Assessment of cyclosporine pharmacokinetic parameters to facilitate conversion from C0 to C2 monitoring in heart transplant recipients.

BACKGROUND: Cyclosporine (CsA) 2-hour postdose (C2) monitoring is recommended to assess CsA exposure and predict clinical outcomes among heart transplant recipients. We correlated pharmacokinetic parameters and clinical outcomes in stable long-term heart transplant recipients monitored with C0 to develop an algorithm to convert patients from C0 to C2 monitoring. METHODS: Paired CsA C0-C2 measurements and serum creatinine levels were obtained from 35 heart transplant recipients more than 2 years posttransplantation (mean 8.8+/-4.7 years). RESULTS: The mean CsA dose and C0, C2, and C0/C2 ratio were 85+/-23 mg/12 hours, 123+/-41 ng/mL, 572+/-274 ng/mL and 4.8+/-2.1, respectively. C0 correlated weakly with C2 (r=.42, P=.011). The CsA dose correlated better with C2 (r=.58; P<.001) than with C0 (r=.37; P=.026). A good correlation was noted between C2 and the C2/C0 ratio (r=.73; P<.001), but none between C0 and the C2/C0 ratio. A borderline significant inverse correlation was noted between C0 and the worst endomyocardial biopsy score (r=-.34; P=.045), whereas none was noted with C2. Serum creatinine level did not correlate with either C2 or C0. Among patients with C0 within our target of 100 to 150 ug/L, six had C2 above 300 to 600 ug/L as suggested by the literature. CONCLUSIONS: In long-term heart transplant recipients, we could not identify a single pharmacokinetic parameter that could be used to develop an algorithm to convert from C0 to C2 monitoring; however, C2 may be better than C0 for identifying patients at risk of overexposure to CsA.

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.

A comparison of intracellular solutions for donor heart preservation.

Numerous solutions have been advocated for the preservation of donor hearts, and there has been much interest in universal and intracellular preservation solutions. This study compared the effects of Euro-Collins, University of Wisconsin, and Bretschneider's solutions with the use of an in vitro human right atrial muscle preparation to assess recovery of function after a 24-hour period of simulated cardiac arrest. There were no statistically significant differences among groups in length, weight, cross-sectional area, initial developed force, or resting force of muscles, including those muscles that were contracted in Krebs-Henseleit solution and served as a control. After the 24-hour arrest period at either 4 degrees or 12 degrees C, the solution was changed back to Krebs-henseleit at 34 degrees C and recovery was assessed over 30 minutes. At 30 minutes, developed forces for muscles that were cooled to 4 degree C were 58.9%, 76.6%, and 60.7% of the control for Euro-Collins, University of Wisconsin, and Bretschneider's solutions, respectively (p = not significant). For those cooled to 12 degrees C, developed forces were 9.5%, 30.5%, and 95.6% of the control for Euro-Collins, University of Wisconsin, and Bretschneider's solutions (p = 0.0001). Bretscheider's solution resulted in greatly improved recovery compared with both Euro-Collins and University of Wisconsin solutions (p = 0.005), and University of Wisconsin solution was better than Euro-Collins solution (p = 0.02). Recovery of developed force was affected by temperature for Euro-Collins and University of Wisconsin solutions (p = 0.005 and p = 0.001, respectively) but not for Bretschneider's solution. Resting force was elevated in muscles that were cooled in both Euro-Collins and University of Wisconsin solutions at 12 degrees C compared with almost normal values for Bretschneider's solution at either temperature (p = 0.07). Bretschneider's solution has a very high buffering capacity, which may be beneficial for long-term preservation. In conclusion, Bretschneider's solution resulted in the best recovery of human atrial myocardial function after a 24-hour preservation period compared with Euro-Collins and University of Wisconsin solutions and should be considered for use in donor heart transportation. The variability in quality of preservation at different temperatures with either Euro-Collins or University of Wisconsin solution make them less desirable as preservation solutions because uniform temperatures are seldom obtained during donor heart transplantation.

Are temperatures attained by donor hearts during transport too cold?

Excessive myocardial cooling may have detrimental effects on donor heart integrity. This study assessed the standard technique for donor myocardial preservation using hearts from seven mongrel dogs (mean weight 192.7 gm), which were arrested, excised, and placed in a cooler containing saline and ice. Temperature probes placed in both the left and right ventricular free walls and the septum revealed that, after cardioplegia, temperatures fell to 10.3 degrees, 7.5 degrees, and 7.6 degrees C, respectively. Temperature decreased to below 1 degree C after 75, 75, and 60 minutes for the left ventricle, right ventricle, and septum, respectively, independent of the size of the heart (range = 104 to 322 gm). After 4 hours of cooling, temperature was below 0 degrees C throughout the myocardium. Examination with an electron microscope showed similar serial changes over 4 hours in all hearts, including moderate-to-severe cytoplasmic and nuclear swelling and mitochondrial calcium deposits. Cell membranes remained intact, which suggests that the damage was not irreversible. We conclude that current donor heart preservation techniques may result in unacceptably low myocardial temperatures that cause reversible myocardial injury.

An assessment of crystalloid solutions for donor heart preservation.

The optimal technique for donor heart protection remains controversial. One component of preservation is the transport solution. Although saline solution is most frequently used as a transport medium, other crystalloid solutions may be superior. Accordingly, human right atrial trabeculae contracting isometrically in vitro were used to assess five crystalloid solutions at two different temperatures (12 degrees and 4 degrees C): St. Thomas' Hospital solution, modified Krebs-Henseleit (K+ = 16 mEq/L), Krebs-Henseleit (K+ = 4.5 mEq/L, saline, and Euro-Collins. After a 24-hour preservation period the muscles were restimulated at 34 degrees C and recovery of function was monitored for 30 minutes. Recovery of developed force was not affected by temperature (p = 0.13 by two-way analysis of variance). However, St. Thomas' Hospital solution provided the best recovery of developed force (103.3 +/- 6.2% of control) compared with saline, which had the worst developed force (2.8% +/- 1.3%) (p less than 0.002). Modified Krebs-Henseleit, Krebs-Henseleit, and Euro-Collins demonstrated intermediate performance. Although there were no differences between groups in recovery of resting force, it was greater in all groups with muscles cooled to 4 degrees C (238.7% +/- 17.6% of control) (p less than 0.001). Dry/wet weight ratios did not demonstrate statistically significant differences between groups. We conclude that, of the solutions tested, St. Thomas' Hospital solution provides the best preservation of atrial myocardium. Storage in crystalloid solutions leads to impaired relaxation, which is more apparent in tissue cooled to 4 degrees C and does not appear to be solely due to increased tissue swelling.

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.

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.

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.

Analysis of deaths after heart transplantation: the University of Ottawa Heart Institute experience.

This study reviews the clinical outcome of the 132 orthotopic heart transplantations performed at our institute from 1984 through 1991 and focuses on the pathology of those patients who died. The study comprised 124 adults (mean age, 45.6 +/- 0.9 years) and eight children. Twenty-six adult and one pediatric deaths occurred. Operative mortality (within 30 days) was 10.6%, with 84.8% of patients surviving to discharge. Actuarial probabilities of survival at 1 and 5 years were 84% +/- 3% and 71% +/- 6%, respectively. Of the 27 deaths, six (22.2%) occurred in the operating room (from hemorrhage, graft failure, and hyperacute rejection); 14 (51.9%) occurred in-hospital after surgery (from sepsis, rejection, cytomegalovirus disease, or myocardial infarct), and seven (25.9%) occurred after discharge (from rejection and/or recurrent coronary artery disease). Two groups of patients were at higher risk: patients in cardiogenic shock requiring pretransplantation mechanical support, with in-hospital mortality of 39.1%; and patients with previous valve replacement who were taking oral anticoagulants, with intraoperative mortality of 50.0%. Pathologic examination revealed occasional instances of unsuspected coronary artery disease in the donor hearts with more than 50% stenoses of the left anterior descending coronary arteries in three of 21 (14.3%) of cases. Complications of the transplantation or related therapeutic procedures were common among those who died. The complications ranged from functionally insignificant anatomic curiosities to life-threatening problems. These complications are tabulated and shown.

Improved donor myocardial recovery with a new lazaroid lipid antiperoxidant in the isolated canine heart.

U74006F is a new 21-amino steroid (lazaroid) that prevents lipid peroxidation without glucocorticoid or mineralocorticoid side effects. Reperfusion injury has been reduced by the addition of various free radical scavengers and antiperoxidants to the reperfusate. To assess the effect of U74006F on reperfusion of donor hearts subjected to prolonged hypothermic ischemia, 21 isolated canine hearts were divided into three groups: control (group 1), drug (2 mg/kg) injected into the oxygenated blood perfusate immediately before 4 hours of preservation (group 2), and drug (2 mg/kg) injected 1 hour before heart isolation and again 15 minutes before reperfusion (group 3). After control left ventricular function studies (with an intraventricular balloon) and biopsy for high-energy phosphates and dry/wet ratios, the hearts were arrested with cold cardioplegia and cooled for 4 hours then reperfused for 3 hours. Left ventricular work was calculated by systolic and diastolic pressure curves, which showed a better return of function in group 3 hearts (1625, 2150, and 3493 mm Hg/ml in groups 1, 2, and 3, respectively, at 180 minutes of reperfusion; p = 0.02). This was likely the result of improved diastolic compliance in group 3. Dry/wet ratios showed increased tissue edema in all hearts at the end of reperfusion. Although high-energy phosphate concentrations were not different between groups, adenosine was best preserved in group 3 (p = 0.03), suggesting reduced washout of this precursor. In conclusion, administration of U74006F before preservation and reperfusion may be useful for donor heart protection.

Mechanical cardiac actuation achieves hemodynamics similar to cardiopulmonary bypass.

The disadvantages of blood/interface interactions and difficult installation are common to current circulatory support devices. Direct mechanical ventricular actuation (DMVA) is a method of biventricular cardiac massage that avoids contact of blood with various surfaces. The purpose of this study was to compare hemodynamic responses and organ perfusion between DMVA and cardiopulmonary bypass (CPB). Twenty adult mixed-breed dogs randomized for DMVA or CPB were anesthetized with alpha-chloralose. During 4 hours of ventricular fibrillation, animals received either DMVA or CPB with aortic arch perfusion (90 to 120 ml/kg/min), bicaval venous return, and full left ventricle venting. Hemodynamics and organ perfusion were assessed by multivariant analysis of variance with repeated measures. Blood flow was similar to normal sinus rhythm (control) with either method; however, average CPB flows (control, 110%) were increased significantly over DMVA flows (control, 75%) (p = 0.016). The resulting mean arterial pressures were significantly greater during DMVA (control, 66%) compared to CPB (control, 49%) (p = 0.0011). Radiolabeled microspheres were the measure of organ perfusion during sinus rhythm and at 2 and 4 hours of circulatory support. Myocardial blood flow was equal to control in all regions during DMVA; CPB resulted in increased flows to the left ventricular epicardium, septum, and right ventricle. DMVA generated significantly greater flows to the renal cortex. All other organs demonstrated similar perfusion with either method. However, CPB displayed declining cerebral flows at 4 hours compared to DMVA (42% vs 55% control, respectively). Overall, DMVA provided hemodynamic stability equal to that of CPB. Rapid application and avoidance of blood/surface contact make DMVA a favorable method of temporary circulatory support.

Is there a place for cold crystalloid cardioplegia in the 1990s?

New cardioplegic techniques have been advocated as advantageous when compared with previously accepted standard methods. This study assessed results of a recent cohort of 388 consecutive patients undergoing coronary artery bypass grafting between 1990 and 1992 using a standard cold crystalloid cardioplegia. The mean age of patients was 61.0 +/- 0.5 years; there were 324 male and 64 female patients. Risk factor distribution has not changed recently. Preoperative left ventricular dysfunction (grade III/IV) was significant in 35.1% of patients, and 63.3% had previous myocardial infarctions. Intraoperative cardiac arrest was achieved using an average of 1,254 +/- 14 mL of St. Thomas' solution in multiple doses. Patients had a mean of 3.1 +/- 0.04 grafts constructed, with 87.7% receiving at least one internal thoracic artery graft. Anoxia and total cardiopulmonary bypass times were 40.6 +/- 0.6 and 90.3 +/- 1.4 minutes, respectively. Perioperative myocardial infarction was identified in 5.7% of patients with elevated creatine kinase levels and electrocardiographic measurement changes, inotropic agents were required in 17.8%, and the intraaortic balloon was required in 3.6% of patients. Hospital stays averaged 11.2 +/- 0.5 days. Overall 30-day mortality was 1.0%, whereas those patients undergoing elective operation (n = 219) had a mortality of 0%. In conclusion, cold crystalloid cardioplegia has the advantages of being inexpensive and simple to use. These results suggest that coronary artery bypass grafting still may be performed very safely using this technique.

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.

The myocardial contractile responses to protamine sulfate and heparin.

The administration of protamine sulfate for the reversal of heparin anticoagulation has been associated with adverse hemodynamic changes including hypotension and decreased cardiac output. The possible direct toxic effect of protamine on human right atrial trabeculae contracting isometrically in vitro was studied. Muscles were stimulated to contract at 1 Hz in Tyrode's solution (maintained at 34 degrees C, pH 7.4) into which protamine was continuously added. Following a polynomial regression analysis, a parabolic dose-response curve resulted. The equation was: y = 95.13 + 38.76x - 278.71x2 where y = relative developed force and x = concentration of protamine (milligrams per milliliters) (r = 0.82). The estimated concentration of protamine resulting in 50% developed force was 0.48 mg/ml. In a second series of experiments, protamine was added to the bath along with a neutralizing amount of heparin. This resulted in a limited reduction in the fall of relative developed force. Thus, protamine in high concentrations alone or in complex with heparin has a direct toxic effect on human myocardial muscle mechanics, and care is warranted in its clinical use.

Cardiac transplantation: the ideal myocardial temperature for graft transport.

The ideal preservation method and cooling temperature for transport of donor hearts are not known. Serious derangements in myocardial relaxation are well described with different methods of cooling. To assess this problem, human right atrial trabeculae contracting isometrically at 34 degrees C in vitro were subjected to hypothermic arrest at 1, 4, 12, and 20 degrees C for 1, 2, 4, 24, and 48 hours. Control conditions were resumed, and myocardial mechanical recovery was assessed over 1 hour. Contraction was 50% depressed after a 1- to 2-hour exposure to 1 degree C and was almost completely arrested following a 4-hour exposure. Muscles cooled to 4 degrees C recovered poorly, whereas those cooled to 12 and 20 degrees C did well. In the latter 2 groups, force development increased rapidly on rewarming and exceeded the precooling contraction force (p less than 0.05). A 100% increase in relative resting force was seen in muscles cooled to 1 and 4 degrees C (p less than 0.05). This finding suggests a failure of calcium homeostasis at very low temperatures. We conclude that atrial preservation is optimal at about 12 degrees C.

Surgical treatment of automatic atrial tachycardias.

From 1979 to 1989, 18 patients were seen in the Electrophysiology Service, Duke University Medical Center, with automatic atrial tachycardia. There were 8 male and 10 female patients with a mean age of 28.1 +/- 2.9 years. Electrophysiological mapping localized automatic foci to right atrial sites (14 patients) and left atrial sites (4 patients). Depending on origin of the focus, patients were further diagnosed as having either chronic ectopic atrial tachycardia or inappropriate sinus tachycardia. Of the 15 patients with chronic ectopic atrial tachycardia, 6 responded to medical treatment; in 9, the tachycardia was not adequately controlled. Six of them were referred for surgical intervention. All 3 patients with inappropriate sinus tachycardia underwent operative therapy. In the surgical group of patients with chronic ectopic atrial tachycardia, all 6 had a tachycardia-induced cardiomyopathy with ejection fractions ranging from 14% to 27% (mean ejection fraction, 21% +/- 2.7%). Surgical techniques used (alone or in combination) included an isolation procedure in 1 patient, cryoablation in 4 patients, and excision of atrial appendages or portions of atrial free walls in 7. Normal sinus rhythm developed in all surgical patients except 1 patient who had intractable congestive heart failure preoperatively and died of this condition and stroke. The overall success rates for medical and surgical therapy were 33.3% and 88.9%, respectively (p less than 0.01). Long-term follow-up was possible for 7 (87.5%) of 8 patients 3 to 7 years after operation. All patients with chronic ectopic atrial tachycardia were cured, but only 1 of 3 patients with inappropriate sinus tachycardia was in sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Argon beam coagulation compared with cryoablation of ventricular subendocardium.

The Argon Beam Coagulator uses radiofrequency energy to excite argon gas that may be used for ventricular ablation. The effects of power level and number of applications of the Argon Beam Coagulator were compared wtih cryothermia. Ten mongrel dogs underwent cardiac extirpation. The endocardial surfaces of 5 hearts were used for the creation of lesions using the Argon Beam Coagulator at five power levels with either one or two applications. Five hearts were used for endocardial and epicardial lesions using cryothermia (15-mm-diameter probe at -70 degrees C) for 1, 2, 3, or 4 minutes. The Argon Beam Coagulator lesions showed an increase in depth with increasing power levels (2.25 +/- 1.05 mm at 50 W to 6.64 +/- 0.75 mm at 150 W) and number of applications (maximum depth of 6.64 +/- 0.75 mm with one application, 11.2 +/- 1.1 mm with two applications). Cryothermia lesions were similar in depth regardless of duration or site of application (range, 6.1 to 10.2 mm). Both techniques resulted in homogeneous and well-demarcated lesions. These data show that the Argon Beam Coagulator results in discrete endocardial lesions, which may be created quickly and reproducibly. This may be a useful alternative for the operative ablation of endocardial scar in the treatment of ventricular tachycardia.