Transplantation of the canine cadaver heart using a core-cooling technique.

We studied whether a cardiopulmonary bypass (CPB) and a core-cooling technique could resuscitate an arrested heart, and whether this procedure benefited canine cadaveric heart transplantation. Donor dogs were subjected to brain death by an intracranial balloon technique, and then, to cardiac arrest conducted by cutting off ventilatory support. In the control group (Group 1; n = 8), arrested hearts were flushed with cardioplegic solution and harvested thereafter without any resuscitation technique. In the experimental group (Group 2; n = 8), arrested hearts were once resuscitated using CPB, and then harvested using a core-cooling technique and cardioplegia. These hearts were transplanted orthotopically. Seven of eight recipients in Group 1 were weaned from CPB, and five of them finally became independent of dopamine administration. All recipients in Group 2 were successfully weaned from CPB, and also became dopamine free eventually. In Group 2, all post-transplantation hemodynamic values such as cardiac output during the period of dopamine administration were equivalent to those of post-brain death period. Chemical analysis of the serum and myocardial muscle demonstrated no difference between groups. We conclude that CPB combined with a core-cooling technique makes it possible to utilize an arrested heart as a donor organ for transplantation.</p

Transplantation of the cadaver heart harvested one hour after hypoxic cardiac arrest using the core-cooling technique in dogs.

A shortage of donor organs in clinical transplantation prompted us to study whether resuscitated dead hearts could be utilized for successful orthotopic heart transplantation. After 60 min of hypoxic cardiac arrest, one group of canine hearts was resuscitated (Res group, n = 6). The other group was harvested directly (Non-Res group, n = 6). In the Res group, cardiopulmonary bypass was utilized for resuscitation at 37 degrees C and the animals were then core-cooled to 15 degrees C. The hearts then were preserved in University of Wisconsin solution and orthotopically transplanted. Stable prostacyclin analogue (OP2507) and verapamil, a calcium antagonist, were added to the cardioplegia, and substrate-enriched warm blood cardioplegia and a hydroxy radical scavenger (EPC) were administered at the time of reperfusion of the transplanted heart. All animals in each group were successfully weaned from cardiopulmonary bypass with dopamine (5 micrograms/kg/min). Cardiac function without dopamine was better preserved in the Res group than the Non-Res group (Emax: 130.6 +/- 41.5% vs. 47.1 +/- 24.7%; mean +/- SD, as percent of postbrain death values, P &#60; 0.01 by unpaired t-test). Cadaver hearts 60 min after anoxic arrest can be successfully re-animated and orthotopically engrafted. In addition, the core-cooling technique is useful. We believe this study serves as the key step in the clinical application of dead hearts to successful cardiac transplantation.</p

Doppler echocardiographic evaluation of Bjork-Shiley and St. Jude Medical prostheses in the mitral position.

The left ventricular studies by Doppler echocardiography were performed in 50 patients with a Bjork-Shiley (B-S) mitral valve and 50 patients after implantation of a St. Jude Medical (SJM) mitral valve; the effect of valve replacement on the hemodynamic performance at rest and during bicycle exercise was determined from serial echocardiographic data. Twenty-eight patients (56%) of the B-S group and 42 patients (84%) of the SJM group showed a good response to the exercise. There was no significant difference in the effective orifice area at rest among each sizes of the B-S valve. In the SJM valve, on the contrary, the effective valve orifice area increases in parallel to the size of the SJM valve. There was a clear relation between the valve size and pressure gradient. The pressure gradient directly depends on the valve size and the effective orifice area in the SJM valve. High pressure gradient group in both prostheses had a tendency to take negative values of percent increase in stroke volume. Further, there were no cases showing positive values of percent increase in end-diastolic volume among the patients whose pressure gradients were assumed to be more than 10 mmHg at rest. It is suggested that impairment of inflow caused by the artificial valve, prosthetic valve stenosis, is possibly a significant factor causing left ventricular dysfunction, notably a decrease in stroke volume during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)</p

A sheep survived for 48 days with the biventricular bypass type total artificial heart.

A biventricular bypass type total artificial heart (BVB-TAH) utilizing two pusher-plate pumps was developed and implanted in a sheep for 48 days with excellent results. A Hall effect sensor was utilized to operate each pump independently with a full stroke at variable rates (VR). With this system, the animal's hemodynamics was kept physiologically, and all metabolic parameters except hemoglobin and hematocrit returned to normal three weeks after implantation. However, signs of infection appeared on the forty-second day, and consequently the animal fell into a state of shock. Even at that time the BVB-TAH maintained circulation by increasing pumping rate automatically. On the forty-eighth day, the animal could not stand and suffered from anuria; the experiment was then terminated after 1,140 h pumping. At autopsy, there was an enlarged heart with an atrophic change, 1,900 ml of pleural effusion, and 3,100ml of ascites fluid. Blood culture taken on the forty-seventh day yielded Acinetobacter calcoaceticus. The BVB-TAH operated in an independent VR mode maintained entire circulation, and has a capability of substituting the native heart function in any situation.</p

Mid-term results of bilateral internal thoracic artery grafting.

Forty patients underwent coronary revascularization using bilateral internal thoracic artery (ITA) grafts between 1988 and 1992. A total of 111 coronary grafts were performed, or an average of 2.8 grafts per patient. Each patient received bilateral ITA grafts, and in 20 patients an additional 29 grafts were constructed with 18 autologous veins and 11 gastroepiploic arteries. The right ITA was grafted as a free graft in 20 patients. The ITA graft patency rate was 96 per cent (67/70) at the time of hospital discharge. The operative morbidity included 3 reoperations for bleeding, 1 perioperative myocardial infarction, 1 renal failure, 2 postcardiotomy shock, and 1 colon perforation. Two hospital deaths occurred; one due to colon perforation and the other due to postcardiotomy cardiogenic shock. One patient died of cerebral infarction 6 month after the operation. Thirty-four patients were in New York Heart Association functional class I, 2 were in class II and 1 was in class III. Cardiac function evaluated by echocardiography and scintigraphy showed significant improvement postoperatively. These data suggest that the use of bilateral ITA grafts is associated with an acceptable mortality and increases the versatility of arterial grafting.</p

Nitric oxide inhibition attenuates systemic hypotension produced by protamine

AbstractBackground: Protamine reversal of heparin anticoagulation often causes systemic hypotension, and in vitro studies suggest that this may be mediated by release of nitric oxide from the endothelium. The present investigations were designed to evaluate the direct myocardial effects of protamine and to determine in vivo whether nitric oxide inhibition can prevent hypotension during protamine infusion. Methods/Results: Protamine sulfate (50 μg/ml) was added to perfusate of eight isolated rabbit heart preparations; in six other preparations, a similar concentration of protamine was added to heparinized (5 U/ml) Krebs perfusate. Left ventricular developed pressure, maximum rate of pressure rise, and heart rate declined significantly (p < 0.01) in hearts exposed to protamine only (65.0% ± 6.6%, 55.5% ± 6.0%, and 87.6% ± 2.5% of baseline, respectively), whereas protamine added to heparinized perfusate caused little change in developed pressure, maximum rate of pressure rise, and heart rate (85.3% ± 5.4%, 84.9% ± 5.5%, and 98.8% ± 1.6%). To study systemic effects of protamine, we measured hemodynamic parameters in 12 heparinized dogs (150 U/kg). During protamine infusion (1.5 mg/kg intravenously over 30 seconds), mean blood pressure decreased by 46% ± 7% from baseline (p < 0.05), cardiac output decreased by 38% ± 4% (p < 0.05), and systemic vascular resistance decreased by 14% ± 9%. After hemodynamic stabilization, N g-monomethyl-f123503d (2 mg/kg), a competitive inhibitor of nitric oxide synthesis, was administered to six dogs, and methylene blue (2 mg/kg), an inhibitor of cyclic guanosine monophosphate synthesis, was administered to the remaining six dogs. After treatment with N g-monomethyl-l-arginine and methylene blue, the second infusion of protamine sulfate caused no significant change in blood pressure or cardiac output. In an additional six dogs, N g-monomethyl-l-arginine pretreatment (5 mg/kg) blocked the effects of the first dose of protamine. The effect of N g-monomethyl-l-arginine could be reversed by the addition of (6 mg/kg) l-arginine but not d-arginine. Conclusions: Protamine-heparin complex does not cause direct myocardial depression but does lead to severe hypotension in vivo. The finding that hypotension can be blocked by inhibitors of the nitric oxide pathway confirms previous in vitro studies indicating that the effects of protamine are mediated, in part, by the vascular endothelium. Further, these studies suggest a novel approach to prevention of hemodynamic complications caused by heparin reversal after cardiopulmonary bypass. (J THORAC C ARDIOVASC S URG 1996;111:1240-7