Virgilio Sangalang

The heart reinnervates after transplantation

BACKGROUND Whether cardiac reinnervation occurs after transplantation remains controversial. If reinnervation does occur, how sympathetic and parasympathetic efferent neurons do this remains unknown. METHODS Power spectral analysis of heart rate variability was assessed for 1 year after cardiac autotransplantation in 9 dogs. After induction of anesthesia 13 months after transplantation, cardiac and intrinsic cardiac neuronal responses elicited by both electrical stimulation of parasympathetic or sympathetic efferent neurons and systemic or local coronary artery administration of nicotine (5 microg/kg), angiotensin II (0.75 microg/kg), and tyramine (1.2 microg/kg) were studied. The transmembrane electrical properties of intrinsic cardiac neurons were studied in vitro. Ventricular tissue catecholamine content, alpha-tubulin expression, and beta-adrenergic receptor density and affinity were studied. The presence of axons crossing suture lines was sought histologically. RESULTS Nerves were identified crossing suture lines. Electrical or chemical (ie, nicotine or angiotensin II) activation of sympathetic efferent neurons enhanced cardiodynamics, as did tyramine. Stimulating vagal efferent preganglionic axons induced bradycardia in half of the dogs. Functional reinnervation did not correlate with specific power spectra derived from rate variability in the conscious state. Responding to nicotine and angiotensin II in situ, transplanted intrinsic cardiac neurons generated spontaneous activity. These neurons displayed nicotine-dependent synaptic inputs in vitro. Ventricular tissue had normal beta-adrenergic receptor affinity and density but reduced catecholamine and alpha-tubulin contents. CONCLUSIONS The intrinsic cardiac nervous system receives reduced input from extracardiac sympathetic efferent neurons after transplantation and inconsistent input from parasympathetic efferent preganglionic neurons. These heterogeneous neuronal inputs are not reflected in heart rate variability or ventricular beta-adrenergic receptor function. Transplanted angiotensin II-sensitive intrinsic cardiac neurons exert greater cardiac control than do nicotine-sensitive ones. The intrinsic cardiac nervous system remodels itself after cardiac transplantation, and this indicates that direct assessment of extracardiac and intrinsic cardiac neuronal behavior is required to fully understand cardiac control after transplantation.

Retrospective Diagnosis of Dementia Using an Informant Interview Based on the Brief Cognitive Rating Scale

The accuracy of a dementia diagnosis by specialist physicians, as verified at an autopsy, is greater than 90% in many series. Donations of brains to the Maritime Brain Tissue Bank (MBTB) by individuals who did not have expert dementia diagnoses before death led us to investigate whether clinical features could also be detected retrospectively. Informants for 36 individuals whose brains were in the MBTB (18 women, mean age = 79 years; pathologic diagnoses: 75% Alzheimers disease [AD]; 8.4% vascular or mixed dementia) were interviewed by specialist physicians using a semistructured retrospective interview based on the Brief Cognitive Rating Scale (BCRS) (range = 1 [no impairment] to 7 [terminal dementia]). The mean duration of dementia was 8.5 +/- 12.8 years based on proxy reports, and most cases suggested severe dementia--(stage 6 [severe] or 7 [terminal])--on the retrospective BCRS (RetroBCRS) before death. A score of 4 or more on the RetroBCRS had 100% sensitivity and specificity in detecting dementia. The RetroBCRS score correlated moderately with duration (.51). In linear and logistic regression models adjusted for age and sex, RetroBCRS staging helped explain 93% of the variation in duration. The accuracy of the retrospective diagnosis of the cause of dementia, compared with autopsy, was 92%. The RetroBCRS used by an expert physician with a reliable informant is a valid method of detecting dementia and determining whether AD was present.

Acute endothelial swelling is induced in endoneurial microvessels by ischemia

Structural alterations of endoneurial microvessels occur in diabetic neuropathy and are statistically associated with severity of nerve fiber loss and teased fiber abnormality. It is therefore hypothesized that the microvessel alterations may cause or contribute to pathologic alterations of nerve fibers in diabetic neuropathy, possibly through hypoxic injury. The mechanism of the microvessel change in diabetic neuropathy is unknown. The role of microvessels and details of microvessel structure in other possible ischemic neuropathies has not been studied completely. Already there is evidence that hypoxia induces endothelial swelling but this has not been characterized or quantitated in nerve. To determine the acute morphologic effect of ischemia on ultrastructural features of transverse profiles of endoneurial microvessels major pelvic arteries were ligated in rats. At 36 h mean lumen and mural areas were greater in ischemic than in control nerves. All components (endothelium, pericytes and basement membrane) were on average greater in ischemic than controls. The greatest increase was in endothelial cells. In these cells swollen mitochondria were abundant. This study demonstrates that acute ischemia induces swelling of the cells and organelles of endoneurial microvessels.

Nerve microvessel changes in diabetes are prevented by aldose reductase inhibition.

BACKGROUND Despite the potential importance of endoneurial microvessel abnormalities in diabetic neuropathy, the pathogenesis of these abnormalities is incompletely understood. We wished to evaluate the effect of experimental diabetes on endoneurial microvessels and determine if an aldose reductase inhibitor alters any of the changes induced by diabetes. METHODS We compared streptozocin diabetic rats with and without aldose reductase inhibitor treatment to non-diabetic rats after 10 months of diabetes. Transverse microvessels from the mid-sciatic level were studied by electron microscopic morphometric evaluation. RESULTS Microvessel endothelial, pericyte, basement membrane and total mural area were greater in untreated diabetic animals than non-diabetic animals. Aldose reductase inhibitor treated diabetic animals had greater endothelial area and possibly pericyte area but not basement membrane or total mural area. CONCLUSIONS This study demonstrates that endoneurial microvessel abnormalities can be detected in experimental diabetic neuropathy. Microvessel basement membrane thickening will be prevented by an aldose reductase inhibitor. One mechanism by which abnormal polyol pathway activity may contribute to diabetic neuropathy could be through damage to microvessels.

Inner perineurial cell vulnerability in ischemia

The perineurium of peripheral nerve plays important roles in anatomical organization of fiber groups, in endoneurial fluid homeostasis and in maintenance of tensile strength but little is known about the functional and structural alterations of the perineurium with injury. Large arteries of supply to lower limb of Sprague-Dawley rats were ligated to study the structural reactions of perineurium at 36 h and at 7 days after induction of ischemic injury. Lipid droplets were found to be an early reactive change to ischemia in multiple cell types including perineurial, endothelial and Schwann cells. In peripheral nerve levels showing early myelinated fiber injury the inner perineurial sheath was widened and was undergoing degeneration. The inner layers of perineurial cells showed swelling, organelle disruption and membrane dissolution while outer layers remained intact. Inner perineurial cell degeneration is a prominent early feature of ischemic injury and may be an important mechanism of altered endoneurial homeostasis, fiber function and structure.

Focal myocardial necrosis associated with multiple sclerosis of the medulla

Abstract A debate exists as to the capacity of the central nervous system to induce vasospasm of resistance vessels in the coronary circulation both in healthy persons and in patients with coronary artery disease. A view exists suggesting that direct central neural stimulatory effects on the coronary arteries are minimal1 and that central nervous system stimulation as occurs in head injury results in a generalized autonomie response with circulating catecholamines arising from the adrenal gland causing toxic damage to the myocardium.2 A contrasting view is that the extensive intrathoracic sympathetic nervous system that directly innervates the coronary arteries when stimulated can induce myocardial ischemia, which, if prolonged, induces myocardial infarction.3 In this report, we describe a young woman with a brief history of multiple sclerosis involving the medulla who presented with myocardial infarction, and subsequently died.