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Biomedical subjects

P J Hendry

Publications and source records attributed to P J Hendry.

At least 19 recordsLinked to original sources
PubMed1999

Discoordinate modulation of natriuretic peptides during acute cardiac allograft rejection in humans.

BACKGROUND: Increased circulating levels of the cardiac polypeptide hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) may be observed after orthotopic cardiac transplantation. Both the hypertrophic and inflammatory processes in the allograft may contribute to this increase, but no mechanistic explanation has been suggested for this observation. METHODS AND RESULTS: Plasma immunoreactive ANF and BNP determinations were performed in 10 consecutive transplant patients. These were correlated with degree of rejection as reflected by histopathological findings at serial endomyocardial biopsies. Three patients had associated hemodynamic measurements and blood samples 24 hours before and after transplantation. All rejection episodes that received treatment were accompanied by a marked increase in BNP plasma levels to > approximately 400 pg/mL. Steadily increasing BNP levels preceded overt rejection as assessed by histopathological criteria. The increase in plasma BNP was not always accompanied by an increase in ANF, which suggests the specific upregulation of BNP gene expression during acute rejection episodes. Treatment of the acute rejection episodes led to a substantial decrease of BNP plasma levels. CONCLUSIONS: The significant selective increase in plasma BNP levels found in the present study has not been previously described. This finding provides a new insight into the mechanism of allograft rejection and the modulation of natriuretic peptide synthesis and release. Furthermore, although preliminary, the data suggest that BNP plasma levels could form the basis for a new, noninvasive screening test to predict acute cardiac allograft rejection. Because treatment with the antilymphocyte monoclonal antibody OKT3 (murine monoclonal antibody to the CD3 antigen of the human T-cell) decreased BNP plasma levels, cytokine production by T-cells may mediate the selective increase in circulating BNP.

Adult↗
PubMed1999

Progress with the HeartSaver Ventricular Assist Device.

BACKGROUND: Ventricular assist devices (VADs) have been shown to be effective for short- or long-term circulatory support. Devices are either being adapted or newly designed for longer term or permanent support, with the goal to provide patients with improved quality of life. Since 1990, a program has been in place to develop a totally implantable, permanent VAD. METHODS: A multidisciplinary team is developing this VAD with specific goals in mind: (1) that it have an intrathoracic position, (2) that it be a totally implantable device without any percutaneous connections, and (3) that it be possible to communicate with the device from remote locations. These goals would allow for complete patient mobility and flexibility for follow-up. RESULTS: The electrohydraulically actuated VAD combines the blood pump, volume displacement chamber, energy converter, and internal electronic module into a single compact unit. The device called the HeartSaver VAD is powered by a transcutaneous energy transfer system and can be remotely monitored and controlled. Prototypes of different versions of the device have been tested in vitro and in vivo with satisfactory performance. CONCLUSIONS: The prototypes of the HeartSaver VAD have functioned well under test conditions and fulfilled the outlined goals. Further development and testing of the design are being conducted before clinical availability.

Animals↗
PubMed1999

Development of a ventricular assist device for out-of-hospital use.

BACKGROUND: Success with temporary ventricular assist devices, has prompted interest in devices developed for long term use outside of the hospital setting. METHODS: A totally implantable intrathoracic electro-hydraulic ventricular assist device has been developed. Design focused on providing the recipient with a near normal quality of life. To meet this goal the system utilizes transcutaneous energy transfer and biotelemetry to eliminate percutaneous drive-lines/cables as well as a displacement chamber capable of pressure equalization to atmospheric pressures, so as to eliminate the need for percutaneous venting. An implanted battery provides backup power to allow the recipient the ability to bathe, shower, or swim without connection to an external power source. An integrated telemedicine capability allows the device to be monitored/controlled remotely, using telephone lines. RESULTS: The system has been tested in vitro with early prototypes running for up to 5 1/2 years. The system was studied in calves (n = 25) with durations of support of up to 30 days, demonstrating the ability of the device to function as a totally implantable device without percutaneous connections. CONCLUSIONS: The various in vitro and in vivo studies have demonstrated the feasibility of the totally implantable device. Chronic in vivo experiments will follow in preparation for regulatory submissions for human use.

Animals↗
PubMed1999

Circulatory support for cardiogenic shock due to acute myocardial infarction: a Canadian experience.

BACKGROUND: Cardiogenic shock due to acute myocardial infarction (AMI) is associated with high mortality. Circulatory support devices may be used to assist these patients while they await cardiac transplantation. METHODS AND RESULTS: From 1986 to 1997, 25 patients in cardiogenic shock complicating AMI within 3.6+/-0.7 days of the event were supported with artificial hearts. Of the 25 patients, 21 were men with a mean age of 48.4 +/- 1.8 years. The age range was 26 to 62 years. Patients were considered for a device when the following criteria were met: cardiac index less than 1.8 L/min/m2, wedge pressure greater than 20 mmHg despite one or two inotropes and/or intra-aortic balloon support. They received either a CardioWest total artificial heart (n=13), a Thoratec biventricular assist device (n=6) or left ventricular assist device (LVAD) (n=6). Three patients were not considered transplant candidates and died while on the devices (two with multiorgan failure and one found to have a bronchogenic carcinoma after implant), with 22 undergoing cardiac transplantation within 8.6+/-2.2 days of device implant. Six patients died in hospital after the transplants (27.3% mortality). Complications included bleeding or tamponade in seven (28%), pneumonia in six (24%) and right ventricular failure in three LVAD patients (12%). Post-transplant actuarial one-, two- and five-year survival rates were 71.4%, 71.4% and 51%, respectively. CONCLUSIONS: Circulatory support devices offer a means to maintain organ perfusion in patients who develop cardiogenic shock due to AMI. Patients can then undergo transplantation with a reasonable expectation for survival when the alternative is death. Eventually the availability of permanent support devices may obviate the need for transplant in these patients.

Acute Disease↗
PubMed1998

Delay in revascularization is associated with increased mortality rate in patients with severe left ventricular dysfunction and viable myocardium on fluorine 18-fluorodeoxyglucose positron emission tomography imaging.

BACKGROUND: The identification of high-risk patients who require early revascularization has become increasingly important with the present emphasis on reducing health care resources. This is particularly relevant to health care systems with prolonged waiting times for interventions. Myocardial viability imaging with the use of fluorine 18-fluorodeoxyglucose (FDG) PET may help to identify high-risk patients with severe left ventricular dysfunction. The aim of this study was to evaluate the consequences of prolonged waiting time on cardiac outcomes in patients with left ventricular dysfunction directed to revascularization based on FDG PET imaging. METHODS AND RESULTS: Forty-six patients with coronary disease and an ejection fraction of < or = 35% were considered candidates for revascularization based on FDG PET viability imaging. Thirty-five of 46 patients were subsequently accepted for revascularization. Patients were divided into 2 groups based on the median waiting time after PET: an early group (< 35 days; n = 18) and a late group (> or = 35 days; n = 17). Preoperative mortality rates were significantly increased in the late group (4 of 17 [24%] versus 0 of 18 in the early group; P < 0.05). In postoperative follow-up (17 +/- 7 months), cardiac events occurred in 2 of 18 (11%) and 1 of 13 (7.8%) patients in the early and late groups, respectively. Left ventricular ejection fraction increased after early revascularization (24 +/- 7% to 29 +/- 8%, P < 0.001, baseline versus 3 months) but not in the late group (27 +/- 5% to 28 +/- 6%, P = NS). CONCLUSIONS: Preoperative FDG PET can be used to identify a high-risk group of patients who may benefit from early revascularization. A long waiting time for revascularization is associated with a high mortality rate and suggests that early revascularization is desirable after the identification of hibernating viable myocardium.

Aged↗
PubMed1998

Evaluation of porcine valves prepared by dye-mediated photooxidation.

BACKGROUND: Previous studies demonstrated that dye-mediated photooxidation can stabilize bovine pericardium. Here, photooxidized porcine valve cusp and root tissue were assessed in comparison to fresh and glutaraldehyde-treated samples. METHODS AND RESULTS: In an in vitro tissue solubility test, both photooxidized and glutaraldehyde-treated tissues were resistant to protein extraction compared to fresh tissue. A rat subcutaneous model was used to test in vivo stability and calcification potential. In this study, four of the six fresh leaflets were not visible because of resorption while both photooxidized and glutaraldehyde-treated tissues were biostable. Mineral contents of the rat explants were much lower for both fresh and photooxidized leaflets when compared with glutaraldehyde-treated leaflets. Also, the aortic root calcified whether treated or not with the most mineral being associated with glutaraldehyde-treated root. Analysis of photooxidized porcine valves explanted from the mitral position in sheep indicated a material that was biostable and contained only minor calcification, perhaps due to deformed stents. CONCLUSIONS: Porcine valve tissue treated by dye-mediated photooxidation is biostable and resistant to calcification, and has potential for use in heart valve bioprostheses.

Animals↗
PubMed1997

Preoperative and postoperative comparison of patients with univentricular and biventricular support with the thoratec ventricular assist device as a bridge to cardiac transplantation.

OBJECTIVES: The goal of this study was to determine whether there are differences in populations of patients with heart failure who require univentricular or biventricular circulatory support. METHODS: Two hundred thirteen patients who were in imminent risk of dying before donor heart procurement and who received Thoratec left (LVAD) and right (RVAD) ventricular assist devices at 35 hospitals were divided into three groups: group 1 (n = 74), patients adequately supported with isolated LVADs; group 2 (n = 37), patients initially receiving an LVAD and later requiring an RVAD; and group 3 (n = 102), patients who received biventricular assistance (BiVAD) from the beginning. RESULTS: There were no significant differences in any preoperative factors between the two BiVAD groups. In the combined BiVAD groups, pre-VAD cardiac index (BiVAD, 1.4 +/- 0.6 L/min per square meter, vs LVAD, 1.6 +/- 0.6 L/min per square meter) and pulmonary capillary wedge pressure (BiVAD, 27 +/- 8 mm Hg, vs LVAD, 30 +/- 8 mm Hg) were significantly lower than those in the LVAD group, and pre-VAD creatinine levels were significantly higher (BiVAD, 1.9 +/- 1.1 mg/dl, vs LVAD, 1.4 +/- 0.6 mg/dl). In addition, greater proportions of patients in the BiVAD groups required mechanical ventilation before VAD placement (60% vs 35%) and were implanted under emergency conditions than in the LVAD group (22% vs 9%). The survival of patients through heart transplantation was significantly better in patients who had an LVAD (74%) than in those who had BiVADs (58%). However, there were no significant differences in posttransplantation survival through hospital discharge (LVAD, 89%; BiVAD, 81%). CONCLUSION: Patients who received LVADs were less severely ill before the operation and consequently were more likely to survive after the operation. As the severity of illness increases, patients are more likely to require biventricular support.

Heart Transplantation↗
PubMed1997

Multi-purpose mechanical circulatory device.

A mechanical circulatory assist device for long term use outside the hospital setting has been developed. The device can be used for left, right or bi-ventricular support, and several of the developed technologies are applicable for total artificial hearts and non-pulsatile flow systems. The totally implantable device is principally designed for left ventricular support with implantation in the left hemithorax. The system utilizes transcutaneous energy and information transfer sub-systems, and has no percutaneous connections. In vitro durability testing has been conducted for periods from 1-4 years. Bovine experiments have been conducted with sustained circulation for periods form 1.5 to 96 hours. The in vitro and in vivo evaluation to date has demonstrated that the system can function effectively as a totally implantable ventricular assist device. The transcutaneous energy and information transfer sub-systems provided the ability to power, monitor and control the device, without the need for percutaneous connections. Design optimization and chronic in vivo evaluation is planned.

Animals↗
PubMed1996

Totally implantable intrathoracic ventricular assist device.

BACKGROUND: A totally implantable, intrathoracic electrohydraulic ventricular assist device (EVAD) is being developed for permanent use or as a bridge to transplantation. METHODS: The blood pump with 70-mL nominal stroke volume, volume displacement chamber, reversible turbine, internal electronics and infrared diaphragm position sensor are combined in one compact unit (unified system). The size and geometry are based on human anatomic measurements and fluid dynamic studies. A transcutaneous energy transfer powers the system and recharges the implantable nickel-cadmium battery pack. Autotuning circuitry optimizes energy transfer efficiency over a range of transcutaneous energy transfer coil spacings and misalignments. An infrared diaphragm position sensor detects end-systole and diastole points. RESULTS: In vitro and acute in vivo tests have demonstrated flow rates greater than 6 L/min. The transcutaneous energy transfer system demonstrated power transfer efficiencies of 60% to 80% for power demands from 5 to 60 W. Thirteen systems are currently undergoing durability testing; one has run for more than 750 days failure-free. The system recently sustained circulation in an acute calf implantation for 96 hours. CONCLUSIONS: Results of the in vitro and in vivo testing to date have demonstrated that the developed system can function effectively as a totally implantable ventricular assist device. Chronic in vivo evaluation is planned.

Animals↗
PubMed1996

Right ventricular blood flow during left ventricular support in an experimental porcine model.

BACKGROUND: Right ventricular blood flow may be adversely affected during left ventricular assist device (LVAD) use leading to right ventricular (RV) ischemia and RV dysfunction. This study characterized normal RV blood flow responses to LVAD operation. METHODS: Seven Yorkshire pigs weighing 74.4 +/- 3.4 kg underwent right coronary artery blood flow measurements with an ultrasonic flow probe and injection of radiolabeled microspheres. A Thoratec LVAD was used in either synchronous or asynchronous modes and RV loading was increased using a pulmonary artery snare. RESULTS: The RV blood flow was compared between three regions that differed in proximity to the right coronary artery: proximal segment, mid-RV, and distal. The right ventricular distal flow was 0.93 +/- 0.07 mL x min-1 x g-1 compared with 0.74 +/- 0.06 mL x min-1 x g-1 at right ventricular proximal flow during control measurements (p = 0.0001). This difference was maintained during LVAD operation in either synchronous or asynchronous modes and also during pulmonary artery constriction. CONCLUSIONS: Global RV flow is not adversely affected by LVAD use. A flow gradient occurs along the right coronary artery with the distal vascular bed having relatively less reserve, which may be more susceptible to ischemia in patients with preexisting coronary disease or RV distention during LVAD use.

Animals↗
PubMed1996

Cardiac transplantation after mechanical circulatory support: a Canadian perspective.

BACKGROUND: To assess the relative efficacy of cardiac transplantation after mechanical circulatory support with a variety of support systems, we analyzed our consecutive series of patients who had and did not have mechanical support before transplantation. METHODS: A review of 209 patients undergoing cardiac transplantation from 1984 to May 1995 was performed. Group 1 consisted of 110 patients who were maintained on oral medications while awaiting transplantation, and group 2 consisted of 60 patients who required intravenous inotropic support. Group 3 included 39 patients who had transplantation after mechanical circulatory support for cardiogenic shock. The indication for device implantation was acute onset of cardiogenic shock in 38 patients and deterioration while awaiting transplantation in 1 patient. The support systems were an intraaortic balloon pump in 13 (subgroup 3A), a ventricular assist device in 7 (subgroup 3B), and a total artificial heart in 19 patients (subgroup 3C). RESULTS: After transplantation, infection was more common in group 3 (56%) than in group 1 (28%) or group 2 (32%) (p = 0.005). Survival to discharge was lower for group 3 (71.7%) than for group 1 (90.9%) or 2 (88.3%) (p = 0.009). For mechanically supported patients, survival to discharge was 84.6% in subgroup 3A, 71.4% in subgroup 3B, and 63.1% in subgroup 3C (p = not significant). CONCLUSIONS: Transplantation after mechanical support offers acceptable results in this group of patients for whom the only alternative is certain death. Patient selection and perioperative management remain the challenge to improving these results.

Administration, Oral↗
PubMed1996

Chronic hypoxia induces adaptive metabolic changes in neonatal myocardium.

The effect of chronic hypoxia on neonatal myocardial metabolism remains undefined. With a new neonatal piglet model, we determined changes in myocardial metabolism during global ischemia after chronic hypoxia. Five-day-old piglets (N = 30) were randomly assigned to two groups and exposed to an atmosphere of 8% oxygen or to room air for 28 days before they were killed. Left ventricular myocardium was then analyzed at control and at 15-minute intervals during 60 minutes of global normothermic ischemia to determine high-energy phosphate levels, glycogen stores, and lactate accumulation. Time to peak ischemic myocardial contracture was measured with intramyocardial needle-tipped Millar catheters as a marker of the onset of irreversible ischemic injury. Results showed an initially greater level of myocardial adenosine triphosphate in the hypoxic group (27 +/- 1.2 vs 19 +/- 1.8 micromol/gm dry wt, p = 0.001) and a delay in adenosine triphosphate depletion during 60 minutes of global ischemia compared with the control group. Initial energy charge ratios (1/2 adenosine diphosphate + adenosine triphosphate/adenosine monophosphate + adenosine diphosphate + adenosine triphosphate) were also greater in the hypoxic group (0.96 +/- 0.01 vs 0.81 +/- 0.04, p = 0.01) and remained so throughout global ischemia. Initial glycogen stores were greater in the hypoxic group (273 +/- 13.3 vs 215 +/- 14.7 micromol/gm dry weight, p = 0.02) when compared with the control group. Lactate levels in the hypoxic group were initially higher (19.1 +/- 6.4 vs 8.9 +/- 3.1 micromol/gm dry weight, p = 0.001) compared with control levels and remained elevated throughout 60 minutes of ischemia. Time to peak ischemic contracture was prolonged in the hypoxic group (69.5 +/- 1.8 vs 48.9 +/- 1.4 minutes, p = 0.001) compared with the controls group. These data show that chronic hypoxia results in significant myocardial metabolic adaptive changes, which in turn result in an improved tolerance to severe normothermic ischemia. These beneficial effects are associated with elevated baseline glycogen storage levels and an accelerated rate of anaerobic glycolysis during ischemia.

Animals↗
PubMed1996

A remotely controlled and powered artificial heart pump.

An intrathoracic pulsatile artificial heart pump has been developed. Transcutaneous energy transfer and biotelemetry systems provide continuous power and remote monitoring and control, with no percutaneous connections required. The electrohydraulic system can be used either as a ventricular assist device or with modifications as a total artificial heart. The device uses a unidirectional axial flow pump coupled with a pressure activated one-way valve to allow hydraulic fluid to passively return to the volume displacement chamber during diastole. The transcutaneous energy transfer system provides power to the device and recharges the implantable battery pack. A wearable external controller and external battery pack provide the patient enhanced mobility and thus an improved quality of life. The biotelemetry system allows control and monitoring of the device after implantation, as well as an added capability to monitor and control the device remotely over public communication lines. Early prototypes have functioned failure free for up to 3 years in vitro. The device has sustained circulation in vivo for up to 4 days. Design optimization is continuing, and chronic in vivo evaluation is planned.

Animals↗
PubMed1996

Effect of issuing an invitation for breast cancer screening to women aged 65 to 69.

OBJECTIVE: Breast cancer screening is available to all women over 50 in the United Kingdom on the National Health Service breast screening programme. Only women aged between 50 and 64 receive a written invitation, with women over 64 being expected to self refer. Unfortunately, despite the higher incidence of breast cancer in the older age group only a very small proportion of women over 64 attend for screening. The aim of the study was to test the hypothesis that women between the ages of 65 and 69 will attend for screening if invited. METHOD: Women aged 65 to 69 were invited for screening from general practices in the Inverness area and were treated in all respects as the usual screening age group. RESULTS: An uptake of 76% was achieved with a cancer detection rate of 9.3 per thousand. CONCLUSION: These results lend weight to the suggestion that women in this age group should receive a specific invitation for breast cancer screening.

Age Factors↗
PubMed1995

Postoperative symptomatic internal thoracic artery stenosis and successful treatment with PTCA.

From 1988 to 1992, 4,182 coronary bypass grafting procedures were performed at the University of Ottawa Heart Institute. The left internal thoracic artery (ITA) was used in 2,913 patients, the right ITA in 79, and bilateral ITAs in 61 for a total of 3,053 patients with ITAs. This study assessed patients requiring angioplasty for symptomatic ITA stenosis after operation. A total of 29 patients (0.95%) with a mean age of 55.3 +/- 1.9 years underwent angioplasty for ITA stenosis from 4 days to 34 months after operation (mean, 6.5 +/- 1.6 months). Internal thoracic artery stenosis was identified in 18 patients (62.1%) within 3 months after operation. Angina was present in 26 patients (89.7%), a positive stress test in 8 (27.6%), and myocardial infarction in 1 (3.4%). At angiography, a total of 34 stenotic sites were identified in ITA grafts. Angioplasty was successful (< 50% residual stenosis) in 31 sites (91.2%). Follow-up was available for 28 of 29 patients (96.6%) at 24.6 +/- 2.3 months. Four patients (14.3%) returned with restenosis within 3 months, 2 of whom had successful repeat angioplasty, and 1 required reoperation. Canadian Cardiovascular Society anginal class after angioplasty was less than class II in 84.6% of patients. In conclusion, symptomatic postoperative ITA stenosis is uncommon, occurs most frequently at the site of distal anastomosis, and generally presents within 3 months of operation. It may be safely and effectively treated with angioplasty with a low recurrence rate.

Adult↗
PubMed1995

Determinants of hospital survival after cardiac transplantation.

To identify the preoperative factors that influence hospital survival after transplantation we analyzed our consecutive experience of 183 transplantations in 179 patients over a 10-year period. There were 151 male and 29 female transplant recipients ranging in age from 10 days to 70 years (mean, 48 +/- 1 years). Diagnoses included coronary disease in 110 patients, cardiomyopathy in 55 patients, valvular disease in 6 patients, and congenital heart disease in 9 patients. Seventy-seven had undergone a previous cardiac operation, and 30 patients required preoperative mechanical support. Forty patients received hearts from donors who were 40 years old or older (range, 40 to 62 years). Ischemic time was greater than 240 minutes in 32 cases, and pulmonary vascular resistance was greater than 3 Wood units in 40 patients (range, 3.1 to 10.0 Wood units). Cyclosporine induction was used in 52 patients, whereas 128 recipients received polyclonal antibody prophylaxis. There were 25 hospital deaths. Recipient diagnosis, use of mechanical support, donor age, and the immune suppression protocol were related to hospital survival according to univariate analysis. Using multiple logistic regression, only the method of immune suppression induction and the use of mechanical assists were significant independent determinants of survival. In conclusion, we believe that extended ischemic times and donor age do not adversely affect the early success of transplantation, whereas induction with immune globulin may reduce early mortality. Patients requiring mechanical support before transplantation continue to be a challenge.

Adolescent↗