neuropeptide-y and Hyperemia

The implanted cardioverter defibrillator represents an alternative therapy for patients with drug-refractory malignant ventricular arrhythmias. Implantation and testing of the device requires that ventricular fibrillation be evoked and converted, thus providing a situation in which cardiovascular haemodynamics can be studied. In this study we have evaluated the effects of electrically induced ventricular fibrillation, followed by defibrillation, on coronary sinus blood flow and cardiac outflow of endothelin- and neuropeptide Y-like immunoreactivity (-LI) and of noradrenaline. Twelve patients were studied during implantation of a defibrillator. Ventricular fibrillation was induced and terminated after 17 +/- 1 s 5 +/- 1 times in each patient. In six patients coronary sinus blood flow was measured continuously. Plasma samples were obtained from four of these patients and another six patients, from the coronary sinus, radial artery and central vein before and during fibrillation and at two time points ( < 30 s and 5 min). Basal coronary sinus blood flow decreased to 38% at 14 +/- 2 s of ventricular fibrillation. Immediately following defibrillation there was a short-lasting increase in coronary sinus blood flow to 244% and a significant increase in the levels of neuropeptide Y-LI (146%) and noradrenaline (158%) in the coronary sinus while endothelin-LI remained unchanged (97%). Neither fibrillation nor defibrillation evoked any changes in the peripheral arterial and venous levels of endothelin-, neuropeptide Y-LI or noradrenaline. It is concluded that coronary sinus blood flow is markedly reduced during fibrillation and that restoration of normal impulse activity is followed by short-lasting hyperaemia. There was no evidence for effects on the vascular endothelium as assessed by endothelin levels.

Topics: Adult; Aged; Cardiac Pacing, Artificial; Coronary Circulation; Defibrillators, Implantable; Electrocardiography; Endothelins; Female; Hemodynamics; Humans; Hyperemia; Male; Middle Aged; Myocardium; Neuropeptide Y; Norepinephrine; Reference Values; Ventricular Fibrillation

Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p less than 0.01). CBF returned to preischemic levels approximately 45 min after reperfusion and was reduced to approximately 65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p less than 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p less than 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 nM; 50 microliters) to the middle or posterior temporal branch of the MCA 10-14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (PaCO2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to red

Topics: Adenosine Triphosphate; Animals; Calcitonin Gene-Related Peptide; Capsaicin; Cats; Cerebrovascular Circulation; Female; Ganglionectomy; Hyperemia; Ischemic Attack, Transient; Male; Nerve Fibers; Neuropeptide Y; Pia Mater; Substance P; Trigeminal Ganglion; Vasoactive Intestinal Peptide

The effect of neuropeptide Y (NPY) on tension development was examined in isolated canine coronary arteries, and the effects on local myocardial blood flow rate were studied in open-chest anesthetized dogs by the local 133Xe washout technique. By immunohistochemistry, numerous NPY-like immunoreactive nerve fibers were identified in the adventitia of canine coronary arteries. NPY (10(-9)-10(-6) M) supplied to isolated epicardial segments of the left anterior descending coronary artery induced a modest vasoconstriction, with a maximum tension of 0.95 mN, that was only 6.9% of the response to K+. In contrast, intracoronary NPY (0.01-10 micrograms) induced a considerable degree of vasoconstriction; the reduction of blood flow rate was dose related, with a maximum reduction to 52% of control values. The effect of intracoronary NPY (1 microgram) on maximally relaxed arterioles elicited by 30 s of ischemia was studied in separate experiments during reactive hyperemia. NPY induced a decrease in maximum blood flow during reactive hyperemia (166.6 vs. 214.6% of preocclusive blood flow rate, mean values; P = 0.05), an increase in the cumulative excess blood flow (61.0 vs. 35.3 ml/100 g; P = 0.02), and an increase in the duration of reactive hyperemia compared with control values (66 vs. 41 s; P = 0.02). Thus we conclude that in the heart NPY is a potent vasoconstrictor that seems to act preferentially on smaller intramyocardial arterioles. Furthermore, NPY inhibits vascular relaxation of myocardial resistance vessels after ischemia, suggesting that this peptide may participate in the regulation of myocardial blood flow not only during physiological conditions but also after ischemia.

Topics: Animals; Coronary Circulation; Dogs; Dose-Response Relationship, Drug; Hyperemia; Immunohistochemistry; In Vitro Techniques; Myocardium; Neuropeptide Y; Time Factors

In the present study we have tried to characterize and quantify the post-occlusive hyperaemia in the pig heart, skeletal muscle and skin circulation. In addition, the possible involvement of caspaicin-sensitive sensory nerves in the reactive hyperaemia was investigated. Reperfusion after total stop-flow ischaemia for 1, 5 or 15 min elicited a marked hyperaemia in all vascular beds studied. The post-occlusive hyperaemia after 5 min ischaemia was 512 +/- 74%, 328 +/- 94% and 444 +/- 87% in the heart, femoral artery and saphenous artery respectively. Also, in the skin the blood flow following 5 min ischaemia was increased fivefold. Furthermore, the duration of the hyperaemia after 5 min ischaemia was significantly (P less than 0.01) longer in the heart (382 +/- 32 s) than that in the femoral artery (192 +/- 27 s), saphenous artery (182 +/- 48 s) and skin (95 +/- 14 s). Increasing the ischaemic time period prolonged the duration as well as elevated the peak increase of the hyperaemia. Capsaicin pre-treatment significantly reduced (by about 70%) the tissue levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI), which is present in sensory nerves, but not neuropeptide Y-LI, which is of sympathetic origin, in the left ventricle of the heart, quadriceps muscle and skin in the pig. However, there were no differences in the post-occlusive hyperaemia in control and capsaicin-pre-treated pigs. Capsaicin administered intracutaneously caused a long-lasting (about 20 min) increase in skin blood flow in the pig. This enhanced blood flow was completely abolished after systemic capsaicin pre-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Calcitonin Gene-Related Peptide; Capsaicin; Coronary Circulation; Hyperemia; Muscles; Neuropeptide Y; Skin; Swine