Multivariate analysis of factors affecting waiting time to heart transplantation.

BACKGROUND: The growing clinical success of cardiac transplantation has resulted in a dramatic increase in the number of patients referred and subsequently listed for cardiac transplantation. Paradoxically, in the presence of a limited donor organ pool, such expansion has increased both the waiting time for transplantation and the number of patients dying while on the waiting list. METHODS: We performed univariate and multivariate analyses of the waiting times of 301 patients listed for transplantation using a Cox proportional hazards model to evaluate the simultaneous effect of multiple variables on the waiting time of heart transplant candidates. Variables considered included age, sex, race, blood type, weight at listing, United Network for Organ Sharing (UNOS) status at listing, UNOS status at transplantation, and proportion of time on the waiting list as UNOS status 1. RESULTS: The mean waiting time for patients ultimately having transplantation was 170.2 +/- 206.0 days; the median waiting time was 103.5 days. Age, sex, weight, blood type, and percent of time as UNOS status 1 all had a significant impact on waiting time in the univariate analysis. By multivariate analysis, proportion of time as UNOS status 1, lower weight at listing, and blood type AB were all highly associated as predictors of a shorter waiting time. Weight at listing represented a continuous variable whose risk ratio for a shorter waiting time correlated in such a way that the risk of a longer waiting time increased 2.3 per 22.5-kg (50-pound) increase in weight. Blood types A and B, although associated with a shorter waiting time, correlated less strongly than the other three variables. CONCLUSIONS: Our findings from this multivariate analysis demonstrate that UNOS status, blood type, and weight were the variables that most strongly affected overall waiting time for transplantation. It is our hope to define more accurately a group of patients with both a high likelihood of a long waiting time and a prohibitive risk of death while on the waiting list, who therefore may benefit from surgical alternatives to transplantation.

A light and electron microscopic study of the innervation of pulmonary arteries in the cat.

Nerve terminal-smooth muscle relationships were studied in pulmonary arteries of the cat using 5-hydroxydopamine to help differentiate adrenergic and nonadrenergic terminals. There was a periarterial plexus of nerves in the walls of pulmonary arteries that extended into the lung to innervate even small arteries having a single layer of smooth muscle cells. Adrenergic nerves surrounded all arteries and extended into the tunica media of the large arteries. There were also apparent cholinergic nerves around the pulmonary arteries, although this was confirmed by electron microscopy for medium- and small-sized arteries only. The relationships of nerve terminals to smooth muscle cells in pulmonary arteries suggest that release of norepinephrine by adrenergic terminals can produce both decreased compliance and increased resistance in the pulmonary vascular bed, and that acetylcholine released by cholinergic terminals may act directly on vascular smooth muscle or on adrenergic terminals to modulate release of norepinephrine. These results suggest that both sympathetic and parasympathetic nerves may have a regulatory role in the pulmonary circulation.

Influence of 5- and 6-hydroxydopamine on adrenergic transmission and nerve terminal morphology in the canine pulmonary vascular bed.

We studied the effects of 5- and 6-hydroxydopamine on adrenergic neurotransmission, fluorescence histochemistry, and nerve terminal ultrastructure in the canine pulmonary vascular bed. Fluorescence histochemistry on stretched preparations and sections of intrapulmonary artery and vein demonstrated that these vessels are well supplied with adrenergic nerves electron microscopy revealed adrenergic terminals in the adventitia and outer third of the media in the artery, but only in the adventitia in the vein. Adrenergic terminals in artery and vein contained many small and a few large dense-core vesicles. At least 20% of the terminals in the artery contained many small agranular vesicles and a few large opaque vesicles; this suggests that they were of the cholinergic type; Such terminals were not found in intrapulmonary veins. Under conditions of controlled blood flow, stimulation of the sympathetic nerves to the lung and intralobar injection of norepinephrine increased pressure in the perfused lobar artery and small intrapulmonary vein in a stimulus-related manner. The rise in pressure in the lobar artery and vein in response to nerve stimulation was blocked after administration of either 5- and 6-hydroxydopamine; Neither agent modified the response of the pulmonary vascular bed to norepinephrine; In contrast, the rise in pressure in the lobar artery and vein in response to both norepinephrine and to nerve stimulation was blocked by phenoxybenzamine, an alpha-receptor blocking agent. The attenuated neurogenic vasoconstrictor response in dogs treated with 5- and 6-hydroxydopamine was associated with a marked decrease in intensity of fluorescence of the abundant adrenergic innervation in both intrapulmonary artery and vein, and with the appearance of an osmiophilic material in dense-core vesicles of adrenergic terminals in artery and vein. We believe that these data suggest that 5- and 6-hydroxydopamine interfere with adrenergic transmission in intrapulmonary vessels by depleting norepinephrine from adrenergic terminals. Furthermore, we conclude from hemodynamic, histochemical, and ultrastructural studies that vasomotor tone in the pulmonary vascular bed can be regulated by the sympathetic nervous system.

Cryostat technique for central nervous system histofluorescence.

This paper offers a technique for obtaining monoamine histofluorescence in the CNS by means of formaldehyde perfusion followed by cryostat sectioning. No freeze-drying is involved. Cryostat sections are exposed to formaldehyde vapor to complete the fluorophore formation. The fluorescence thus obtained is bright, well localized, and does not require loading the animals with precursors. The anatomical distribution of the pathways is identical to that obtained with the classical technique. Furthermore, the fluorescence is reversible by sodium borohydride, and exhibits the expected changes in intensity with pharmacological manipulations. The sections can be exposed to a cold aqueous medium for as long as 15 min with minimal diffusion of fluorophore; this suggests potential for combining monoamine histofluorescence with other visualization techniques.

Retrograde axonal transport of horseradish peroxidase in peripheral autonomic nerves.

An exogeneous marker protein, horseradish peroxidase (HRP) was used to race peripheral autonomic pathways in adult guinea pigs and cats. Small doses of HRP were injected into various organs and after a brief survival period, HRP activity appeared in the perikarya of autonomic neurons that supplied each injection site. After injection of HRP into the anterior chamber of the eye, reaction product was detected in the postganglionic sympathetic neurons of the superior cervical sympathetic ganglion. In another experiment, HRP reaction product was found in the cell bodies of the preganglionic sympathetic neurons that supply the adrenal medulla. These were located in the lateral gray column of the spinal cord at T6 and T7 segmental levels. Reaction product appeared in intramural postganglionic parasympathetic neurons close to an injection site in the wall of the urinary bladder and in a similiar situation in Meissner's ganglia of the ileum. Following injection into the walls of the stomach and ileum, HRP labelled cells were detected in the nodose ganglion of the vagus and in preganglionic parasympathetic neurons in the dorsal motor nucleus of this nerve. After injection into the subepicardial tissue of the heart, reaction product appeared in the stellate ganglion and also in an upper thoracic dorsal root ganglion. These data suggest that HRP is taken up by peripheral autonomic nerves of all types, and then undergoes rapid retrograde axonal transport to the perikaryon. It appears, therefore, that HRP may be useful in tracing both motor and sensory peripheral autonomic pathways.