Prolonged survival of orthotopically transplanted heart xenograft in infant baboons.

Orthotopic concordant xenotransplantation in a juvenile primate model was examined. Eighteen donor rhesus monkeys weighing 2.4 to 3.8 kg (mean 2.9 kg) were matched with juvenile baboons, aged 9 to 19 months (mean 12.7 months) and weighing 3.2 to 4.8 kg (mean 3.9 kg), using ABH blood type and mixed lymphocyte culture. Rhesus monkey hearts were orthotopically transplanted without immunosuppression into six control baboons (group I). In five baboons (group II), 4 mg/kg per day of antilymphocyte globulin was administered for 3 days before the operation and 5 days after the operation. Splenectomy was also performed, and 18 mg/kg per day of FK 506 was administered orally. Intravenous methotrexate, methylprednisolone, or both were used as rescue therapy. Seven baboons (group III) received the same immunosuppression as those in group II, but an intravenous dose of methotrexate (0.1 to 5 mg) was given twice weekly to suppress the proliferative response as monitored by in vitro immunologic assays. Baboons in group I had a mean survival of 8 days; all died as a result of classic cellular rejection. Baboons in group II had a mean survival of 48.4 days (p < 0.05 versus group I). Two died during rescue therapy for rejection, and three died of cytomegalovirus infection. Two group II baboons showed mild rejection at autopsy. Baboons in group III had a mean survival of 127 days, and one baboon was still alive after 286 days. Two died of cytomegalovirus infection, one of toxoplasmosis, one of Klebsiella pneumoniae, one of massive micropulmonary embolism, one of renal failure aggravated by ganciclovir. Only two of the baboons that died showed rejection (estimated as mild) at autopsy. The baboon still alive at 286 days had no rejection on myocardial biopsy on the two hundred forty-fourth postoperative day. FK 506 coupled with low-dose maintenance methotrexate and splenectomy has produced prolonged host survival in this xenotransplantation model. Results suggest that concordant xenotransplantation would be a suitable biologic bridge to allotransplantation.

Transesophageal echocardiographic recognition of subaortic complications in aortic valve endocarditis. Clinical and surgical implications.

BACKGROUND: Secondary involvement of the mitral-aortic intervalvular fibrosa and the anterior mitral leaflet (subaortic structures) can occur in patients with aortic valve endocarditis. The secondary involvement of these structures occurs as a result of direct extension of the infection from the aortic valve or as a result of an infected aortic regurgitant jet striking the ventricular surfaces of the mitral-aortic intervalvular fibrosa and the anterior mitral leaflet. The abscess of mitral-aortic intervalvular fibrosa can expand to form an aneurysm. Subsequently, this mitral-aortic intervalvular fibrosa aneurysm can develop a perforation and communicate with the left atrium, resulting in the systolic regurgitation of blood from the left ventricular outflow tract into the left atrium. Secondary infection can also occur on the ventricular surface of the anterior mitral leaflet and result in the formation of an aneurysm or perforation of anterior mitral leaflet. METHODS AND RESULTS: This study examines the utility of transesophageal echocardiography in the detection of these subaortic complications in 55 consecutive patients with aortic valve endocarditis. A total of 24 patients (44%) had involvement of subaortic structures, including four with an abscess in the mitral-aortic intervalvular fibrosa, four with mitral-aortic intervalvular fibrosa aneurysm, seven with perforation of the mitral-aortic intervalvular fibrosa with communication into the left atrium, two with an aneurysm of the anterior mitral leaflet, and seven with perforation of the anterior mitral leaflet. The transesophageal echocardiographic findings were confirmed at surgery in 20 patients and at necropsy in two. By comparison, transthoracic echocardiography visualized these lesions in five of 24 patients (21%), including none of four with mitral-aortic intervalvular fibrosa abscesses, two of four with mitral-aortic intervalvular fibrosa aneurysms, one of seven with mitral-aortic intervalvular fibrosa perforations, one of two with anterior mitral leaflet aneurysms, and one of seven anterior mitral leaflet perforations. Eccentric mitral regurgitation-type systolic jets were noted in eight additional patients by transthoracic color flow imaging, and this finding suggested the possibility of these unusual subaortic complications. If these patients are included, then transthoracic echocardiography suggested the presence of these subaortic complications in 13 of 24 patients (54%). CONCLUSIONS: The results indicate that 1) involvement of the subaortic structures in patients with aortic valve endocarditis may be more common than previously recognized, 2) patients with aortic valve endocarditis and eccentric jets of mitral regurgitation on transthoracic echocardiography should undergo further evaluation by transesophageal echocardiography to exclude these unusual complications, 3) precise recognition of these complications is of value in the optimal medical and surgical management of these patients, and 4) these complications may be responsible for unexplained congestive heart failure and hemodynamic deterioration in some patients with aortic valve endocarditis.

Can anatomical left ventricular mass be estimated reliably by M-mode echocardiography? A clinicopathological study of ninety-three patients.

To evaluate the accuracy of M-mode echocardiography in the assessment of left ventricular mass, we compared various echocardiography-derived regression equations for left ventricular mass to postmortem left ventricular weights in 93 patients (mean age 68 +/- 11 years) who had autopsy within 30 days of technically adequate two-dimensional guided M-mode echocardiography and who had normal left ventricular shape. The left ventricle was enlarged in 36 patients (39%) and was involved by chronic ischemic disease in 48 patients (52%). Only a modest correlation was found between M-mode echocardiography and anatomical left ventricular mass (range of correlation coefficients, 0.58 to 0.67). Each echocardiographic formula demonstrated increasing deviations as left ventricular mass increased. A previously suggested correction formula lessened overestimation, but considerable data dispersion remained. Regional wall-motion abnormalities, present in 22%, did not affect the correlation. We conclude that M-mode echocardiography, performed with standard methods, does not reliably estimate anatomical left ventricular mass, especially in patients with large hearts.

Embolism of brain tissue to the lung in a neonate. Report of a case and review of the literature.

Embolic cerebellar tissue was observed microscopically in the pulmonary and coronary arteries of a full-term male infant who died 1 hour after forceps delivery. Although embolization of brain tissue has been well documented after severe head trauma in adults and children, to our knowledge only 17 cases associated with birth trauma have been previously reported.

Mitral and aortic valve disease associated with ergotamine therapy for migraine. Report of two cases and review of literature.

Ergotamine has been associated with numerous vascular complications but only rarely with fibrosing disorders or valvular heart disease. Two patients are described in whom severe valvular dysfunction developed during ergotamine therapy for migraine headache. The surgically excised mitral and aortic valves were involved by a proliferative process that was strikingly similar to lesions described in patients with carcinoid heart disease and methysergide-associated valvular disease.

Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error.

Among 38 hearts from autopsies in which lymphocytic myocarditis contributed to death, 10 endomyocardial specimens from the apical septal aspect of each ventricle (760 specimens) and 6 slices of ventricular myocardium (228 slices) were evaluated for myocarditis by the Dallas criteria. For each case, the number of positive biopsy samples correlated well with the mean lymphocyte counts in biopsy tissues (P less than 0.0001) and the mean number of inflammatory foci per square centimeter in myocardial slices (P less than 0.001). Right ventricular biopsy specimens, however, were positive in only 63% of the 38 cases and 17% of the 380 specimens. Similarly, left ventricular biopsy tissues were positive in only 55% of the cases and 20% of the specimens. Sampling error was somewhat more prevalent among the 11 cases with isolated myocarditis than in the 27 with myocarditis and other illnesses. Even when 10 biopsy specimens per ventricle were evaluated, the frequency of false-negative results was 45% for the left and 37% for the right ventricle. Although myocarditis was noted in 68% of the 38 septal slices, it involved the subendocardium of the right ventricle (from which biopsy specimens are usually obtained) in only 24%. Because of the mild and focal nature of the inflammatory infiltrates and involvement of regions inaccessible to the bioptome, sampling error contributes appreciably to false-negative results in endomyocardial biopsy tissue from patients with myocarditis. Thus, when myocarditis is evaluated by biopsy alone, only positive findings are considered diagnostic.

Surgical pathology of the tricuspid valve: a study of 363 cases spanning 25 years.

Surgical pathologic features of the tricuspid valve were reviewed in 363 patients who had undergone tricuspid valve replacement at our institution during the period 1963 through 1987. Valves were purely regurgitant in 74%, stenotic and regurgitant in 23%, and purely stenotic in 2%; two valves were neither stenotic nor regurgitant. Among 269 purely insufficient tricuspid valves, the four most common causes were postinflammatory disease (41%), congenital disorder (32%), pulmonary venous hypertension (21%), and infective endocarditis (4%). Of 92 cases of tricuspid stenosis, with or without regurgitation, postinflammatory disease was observed in 92%. Female patients accounted for 66% of the 363 cases, including 84% of those with postinflammatory disease and 64% of those with pulmonary venous hypertension. In contrast, male patients accounted for 73% of cases with endocarditis and 61% with congenital heart disease. Although postinflammatory disease accounted for 53% of the 363 cases, its relative frequency diminished from 79% during 1963 through 1967 to only 24% during 1983 through 1987. This trend may reflect the decreasing incidence of acute rheumatic fever reported in Western countries. During the same time interval, the relative frequency of congenital heart disease as a cause of tricuspid dysfunction increased from 7% to 53%, and it is currently the most common cause in our surgical population. This finding apparently reflects changes in patient referral practices and the development of new operative procedures.

Mechanism of reduction of aortic valvular stenosis by percutaneous transluminal balloon valvuloplasty: report of five cases and review of literature.

Among five patients (69 to 93 years of age) in whom percutaneous transluminal balloon valvuloplasty was performed for severe aortic stenosis, fractures of cuspid calcium were observed in three, fractures and a cuspid tear in one, and no gross alterations in one. Aortic stenosis resulted from degenerative (senile) calcification of tricuspid aortic valves in two patients, calcification of congenitally bicuspid aortic valves in two, and postinflammatory (presumably rheumatic) fibrocalcific disease in one. Fractures of calcific lesions, by allowing hingelike motion along their sites, seemed to facilitate cuspid mobility and thereby provided the apparent morphologic substrate for reduction in functional stenosis. Among three cases with fused commissures (two bicuspid and one postinflammatory), however, mobility of the conjoined cusps was not achieved after valvuloplasty, despite fracture of calcific nodules in the adjacent valve pocket of one case, because the fused and calcified commissures were not split or fractured and therefore continued to act as rigid struts that impeded cuspid motion. In the current autopsy evaluation of the effects of aortic balloon valvuloplasty, greater cuspid mobility seemed to be achieved in subjects with degenerative calcific stenosis than in those with calcified bicuspid valves or distortion by postinflammatory disease.