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Biomedical subjects

A E Farnsworth

Publications and source records attributed to A E Farnsworth.

33 records · Page 2Linked to original sources

Effects of low-dose cyclosporine A on toxicity and rejection in cardiac transplantation.

In conclusion, the low doses of CsA have significantly reduced nephrotoxicity and infectious complications. The patient survival has been acceptable, but there has been a disappointing incidence of rejection and graft loss in patients who have survived the first 3 months. We feel our experience would indicate that by targeting our CsA dosages to such low serum levels some of our patients receive suboptimal immunosuppression. Perhaps the best way of overcoming this is add a third maintenance immunosuppressive agent such as azathioprine to supplement immunosuppression. In fact, we have now changed our immunosuppressive protocol to include azathioprine while maintaining our CsA therapy at its current level.

Adolescent↗

Rationale for simultaneous carotid endarterectomy and aortocoronary bypass.

Seventy-eight patients were treated for coexistent carotid and coronary stenosis by simultaneous reconstructions. Five patients died (6.4%), one from a stroke contralateral to the carotid reconstruction. Four others suffered a perioperative stroke (total stroke incidence 6.4%). Three myocardial infarctions occurred (3.8%) including one fatal infarct. Analysis of the most recent 36 combined reconstructions indicates that the extramorbidity in this group increased the stroke or death rate for all carotid endarterectomies carried out in the same period by only 1%. Alternatively if these patients had been operated upon by aortocoronary grafting alone the mortality would have increased by 0.1% assuming no neurologic complications. Since these 36 patients had severe carotid stenosis and would have been refused carotid endarterectomy as an isolated procedure the results seem better than would have been achieved by staged operations.

Adult↗

Combined carotid coronary reconstructions--synchronous or sequential?

Analysis of 16 synchronous with 26 sequential combined carotid coronary reconstructions showed no statistical advantage of either approach. Sequential operations are more convenient but increase the total operating time by an hour or so. Synchronous operations can be carried out without carotid shunting despite hypotension provided hypothermia is established. In other circumstances the internal carotid back pressure is used to indicate the need for carotid shunting. In the 42 patients there were three strokes (7%) including one fatal stroke (2%) and two myocardial infarctions, both fatal (5%).

Cardiopulmonary Bypass↗

Patient selection for cardiac transplantation.

Since February 1984, 27 isotopic cardiac transplants have been performed in 25 patients. These 25 patients were from a pool of 45 patients who were accepted into the Programme. Sixteen patients have died awaiting a transplant, and four patients are presently on the waiting list. All patients accepted for cardiac transplantation were NYHA Class IV. There were 136 referrals during this period for cardiac transplantation, and 14 referrals for heart-lung transplantation. The commonest reason for non-acceptance into the Programme is that patients were considered not to be ill enough and to have a prognosis of more than six months. Patient selection is a key factor in ensuring a successful outcome with cardiac transplantation.

Adolescent↗

Measurement of the circulatory effects of dobutamine, a new inotropic agent, in patients following cardiac surgery.

The use of an extractable aortic electromagnetic flow probe to provide a continuous on-line display of ascending aortic flow and cardiac output following open heart surgery is described. Utilizing this equipment, the hemodynamic actions of dobutamine and isoprenaline are compared in 14 patients immediately following cardiac surgery. The study confirmed an inotropic action produced by dobutamine at a heart rate 10 to 15 per cent lower than isoprenaline, with less peripheral vascular action. Arterial and coronary sinus blood analyses revealed little difference in the myocardial metabolic actions of either drug. Because inotropic drugs produce only relatively small increases in stroke volume in this group of patients, the rise in cardiac output caused by these agents is more dependent on the effects upon heart rate rather than improved myocardial contractile state and consequently dobutamine has little advantage over isoprenaline in this situation.

Adult↗

Effects of PEEP on cardiovascular dynamics after open-heart surgery: a new postoperative monitoring technique.

The circulatory effects of incremental increases in positive end-expiratory pressure ventilation (PEEP) were assessed on 11 occasions in post-operative cardiac surgical patients by phasic aortic blood flow measurements and high-fidelity pressure recordings from which flow and pressure-flow derivatives of cardiac performance were calculated. At 15 cm H2O PEEP, mean arterial blood pressure was decreased by 10%, stroke volume and cardiac output by 15%, and peak left ventricular power by 21%. Although these indices promptly returned to control levels when PEEP was discontinued, levels of PEEP above 10 cm H2O should be used with caution for this group of patients.

Adolescent↗

A monitor for the continuous assessment of left ventricular performance after open-heart operations.

A cardiac monitoring system has been developed that incorporated phasic aortic blood flow measurement by an extractable electromagnetic flow probe and high-fidelity arterial blood pressure recordings. Cardiac output, stroke volume, and peak aortic blood flow are measured continuously; using logarithmic amplifiers, the pressure-flow derivatives of left ventricular function, such as cardiac power and stroke work, are obtained beat by beat. This monitor is used to follow the postoperative course of patients undergoing cardiac operations and to evaluate the hemodynamic effect of therapeutic agents.

Cardiac Surgical Procedures↗

Papaverive abolishes endothelium-dependent dilatation of human internal mammary arteries in vitro.

1. The purpose of the present study was to examine the effects of papaverine-HCl, administered into the lumen of the human internal mammary artery (IMA) during harvesting of this vessel, on vascular reactivity in vitro and to specifically test the hypothesis that intraluminal administration of papaverine-HCl impairs endothelium-dependent vasodilation. 2. The present study measured in vitro dilator and constrictor responses of terminal segments of human IMA. Internal mammary artery segments were obtained either prior to routine administration of intraluminal papaverine (pre-P) or after papaverine administration (post-P) in patients undergoing coronary artery bypass grafting. In addition, the viability of cultured human saphenous vein endothelial cells exposed to papaverine-HCl was examined. 3. Cumulative concentrations of U46619, 5-hydroxytryptamine and phenylephrine (PE) produced active contractions in post-P IMA rings. Contractile responses to low concentrations of endothelin-1 were significantly enhanced in post-PIMA compared with pre-P IMA segments. 4. Maximal endothelium-dependent vasodilator responses of pre-P IMA segments to cumulative concentrations of acetylcholine (ACh) and the calcium ionophore A23187 were 49 +/- 7 and 66 +/- 4%, respectively, of the initial active tension induced by PE (1 mumol/L). 5. Maximal endothelium-dependent vasodilator responses were markedly attenuated in post-P IMA (6 +/- 6 and 11 +/- 10% for ACh and A23187, respectively; P < 0.0001 for both vasodilators compared with pre-P). Post-P IMA relaxed completely to the endothelium-independent vasodilator sodium nitroprusside. 6. Exposure of cultured human saphenous vein endothelial cells to papaverine-HCl (1.2 and 12.0 mg/mL) for 1 h resulted in the reduced viability of these cells. 7. The loss of endothelium-dependent relaxation could dangerously predispose the IMA graft to vasospasm in the postoperative period.

Aged↗

Right ventricular assist and prostacyclin infusion for allograft failure in the presence of high pulmonary vascular resistance.

The presence of high pulmonary vascular resistance (PVR) greater than 4 Wood units contributes to significant early posttransplant mortality, and remains a negative predictor of long-term survival. Current trends have been toward exclusion of the recipient with high PVR from the orthotopic procedure; elective heterotopic allograft placement is increasingly advocated. A patient with a PVR of 6 Wood units underwent orthotopic transplantation; the cardiac allograft from a 12 kg heavier donor was implanted after an ischemic time of 115 minutes. Early graft failure at 4 hours and subsequent cardiac arrest were followed by reinstitution of cardiopulmonary bypass, during which time optimal pharmacologic manipulation of the pulmonary vasculature was undertaken, including the use of high-dose prostacyclin. Refractory right heart failure indicated the requirement for right ventricular assistance (RVA) for patient survival. RVA with a Bio-Medicus pump was instituted in association with high-dose prostacyclin; an intraaortic balloon pump was inserted 12 hours later. Maintenance immunosuppression consisted of cyclosporine and azathioprine alone. RVA was maintained for 3 days; during this time the patient was totally pump dependent. Over an 18-hour period the patient was weaned and successfully withdrawn from RVA. Intraaortic balloon pump counterpulsation and the prostacyclin infusion were continued for 6 and 10 days, respectively. The clinical implications of the various interventions that resulted in the patient's survival are discussed.

Cardiac Output, Low↗

The Bentall procedure: a surgical option in Ehlers-Danlos syndrome.

The Ehlers-Danlos syndrome (EDs) is one of the most frequently encountered inherited disorders of connective tissue. The arterial-ecchymotic type IV is notorious for large vessel involvement associated with spontaneous catastrophic bleeding. Most of these patients who require cardiovascular surgical procedures have a poor prognosis. Our experience of two patients, with aneurysmal dilatation of the ascending aorta is presented. The first patient presented with an aortic dissection extending from the ascending aorta to the common iliac arteries. The second patient presented with asymptomatic but progressive aneurysmal dilatation of the aortic root. Both patients underwent the Bentall procedure using a 25 mm St. Jude composite valved conduit. Despite increased vascular friability, both of these patients tolerated the operative procedure without complication and are doing well on early follow-up. This experience suggests that the Bentall procedure may be used to decrease the risks of dissection and rupture of the ascending aorta in patients with Ehlers-Danlos syndrome.

Adult↗

Effectiveness of minimal dosage cyclosporine in limiting toxicity and rejection.

The optimal dose of cyclosporine to achieve minimal toxicity and adequate control of rejection remains undetermined. We initiated our program with an immunosuppressive protocol designed to reduce drug toxicity, to reduce early severe rejection, and to provide adequate long-term immunosuppression. Because of increasing reports of nephrotoxicity associated with cyclosporine, we adopted a protocol of low-dose cyclosporine combined with steroids and equine antithymocyte globulin. The mean preoperative creatinine was 0.12 +/- 0.08 mmol/L and by 1 year after transplant was 0.13 +/- 0.04 mmol/L. Cyclosporine dose at 1 year was 5 +/- 2 mg/kg/day, and the serum cyclosporine level was 120 +/- 40 ng/ml. However, at 1 year 85% of the patients were hypertensive. The incidence of rejection in the first year after transplantation was 1.46 episodes per patient. Incidence of infection was 0.85 episodes per patient. The 3-month survival was 91%, and the actuarial 1-year survival was 76%. Seventy percent of our mortality was due to rejection, and four patients suffered significant graft damage in the period 3 months to 1 year, two requiring retransplantation. Although these low doses of cyclosporine have reduced nephrotoxicity and infectious complications, hypertension remains a significant problem. Moreover, although survival is acceptable, the incidence of graft rejection causing death or loss of function is of concern. This may indicate that cyclosporine at this dosage needs supplementation by a third immunosuppressive agent such as azathioprine.

Actuarial Analysis↗