart Association class from IV to I in 9 patients. Mean oxygen consumption, which was 10 mL.kg-1.min-1 30 days after implantation (mean exercise time, 10 minutes) had risen to 15 mL.kg-1.min-1 before transplantation (mean exercise time, 16 minutes). This series suggests that long-term circulatory support is compatible with low morbidity, significant physical and hemodynamic rehabilitation, and an outpatient setting.

Adolescent↗

PubMed1994

A lipopolysaccharide-binding hemagglutinin with specificity for acetylated aminosugars in the serum of the hermit crab Diogenes affinis (Henderson).

A naturally occurring hemagglutinin was detected in the serum of the hermit crab Diogenes affinis, and its erythrocyte (RBC) binding activities, physicochemical properties, and carbohydrate binding specificity were characterized. Both the hemagglutination profile and the pattern of cross-reactivity of the serum with different RBC types in cross-adsorption tests suggested a strong affinity of the serum agglutinin for rat RBC. Further analysis revealed that the agglutinin was specifically dependent on Ca2+ for its hemagglutinating activity and reversibly sensitive to EDTA. The activity was found to be stable between pH 6.0 and 7.5, heat-labile, and completely precipitable by ammonium sulphate or TCA, suggesting the proteinaceous nature of the serum agglutinin. In hemagglutination-inhibition assays, the serum agglutinin of D. affinis showed a distinct and unique specificity for acetyl group-containing carbohydrates and glycoprotein. Furthermore, the hemagglutinating activity of the serum agglutinin was also inhibited by lipopolysaccharide from Salmonella abortus equi, which might indicate a significant role of humoral agglutinin in the immune response of crustaceans against bacterial infection.

Acetylation↗

PubMed1994

Intra-aortic balloon counterpulsation as a 'bridge' to cardiac transplantation. Effects in nonischemic and ischemic cardiomyopathy.

Intra-aortic balloon (IAB) counterpulsation has been utilized as an effective "bridge" to transplantation in patients with end-stage heart failure. To determine if patients with heart failure with nonischemic cardiomyopathy (NICM) derive the same benefit from IAB support as those with ischemic cardiomyopathy (ISCM), we evaluated 27 patients with NICM and 16 patients with ISCM who required IAB support while awaiting transplantation. Hemodynamic changes, effects on organ function (renal and hepatic), frequency of complications, and clinical outcomes were analyzed. Baseline demographics and hemodynamics were comparable in both groups (p = NS). Hemodynamics improved in both groups, immediately (15 to 30 min) following IAB insertion, with greater improvement (p < 0.05) in cardiac index and a trend toward greater reduction in filling pressures in the NICM group. Systemic vascular resistance fell to a similar degree in both groups. During continued IAB support (0.13 to 38 days in NICM, 1 to 54 days in ISCM), all hemodynamic changes persisted in both groups, with larger decrease (p < 0.05) in systemic vascular resistance and greater increase (p < 0.05) in cardiac index in the patients with NICM. The reduction in filling pressures, however, tended to be greater in patients with ISCM. Renal and hepatic function parameters improved to a similar extent in both groups. The frequency of complications and clinical outcome during IAB support were also similar in the two groups. These data confirm that IAB counterpulsation is a safe and effective "bridge" in patients with both NICM and ISCM with end-stage heart failure. The mechanism of sustained benefit in the two groups, however, may be different; afterload reduction appears to be more important in patients with NICM whereas reduction in filling pressures (increased coronary perfusion pressure) may be the main mechanism in patients with ISCM.

Cardiomyopathies↗

PubMed1994

Maximal exercise tolerance in chronic congestive heart failure. Relationship to resting left ventricular function.

The relationship between maximal exercise tolerance and resting radionuclide indexes of left ventricular systolic and diastolic function were evaluated in 20 ischemic and 44 idiopathic cardiomyopathy patients with New York Heart Association class 2-4 chronic congestive heart failure. Left ventricular ejection fraction, peak systolic ejection rate, peak diastolic filling rate, time to peak filling from end-systolic volume, and fractional filling in early diastole were measured from the radionuclide ventriculogram. All patients underwent symptom-limited exercise testing with on-line measurement of oxygen consumption. In the ischemic group, all of the radionuclide indexes correlated poorly with maximal exercise oxygen consumption (VO2max) except the peak systolic ejection rate which correlated modestly (r = 0.58, p < 0.05). Peak systolic ejection rate was significantly lower (p < 0.01) as were the peak diastolic filling rate and fractional filling in the first third of diastole (p < 0.05) in ischemic patients with marked exercise intolerance (VO2max < or = 14 mL/kg/min) compared with those with preserved exercise tolerance (VO2max > 14 mL/kg/min). In the idiopathic group, none of the radionuclide indexes correlated well with VO2max; and all indexes were similar in patients with and without marked exercise intolerance. These data suggest that (1) resting left ventricular ejection fraction poorly predicts maximal exercise capacity in both ischemic and idiopathic cardiomyopathy and (2) resting peak systolic ejection rate, peak diastolic filling rate, and fractional filling in early diastole may predict exercise tolerance in ischemic but not idiopathic cardiomyopathy.

Adult↗

PubMed1994

Effect of topically administered platelet-derived growth factor on corneal wound strength.

Since the cornea is an avascular tissue, the wound healing process is lengthy, with a need for sutures to stabilize the wound for a long time. Platelet-derived growth factor (PDGF) has been shown to accelerate wound healing in rat dermal models. Accelerated healing, if unaccompanied by side effects may reduce suture related complications such as astigmatism and infectious keratitis. This study evaluated the effect of PDGF on wound strength in corneal laceration and penetrating keratoplasty models using New Zealand white albino rabbits. Twenty-two rabbits were used in the corneal laceration model and sixteen rabbits in the penetrating keratoplasty model. The treated rabbits received 385 picomoles/drop of PDGF-BB dissolved in balanced salt solution six times on day 1 and three times a day for the remainder of the study. The control rabbits received balanced salt solution in the same dosing schedule. The pressure required to rupture the wound was measured using a pressure transducer. In the laceration model the PDGF treated group had mean (+/- standard deviation) average pressures on day 7 of 360 +/- 102 mm Hg for wound rupture compared to 210 +/- 102 mm Hg in the control group. (p = 0.005). The average pressures in the penetrating keratoplasty model on day 17 were 707 +/- 201 mm Hg for the controls and 1042 +/- 292 mm Hg for the PDGF treated group (p = 0.026). Histopathological evaluation of eyes not subjected to bursting showed increased fibroblasts at the wound junction with an increase in types III and type IV collagen production.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

PubMed1994

Cardiac transplantation at the University of Pittsburgh: 1994 update.

During the past 14 years, 746 hearts have been transplanted at the University of Pittsburgh. Immunosuppression has evolved from a CsA-based protocol with or without lympholytic prophylaxis to a tacrolimus-based protocol. Tacrolimus offers comparable survival to the conventional immunosuppression but is associated with lesser side effects and lower recurrent rejection. It also serves as an effective rescue agent for intractable rejection in patients receiving CsA-based immunosuppression. However, the shortage of donors, chronic rejection, and the morbidity associated with chronic use of nonspecific immunosuppression remain the major limitations in clinical transplantation. Currently, research at the University of Pittsburgh focuses on the induction of donor-specific transplantation tolerance in order to eliminate the morbidity associated with nonspecific immunosuppression and on left ventricular-assist devices as a bridge and/or an alternative to cardiac transplantation.

Actuarial Analysis↗

PubMed1993

Invasive testing in congestive heart failure. When is it useful?

Not only are findings from invasive studies in patients with congestive heart failure important for diagnosis, they may also be crucial in deciding on appropriate treatment and predicting prognosis. Hemodynamic evaluation may be useful for tailoring medical therapy, determining the need for mechanical support, predicting survival, deciding when valve surgery is needed, locating intracardiac shunts precisely, assessing the severity of pulmonary hypertension before cardiac transplantation, or diagnosing unexplained dyspnea. Contrast angiography can be used to evaluate systolic function if information from non-invasive studies is inadequate. Coronary arteriography can help determine the severity and extent of coronary artery disease and is needed if revascularization is being contemplated. Endomyocardial biopsy can be used to identify the cause of cardiomyopathy.

Biopsy↗

PubMed1993

Preoperative pulmonary hemodynamics and early mortality after orthotopic cardiac transplantation: the Pittsburgh experience.

The influence of preoperative transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) on early post-transplant mortality was evaluated in 425 orthotopic transplant recipients. The overall 30-day post-transplant mortality rate was 12.5%; the majority of the deaths (52.8%) were due to primary allograft failure. The 0- to 2-day mortality rate was threefold higher in patients with severe preoperative pulmonary hypertension (TPG > or = 15 mm Hg or PVR > or = 5 Wood units), whereas the 3- to 7-day and 8- to 30-day mortality rates were similar. Early post-transplant mortality (0 to 2 days and 8 to 30 days) was also significantly higher (15.9% vs 3.9% and 9.9% vs 2.8%, respectively; p < 0.05) in women compared with men. Women with severe preoperative pulmonary hypertension had higher (p < 0.05) 0- to 2-day post-transplant mortality than comparable men. According to univariate analysis, recipients with preoperative TPG > or = 15 mm Hg had a significantly higher 30-day postoperative mortality rate, irrespective of their level of PVR. Furthermore, patients with severe preoperative pulmonary hypertension who underwent transplantation between 1980 and 1987 had a higher 0- to 2-day post-transplant mortality rate compared with patients operated on after that time. Multiple logistic regression analysis identified female recipient sex and preoperative TPG but not preoperative PVR, era of transplantation, or recipient age as significant (p < 0.001 and p < 0.01, respectively) independent predictors of early post-transplant mortality.

Adolescent↗

PubMed1992

Prolonged intraaortic balloon support for septal rupture after myocardial infarction.

Timing of surgical repair of ventricular septal defect developing after acute myocardial infarction remains controversial. We report the case of a 75-year-old man in whom a ventricular septal defect developed 7 days after myocardial infarction. The patient was maintained on intraaortic balloon pump support for 33 days before successful surgical closure. In the present era of aggressive preoperative hemodynamic management, the strategy of prolonged support before definitive operation on patients with myocardial infarction in whom a ventricular septal defect develops must be reconsidered.

Aged↗

PubMed1991

Vascular entrapment of intra-aortic balloon after short-term balloon counterpulsation.

Prolonged, continuous intra-aortic balloon (IAB) counterpulsation for several weeks can result in balloon entrapment secondary to thrombus formation in the balloon lumen. In this report, we describe a patient who developed IAB entrapment, early (1 wk) after initiation of counterpulsation. A trace amount of blood was noted in the tubing connecting the balloon catheter to the console for 3 days prior to IAB malfunction and vascular entrapment. We suggest that the balloon catheter be removed immediately when blood is detected in the external connecting tubing even if the IAB is functioning satisfactorily.

Adult↗

PubMed1991

Reversibility of pulmonary hypertension in congestive heart failure patients evaluated for cardiac transplantation: comparative effects of various pharmacologic agents.

Congestive heart failure patients with severe pulmonary hypertension are at risk of death from acute right ventricular failure of the donor heart in the early postoperative period after orthotopic cardiac transplantation. Therefore in the preoperative evaluation of these patients, it is extremely important to determine whether pulmonary hypertension can be reversed by pharmacologic means. Patients with reactive pulmonary hypertension can be considered suitable for orthotopic transplantation and the effective drug utilized postoperatively to reverse pulmonary hypertension and prevent failure of the donor right ventricle. To determine which pharmacologic agent is most effective in reversing pulmonary hypertension in congestive heart failure, the acute pulmonary hemodynamic effects of comparable doses of direct intravenous vasodilators including nitroglycerin, nitroprusside, and prostaglandin E1, and intravenous inotropic agents dobutamine and enoximone, were evaluated in 66 patients undergoing cardiac transplantation evaluation. All drugs significantly increased cardiac output and decreased calculated pulmonary vascular resistance. All drugs except dobutamine significantly lowered pulmonary artery and pulmonary artery wedge pressures. Prostaglandin E1 was the only drug that significantly lowered transpulmonary pressure gradient (pulmonary artery mean pressure minus mean pulmonary wedge pressure). The magnitude of decline of pulmonary vascular resistance and transpulmonary pressure gradient was greatest with prostaglandin E1 compared with other drugs. These observations indicate that prostaglandin E1 may be more effective than the other studied drugs for acute reversal of pulmonary hypertension in congestive heart failure.

Analysis of Variance↗

PubMed1991

Continuous six-month infusion of intravenous nitroglycerin in a patient awaiting cardiac transplantation.

We report a patient with ischemic cardiomyopathy who was treated with a continuous high dose infusion of intravenous nitroglycerin for six months while awaiting cardiac transplantation. Surprisingly, methemoglobinemia did not develop and nitroglycerin continued to be clinically effective in relieving angina during the six-month period. We believe this to be the first reported instance of the safe use of such prolonged infusion of intravenous nitroglycerin.

Angina Pectoris↗

PubMed1991

Cardiac transplantation at the University of Pittsburgh: 1980 to 1991.

When examining survival rates following cardiac transplantation, it is important to examine the risk factors for both early (30-day) and late (greater than 30-day) survival as they may well be different. Factors affecting early survival appear related more to the preoperative condition of the patient (including degree of pulmonary hypertension) as well as advances that have been made in postoperative care. It is not immediately obvious why gender has such a profound effect on early survival and why primary graft failure rates appear higher in this group. Donor organ factors did not appear to relate to this difference. On the other hand, late survival appears to be influenced mainly by immunologic factors such as panel reactive antibody level and immunosuppressive protocol. A less dramatic effect of transpulmonary gradient appears to have a lasting effect on recipients even when they survive the initial 30-day period. Thus, pulmonary hypertension may have prolonged effects on the cardiac allograft which as yet we do not understand completely. The majority of late mortality is still due to graft atherosclerosis, infection, and acute cellular rejection, the latter 2 occurring most frequently within the first year after transplantation whereas death from graft atherosclerosis becomes most prominent beyond 5 years. Despite persistent improvements in 30-day survival, late survival following cardiac transplantation will only improve with the advent of better tissue matching and improved immunosuppression. The results with FK506, for example, are promising.

Adult↗