Fumio Fukumura

Adaptation of Tissue to a Chronic Heat Load

Determination of the chronic effect of heat on tissue is one of the important issues facing mechanically actuated total artificial heart (TAH) development. In an effort to characterize this effect, implantations of heating devices producing constant heat fluxes of 0.04 watts/cm2, 0.06 W/cm2, and 0.08 W/cm2 were performed in 11 calves (H-series). Heated disks were implanted adjacent to lung and muscle tissue for a period of 7 weeks. Temperature sensors were placed at the surface as part of the heater assemblies. The results showed that initially, temperature elevations above body temperature (delta T) were 6.4 +/- 0.6 degrees C, 4.5 +/- 0.2 degrees C, and 1.8 +/- 0.5 degrees C at the muscle heater surface for 0.08, 0.06, and 0.04 W/cm2, respectively. At 2 weeks after implant delta T values changed to 5.5 +/- 0.6 degrees C, 3.4 +/- 0.2 degrees C, and 1.8 +/- 0.2 degrees C, respectively. Seven weeks after implant, delta T values decreased to 3.7 +/- 1.2 degrees C, 2.8 +/- 0.1 degrees C, and 0.8 degrees C for 0.08, 0.06, and 0.04 W/cm2, respectively. The authors think this change is attributable to an adaptive response of the tissue to increase heat dissipation through angiogenesis. Results from three TAH cases indicated that at two measured tissue interfaces, delta T decreased by 1 degrees C during a 15 day period. At the same time, the waste heat (volts x current in-flow x afterload to the blood) remained constant at 11.1 +/- 0.5 W during this period. This decrease in delta T corresponded to that observed for the H-series experiments at the higher heat fluxes. Thus, it appears that adaptation observed in the H-series experiments also is seen for tissues surrounding heat sources such as the TAH.

Ventricular energetics in endoventricular circular patch plasty for dyskinetic anterior left ventricular aneurysm

BACKGROUND The endoventricular circular patch plasty (Dor procedure) applies to patients with a left ventricular dysfunction due to an ischemic dilated ventricle. In the present study, we analyzed left ventricular energetics in patients who underwent the Dor procedure. METHODS We measured left ventricular contractility (end-systolic elastance; Ees), afterload (effective arterial elastance; Ea), and efficiency (ventriculoarterial coupling; Ea/Ees, and the ratio of stroke work and pressure-volume area; SW/PVA) based on the cardiac catheterization data before and after the Dor procedure in 8 patients with a postinfarction dyskinetic anterior left ventricular aneurysm. Concomitant procedures included coronary artery bypass grafting in all patients, mitral valve repair in one patient, and cryoablation in one patient. End-systolic elastance (Ees) and Ea were approximated as follows: Ees = mean arterial pressure/minimal left ventricular volume, and Ea = maximal left ventricular pressure/(maximal left ventricular volume-minimal left ventricular volume), and thereafter Ea/Ees and SW/PVA were calculated. The left ventricular volume was normalized with the body surface area. RESULTS End-systolic elastance (Ees) increased after the Dor procedure (from 1.15 +/- 0.60 to 1.86 +/- 0.84 mm Hg x m2 x mL(-1), p < 0.01), thus resulting in an improvement in Ea/Ees and SW/PVA (from 2.94 +/- 1.11 to 1.64 +/- 0.49, p < 0.01, and from 0.426 +/- 0.110 to 0.559 +/- 0.082, p < 0.01, respectively), even though Ea did not substantially change (from 2.96 +/- 0.78 to 2.74 +/- 0.55 mm Hg x m2 x mL(-1), p = 0.4). CONCLUSIONS Left ventricular contractility and efficiency improves after the Dor procedure in patients with a dyskinetic anterior left ventricular aneurysm. However, afterload does not change. The use of appropriate afterload-reducing therapy thus plays an especially important role in the management of patients who undergo the Dor procedure.

Comparison of pulsatile and non-pulsatile cardiopulmonary bypass on regional renal blood flow in sheep.

Objective—The purpose of the present study was to evaluate the effects of pulsatile cardiopulmonary bypass (CPB) on sheep regional renal blood flow by comparing pulsatile and non‐pulsatile perfusion at two different flow rates. Design—Seven female Suffolk sheep were used and the animals were perfused with pulsatile and non‐pulsatile CPB at flow rates of 60 and 100 ml/min/kg. Regional renal blood flow was measured by the colored microsphere method. General linear model ANOVA was performed to analyze the data. Results—Regional renal blood flow was significantly higher in both outer and middle cortices of pulsatile CPB compared with non‐pulsatile CPB (outer cortex: pulsatile CPB, 381 ± 192 ml/min/100 g, non‐pulsatile CPB, 255 ± 151 ml/min/100 g, p = 0.002; middle cortex: pulsatile CPB, 239 ± 114 ml/min/100 g, non‐pulsatile CPB, 176 ± 80 ml/min/100 g, p = 0.02). The increase of flow rate from 60 to 100 ml/min/kg improved renal cortical blood flow significantly. Conclusion—The regional renal blood flow was significantly higher in both outer and middle cortices of pulsatile CPB compared with the non‐pulsatile CPB.

Development of a magnetically operated artificial urethral sphincter : chronic effects of compression on the skin structure and blood flow

Hierarchical hybrid vascular grafts were constructed with an endothelial cell (EC) monolayer and hybrid medial layer composed of smooth muscle cells (SMCs) and type I collagen gel. The grafts, implanted into canine carotid arteries for up to 12 weeks, were ultrastructurally examined with a transmission electron microscope. Before implantation, SMCs incorporated into hybrid media were round and intracellularly filled with synthetic organelles such as rough endoplasmic reticula, mitochondria, free ribosomes, and Golgi complexes. Two weeks after implantation, bipolar spindle shaped SMCs still remained in a synthetic phenotype. At 12 weeks, circumferentially aligned SMCs were abundant in contractile apparatus such as myofilaments, dense bodies, and basement membranes. In a morphometric evaluation, the populations of three phenotypic SMCs (synthetic, intermediate, and contractile SMCs) were quantified. At 2 weeks, the proportions were 50.5, 41.8, and 7.7% for synthetic, intermediate, and contractile phenotypes, respectively. At 12 weeks, they were 9.9, 26.2, and 63.8%. These findings indicated that SMCs incorporated into hybrid grafts were transformed from a synthetic to a contractile phenotype under pulsatile stressed conditions after 12 weeks in vivo. Thus, the intima/media incorporated hybrid graft reconstructed a vessel wall similar to a native one in terms of structure and function.

Progress in Cleveland Clinic-Nimbus total artificial heart development

A totally implantable, Cleveland Clinic-Nimbus total artificial heart (TAH) uses electrohydraulic energy conversion and an automatic left master-alternate mode control scheme, with a filling sensitivity of 1.0 l/min/mmHg and a maximum output of 9.5 l/min. The TAHs were tested in 12 calves for 1-120 days with normal major organ and blood cell function. Post-operative suppression of platelet aggregation recovered by the second post-operative week. The gelatin-coated pump surface generally was clean without any anticoagulants and free from infection. Embolism, which occurred in two cases, was caused by complications attributable to fungal infection in a Dacron graft and by thrombus formed around a jugular vein catheter. A system with a hybridized microcircuit controller in the interventricular space has been tested successfully in the three most recent cases, with a peak device surface temperature elevation of 6.5 degrees C. Heat effects were confined to the tissues immediately adjacent to the hottest spots. The carbon fiber-reinforced epoxy housing and 60 ml butyl rubber compliance chamber showed good tissue compatibility with a thin, fibrous tissue capsule. The transcutaneous energy transmission system and the internal battery functioned well as designed in the most recent animal implant.

Tranexamic acid reduces blood loss after cardiopulmonary bypass

To evaluate the effect of tranexamic acid (TA) on blood loss after cardiopulmonary bypass (CPB), 157 patients who underwent elective valve replacement operations were studied, with one group of 90 patients receiving tranexamic acid (Group TA) and 67 patients serving as the control group (Group N). In group TA, 50 mg/kg of tranexamic acid was administered just before and after CPB, and every 90 minutes during CPB. The activated coagulation time was maintained at more than 450 seconds during CPB in both groups. There was no significant difference in the CPB time between the groups (163 +/- 32 min in group N and 152 +/- 38 min in group TA:NS). The time required for hemostasis was shortened in group TA, which resulted in a shorter operation time (6.7 +/- 1.5 hrs vs 6.0 +/- 1.5 hrs in group N and group TA, respectively: p = 0.006). The amount of chest tube drainage within 12 hours after surgery was significantly reduced (225 +/- 129 ml vs. 180 +/- 118 ml in group N and group TA, respectively: p = 0.026). The chest tube was able to be removed earlier in group TA, and the total blood loss was significantly smaller in group TA (402 +/- 292 ml) than in group N (631 +/- 609 ml; p = 0.004). The authors thus conclude that antifibrinolytic therapy during CPB with tranexamic acid reduces postoperative blood loss, and shortens the operation time due to an improvement in hemostasis.

Haemostatic profile of small children during and following cardiopulmonary bypass

OBJECTIVE We evaluated changes of the haemostatic system during pediatric cardiac surgery during and after cardiopulmonary bypass (CPB). METHOD Twenty-five children under 15 kg of body weight undergoing open-heart surgery were divided into three groups; 9 patients (Group A), no bank blood was used throughout the surgery; 8 patients (Group B), packed red cells were used in the priming of CPB circuit; 8 patients (Group C) in cyanotic condition, for whom surgery was performed without bank blood. CPB caused a significant decrease of platelet counts in all three groups, the levels of which remained similar next morning. RESULTS Platelet counts decreased more significantly in Group C (59+/-27 k/mm3) than in Group A (119+/-42 k/mm3) and B (104+/-27 k/mm3). Platelet function-platelet activating factor test (HemoSTATUS) did not significantly decrease throughout the perioperative period in Group A. HemoSTATUS value decreased during CPB and recovered after CPB in Group B and C. Prothrombin time international ratio (PT-INR) and activated partial thromboplastin time were significantly prolonged just after CPB and recovered until next morning in all three groups. PT-INR was more prolonged in Group C (2.92+/-0.62) than in Group A (2.08+/-0.27) and B (2.42+/-0.42). There was no significant difference in postoperative bleeding for the first 12 hours among the three groups. CONCLUSION Although extreme hemodilution during CPB significantly impairs the coagulation and platelet system, these changes are usually transient and tolerable with minimal postoperative hemorrhage. However, a prolonged CPB and preoperative cyanotic condition may induce a critical decrease of platelet counts and increase postoperative bleeding.

Development of an Implantable Total Artificial Heart: Initial Animal Experiments

After 35 years of research and development, the artificial heart program at the Cleveland Clinic is approaching one of its goals; development of a totally implantable total artificial heart. This total artificial heart, actuated by an electrohydraulic energy converter developed by Nimbus, has been tested in seven calves for up to 45 days. A left master mode of operational control has proven workable, maintaining both right and left atrial pressures within the physiological ranges. A maximum in vivo output of 8.7 ± 0.81/min was obtained with a left side pump sensitivity of approximately 1.01/min-mmHg filling pressure. These data indicate that our system meets the design goal specified by the National Heart, Lung, and Blood Institute (NHLBI). Details of animal experiments currently underway are described.

Effects of pump flow rate on oxygen use during moderate hypothermic cardiopulmonary bypass

The authors investigated the effects of pump flow rate on oxygen use during a moderate hypothermic cardiopulmonary bypass (CPB) in 31 patients during either coronary artery bypass grafting or valve replacement and aortic cross clamping. Intravenous anesthesia was performed with high dose fentanyl. A neuromuscular blockade was achieved with an intravenous infusion of pancuronium. After a stable rectal temperature of 29 °C was obtained by both surface cooling with a blanket and core cooling with CPB, the pump flow rate was changed from 2.4 L/min/m2 to 2.2, 2.0, 1.8 and 1.6, keeping the same flow rate for at least 5 min. Both arterial and venous blood was sampled for blood gas analysis; serum lactate measurement and hemodynamic changes were monitored and recorded at each flow rate. In 10 of 31 patients, whose aortic cross clamping time was longer than 90 min, the same measurements were followed 10 min after the induction of prost/aglandin E, (PGE,) (40±13 ng/kg/min) at pump flow rates of 2.4, 2.0, and 1.6 L/min/m2. Oxygen consumption significantly decreased at 1.6 L/min/m2 compared to the other flow rates (52.4±13.6, 54.3±11.8, 56.4±14.7, and 56.7±11.0 ml/min/m2, at flow rates of 2.4, 2.2, 2.0 and 1.8 L/min/m2, respectively, versus 48.4±10.9 ml/min/m2, at 1.6 L/min/m2, p<0.01, paired t-test). After the induction of PGE,, both aortic pressure and systemic vascular resistance decreased significantly (p<0.01, paired t-test) at flow rates of 2.0 and 1.6 L/min/m2. There was a significant increase in oxygen consumption at 1.6 L/min/m2 from 46.0±12.5 to 56.2±8.5 ml/min/m2 (p<0.01, paired ttest) after the induction of PGE,. No significant changes in oxygen consumption were revealed by PGE1 administration at 2.4 and 2.0 L/min/m2. These results suggest that the critical flow rate to maintain adequate tissue oxygenation is somewhere between 1.6 and 1.8 L/min/m2 during moderate hypothermic CPB, and that PGE, increased the oxygen consumption at a lower rate than the critical flow rate, probably by improving tissue level microcirculation.

Hemodynamic changes with posture in calves with total artificial heart

Hemodynamic changes with posture, sitting versus standing, were analyzed in five Holstein calves with the Cleveland Clinic-Nimbus TAH. This total artificial heart (TAH) has a left master alternate control mode that adjusts the pump rate and consequently pump flow proportional to the pulmonary venous return to the left pump (AUTO period). However, in this series of experiments, the pump reached its maximum beat rate within 1-5 days post operatively, after which pump flow could not increase (MAX period). Hemodynamic parameters (RAP, LAP, PAP, AoP, and pump flow) were obtained every 15-20 min throughout the experiments for as long as 120 days and averaged for each posture for each period. During the AUTO period, the flow while standing was significantly higher than that while sitting (standing: 8.7 +/- 0.2 L/min; sitting: 7.5 +/- 0.4 L/min; p < 0.05), and the systemic vascular resistance (SVR) was significantly lower (standing: 895 +/- 93 dyne.sec.m-5; sitting: 1,041 +/- 124 dyne.sec.m-5; p < 0.05). During the MAX period, the AoP and SVR standing were significantly lower than those sitting (AoP standing: 91 +/- 7 mmHg; AoP sitting: 98 +/- 7 mmHg; p < 0.05; SVR standing: 652 +/- 75 mmHg; SVR sitting: 730 +/- 96 mmHg; p < 0.05). The Cleveland Clinic-Nimbus TAH responded well to these changes in position, increasing pump flow and maintaining the AoP during the AUTO period.