Transplanted cardiomyocytes survive in scar tissue and improve heart function.
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Biomedical subjects
Publications and source records attributed to V Rao.
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This paper uses ethnographic and econometric methods to study the determinants of wife abuse in a community of potters in Southern India. The qualitative work demonstrates that wife abuse is more likely when dowries are perceived as inadequate, when husbands are alcoholic, and when the cause of the abuse is perceived as "legitimate" by the community. Hypotheses generated from the qualitative work are tested with survey data, which confirm that the risk of wife abuse significantly increases with smaller dowry payments and alcohol consumption. Furthermore, the statistical analysis reveals that women who are sterilized or have fewer male children are more likely to be abused.
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We showed previously that 20 min of low-volume anoxia ("ischemia") and 20 min of "reperfusion" preconditions quiescent pediatric myocyte cultures against damage resulting from 90 min of subsequent prolonged ischemia and 30 min of reperfusion. The purpose of this study was to assess the roles of adenosine and protein kinase C (PKC) in this preconditioning model. Our results suggest that 1) preconditioned myocytes secrete a protective mediator(s) into the "ischemic" supernatant that is transferable to other cells, and adenosine is released into the supernatant in quantities sufficient for adenosine-receptor activation (2) preconditioning is inhibited by adenosine-receptor antagonism, and myocyte protection similar to preconditioning can be achieved with exogenously administered adenosine or adenosine-receptor stimulation; (3) brief ischemic and adenosine-induced myocyte preconditioning is mimicked by the phorbol ester 4beta-phorbol 12-myristate 13-acetate (PKC agonist) and inhibited by PKC antagonists; and (4) brief ischemic and adenosine-induced myocyte preconditioning both induce PKC translocation to myocyte membranes and increase the PKC phosphorylation rate. These data suggest that adenosine released from ischemic human pediatric myocytes mediates preconditioning through activation of PKC.
The clinical and radiological features are described in male and female siblings with a unique form of spondyloepimetaphyseal dysplasia. In addition to generalized platyspondyly with epiphyseal and metaphyseal involvement, these children also have thin tapering fingers with accentuated palmar creases and abnormal dentition with oligodontia and pointed incisors. Parental consanguinity suggests that this is an autosomal recessive disorder.
BACKGROUND: Improved methods of donor heart preservation may allow for prolonged storage and permit remote procurement. Previous attempts to use oxygenated perfusion circuits during storage have not gained widespread acceptance because they were either too impractical or complicated to use for remote harvest. We hypothesized that collection and perfusion of donor blood during prolonged storage may improve myocardial recovery. Our aim was to devise a safe, simple, cost-effective system that could be used in any hospital setting. METHODS: Yorkshire pigs (40 to 50 kg) were used to perform 16 orthotopic heart transplantations with either continuous perfusion with donor blood (BL, n = 8) or standard hypothermic storage (CON, n = 8). After administration of heparin, hypothermic (4 degrees C) cardioplegic arrest, and donor heart extraction, donor blood (2688 +/- 166 ml) was harvested in the BL group. After filtration for particulate matter, blood perfusion was initiated via a standard intravenous transfusion apparatus at room temperature (20 degrees C) and a pressure of 60 mm Hg and maintained during storage. Arterial and coronary sinus blood samples were obtained to examine myocardial oxygen extraction, lactate release, and acid production. A Millar micromanometer was used to measure left ventricular developed pressures at an end-diastolic pressure of 2 and 10 mm Hg both before and after transplantation. RESULTS: All pigs (eight of eight) in the BL group were successfully weaned off bypass compared to three of eight in the CON group (p < 0.01). Developed pressures (at left ventricular end-diastolic pressure = 10 mm Hg) was improved in the BL group (mean +/- SD: baseline: BL: 90 +/- 16 mm Hg vs CON: 83 +/- 12 mm Hg, p = NS; posttransplantation: BL: 66 +/- 8 mm Hg vs CON: 35 +/- 29 mm Hg, p < 0.05). Similarly, maximum dP/dt was higher in the BL group. Lactate release was higher at cross-clamp removal in the BL group (2.4 +/- 0.3 mmol/L vs 0.7 +/- 0.2 mmol/L, p < 0.01). There were no differences in oxygen extraction or acid production during reperfusion. CONCLUSIONS: Perfusion of donor blood improved the ability to wean off bypass after 4 hours of storage. Blood perfusion permitted persistent myocardial metabolism during the ischemic period, which led to improved functional recovery. Harvesting donor blood for subsequent perfusion during prolonged storage may improve the results of orthotopic heart transplantation and allow for more distant procurement of donor organs.
BACKGROUND: Advances in surgical technique and perioperative myocardial protection have reduced the risk of aortic and mitral valve surgery. Improved methods of valve repair have reduced the proportion of patients who require valve replacement. However, patients who require valve replacement often have advanced disease and/or extensive calcification and may therefore be at increased risk for perioperative morbidity and mortality. METHODS AND RESULTS: We reviewed the results of 2898 patients who underwent aortic (AVR) or mitral (MVR) valve replacement at the Toronto Hospital. We compared patients who underwent surgery between January 1982 and December 1986 (early group) with those who were operated on between January 1989 and December 1993 (late group). The univariable and multivariable predictors of postoperative low-output syndrome (LOS) and operative mortality (OM) were determined for each time period. A total of 1779 patients underwent AVR (late, n = 997; early, n = 782). Multivariable analyses revealed that the late group had significantly more patients with independent pre-epidemiology operative risk factors for both OM and LOS. Despite the greater proportion of high risk patients, the incidence of postoperative LOS was lower in the late group (10% versus early, 14%; P = .012). There was no difference in OM between the two groups (late, 3.4% versus early, 3.7%; P = .732). A Total of 1119 patients underwent MVR (late, n = 493; early, n = 626). Compared with the early group, the late group had significantly more patients with preoperative multivariable risk factors for OM and LOS. There was no difference in postoperative LOS (late, 19% versus early, 21%; P = .361) or OM between the two groups (late, 5.8% versus early, 6.9%; P = .432). CONCLUSIONS: Despite an increase in high-risk patients, there was no significant increase in mortality or morbidity associated with aortic or mitral valve surgery.
Major advances in the composition and delivery of cardioplegia have helped to reduce the morbidity and mortality associated with coronary bypass surgery. The discovery of the preconditioning response should facilitate the development of more powerful myocardial protective agents. These new agents may act to directly stimulate the preconditioning response or may act in a supplementary fashion to either augment the response or provide protection from alternate pathways. As new techniques of myocardial protection continue to be developed, the risk-to-benefit ratio of coronary bypass surgery will continue to improve. As a result of these improvements, surgeons will be able to offer surgery to an increasingly high risk patient population without increasing the morbidity or mortality currently associated with coronary bypass.
The molecular organization in ultrathin polymer films (thicknesses less than 1000 angstroms) and thin polymer films (thicknesses between 1000 and 10,000 angstroms) may differ substantially from that of bulk polymers, which can lead to important differences in resulting thermophysical properties. Such constrained geometry films have been fabricated from amorphous poly(3-methyl-4-hydroxy styrene) (PMHS) and semicrystalline poly(di-n-hexyl silane) (PD6S) by means of spin-casting. The residual solvent content is substantially greater in ultrathin PMHS films, which suggests a higher glass transition temperature that results from a stronger hydrogen-bonded network as compared with that in thicker films. Crystallization of PD6S is substantially hindered in ultrathin films, in which a critical thickness of 150 angstroms is needed for crystalline morphology to exist and in which the rate of crystallization is initially slow but increases rapidly as the film approaches 500 angstroms in thickness.
The activation mechanism of glycosylasparaginase of Flavobacterium meningosepticum has been analyzed by site-directed mutagenesis and activation of purified precursors in vitro. Mutation of Thr-152 to Ser or Cys leads to gene products that are not activated in vivo but are activated in vitro because processing of the mutant precursors is inhibited by certain amino acids in the cell. Kinetic studies reveal that activation is an intramolecular autoproteolytic process. The involvement of His-150 and Thr/Ser/Cys-152 in activation suggests that autoproteolysis resembles proteolysis by serine/cysteine proteases. Multiple functions of the highly conserved active threonine residue are implicated.
BACKGROUND: The economic impact of health care reforms may result in waiting lists for coronary artery bypass grafting. This study was designed to examine the clinical results of patients with left main stenosis who were placed on a triaged wait list for operation. METHODS: Data were collected prospectively on 2,145 patients undergoing isolated coronary artery bypass grafting between 1989 and 1994. Critical left main stenosis (LMS, 50% or more stenosis) was present in 281 patients, and 1,864 patients had no left main disease, or a left main stenosis of less than 50% (no LMS). RESULTS: The average time from angiography to operation was shorter in patients with LMS (LMS 38 +/- 46 days versus no LMS 84 +/- 71 days; p = 0.0001). Two patients in the LMS group died; they had declined operation. Four patients suffered non-Q wave myocardial infarctions, all of whom subsequently underwent operation with no perioperative complications. The presence of LMS did not influence operative mortality (LMS 2.8% versus no LMS 1.3%), the incidence of low output syndrome (LMS 8.3% versus no LMS 5.4%), or the incidence of perioperative myocardial infarction (LMS 3.8% versus no LMS 4.2%). To examine the effect of waiting time on outcomes, patients with LMS were divided into early (operation 10 days or less after angiography) and late revascularization groups (more than 10 days). Operative mortality, low output syndrome, and myocardial infarction were similar in the early and late groups. Patients in the early group were more likely to have New York Heart Association functional class IV symptoms (64% versus late 22%; p < 0.0001), unstable angina (87% versus late 65%; p < 0.0001), or a recent preoperative myocardial infarction (17% versus late 2%; p < 0.0001). CONCLUSIONS: Carefully selected patients with significant left main stenosis can safely wait for operation with a low risk of complications. Early surgical intervention is allocated to patients with severe symptoms or recent preoperative myocardial infarction.
BACKGROUND: Transient right ventricular dysfunction has been previously documented after bypass operations despite adequate myocardial protection with intermittent antegrade cold blood cardioplegia. Recently warm blood cardioplegia has been interrupted during construction of distal anastomoses to improve visualization. The effects of intermittent antegrade warm blood cardioplegia, and the resultant periods of right ventricular normothermic ischemia, on postoperative right ventricular function are unknown. METHODS: To assess the effects of cardioplegia on right ventricular protection, 52 patients undergoing isolated bypass grafting were randomized to intermittent warm or cold blood cardioplegia. The two groups were similar with respect to age, sex, ventricular function, and right coronary stenoses. Cross-clamp times were similar (warm, 64 +/- 22 minutes; cold, 63 +/- 15 minutes; not significant). The cumulative time of cardioplegia interruption was longer in the cold group (42 +/- 8 minutes) than in the warm group (31 +/- 14 minutes; p < 0.002). A rapid-response thermodilution catheter was employed to assess postoperative right ventricular ejection fraction and end-diastolic and end-systolic volume indices. RESULTS: The right ventricular ejection fraction was greater in the warm group at 6 hours (warm, 0.46 +/- 0.06; cold, 0.37 +/- 0.08; p < 0.05) and 8 hours (warm, 0.43 +/- 0.08; cold, 0.37 +/- 0.08; p < 0.05) postoperatively. The right ventricular end-diastolic volume index was less in the warm group 8 hours postoperatively (warm, 83 +/- 11 mL/m2; cold, 94 +/- 16 mL/m2; p < 0.05). There were no differences in pulmonary arterial pressures or right ventricular stroke work index. CONCLUSIONS: Despite intermittent normothermic ischemia of half the cross-clamp time, patients receiving warm cardioplegia maintained right ventricular hemodynamics after bypass grafting.
BACKGROUND: Previous studies have shown that preservation of the chordae tendineae improves early and late postoperative left ventricular function after mitral valve replacement. This report describes the results of represervation of the chordae tendineae during redo mitral valve replacement in patients who had their chordae tendineae preserved during their initial operation. METHODS: Fifty-four patients undergoing reoperative mitral valve replacement with preservation of their chordal annular attachments (chordae group) were compared with 187 patients who had redo mitral valve replacement without preservation of the chordae (nonchordae group). The interval between the initial operation and the reoperation was 8.7 +/- 4.4 years in the chordae group and 8.6 +/- 4.9 years in the nonchordae group (p = 0.315). Seventy-three patients underwent aortic valve replacement during their redo mitral valve replacement compared with 168 patients who had mitral valve replacement alone. There were 15 patients who had their chordal attachments represerved during redo double-valve replacement. RESULTS: In the chordae group, intraoperative assessment revealed excellent chordal connection between the preserved papillary muscles and the mitral annulus in all patients. One patient had adhesions between the preserved chordae and the stent of the tissue valve. The chordal attachments were preserved during insertion of the second valve in all patients. The incidence of low output syndrome and operative mortality in the chordae group was 16.7% and 7.4%, respectively. In the nonchordae group, the incidence of low output syndrome was 27.3% (p = 0.112 compared with the chordae group) and the operative mortality was 13.4% (p = 0.236 compared with the chordae group). In patients with double-valve replacement, represervation of the chordae was associated with a reduction in low output syndrome (0% versus 24%; p = 0.034) and mortality (6.7% versus 15.5%; p = 0.374). CONCLUSIONS: Preservation of the chordal attachments between the papillary muscles and the mitral annulus can be accomplished during reoperative mitral valve replacement. Represervation of the chordae tendineae may reduce postoperative low output syndrome, especially in high-risk patients undergoing redo double-valve replacement.
BACKGROUND: The left internal thoracic artery (LITA) bypass graft to the left anterior descending artery has greater long-term patency than a saphenous vein graft. However, surgeons may be reluctant to use the LITA graft in some patients because they are unable to deliver cardioplegia to the left anterior descending artery territory. METHODS: We compared the myocardial levels of high-energy phosphates and their metabolites in patients who received an LITA graft with those in patients who received a saphenous vein graft to the left anterior descending artery territory during elective coronary artery bypass grafting. Right and left ventricular biopsy specimens were obtained at three times: before aortic cross-clamping, after cross-clamp removal, and after 10 minutes of reperfusion. RESULTS: No differences were found between the LITA graft group and the saphenous vein graft group in any right ventricular metabolites. There was an improvement in myocardial protection over time and a higher proportion of LITA graft patients in the late time period (early group, 63% versus late group, 80%; p < 0.01). Within each time period, there were no differences between the LITA and saphenous vein graft groups. Among patients receiving cold antegrade cardioplegia, the myocardial levels of high-energy phosphates were better preserved in those receiving an LITA graft. CONCLUSIONS: Advances in myocardial protection have led to improved preservation of high-energy phosphate levels after cardioplegic arrest. In patients undergoing elective coronary artery bypass grafting, the use of an LITA graft does not adversely affect myocardial metabolism. Further investigations are required to determine the effects of the use of the LITA during urgent or emergent procedures.
BACKGROUND: Regression of left ventricular hypertrophy is an important and well-recognized salutary effect of aortic valve replacement. The earliest evidence of left ventricular mass regression after aortic valve replacement and the influence of prosthesis type are not well known, and were the focus of this study. METHODS: Transthoracic echocardiography was used to measure left ventricular mass index preoperatively and before discharge in 57 consecutive patients undergoing isolated aortic valve replacement (with or without coronary artery bypass grafting). RESULTS: Three patients were excluded from the study because of inability to obtain accurate M-mode echocardiographic images for left ventricular mass measurement preoperatively (1) or postoperatively (2). Of the remaining 54 patients, mechanical bileaflet valves were used in 19, stented tissue bioprostheses were implanted in 15, and a stentless porcine bioprosthesis was chosen for 20. Postoperative echocardiograms were obtained 4.9 +/- 2.3 days after aortic valve replacement (range, 2 to 9 days). A two-way repeated-measures analysis of variance demonstrated a significant reduction of left ventricular mass index before discharge (preoperative 141.4 +/- 45.2 g/m2, postoperative 127.5 +/- 32.8 g/m2; p = 0.0005) but no differences between prostheses. CONCLUSIONS: Left ventricular mass regression begins early after aortic valve replacement, probably because of reduction of transvalvular gradients and left ventricular wall stress. At least in the very early postoperative period, the type of prosthesis does not influence the extent of mass regression.
In the Canadian single-payer system, all hospital payments, including payments for cardiac operations, are negotiated with the government annually. Each hospital is required to remain within 50 cases of its negotiated surgical target. Physicians are paid on a capitated basis and are subject to penalties if negotiated targets are exceeded. There is a computerized waiting list for cardiac operation, with patients classified by an urgency rating scale and objectives set for the maximum period for any given urgency category. Experience has shown that many patients are delayed in the queue, waiting longer than expected for surgical procedures. Waiting times are not influenced by age, sex, or reoperative status, but are influenced by factors such as the presence of multiple risk factors, the number of diseased vessels, stability or unstability of angina, left main coronary artery disease, and recent angioplasty. Waiting time has not been shown to affect operative mortality, the incidence of postoperative low-output syndrome, or length of hospital stay. Canada's 30-year experience with the provision of cardiac services under managed care may provide useful information to hospitals and physicians in the United States currently confronting capitation. The following overview focuses on two critical issues: negotiation of costs and management of patient waiting lists.
Prolonged intensive care unit treatment (> 3 days) contributes to increased health costs and resource utilization. In order to devise strategies to limit intensive care unit stay, and provide cost-effective medical care, it is necessary to identify the pre- and perioperative risk factors of prolonged treatment. Over 100 potential risk variables were collected prospectively in 889 consecutive patients undergoing isolated coronary bypass surgery between 1990 and 1992. The incidence of intensive care unit therapy lasting > 3 days was 6.8%. Univariate statistics identified 23 pre- and perioperative variables that were potential contributors to prolonged intensive care unit therapy. However, multivariate analysis of preoperative risk variables identified only recent myocardial infarction (within 30 days of surgery) and continued preoperative smoking (within 30 days of surgery) to be independent risk factors. Only 6.3% of patients without preoperative myocardial infarction and 6.1% of non-smokers required prolonged intensive care unit treatment, compared with 14.8% of patients with preoperative myocardial infarction (P = 0.01) and 10.1% of smokers (P = 0.07). When multivariate analysis was repeated with both pre- and perioperative variables, only ischemic morbidity (inotropes, myocardial infarction and low-output syndrome; 138 patients) and non-ischemic morbidity (infection, stroke or bleeding; 37 patients) predicted prolonged intensive care unit treatment. Intensive care unit treatment for > 3 days occurred in 26.8% of patients with ischemic morbidity compared with 3.2% of patients without ischemic morbidity (P = 0.001). Prolonged intensive care stay occurred in 32.4% of patients who suffered non-ischemic complications compared with 5.7% of patients who did not suffer these complications. The multiple logistic regression analysis odds ratio for ischemic morbidity was 7.4 (95% c.i. 4.0-13.4) compared with 4.8 (95% c.i. 1.9-10.1) for non-ischemic morbidity. Strategies designed to reduce the incidence of prolonged intensive care unit treatment should include prevention of stroke, infection and bleeding. However, the greatest reduction of intensive care unit utilization would be mediated by prevention of ventricular dysfunction secondary to myocardial ischemia or inadequate myocardial preservation.