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Biomedical subjects

J R Pepper

Publications and source records attributed to J R Pepper.

At least 91 records · Page 5Linked to original sources
PubMed1995

Reduced contraction and altered frequency response of isolated ventricular myocytes from patients with heart failure.

BACKGROUND: Previous work has failed to demonstrate reduced maximal contraction of isolated ventricular myocytes from failing human hearts compared with nonfailing control hearts. The effect of alterations in stimulation frequency and temperature on the contraction of isolated ventricular myocytes has been investigated. Left ventricular myocytes were isolated from the hearts of patients with severe heart failure undergoing heart transplantation and compared with myocytes isolated from myocardial biopsies from patients with coronary disease but preserved left ventricular systolic function or from myocytes from rejected donor hearts. METHODS AND RESULTS: Myocytes were exposed to either a maximally activating level of extracellular calcium at 37 degrees C or to 2 mmol/L calcium at 32 degrees C. There was no significant difference in the contraction amplitude between myocytes from failing and nonfailing hearts at 0.2 Hz. With increasing stimulation frequency, there was a reduction in contraction amplitude in cells from failing hearts relative to control hearts in both maximal calcium from 0.33 Hz (4.5% versus 6.6%) to 1.4 Hz (3.9% versus 8.8%) (ANCOVA, P < .001) and at 2 mmol/L calcium from 0.50 Hz (2.3% versus 3.5%) to 1.4 Hz (1.8% versus 3.9%) (ANCOVA, P < .001). The time to peak contraction and the times to 50% and 90% relaxation were prolonged in myocytes from failing hearts at stimulation rate of 0.2 Hz (P < .01), but only the time to 50% relaxation was prolonged at 1.0 Hz (P < .05). CONCLUSIONS: Reduced contraction, slowed relaxation, and impaired frequency response occurring at the level of the individual ventricular myocyte can be demonstrated in human heart failure. This demonstrates that disruption of myocyte function can contribute to both the systolic and the diastolic abnormalities that occur in the failing human heart.

Adult↗
PubMed1995

Perioperative assessment of aortic homograft, Toronto stentless valve, and stented valve in the aortic position.

We investigated aortic valve hemodynamic performance and perioperative left ventricular function in 50 patients (mean [+/- SD] age, 64 +/- 9 years; 34 men, 16 women) undergoing elective aortic valve replacement, using an aortic homograft (n = 20), a Toronto stentless porcine valve (n = 20), or a stented bioprosthesis (n = 10), by transesophageal echocardiography combined with high-fidelity cavity pressure recordings and thermodilution cardiac output measurements. Thirty-nine patients had aortic stenosis; 11 had predominant regurgitation. Thirteen patients with concomitant coronary artery stenosis underwent grafting. Left ventricular mass index in all patients was 280 +/- 110 g/m2. The transvalvular pressure drop and energy consumption were significantly higher with stented than stentless valves (5 with aortic homograft and 11 with Toronto valve, with matched age and valve size; 20 +/- 12 versus 3 +/- 9 mm Hg; 21% +/- 13% versus 8% +/- 8%, both p < 0.01). However, there was no difference in these variables between the Toronto valve and the aortic homograft (3 +/- 12 versus 2 +/- 10 mm Hg; 5% +/- 14% versus 2% +/- 12%, both p > 0.05), although the Toronto valves (normalized to body surface area) were larger than the aortic homografts (14.4 +/- 1.9 versus 12.6 +/- 1.8 mm/m2, p < 0.01). There was no significant difference in left ventricular stroke volume index or stroke work index in the systemic circulation, either between stentless and stented valves or between aortic homografts and Toronto valves, although the cross-clamp time required to insert a stentless valve was 20 minutes longer than that for a stented valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Early experience with the Toronto stentless porcine valve.

Stentless porcine valves in the aortic position offer many theoretic advantages, but their clinical performance has not been adequately defined. We evaluated the clinical and echocardiographic results of 103 patients who had aortic valve replacement with the Toronto stentless porcine valve over a 2-year period. There were 67 men with a mean age of 68 years. The predominant native valve lesion was aortic stenosis (64%), and 4 patients had prosthetic valve dysfunction. Forty-two patients had concomitant procedures. The 30-day mortality rate was 3.3% (n = 2) for isolated valve replacement and 5.8% (n = 6) for the series. The sole determinant of early death was poor left ventricular function. There were three late deaths due to non-valve-related complications over a median follow-up of 11.87 months. In addition, prosthetic valve endocarditis developed in 1 patient, necessitating a homograft valve replacement at 6 weeks. Doppler echocardiography performed at 3 to 6 months showed low peak and mean transvalvular gradients, with no substantial change at 1 year. None of the patients showed signs of clinically significant aortic regurgitation, although echocardiography demonstrated trivial or mild regurgitation in 12 patients at discharge or early follow-up, which was less marked or absent at 1 year. We conclude that the Toronto stentless porcine valve appears to offer promising early results.

Adult↗
PubMed1995

Blood cardioplegia increases plasma iron overload and thiol levels during cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass and crossclamping of the ascending aorta introduce two well-characterized phases of oxidative stress, namely, the extracorporeal circulation of blood and the reoxygenation of ischemic tissue. A feature of both forms of stress is the release of reactive and damaging oxygen species. METHODS: Forty-seven patients undergoing aortic valve replacement received either cold crystalloid, cold blood, or warm blood cardioplegia. Plasma thiol levels were measured in all groups before and during bypass. All cardiopulmonary bypass patients had, before going onto bypass, low plasma thiol levels (3.80 +/- 0.22 nmol/mg protein) compared with normal healthy controls (5.48 +/- 0.14 nmol/mg protein). RESULTS: Thiol values remained low throughout bypass in patients receiving cold crystalloid cardioplegia, but rose in patients receiving cold blood cardioplegia, and rose even more in patients receiving warm blood cardioplegia to reach normal plasma values. During cardiopulmonary bypass it has previously been reported that plasma transferrin can become fully saturated with iron and cause transient iron overload. Two patients (13%) receiving cold crystalloid cardioplegia went into plasma iron overload, whereas 18% receiving cold blood and 27% receiving warm blood cardioplegia showed plasma iron overload. CONCLUSIONS: We suggest that blood cardioplegia provides an additional source of thiols as well as a source of reactive iron. However, the reactive iron and thiol-containing molecules have the potential to interact and exacerbate oxidative stress, already a feature of bypass. Control of reactive iron by chelation may be strongly indicated when blood cardioplegia is used.

Adult↗
PubMed1995

Heart transplantation.

Increased experience and knowledge in the field of heart transplantation has resulted in continued expansion of this clinical activity. The same experience has served to identify many problems and provided some answers which are in many instances incomplete. The outstanding problems in heart transplantation are firstly the availability of donor organs, secondly, the limited storage of excised donor hearts and thirdly the conundrum of transplant vascular disease as it is manifested in the coronary arteries of the donor heart. Despite these problems, heart transplantation remains a very effective form of treatment particularly for young, well-motivated patients in end-stage heart failure. Although there is considerable agreement on many of the issues relating to heart transplantation, there are several areas of controversy. Neonatal heart transplantation is one example, though with accumulated experience, acceptance of the procedure has grown. The purpose of this article is to provide an overview of the present situation and to highlight areas of controversy and ignorance which require investigation.

Adult↗
PubMed1995

Difficulties in predicting outcome in cardiac surgery patients.

OBJECTIVE: To evaluate a novel combination of preoperative, intraoperative, and postoperative variables (including the Parsonnet, and the Acute Physiology and Chronic Health Evaluation II and III [APACHE II and III] scores) in cardiac surgery patients in order to predict hospital outcome, complications, and length of stay. DESIGN: Prospective survey. SETTING: Adult intensive care unit (ICU) at a tertiary care cardiothoracic surgery center. PATIENTS: All cardiac surgery patients admitted to the ICU over a 1-yr period. INTERVENTIONS: Medical history, Parsonnet score, intraoperative data (including bypass and ischemic times), APACHE II and III scores, complications, and outcome were collected for each patient. MEASUREMENTS AND MAIN RESULTS: One thousand eight patients were entered into the study. The mean Parsonnet score was 7.8 (range 0 to 33), mean APACHE II score 11.8 (range 2 to 33), and mean APACHE III score 42.5 (range 9 to 132). ICU mortality rate was 2.7% and hospital mortality rate was 3.8%. The mean APACHE II predicted risk of dying was 5.31%, which gave a standardized mortality ratio of 0.71. The above scores were all statistically well correlated with hospital mortality. Further, a logistic regression model was developed for the probability of hospital death. This model (which included bypass time, need for inotropes, mean arterial pressure, urea, and Glasgow Coma Scale) had an area under the receiver operating characteristic curve of 0.87, while the Parsonnet score had an area of 0.82 and the APACHE II risk of dying had an area of 0.84. CONCLUSIONS: Cardiac surgery remains a difficult area for outcome prediction. A combination of intraoperative and postoperative variables can improve predictive ability.

APACHE↗
PubMed1995

The effect of cardiopulmonary bypass on intestinal and pulmonary endothelial permeability.

STUDY OBJECTIVE: To quantify simultaneously the pulmonary and gastrointestinal (GI) damage that occurs during uncomplicated surgery requiring cardiopulmonary bypass (CPB), and to examine the relationships between markers of such damage. DESIGN: Prospective, open. SETTING: Adult ICU of a national referral hospital. PATIENTS: Twenty patients undergoing elective CPB surgery. MEASUREMENTS AND RESULTS: Pulmonary vascular injury was assessed using the protein accumulation index (PAI), a double isotope technique specific for high permeability pulmonary edema. The relationships of the PAI with percent neutrophils in bronchoalveolar lavage (BAL), serum, and BAL myeloperoxidase (MPO), and bypass time were examined. Splanchnic vascular injury was assessed using tonometry to measure intramucosal pH (pHi) and the ratio of absorbed lactulose to L-rhamnose (L/R ratio) to determine gut mucosal permeability. Positive correlations were observed between bypass time and PAI (r = 0.64, p < 0.01), percent neutrophils in the postoperative BAL and PAI (r = 0.51, p < 0.05), and postoperative serum MPO and PAI (r = 0.77, p < 0.001). The L/R ratio rose significantly following CPB from 0.04 +/- 0.01 in controls to 0.48 +/- 0.05 (p < 0.0001). The L/R ratio in patients who developed a low pHi was 0.59 +/- 0.06 compared with 0.32 +/- 0.07 in those whose pHi remained normal (p < 0.05). No significant correlation between bypass time and pHi (r = -0.3, p = 0.33), bypass time and L/R ratio (r = 0.27, p = 0.26), PAI and L/R ratio (r = 0.2, p = 0.42), PAI and pHi (r = -0.34, p = 0.16), postoperative serum MPO and L/R ratio (r = 0.03, p = 0.90), or postoperative serum MPO and pHi (r = -0.10, p = 0.67) could be demonstrated. CONCLUSIONS: Pulmonary and GI injury are detectable following uncomplicated CPB. The absence of any relationship between the respective markers of dysfunction suggests that differing pathologic processes are responsible.

Aortic Valve↗
PubMed1994

Early changes in left ventricular function after aortic valve replacement for isolated aortic stenosis.

To assess the immediate effects of aortic valve replacement (AVR) for valvular aortic stenosis (AS) on left ventricular (LV) systolic and diastolic function and global hemodynamics, 17 patients with AS underwent transesophageal echocardiography combined with high-fidelity LV pressure recording and thermodilution cardiac output measurements before cardiopulmonary bypass and 0.5, 6, 12, and 20 hours after AVR. Compared with results before bypass, LV systolic function had already changed 30 minutes after AVR, and remained constant thereafter: peak LV systolic wall stress decreased (from 210 +/- 60 to 130 +/- 40 g.cm-2), peak rate of dimension shortening increased (from 7.3 +/- 2.2 to 9.7 +/- 2.1 cm.s-1), both p < 0.01. Peak segmental external power thus remained constant (16.6 +/- 6.7 vs 17.7 +/- 7.6 mW.cm-3); p = NS. Changes in LV diastolic function and global hemodynamics were delayed. The peak rate of ventricular pressure decrease, normalized to developed end-systolic pressure, increased (from 15 +/- 3.2 to 19 +/- 5.2 s-1) by 6 hours. The minimal ventricular pressure of early diastole decreased (from 8.9 +/- 4.9 to 4.3 +/- 3.7 mm Hg), the peak rate of dimension lengthening of early diastole increased (from 6.0 +/- 3.0 to 8.8 +/- 2.0 cm.s-1), and LV stroke volume index increased (from 24 +/- 7 to 31 +/- 6 ml.m-2) by 12 hours, all p < 0.01. LV incoordination, defined as the dimension changes during isovolumic periods, had also improved significantly at 20 hours. Heart rate and LV enddiastolic dimension did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Ultrastructural analysis of skeletal muscle. Microvascular dimensions and basement membrane thickness in chronic heart failure.

Chronic heart failure (CHF) is characterized by increased systemic vascular resistance and diminished blood flow to exercising skeletal muscle. The pathogenesis of the increased resistance is not known, and may be due to muscle atrophy, functional abnormalities of resistance vessels or to structural changes in the microcirculation such as endothelial cell swelling. We have compared the ultrastructure of the microvasculature in needle biopsies of the quadriceps muscle from seven control subjects with normal left ventricular function to 10 patients with moderate or severe heart failure, optimally treated and without evidence of fluid overload. Samples were processed for ultrathin sectioning using ruthenium red as a specific basement membrane (BM) stain. Electron micrographs were taken of 10 transversely cut capillaries from each specimen. The total cross-sectional area of the vessels and the area of the endothelium was determined, and the short axis diameter was measured as an index of vessel diameter. The BM thickness was calculated from the mean of six readings around the periphery of the vessel. The short axis diameter in the two groups was not significantly different (controls 3.37 +/- 0.21 microns, CHF 3.56 +/- 0.37 microns, mean +/- 1SD). No difference in total cross-sectional area (controls 11.64 +/- 1.86 microns 2, CHF 13.56 +/- 2.78 microns 2) or area of the endothelium (controls 4.90 +/- 1.18 microns 2, CHF 6.00 +/- 1.58 microns 2) was observed. The thickness of the BM was marginally increased in subjects with CHF when compared to control subjects (0.31 +/- 0.077 microns vs 0.246 +/- 0.047 microns, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Transient iron-overload with bleomycin-detectable iron present during cardiopulmonary bypass surgery.

Extracorporeal circulation of blood during cardiopulmonary bypass surgery exposes cells to non-physiological surfaces and shear stress which can activate several regulatory cascades, and neutrophils to release superoxide and hydrogen peroxide. Shear stresses generated by pumps and suction systems cause lysis of red blood cells and the release of haemoglobin. Together the release of reactive forms of oxygen and haemoglobin can lead to the appearance of low molecular mass chelatable iron (bleomycin-detectable iron). All patients undergoing open heart surgery appear to release iron to plasma transferrin, increasing its iron saturation. In 13% of patients, however, the transferrin became fully iron-saturated, and by the end of open-heart surgery we could detect bleomycin-chelatable iron in the plasma. Saturation of transferrin with iron eliminates its iron-binding antioxidant properties, which can result in a stimulation of iron-dependent radical damage to selected detector molecules.

Adult↗
PubMed1993

Dynamic cardiomyoplasty in chronic left ventricular failure: an experimental model.

Dynamic cardiomyoplasty continues to attract interest as a therapeutic option in the management of heart failure. In a large animal model of ischemic heart failure, we have compared dynamic cardiomyoplasty with both adynamic cardiomyoplasty and a control group. Heart failure was induced by coronary artery ligation in sheep, and under the same anesthetic dynamic cardiomyoplasty (n = 5), adynamic cardiomyoplasty (n = 4), or no further procedure was performed (n = 5). After recovery the animals were housed for a further 3 months. The dynamic cardiomyoplasty underwent a recognized muscle transformation protocol during this period. At terminal studies, the animals were hemodynamically assessed, both under baseline conditions and after colloid volume loading. The data at baseline were compared with unpaired t tests, and the function curves created by volume loading were compared by analysis of variance. Although the changes at baseline were small, there were highly significant improvements in the function curves in the dynamic cardiomyoplasty group when the stimulators were turned on compared with stimulators off (p = 0.005) for cardiac output; p = 0.035 for left ventricular end-diastolic pressure; p = 0.002 for pulmonary artery capillary wedge pressure; p = 0.004 for stroke volume; and p = 0.003 for cardiac power). There were also significant improvements in indices of cardiac performance when the dynamic cardiomyoplasty group was compared with both the control and adynamic cardiomyoplasty groups. We conclude that there is experimental evidence that cardiomyoplasty augments cardiac function in a model of chronic left ventricular failure.

Animals↗
PubMed1993

A randomised prospective trial of surgical against medical tetracycline pleurodesis in the management of malignant pleural effusions secondary to breast cancer.

Malignant pleural effusion is a frequent complication of metastatic breast cancer leading to a significant degree of morbidity. Drainage of the effusion by thoracocentesis and pleurodesis with tetracycline as the sclerosing agent is an established means of symptomatic relief in these patients. To determine whether the efficacy of tetracycline pleurodesis is improved by surgical rather than medical drainage and instillation of sclerosant, 34 patients were prospectively randomised to a trial comparing the two treatment modalities, of whom 29 were evaluable for response. The total failure rate of primary pleurodesis was 13.4%, the rate of recurrence of effusion within the first month was 24%, and only 1 patient (3.4%) required repeat aspiration in that time period. There was no significant difference in the rate of recurrence or reaspiration of effusion between the two treatment groups. Although the overall survival time from treatment of effusion is significantly longer in the surgical treatment group than in the medical treatment group (P = 0.03), this is likely to be due to factors other than the method of treating the effusion. We conclude that surgical tetracycline pleurodesis has no advantage over medical tetracycline pleurodesis.

Adult↗
PubMed1993

Disability and distress following cardiac surgery in patients over 70 years of age.

We have reviewed the outcome in a consecutive series of 254 patients over the age of 70 undergoing cardiac surgery between 1987-89. Of the patients, 62% were male and the median age was 73 years. Operations included: coronary bypass 57%, valve replacement 26%, combinations 14% and other procedures 3%. The hospital mortality was 7.5% and late mortality was 13.8%. Complications included: intraaortic balloon 6%, resternotomy for bleeding 4%, permanent pacing 3%, chest infection 14%, tracheostomy 5%, major cerebrovascular events 3% and minor 4%. Eighty-two percent left the intensive care unit within 24 h and 89% left hospital within 8 days. Two questionnaires (York University) were sent to 207 patients believed to be alive in order to evaluate the change in their quality of life following surgery. Of the 207 questionnaires 197 (95%) were returned, 7 of which were from relatives of patients who had died and 7 were incomplete. The responses of 183 assessable patients (at a mean follow-up of 36 months) were converted into Rosser disability (I-VIII) and distress (A-D) groups. There was a decrease in disability and distress in 60% and 67%, respectively, no change in 34% and 30% and deterioration in 6% and 3%. Cardiac surgery can be carried out in elderly patients with an acceptable early morbidity and mortality, and although many patients show sustained improvement in their quality of life, this was not demonstrated in about a third of patients. As the emphasis in the elderly should be on quality of life we ought to continue to concentrate on careful selection in this age group.

Aged↗
PubMed1993

Different responses of the human gastroepiploic and internal mammary arteries to vasoactive peptides.

Peptidergic influences have been implicated in the control of tone in human arteries. We have examined the response of human gastroepiploic arteries (GEA) and internal mammary arteries (IMA) to three vasoactive peptides in vitro. Vasoactive intestinal peptide (VIP, 10(-11) to 3 x 10(-7) M) elicited relaxations in the GEA and IMA [maximum generated response (Emax) 74.6 +/- 9.4 and 56.5 +/- 7.7%, respectively] that were significantly reduced after removal of endothelium. NG-monomethyl-L-arginine (L-NMMA) and indomethacin partially inhibited the response of the GEA to VIP (P < 0.05). In the IMA, VIP-induced relaxation was significantly attenuated by L-NMMA but not indomethacin. Bombesin (10(-10) to 3 x 10(-6) M) produced endothelium-dependent relaxation selectively in the GEA, which was only inhibited by indomethacin (Emax reduced from 59.0 +/- 10.0 to 12.8 +/- 4.9%, P < 0.001). Bombesin elicited a weak endothelium-independent constriction in the IMA, giving 12.7 +/- 1.2% of the response to 90 mM KCl. Gastrin (10(-10) to 3 x 10(-7) M) had no effect on IMA segments but induced a relaxation of 40.0 +/- 3.2% in the GEA via a direct action on the smooth muscle. It is concluded that human GEA and IMA exhibit heterogenous responses to VIP, bombesin, and gastrin that may have important physiological and clinical implications.

Adolescent↗
PubMed1993

Metabolic analysis of latissimus dorsi coupled to a mock circulation.

A mock circulation system has been used to examine the metabolic and hemodynamic responses of untrained and trained latissimus dorsi muscle in a normal animal model. The metabolic response of untrained latissimus dorsi to differing stimulation regimes runs parallel to its mechanical performance. The ratio of power generated to oxidative capacity (a measure of metabolic efficiency) was maintained to a greater extent in muscle trained for 5 months subjected to specific fatigue tests, falling by only 20% (as opposed to 80% observed in untrained control muscle). This approach to studying metabolic and hemodynamic performance may have relevance when skeletal muscle is used for cardiac assistance.

Adenosine Triphosphate↗
PubMed1992

Clinical and hemodynamic evaluation of the 19-mm Carpentier-Edwards supraannular aortic valve.

The clinical and hemodynamic performance of the 19-mm Carpentier-Edwards supraannular aortic valve is largely unknown compared with that of the larger valves. Over 4 years we implanted the 19-mm Carpentier-Edwards supraannular aortic valve into 21 patients (20 female) with a mean age of 75 +/- 1.2 years (range, 59 to 86 years) and a mean body surface area of 1.6 +/- 0.03 m2 (range, 1.3 to 1.7 m2). There were four deaths, one operative and three late noncardiac deaths. Follow-up of the 17 survivors for a mean of 20 +/- 3.1 months (range, 2 to 42 months) demonstrated symptomatic improvement in all 17 (all are now in New York Heart Association functional class I or II). There were no valve-related complications and no patient required long-term anticoagulation. Doppler echocardiographic studies were used to assess the in vivo hemodynamic profile of the valve. Mean postoperative aortic valve gradient was 34.1 +/- 2.7 mm Hg (range, 19 to 52 mm Hg). Functional valve orifice area was 1.1 +/- 0.09 cm2 (range, 0.6 to 1.8 cm2). Mean cardiac output was 3.92 +/- 0.17 L/min (range, 3.2 to 5.1 L/min) with a mean cardiac index of 2.5 +/- 0.11 L.min-1 x m-2 (range, 2.1 to 3.2 L.min-1 x m-2). In conclusion, we have demonstrated that aortic valve replacement with the 19-mm Carpentier-Edwards supraannular aortic valve has a low operative mortality and offers major clinical benefits despite moderate transprosthetic gradients. This approach provides an alternative management strategy in elderly patients who would otherwise require low-profile mechanical valves or aortic root enlargement.

Aged↗
PubMed1992

Role of basal release of nitric oxide on coronary flow and mechanical performance of the isolated rat heart.

1. The role of nitric oxide (NO) in the regulation of coronary flow and mechanical function was studied in isolated working rat hearts. 2. The inhibition of basal release of NO by L-Ng-monomethylarginine (L-NMMA; 500 microM), a specific inhibitor of its synthesis, induced a reduction of coronary flow to 39.1% (+/- 3.4) of its basal level. 3. Associated with this was a drop of cardiac output to 58.10% (+/- 5.42) of control values. 4. This mechanical dysfunction, which was more pronounced in hypertrophied hearts, appears to be related to ischaemia, as it was prevented by simultaneously administered glyceryl trinitrate. Furthermore, L-NMMA did not alter the contractile activity of isolated cardiac myocytes, thereby excluding a direct toxic effect. 5. These findings provide evidence that NO plays a crucial role in the maintenance of basal coronary flow and appears to be essential for sustaining mechanical activity.

Animals↗