Differential perfusion: a new technique for isolated brain cooling during cardiopulmonary bypass.

BACKGROUND: The purpose of this study was to determine the feasibility of differential perfusion of the aortic arch and descending aorta during cardiopulmonary bypass using a cannula designed for aortic segmentation. METHODS: Pigs weighing 57 kg (n = 8), underwent cardiopulmonary bypass using the dual lumen aortic cannula. An inflatable balloon separated proximal (aortic arch) and distal (descending aorta) ports. During differential perfusion, the aorta was segmented and the arch and descending aorta perfused differentially using parallel heat exchangers. Ability to independently control brain and body temperature, cardiopulmonary bypass flow rate and mean arterial blood pressure was determined. RESULTS: During differential perfusion cerebral hypothermia (27 degrees C) with systemic normothermia (38 degrees C) was established in 23 minutes. Independent control of arch and descending aortic flow and mean arterial blood pressure was possible. Analysis of internal jugular venous O2 saturation data indicated an increase in the ratio of cerebral O2 supply to demand during differential perfusion. CONCLUSIONS: A cannulation system segmenting the aorta allows independent control of cerebral and systemic perfusion. This device could provide significant cerebral protection while maintaining the advantages of warm systemic cardiopulmonary bypass temperatures.

Mechanical cardiac assistance and replacement.

This article aims not to review the limited and difficult to compare clinical results with mechanical cardiac assist devices. Instead, a practical classification and analysis of these devices is presented, which will afford the clinician insights about when, how, and why to use specific mechanical support.

The perioperative and surgical aspects of heart transplantation.

This article deals with the practical performance of both orthotopic and heterotopic heart transplantation. The surgical techniques, as well as the immediate preoperative and postoperative logistical management approaches to these procedures are presented.

Chronic injury of human renal microvessels with low-dose cyclosporine therapy.

Physiologic and morphologic techniques were used to study kidneys of cardiac transplant recipients treated with either low-dose (low-CsA) or high-dose (high-CsA) cyclosporine. After 12 months both low-CsA (4.6 +/- 0.4) and high-CsA (6.3 +/- 0.3 mg/Kg/24 hr, p less than 0.01) were associated with azotemia and hypertension; GFR with each regimen was depressed below values in a third group treated without CsA (no-CsA) by 40-47%, while corresponding renal vascular resistance was elevated greater than 2-fold (P less than 0.01). Morphologic changes in both CsA groups included an obliterative arteriolopathy with downstream collapse or sclerosis of glomeruli. Determination of renal arcuate vein occlusion pressure revealed an increasing renal artery-to-peritubular capillary pressure gradient between 1 and 12 months of CsA therapy. Fractional clearances of dextrans of graded size were elevated at each time compared with the no-CsA group. Analysis of dextran transport with an isoporous membrane model indicates that transglomerular hydraulic pressure difference (delta P) approximated 39 with no-CsA, but was reduced with low-CsA therapy to about 30 at 1 month, and about 34 mmHg after 12 months. We conclude that chronic CsA therapy induces constriction and eventual occlusion of afferent arterioles, causing downstream glomerular damage that is irreversible. Low versus high dosage of CsA confers only marginal protection against this serious microvascular injury.

Orthotopic cardiac transplantation for univentricular heart.

The technical aspects of orthotopic cardiac transplantation for univentricular heart in a 22-year-old man are discussed. Abnormal pulmonary artery anatomy resulted in right ventricular failure, which was successfully treated.

Diagnostic performance of sensitive measurements of serum thyrotropin during severe nonthyroidal illness: their role in the diagnosis of hyperthyroidism.

Serum thyrotropin (TSH) concentrations were measured serially in 14 heart-transplant recipients (group 1) and 21 patients undergoing coronary artery bypass surgery (group 2), all without thyroid disease, and randomly in 158 patients hospitalized for various other nonthyroidal illnesses, including 144 judged euthyroid (group 3), six with increased FT4 and (or) T3 (group 4), and eight classified hypothyroid by conventional tests. The serial measurements indicated profound fluctuations. In group 1, TSH was subnormal in 21% of studies and increased in 10%. In group 2, corresponding abnormalities were found in 7% and 13%, respectively. Transiently low or high TSH tended to be associated with normal free thyroxin (FT4), prolonged subnormal TSH (greater than 1 week) with subnormal FT4. By contrast, subnormal TSH plus elevated FT4, or high TSH plus low FT4, were not encountered, making it unlikely that they occur by chance in severely ill patients who are not also hyper- or hypothyroid. In group 3, a suppressed TSH (plus borderline high FT4, T3/FT3) identified four cases of subclinical hyperthyroidism; however, another 11% of patients had subnormal and 10% had above-normal TSH, paired with normal FT4 and no evidence of thyroid disease. In group 4, suppressed TSH confirmed hyperthyroidism in five of six patients, and all in group 5 had increased TSH. We conclude that, in the hospital setting, sensitive TSH measurement can help to detect or confirm mild hyperthyroidism, but the positive predictive value of TSH alone may be as low as 35%.

Significance of thyroid dysfunction in human cardiac allograft procurement.

Twenty-two potential cardiac allograft donors had evaluation of thyroid function performed just prior to cardiectomy. Despite statistically significant abnormal thyroid function, no correlation to graft function or failure was observable. Multiple myocardial microinfarcts, undetected at the time of donor selection were detected in two hearts that were abandoned prior to transplantation and possibly another heart that failed as an allograft in a heart-lung transplant recipient.

Myoventriculoplasty and neoventricle myograft cardiac augmentation to establish pulmonary blood flow. Preliminary observations and feasibility studies.

In 10 dogs, a latissimus dorsi muscle (myograft) was neuroelectrically stimulated at 120 cycles/min for as long as 80 days. The higher thresholds and multiple lead penetrations required of direct muscle stimulation for muscle conditioning were avoided. Vascular delay and protective wrapping of the myograft in four dogs resulted in rapid seroma and fibrous sheath formation, which precluded further study. Of the six other myografts that were stimulated, two were used as functional right ventricular myoventriculoplasties and four were employed as neoventricle myografts with inflow and outflow valved conduits that were used to provide total pulmonary blood flow. Myoventriculoplasty produced functional enlargement of the right ventricle with synchronously contractile muscle. Neoventricles provided hemodynamically stable total pulmonary blood flow for as long as 20 hours, until internal chamber thrombus formed. Transpulmonary blood pressure generation by the neoventricle was found to be programmable up to physiologic systemic pressures by modulation of chamber preload and burst stimulation frequency at 50 msec intervals, delivered 120 times per minute. Synchronization capabilities for implantable burst pulse generators would further improve the efficacy of these myograft techniques designed to augment or supplant ventricular function, particularly to provide transpulmonary blood flow at programmable pressures.

The spectrum of cytomegalovirus infection following human heart-lung transplantation.

Data were analyzed from 19 long-term survivors of cardiopulmonary transplantation in this institution, including nine patients with normal pulmonary function and 10 recipients with posttransplant obliterative bronchiolitis. In all cases, donor cytomegalovirus titers (IgG), preoperative recipient titers (IgG), and serial postoperative recipient titers (IgM, IgG, and complement fixation) were available. In addition, surveillance cytomegalovirus cultures and pulmonary function tests were obtained prospectively after surgery in all 19 patients. A total of 12 patients developed active cytomegalovirus infection (serologic conversion confirmed by positive cultures) after transplantation, six of whom subsequently developed obliterative bronchiolitis. However, infection was clinically associated with pulmonary deterioration in only four of these patients, three of whom had cytomegalovirus pneumonitis. With the exception of obliterative bronchiolitis, no other permanent sequelae of cytomegalovirus infection were evident in this small group. Progressive obliterative bronchiolitis was also seen in four of the seven recipients who had no evidence of cytomegalovirus infection at any time. Although viral causes have been associated with obliterative bronchiolitis, the current data suggest that cytomegalovirus infection in the absence of pneumonitis does not appear to be a significant risk factor for obliterative bronchiolitis in cardiopulmonary transplant recipients. A larger group of patients will be required to ultimately establish the role of cytomegalovirus infection in this setting.

Percutaneous transhepatic electrohydraulic lithotripsy.

Calculi can be fragmented by hydraulic shock waves generated by an electrical discharge across the tip of a coaxial electrode. After testing a device by using this technique in the biliary trees of dogs, the authors fragmented a large common bile duct stone in a patient through a percutaneous transhepatic approach. The fragmentation allowed nonsurgical drainage of the obstructed duct.

Tetracycline pleurodesis during active pulmonary-pleural air leak for prevention of recurrent pneumothorax.

Pleurodesis with a sclerosing agent was attempted in an animal model in which a pneumothorax with an active air leak was created. Adult rabbits had a small left thoracotomy and then a 1-cm controlled cut in the lung surface. Animals served as control, or tetracycline was administered. The chest tube was removed after the air leak stopped. Animals were sacrificed after 20 days. Group A was control rabbits (6); group B had powdered tetracycline placed at thoracotomy; group C, tetracycline solution, 2 ml/kg, 25 mg/ml (4); and group D, tetracycline solution, 1 ml/kg, 50 mg/ml (10). Control rabbits showed few adhesions, and the pleura appeared to be normal by histologic examination. There was a spectrum of results with tetracycline, but with the concentrated tetracycline solution (group D) histologic examination showed uniform pleurodesis and thickening of the pleura. In group D it took no longer for the pulmonary air leak to seal than with the group A (control) rabbits. We conclude that concentrated tetracycline solution is effective in causing pleurodesis even when an active air leak is present. The lung, however, must be kept expanded so that symphysis can occur between the visceral and parietal pleura.

Effect of electrical stimulation on diaphragmatic muscle used to enlarge right ventricle.

The effect of chronic electrical stimulation on muscle mass of pedicled diaphragmatic muscle grafts (DMGs) implanted into the right ventricle was studied in 21 dogs. Nineteen dogs, followed up to 70 days (mean, 34 days), were divided into three groups. In six dogs (control) the DMG was not stimulated. In six other dogs the DMG was stimulated at 50 stimuli/min with a fixed-rate unipolar pacemaker. In seven animals the graft was paced 1:1 with the dog's own rhythm with an R-wave synchronous pacemaker. Surface area of the DMG decreased 34% to 43% (P less than 0.05) in all dogs. DMG thickness increased in all dogs (P less than 0.05). The increase was 29% for control animals and 132% and 134% for the two paced groups. The volume of the DMG decreased 24% in the nonpaced animals but increased 29% and 51% in the two paced groups. Histologic studies showed some degree of muscle degeneration and atrophy in all grafts. However, morphometric studies showed relatively normal fiber diversity in paced grafts. Fiber size decreased in nonpaced grafts, indicating muscle atrophy. Perfusion studies with labeled microspheres and silicone injections demonstrated collateral circulation with the host ventricle as early as 28 days. However, total blood flow to DMGs implanted for 4 to 6 weeks averaged only 32% of the blood flow to normal ventricular myocardium. Chronic electrical stimulation of DMGs reduces muscle degeneration and atrophy and is associated with an increase in graft thickness and volume.

Replacement of ventricular myocardium with diaphragmatic skeletal muscle: short-term studies.

A pedicled diaphragmatic skeletal muscle graft was used to replace a portion of resected right ventricle in 35 dogs. The graft contracted when electrically stimulated directly or via the phrenic nerve before and after insertion. The electrical pacing threshold was lower for phrenic nerve stimulation (0.9 +/- 0.20 mamp) than for direct graft stimulation (2.3 +/- 1.19 mamp). The heart could be captured and paced by stimulating the muscle graft with higher current (16.2 +/- 4.49 mamp). The delay from pacing stimulus to muscle graft contraction when the graft was paced directly was 10 msec. The epicardial activation time delay when the heart was paced through the muscle graft was 27.0 +/- 9.08 msec. When the muscle graft pedicle was transected, the graft lost its ability to contract. The heart, however, could still be captured electrically through the graft for up to 4 hours. Strain gauge studies of the nonstimulated muscle graft showed tension development during pre-ejection ventricular contraction identical to that of the right ventricle. In the ejection phase, muscle graft tension slowly declined. The stimulated muscle graft developed active tension and echographically demonstrated muscle thickening during contraction. This study demonstrates that a vascularized, neurally innervated diaphragmatic muscle graft can be placed into the right ventricle. The graft retains its ability to contract in response to direct or phrenic nerve stimulation. It can be made to contract during any phase of the cardiac cycle. Thus diaphragmatic muscle grafts may provide a method to augment ventricular cavity size with synchronously contracting muscle.

Comparison of polymerization of ancrod and thrombin fibrin monomers.

The polymerization of thrombin and ancrod fibrin monomers was studied with a standardized technique that evaluated turbidity changes and protein incorporation into the clot. Ancrod fibrin monomers were found to polymerize more slowly and form less turbid clots (at identical protein concentrations). Changes in ionic strength and pH influences ancrod fibrin monomer polymerization to a greater extent than thrombin fibrin monomer polymerization. Benzyltriethylammonium chloride was shown to be a potent inhibitor of fibrin monomer polymerization, with a greater inhibitory effect on ancrod fibrin monomers than on thrombin fibrin monomers. The differences between ancrod and thrombin fibrin may play a role in the infrequent thrombotic complications reported with ancrod therapy.